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who is the managing director of international litigation services

qpjf0226

qpjf0226_p0, qpjf0226_p1, qpjf0226_p2, qpjf0226_p3

Joseph Thorpe

Comprehensive Product Strategy Meeting Material Field I: Diabetic Medicine Field Prepared on: 8/5/2002 Proposing Dept.: Pharmaceutical Research Div. HQ Name of issue: Actos Purpose of Submission Date Submission Date Submission date Priority (Fastest Top priority . Priority submission: ( transition) ( transition) 8/6/2002 General) Course of action in U.S. 1. Summary of the Proposal On July 22, 2002, Novo Nordisk announced that "with regard to the insulin sensitizer NN622 (Ragaglitazar) which is a PPAR dual agonist" being development by the company, it will stop the clinical study and postpone all planned clinical studies in response to the results of the carcinogenicity study in which bladder tumor was observed in multiple rats as well as one mouse. Following the announcement, FDA requested TPNA for a conference call, and a conference call between FDA and TPNA took place on July 31 (U.S. time). The contents of the conference are summarized below. We propose the following measures with regard to this matter for your review and approval. [Summary of the Conference Call] FDA indicated its opinion that bladder tumor is a class effect of the PPAR dual agonist (the PPAR hypothesis) and that bladder tumor in Actos rats is not caused by Takeda's hypothesis (Dr. Cohen's hypothesis, see Exhibit 1) but the PPAR hypothesis. Also, we received the following three requests and were instructed to submit to FDA our responses in writing within three to four weeks. 1. Monitor pathological changes in bladder: Submit a method for monitoring pathological changes in bladder in the phase IV long- term administration clinical study with a dosing period of one year or longer currently being conducted in the U.S. 2. Adding efficacy in children: Due to the concern for bladder tumor, abandon adding efficacy in children for which a clinical study is being prepared (the purpose is to prolong the exclusive marketing rights for six months). 3. Revising the label: Consider changing a part of the wording in the carcinogenicity study item in the label as follows: Current wording: "Relevance of findings of bladder tumor in male rats to humans is unclear" FDA's proposal: "The mechanism of the PPAR dual agonist (Note 1) may be related to the incidence of bladder tumor" Note 1: PPAR has known sub-types of a, y, and 8, and Actos is a y agonist and a weak a agonist. On the other hand, Avandia is a V agonist only. A compound that is both a and y agonist is known as a "PPAR dual agonist," and the TAK-559 and most of insulin sensitizers currently being developed (NN622, Merk, AstraZeneca, BMS, Mitsubishi Pharma and others) belong to this category. [Other items discussed with FDA] 1. With regard to Avandia, FDA said what is at issue is one product on the market, and clearly stated that it is a class effect of the PPAR dual agonist. However, at this stage it is unclear whether Avandia is receiving the same response from FDA as Actos. 2. Bladder tumor in the carcinogenicity study of the NN622, which is a PPAR dual agonist, was not specific to male rats and it was not accompanied by bladder stones. 3. FDA has obtained information that, in a bladder tumor manifestation promotion study conducted separately by a different company (Note 2), Actos, which was used as a control drug, increased bladder tumor. Note 2: Details of this study is unclear as FDA did not disclose any more information. However, it may be a study conducted by Novo Nordisk. 2. Responses to FDA (1) Response schedule: 1 On August 6, we will hold a four-way conference call with TPNA, EuR&D, TCI and Lilly HQ to stress the importance of managing information regarding this matter and confirm the future communication routes. 2 On August 12 and 13, we will hold a face-to-face, three-way meeting with TPNA, EuR&D and TCI to discuss our responses to the three requests from FDA described above, as well as how the work will be divided. From TCI, researchers in charge of toxicity and pharmacology will attend, with cooperation from the Strategic Development Department and the Research Division HQ. 3 We will actively seek cooperation from outside experts in toxicity, pharmacology and epidemiology. We've already begun to contact Dr. Cohen. 4 We will prepare (draft) responses to FDA by August 20 and obtain consent from relevant departments and CEO. 5 We plan to submit our responses to FDA on August 26. Confidential - Subject to Protective Order TAK-SATOKE-00091272 TAK-SATOKE-00091272P-0001 Source: Comprehensive Product Strategy Meeting Material Field I: Diabetic Medicine Field Prepared on: 8/5/2002 Proposing Dept.: Pharmaceutical Research Div. HQ Name of issue: Actos Purpose of Submission Date Submission Date Submission date Priority (Fastest Top priority . Priority submission: ( transition) ( transition) 8/6/2002 General) Course of action in U.S. (2) Current plan for responding to FDA's requests 1) Monitor pathological changes in bladder: 1 We will urgently consider a method for monitoring pathological changes in bladder in clinical studies (Note 3), and consider implementing the monitoring of pathological changes in bladder in long-term administration clinical studies being conducted not only in the U.S. but also in Europe and Japan. Note 3: As a general monitoring method, we will conduct a urinalysis, and if the urine occult blood reaction is positive, we will conduct a urine cytology and an ultrasound tomography test. Further, if there is a suspicious finding, we will conduct a cystoscopy. We will seek experts' opinions to see if there are appropriate monitoring methods other than this. 2 Already in Japan, 1,180 cases after the clinical trial (administration period: two months to one year) were followed up for two to three years (without administering Actos), and we obtained the result in which no bladder tumor with suspected association with the drug was reported. Therefore, we will evaluate this result and, if it is useful, we will use it in our response. 2) Adding efficacy in children: We will argue that the class effect of the PPAR dual agonist suggested by FDA lacks scientific basis, mainly based on the supporting data from nonclinical studies (see Exhibit 2 for details), and negotiate so that we can proceed to conduct the clinical study on children as initially planned. 3) Revising the label: With regard to the revision of the label, we will argue against the PPAR hypothesis FDA is asserting by reinforcing the Cohen hypothesis and constructing a theory from the perspectives of toxicity and pharmacology, and we will respond so as not to accept the revision of the label. (Exhibit 2) (3) Contingency plan With regard to the three requests from FDA, we will consider their impact on the market and other factors and rank their impact as shown below, clarify which request is acceptable and which is not, and consider our response. [Magnitude of impact] Revise label >> Abandon adding efficacy in children > Monitor pathological changes in bladder in clinical studies 1) It would be best if we can persuade FDA and we won't have to accept any of the three requests, but realistically we believe that is difficult. We will pursue a direction in which we will firmly refuse to accept the revision of the label which will have the most serious impact on the market. 2) With regard to the clinical study on children, if the situation forces us to accept it in order to avoid the label revision, we will cautiously proceed to discuss with FDA and look for a compromise. If possible, we will offer to postpone the start of the clinical study temporarily instead of abandoning the addition of efficacy. 3) We will try to persuade FDA by stating that monitoring results of pathological changes in bladder in long-term administration clinical studies are weak as supporting data. However, we will assume that we will eventually accept it and make preparations. 4) At worst, if FDA orders us to revise the label, we will insist on a class-labeling of PPAR agonists on the ground that FDA's PPAR hypothesis has no scientific basis, so that it will not lead to a differentiation from Avandia. 3. Response to regulatory authorities in Japan and Europe (1) Response to the Japanese government We will proceed as follows while consulting with the Pharmaceutical Sales HQ if necessary. 1 FDA may take some action in the future, but at this time FDA has not indicated any specific action. Therefore, we will not report to the Japanese authorities immediately. 2 However, if we don't report to the Japanese authorities until after FDA decides on its action, we are afraid that it may invite an overreaction from the authorities. In our judgment it is preferable to provide information in advance to avoid it. Therefore, after submitting the responses to FDA (August 26), TPNA will, in short order (on August 27 or 28), summarize FDA's requests and TPNA's responses into a memorandum and provide the information to officers in charge of the authorities (the Safety Division and the Center for Product Evaluation). 3 Subsequently, through TPNA, we will watch FDA's reactions, etc., and provide additional information to the authorities and maintain contact. Confidential - Subject to Protective Order TAK-SATOKE-00091273 TAK-SATOKE-00091272P-0002 Source: Comprehensive Product Strategy Meeting Material Field I: Diabetic Medicine Field Prepared on: 8/5/2002 Proposing Dept.: Pharmaceutical Research Div. HQ Name of issue: Actos Purpose of Submission Date Submission Date Submission date Priority (Fastest Top priority . Priority submission: ( transition) ( transition) 8/6/2002 General) Course of action in U.S. 4 If label indication is likely to be revised based on the discussion between FDA and TPNA, we will discuss internally the revision of the domestic label and determine our course of action. (2) Responding to the European authorities Currently, we don't have any legal obligation to officially report to EMEA regarding FDA's action. However, as in Japan, TPNA will, after submitting the responses to FDA, unofficially communicate to EMEA (rapporteur) FDA's requests and the summary of TPNA's responses. Incidentally, EMEA (rapporteur) and EuR&D are planning to meet on August 21, 2002 to discuss the application of an addition of efficacy planned for the second quarter of next year, and we assume that the issue of NN622 will come up at the meeting. At the meeting, we won't explain FDA's requests specifically, but we believe we have no choice but to say, "It seems that FDA contacted TPNA in the U.S. We will let you know about the details later." 4. Responding organizations for this matter Basically, we will utilize the organization of the current Actos Safety Measures Study Committee. However, with regard to this matter, we will limit the participants, and the secretariat will be in the Strategic Development Department (previously it was in the Pharmaceutical Information Department) to strengthen the communication with TPNA and EuR&D. Also, we will coordinate with the Corporate Strategy Division and the Strategic Development Department to unify the intentions among the relevant departments in the company. (The chart of responding organizations will be distributed separately.) 5. Communication to distributors (1) We have already notified Lilly HQ of the facts of this matter, and obtained their consent not to disclose information to Lilly distributors until they receive Takeda's instruction. (2) If FDA notifies us of specific actions, we will discuss with the Pharmaceutical International Division, Pharmaceutical Sales HQ, and Corporate Communication Department and decide how to notify overseas distributors and domestic sales offices. 6. Impact on post-Actos TAK-559 (PPAR dual agonist) (1) The post-Actos TAK-559 is categorized as a PPAR dual agonist as is the NN622, and currently, Phase II is being conducted in Europe under IND of FDA. (2) In the results of long-term toxicity tests obtained so far, there is no finding of toxicity that is indicative of bladder tumor, and at this time, there is no problem in the implementation of Phase II. (3) However, since FDA sees bladder tumor as a class effect of the PPAR dual agonist, we cannot deny the possibility that it will affect TAK-559 as well. (4) The TAK-559's carcinogenicity study is currently being conducted, and a preliminary report of histopathological tests will be obtained in October 2003 which will allow us to determine the presence or absence of bladder tumor. END Confidential - Subject to Protective Order TAK-SATOKE-00091274 TAK-SATOKE-00091272P-0003 Source: is INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SATOKE-00091272P-0001 I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 27th day of August 2013, in Aliso Viejo, California. Joseph Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. - 65 Enterprise * Aliso Viejo, California 92686 Phone: 888.313.4457 Fax: 213.674.4191 * NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source:

who conducted pivotal studies

yljf0226

yljf0226_p0, yljf0226_p1

Takeda

ACTOS FDA Response Strategy TASK FORCE -TPNA Alfonso Perez Janet Haskins* Mary Ramstack* Ingrid Hoos Michael Elisseou John Page (Rich Wilson) Claire Thom Dan Orlando David Baron (Chris Durack) Larry Hancock Karen Kaluzny Masatake Kashiyae Chuck Burant *Task Force Coordinators TASK FORCE STRATEGIES: The FDA has 3 key issues with respect to the non-clinical data related to bladder tumors, 1. They requested us to propose a method by which to monitor bladder toxicity in patients in our long term phase 4 clinical trials (long term was defined as at least 1 year). a, TPNA will challenge the FDA request to conduct clinical monitoring in long-term studies. 2. They requested us to give some consideration to a label change that would reflect possible relatedness of tumor formation to mechanism (dual PP AR agonist) instead of the current language ("The relationship of these findings in male rats to humans is unclear.") a. TPNA would like to challenge FDA hypothesis around tumor formation relationship to dual PPAR mechanism. b. TPNA goal is to supply justification to support maintaining current labeling. 3. They indicated an inclination to rescind the written request for pediatric exclusivity based on their concern about bladder tumors. a. Based on current verbiage in PI TPNA requests to conduct pediatric trial as scheduled. Last revision; August 7, 2002 EXHIBIT 2) WIT: Ramslude DATE: 10-1-13 Confidential - Subject to Protective Order Juliana Zajicek CSR TAK-RAMSTM-00236225 Produced in MDL on 09/18/12 Source: ACTOS FDA Response Strategy 1.0: INTRODUCTION Restate questions from FDA Raise feasibility issues - theoretical versus clinical questions Summarize assessment and action plan around each question Frame response as risk/benefit assessment of Actos clinical program (Frame broadly). 2.0: NONCLINICAL Key Messages: Pivotal studies conducted by Takeda followed GLPs versus anecdotally reported promoter model studies, which did not. Rat findings not duplicated in mouse, monkey, or dog. Therefore, the findings appear to be species specific and not relevant to humans (Rat studies - females had benign tumors only) Clinical and post-marketing data to date shows a very low incidence of bladder cancer and strengthens argument that rat findings are species specific. Supporting arguments Question source of pioglitazone used by Novo Nordisk Examine bladder concentrations in rodent studies 3.0: PPAR MECHANISM Key Points: Revalidate Sam Cohen's original hypothesis 1996, using 1999 EMEA argument for support Background on PPARs. Dual versus gamma versus alpha Structure Mechanism of action, in particular urinary tract tumorígenesis Promoter models Application of model to standard acceptable GLP models NN622 Compare/contrast structure of pioglitazone to NN622 Determine correlation between fibrates and bladder cancer (Section 6.0?) Determine correlation between PPAR-alpha agonists and bladder cancer (Section 6.0?) Argument will answer FDA's theoretical hypotheses with facts 4.0: CLINICAL Key Message: Epidemiological evaluations strongly indicate that there is no increased risk of bladder cancer associated with pioglitazone. Frequency of bladder cancer incidents in ACTOS trials is in line with the frequency observed in the general population. Monitoring is not possible because it in unreliable (not sensitive enough, many false positives). There may also be ethical and logistic issues. Supporting arguments Forms of monitoring done [US (011,031), EU, JP (OCT020)], investigate what worked/what didn't without invalidating what was done Additional assessments of data - Searching current clinical and post-marketing databases Last revision: August 7, 2002 Confidential - Subject to Protective Order TAK-RAMSTM-00236226 Produced in MDL on 09/18/12 Source: ts.ucsf.edu/docs/yljf0226

What findings are not duplicated in mouse, monkey, or dog?

yljf0226

yljf0226_p0, yljf0226_p1

Rat, Rat Findings

ACTOS FDA Response Strategy TASK FORCE -TPNA Alfonso Perez Janet Haskins* Mary Ramstack* Ingrid Hoos Michael Elisseou John Page (Rich Wilson) Claire Thom Dan Orlando David Baron (Chris Durack) Larry Hancock Karen Kaluzny Masatake Kashiyae Chuck Burant *Task Force Coordinators TASK FORCE STRATEGIES: The FDA has 3 key issues with respect to the non-clinical data related to bladder tumors, 1. They requested us to propose a method by which to monitor bladder toxicity in patients in our long term phase 4 clinical trials (long term was defined as at least 1 year). a, TPNA will challenge the FDA request to conduct clinical monitoring in long-term studies. 2. They requested us to give some consideration to a label change that would reflect possible relatedness of tumor formation to mechanism (dual PP AR agonist) instead of the current language ("The relationship of these findings in male rats to humans is unclear.") a. TPNA would like to challenge FDA hypothesis around tumor formation relationship to dual PPAR mechanism. b. TPNA goal is to supply justification to support maintaining current labeling. 3. They indicated an inclination to rescind the written request for pediatric exclusivity based on their concern about bladder tumors. a. Based on current verbiage in PI TPNA requests to conduct pediatric trial as scheduled. Last revision; August 7, 2002 EXHIBIT 2) WIT: Ramslude DATE: 10-1-13 Confidential - Subject to Protective Order Juliana Zajicek CSR TAK-RAMSTM-00236225 Produced in MDL on 09/18/12 Source: ACTOS FDA Response Strategy 1.0: INTRODUCTION Restate questions from FDA Raise feasibility issues - theoretical versus clinical questions Summarize assessment and action plan around each question Frame response as risk/benefit assessment of Actos clinical program (Frame broadly). 2.0: NONCLINICAL Key Messages: Pivotal studies conducted by Takeda followed GLPs versus anecdotally reported promoter model studies, which did not. Rat findings not duplicated in mouse, monkey, or dog. Therefore, the findings appear to be species specific and not relevant to humans (Rat studies - females had benign tumors only) Clinical and post-marketing data to date shows a very low incidence of bladder cancer and strengthens argument that rat findings are species specific. Supporting arguments Question source of pioglitazone used by Novo Nordisk Examine bladder concentrations in rodent studies 3.0: PPAR MECHANISM Key Points: Revalidate Sam Cohen's original hypothesis 1996, using 1999 EMEA argument for support Background on PPARs. Dual versus gamma versus alpha Structure Mechanism of action, in particular urinary tract tumorígenesis Promoter models Application of model to standard acceptable GLP models NN622 Compare/contrast structure of pioglitazone to NN622 Determine correlation between fibrates and bladder cancer (Section 6.0?) Determine correlation between PPAR-alpha agonists and bladder cancer (Section 6.0?) Argument will answer FDA's theoretical hypotheses with facts 4.0: CLINICAL Key Message: Epidemiological evaluations strongly indicate that there is no increased risk of bladder cancer associated with pioglitazone. Frequency of bladder cancer incidents in ACTOS trials is in line with the frequency observed in the general population. Monitoring is not possible because it in unreliable (not sensitive enough, many false positives). There may also be ethical and logistic issues. Supporting arguments Forms of monitoring done [US (011,031), EU, JP (OCT020)], investigate what worked/what didn't without invalidating what was done Additional assessments of data - Searching current clinical and post-marketing databases Last revision: August 7, 2002 Confidential - Subject to Protective Order TAK-RAMSTM-00236226 Produced in MDL on 09/18/12 Source: ts.ucsf.edu/docs/yljf0226

quantity of the product code 15102

szjf0226

szjf0226_p0, szjf0226_p1, szjf0226_p2, szjf0226_p3, szjf0226_p4, szjf0226_p5, szjf0226_p6, szjf0226_p7, szjf0226_p8, szjf0226_p9, szjf0226_p10, szjf0226_p11, szjf0226_p12

1

TRANSACTION PRODUCT_ C LOT_NUMBE DATE HCP_NAME ODE PRODUCT DESCRIPTION R QUANTITY REP_NAME LAMB, Corraini, 15-Aug-06 ANNA H 15102 ACTOS 15MG 6/7CT BLISTER/SLV C11705 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 15-Aug-06 ANNA H 15841 4/14CT BLSTR/SLV A11681 1 Jeff LAMB, Corraini, 15-Aug-06 ANNA H 45102 ACTOS 45MG 6/7CT BLISTER/SLV A11654 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Corraini, 15-Aug-06 ANNA H 15541 4/14CT BLSTR/SLV A11666 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 04-Aug-06 ANNA M 15541 4/14CT BLSTR/SLV A11677 2 Paul LAMB, Schlicht, 04-Aug-06 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C11794 4 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 04-Aug-06 ANNA M 15841 4/14CT BLSTR/SLV A11684 2 Paul LAMB, Schlicht, 04-Aug-06 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A11718 4 Paul LAMB, Schlicht, 04-Aug-06 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A11735 4 Paul LAMB, Schlicht, 22-Aug-06 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A11727 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 22-Aug-06 ANNA M 15541 4/14CT BLSTR/SLV A11677 1 Paul LAMB, Schlicht, 22-Aug-06 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A11777 1 Paul LAMB, Schlicht, 22-Aug-06 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C11791 1 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 22-Aug-06 ANNA M 15841 4/14CT BLSTR/SLV A11684 1 Paul LAMB, Corraini, 08-Sep-06 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A11727 2 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 08-Sep-06 ANNA M 15841 4/14CT BLSTR/SLV A11681 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Corraini, 08-Sep-06 ANNA M 15541 4/14CT BLSTR/SLV A11666 1 Jeff LAMB, Corraini, 08-Sep-06 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A11766 1 (Jeff LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 13-Sep-06 ANNA M 15541 4/14CT BLSTR/SLV A11578 1 Paul LAMB, Schlicht, 13-Sep-06 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A11777 1 Paul LAMB, Schlicht, 13-Sep-06 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A11727 1 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 13-Sep-06 ANNA M 15841 4/14CT BLSTR/SLV A11748 1 Paul LAMB, Schlicht, 13-Sep-06 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C11791 1 Paul EXHIBIT X 6 P7140-00001 bab PLA-TAK-00062729 Source: LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 13-Feb-07 ANNA M 15841 4/14CT BLSTR/SLV A12135 2 Paul LAMB, Schlicht, 13-Feb-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C11989 3 Paul LAMB, DUETACT 30MG/2MG 30CT Schlicht, 13-Feb-07 ANNA M 30233 SAMPLE BOTTLE A12259 3 Paul LAMB, Schlicht, 13-Feb-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C11939 3 Paul LAMB, Schlicht, 13-Feb-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12121 3 Paul LAMB, DUETACT 30MG/4MG 30CT Schlicht, 13-Feb-07 ANNA M 30433 SAMPLE BOTTLE A12283 3 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 13-Feb-07 ANNA M 15541 4/14CT BLSTR/SLV A11841 2 Paul LAMB, ACTOPLUSMET 15MG/500MG Corraini, 06-Mar-07 ANNA M 15541 4/14CT BLSTR/SLV A12358 1 Jeff LAMB, Corraini, 06-Mar-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12181 1 Jeff LAMB, Corraini, 06-Mar-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C11994 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 06-Mar-07 ANNA M 15841 4/14CT BLSTR/SLV A12375 1 Jeff LAMB, Corraini, 06-Mar-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12004 1 Jeff LAMB, Schlicht, 27-Mar-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C11985 1 Paul LAMB, Schlicht, 27-Mar-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A12183 1 Paul LAMB, DUETACT 30MG/4MG 30CT Schlicht, 27-Mar-07 ANNA M 30433 SAMPLE BOTTLE A12283 1 Paul LAMB, DUETACT 30MG/2MG 30CT Schlicht, 27-Mar-07 ANNA M 30233 SAMPLE BOTTLE A12255 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 27-Mar-07 ANNA M 15541 4/14CT BLSTR/SLV A12169 1 Paul LAMB, Schlicht, 27-Mar-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12251 1 Paul LAMB, Corraini, 03-Apr-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12181 1 Jeff LAMB, Corraini, 03-Apr-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12004 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Corraini, 03-Apr-07 ANNA M 15541 4/14CT BLSTR/SLV A12358 1 Jeff LAMB, Corraini, 03-Apr-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C11994 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 03-Apr-07 ANNA M 15841 4/14CT BLSTR/SLV A12498 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 11-Apr-07 ANNA M 15841 4/14CT BLSTR/SLV A12498 2 Paul P7140-00002 PLA-TAK-00062730 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Schlicht, 11-Apr-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12260 2 Paul LAMB, DUETACT 30MG/4MG 30CT Schlicht, 11-Apr-07 ANNA M 30433 SAMPLE BOTTLE A12627 2 Paul LAMB, DUETACT 30MG/2MG 30CT Schlicht, 11-Apr-07 ANNA M 30233 SAMPLE BOTTLE A12255 2 Paul LAMB, Schlicht, 11-Apr-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12792 2 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 11-Apr-07 ANNA M 15541 4/14CT BLSTR/SLV A12353 2 Paul LAMB, Schlicht, 11-Apr-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12441 2 Paul LAMB, Corraini, 17-Apr-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A12183 1 Jeff LAMB, Corraini, 17-Apr-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12251 1 Jeff LAMB, Corraini, 17-Apr-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12004 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 17-Apr-07 ANNA M 15841 4/14CT BLSTR/SLV A12498 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Corraini, 17-Apr-07 ANNA M 15541 4/14CT BLSTR/SLV A12476 1 Jeff LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 24-Apr-07 ANNA M 15541 4/14CT BLSTR/SLV A12358 1 Paul LAMB, Schlicht, 24-Apr-07 ANNA M 30102 ACTOS 30MG6/7CT BLISTER/SLV C12792 2 Paul LAMB, Schlicht, 24-Apr-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12260 2 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 24-Apr-07 ANNA M 15841 4/14CT BLSTR/SLV A12368 1 Paul LAMB, Schlicht, 24-Apr-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12559 2 Paul LAMB, ACTOPLUSMET 15MG/500MG Corraini, 03-May-07 ANNA M 15541 4/14CT BLSTR/SLV A12476 1 Jeff LAMB, Corraini, 03-May-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12622 1 Jeff LAMB, Corraini, 03-May-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12559 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 03-May-07 ANNA M 15841 4/14CT BLSTR/SLV A11750 1 Jeff LAMB, Corraini, 03-May-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12251 1 Jeff LAMB, DUETACT 30MG/2MG 30CT Schlicht, 08-May-07 ANNA M 30233 SAMPLE BOTTLE A12255 1 Paul LAMB, DUETACT 30MG/4MG 4/7CT Schlicht, 08-May-07 ANNA M 30447 BOTTLE/SLV A12789 1 Paul LAMB, DUETACT 30MG/4MG 30CT Schlicht, 08-May-07 ANNA M 30433 SAMPLE BOTTLE A12627 1 Paul P7140-00003 PLA-TAK-00062731 Source: :ttps://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, DUETACT 30MG/2MG 4/7CT Schlicht, 08-May-07 ANNA M 30247 BOTTLE/SLV A12781 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 08-May-07 ANNA M 15541 4/14CT BLSTR/SLV A12358 1 Paul LAMB, Schlicht, 08-May-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12792 1 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 08-May-07 ANNA M 15841 4/14CT BLSTR/SLV A12498 1 Paul LAMB, Schlicht, 08-May-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12559 1 Paul LAMB, Schlicht, 08-May-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12251 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Corraini, 14-May-07 ANNA M 15541 4/14CT BLSTR/SLV A12358 1 Jeff LAMB, Corraini, 14-May-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12264 1 Jeff LAMB, ACTOPLUSMET 15MG/850MG Corraini, 14-May-07 ANNA M 15841 4/14CT BLSTR/SLV A12375 1 Jeff LAMB, Corraini, 14-May-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12559 1 Jeff LAMB, Corraini, 14-May-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C12622 1 Jeff LAMB, Schlicht, 25-May-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A12659 2 Paul LAMB, Schlicht, 25-May-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12885 2 Paul LAMB, Schlicht, 25-May-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12533 2 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 25-May-07 ANNA M 15841 4/14CT BLSTR/SLV A12585 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 25-May-07 ANNA M 15541 4/14CT BLSTR/SLV A12476 1 Paul LAMB, DUETACT 30MG/2MG 4/7CT Schlicht, 25-May-07 ANNA M 30247 BOTTLE/SLV A12781 1 Paul LAMB, DUETACT 30MG/4MG 30CT Schlicht, 25-May-07 ANNA M 30433 SAMPLE BOTTLE A12283 1 Paul LAMB, DUETACT 30MG/4MG 4/7CT Schlicht, 25-May-07 ANNA M 30447 BOTTLE/SLV A12789 1 Paul LAMB, DUETACT 30MG/2MG 30CT Schlicht, 25-May-07 ANNA M 30233 SAMPLE BOTTLE A12255 1 Paul LAMB, Schlicht, 06-Jul-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A12884 2 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 06-Jul-07 ANNA M 15541 4/14CT BLSTR/SLV A12576 2 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 17-Aug-07 ANNA M 15841 4/14CT BLSTR/SLV A12714 2 Paul LAMB, Schlicht, 17-Aug-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12799 3 Paul P7140-00004 PLA-TAK-00062732 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 17-Aug-07 ANNA M 15541 4/14CT BLSTR/SLV A12750 2 Paul LAMB, Schlicht, 17-Aug-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A12933 3 Paul LAMB, Schlicht, 17-Aug-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13081 3 Paul LAMB, Schlicht, 04-Sep-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C13149 2 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 04-Sep-07 ANNA M 15841 4/14CT BLSTR/SLV A12862 1 Paul LAMB, Schlicht, 04-Sep-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13079 2 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 04-Sep-07 ANNA M 15541 4/14CT BLSTR/SLV A12750 1 Paul LAMB, Schlicht, 04-Sep-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12948 2 Paul LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 05-Sep-07 ANNA M 30447 BOTTLE/SLV A12791 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 05-Sep-07 ANNA M 30247 BOTTLE/SLV A13048 1 Michael LAMB, Yacos, 24-Sep-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12948 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 24-Sep-07 ANNA M 15841 4/14CT BLSTR/SLV A12868 1 Michael LAMB, Yacos, 24-Sep-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13079 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 24-Sep-07 ANNA M 15541 4/14CT BLSTR/SLV A12764 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 24-Sep-07 ANNA M 30247 BOTTLE/SLV A13048 1 Michael LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 24-Sep-07 ANNA M 30447 BOTTLE/SLV A13052 1 Michael LAMB, Yacos, 24-Sep-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13081 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 12-Oct-07 ANNA M 15541 4/14CT BLSTR/SLV A12843 1 Paul LAMB, Schlicht, 12-Oct-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13079 2 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 12-Oct-07 ANNA M 15841 4/14CT BLSTR/SLV A12971 1 Paul LAMB, Schlicht, 12-Oct-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13238 2 Paul LAMB, Schlicht, 12-Oct-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C12914 2 Paul LAMB, Davis, 30-Oct-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13094 1 Patrick LAMB, Davis, 30-Oct-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13186 1 Patrick P7140-00005 PLA-TAK-00062733 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Davis, 30-Oct-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13486 1 Patrick LAMB, Yacos, 19-Nov-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13186 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 19-Nov-07 ANNA M 15841 4/14CT BLSTR/SLV A12871 1 Michael LAMB, Yacos, 19-Nov-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C13465 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 19-Nov-07 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Michael LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 19-Nov-07 ANNA M 30447 BOTTLE/SLV A13052 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 19-Nov-07 ANNA M 30247 BOTTLE/SLV A13048 1 Michael LAMB, Yacos, 19-Nov-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A12948 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Davis, 26-Nov-07 ANNA M 15841 4/14CT BLSTR/SLV A12871 1 Patrick LAMB, Davis, 26-Nov-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13462 1 Patrick LAMB, ACTOPLUSMET 15MG/500MG Davis, 26-Nov-07 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Patrick LAMB, DUETACT 30MG/4MG 4/7CT Davis, 26-Nov-07 ANNA M 30447 BOTTLE/SLV A13052 1 Patrick LAMB, Davis, 26-Nov-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13194 1 Patrick LAMB, DUETACT 30MG/2MG 4/7CT Davis, 26-Nov-07 ANNA M 30247 BOTTLE/SLV A13048 1 Patrick LAMB, Davis, 26-Nov-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13602 1 Patrick LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 04-Dec-07 ANNA M 15841 4/14CT BLSTR/SLV A12871 1 Paul LAMB, Schlicht, 04-Dec-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13487 1 Paul LAMB, Schlicht, 04-Dec-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13186 1 Paul LAMB, Schlicht, 04-Dec-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C13059 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 04-Dec-07 ANNA M 15541 4/14CT BLSTR/SLV A12843 1 Paul LAMB, Davis, 11-Dec-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13462 1 Patrick LAMB, ACTOPLUSMET 15MG/850MG Davis, 11-Dec-07 ANNA M 15841 4/14CT BLSTR/SLV A12871 1 Patrick LAMB, Davis, 11-Dec-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13194 1 Patrick LAMB, ACTOPLUSMET 15MG/500MG Davis, 11-Dec-07 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Patrick P7140-00006 PLA-TAK-00062734 Source: :ttps://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Davis, 11-Dec-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13602 1 Patrick LAMB, Yacos, 17-Dec-07 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13094 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 17-Dec-07 ANNA M 15841 4/14CT BLSTR/SLV A13107 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 17-Dec-07 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Michael LAMB, Yacos, 17-Dec-07 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13186 1 Michael LAMB, Yacos, 17-Dec-07 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C13569 1 Michael LAMB, Davis, 09-Jan-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13462 1 Patrick LAMB, ACTOPLUSMET 15MG/500MG Davis, 09-Jan-08 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Patrick LAMB, ACTOPLUSMET 15MG/850MG Davis, 09-Jan-08 ANNA M 15841 4/14CT BLSTR/SLV A12871 1 Patrick LAMB, Davis, 09-Jan-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13194 1 Patrick LAMB, Davis, 22-Jan-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13715 1 Patrick LAMB, Davis, 22-Jan-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C13465 1 Patrick LAMB, Yacos, 23-Jan-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13581 1 Michael LAMB, Yacos, 23-Jan-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13737 1 Michael LAMB, Schlicht, 29-Jan-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13727 1 Paul LAMB, Schlicht, 29-Jan-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13581 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 29-Jan-08 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 29-Jan-08 ANNA M 15841 4/14CT BLSTR/SLV A13221 1 Paul LAMB, Davis, 06-Feb-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13727 1 Patrick LAMB, Davis, 06-Feb-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13718 1 Patrick LAMB, Yacos, 11-Feb-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13665 2 Michael LAMB, Yacos, 11-Feb-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13737 2 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 11-Feb-08 ANNA M 15841 4/14CT BLSTR/SLV A13112 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 11-Feb-08 ANNA M 15541 4/14CT BLSTR/SLV A13202 1 Michael P7140-00007 PLA-TAK-00062735 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Yacos, 20-Feb-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13665 1 Michael LAMB, Yacos, 20-Feb-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13737 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 10-Mar-08 ANNA M 15841 4/14CT BLSTR/SLV A13111 1 Michael LAMB, Yacos, 10-Mar-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C13831 1 Michael LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 10-Mar-08 ANNA M 30447 BOTTLE/SLV A13053 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 10-Mar-08 ANNA M 30247 BOTTLE/SLV A13048 1 Michael LAMB, Yacos, 10-Mar-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13665 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 10-Mar-08 ANNA M 15541 4/14CT BLSTR/SLV A13202 1 Michael LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 19-Mar-08 ANNA M 30447 BOTTLE/SLV A13053 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 19-Mar-08 ANNA M 30247 BOTTLE/SLV A13050 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 19-Mar-08 ANNA M 15541 4/14CT BLSTR/SLV A13209 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 19-Mar-08 ANNA M 15841 4/14CT BLSTR/SLV A13111 1 Michael LAMB, Davis, 19-Mar-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13829 1 Patrick LAMB, Davis, 19-Mar-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13850 1 Patrick LAMB, DUETACT 30MG/4MG 4/7CT Schlicht, 25-Mar-08 ANNA M 30447 BOTTLE/SLV A12791 1 Paul LAMB, DUETACT 30MG/2MG 4/7CT Schlicht, 25-Mar-08 ANNA M 30247 BOTTLE/SLV A12781 1 Paul LAMB, ACTOPLUSMET 15MG/850MG Schlicht, 25-Mar-08 ANNA M 15841 4/14CT BLSTR/SLV A12971 1 Paul LAMB, Schlicht, 25-Mar-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13945 1 Paul LAMB, ACTOPLUSMET 15MG/500MG Schlicht, 25-Mar-08 ANNA M 15541 4/14CT BLSTR/SLV A12898 1 Paul LAMB, Schlicht, 25-Mar-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14045 1 Paul LAMB, DUETACT 30MG/4MG 4/7CT Yacos, 15-Apr-08 ANNA M 30447 BOTTLE/SLV A13052 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 15-Apr-08 ANNA M 15841 4/14CT BLSTR/SLV A13985 1 Michael LAMB, Yacos, 15-Apr-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A13945 1 Michael LAMB, Yacos, 15-Apr-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A14060 1 Michael P7140-00008 PLA-TAK-00062736 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, ACTOPLUSMET 15MG/500MG Yacos, 15-Apr-08 ANNA M 15541 4/14CT BLSTR/SLV A13209 1 Michael LAMB, Yacos, 15-Apr-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13850 1 Michael LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 15-Apr-08 ANNA M 30247 BOTTLE/SLV A13050 1 Michael LAMB, Kupczyk, 30-Apr-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C13599 1 Jenny LAMB, Kupczyk, 30-Apr-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A13850 1 Jenny LAMB, ACTOPLUSMET 15MG/500MG Kupczyk, 30-Apr-08 ANNA M 15541 4/14CT BLSTR/SLV A14071 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Kupczyk, 30-Apr-08 ANNA M 15841 4/14CT BLSTR/SLV A14105 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Yacos, 06-May-08 ANNA M 15841 4/14CT BLSTR/SLV A13985 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 06-May-08 ANNA M 15541 4/14CT BLSTR/SLV A14040 1 Michael LAMB, Yacos, 06-May-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A14060 1 Michael LAMB, Yacos, 06-May-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14042 1 Michael LAMB, Yacos, 06-May-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14045 1 Michael LAMB, ACTOPLUSMET 15MG/850MG 13-May-08 ANNA M 15841 4/14CT BLSTR/SLV A13987 1 Chen, Gigi LAMB, 13-May-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14045 1 Chen, Gigi LAMB, 13-May-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14042 1 Chen, Gigi LAMB, DUETACT 30MG/2MG 4/7CT 13-May-08 ANNA M 30247 BOTTLE/SLV A13475 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/500MG 13-May-08 ANNA M 15541 4/14CT BLSTR/SLV A14071 1 Chen, Gigi LAMB, DUETACT 30MG/4MG4/7CT 13-May-08 ANNA M 30447 BOTTLE/SLV A13482 1 Chen, Gigi LAMB, Kupczyk, 10-Jun-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14130 1 Jenny LAMB, Kupczyk, 10-Jun-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13680 1 Jenny LAMB, ACTOPLUSMET 15MG/500MG Kupczyk, 10-Jun-08 ANNA M 15541 4/14CT BLSTR/SLV A14122 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Kupczyk, 10-Jun-08 ANNA M 15841 4/14CT BLSTR/SLV A14113 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Yacos, 17-Jun-08 ANNA M 15841 4/14CT BLSTR/SLV A14105 1 Michael LAMB, Yacos, 17-Jun-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14042 1 Michael P7140-00009 PLA-TAK-00062737 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, ACTOPLUSMET 15MG/500MG Yacos, 17-Jun-08 ANNA M 15541 4/14CT BLSTR/SLV A14040 1 Michael LAMB, Yacos, 17-Jun-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A14061 1 Michael LAMB, Yacos, 17-Jun-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14130 1 Michael LAMB, 24-Jun-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14222 2 Chen, Gigi LAMB, 24-Jun-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14218 1 Chen, Gigi LAMB, Yacos, 30-Jun-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C13680 1 Michael LAMB, Yacos, 30-Jun-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14130 1 Michael LAMB, Yacos, 30-Jun-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13794 1 Michael LAMB, 15-Jul-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14236 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/850MG 15-Jul-08 ANNA M 15841 4/14CT BLSTR/SLV A13220 1 Chen, Gigi LAMB, Kupczyk, 15-Jul-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13794 1 Jenny LAMB, 15-Jul-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14222 1 Chen, Gigi LAMB, 15-Jul-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13794 1 Chen, Gigi LAMB, Kupczyk, 15-Jul-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14236 1 Jenny LAMB, Kupczyk, 15-Jul-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14222 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Kupczyk, 15-Jul-08 ANNA M 15841 4/14CT BLSTR/SLV A14108 1 Jenny LAMB, ACTOPLUSMET 15MG/500MG Kupczyk, 15-Jul-08 ANNA M 15541 4/14CT BLSTR/SLV A14283 1 Jenny LAMB, ACTOPLUSMET 15MG/850MG Yacos, 29-Jul-08 ANNA M 15841 4/14CT BLSTR/SLV A13220 1 Michael LAMB, Yacos, 29-Jul-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14222 1 Michael LAMB, Kupczyk, 12-Aug-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14223 2 Jenny LAMB, ACTOPLUSMET 15MG/850MG Kupczyk, 12-Aug-08 ANNA M 15841 4/14CT BLSTR/SLV A14294 1 Jenny LAMB, Kupczyk, 12-Aug-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13794 1 Jenny LAMB, Kupczyk, 12-Aug-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14236 1 Jenny LAMB, Yacos, 20-Aug-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A13794 1 Michael P7140-00010 PLA-TAK-00062738 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Yacos, 03-Oct-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A14187 1 Michael LAMB, Yacos, 03-Oct-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14236 2 Michael LAMB, Yacos, 03-Oct-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14223 2 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 03-Oct-08 ANNA M 15841 4/14CT BLSTR/SLV A14294 1 Michael LAMB, Kupczyk, 14-Oct-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14445 2 Jenny LAMB, ACTOPLUSMET 15MG/500MG Kupczyk, 14-Oct-08 ANNA M 15541 4/14CT BLSTR/SLV A14612 2 Jenny LAMB, ACTOPLUSMET 15MG/850MG Kupczyk, 14-Oct-08 ANNA M 15841 4/14CT BLSTR/SLV A14497 2 Jenny LAMB, Kupczyk, 14-Oct-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14424 2 Jenny LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 22-Oct-08 ANNA M 30202 BLISTER/SLV A14475 1 Michael LAMB, ACTOPLUSMET 15MG/500MG 28-Oct-08 ANNA M 15541 4/14CT BLSTR/SLV A14612 1 Chen, Gigi LAMB, 28-Oct-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C14542 1 Chen, Gigi LAMB, 19-Nov-08 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C14542 1 Chen, Gigi LAMB, 19-Nov-08 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14533 1 Chen, Gigi LAMB, 19-Nov-08 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A14654 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/500MG 20-Jan-09 ANNA M 15541 4/14CT BLSTR/SLV A14671 1 Chen, Gigi LAMB, 20-Jan-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14525 1 Chen, Gigi LAMB, Kupczyk, 27-Jan-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A14633 1 Jenny LAMB, Kupczyk, 27-Jan-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C14718 1 Jenny LAMB, Kupczyk, 16-Feb-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C14716 1 Jenny LAMB, Kupczyk, 16-Feb-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A14750 1 Jenny LAMB, Kupczyk, 16-Feb-09 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C14896 1 Jenny LAMB, 24-Mar-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C14716 1 Chen, Gigi LAMB, 24-Mar-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C15041 1 Chen, Gigi LAMB, DUETACT 30MG/2MG 4/7CT Yacos, 19-May-09 ANNA M 30202 BLISTER/SLV A14475 1 Michael P7140-00011 PLA-TAK-00062739 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, Yacos, 19-May-09 ANNA M 30102 ACTOS 30MG6/7CT BLISTER/SLV A15238 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 19-May-09 ANNA M 15541 4/14CT BLSTR/SLV A15178 1 Michael LAMB, Yacos, 19-May-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15230 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 19-May-09 ANNA M 15841 4/14CT BLSTR/SLV A14811 1 Michael LAMB, 08-Sep-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15389 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/850MG 08-Sep-09 ANNA M 15841 4/14CT BLSTR/SLV A15449 1 Chen, Gigi LAMB, 08-Sep-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A15387 1 Chen, Gigi LAMB, Yacos, 17-Sep-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15502 1 Michael LAMB, Yacos, 17-Sep-09 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV A15423 1 Michael LAMB, Yacos, 17-Sep-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C15375 1 Michael LAMB, ACTOPLUSMET 15MG/500MG 29-Sep-09 ANNA M 15541 4/14CT BLSTR/SLV A15585 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/850MG 29-Sep-09 ANNA M 15841 4/14CT BLSTR/SLV A15450 1 Chen, Gigi LAMB, 29-Sep-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15757 1 Chen, Gigi LAMB, 29-Sep-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C15511 1 Chen, Gigi LAMB, 20-Oct-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15757 1 Chen, Gigi LAMB, 20-Oct-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C15511 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/500MG 20-Oct-09 ANNA M 15541 4/14CT BLSTR/SLV A15587 1 Chen, Gigi LAMB, ACTOPLUSMET 15MG/500MG Yacos, 18-Nov-09 ANNA M 15541 4/14CT BLSTR/SLV A15588 1 Michael LAMB, Yacos, 18-Nov-09 ANNA M 45102 ACTOS 45MG 6/7CT BLISTER/SLV C15884 1 Michael LAMB, Yacos, 08-Dec-09 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15864 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 08-Dec-09 ANNA M 15541 4/14CT BLSTR/SLV A15588 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 08-Dec-09 ANNA M 15841 4/14CT BLSTR/SLV A15640 1 Michael LAMB, Yacos, 08-Dec-09 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15747 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 09-Feb-10 ANNA M 15541 4/14CT BLSTR/SLV A15589 1 Michael P7140-00012 PLA-TAK-00062740 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226 LAMB, ACTOPLUSMET 15MG/850MG Yacos, 09-Feb-10 ANNA M 15841 4/14CT BLSTR/SLV A15640 1 Michael LAMB, Yacos, 09-Feb-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15747 1 Michael LAMB, Yacos, 09-Feb-10 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A15835 1 Michael LAMB, Yacos, 02-Mar-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15747 1 Michael LAMB, Yacos, 02-Mar-10 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A15835 1 Michael LAMB, 09-Mar-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15971 1 Chen, Gigi LAMB, Yacos, 23-Mar-10 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A15834 1 Michael LAMB, ACTOPLUSMET 15MG/500MG Yacos, 23-Mar-10 ANNA M 15541 4/14CT BLSTR/SLV A16001 1 Michael LAMB, ACTOPLUSMET 15MG/850MG Yacos, 23-Mar-10 ANNA M 15841 4/14CT BLSTR/SLV A16052 1 Michael LAMB, Yacos, 23-Mar-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV C16035 1 Michael LAMB, Yacos, 28-Apr-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15974 1 Michael LAMB, Yacos, 28-Apr-10 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C15873 1 Michael LAMB, ACTOPLUS MET XR Ritzenthaler 18-Aug-10 ANNA M 31007 30MG/1000MG 7 CT BLISTER A16539 4 Jason LAMB, ACTOPLUS MET XR Ritzenthaler 18-Aug-10 ANNA M 51007 15MG/1000MG 7CT BLISTER A16534 4 Jason LAMB, Ritzenthaler 14-Sep-10 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV C16157 1 Jason LAMB, Ritzenthaler 14-Sep-10 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A15388 1 Jason , LAMB, ACTOPLUSMET 15MG/500MG Ritzenthaler 27-Apr-11 ANNA M 15541 4/14CT BLSTR/SLV A17159 1 Jason LAMB, Ritzenthaler 27-Apr-11 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A17271 2 Jason LAMB, ACTOPLUSMET 15MG/850MG Ritzenthaler 27-Apr-11 ANNA M 15841 4/14CT BLSTR/SLV A17093 1 Jason LAMB, Ritzenthaler 27-Apr-11 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A17276 2 Jason LAMB, ACTOPLUSMET 15MG/500MG Ritzenthaler 23-May-11 ANNA M 15541 4/14CT BLSTR/SLV A17159 1 Jason LAMB, 22-Aug-11 ANNA M 30102 ACTOS 30MG 6/7CT BLISTER/SLV A17549 2 Palka, Jenna LAMB, 22-Aug-11 ANNA M 15102 ACTOS 15MG 6/7CT BLISTER/SLV A17569 2 Palka, Jenna P7140-00013 PLA-TAK-00062741 Source: https://www.industrydocuments.ucsf.edu/docs/szjf0226

what are the greatest sources of caffeine?

hjpj0226

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coffee, tea and chocolate, coffee, tea and chocolate.

CAFFEINE Caffeine is an integral part of the flavor of the soft drinks in which it is found. In some cola drinks, small amounts of caffeine occur naturally as a part of the kola nut itself. A small amount of caffeine is also added to some soft drinks because it introduces a bitter element which balances the sweetness of other flavorings to create a distinctive, refreshing taste. Overall, soft drinks contain relatively small amounts of caffeine. Pepsi-Cola, for example, contains 19.2 milligrams (mg) of caffeine in a six-ounce serving. By comparison, an average-strength cup of coffee has about 108 mg of caffeine, while six ounces of average-strength tea contains 54 mg of caffeine. After reviewing caffeine consumption in America, experts acting on behalf of the Food and Drug Administration concluded that soft drinks add little to the total consumption of caffeine in the average diet. Caffeine and Health People have been consuming caffeine since the first tea leaf was brewed about 2700 B.C. It is found in coffee beans, cocoa beans (from which chocolate is produced), tea leaves, kola nuts and other plant materials. Caffeine is a known mild stimulant. In large enough amounts, it will increase muscular agility and endurance, and reduce fatigue. Because of its ability to decrease fatigue, it is an ingredient in many common pain relief and cold medications. On the other hand, too much caffeine can sometimes cause insomnia or irritability. These effects do not last long because our bodies rapidly process and eliminate caffeine. Caffeine and Birth Defects There had been some concern that caffeine consumption was related to birth defects; to date, however, studies of human populations have indicated that there is no relationship between caffeine and birth defects or other reproductive problems. Studies of rats, mice and rabbits show that at very high doses caffeine can cause birth defects in offspring of these species. However, the amount of caffeine fed to each animal in these studies was the equivalent of a person drinking about sixty cups of coffee daily; below these levels, no reproductive or birth defects were observed. In the past decade or so, there have been eight studies of the effects of caffeine on human reproduction. Researchers compared the caffeine consumption of mothers with healthy babies and mothers of children with birth defects. These studies found no relationship between caffeine consumption and the existence of birth defects. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 CAFFEINE -- 2 The greatest sources of caffeine are coffee, tea and chocolate. Soft drinks add little to the average total intake. In 1978, the Federation of American Societies for Experimental Biology reported to the FDA that most adults who drank soft drinks actually consumed four to thirteen times more caffeine from other sources while children received two to four times more caffeine from other sources. For consumers who prefer no caffeine in their diets, Pepsi-Cola produces a number of caffeine-free soft drinks. For Additional Information: American Council on Science and Health. The Health Effects of Caffeine. Summit, NJ, 1983 Jan. Dews, P.B. "Caffeine." Annual Review of Nutrition 1982. 2:323-341. Linn, S., et al. "No association between coffee consumption and adverse outcomes of pregnancy. New England Journal of Medicine 1982. 306(3):141-145. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 Phosphoric acid, which is 31.6% phosphorus by weight, is used in some Pepsi-Cola products for two reasons. It contributes a citric note--a refreshing tart taste--t the soda. And it also acts as a buffer, i.e. it controls acidity and holds the beverages' pH at a steady level. Phosphorus is a necessary dietary component; it is essential to the life of every living cell. Without it, our bodies cannot utilize calcium properly. Excessive phosphorus intake causes our bodies to get rid of calcium too rapidly. The only possible concern about the amount of phosphorus consumed is whether an excess may upset the calcium/phosphorus balance. Since soft drinks normally contain only trace amounts of calcium, the calcium/phosphorus balance does not meet the 1:1 ratio thought to be optimal. However, total dietary intake of calcium and phosphorus is the only relevant consideration. It is estimated that soft drinks provide only two to three percent of the total phosphorus in the human diet. Pepsi-Cola soft drinks contain small amounts of phosphorus. Brand Pepsi-Cola, for example, has only 27.6 milligrams (mg) per six-ounce serving while Pepsi Light contains 13.2 mg. Recommended Daily Allowances (RDA) for phosphorus have been established by the Food and Nutrition Board, National Academy of Sciences and National Research Council. For individuals one year of age or older, the RDA ranges between 800 - 1200 mg per day. Pregnant and nursing women need an additional 400 mg above the daily requirement. Therefore, when soft drinks are consumed as part of a well balanced diet, there should be no concern about the relatively small amount of phosphorus they contain. Phosphorus is an essential component of our diet and the amount in soft drinks will not affect the total dietary ratio of calcium and phosphorus. Additional Information: Greger, J.L., Krystofiak, M. "Phosphorus intake of Americans.' Food Technology 1982. 36 (1) ):78-84. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, D.C., 1980. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 FOOD COLORING As the National Academy of Sciences (NAS) has stated, "The appearance of a food is important in determining its acceptability. The primary purpose of food colorings is to restore the natural color of foods which may be lost through cooking, canning, transportation, storage, or other processes. " The major food colorings used in Pepsi-Cola soft drinks are tartrazine, approved by the Food and Drug Administration as FD&C Yellow #5, and caramel. Caramel Caramel is added to Pepsi-Cola drinks for several reasons. First, of course, it adds the caramel color people expect in a cola. In addition, it preserves the cola from harmful effects of sunlight because its darker color is an effective light barrier. Caramel also improves taste, and acts as an emulsifier to distribute flavorings evenly throughout the bottle or can. Caramel color is made from corn starch and is a source of nitrogen and sulphur. It is labeled "artificial coloring" because any added color, whether natural or not, must be so labeled. Tartrazine (Yellow Dye #5) Tartrazine is used in Mountain Dew. It was approved by the Food and Drug Administration (FDA) in 1916, and has been permanently listed as safe since 1969. Permanent listing required tests for safety and effectiveness that were increasingly more strict and conducted according to modern testing standards. Testing and Safety of Food Coloring The history of food coloring use is also a history of testing and retesting, as scientific understanding of how to test for safety has grown with time. The Bureau of Chemistry, the FDA's predecessor, first investigated the safety of colors in the early 1900's and established an informal list of approved colors. In 1938, more stringent standards for purity and safety were applied, and manufacturers began sending samples from each batch of food coloring for purity and identity certification. In 1960, standards for safety testing were updated. Scientists began to establish limits for safe consumption of food colorings. Today, tartrazine has been approved as safe for human consumption up to 3.4 mg per pound of body weight. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 FOOD COLORING -- 2 Food Coloring and Health Recently, questions have been raised about the relationship of all food additives to hyperactivity (hyperkinesis) in children. The National Institute for Health, the American Council on Science and Health, and the Nutrition Foundation reviewed studies in which hyperactive children were placed on additive-free diets. The children showed no substantial behavioral change when food coloring was removed from their diets. It would appear that there is no proven relationship between food coloring and hyperkinesis. A minor, but real, health effect of Yellow Dye #5 is a mild hypersensitivity experienced by a small group of individuals sensitive to this substance. Food and drinks containing tartrazine are so labeled. Pepsi-Cola Company began voluntarily listing Yellow #5 on its labels well before the FDA required it to alert those with this sensitivity to its presence in Mountain Dew. Artificial Versus Natural Coloring It is a federal labeling requirement that any ingredient used to color a food product--whether derived from a natural source or synthetically produced--is to be declared an "artificial color." Therefore, "artificial color" only fulfills federal labeling requirements and has no bearing on whether it is a natural or artificial substance. For Additional Information: Committee on Food Protection, Food and Nutrition Board, Division of Biology and Agriculture, National Research Council. Food Colors. National Academy of Sciences, Washington, DC 1971. Source: :https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SODIUM The amount of sodium contained in Pepsi-Cola soft drinks is very small, and contributes little to the total sodium in the average American diet. The Food and Drug Administration has adopted regulations requiring that sodium content be included in nutrition labeling on diet products. Under these regulations, most diet soft drinks are classified as "low sodium" -containing less than 140 milligrams (mg) per serving, or "very low sodium"--less than 35 mg of sodium per six ounce serving. All Pepsi-Cola's diet soft drinks are low or very low sodium and are labeled as such. Pepsi-Cola's regular soft drinks, which are not subject to the sodium labeling requirements, are also low, or very low sodium products. Sodium in Pepsi-Cola beverages may come from various sources: sodium chloride (salt), sodium benzoate, sodium phosphate or sodium citrate, which are used in some of the beverage concentrates; juices and caramel can also be minor sources of sodium. Since almost all water contains small amounts of sodium chloride, the local water supply is also a source of sodium. Sodium content varies by location and season. And since water is added to beverage concentrate at the local bottling plant, the amount of sodium in Pepsi-Cola soft drinks will also vary from city to city. Nevertheless, the total amount of sodium from soft drinks will still be five percent or less of the sodium in the average diet. How Much Salt Should We Have? The average person consumes 10 to 12 grams of salt daily. This amount represents approximately 3900 to 4700 mg of sodium, as salt is 39% sodium by weight. With the average person consuming two six-ounce servings of a soft drink daily, the contribution from Pepsi products to total sodium consumed would be 120 mg or less. The estimated safe and adequate level of dietary intake for sodium has been set at between 600 to 1800 mg for children 7 to 10 years of age and 1100 to 3300 mg for adults. This is equivalent to a safe and adequate daily intake of 2.8 - 8.4 grams of salt for adults. How much is too much? This is a hotly debated question. When reports first indicated a link between sodium and high blood pressure, many experts said the less salt the better. Since then, scientists have questioned the presumed cause-effect relationship between salt and high blood pressure. There are certain groups of people who are "salt-sensitive": persons who are already hytpertensive, and others whose sodium balance is easily upset. For these individuals, sodium does appear to have a direct relatonship with high blood pressure and they should consult their doctor about a sodium-restricted diet. PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 SODIUM -- 2 Today, we have new information indicating that a lack of certain nutrients -- calcium, potassium, vitamin A and vitamin C -- may have a stronger relationship to high blood pressure than previously realized. These findings come from an examination of the data provided by the government's HANES I (Health and Nutrition Examination Survey I) study, performed by the National Center for Health Statistics. Researchers also found that people who consume the highest amounts of calcium, potassium and sodium were at the lowest risk for high blood pressure. Since Pepsi-Cola products provide such a minor amount of sodium compared to most other sources in the diet, they can be enjoyed for the great refreshment value they provide. For Additional Information: "The Sodium Content of Your Food" Home and Garden Bulletin Number 233 Science & Education Administration Information Staff U.S. Department of Agriculture Room 6007 - South Buildiing Washington, DC 20250 Council on Scientific Affairs. "Sodium in processed foods.' Journal of the American Medical Association 1983. 249(6) : 784. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, DC 1980. Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SWEETENERS Sweeteners perform a primary role of making foods taste good; they provide major appeal and flavor gratification. A preference for sweetness may help us to distinguish between wholesome and harmful foods. Children have the greatest sugar craving, and least enjoy tart, sour or bitter flavors. Sweeteners fall into two categories: sugars, which provide calories and are used in regular soft drinks like Pepsi-Cola itself; and alternative sweeteners, which have few or no calories, and are used in diet soft drinks like Diet Pepsi. Sweeteners in Soft Drinks Sweetness is an essential part of the flavor profile of soft drinks. Four major sweeteners are used in soft drinks. Of the sugars, sucrose and high fructose corn sweetener are found in regular soft drinks. These are called nutritive sweeteners because they contain calories and therefore provide energy. Like sucrose, which most of us know as common table sugar, high fructose corn sweetener (HFCS), is made up of two simple sugars, fructose and glucose. As its name suggests, it is derived from corn. Sucrose and HFCS are not the same substance; however, their tastes are nearly identical, and they function about the same in soft drinks. The sweetening agents in diet soft drinks are aspartame (NutraSweetR * brand) and saccharin. Saccharin is an artificial sweetener, and has no calories. Aspartame is made of ingredients similar to those found in nature, and it does have calories. However, it is so intensely sweet that only a tiny amount is needed, and it adds less than one calorie to a six ounce serving of soft drink. Today, Pepsi-Cola uses a variety of sweeteners in its beverages. We primarily use high fructose corn syrup in our regular soft drinks, and aspartame in our bottled and canned diet products. Our fountain service diet products contain a blend of NutraSweetR and saccharin. NutraSweet is a registered trademark of G.D.Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SUGAR Sucrose, which most of us know as table sugar, is made up of two simple sugars, fructose and glucose. It is derived from sugar cane and sugar beets. Sugars are simple carbohydrates which perform a necessary role in the body. They are starter fuels, providing energy and helping the body do its work. Carbohydrates are one of the three macro-nutrients the body needs to function effectively; the other two are proteins and fats. Complex carbohydrates such as grains, cereals and pasta are ultimately broken down in the body to glucose and other simple sugars. Sugar and Health Questions have arisen from time to time about the usefulness of sugar as a food substance. Today, experts basically agree that in moderation, sugar is pleasurable, and not harmful. However, a balanced diet is the key -- too much sugar in place of other important nutrients does not constitute a healthful eating program. Some people have questioned whether sugar contributes to a clinical condition of hyperactivity, known as hyperkinesis, in children. Studies have shown fairly conclusively that the presence or absence of sugar does not have a bearing upon hyperkinetic behavior. Sugar and Cavities Sugar can create conditions in the mouth which lead to tooth decay. That is, sugar acidifies saliva, and this creates an environment in which cavity-causing bacteria can grow. However, studies have shown that the time of day in which a sugar is consumed, the form of the sugar (is it hard, sticky?), and the individual's oral hygiene practices are factors which are important in the development of dental cavities. Soft drinks contain sugars in solution, so that the sugar passes quickly through the mouth indicating a lower risk for cavity development if the individual has good oral hygiene practices. For Additional Information: Bierman, E.L., et al. "Carbohydrates, sucrose, and human disease." American Journal of Clinical Nutrition 1979. 32:2712-2722 "Consensus on diets and hyperactivity. Science 1982 Feb. 215(4535) : 958. Sugars and Nutritive Sweeteners in Processed Foods. Food Technology 1979 May. 33(5): 101-105. Life Sciences Research Office, Federation of American Societies for Experimental Biology. Evaluation of the Health Aspects of Sucrose as a Food Ingredient. 1976 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS ASPARTAME Aspartame is the sweetener Pepsi-Cola uses in its diet bottled and canned soft drinks. The brand name for aspartame is NutraSweet * (which is why our Tabels say "sweetened with 100 percent NutraSweet"). Aspartame is made up of two amino acids, aspartic acid and the methyl ester of phenylalanine. These amino acids are components of protein, and they are plentiful in our diets because all protein foods contain them--meat, fish, dairy products, and some fruits and vegetables. They are also present in our blood plasma and in our tissues. Aspartame has a clean, sweet flavor. Alone, neither aspartic acid nor phenylalanine is sweet, but together in the form of aspartame they provide a taste closer to sugar than any other diet sweetener. In fact, taste tests with some foods demonstrated that people could not tell whether their samples had been sweetened with sugar or aspartame. Aspartame is a nutritive sweetener, that is, it does have calories. However, it is so intensely sweet--200 times sweeter than sugar--that very little provides the same sweetness as a teaspoon of sugar. A six-ounce serving of soft drink sweetened with aspartame contains less than one calorie. Aspartame and Health Aspartame underwent a decade of extensive testing before the Food and Drug Administration approved it for use in certain foods and as a table-top sweetener in 1981. The FDA extended its approval to include use in soft drinks in 1983. The FDA noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption by both adults and children. Health questions raised during the testing of aspartame focused on whether or not we could get too much aspartic acid and phenylalanine from soft drinks, and whether there was a risk if aspartame broke down during extended periods of storage or at high temperatures. To the first question, the FDA responded that it is "inconceivable" that anyone could consume too much of either amino acid by drinking aspartame-sweetened soft drinks. In response to the second question, while some methanol would indeed be formed if aspartame broke down, that amount would not be harmful. A six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. Small amounts of methanol are present in our bodies normally, with dietary sources such as fresh fruits and vegetables being only partial contributors to the total amount of methanol in our bodies. * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 ASPARTAME -- 2 Since the FDA approved aspartame for use in soft drinks, government agencies have continued to study the sweetener, and have found no link between it and any serious health effects. Over time, and in extremely warm temperatures, aspartame may begin to lose its sweetness; this will not affect the product's safety. We do, however, suggest that consumers store beverages in a cool place out of direct sunlight. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks you take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. For Additional Information: Consumer Affairs Food and Drug Administration 5600 Fishers Lane Room #16-63 Rockville, MD 20857 (202) 443-3170 NutraSweet Consumer Center P. 0. Box 1111 Skokie, IL 60076 1-800-842-9000 Consumer Information National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS QUESTIONS AND ANSWERS ON ASPARTAME Q: What is aspartame? A: Aspartame is a nutritive substance made of protein components (amino acids) similar to those found in many foods in the average diet such as milk or meats. It is a sweetening ingredient that has the taste of sugar without the calories and is metabolized by the body just like protein. Aspartame is manufactured and sold by the G.D. Searle Company (Skokie, Illinois) under the brand name NutraSweetR. In addition to its use in soft drinks, aspartame is used in a wide variety of other foods. Q: Is aspartame safe? A: The U.S. Food and Drug Administration has determined that aspartame is completely safe. In fact, it is one of the most thoroughly tested substances ever approved for use in foods by the FDA. After considering more than 100 scientific tests and studies, the FDA approved aspartame in 1981 for use as a table top sweetener (under the brand name Equal) and in certain dry foods. In 1983, the FDA approved aspartame for use in carbonated beverages. Independent scientists in the World Health Organization have also determined aspartame to be suitable for use in food. This worldwide endorsement has resulted in the approval of aspartame in more than 40 countries. The FDA has noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption. Q. How many calories are there in aspartame? A teaspoon of sugar contains 16 calories. It takes only one tenth of a calorie of aspartame to equal the sweetness of a teaspoon of sugar. That is because aspartame is approximately 200 times sweeter than sugar. So a 12-ounce can of Diet Pepsi sweetened with aspartame contains less than one calorie per serving. Q: Is it true that aspartame breaks down in soft drinks? A: Over time, and in extremely warm temperatures, aspartame does break down. This will not affect the product's safety, as the by-products of this process have not been found to be harmful. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks consumers take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. Q: Methanol is a by-product of the breakdown of aspartame. Is it dangerous to humans? A: The amount of methanol that would be formed from the break down of aspartame would not be harmful. In fact, a six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 QUESTIONS AND ANSWERS ON ASPARTAME -- 2 Q: What is phenylketonuria (PKU)? A: Approximately one out of every 15,000 infants is born with a rare genetic deficiency that results in the inability to metabolize an amino acid called phenylalanine. This amino acid, which is present in aspartame, is found in many foods in the normal diet such as milk and meats. (An eight-ounce glass of milk has more than 50 times as much phenylalanine as a 12-ounce Diet Pepsi.) All products sweetened with aspartame carry a statement on the label to alert those individuals who must restrict their intake of phenylalanine. Q. Is there anyone else who should avoid intake of aspartame, such as pregnant women or diabetics? A: On the basis of scientific studies, the FDA concluded that aspartame did not present a health risk to pregnant women. However, every pregnant woman should ask her physician for recommendations about diet during pregnancy. Aspartame is not a carbohydrate; clinical studies have shown that it is well tolerated by both insulin-dependent and noninsulin-dependent diabetics. The American Diabetes Association has found aspartame acceptable as a sweetener for products that may be included in diabetic meal plans. Check with your dietitian or doctor for specific recommendations. Q: Is there any scientific evidence that aspartame consumption causes adverse behavior in some individuals? A: All of the current data suggest there is no scientific evidence that aspartame ingestion has any relationship with behavior in individuals. Q: What about reports that use of aspartame may affect blood pressure? A: The FDA has concluded that there is no scientific data to substantiate the claim that aspartame has any effect on blood pressure. Q: Does aspartame contribute to dental decay? A: Aspartame does not promote tooth decay; it is an amino acid-based rather than a carbohydrate-based sweetener. A study conducted by the National Institute of Dental Research showed that NutraSweetR was not associated with the formation of cavities in animals. Q: Are there any guidelines concerning the amount of aspartame an individual may consume? A: Aspartame has undergone rigorous studies with respect to consumption. The FDA has determined the allowable daily intake to be 22.7 mg per pound of body weight, or 3,405 mg for a 150 1b. individual. With 14.75 mg of aspartame per fluid ounce of Diet Pepsi (177 mg in a 12 OZ can), an individual consuming aspartame through soda only would have to drink 19 12 oz. cans of Diet Pepsi to reach the limit set by the FDA. There are no demonstrated effects of aspartame ingestion in persons who do not have phenylketonuria. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS HIGH FRUCTOSE CORN SYRUP High fructose corn syrup (HFCS) is found in most regular soft drinks, including Pepsi-Cola products. It is a nutritive sweetener that contains approximately 80 calories per 6 ounce serving and therefore provides energy. HFCS, like table sugar (sucrose), is made up primarily of two simple sugars, fructose and dextrose. A key difference between HFCS and sucrose is their respective sources. While HFCS is made from corn, sucrose is derived from sugar cane or sugar beets. HFCS is produced by a new technology that enhances the amount of fructose in the final product and is not to be confused with corn syrup, which is mostly glucose. HFCS is produced with varying amounts of fructose depending on its intended food purpose. The HFCS used in soft drinks contains 55% to 57% fructose; in this form, it is generally perceived as slightly sweeter than sugar. Why use HFCS instead of sugar? For two good reasons : availability and economics. While our sugar supply comes from both foreign and domestic sources, HFCS is produced from corn, which is grown in abundance in this country. Government-imposed quotas have created high domestic sugar prices while causing volatility in world supply. HFCS is not subject to such government quotas and is a high quality product that is competitively priced. Using HFCS helps keep the price of our products stable for our customers. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Corn Refiners Association Inc. 10001 Connecticut Ave. N.W. Suite 1022 Washington, DC 20036 (202) 331-1634 77 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj022 SWEETENERS SACCHARIN Before the introduction of aspartame, saccharin was the primary sugar substitute for people who could not have sugar or who wished to restrict calories. Approximately three hundred times sweeter than sucrose, saccharin has been used in a wide variety of foods and beverages, and as a table-top sweetener for almost one hundred years. Until very recently, Pepsi-Cola sweetened its diet soft drinks with saccharin. When aspartame was approved for use in beverages in 1983, we began using a saccharin/aspartame blend. However, ingredient-identifier taste tests showed us that people preferred aspartame alone over the blend by nearly two to one. In response to consumer preference, Pepsi-Cola has begun sweetening its diet bottled and canned soft drinks with 100% NutraSweet R Saccharin and Health Today, saccharin-containing products have a government-mandated warning statement on the label. This warning statement is related to concerns over studies that have shown saccharin to cause bladder cancer in male rats when given in extremely high doses for very long periods of time. However, no adverse health effects have been found with people who use saccharin, and Congress has enacted legislation preventing the FDA from banning saccharin while further studies are being conducted. The fact that saccharin has been consumed by humans for nearly one hundred years without any apparent adverse effects supports its safety for human beings. Pepsi-Cola has switched from saccharin to aspartame solely for reasons of consumer preference. We remain convinced of saccharin's safety, and continue to use it in blends with aspartame in our fountain syrup diet products. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

In which year did American Council on Science and Health , published "the health effects of caffeine"?

hjpj0226

hjpj0226_p4, hjpj0226_p5, hjpj0226_p6, hjpj0226_p7, hjpj0226_p8, hjpj0226_p9, hjpj0226_p10, hjpj0226_p11, hjpj0226_p12, hjpj0226_p13, hjpj0226_p14, hjpj0226_p15, hjpj0226_p16, hjpj0226_p17, hjpj0226_p18

1983

CAFFEINE Caffeine is an integral part of the flavor of the soft drinks in which it is found. In some cola drinks, small amounts of caffeine occur naturally as a part of the kola nut itself. A small amount of caffeine is also added to some soft drinks because it introduces a bitter element which balances the sweetness of other flavorings to create a distinctive, refreshing taste. Overall, soft drinks contain relatively small amounts of caffeine. Pepsi-Cola, for example, contains 19.2 milligrams (mg) of caffeine in a six-ounce serving. By comparison, an average-strength cup of coffee has about 108 mg of caffeine, while six ounces of average-strength tea contains 54 mg of caffeine. After reviewing caffeine consumption in America, experts acting on behalf of the Food and Drug Administration concluded that soft drinks add little to the total consumption of caffeine in the average diet. Caffeine and Health People have been consuming caffeine since the first tea leaf was brewed about 2700 B.C. It is found in coffee beans, cocoa beans (from which chocolate is produced), tea leaves, kola nuts and other plant materials. Caffeine is a known mild stimulant. In large enough amounts, it will increase muscular agility and endurance, and reduce fatigue. Because of its ability to decrease fatigue, it is an ingredient in many common pain relief and cold medications. On the other hand, too much caffeine can sometimes cause insomnia or irritability. These effects do not last long because our bodies rapidly process and eliminate caffeine. Caffeine and Birth Defects There had been some concern that caffeine consumption was related to birth defects; to date, however, studies of human populations have indicated that there is no relationship between caffeine and birth defects or other reproductive problems. Studies of rats, mice and rabbits show that at very high doses caffeine can cause birth defects in offspring of these species. However, the amount of caffeine fed to each animal in these studies was the equivalent of a person drinking about sixty cups of coffee daily; below these levels, no reproductive or birth defects were observed. In the past decade or so, there have been eight studies of the effects of caffeine on human reproduction. Researchers compared the caffeine consumption of mothers with healthy babies and mothers of children with birth defects. These studies found no relationship between caffeine consumption and the existence of birth defects. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 CAFFEINE -- 2 The greatest sources of caffeine are coffee, tea and chocolate. Soft drinks add little to the average total intake. In 1978, the Federation of American Societies for Experimental Biology reported to the FDA that most adults who drank soft drinks actually consumed four to thirteen times more caffeine from other sources while children received two to four times more caffeine from other sources. For consumers who prefer no caffeine in their diets, Pepsi-Cola produces a number of caffeine-free soft drinks. For Additional Information: American Council on Science and Health. The Health Effects of Caffeine. Summit, NJ, 1983 Jan. Dews, P.B. "Caffeine." Annual Review of Nutrition 1982. 2:323-341. Linn, S., et al. "No association between coffee consumption and adverse outcomes of pregnancy. New England Journal of Medicine 1982. 306(3):141-145. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 Phosphoric acid, which is 31.6% phosphorus by weight, is used in some Pepsi-Cola products for two reasons. It contributes a citric note--a refreshing tart taste--t the soda. And it also acts as a buffer, i.e. it controls acidity and holds the beverages' pH at a steady level. Phosphorus is a necessary dietary component; it is essential to the life of every living cell. Without it, our bodies cannot utilize calcium properly. Excessive phosphorus intake causes our bodies to get rid of calcium too rapidly. The only possible concern about the amount of phosphorus consumed is whether an excess may upset the calcium/phosphorus balance. Since soft drinks normally contain only trace amounts of calcium, the calcium/phosphorus balance does not meet the 1:1 ratio thought to be optimal. However, total dietary intake of calcium and phosphorus is the only relevant consideration. It is estimated that soft drinks provide only two to three percent of the total phosphorus in the human diet. Pepsi-Cola soft drinks contain small amounts of phosphorus. Brand Pepsi-Cola, for example, has only 27.6 milligrams (mg) per six-ounce serving while Pepsi Light contains 13.2 mg. Recommended Daily Allowances (RDA) for phosphorus have been established by the Food and Nutrition Board, National Academy of Sciences and National Research Council. For individuals one year of age or older, the RDA ranges between 800 - 1200 mg per day. Pregnant and nursing women need an additional 400 mg above the daily requirement. Therefore, when soft drinks are consumed as part of a well balanced diet, there should be no concern about the relatively small amount of phosphorus they contain. Phosphorus is an essential component of our diet and the amount in soft drinks will not affect the total dietary ratio of calcium and phosphorus. Additional Information: Greger, J.L., Krystofiak, M. "Phosphorus intake of Americans.' Food Technology 1982. 36 (1) ):78-84. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, D.C., 1980. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 FOOD COLORING As the National Academy of Sciences (NAS) has stated, "The appearance of a food is important in determining its acceptability. The primary purpose of food colorings is to restore the natural color of foods which may be lost through cooking, canning, transportation, storage, or other processes. " The major food colorings used in Pepsi-Cola soft drinks are tartrazine, approved by the Food and Drug Administration as FD&C Yellow #5, and caramel. Caramel Caramel is added to Pepsi-Cola drinks for several reasons. First, of course, it adds the caramel color people expect in a cola. In addition, it preserves the cola from harmful effects of sunlight because its darker color is an effective light barrier. Caramel also improves taste, and acts as an emulsifier to distribute flavorings evenly throughout the bottle or can. Caramel color is made from corn starch and is a source of nitrogen and sulphur. It is labeled "artificial coloring" because any added color, whether natural or not, must be so labeled. Tartrazine (Yellow Dye #5) Tartrazine is used in Mountain Dew. It was approved by the Food and Drug Administration (FDA) in 1916, and has been permanently listed as safe since 1969. Permanent listing required tests for safety and effectiveness that were increasingly more strict and conducted according to modern testing standards. Testing and Safety of Food Coloring The history of food coloring use is also a history of testing and retesting, as scientific understanding of how to test for safety has grown with time. The Bureau of Chemistry, the FDA's predecessor, first investigated the safety of colors in the early 1900's and established an informal list of approved colors. In 1938, more stringent standards for purity and safety were applied, and manufacturers began sending samples from each batch of food coloring for purity and identity certification. In 1960, standards for safety testing were updated. Scientists began to establish limits for safe consumption of food colorings. Today, tartrazine has been approved as safe for human consumption up to 3.4 mg per pound of body weight. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 FOOD COLORING -- 2 Food Coloring and Health Recently, questions have been raised about the relationship of all food additives to hyperactivity (hyperkinesis) in children. The National Institute for Health, the American Council on Science and Health, and the Nutrition Foundation reviewed studies in which hyperactive children were placed on additive-free diets. The children showed no substantial behavioral change when food coloring was removed from their diets. It would appear that there is no proven relationship between food coloring and hyperkinesis. A minor, but real, health effect of Yellow Dye #5 is a mild hypersensitivity experienced by a small group of individuals sensitive to this substance. Food and drinks containing tartrazine are so labeled. Pepsi-Cola Company began voluntarily listing Yellow #5 on its labels well before the FDA required it to alert those with this sensitivity to its presence in Mountain Dew. Artificial Versus Natural Coloring It is a federal labeling requirement that any ingredient used to color a food product--whether derived from a natural source or synthetically produced--is to be declared an "artificial color." Therefore, "artificial color" only fulfills federal labeling requirements and has no bearing on whether it is a natural or artificial substance. For Additional Information: Committee on Food Protection, Food and Nutrition Board, Division of Biology and Agriculture, National Research Council. Food Colors. National Academy of Sciences, Washington, DC 1971. Source: :https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SODIUM The amount of sodium contained in Pepsi-Cola soft drinks is very small, and contributes little to the total sodium in the average American diet. The Food and Drug Administration has adopted regulations requiring that sodium content be included in nutrition labeling on diet products. Under these regulations, most diet soft drinks are classified as "low sodium" -containing less than 140 milligrams (mg) per serving, or "very low sodium"--less than 35 mg of sodium per six ounce serving. All Pepsi-Cola's diet soft drinks are low or very low sodium and are labeled as such. Pepsi-Cola's regular soft drinks, which are not subject to the sodium labeling requirements, are also low, or very low sodium products. Sodium in Pepsi-Cola beverages may come from various sources: sodium chloride (salt), sodium benzoate, sodium phosphate or sodium citrate, which are used in some of the beverage concentrates; juices and caramel can also be minor sources of sodium. Since almost all water contains small amounts of sodium chloride, the local water supply is also a source of sodium. Sodium content varies by location and season. And since water is added to beverage concentrate at the local bottling plant, the amount of sodium in Pepsi-Cola soft drinks will also vary from city to city. Nevertheless, the total amount of sodium from soft drinks will still be five percent or less of the sodium in the average diet. How Much Salt Should We Have? The average person consumes 10 to 12 grams of salt daily. This amount represents approximately 3900 to 4700 mg of sodium, as salt is 39% sodium by weight. With the average person consuming two six-ounce servings of a soft drink daily, the contribution from Pepsi products to total sodium consumed would be 120 mg or less. The estimated safe and adequate level of dietary intake for sodium has been set at between 600 to 1800 mg for children 7 to 10 years of age and 1100 to 3300 mg for adults. This is equivalent to a safe and adequate daily intake of 2.8 - 8.4 grams of salt for adults. How much is too much? This is a hotly debated question. When reports first indicated a link between sodium and high blood pressure, many experts said the less salt the better. Since then, scientists have questioned the presumed cause-effect relationship between salt and high blood pressure. There are certain groups of people who are "salt-sensitive": persons who are already hytpertensive, and others whose sodium balance is easily upset. For these individuals, sodium does appear to have a direct relatonship with high blood pressure and they should consult their doctor about a sodium-restricted diet. PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 SODIUM -- 2 Today, we have new information indicating that a lack of certain nutrients -- calcium, potassium, vitamin A and vitamin C -- may have a stronger relationship to high blood pressure than previously realized. These findings come from an examination of the data provided by the government's HANES I (Health and Nutrition Examination Survey I) study, performed by the National Center for Health Statistics. Researchers also found that people who consume the highest amounts of calcium, potassium and sodium were at the lowest risk for high blood pressure. Since Pepsi-Cola products provide such a minor amount of sodium compared to most other sources in the diet, they can be enjoyed for the great refreshment value they provide. For Additional Information: "The Sodium Content of Your Food" Home and Garden Bulletin Number 233 Science & Education Administration Information Staff U.S. Department of Agriculture Room 6007 - South Buildiing Washington, DC 20250 Council on Scientific Affairs. "Sodium in processed foods.' Journal of the American Medical Association 1983. 249(6) : 784. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, DC 1980. Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SWEETENERS Sweeteners perform a primary role of making foods taste good; they provide major appeal and flavor gratification. A preference for sweetness may help us to distinguish between wholesome and harmful foods. Children have the greatest sugar craving, and least enjoy tart, sour or bitter flavors. Sweeteners fall into two categories: sugars, which provide calories and are used in regular soft drinks like Pepsi-Cola itself; and alternative sweeteners, which have few or no calories, and are used in diet soft drinks like Diet Pepsi. Sweeteners in Soft Drinks Sweetness is an essential part of the flavor profile of soft drinks. Four major sweeteners are used in soft drinks. Of the sugars, sucrose and high fructose corn sweetener are found in regular soft drinks. These are called nutritive sweeteners because they contain calories and therefore provide energy. Like sucrose, which most of us know as common table sugar, high fructose corn sweetener (HFCS), is made up of two simple sugars, fructose and glucose. As its name suggests, it is derived from corn. Sucrose and HFCS are not the same substance; however, their tastes are nearly identical, and they function about the same in soft drinks. The sweetening agents in diet soft drinks are aspartame (NutraSweetR * brand) and saccharin. Saccharin is an artificial sweetener, and has no calories. Aspartame is made of ingredients similar to those found in nature, and it does have calories. However, it is so intensely sweet that only a tiny amount is needed, and it adds less than one calorie to a six ounce serving of soft drink. Today, Pepsi-Cola uses a variety of sweeteners in its beverages. We primarily use high fructose corn syrup in our regular soft drinks, and aspartame in our bottled and canned diet products. Our fountain service diet products contain a blend of NutraSweetR and saccharin. NutraSweet is a registered trademark of G.D.Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SUGAR Sucrose, which most of us know as table sugar, is made up of two simple sugars, fructose and glucose. It is derived from sugar cane and sugar beets. Sugars are simple carbohydrates which perform a necessary role in the body. They are starter fuels, providing energy and helping the body do its work. Carbohydrates are one of the three macro-nutrients the body needs to function effectively; the other two are proteins and fats. Complex carbohydrates such as grains, cereals and pasta are ultimately broken down in the body to glucose and other simple sugars. Sugar and Health Questions have arisen from time to time about the usefulness of sugar as a food substance. Today, experts basically agree that in moderation, sugar is pleasurable, and not harmful. However, a balanced diet is the key -- too much sugar in place of other important nutrients does not constitute a healthful eating program. Some people have questioned whether sugar contributes to a clinical condition of hyperactivity, known as hyperkinesis, in children. Studies have shown fairly conclusively that the presence or absence of sugar does not have a bearing upon hyperkinetic behavior. Sugar and Cavities Sugar can create conditions in the mouth which lead to tooth decay. That is, sugar acidifies saliva, and this creates an environment in which cavity-causing bacteria can grow. However, studies have shown that the time of day in which a sugar is consumed, the form of the sugar (is it hard, sticky?), and the individual's oral hygiene practices are factors which are important in the development of dental cavities. Soft drinks contain sugars in solution, so that the sugar passes quickly through the mouth indicating a lower risk for cavity development if the individual has good oral hygiene practices. For Additional Information: Bierman, E.L., et al. "Carbohydrates, sucrose, and human disease." American Journal of Clinical Nutrition 1979. 32:2712-2722 "Consensus on diets and hyperactivity. Science 1982 Feb. 215(4535) : 958. Sugars and Nutritive Sweeteners in Processed Foods. Food Technology 1979 May. 33(5): 101-105. Life Sciences Research Office, Federation of American Societies for Experimental Biology. Evaluation of the Health Aspects of Sucrose as a Food Ingredient. 1976 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS ASPARTAME Aspartame is the sweetener Pepsi-Cola uses in its diet bottled and canned soft drinks. The brand name for aspartame is NutraSweet * (which is why our Tabels say "sweetened with 100 percent NutraSweet"). Aspartame is made up of two amino acids, aspartic acid and the methyl ester of phenylalanine. These amino acids are components of protein, and they are plentiful in our diets because all protein foods contain them--meat, fish, dairy products, and some fruits and vegetables. They are also present in our blood plasma and in our tissues. Aspartame has a clean, sweet flavor. Alone, neither aspartic acid nor phenylalanine is sweet, but together in the form of aspartame they provide a taste closer to sugar than any other diet sweetener. In fact, taste tests with some foods demonstrated that people could not tell whether their samples had been sweetened with sugar or aspartame. Aspartame is a nutritive sweetener, that is, it does have calories. However, it is so intensely sweet--200 times sweeter than sugar--that very little provides the same sweetness as a teaspoon of sugar. A six-ounce serving of soft drink sweetened with aspartame contains less than one calorie. Aspartame and Health Aspartame underwent a decade of extensive testing before the Food and Drug Administration approved it for use in certain foods and as a table-top sweetener in 1981. The FDA extended its approval to include use in soft drinks in 1983. The FDA noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption by both adults and children. Health questions raised during the testing of aspartame focused on whether or not we could get too much aspartic acid and phenylalanine from soft drinks, and whether there was a risk if aspartame broke down during extended periods of storage or at high temperatures. To the first question, the FDA responded that it is "inconceivable" that anyone could consume too much of either amino acid by drinking aspartame-sweetened soft drinks. In response to the second question, while some methanol would indeed be formed if aspartame broke down, that amount would not be harmful. A six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. Small amounts of methanol are present in our bodies normally, with dietary sources such as fresh fruits and vegetables being only partial contributors to the total amount of methanol in our bodies. * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 ASPARTAME -- 2 Since the FDA approved aspartame for use in soft drinks, government agencies have continued to study the sweetener, and have found no link between it and any serious health effects. Over time, and in extremely warm temperatures, aspartame may begin to lose its sweetness; this will not affect the product's safety. We do, however, suggest that consumers store beverages in a cool place out of direct sunlight. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks you take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. For Additional Information: Consumer Affairs Food and Drug Administration 5600 Fishers Lane Room #16-63 Rockville, MD 20857 (202) 443-3170 NutraSweet Consumer Center P. 0. Box 1111 Skokie, IL 60076 1-800-842-9000 Consumer Information National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS QUESTIONS AND ANSWERS ON ASPARTAME Q: What is aspartame? A: Aspartame is a nutritive substance made of protein components (amino acids) similar to those found in many foods in the average diet such as milk or meats. It is a sweetening ingredient that has the taste of sugar without the calories and is metabolized by the body just like protein. Aspartame is manufactured and sold by the G.D. Searle Company (Skokie, Illinois) under the brand name NutraSweetR. In addition to its use in soft drinks, aspartame is used in a wide variety of other foods. Q: Is aspartame safe? A: The U.S. Food and Drug Administration has determined that aspartame is completely safe. In fact, it is one of the most thoroughly tested substances ever approved for use in foods by the FDA. After considering more than 100 scientific tests and studies, the FDA approved aspartame in 1981 for use as a table top sweetener (under the brand name Equal) and in certain dry foods. In 1983, the FDA approved aspartame for use in carbonated beverages. Independent scientists in the World Health Organization have also determined aspartame to be suitable for use in food. This worldwide endorsement has resulted in the approval of aspartame in more than 40 countries. The FDA has noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption. Q. How many calories are there in aspartame? A teaspoon of sugar contains 16 calories. It takes only one tenth of a calorie of aspartame to equal the sweetness of a teaspoon of sugar. That is because aspartame is approximately 200 times sweeter than sugar. So a 12-ounce can of Diet Pepsi sweetened with aspartame contains less than one calorie per serving. Q: Is it true that aspartame breaks down in soft drinks? A: Over time, and in extremely warm temperatures, aspartame does break down. This will not affect the product's safety, as the by-products of this process have not been found to be harmful. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks consumers take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. Q: Methanol is a by-product of the breakdown of aspartame. Is it dangerous to humans? A: The amount of methanol that would be formed from the break down of aspartame would not be harmful. In fact, a six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 QUESTIONS AND ANSWERS ON ASPARTAME -- 2 Q: What is phenylketonuria (PKU)? A: Approximately one out of every 15,000 infants is born with a rare genetic deficiency that results in the inability to metabolize an amino acid called phenylalanine. This amino acid, which is present in aspartame, is found in many foods in the normal diet such as milk and meats. (An eight-ounce glass of milk has more than 50 times as much phenylalanine as a 12-ounce Diet Pepsi.) All products sweetened with aspartame carry a statement on the label to alert those individuals who must restrict their intake of phenylalanine. Q. Is there anyone else who should avoid intake of aspartame, such as pregnant women or diabetics? A: On the basis of scientific studies, the FDA concluded that aspartame did not present a health risk to pregnant women. However, every pregnant woman should ask her physician for recommendations about diet during pregnancy. Aspartame is not a carbohydrate; clinical studies have shown that it is well tolerated by both insulin-dependent and noninsulin-dependent diabetics. The American Diabetes Association has found aspartame acceptable as a sweetener for products that may be included in diabetic meal plans. Check with your dietitian or doctor for specific recommendations. Q: Is there any scientific evidence that aspartame consumption causes adverse behavior in some individuals? A: All of the current data suggest there is no scientific evidence that aspartame ingestion has any relationship with behavior in individuals. Q: What about reports that use of aspartame may affect blood pressure? A: The FDA has concluded that there is no scientific data to substantiate the claim that aspartame has any effect on blood pressure. Q: Does aspartame contribute to dental decay? A: Aspartame does not promote tooth decay; it is an amino acid-based rather than a carbohydrate-based sweetener. A study conducted by the National Institute of Dental Research showed that NutraSweetR was not associated with the formation of cavities in animals. Q: Are there any guidelines concerning the amount of aspartame an individual may consume? A: Aspartame has undergone rigorous studies with respect to consumption. The FDA has determined the allowable daily intake to be 22.7 mg per pound of body weight, or 3,405 mg for a 150 1b. individual. With 14.75 mg of aspartame per fluid ounce of Diet Pepsi (177 mg in a 12 OZ can), an individual consuming aspartame through soda only would have to drink 19 12 oz. cans of Diet Pepsi to reach the limit set by the FDA. There are no demonstrated effects of aspartame ingestion in persons who do not have phenylketonuria. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS HIGH FRUCTOSE CORN SYRUP High fructose corn syrup (HFCS) is found in most regular soft drinks, including Pepsi-Cola products. It is a nutritive sweetener that contains approximately 80 calories per 6 ounce serving and therefore provides energy. HFCS, like table sugar (sucrose), is made up primarily of two simple sugars, fructose and dextrose. A key difference between HFCS and sucrose is their respective sources. While HFCS is made from corn, sucrose is derived from sugar cane or sugar beets. HFCS is produced by a new technology that enhances the amount of fructose in the final product and is not to be confused with corn syrup, which is mostly glucose. HFCS is produced with varying amounts of fructose depending on its intended food purpose. The HFCS used in soft drinks contains 55% to 57% fructose; in this form, it is generally perceived as slightly sweeter than sugar. Why use HFCS instead of sugar? For two good reasons : availability and economics. While our sugar supply comes from both foreign and domestic sources, HFCS is produced from corn, which is grown in abundance in this country. Government-imposed quotas have created high domestic sugar prices while causing volatility in world supply. HFCS is not subject to such government quotas and is a high quality product that is competitively priced. Using HFCS helps keep the price of our products stable for our customers. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Corn Refiners Association Inc. 10001 Connecticut Ave. N.W. Suite 1022 Washington, DC 20036 (202) 331-1634 77 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj022 SWEETENERS SACCHARIN Before the introduction of aspartame, saccharin was the primary sugar substitute for people who could not have sugar or who wished to restrict calories. Approximately three hundred times sweeter than sucrose, saccharin has been used in a wide variety of foods and beverages, and as a table-top sweetener for almost one hundred years. Until very recently, Pepsi-Cola sweetened its diet soft drinks with saccharin. When aspartame was approved for use in beverages in 1983, we began using a saccharin/aspartame blend. However, ingredient-identifier taste tests showed us that people preferred aspartame alone over the blend by nearly two to one. In response to consumer preference, Pepsi-Cola has begun sweetening its diet bottled and canned soft drinks with 100% NutraSweet R Saccharin and Health Today, saccharin-containing products have a government-mandated warning statement on the label. This warning statement is related to concerns over studies that have shown saccharin to cause bladder cancer in male rats when given in extremely high doses for very long periods of time. However, no adverse health effects have been found with people who use saccharin, and Congress has enacted legislation preventing the FDA from banning saccharin while further studies are being conducted. The fact that saccharin has been consumed by humans for nearly one hundred years without any apparent adverse effects supports its safety for human beings. Pepsi-Cola has switched from saccharin to aspartame solely for reasons of consumer preference. We remain convinced of saccharin's safety, and continue to use it in blends with aspartame in our fountain syrup diet products. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

What add little to the average total intake of caffeine?

hjpj0226

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soft drinks

CAFFEINE Caffeine is an integral part of the flavor of the soft drinks in which it is found. In some cola drinks, small amounts of caffeine occur naturally as a part of the kola nut itself. A small amount of caffeine is also added to some soft drinks because it introduces a bitter element which balances the sweetness of other flavorings to create a distinctive, refreshing taste. Overall, soft drinks contain relatively small amounts of caffeine. Pepsi-Cola, for example, contains 19.2 milligrams (mg) of caffeine in a six-ounce serving. By comparison, an average-strength cup of coffee has about 108 mg of caffeine, while six ounces of average-strength tea contains 54 mg of caffeine. After reviewing caffeine consumption in America, experts acting on behalf of the Food and Drug Administration concluded that soft drinks add little to the total consumption of caffeine in the average diet. Caffeine and Health People have been consuming caffeine since the first tea leaf was brewed about 2700 B.C. It is found in coffee beans, cocoa beans (from which chocolate is produced), tea leaves, kola nuts and other plant materials. Caffeine is a known mild stimulant. In large enough amounts, it will increase muscular agility and endurance, and reduce fatigue. Because of its ability to decrease fatigue, it is an ingredient in many common pain relief and cold medications. On the other hand, too much caffeine can sometimes cause insomnia or irritability. These effects do not last long because our bodies rapidly process and eliminate caffeine. Caffeine and Birth Defects There had been some concern that caffeine consumption was related to birth defects; to date, however, studies of human populations have indicated that there is no relationship between caffeine and birth defects or other reproductive problems. Studies of rats, mice and rabbits show that at very high doses caffeine can cause birth defects in offspring of these species. However, the amount of caffeine fed to each animal in these studies was the equivalent of a person drinking about sixty cups of coffee daily; below these levels, no reproductive or birth defects were observed. In the past decade or so, there have been eight studies of the effects of caffeine on human reproduction. Researchers compared the caffeine consumption of mothers with healthy babies and mothers of children with birth defects. These studies found no relationship between caffeine consumption and the existence of birth defects. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 CAFFEINE -- 2 The greatest sources of caffeine are coffee, tea and chocolate. Soft drinks add little to the average total intake. In 1978, the Federation of American Societies for Experimental Biology reported to the FDA that most adults who drank soft drinks actually consumed four to thirteen times more caffeine from other sources while children received two to four times more caffeine from other sources. For consumers who prefer no caffeine in their diets, Pepsi-Cola produces a number of caffeine-free soft drinks. For Additional Information: American Council on Science and Health. The Health Effects of Caffeine. Summit, NJ, 1983 Jan. Dews, P.B. "Caffeine." Annual Review of Nutrition 1982. 2:323-341. Linn, S., et al. "No association between coffee consumption and adverse outcomes of pregnancy. New England Journal of Medicine 1982. 306(3):141-145. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 Phosphoric acid, which is 31.6% phosphorus by weight, is used in some Pepsi-Cola products for two reasons. It contributes a citric note--a refreshing tart taste--t the soda. And it also acts as a buffer, i.e. it controls acidity and holds the beverages' pH at a steady level. Phosphorus is a necessary dietary component; it is essential to the life of every living cell. Without it, our bodies cannot utilize calcium properly. Excessive phosphorus intake causes our bodies to get rid of calcium too rapidly. The only possible concern about the amount of phosphorus consumed is whether an excess may upset the calcium/phosphorus balance. Since soft drinks normally contain only trace amounts of calcium, the calcium/phosphorus balance does not meet the 1:1 ratio thought to be optimal. However, total dietary intake of calcium and phosphorus is the only relevant consideration. It is estimated that soft drinks provide only two to three percent of the total phosphorus in the human diet. Pepsi-Cola soft drinks contain small amounts of phosphorus. Brand Pepsi-Cola, for example, has only 27.6 milligrams (mg) per six-ounce serving while Pepsi Light contains 13.2 mg. Recommended Daily Allowances (RDA) for phosphorus have been established by the Food and Nutrition Board, National Academy of Sciences and National Research Council. For individuals one year of age or older, the RDA ranges between 800 - 1200 mg per day. Pregnant and nursing women need an additional 400 mg above the daily requirement. Therefore, when soft drinks are consumed as part of a well balanced diet, there should be no concern about the relatively small amount of phosphorus they contain. Phosphorus is an essential component of our diet and the amount in soft drinks will not affect the total dietary ratio of calcium and phosphorus. Additional Information: Greger, J.L., Krystofiak, M. "Phosphorus intake of Americans.' Food Technology 1982. 36 (1) ):78-84. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, D.C., 1980. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 FOOD COLORING As the National Academy of Sciences (NAS) has stated, "The appearance of a food is important in determining its acceptability. The primary purpose of food colorings is to restore the natural color of foods which may be lost through cooking, canning, transportation, storage, or other processes. " The major food colorings used in Pepsi-Cola soft drinks are tartrazine, approved by the Food and Drug Administration as FD&C Yellow #5, and caramel. Caramel Caramel is added to Pepsi-Cola drinks for several reasons. First, of course, it adds the caramel color people expect in a cola. In addition, it preserves the cola from harmful effects of sunlight because its darker color is an effective light barrier. Caramel also improves taste, and acts as an emulsifier to distribute flavorings evenly throughout the bottle or can. Caramel color is made from corn starch and is a source of nitrogen and sulphur. It is labeled "artificial coloring" because any added color, whether natural or not, must be so labeled. Tartrazine (Yellow Dye #5) Tartrazine is used in Mountain Dew. It was approved by the Food and Drug Administration (FDA) in 1916, and has been permanently listed as safe since 1969. Permanent listing required tests for safety and effectiveness that were increasingly more strict and conducted according to modern testing standards. Testing and Safety of Food Coloring The history of food coloring use is also a history of testing and retesting, as scientific understanding of how to test for safety has grown with time. The Bureau of Chemistry, the FDA's predecessor, first investigated the safety of colors in the early 1900's and established an informal list of approved colors. In 1938, more stringent standards for purity and safety were applied, and manufacturers began sending samples from each batch of food coloring for purity and identity certification. In 1960, standards for safety testing were updated. Scientists began to establish limits for safe consumption of food colorings. Today, tartrazine has been approved as safe for human consumption up to 3.4 mg per pound of body weight. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 FOOD COLORING -- 2 Food Coloring and Health Recently, questions have been raised about the relationship of all food additives to hyperactivity (hyperkinesis) in children. The National Institute for Health, the American Council on Science and Health, and the Nutrition Foundation reviewed studies in which hyperactive children were placed on additive-free diets. The children showed no substantial behavioral change when food coloring was removed from their diets. It would appear that there is no proven relationship between food coloring and hyperkinesis. A minor, but real, health effect of Yellow Dye #5 is a mild hypersensitivity experienced by a small group of individuals sensitive to this substance. Food and drinks containing tartrazine are so labeled. Pepsi-Cola Company began voluntarily listing Yellow #5 on its labels well before the FDA required it to alert those with this sensitivity to its presence in Mountain Dew. Artificial Versus Natural Coloring It is a federal labeling requirement that any ingredient used to color a food product--whether derived from a natural source or synthetically produced--is to be declared an "artificial color." Therefore, "artificial color" only fulfills federal labeling requirements and has no bearing on whether it is a natural or artificial substance. For Additional Information: Committee on Food Protection, Food and Nutrition Board, Division of Biology and Agriculture, National Research Council. Food Colors. National Academy of Sciences, Washington, DC 1971. Source: :https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SODIUM The amount of sodium contained in Pepsi-Cola soft drinks is very small, and contributes little to the total sodium in the average American diet. The Food and Drug Administration has adopted regulations requiring that sodium content be included in nutrition labeling on diet products. Under these regulations, most diet soft drinks are classified as "low sodium" -containing less than 140 milligrams (mg) per serving, or "very low sodium"--less than 35 mg of sodium per six ounce serving. All Pepsi-Cola's diet soft drinks are low or very low sodium and are labeled as such. Pepsi-Cola's regular soft drinks, which are not subject to the sodium labeling requirements, are also low, or very low sodium products. Sodium in Pepsi-Cola beverages may come from various sources: sodium chloride (salt), sodium benzoate, sodium phosphate or sodium citrate, which are used in some of the beverage concentrates; juices and caramel can also be minor sources of sodium. Since almost all water contains small amounts of sodium chloride, the local water supply is also a source of sodium. Sodium content varies by location and season. And since water is added to beverage concentrate at the local bottling plant, the amount of sodium in Pepsi-Cola soft drinks will also vary from city to city. Nevertheless, the total amount of sodium from soft drinks will still be five percent or less of the sodium in the average diet. How Much Salt Should We Have? The average person consumes 10 to 12 grams of salt daily. This amount represents approximately 3900 to 4700 mg of sodium, as salt is 39% sodium by weight. With the average person consuming two six-ounce servings of a soft drink daily, the contribution from Pepsi products to total sodium consumed would be 120 mg or less. The estimated safe and adequate level of dietary intake for sodium has been set at between 600 to 1800 mg for children 7 to 10 years of age and 1100 to 3300 mg for adults. This is equivalent to a safe and adequate daily intake of 2.8 - 8.4 grams of salt for adults. How much is too much? This is a hotly debated question. When reports first indicated a link between sodium and high blood pressure, many experts said the less salt the better. Since then, scientists have questioned the presumed cause-effect relationship between salt and high blood pressure. There are certain groups of people who are "salt-sensitive": persons who are already hytpertensive, and others whose sodium balance is easily upset. For these individuals, sodium does appear to have a direct relatonship with high blood pressure and they should consult their doctor about a sodium-restricted diet. PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 SODIUM -- 2 Today, we have new information indicating that a lack of certain nutrients -- calcium, potassium, vitamin A and vitamin C -- may have a stronger relationship to high blood pressure than previously realized. These findings come from an examination of the data provided by the government's HANES I (Health and Nutrition Examination Survey I) study, performed by the National Center for Health Statistics. Researchers also found that people who consume the highest amounts of calcium, potassium and sodium were at the lowest risk for high blood pressure. Since Pepsi-Cola products provide such a minor amount of sodium compared to most other sources in the diet, they can be enjoyed for the great refreshment value they provide. For Additional Information: "The Sodium Content of Your Food" Home and Garden Bulletin Number 233 Science & Education Administration Information Staff U.S. Department of Agriculture Room 6007 - South Buildiing Washington, DC 20250 Council on Scientific Affairs. "Sodium in processed foods.' Journal of the American Medical Association 1983. 249(6) : 784. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, DC 1980. Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SWEETENERS Sweeteners perform a primary role of making foods taste good; they provide major appeal and flavor gratification. A preference for sweetness may help us to distinguish between wholesome and harmful foods. Children have the greatest sugar craving, and least enjoy tart, sour or bitter flavors. Sweeteners fall into two categories: sugars, which provide calories and are used in regular soft drinks like Pepsi-Cola itself; and alternative sweeteners, which have few or no calories, and are used in diet soft drinks like Diet Pepsi. Sweeteners in Soft Drinks Sweetness is an essential part of the flavor profile of soft drinks. Four major sweeteners are used in soft drinks. Of the sugars, sucrose and high fructose corn sweetener are found in regular soft drinks. These are called nutritive sweeteners because they contain calories and therefore provide energy. Like sucrose, which most of us know as common table sugar, high fructose corn sweetener (HFCS), is made up of two simple sugars, fructose and glucose. As its name suggests, it is derived from corn. Sucrose and HFCS are not the same substance; however, their tastes are nearly identical, and they function about the same in soft drinks. The sweetening agents in diet soft drinks are aspartame (NutraSweetR * brand) and saccharin. Saccharin is an artificial sweetener, and has no calories. Aspartame is made of ingredients similar to those found in nature, and it does have calories. However, it is so intensely sweet that only a tiny amount is needed, and it adds less than one calorie to a six ounce serving of soft drink. Today, Pepsi-Cola uses a variety of sweeteners in its beverages. We primarily use high fructose corn syrup in our regular soft drinks, and aspartame in our bottled and canned diet products. Our fountain service diet products contain a blend of NutraSweetR and saccharin. NutraSweet is a registered trademark of G.D.Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SUGAR Sucrose, which most of us know as table sugar, is made up of two simple sugars, fructose and glucose. It is derived from sugar cane and sugar beets. Sugars are simple carbohydrates which perform a necessary role in the body. They are starter fuels, providing energy and helping the body do its work. Carbohydrates are one of the three macro-nutrients the body needs to function effectively; the other two are proteins and fats. Complex carbohydrates such as grains, cereals and pasta are ultimately broken down in the body to glucose and other simple sugars. Sugar and Health Questions have arisen from time to time about the usefulness of sugar as a food substance. Today, experts basically agree that in moderation, sugar is pleasurable, and not harmful. However, a balanced diet is the key -- too much sugar in place of other important nutrients does not constitute a healthful eating program. Some people have questioned whether sugar contributes to a clinical condition of hyperactivity, known as hyperkinesis, in children. Studies have shown fairly conclusively that the presence or absence of sugar does not have a bearing upon hyperkinetic behavior. Sugar and Cavities Sugar can create conditions in the mouth which lead to tooth decay. That is, sugar acidifies saliva, and this creates an environment in which cavity-causing bacteria can grow. However, studies have shown that the time of day in which a sugar is consumed, the form of the sugar (is it hard, sticky?), and the individual's oral hygiene practices are factors which are important in the development of dental cavities. Soft drinks contain sugars in solution, so that the sugar passes quickly through the mouth indicating a lower risk for cavity development if the individual has good oral hygiene practices. For Additional Information: Bierman, E.L., et al. "Carbohydrates, sucrose, and human disease." American Journal of Clinical Nutrition 1979. 32:2712-2722 "Consensus on diets and hyperactivity. Science 1982 Feb. 215(4535) : 958. Sugars and Nutritive Sweeteners in Processed Foods. Food Technology 1979 May. 33(5): 101-105. Life Sciences Research Office, Federation of American Societies for Experimental Biology. Evaluation of the Health Aspects of Sucrose as a Food Ingredient. 1976 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS ASPARTAME Aspartame is the sweetener Pepsi-Cola uses in its diet bottled and canned soft drinks. The brand name for aspartame is NutraSweet * (which is why our Tabels say "sweetened with 100 percent NutraSweet"). Aspartame is made up of two amino acids, aspartic acid and the methyl ester of phenylalanine. These amino acids are components of protein, and they are plentiful in our diets because all protein foods contain them--meat, fish, dairy products, and some fruits and vegetables. They are also present in our blood plasma and in our tissues. Aspartame has a clean, sweet flavor. Alone, neither aspartic acid nor phenylalanine is sweet, but together in the form of aspartame they provide a taste closer to sugar than any other diet sweetener. In fact, taste tests with some foods demonstrated that people could not tell whether their samples had been sweetened with sugar or aspartame. Aspartame is a nutritive sweetener, that is, it does have calories. However, it is so intensely sweet--200 times sweeter than sugar--that very little provides the same sweetness as a teaspoon of sugar. A six-ounce serving of soft drink sweetened with aspartame contains less than one calorie. Aspartame and Health Aspartame underwent a decade of extensive testing before the Food and Drug Administration approved it for use in certain foods and as a table-top sweetener in 1981. The FDA extended its approval to include use in soft drinks in 1983. The FDA noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption by both adults and children. Health questions raised during the testing of aspartame focused on whether or not we could get too much aspartic acid and phenylalanine from soft drinks, and whether there was a risk if aspartame broke down during extended periods of storage or at high temperatures. To the first question, the FDA responded that it is "inconceivable" that anyone could consume too much of either amino acid by drinking aspartame-sweetened soft drinks. In response to the second question, while some methanol would indeed be formed if aspartame broke down, that amount would not be harmful. A six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. Small amounts of methanol are present in our bodies normally, with dietary sources such as fresh fruits and vegetables being only partial contributors to the total amount of methanol in our bodies. * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 ASPARTAME -- 2 Since the FDA approved aspartame for use in soft drinks, government agencies have continued to study the sweetener, and have found no link between it and any serious health effects. Over time, and in extremely warm temperatures, aspartame may begin to lose its sweetness; this will not affect the product's safety. We do, however, suggest that consumers store beverages in a cool place out of direct sunlight. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks you take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. For Additional Information: Consumer Affairs Food and Drug Administration 5600 Fishers Lane Room #16-63 Rockville, MD 20857 (202) 443-3170 NutraSweet Consumer Center P. 0. Box 1111 Skokie, IL 60076 1-800-842-9000 Consumer Information National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS QUESTIONS AND ANSWERS ON ASPARTAME Q: What is aspartame? A: Aspartame is a nutritive substance made of protein components (amino acids) similar to those found in many foods in the average diet such as milk or meats. It is a sweetening ingredient that has the taste of sugar without the calories and is metabolized by the body just like protein. Aspartame is manufactured and sold by the G.D. Searle Company (Skokie, Illinois) under the brand name NutraSweetR. In addition to its use in soft drinks, aspartame is used in a wide variety of other foods. Q: Is aspartame safe? A: The U.S. Food and Drug Administration has determined that aspartame is completely safe. In fact, it is one of the most thoroughly tested substances ever approved for use in foods by the FDA. After considering more than 100 scientific tests and studies, the FDA approved aspartame in 1981 for use as a table top sweetener (under the brand name Equal) and in certain dry foods. In 1983, the FDA approved aspartame for use in carbonated beverages. Independent scientists in the World Health Organization have also determined aspartame to be suitable for use in food. This worldwide endorsement has resulted in the approval of aspartame in more than 40 countries. The FDA has noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption. Q. How many calories are there in aspartame? A teaspoon of sugar contains 16 calories. It takes only one tenth of a calorie of aspartame to equal the sweetness of a teaspoon of sugar. That is because aspartame is approximately 200 times sweeter than sugar. So a 12-ounce can of Diet Pepsi sweetened with aspartame contains less than one calorie per serving. Q: Is it true that aspartame breaks down in soft drinks? A: Over time, and in extremely warm temperatures, aspartame does break down. This will not affect the product's safety, as the by-products of this process have not been found to be harmful. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks consumers take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. Q: Methanol is a by-product of the breakdown of aspartame. Is it dangerous to humans? A: The amount of methanol that would be formed from the break down of aspartame would not be harmful. In fact, a six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 QUESTIONS AND ANSWERS ON ASPARTAME -- 2 Q: What is phenylketonuria (PKU)? A: Approximately one out of every 15,000 infants is born with a rare genetic deficiency that results in the inability to metabolize an amino acid called phenylalanine. This amino acid, which is present in aspartame, is found in many foods in the normal diet such as milk and meats. (An eight-ounce glass of milk has more than 50 times as much phenylalanine as a 12-ounce Diet Pepsi.) All products sweetened with aspartame carry a statement on the label to alert those individuals who must restrict their intake of phenylalanine. Q. Is there anyone else who should avoid intake of aspartame, such as pregnant women or diabetics? A: On the basis of scientific studies, the FDA concluded that aspartame did not present a health risk to pregnant women. However, every pregnant woman should ask her physician for recommendations about diet during pregnancy. Aspartame is not a carbohydrate; clinical studies have shown that it is well tolerated by both insulin-dependent and noninsulin-dependent diabetics. The American Diabetes Association has found aspartame acceptable as a sweetener for products that may be included in diabetic meal plans. Check with your dietitian or doctor for specific recommendations. Q: Is there any scientific evidence that aspartame consumption causes adverse behavior in some individuals? A: All of the current data suggest there is no scientific evidence that aspartame ingestion has any relationship with behavior in individuals. Q: What about reports that use of aspartame may affect blood pressure? A: The FDA has concluded that there is no scientific data to substantiate the claim that aspartame has any effect on blood pressure. Q: Does aspartame contribute to dental decay? A: Aspartame does not promote tooth decay; it is an amino acid-based rather than a carbohydrate-based sweetener. A study conducted by the National Institute of Dental Research showed that NutraSweetR was not associated with the formation of cavities in animals. Q: Are there any guidelines concerning the amount of aspartame an individual may consume? A: Aspartame has undergone rigorous studies with respect to consumption. The FDA has determined the allowable daily intake to be 22.7 mg per pound of body weight, or 3,405 mg for a 150 1b. individual. With 14.75 mg of aspartame per fluid ounce of Diet Pepsi (177 mg in a 12 OZ can), an individual consuming aspartame through soda only would have to drink 19 12 oz. cans of Diet Pepsi to reach the limit set by the FDA. There are no demonstrated effects of aspartame ingestion in persons who do not have phenylketonuria. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS HIGH FRUCTOSE CORN SYRUP High fructose corn syrup (HFCS) is found in most regular soft drinks, including Pepsi-Cola products. It is a nutritive sweetener that contains approximately 80 calories per 6 ounce serving and therefore provides energy. HFCS, like table sugar (sucrose), is made up primarily of two simple sugars, fructose and dextrose. A key difference between HFCS and sucrose is their respective sources. While HFCS is made from corn, sucrose is derived from sugar cane or sugar beets. HFCS is produced by a new technology that enhances the amount of fructose in the final product and is not to be confused with corn syrup, which is mostly glucose. HFCS is produced with varying amounts of fructose depending on its intended food purpose. The HFCS used in soft drinks contains 55% to 57% fructose; in this form, it is generally perceived as slightly sweeter than sugar. Why use HFCS instead of sugar? For two good reasons : availability and economics. While our sugar supply comes from both foreign and domestic sources, HFCS is produced from corn, which is grown in abundance in this country. Government-imposed quotas have created high domestic sugar prices while causing volatility in world supply. HFCS is not subject to such government quotas and is a high quality product that is competitively priced. Using HFCS helps keep the price of our products stable for our customers. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Corn Refiners Association Inc. 10001 Connecticut Ave. N.W. Suite 1022 Washington, DC 20036 (202) 331-1634 77 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj022 SWEETENERS SACCHARIN Before the introduction of aspartame, saccharin was the primary sugar substitute for people who could not have sugar or who wished to restrict calories. Approximately three hundred times sweeter than sucrose, saccharin has been used in a wide variety of foods and beverages, and as a table-top sweetener for almost one hundred years. Until very recently, Pepsi-Cola sweetened its diet soft drinks with saccharin. When aspartame was approved for use in beverages in 1983, we began using a saccharin/aspartame blend. However, ingredient-identifier taste tests showed us that people preferred aspartame alone over the blend by nearly two to one. In response to consumer preference, Pepsi-Cola has begun sweetening its diet bottled and canned soft drinks with 100% NutraSweet R Saccharin and Health Today, saccharin-containing products have a government-mandated warning statement on the label. This warning statement is related to concerns over studies that have shown saccharin to cause bladder cancer in male rats when given in extremely high doses for very long periods of time. However, no adverse health effects have been found with people who use saccharin, and Congress has enacted legislation preventing the FDA from banning saccharin while further studies are being conducted. The fact that saccharin has been consumed by humans for nearly one hundred years without any apparent adverse effects supports its safety for human beings. Pepsi-Cola has switched from saccharin to aspartame solely for reasons of consumer preference. We remain convinced of saccharin's safety, and continue to use it in blends with aspartame in our fountain syrup diet products. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

what produces a number of caffeine free soft drink for those who prefer no caffeine in their diets?

hjpj0226

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pepsi-cola, Pepsi-Cola

CAFFEINE Caffeine is an integral part of the flavor of the soft drinks in which it is found. In some cola drinks, small amounts of caffeine occur naturally as a part of the kola nut itself. A small amount of caffeine is also added to some soft drinks because it introduces a bitter element which balances the sweetness of other flavorings to create a distinctive, refreshing taste. Overall, soft drinks contain relatively small amounts of caffeine. Pepsi-Cola, for example, contains 19.2 milligrams (mg) of caffeine in a six-ounce serving. By comparison, an average-strength cup of coffee has about 108 mg of caffeine, while six ounces of average-strength tea contains 54 mg of caffeine. After reviewing caffeine consumption in America, experts acting on behalf of the Food and Drug Administration concluded that soft drinks add little to the total consumption of caffeine in the average diet. Caffeine and Health People have been consuming caffeine since the first tea leaf was brewed about 2700 B.C. It is found in coffee beans, cocoa beans (from which chocolate is produced), tea leaves, kola nuts and other plant materials. Caffeine is a known mild stimulant. In large enough amounts, it will increase muscular agility and endurance, and reduce fatigue. Because of its ability to decrease fatigue, it is an ingredient in many common pain relief and cold medications. On the other hand, too much caffeine can sometimes cause insomnia or irritability. These effects do not last long because our bodies rapidly process and eliminate caffeine. Caffeine and Birth Defects There had been some concern that caffeine consumption was related to birth defects; to date, however, studies of human populations have indicated that there is no relationship between caffeine and birth defects or other reproductive problems. Studies of rats, mice and rabbits show that at very high doses caffeine can cause birth defects in offspring of these species. However, the amount of caffeine fed to each animal in these studies was the equivalent of a person drinking about sixty cups of coffee daily; below these levels, no reproductive or birth defects were observed. In the past decade or so, there have been eight studies of the effects of caffeine on human reproduction. Researchers compared the caffeine consumption of mothers with healthy babies and mothers of children with birth defects. These studies found no relationship between caffeine consumption and the existence of birth defects. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 CAFFEINE -- 2 The greatest sources of caffeine are coffee, tea and chocolate. Soft drinks add little to the average total intake. In 1978, the Federation of American Societies for Experimental Biology reported to the FDA that most adults who drank soft drinks actually consumed four to thirteen times more caffeine from other sources while children received two to four times more caffeine from other sources. For consumers who prefer no caffeine in their diets, Pepsi-Cola produces a number of caffeine-free soft drinks. For Additional Information: American Council on Science and Health. The Health Effects of Caffeine. Summit, NJ, 1983 Jan. Dews, P.B. "Caffeine." Annual Review of Nutrition 1982. 2:323-341. Linn, S., et al. "No association between coffee consumption and adverse outcomes of pregnancy. New England Journal of Medicine 1982. 306(3):141-145. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 Phosphoric acid, which is 31.6% phosphorus by weight, is used in some Pepsi-Cola products for two reasons. It contributes a citric note--a refreshing tart taste--t the soda. And it also acts as a buffer, i.e. it controls acidity and holds the beverages' pH at a steady level. Phosphorus is a necessary dietary component; it is essential to the life of every living cell. Without it, our bodies cannot utilize calcium properly. Excessive phosphorus intake causes our bodies to get rid of calcium too rapidly. The only possible concern about the amount of phosphorus consumed is whether an excess may upset the calcium/phosphorus balance. Since soft drinks normally contain only trace amounts of calcium, the calcium/phosphorus balance does not meet the 1:1 ratio thought to be optimal. However, total dietary intake of calcium and phosphorus is the only relevant consideration. It is estimated that soft drinks provide only two to three percent of the total phosphorus in the human diet. Pepsi-Cola soft drinks contain small amounts of phosphorus. Brand Pepsi-Cola, for example, has only 27.6 milligrams (mg) per six-ounce serving while Pepsi Light contains 13.2 mg. Recommended Daily Allowances (RDA) for phosphorus have been established by the Food and Nutrition Board, National Academy of Sciences and National Research Council. For individuals one year of age or older, the RDA ranges between 800 - 1200 mg per day. Pregnant and nursing women need an additional 400 mg above the daily requirement. Therefore, when soft drinks are consumed as part of a well balanced diet, there should be no concern about the relatively small amount of phosphorus they contain. Phosphorus is an essential component of our diet and the amount in soft drinks will not affect the total dietary ratio of calcium and phosphorus. Additional Information: Greger, J.L., Krystofiak, M. "Phosphorus intake of Americans.' Food Technology 1982. 36 (1) ):78-84. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, D.C., 1980. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 FOOD COLORING As the National Academy of Sciences (NAS) has stated, "The appearance of a food is important in determining its acceptability. The primary purpose of food colorings is to restore the natural color of foods which may be lost through cooking, canning, transportation, storage, or other processes. " The major food colorings used in Pepsi-Cola soft drinks are tartrazine, approved by the Food and Drug Administration as FD&C Yellow #5, and caramel. Caramel Caramel is added to Pepsi-Cola drinks for several reasons. First, of course, it adds the caramel color people expect in a cola. In addition, it preserves the cola from harmful effects of sunlight because its darker color is an effective light barrier. Caramel also improves taste, and acts as an emulsifier to distribute flavorings evenly throughout the bottle or can. Caramel color is made from corn starch and is a source of nitrogen and sulphur. It is labeled "artificial coloring" because any added color, whether natural or not, must be so labeled. Tartrazine (Yellow Dye #5) Tartrazine is used in Mountain Dew. It was approved by the Food and Drug Administration (FDA) in 1916, and has been permanently listed as safe since 1969. Permanent listing required tests for safety and effectiveness that were increasingly more strict and conducted according to modern testing standards. Testing and Safety of Food Coloring The history of food coloring use is also a history of testing and retesting, as scientific understanding of how to test for safety has grown with time. The Bureau of Chemistry, the FDA's predecessor, first investigated the safety of colors in the early 1900's and established an informal list of approved colors. In 1938, more stringent standards for purity and safety were applied, and manufacturers began sending samples from each batch of food coloring for purity and identity certification. In 1960, standards for safety testing were updated. Scientists began to establish limits for safe consumption of food colorings. Today, tartrazine has been approved as safe for human consumption up to 3.4 mg per pound of body weight. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 FOOD COLORING -- 2 Food Coloring and Health Recently, questions have been raised about the relationship of all food additives to hyperactivity (hyperkinesis) in children. The National Institute for Health, the American Council on Science and Health, and the Nutrition Foundation reviewed studies in which hyperactive children were placed on additive-free diets. The children showed no substantial behavioral change when food coloring was removed from their diets. It would appear that there is no proven relationship between food coloring and hyperkinesis. A minor, but real, health effect of Yellow Dye #5 is a mild hypersensitivity experienced by a small group of individuals sensitive to this substance. Food and drinks containing tartrazine are so labeled. Pepsi-Cola Company began voluntarily listing Yellow #5 on its labels well before the FDA required it to alert those with this sensitivity to its presence in Mountain Dew. Artificial Versus Natural Coloring It is a federal labeling requirement that any ingredient used to color a food product--whether derived from a natural source or synthetically produced--is to be declared an "artificial color." Therefore, "artificial color" only fulfills federal labeling requirements and has no bearing on whether it is a natural or artificial substance. For Additional Information: Committee on Food Protection, Food and Nutrition Board, Division of Biology and Agriculture, National Research Council. Food Colors. National Academy of Sciences, Washington, DC 1971. Source: :https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SODIUM The amount of sodium contained in Pepsi-Cola soft drinks is very small, and contributes little to the total sodium in the average American diet. The Food and Drug Administration has adopted regulations requiring that sodium content be included in nutrition labeling on diet products. Under these regulations, most diet soft drinks are classified as "low sodium" -containing less than 140 milligrams (mg) per serving, or "very low sodium"--less than 35 mg of sodium per six ounce serving. All Pepsi-Cola's diet soft drinks are low or very low sodium and are labeled as such. Pepsi-Cola's regular soft drinks, which are not subject to the sodium labeling requirements, are also low, or very low sodium products. Sodium in Pepsi-Cola beverages may come from various sources: sodium chloride (salt), sodium benzoate, sodium phosphate or sodium citrate, which are used in some of the beverage concentrates; juices and caramel can also be minor sources of sodium. Since almost all water contains small amounts of sodium chloride, the local water supply is also a source of sodium. Sodium content varies by location and season. And since water is added to beverage concentrate at the local bottling plant, the amount of sodium in Pepsi-Cola soft drinks will also vary from city to city. Nevertheless, the total amount of sodium from soft drinks will still be five percent or less of the sodium in the average diet. How Much Salt Should We Have? The average person consumes 10 to 12 grams of salt daily. This amount represents approximately 3900 to 4700 mg of sodium, as salt is 39% sodium by weight. With the average person consuming two six-ounce servings of a soft drink daily, the contribution from Pepsi products to total sodium consumed would be 120 mg or less. The estimated safe and adequate level of dietary intake for sodium has been set at between 600 to 1800 mg for children 7 to 10 years of age and 1100 to 3300 mg for adults. This is equivalent to a safe and adequate daily intake of 2.8 - 8.4 grams of salt for adults. How much is too much? This is a hotly debated question. When reports first indicated a link between sodium and high blood pressure, many experts said the less salt the better. Since then, scientists have questioned the presumed cause-effect relationship between salt and high blood pressure. There are certain groups of people who are "salt-sensitive": persons who are already hytpertensive, and others whose sodium balance is easily upset. For these individuals, sodium does appear to have a direct relatonship with high blood pressure and they should consult their doctor about a sodium-restricted diet. PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj226 SODIUM -- 2 Today, we have new information indicating that a lack of certain nutrients -- calcium, potassium, vitamin A and vitamin C -- may have a stronger relationship to high blood pressure than previously realized. These findings come from an examination of the data provided by the government's HANES I (Health and Nutrition Examination Survey I) study, performed by the National Center for Health Statistics. Researchers also found that people who consume the highest amounts of calcium, potassium and sodium were at the lowest risk for high blood pressure. Since Pepsi-Cola products provide such a minor amount of sodium compared to most other sources in the diet, they can be enjoyed for the great refreshment value they provide. For Additional Information: "The Sodium Content of Your Food" Home and Garden Bulletin Number 233 Science & Education Administration Information Staff U.S. Department of Agriculture Room 6007 - South Buildiing Washington, DC 20250 Council on Scientific Affairs. "Sodium in processed foods.' Journal of the American Medical Association 1983. 249(6) : 784. National Research Council and National Academy of Sciences. Food and Nutrition Board. Recommended Dietary Allowances. 9th ed. Washington, DC 1980. Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SWEETENERS Sweeteners perform a primary role of making foods taste good; they provide major appeal and flavor gratification. A preference for sweetness may help us to distinguish between wholesome and harmful foods. Children have the greatest sugar craving, and least enjoy tart, sour or bitter flavors. Sweeteners fall into two categories: sugars, which provide calories and are used in regular soft drinks like Pepsi-Cola itself; and alternative sweeteners, which have few or no calories, and are used in diet soft drinks like Diet Pepsi. Sweeteners in Soft Drinks Sweetness is an essential part of the flavor profile of soft drinks. Four major sweeteners are used in soft drinks. Of the sugars, sucrose and high fructose corn sweetener are found in regular soft drinks. These are called nutritive sweeteners because they contain calories and therefore provide energy. Like sucrose, which most of us know as common table sugar, high fructose corn sweetener (HFCS), is made up of two simple sugars, fructose and glucose. As its name suggests, it is derived from corn. Sucrose and HFCS are not the same substance; however, their tastes are nearly identical, and they function about the same in soft drinks. The sweetening agents in diet soft drinks are aspartame (NutraSweetR * brand) and saccharin. Saccharin is an artificial sweetener, and has no calories. Aspartame is made of ingredients similar to those found in nature, and it does have calories. However, it is so intensely sweet that only a tiny amount is needed, and it adds less than one calorie to a six ounce serving of soft drink. Today, Pepsi-Cola uses a variety of sweeteners in its beverages. We primarily use high fructose corn syrup in our regular soft drinks, and aspartame in our bottled and canned diet products. Our fountain service diet products contain a blend of NutraSweetR and saccharin. NutraSweet is a registered trademark of G.D.Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS SUGAR Sucrose, which most of us know as table sugar, is made up of two simple sugars, fructose and glucose. It is derived from sugar cane and sugar beets. Sugars are simple carbohydrates which perform a necessary role in the body. They are starter fuels, providing energy and helping the body do its work. Carbohydrates are one of the three macro-nutrients the body needs to function effectively; the other two are proteins and fats. Complex carbohydrates such as grains, cereals and pasta are ultimately broken down in the body to glucose and other simple sugars. Sugar and Health Questions have arisen from time to time about the usefulness of sugar as a food substance. Today, experts basically agree that in moderation, sugar is pleasurable, and not harmful. However, a balanced diet is the key -- too much sugar in place of other important nutrients does not constitute a healthful eating program. Some people have questioned whether sugar contributes to a clinical condition of hyperactivity, known as hyperkinesis, in children. Studies have shown fairly conclusively that the presence or absence of sugar does not have a bearing upon hyperkinetic behavior. Sugar and Cavities Sugar can create conditions in the mouth which lead to tooth decay. That is, sugar acidifies saliva, and this creates an environment in which cavity-causing bacteria can grow. However, studies have shown that the time of day in which a sugar is consumed, the form of the sugar (is it hard, sticky?), and the individual's oral hygiene practices are factors which are important in the development of dental cavities. Soft drinks contain sugars in solution, so that the sugar passes quickly through the mouth indicating a lower risk for cavity development if the individual has good oral hygiene practices. For Additional Information: Bierman, E.L., et al. "Carbohydrates, sucrose, and human disease." American Journal of Clinical Nutrition 1979. 32:2712-2722 "Consensus on diets and hyperactivity. Science 1982 Feb. 215(4535) : 958. Sugars and Nutritive Sweeteners in Processed Foods. Food Technology 1979 May. 33(5): 101-105. Life Sciences Research Office, Federation of American Societies for Experimental Biology. Evaluation of the Health Aspects of Sucrose as a Food Ingredient. 1976 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS ASPARTAME Aspartame is the sweetener Pepsi-Cola uses in its diet bottled and canned soft drinks. The brand name for aspartame is NutraSweet * (which is why our Tabels say "sweetened with 100 percent NutraSweet"). Aspartame is made up of two amino acids, aspartic acid and the methyl ester of phenylalanine. These amino acids are components of protein, and they are plentiful in our diets because all protein foods contain them--meat, fish, dairy products, and some fruits and vegetables. They are also present in our blood plasma and in our tissues. Aspartame has a clean, sweet flavor. Alone, neither aspartic acid nor phenylalanine is sweet, but together in the form of aspartame they provide a taste closer to sugar than any other diet sweetener. In fact, taste tests with some foods demonstrated that people could not tell whether their samples had been sweetened with sugar or aspartame. Aspartame is a nutritive sweetener, that is, it does have calories. However, it is so intensely sweet--200 times sweeter than sugar--that very little provides the same sweetness as a teaspoon of sugar. A six-ounce serving of soft drink sweetened with aspartame contains less than one calorie. Aspartame and Health Aspartame underwent a decade of extensive testing before the Food and Drug Administration approved it for use in certain foods and as a table-top sweetener in 1981. The FDA extended its approval to include use in soft drinks in 1983. The FDA noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption by both adults and children. Health questions raised during the testing of aspartame focused on whether or not we could get too much aspartic acid and phenylalanine from soft drinks, and whether there was a risk if aspartame broke down during extended periods of storage or at high temperatures. To the first question, the FDA responded that it is "inconceivable" that anyone could consume too much of either amino acid by drinking aspartame-sweetened soft drinks. In response to the second question, while some methanol would indeed be formed if aspartame broke down, that amount would not be harmful. A six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. Small amounts of methanol are present in our bodies normally, with dietary sources such as fresh fruits and vegetables being only partial contributors to the total amount of methanol in our bodies. * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: :ttps://www.industrydocuments.ucsf.edu/docs/hjpj0226 ASPARTAME -- 2 Since the FDA approved aspartame for use in soft drinks, government agencies have continued to study the sweetener, and have found no link between it and any serious health effects. Over time, and in extremely warm temperatures, aspartame may begin to lose its sweetness; this will not affect the product's safety. We do, however, suggest that consumers store beverages in a cool place out of direct sunlight. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks you take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. For Additional Information: Consumer Affairs Food and Drug Administration 5600 Fishers Lane Room #16-63 Rockville, MD 20857 (202) 443-3170 NutraSweet Consumer Center P. 0. Box 1111 Skokie, IL 60076 1-800-842-9000 Consumer Information National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS QUESTIONS AND ANSWERS ON ASPARTAME Q: What is aspartame? A: Aspartame is a nutritive substance made of protein components (amino acids) similar to those found in many foods in the average diet such as milk or meats. It is a sweetening ingredient that has the taste of sugar without the calories and is metabolized by the body just like protein. Aspartame is manufactured and sold by the G.D. Searle Company (Skokie, Illinois) under the brand name NutraSweetR. In addition to its use in soft drinks, aspartame is used in a wide variety of other foods. Q: Is aspartame safe? A: The U.S. Food and Drug Administration has determined that aspartame is completely safe. In fact, it is one of the most thoroughly tested substances ever approved for use in foods by the FDA. After considering more than 100 scientific tests and studies, the FDA approved aspartame in 1981 for use as a table top sweetener (under the brand name Equal) and in certain dry foods. In 1983, the FDA approved aspartame for use in carbonated beverages. Independent scientists in the World Health Organization have also determined aspartame to be suitable for use in food. This worldwide endorsement has resulted in the approval of aspartame in more than 40 countries. The FDA has noted that the two amino acids which comprise aspartame are found in our bodies and throughout our normal food supply; it considers aspartame safe for consumption. Q. How many calories are there in aspartame? A teaspoon of sugar contains 16 calories. It takes only one tenth of a calorie of aspartame to equal the sweetness of a teaspoon of sugar. That is because aspartame is approximately 200 times sweeter than sugar. So a 12-ounce can of Diet Pepsi sweetened with aspartame contains less than one calorie per serving. Q: Is it true that aspartame breaks down in soft drinks? A: Over time, and in extremely warm temperatures, aspartame does break down. This will not affect the product's safety, as the by-products of this process have not been found to be harmful. Pepsi-Cola has initiated an in-store beverage monitoring program to make sure the diet soft drinks consumers take home are fresh. Our program includes production date-coding and product rotation, and allows our bottlers and retailers to maintain the highest quality beverages possible. Q: Methanol is a by-product of the breakdown of aspartame. Is it dangerous to humans? A: The amount of methanol that would be formed from the break down of aspartame would not be harmful. In fact, a six-ounce serving of fruit juice contains approximately three times more methanol than six ounces of soft drink in which the aspartame has totally broken down. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 QUESTIONS AND ANSWERS ON ASPARTAME -- 2 Q: What is phenylketonuria (PKU)? A: Approximately one out of every 15,000 infants is born with a rare genetic deficiency that results in the inability to metabolize an amino acid called phenylalanine. This amino acid, which is present in aspartame, is found in many foods in the normal diet such as milk and meats. (An eight-ounce glass of milk has more than 50 times as much phenylalanine as a 12-ounce Diet Pepsi.) All products sweetened with aspartame carry a statement on the label to alert those individuals who must restrict their intake of phenylalanine. Q. Is there anyone else who should avoid intake of aspartame, such as pregnant women or diabetics? A: On the basis of scientific studies, the FDA concluded that aspartame did not present a health risk to pregnant women. However, every pregnant woman should ask her physician for recommendations about diet during pregnancy. Aspartame is not a carbohydrate; clinical studies have shown that it is well tolerated by both insulin-dependent and noninsulin-dependent diabetics. The American Diabetes Association has found aspartame acceptable as a sweetener for products that may be included in diabetic meal plans. Check with your dietitian or doctor for specific recommendations. Q: Is there any scientific evidence that aspartame consumption causes adverse behavior in some individuals? A: All of the current data suggest there is no scientific evidence that aspartame ingestion has any relationship with behavior in individuals. Q: What about reports that use of aspartame may affect blood pressure? A: The FDA has concluded that there is no scientific data to substantiate the claim that aspartame has any effect on blood pressure. Q: Does aspartame contribute to dental decay? A: Aspartame does not promote tooth decay; it is an amino acid-based rather than a carbohydrate-based sweetener. A study conducted by the National Institute of Dental Research showed that NutraSweetR was not associated with the formation of cavities in animals. Q: Are there any guidelines concerning the amount of aspartame an individual may consume? A: Aspartame has undergone rigorous studies with respect to consumption. The FDA has determined the allowable daily intake to be 22.7 mg per pound of body weight, or 3,405 mg for a 150 1b. individual. With 14.75 mg of aspartame per fluid ounce of Diet Pepsi (177 mg in a 12 OZ can), an individual consuming aspartame through soda only would have to drink 19 12 oz. cans of Diet Pepsi to reach the limit set by the FDA. There are no demonstrated effects of aspartame ingestion in persons who do not have phenylketonuria. Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226 SWEETENERS HIGH FRUCTOSE CORN SYRUP High fructose corn syrup (HFCS) is found in most regular soft drinks, including Pepsi-Cola products. It is a nutritive sweetener that contains approximately 80 calories per 6 ounce serving and therefore provides energy. HFCS, like table sugar (sucrose), is made up primarily of two simple sugars, fructose and dextrose. A key difference between HFCS and sucrose is their respective sources. While HFCS is made from corn, sucrose is derived from sugar cane or sugar beets. HFCS is produced by a new technology that enhances the amount of fructose in the final product and is not to be confused with corn syrup, which is mostly glucose. HFCS is produced with varying amounts of fructose depending on its intended food purpose. The HFCS used in soft drinks contains 55% to 57% fructose; in this form, it is generally perceived as slightly sweeter than sugar. Why use HFCS instead of sugar? For two good reasons : availability and economics. While our sugar supply comes from both foreign and domestic sources, HFCS is produced from corn, which is grown in abundance in this country. Government-imposed quotas have created high domestic sugar prices while causing volatility in world supply. HFCS is not subject to such government quotas and is a high quality product that is competitively priced. Using HFCS helps keep the price of our products stable for our customers. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 Corn Refiners Association Inc. 10001 Connecticut Ave. N.W. Suite 1022 Washington, DC 20036 (202) 331-1634 77 PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj022 SWEETENERS SACCHARIN Before the introduction of aspartame, saccharin was the primary sugar substitute for people who could not have sugar or who wished to restrict calories. Approximately three hundred times sweeter than sucrose, saccharin has been used in a wide variety of foods and beverages, and as a table-top sweetener for almost one hundred years. Until very recently, Pepsi-Cola sweetened its diet soft drinks with saccharin. When aspartame was approved for use in beverages in 1983, we began using a saccharin/aspartame blend. However, ingredient-identifier taste tests showed us that people preferred aspartame alone over the blend by nearly two to one. In response to consumer preference, Pepsi-Cola has begun sweetening its diet bottled and canned soft drinks with 100% NutraSweet R Saccharin and Health Today, saccharin-containing products have a government-mandated warning statement on the label. This warning statement is related to concerns over studies that have shown saccharin to cause bladder cancer in male rats when given in extremely high doses for very long periods of time. However, no adverse health effects have been found with people who use saccharin, and Congress has enacted legislation preventing the FDA from banning saccharin while further studies are being conducted. The fact that saccharin has been consumed by humans for nearly one hundred years without any apparent adverse effects supports its safety for human beings. Pepsi-Cola has switched from saccharin to aspartame solely for reasons of consumer preference. We remain convinced of saccharin's safety, and continue to use it in blends with aspartame in our fountain syrup diet products. For Additional Information: Consumer Information Center National Soft Drink Association 1101 Sixteenth Street Northwest Washington, DC 20036 (202) 463-6732 * NutraSweet is a registered trademark of G.D. Searle & Co. PEPSI PEPSI-COLA COMPANY, PURCHASE, NEW YORK 10577 Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

Where is the Coca-cola company foods division located?

hfpj0226

hfpj0226_p2, hfpj0226_p3, hfpj0226_p4

Houston, Texas

2 Vitamins A, D, E, B-1, B-2, B-6. and B-12, niacin, folic acid and panto- thenic acid, and 10% U.S. RDA of calcium, iron and phosphorus. Behind the evolution of Samson are nearly eight years of creative invention, research and experiment by an international team of scientists assembled by The Coca-Cola Company. When the program was launched, J. Paul Austin, then president and now Board Chairman, voiced the Company's concern about the continuing problem of malnutrition affecting progress in many developing areas of the world. The assignment given the scientific team was monumental -- to develop a quality nutritional beverage with a pleasant taste readily acceptable, and feasibly priced to the consumer. Three generations of nutritional beverages have resulted. The first, Saci, was introduced in 1968 in a low-income area of Brazil where soybeans for the protein source were easily available. Experience with Saci led to the conclusion that a less viscous beverage, closer to the consistency of a soft drink, would be more acceptable. A second nutritional beverage, called Samson, was launched in Surinam in 1970. Fruit flavored, it contains 2% protein plus seven vitamins and is non-carbonated. Samson continues to be sold in Surinam attracting a broad range of consumers and, in addition to the beverage form, is also available as a frozen bar on a stick. A third beverage, Tai, emerged from the Company laboratories in 1971 and was introduced in a small Brazilian rural community where it quickly proved to be one of the best selling beverages. Tai is carbonated and chemically preserved, and containes 12/2% protein derived from cheese whey. Source: https://www.industrydocuments.ucsf.edu/docs/hfpj0226 3 For the U.S. market, where it is estimated that some 5% of the population lack the proper amount of protein in their diet, the decision was made to offer a whey-based beverage in an instant powder form. This is the nutritionally fortified beverage mix, Samson, now being introduced to the foodservice industry in Atlanta. Sales and distribution of Samson are under supervision of the direct sales force of the Foodservice Department of The Coca-Cola Company Foods Division. Source: https://www.industrydocuments.ucsf.edu/docs/hfpj0226 procict brief Heri't another SAMS for enemics the list. a Nutritionally Fortified Beverage Mix "The wholesome new experient' fleve SAMSONT30 THE COCA-COLA COMPANY Foods DIVISION HOUSTON, TEXAS Product Concept and Positioning: A fortified beverage mix, SamsonT", may substantially add to nutrition pro- grams in hospitals, schools and foodservice institutions. The product, originating in 1966 from a nutritional bev- erage program in underdeveloped countries undertaken by Coca-Cola, is now in test market as a noncarbonated beverage for U.S. foodservice use. Samson is positioned as a pleasant tasting, nutritious drink as a meal component or snack for all age groups at a cost of less than a penny an ounce. Ingredients and Description: Nutrient fortification added to sugar; partially delactosed and demineralized cheese whey; natural and artificial flavor, and artificial color to produce the instant high-protein content beverage mix. When reconstituted with water, an 8-ounce serving pro- vides 3.6 grams of protein; 100% of U.S. Recommended Dietary Allowance of vitamin C; 25% RDA of vitamins A, D, E, thiamine, riboflavin, Ba, and B1:, niacin, folic acid; and 25% RDA of iron. The mix comes in a sealed foil/paper laminate bag for moisture protection. Varieties are orange, lemon, and tropical fruit. Packaging: The flavored mix dissolves instantly when stirred in either hot or cold water. One bag mixes with one gallon of water and can be stored under refrigeration for future use. The 26-ounce bag yields 17, eight fluid- ounce drinks. food product development February, 1974 Source: https://www.industrydocuments.ucsf.edu/docs/hfpj0226

From which department the letter is issued?

ggpj0226

ggpj0226_p0

Department of health, education, and welfare

o : DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE USA FOOD AND DRUG ADMINISTRATION ROCKVILLE. MARYLAND 20857 December 4, 1978 Dear Consumer: A great deal of consumer interest in food labeling issues was generated by the Food Labeling Hearings sponsored by FDA, USDA, and FTC, this past August - October. Over 452 people testified at the five hearings and over 5,000 written comments were received. This is indeed an impressive record and we would like to thank all of you who shared your views and concerns with us. We are now sending you the first of several communica- tions to provide you with a preliminary feedback on the comments and oral presentations made at the pre-meetings and the hearings themselves. In the next six months the Agency approach to analyzing all the oral and written comments will take place in three stages: 1. Quantitative review and analysis of the written comments and oral testimony. 2. Interpretive anlaysis and development of a proposed labeling plan for Federal Register publication seeking additional public comment. 3. Development of a final labeling plan. When this information is finalized, we will send you additional completed reports and notification of Federal Register announcements for your comment. Sincerely yours, Alixanier Glort Alexander Grant Special Assistant to the Commissioner for Consumer Affairs Source: https://www.industrydocuments.ucsf.edu/docs/ggpj0226

whose signature at the bottom of page ?

ggpj0226

ggpj0226_p0

Alexander Grant, alexander grant

o : DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE USA FOOD AND DRUG ADMINISTRATION ROCKVILLE. MARYLAND 20857 December 4, 1978 Dear Consumer: A great deal of consumer interest in food labeling issues was generated by the Food Labeling Hearings sponsored by FDA, USDA, and FTC, this past August - October. Over 452 people testified at the five hearings and over 5,000 written comments were received. This is indeed an impressive record and we would like to thank all of you who shared your views and concerns with us. We are now sending you the first of several communica- tions to provide you with a preliminary feedback on the comments and oral presentations made at the pre-meetings and the hearings themselves. In the next six months the Agency approach to analyzing all the oral and written comments will take place in three stages: 1. Quantitative review and analysis of the written comments and oral testimony. 2. Interpretive anlaysis and development of a proposed labeling plan for Federal Register publication seeking additional public comment. 3. Development of a final labeling plan. When this information is finalized, we will send you additional completed reports and notification of Federal Register announcements for your comment. Sincerely yours, Alixanier Glort Alexander Grant Special Assistant to the Commissioner for Consumer Affairs Source: https://www.industrydocuments.ucsf.edu/docs/ggpj0226

what is the date mentioned at the top of the page?

hjpj0226

hjpj0226_p0

November 14, 1986

PEPSI-COLA COMPANY PUROHASE-NEW YORK 10577 November 14, 1986 Ms. Laurie Quint Center for Science in the Public Interest 1501 Sixteenth St. N.W. Washington, DC 20036 Dear Ms. Quint: Thank you for your recent letter to Pepsi-Cola requesting information about our products. A complete listing of the ingredients in our Pepsi products appears on each package. In answer to your question regarding the nutritional breakdown of our carbonated beverages, we are enclosing a Product Ingredient Data Sheet. Please note that the amounts of sodium, potassium and calcium depend on the local water supply. Our independently owned and operated Pepsi-Cola franchise bottlers have the choice of using one of the sweeteners authorized for use by the Pepsi-Cola system. The bottlers primarily use sucrose and high fructose corn syrup. The sweetener used in Pepsi-Cola determines its exact caloric content. When sweetened with sucrose, Pepsi-Cola has 13.1 calories per ounce, or 157 calories in a 12-ounce can. When sweetened with high fructose corn syrup, it contains 13,3 calories, for a total of 160 calories per 12-ounce serving. The caloric content indicated on the enclosed sheet is for Pepsi-Cola sweetened with sucrose. This calculation is based on the standard multiplier of 3.8 calories per gram of carbohydrate. We appreciate your interest in Pepsi-Cola Company and its products and hope this information has been helpful to you. Sincerely, Amita Pancatte Anita Pancotto Consumer Correspondent AP/es Enclosure Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

who is the consumer correspondent?

hjpj0226

hjpj0226_p0

Anita Pancotto, anita pancotto

PEPSI-COLA COMPANY PUROHASE-NEW YORK 10577 November 14, 1986 Ms. Laurie Quint Center for Science in the Public Interest 1501 Sixteenth St. N.W. Washington, DC 20036 Dear Ms. Quint: Thank you for your recent letter to Pepsi-Cola requesting information about our products. A complete listing of the ingredients in our Pepsi products appears on each package. In answer to your question regarding the nutritional breakdown of our carbonated beverages, we are enclosing a Product Ingredient Data Sheet. Please note that the amounts of sodium, potassium and calcium depend on the local water supply. Our independently owned and operated Pepsi-Cola franchise bottlers have the choice of using one of the sweeteners authorized for use by the Pepsi-Cola system. The bottlers primarily use sucrose and high fructose corn syrup. The sweetener used in Pepsi-Cola determines its exact caloric content. When sweetened with sucrose, Pepsi-Cola has 13.1 calories per ounce, or 157 calories in a 12-ounce can. When sweetened with high fructose corn syrup, it contains 13,3 calories, for a total of 160 calories per 12-ounce serving. The caloric content indicated on the enclosed sheet is for Pepsi-Cola sweetened with sucrose. This calculation is based on the standard multiplier of 3.8 calories per gram of carbohydrate. We appreciate your interest in Pepsi-Cola Company and its products and hope this information has been helpful to you. Sincerely, Amita Pancatte Anita Pancotto Consumer Correspondent AP/es Enclosure Source: https://www.industrydocuments.ucsf.edu/docs/hjpj0226

Who is this letter sent to?

sfpj0226

sfpj0226_p0

Mr. Alm, Mr. John R. Alm

THE SECRETARY OF HEALTH AND HUMAN SERVICES WASHINGTON, D.C. 20201 OCT 0 32003 Mr. John R. Alm President and Chief Operating Officer Coca-Cola Enterprise, Inc. P.O. Box 723040 Atlanta, Georgia 31139-0040 Dear Mr. Alm: Thank you for your letter regarding our recent meeting concerning the nation's obesity epidemic. I appreciate your willingness to join with me in attacking this most serious public health concern. The five steps that Coca-Cola Enterprises, Inc. is taking to address the obesity epidemic, especially among our nation's children, represents an important beginning and commitment. As we discussed, my prevention initiative, Steps To A HealthierUS, focuses on preventing obesity and such diseases as diabetes and asthma by promoting physical activity, good nutrition, and preventive health services. The initiative advances the President's HealthierUS goal of helping Americans live longer, better and healthier lives. The challenge is to create a comprehensive multifaceted public health approach capable of delivering long-term improvements in the lifestyles of Americans. Effective action requires the close cooperation and collaboration of a variety of corporate enterprises, organizations and individuals at all levels. Only with the support and investment from a broad array of public and private partners, such as yourself and others, will we succeed. 1 commend you for leadership in taking action to promote health beverage choice, nutrition education, and physical activity, especially for our children in and out of school. In addition to the actions that you mentioned, my staff tells me that your company is now selling 8 ounce bottles and cans of beverages: This seems to be an excellent way to draw attention to the importance of portion size and help consumers limit their intake of excess calories by controlling portion sizes. 1 encourage you to continue your efforts and identify even more ways to help us decrease overweight and obesity in this country and I look forward to future collaborations. Finally, on a separate note, I applaud your personal commitment to helping the children of Los Angeles build bright futures through Camp Paintrock, and I hope to take you up on your invitation to visit. Sincerely, Journey Tommy G Thompson S. Phonyson Source: https://www.industrydocuments.ucsf.edu/docs/sfpj0226

what is the designation of Mr.john r alm?

sfpj0226

sfpj0226_p0

president and chief operating officer, President and Chief Operating Officer

THE SECRETARY OF HEALTH AND HUMAN SERVICES WASHINGTON, D.C. 20201 OCT 0 32003 Mr. John R. Alm President and Chief Operating Officer Coca-Cola Enterprise, Inc. P.O. Box 723040 Atlanta, Georgia 31139-0040 Dear Mr. Alm: Thank you for your letter regarding our recent meeting concerning the nation's obesity epidemic. I appreciate your willingness to join with me in attacking this most serious public health concern. The five steps that Coca-Cola Enterprises, Inc. is taking to address the obesity epidemic, especially among our nation's children, represents an important beginning and commitment. As we discussed, my prevention initiative, Steps To A HealthierUS, focuses on preventing obesity and such diseases as diabetes and asthma by promoting physical activity, good nutrition, and preventive health services. The initiative advances the President's HealthierUS goal of helping Americans live longer, better and healthier lives. The challenge is to create a comprehensive multifaceted public health approach capable of delivering long-term improvements in the lifestyles of Americans. Effective action requires the close cooperation and collaboration of a variety of corporate enterprises, organizations and individuals at all levels. Only with the support and investment from a broad array of public and private partners, such as yourself and others, will we succeed. 1 commend you for leadership in taking action to promote health beverage choice, nutrition education, and physical activity, especially for our children in and out of school. In addition to the actions that you mentioned, my staff tells me that your company is now selling 8 ounce bottles and cans of beverages: This seems to be an excellent way to draw attention to the importance of portion size and help consumers limit their intake of excess calories by controlling portion sizes. 1 encourage you to continue your efforts and identify even more ways to help us decrease overweight and obesity in this country and I look forward to future collaborations. Finally, on a separate note, I applaud your personal commitment to helping the children of Los Angeles build bright futures through Camp Paintrock, and I hope to take you up on your invitation to visit. Sincerely, Journey Tommy G Thompson S. Phonyson Source: https://www.industrydocuments.ucsf.edu/docs/sfpj0226

what is the president's healthierUS goal ?

sfpj0226

sfpj0226_p0

helping americans live longer, better and healthier lives.

THE SECRETARY OF HEALTH AND HUMAN SERVICES WASHINGTON, D.C. 20201 OCT 0 32003 Mr. John R. Alm President and Chief Operating Officer Coca-Cola Enterprise, Inc. P.O. Box 723040 Atlanta, Georgia 31139-0040 Dear Mr. Alm: Thank you for your letter regarding our recent meeting concerning the nation's obesity epidemic. I appreciate your willingness to join with me in attacking this most serious public health concern. The five steps that Coca-Cola Enterprises, Inc. is taking to address the obesity epidemic, especially among our nation's children, represents an important beginning and commitment. As we discussed, my prevention initiative, Steps To A HealthierUS, focuses on preventing obesity and such diseases as diabetes and asthma by promoting physical activity, good nutrition, and preventive health services. The initiative advances the President's HealthierUS goal of helping Americans live longer, better and healthier lives. The challenge is to create a comprehensive multifaceted public health approach capable of delivering long-term improvements in the lifestyles of Americans. Effective action requires the close cooperation and collaboration of a variety of corporate enterprises, organizations and individuals at all levels. Only with the support and investment from a broad array of public and private partners, such as yourself and others, will we succeed. 1 commend you for leadership in taking action to promote health beverage choice, nutrition education, and physical activity, especially for our children in and out of school. In addition to the actions that you mentioned, my staff tells me that your company is now selling 8 ounce bottles and cans of beverages: This seems to be an excellent way to draw attention to the importance of portion size and help consumers limit their intake of excess calories by controlling portion sizes. 1 encourage you to continue your efforts and identify even more ways to help us decrease overweight and obesity in this country and I look forward to future collaborations. Finally, on a separate note, I applaud your personal commitment to helping the children of Los Angeles build bright futures through Camp Paintrock, and I hope to take you up on your invitation to visit. Sincerely, Journey Tommy G Thompson S. Phonyson Source: https://www.industrydocuments.ucsf.edu/docs/sfpj0226

what is the reason to applaud Alm?

sfpj0226

sfpj0226_p0

personal commitment to helping the children of los angeles build bright futures through camp paintrock

THE SECRETARY OF HEALTH AND HUMAN SERVICES WASHINGTON, D.C. 20201 OCT 0 32003 Mr. John R. Alm President and Chief Operating Officer Coca-Cola Enterprise, Inc. P.O. Box 723040 Atlanta, Georgia 31139-0040 Dear Mr. Alm: Thank you for your letter regarding our recent meeting concerning the nation's obesity epidemic. I appreciate your willingness to join with me in attacking this most serious public health concern. The five steps that Coca-Cola Enterprises, Inc. is taking to address the obesity epidemic, especially among our nation's children, represents an important beginning and commitment. As we discussed, my prevention initiative, Steps To A HealthierUS, focuses on preventing obesity and such diseases as diabetes and asthma by promoting physical activity, good nutrition, and preventive health services. The initiative advances the President's HealthierUS goal of helping Americans live longer, better and healthier lives. The challenge is to create a comprehensive multifaceted public health approach capable of delivering long-term improvements in the lifestyles of Americans. Effective action requires the close cooperation and collaboration of a variety of corporate enterprises, organizations and individuals at all levels. Only with the support and investment from a broad array of public and private partners, such as yourself and others, will we succeed. 1 commend you for leadership in taking action to promote health beverage choice, nutrition education, and physical activity, especially for our children in and out of school. In addition to the actions that you mentioned, my staff tells me that your company is now selling 8 ounce bottles and cans of beverages: This seems to be an excellent way to draw attention to the importance of portion size and help consumers limit their intake of excess calories by controlling portion sizes. 1 encourage you to continue your efforts and identify even more ways to help us decrease overweight and obesity in this country and I look forward to future collaborations. Finally, on a separate note, I applaud your personal commitment to helping the children of Los Angeles build bright futures through Camp Paintrock, and I hope to take you up on your invitation to visit. Sincerely, Journey Tommy G Thompson S. Phonyson Source: https://www.industrydocuments.ucsf.edu/docs/sfpj0226

what is the title of the page?

rzyj0226

rzyj0226_p1, rzyj0226_p2, rzyj0226_p3, rzyj0226_p4, rzyj0226_p5, rzyj0226_p6

Sing With Me, sing with me

Mr. Michael F. Jacobson Page 2 September 8, 1972 We have no knowledge of this particular commercial, nor can we find any record of it in our files of commercials written for local bottlers. A great deal of advertising is produced locally by bottlers, and, of course, we would have no record of this material. Please let me know if you need any additional information. Sincerely, Sidney B. McAllister SBMcA/dd Attachments Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 "BUY THE WORLD A COKE" l'd like to buy the world a home and furnish it with love Grow apple trees and honey bees and snow white turtle doves. I'd like to teach the world to sing in perfect harmony I'd like to buy the world a Coke and keep it company. (That's the real thing.) I'd like to teach the world to sing (What the world wants today) In perfect harmony I'd like to buy the world a Coke and keep it company. It's the real thing. Coke is. What the world wants today. Coca-Cola. It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 COUNTRY GIRL You say you find it easy pleasing your Country Girl. Her simple way of living bought real love to your world. A home cooked meals her French cafe A night with you, her Broadway play 0h it really makes me happy knowin' I'm that Country Girl. Real things are her spice of life a piece of shade in the sun and Coke on ice It really makes me happy knowing I'm that Country Girl. It's the real thing. In the back of your mind, what your hoping to find, It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 HAVE A GOOD DAY Hey what you say Give'em a song pass it along tell ' em Have a good day. Rainy day blues got no chance to stay Hey, there ain't no way. Just tell 'em a joke Buy 'em a Coke and say Have a good day They want the real thing (Like Coke is) They want to have a good day. Coca-Cola. What the world wants is (whistle) Coca-Cola. Yeah the real thing. Buy ' em a Coke. Tell ' em you hope they're gonna have a good. Have the real thing (Coke is) It's the real thing. Coca-Cola. It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 SING WITH ME I'm gonna sing my song like I never sang before I'm gonna sing about life and the real things we need more Well I hope you don't mind if I sip on my Coke while I sing my song cause it cools my throat And you can have one too and sing along with me. I'm gonna sing about the mountains and the valleys And the real things in life that surround me Things like the ocean True love and devotion So have a Coke and sing along with me. About the real things. Coke is. It's the real thing. Coca-Cola. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 "BICYCLE" May a. little bitty bit of sunshine come your way. And a little bit of love and happiness every day. I wish you no good-byes But a new friend every morning. Clear blue skies are the simple things in life that are good and true, that's the world I wish for you. It's the real thing. May you always have someone to share all your happy moments through. Somebody who'll sit and laugh and share some Coke with you. 'Cause they're the real things And I like to fill your life with Real things are the simple things in life that are good and true, That's the world I.wish for you. It's the real thing. Like a bottle of Coke. (Coca-Cola) It's the real thing. (Coke is) It's the real thing. Coke is. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226

what happens if i sip on my coke while i sing my song according to letter?

rzyj0226

rzyj0226_p1, rzyj0226_p2, rzyj0226_p3, rzyj0226_p4, rzyj0226_p5, rzyj0226_p6

it cools my throat

Mr. Michael F. Jacobson Page 2 September 8, 1972 We have no knowledge of this particular commercial, nor can we find any record of it in our files of commercials written for local bottlers. A great deal of advertising is produced locally by bottlers, and, of course, we would have no record of this material. Please let me know if you need any additional information. Sincerely, Sidney B. McAllister SBMcA/dd Attachments Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 "BUY THE WORLD A COKE" l'd like to buy the world a home and furnish it with love Grow apple trees and honey bees and snow white turtle doves. I'd like to teach the world to sing in perfect harmony I'd like to buy the world a Coke and keep it company. (That's the real thing.) I'd like to teach the world to sing (What the world wants today) In perfect harmony I'd like to buy the world a Coke and keep it company. It's the real thing. Coke is. What the world wants today. Coca-Cola. It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 COUNTRY GIRL You say you find it easy pleasing your Country Girl. Her simple way of living bought real love to your world. A home cooked meals her French cafe A night with you, her Broadway play 0h it really makes me happy knowin' I'm that Country Girl. Real things are her spice of life a piece of shade in the sun and Coke on ice It really makes me happy knowing I'm that Country Girl. It's the real thing. In the back of your mind, what your hoping to find, It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 HAVE A GOOD DAY Hey what you say Give'em a song pass it along tell ' em Have a good day. Rainy day blues got no chance to stay Hey, there ain't no way. Just tell 'em a joke Buy 'em a Coke and say Have a good day They want the real thing (Like Coke is) They want to have a good day. Coca-Cola. What the world wants is (whistle) Coca-Cola. Yeah the real thing. Buy ' em a Coke. Tell ' em you hope they're gonna have a good. Have the real thing (Coke is) It's the real thing. Coca-Cola. It's the real thing. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 SING WITH ME I'm gonna sing my song like I never sang before I'm gonna sing about life and the real things we need more Well I hope you don't mind if I sip on my Coke while I sing my song cause it cools my throat And you can have one too and sing along with me. I'm gonna sing about the mountains and the valleys And the real things in life that surround me Things like the ocean True love and devotion So have a Coke and sing along with me. About the real things. Coke is. It's the real thing. Coca-Cola. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226 "BICYCLE" May a. little bitty bit of sunshine come your way. And a little bit of love and happiness every day. I wish you no good-byes But a new friend every morning. Clear blue skies are the simple things in life that are good and true, that's the world I wish for you. It's the real thing. May you always have someone to share all your happy moments through. Somebody who'll sit and laugh and share some Coke with you. 'Cause they're the real things And I like to fill your life with Real things are the simple things in life that are good and true, That's the world I.wish for you. It's the real thing. Like a bottle of Coke. (Coca-Cola) It's the real thing. (Coke is) It's the real thing. Coke is. Source: https://www.industrydocuments.ucsf.edu/docs/rzyj0226

where is the place of coca-cola companyas mentioned in the letterhead?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

atlanta,georgia, Atlanta, Georgia

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

What is the letter dated?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

November 1, 1972, November 1 , 1972

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

What is the designation of the sender in this letter?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

Public Relations Assistant, public relations assistant

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

Who is this letter addressed to?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

Ms. Lerza, Ms. Catherine Lerza

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

what was the company's first protein containing beverage?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

saci, Saci

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

what is the page number mentioned in this letter?

phpj0226

phpj0226_p0, phpj0226_p1, phpj0226_p2

-3-

The Cica Cola Gompany ATLANTA, GEORGIA ADDRESS REPLY TO P.O. DRAWER 1734 FIDELES KLOECKLER ATLANTA,GA.30301 PUBLIC RELATIONS DEPARTMENT November 1, 1972 (404) 897-212) Ms. Catherine Lerza Nutrition Coordinator Washington Ecology Center 2000 "p" Street, N. W., Room 612 Washington, D. C. 20036 Dear Ms. Lerza: Our Research Department has shared with us your letter expressing interest in our development of protein beverages. We will be glad to attempt to answer your questions. The Coca-Cola Company for several years has been involved in the research and development of refreshing beverages that contain pro- tein, vitamins and minerals. The long-range objective of this program is to develop a variety of good-tasting nutritional beverages which would be compatible with different consumer food preferences around the world. In support of this objective, every effort is being made to utilize locally available protein sources. Considerable research and development relating to the composition and use of such products is well underway in many parts of the world, including the United States. However, the Latin America project is the most advanced to date. Three protein-containing beverages have been marketed by The Coca-Cola Export Corporation, a subsidiary of The Coca-Cola Company. Saci was the Company's first protein-containing beverage. Begin- ning in 1968, it was test-marketed in chocolate and caramel flavors in suburbs of Rio de Janeiro, Brazil. The beverage was non-carbonated. The protein content was derived from Brazilian soybeans and seven vitamins were added. Brazil was selected for the test-market location because of ready availability of local soybeans as a protein source, local machinery and local talent to assist in the development and launching of the new product. A further consideration was the fact that the Company- owned bottling operation in Rio gave better flexibility in carrying out the experiment. Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -2- November 1, 1972 Saci was milky in appearance and much more viscous than an ordinary soft drink. It found more acceptance with the adult male than with children and women. In an effort to reduce the high viscosity of the beverage, a second product, Samson, was developed to replace Saci. Samson was intro- duced in 1970 in Surinam. It is non-carbonated, uses casein (a milk protein) as the protein source, and has a viscosity approximating that of a conventional soft drink. Samson provides 2 percent pro- tein (4 grams per bottle) and contains seven vitamins. It is offered in tutti-frutti and banana flavors. Although still in the test mar- keting stages, Samson has been well received in Surinam to date. In addition to the beverage, a frozen version of Samson has been introduced. Each frozen bar offers the same amount of protein and vitamins as one bottle of Samson. It is also priced the same as the beverage, Sf 0.15 (8c U.S.) It is believed that this is one of the few flavored frozen bars enriched with protein and vitamins offered for sale. Tai, the third protein-containing beverage, was introduced in February, 1971, on a test-market basis in two small cities in northeast Brazil. Tai is an acidified and carbonated protein beverage and is currently orange flavored. The 1.5% protein content is derived from milk whey and the drink contains nine added vitamins. Since Tai is chemically preserved, whereas Saci and Samson are heat sterilized, we can add the two extra vitamins to Tai which are heat sensitive, namely folic and pantothenic acids. Whey, the liquid that remains after milk is used to make cheese, is often discarded and can be a serious environ- mental pollutant. These beverages should be thought of as dietary supplements and not as balanced foods. However, even by themselves, they may offer a significant amount of protein and vitamins, especially for young children. In the United States, the Company has in test a nutritional beverage which could make a contribution to the diet of children. This new beverage is in the form of a powder to which water is added at the place and time of use. It utilizes whey as the source of protein and contains nine added vitamins and iron. At the present time, it is posi- tioned for use in the school feeding programs because of its nutritional contribution, economy and logistics. This beverage, along with a com- plementary cake, serves as a complete breakfast (cost 15c for the Source: https://www.industrydocuments.ucsf.edu/docs/phpj0226 Ms. Catherine Lerza Washington Ecology Center -3- November 1, 1972 combination per child) . The product has been provided free of charge to several Atlanta schools for several months and student acceptance has been good. Again, we appreciate your interest in our developments and hope the above will be helpful. Sincerely, (has ) Sidelin Alouckly Public Relations Assistant FK:sga Source: ttps://www.industrydocuments.ucsf.edu/docs/phpj0226

who is the senior vice president ?

gjpj0226

gjpj0226_p0, gjpj0226_p1

Alan L. Hoffman

PEPSICO F Alan L. Hoffman Senior Vice President Global Public Policy and Government Affairs April 15, 2014 Mr. Michael Jacobson Executive Director Center for Science in the Public Interest 1220 L Street, NW Suite 300 Washington, DC 20005-4053 Dear Michael: As a global company operating in more than 220 countries, PepsiCo faces a wide array of public policy challenges. On a daily basis, my office handles diverse issues ranging from human rights to trade to environmental sustainability. One of the more vexing issues is the appropriate role of genetically modified ("GM") ingredients in our food supply. This issue is so challenging because, even though the World Health Organization, the American Medical Association, the Food and Drug Administration, the National Academy of Sciences, and the American Association for the Advancement of Science have all determined that foods containing GM ingredients are safe to eat, some consumers have concerns. In addition to being safe, GM ingredients provide other benefits. For example, some GM crops are able to resist disease better and use less water and pesticides than their non-GM counterparts. Moreover, food demand is expected to increase by at least 70% by mid-century, and GM foods can play an important role in assuring an adequate food supply. In fact, many advocates for developing populations, including Microsoft founder Bill Gates, support the use of GM ingredients as a way to feed the world. Notwithstanding these benefits, I know that many consumers have questions about these foods. To this end, I am proud to say that PepsiCo supports federal legislation that would establish a mechanism to help consumers identify products not containing GM ingredients. I understand that people have strongly held views about the use of GM ingredients and look forward to working with all interested parties in reaching a solution that addresses consumer concerns while allowing the world to continue to benefit from the great potential that GM products have to offer. All my best, Alan Alan L. Hoffman 700 Anderson Hill Road, Purchase, New York 10577 Bus: 914-253-3600 M Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226 The Newuljork Tinnes no genetically engineered ingredients, or at most inadvertent trace amounts. Why Label Genetically Engineered Food? March 14, 2013 SCIENTIFIC The Editorial Board AMERICAN Whole Foods Market caused a stir last week when it announced that it would require all Labels for GMO Foods Are a Bad Idea products sold in its stores in the United States and Canada to carry labels indicating whether August 20, 2013 The Editors they contain genetically modified ingredients by 2018. Food advocacy groups hailed its action as a possible "game changer" that would push the This past June, Connecticut and Maine became entire food industry to adopt similar labels. the first states to pass bills requiring labels on all foods made from genetically modified Any private company has the right to require its organisms (GMOs). In November 2012 suppliers to meet labeling standards it chooses California voters rejected the similar Proposition to set, and consumers have a right to know 37 by a narrow majority of 51.4 percent. "All what's in the food they are buying. But there is we want is a simple label/For the food that's on our table," chanted marchers before the no reliable evidence that genetically modified foods now on the market pose any risk to elections. The issue, however, is in no way simple. consumers. The Food and Drug Administration says it has We have been tinkering with our food's DNA no basis for concluding that foods developed by since the dawn of agriculture. By selectively bioengineering techniques present different or breeding plants and animals with the most greater safety concerns than foods developed by desirable traits, our predecessors transformed traditional plant breeding. Nevertheless, bills are organisms' genomes, turning a scraggly grass pending in several states to require mandatory into plump-kerneled corn, for example. For the labeling of genetically modified ingredients (a past 20 years Americans have been eating plants in which scientists have used modern tools to referendum to compel such labeling was narrowly defeated in California last November). insert a gene here or tweak a gene there, helping For now, there seems little reason to make the crops tolerate drought and resist herbicides. labeling compulsory. Around 70 percent of processed foods in the U.S. contain genetically modified ingredients. Consumers can already find products free of genetically engineered ingredients, with labels Instead of providing people with useful voluntarily placed by the manufacturers. information, mandatory GMO labels would only intensify the misconception that so-called For those who want to avoid such ingredients, Frankenfoods endanger people's health [see the surest way is to buy products certified as "The Truth about Genetically Modified Food"). The American Association for the Advancement "organic" under federal standards. They contain of Science, the World Health Organization and April, 2014 Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226

What kind of study is mentioned in this letter?

mhpj0226

mhpj0226_p0

Study on soft drinks, the study on soft drinks.

July 29, 1972 Fr. Robert L. Goldsmith R arkoting Director Boys' Life 271 Radison Avo. Now York. RY 10016 Dear Ir. Goldsmith: Thank you vory much for sonding me the study on soft drinks. I havo two further questions that you may be able to answer. First, how many boys wero curvoyod and what kind of c. sulvey was it (telephono, form in Boys' Life, IBII cards at scout mocting, otc. Tho consumption chart on pego 11 is astoniching. Can we roliably assumo that no boys drink ROPO soft drinks a day and that 8% drink eight or more c. day? I just can't beliove that anyono would drink ton ox more a day, as the chaxt indicates. Drinking that many would imply thsat those boys obtain half thoir caloric intako from sodal It sounds more liko thoso responses should be chalkrod up to adolescent mischieviousness. Sincoroly yours, Michaol F. Jacobson, Ph. D. ( Source: https://www.industrydocuments.ucsf.edu/docs/mhpj0226

what is the date mentioned in the letter?

gjpj0226

gjpj0226_p0, gjpj0226_p1

April 15,2014, April 15, 2014

PEPSICO F Alan L. Hoffman Senior Vice President Global Public Policy and Government Affairs April 15, 2014 Mr. Michael Jacobson Executive Director Center for Science in the Public Interest 1220 L Street, NW Suite 300 Washington, DC 20005-4053 Dear Michael: As a global company operating in more than 220 countries, PepsiCo faces a wide array of public policy challenges. On a daily basis, my office handles diverse issues ranging from human rights to trade to environmental sustainability. One of the more vexing issues is the appropriate role of genetically modified ("GM") ingredients in our food supply. This issue is so challenging because, even though the World Health Organization, the American Medical Association, the Food and Drug Administration, the National Academy of Sciences, and the American Association for the Advancement of Science have all determined that foods containing GM ingredients are safe to eat, some consumers have concerns. In addition to being safe, GM ingredients provide other benefits. For example, some GM crops are able to resist disease better and use less water and pesticides than their non-GM counterparts. Moreover, food demand is expected to increase by at least 70% by mid-century, and GM foods can play an important role in assuring an adequate food supply. In fact, many advocates for developing populations, including Microsoft founder Bill Gates, support the use of GM ingredients as a way to feed the world. Notwithstanding these benefits, I know that many consumers have questions about these foods. To this end, I am proud to say that PepsiCo supports federal legislation that would establish a mechanism to help consumers identify products not containing GM ingredients. I understand that people have strongly held views about the use of GM ingredients and look forward to working with all interested parties in reaching a solution that addresses consumer concerns while allowing the world to continue to benefit from the great potential that GM products have to offer. All my best, Alan Alan L. Hoffman 700 Anderson Hill Road, Purchase, New York 10577 Bus: 914-253-3600 M Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226 The Newuljork Tinnes no genetically engineered ingredients, or at most inadvertent trace amounts. Why Label Genetically Engineered Food? March 14, 2013 SCIENTIFIC The Editorial Board AMERICAN Whole Foods Market caused a stir last week when it announced that it would require all Labels for GMO Foods Are a Bad Idea products sold in its stores in the United States and Canada to carry labels indicating whether August 20, 2013 The Editors they contain genetically modified ingredients by 2018. Food advocacy groups hailed its action as a possible "game changer" that would push the This past June, Connecticut and Maine became entire food industry to adopt similar labels. the first states to pass bills requiring labels on all foods made from genetically modified Any private company has the right to require its organisms (GMOs). In November 2012 suppliers to meet labeling standards it chooses California voters rejected the similar Proposition to set, and consumers have a right to know 37 by a narrow majority of 51.4 percent. "All what's in the food they are buying. But there is we want is a simple label/For the food that's on our table," chanted marchers before the no reliable evidence that genetically modified foods now on the market pose any risk to elections. The issue, however, is in no way simple. consumers. The Food and Drug Administration says it has We have been tinkering with our food's DNA no basis for concluding that foods developed by since the dawn of agriculture. By selectively bioengineering techniques present different or breeding plants and animals with the most greater safety concerns than foods developed by desirable traits, our predecessors transformed traditional plant breeding. Nevertheless, bills are organisms' genomes, turning a scraggly grass pending in several states to require mandatory into plump-kerneled corn, for example. For the labeling of genetically modified ingredients (a past 20 years Americans have been eating plants in which scientists have used modern tools to referendum to compel such labeling was narrowly defeated in California last November). insert a gene here or tweak a gene there, helping For now, there seems little reason to make the crops tolerate drought and resist herbicides. labeling compulsory. Around 70 percent of processed foods in the U.S. contain genetically modified ingredients. Consumers can already find products free of genetically engineered ingredients, with labels Instead of providing people with useful voluntarily placed by the manufacturers. information, mandatory GMO labels would only intensify the misconception that so-called For those who want to avoid such ingredients, Frankenfoods endanger people's health [see the surest way is to buy products certified as "The Truth about Genetically Modified Food"). The American Association for the Advancement "organic" under federal standards. They contain of Science, the World Health Organization and April, 2014 Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226

who is the executive director?

gjpj0226

gjpj0226_p0, gjpj0226_p1

mr. Michael jacobson, Mr. Michael jacobson

PEPSICO F Alan L. Hoffman Senior Vice President Global Public Policy and Government Affairs April 15, 2014 Mr. Michael Jacobson Executive Director Center for Science in the Public Interest 1220 L Street, NW Suite 300 Washington, DC 20005-4053 Dear Michael: As a global company operating in more than 220 countries, PepsiCo faces a wide array of public policy challenges. On a daily basis, my office handles diverse issues ranging from human rights to trade to environmental sustainability. One of the more vexing issues is the appropriate role of genetically modified ("GM") ingredients in our food supply. This issue is so challenging because, even though the World Health Organization, the American Medical Association, the Food and Drug Administration, the National Academy of Sciences, and the American Association for the Advancement of Science have all determined that foods containing GM ingredients are safe to eat, some consumers have concerns. In addition to being safe, GM ingredients provide other benefits. For example, some GM crops are able to resist disease better and use less water and pesticides than their non-GM counterparts. Moreover, food demand is expected to increase by at least 70% by mid-century, and GM foods can play an important role in assuring an adequate food supply. In fact, many advocates for developing populations, including Microsoft founder Bill Gates, support the use of GM ingredients as a way to feed the world. Notwithstanding these benefits, I know that many consumers have questions about these foods. To this end, I am proud to say that PepsiCo supports federal legislation that would establish a mechanism to help consumers identify products not containing GM ingredients. I understand that people have strongly held views about the use of GM ingredients and look forward to working with all interested parties in reaching a solution that addresses consumer concerns while allowing the world to continue to benefit from the great potential that GM products have to offer. All my best, Alan Alan L. Hoffman 700 Anderson Hill Road, Purchase, New York 10577 Bus: 914-253-3600 M Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226 The Newuljork Tinnes no genetically engineered ingredients, or at most inadvertent trace amounts. Why Label Genetically Engineered Food? March 14, 2013 SCIENTIFIC The Editorial Board AMERICAN Whole Foods Market caused a stir last week when it announced that it would require all Labels for GMO Foods Are a Bad Idea products sold in its stores in the United States and Canada to carry labels indicating whether August 20, 2013 The Editors they contain genetically modified ingredients by 2018. Food advocacy groups hailed its action as a possible "game changer" that would push the This past June, Connecticut and Maine became entire food industry to adopt similar labels. the first states to pass bills requiring labels on all foods made from genetically modified Any private company has the right to require its organisms (GMOs). In November 2012 suppliers to meet labeling standards it chooses California voters rejected the similar Proposition to set, and consumers have a right to know 37 by a narrow majority of 51.4 percent. "All what's in the food they are buying. But there is we want is a simple label/For the food that's on our table," chanted marchers before the no reliable evidence that genetically modified foods now on the market pose any risk to elections. The issue, however, is in no way simple. consumers. The Food and Drug Administration says it has We have been tinkering with our food's DNA no basis for concluding that foods developed by since the dawn of agriculture. By selectively bioengineering techniques present different or breeding plants and animals with the most greater safety concerns than foods developed by desirable traits, our predecessors transformed traditional plant breeding. Nevertheless, bills are organisms' genomes, turning a scraggly grass pending in several states to require mandatory into plump-kerneled corn, for example. For the labeling of genetically modified ingredients (a past 20 years Americans have been eating plants in which scientists have used modern tools to referendum to compel such labeling was narrowly defeated in California last November). insert a gene here or tweak a gene there, helping For now, there seems little reason to make the crops tolerate drought and resist herbicides. labeling compulsory. Around 70 percent of processed foods in the U.S. contain genetically modified ingredients. Consumers can already find products free of genetically engineered ingredients, with labels Instead of providing people with useful voluntarily placed by the manufacturers. information, mandatory GMO labels would only intensify the misconception that so-called For those who want to avoid such ingredients, Frankenfoods endanger people's health [see the surest way is to buy products certified as "The Truth about Genetically Modified Food"). The American Association for the Advancement "organic" under federal standards. They contain of Science, the World Health Organization and April, 2014 Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226

where is Alan L.hoffan working ?

gjpj0226

gjpj0226_p0, gjpj0226_p1

global public policy and government affairs

PEPSICO F Alan L. Hoffman Senior Vice President Global Public Policy and Government Affairs April 15, 2014 Mr. Michael Jacobson Executive Director Center for Science in the Public Interest 1220 L Street, NW Suite 300 Washington, DC 20005-4053 Dear Michael: As a global company operating in more than 220 countries, PepsiCo faces a wide array of public policy challenges. On a daily basis, my office handles diverse issues ranging from human rights to trade to environmental sustainability. One of the more vexing issues is the appropriate role of genetically modified ("GM") ingredients in our food supply. This issue is so challenging because, even though the World Health Organization, the American Medical Association, the Food and Drug Administration, the National Academy of Sciences, and the American Association for the Advancement of Science have all determined that foods containing GM ingredients are safe to eat, some consumers have concerns. In addition to being safe, GM ingredients provide other benefits. For example, some GM crops are able to resist disease better and use less water and pesticides than their non-GM counterparts. Moreover, food demand is expected to increase by at least 70% by mid-century, and GM foods can play an important role in assuring an adequate food supply. In fact, many advocates for developing populations, including Microsoft founder Bill Gates, support the use of GM ingredients as a way to feed the world. Notwithstanding these benefits, I know that many consumers have questions about these foods. To this end, I am proud to say that PepsiCo supports federal legislation that would establish a mechanism to help consumers identify products not containing GM ingredients. I understand that people have strongly held views about the use of GM ingredients and look forward to working with all interested parties in reaching a solution that addresses consumer concerns while allowing the world to continue to benefit from the great potential that GM products have to offer. All my best, Alan Alan L. Hoffman 700 Anderson Hill Road, Purchase, New York 10577 Bus: 914-253-3600 M Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226 The Newuljork Tinnes no genetically engineered ingredients, or at most inadvertent trace amounts. Why Label Genetically Engineered Food? March 14, 2013 SCIENTIFIC The Editorial Board AMERICAN Whole Foods Market caused a stir last week when it announced that it would require all Labels for GMO Foods Are a Bad Idea products sold in its stores in the United States and Canada to carry labels indicating whether August 20, 2013 The Editors they contain genetically modified ingredients by 2018. Food advocacy groups hailed its action as a possible "game changer" that would push the This past June, Connecticut and Maine became entire food industry to adopt similar labels. the first states to pass bills requiring labels on all foods made from genetically modified Any private company has the right to require its organisms (GMOs). In November 2012 suppliers to meet labeling standards it chooses California voters rejected the similar Proposition to set, and consumers have a right to know 37 by a narrow majority of 51.4 percent. "All what's in the food they are buying. But there is we want is a simple label/For the food that's on our table," chanted marchers before the no reliable evidence that genetically modified foods now on the market pose any risk to elections. The issue, however, is in no way simple. consumers. The Food and Drug Administration says it has We have been tinkering with our food's DNA no basis for concluding that foods developed by since the dawn of agriculture. By selectively bioengineering techniques present different or breeding plants and animals with the most greater safety concerns than foods developed by desirable traits, our predecessors transformed traditional plant breeding. Nevertheless, bills are organisms' genomes, turning a scraggly grass pending in several states to require mandatory into plump-kerneled corn, for example. For the labeling of genetically modified ingredients (a past 20 years Americans have been eating plants in which scientists have used modern tools to referendum to compel such labeling was narrowly defeated in California last November). insert a gene here or tweak a gene there, helping For now, there seems little reason to make the crops tolerate drought and resist herbicides. labeling compulsory. Around 70 percent of processed foods in the U.S. contain genetically modified ingredients. Consumers can already find products free of genetically engineered ingredients, with labels Instead of providing people with useful voluntarily placed by the manufacturers. information, mandatory GMO labels would only intensify the misconception that so-called For those who want to avoid such ingredients, Frankenfoods endanger people's health [see the surest way is to buy products certified as "The Truth about Genetically Modified Food"). The American Association for the Advancement "organic" under federal standards. They contain of Science, the World Health Organization and April, 2014 Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226

What is the date mentioned on the top of the letter ?

mhpj0226

mhpj0226_p0

July 29, 1972

July 29, 1972 Fr. Robert L. Goldsmith R arkoting Director Boys' Life 271 Radison Avo. Now York. RY 10016 Dear Ir. Goldsmith: Thank you vory much for sonding me the study on soft drinks. I havo two further questions that you may be able to answer. First, how many boys wero curvoyod and what kind of c. sulvey was it (telephono, form in Boys' Life, IBII cards at scout mocting, otc. Tho consumption chart on pego 11 is astoniching. Can we roliably assumo that no boys drink ROPO soft drinks a day and that 8% drink eight or more c. day? I just can't beliove that anyono would drink ton ox more a day, as the chaxt indicates. Drinking that many would imply thsat those boys obtain half thoir caloric intako from sodal It sounds more liko thoso responses should be chalkrod up to adolescent mischieviousness. Sincoroly yours, Michaol F. Jacobson, Ph. D. ( Source: https://www.industrydocuments.ucsf.edu/docs/mhpj0226

In how many countries global company is operating ?

gjpj0226

gjpj0226_p0, gjpj0226_p1

more than 220

PEPSICO F Alan L. Hoffman Senior Vice President Global Public Policy and Government Affairs April 15, 2014 Mr. Michael Jacobson Executive Director Center for Science in the Public Interest 1220 L Street, NW Suite 300 Washington, DC 20005-4053 Dear Michael: As a global company operating in more than 220 countries, PepsiCo faces a wide array of public policy challenges. On a daily basis, my office handles diverse issues ranging from human rights to trade to environmental sustainability. One of the more vexing issues is the appropriate role of genetically modified ("GM") ingredients in our food supply. This issue is so challenging because, even though the World Health Organization, the American Medical Association, the Food and Drug Administration, the National Academy of Sciences, and the American Association for the Advancement of Science have all determined that foods containing GM ingredients are safe to eat, some consumers have concerns. In addition to being safe, GM ingredients provide other benefits. For example, some GM crops are able to resist disease better and use less water and pesticides than their non-GM counterparts. Moreover, food demand is expected to increase by at least 70% by mid-century, and GM foods can play an important role in assuring an adequate food supply. In fact, many advocates for developing populations, including Microsoft founder Bill Gates, support the use of GM ingredients as a way to feed the world. Notwithstanding these benefits, I know that many consumers have questions about these foods. To this end, I am proud to say that PepsiCo supports federal legislation that would establish a mechanism to help consumers identify products not containing GM ingredients. I understand that people have strongly held views about the use of GM ingredients and look forward to working with all interested parties in reaching a solution that addresses consumer concerns while allowing the world to continue to benefit from the great potential that GM products have to offer. All my best, Alan Alan L. Hoffman 700 Anderson Hill Road, Purchase, New York 10577 Bus: 914-253-3600 M Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226 The Newuljork Tinnes no genetically engineered ingredients, or at most inadvertent trace amounts. Why Label Genetically Engineered Food? March 14, 2013 SCIENTIFIC The Editorial Board AMERICAN Whole Foods Market caused a stir last week when it announced that it would require all Labels for GMO Foods Are a Bad Idea products sold in its stores in the United States and Canada to carry labels indicating whether August 20, 2013 The Editors they contain genetically modified ingredients by 2018. Food advocacy groups hailed its action as a possible "game changer" that would push the This past June, Connecticut and Maine became entire food industry to adopt similar labels. the first states to pass bills requiring labels on all foods made from genetically modified Any private company has the right to require its organisms (GMOs). In November 2012 suppliers to meet labeling standards it chooses California voters rejected the similar Proposition to set, and consumers have a right to know 37 by a narrow majority of 51.4 percent. "All what's in the food they are buying. But there is we want is a simple label/For the food that's on our table," chanted marchers before the no reliable evidence that genetically modified foods now on the market pose any risk to elections. The issue, however, is in no way simple. consumers. The Food and Drug Administration says it has We have been tinkering with our food's DNA no basis for concluding that foods developed by since the dawn of agriculture. By selectively bioengineering techniques present different or breeding plants and animals with the most greater safety concerns than foods developed by desirable traits, our predecessors transformed traditional plant breeding. Nevertheless, bills are organisms' genomes, turning a scraggly grass pending in several states to require mandatory into plump-kerneled corn, for example. For the labeling of genetically modified ingredients (a past 20 years Americans have been eating plants in which scientists have used modern tools to referendum to compel such labeling was narrowly defeated in California last November). insert a gene here or tweak a gene there, helping For now, there seems little reason to make the crops tolerate drought and resist herbicides. labeling compulsory. Around 70 percent of processed foods in the U.S. contain genetically modified ingredients. Consumers can already find products free of genetically engineered ingredients, with labels Instead of providing people with useful voluntarily placed by the manufacturers. information, mandatory GMO labels would only intensify the misconception that so-called For those who want to avoid such ingredients, Frankenfoods endanger people's health [see the surest way is to buy products certified as "The Truth about Genetically Modified Food"). The American Association for the Advancement "organic" under federal standards. They contain of Science, the World Health Organization and April, 2014 Source: https://www.industrydocuments.ucsf.edu/docs/gjpj0226

What is the date of this letter?

mhpj0226

mhpj0226_p0

July 29, 1972, July 29, 1972

July 29, 1972 Fr. Robert L. Goldsmith R arkoting Director Boys' Life 271 Radison Avo. Now York. RY 10016 Dear Ir. Goldsmith: Thank you vory much for sonding me the study on soft drinks. I havo two further questions that you may be able to answer. First, how many boys wero curvoyod and what kind of c. sulvey was it (telephono, form in Boys' Life, IBII cards at scout mocting, otc. Tho consumption chart on pego 11 is astoniching. Can we roliably assumo that no boys drink ROPO soft drinks a day and that 8% drink eight or more c. day? I just can't beliove that anyono would drink ton ox more a day, as the chaxt indicates. Drinking that many would imply thsat those boys obtain half thoir caloric intako from sodal It sounds more liko thoso responses should be chalkrod up to adolescent mischieviousness. Sincoroly yours, Michaol F. Jacobson, Ph. D. ( Source: https://www.industrydocuments.ucsf.edu/docs/mhpj0226

who is the president and chief operating officer?

rfpj0226

rfpj0226_p0, rfpj0226_p1

John R Alm, John R. Alm

Cora-Cola F (CCC Gola Enterprises Inc. *** RECEIVED *** 03 JUL 16 Gill: 57 John R. Alm Jul 16,2003 14:31:29 WS# 15 P.O. Box 723040 OFFICE OF THE SECRETARY ivili President and CORRESPONDENCE Atlanta, GA 31139-0040 Chief Operating Officer CONTROL CENTER 770 989-3001 NTROL CENTER 770 989-3784 Fax July 11, 2003 The Honorable Tommy G. Thompson U.S. Department of Health and Human Services 200 Independence Avenue; S.W. Washington, D.C. 20201 Dear Secretary Thompson: I wanted to take this opportunity to thank you for taking the time out of your very busy schedule to meet with us to discuss the growing obesity problem in America and the role businesses like those of us in the Coca-Cola system can play in addressing this public health issue. Being the market leader in the beverage industry, we believe we have a role and responsibility to be a part of the solution to positively impact and raise awareness of the obesity problem. In our meeting yesterday, you asked us to provide what we are currently working on to assist your department's efforts in combating this serious issue. As John Downs, Clyde Tuggle, and I outlined in our presentation, below are our five major initiatives: 1. Provide consumers a wide array of beverage choices through innovation from pure hydration to fun and refreshment, such as reduced calorie Minute Maid light products, bottled water, and milk-based beverages with the fewest calories in the category. 2. Reaffirm our decades-old strict policy and guidelines regarding the marketing and advertising of our brands to children. 3. Conduct ourselves in the appropriate way through our leading business practices and model guidelines with our schools and school districts. We want to be respectful and responsive to the wishes and requests of a school/school district to provide their choice and selection of a wide variety of beverages that are appropriate to students' age, nutritional needs, and physical activity level. a. No advance payments for long-term contracts with schools. b Nutritional information for beverages sold in schools will be displayed on levery vending machine. C. When responding to a school or school district's request for their choice of beverage selections, we offer specific beverage availability recommendations for elementary, middle, and high schools. Printed on 100% Recycled Paper Coca-Cola Bottera are committed to using recyciable resources 071620030058 Source: https://www.industrydocuments.ucsf.edu/docs/rfpj0226 RECEIVED *** Jul 16,2003 14:31:29 WS# 15 OFFICE OF THE SECRETARY CORRESPONDENCE CONTROL CENTER Page Two 4. Educate and raise awareness with parents, children, schools, and communities about the vital role physical activity and nutrition education play in reversing the trend of childhood obesity. a. Your Power To Choose. Fitness Health Fun publication and videos. b. MayoClinic.com and Minute Maid nutritional information and healthy tips on packages. 5. Promote and support youth development, physical activity, and health/nutrition education. a. Step With It! activation in middle schools and the McDonald's expansion. b. Boys and Girls Clubs' Health and Well-Being Initiative. C. Juvenile Diabetes Research Foundation's Walk for the Cure. d. National PTA Parent Involvement Schools of Excellence Certification Program. e. Camp Coca-Cola and Camp Paintrock. As I mentioned in our meeting, my wife Carolyn and I have made our personal dreams a reality by building a summer camp for inner-city, financially disadvantaged children from Los Angeles. Camp Paintrock is a four year program that includes mentoring programs to assist youth in getting through high school, into college or trade schools, and eventually finding jobs. It is our goal that the students will obtain new skills such as: leadership, teamwork, responsibility, maturity, independence, and such core values as integrity, honesty, selflessness, and concern for others. We would welcome your visit to our ranch and camp in Wyoming, and would like to extend an open invitation to you. Thank you again for your kind words on our major initiatives, and we very much appreciate your using some of this information in future speeches! We are striving to live up to your expectations as a good corporate citizen to complement your efforts in leading constructive. solutions to support healthy and active lifestyles for all of our citizens. Sincerely, gott JRA/Iba C: Mr. John Downs Mr. Kevin Morris Mr. Clyde Tuggle Source: https://www.industrydocuments.ucsf.edu/docs/rfpj0226

what is the 2nd point inthe letter ?

rfpj0226

rfpj0226_p0, rfpj0226_p1

Reaffirm our decades-old strict policy and guidelines regarding the marketing and advertising of our brands to children.

Cora-Cola F (CCC Gola Enterprises Inc. *** RECEIVED *** 03 JUL 16 Gill: 57 John R. Alm Jul 16,2003 14:31:29 WS# 15 P.O. Box 723040 OFFICE OF THE SECRETARY ivili President and CORRESPONDENCE Atlanta, GA 31139-0040 Chief Operating Officer CONTROL CENTER 770 989-3001 NTROL CENTER 770 989-3784 Fax July 11, 2003 The Honorable Tommy G. Thompson U.S. Department of Health and Human Services 200 Independence Avenue; S.W. Washington, D.C. 20201 Dear Secretary Thompson: I wanted to take this opportunity to thank you for taking the time out of your very busy schedule to meet with us to discuss the growing obesity problem in America and the role businesses like those of us in the Coca-Cola system can play in addressing this public health issue. Being the market leader in the beverage industry, we believe we have a role and responsibility to be a part of the solution to positively impact and raise awareness of the obesity problem. In our meeting yesterday, you asked us to provide what we are currently working on to assist your department's efforts in combating this serious issue. As John Downs, Clyde Tuggle, and I outlined in our presentation, below are our five major initiatives: 1. Provide consumers a wide array of beverage choices through innovation from pure hydration to fun and refreshment, such as reduced calorie Minute Maid light products, bottled water, and milk-based beverages with the fewest calories in the category. 2. Reaffirm our decades-old strict policy and guidelines regarding the marketing and advertising of our brands to children. 3. Conduct ourselves in the appropriate way through our leading business practices and model guidelines with our schools and school districts. We want to be respectful and responsive to the wishes and requests of a school/school district to provide their choice and selection of a wide variety of beverages that are appropriate to students' age, nutritional needs, and physical activity level. a. No advance payments for long-term contracts with schools. b Nutritional information for beverages sold in schools will be displayed on levery vending machine. C. When responding to a school or school district's request for their choice of beverage selections, we offer specific beverage availability recommendations for elementary, middle, and high schools. Printed on 100% Recycled Paper Coca-Cola Bottera are committed to using recyciable resources 071620030058 Source: https://www.industrydocuments.ucsf.edu/docs/rfpj0226 RECEIVED *** Jul 16,2003 14:31:29 WS# 15 OFFICE OF THE SECRETARY CORRESPONDENCE CONTROL CENTER Page Two 4. Educate and raise awareness with parents, children, schools, and communities about the vital role physical activity and nutrition education play in reversing the trend of childhood obesity. a. Your Power To Choose. Fitness Health Fun publication and videos. b. MayoClinic.com and Minute Maid nutritional information and healthy tips on packages. 5. Promote and support youth development, physical activity, and health/nutrition education. a. Step With It! activation in middle schools and the McDonald's expansion. b. Boys and Girls Clubs' Health and Well-Being Initiative. C. Juvenile Diabetes Research Foundation's Walk for the Cure. d. National PTA Parent Involvement Schools of Excellence Certification Program. e. Camp Coca-Cola and Camp Paintrock. As I mentioned in our meeting, my wife Carolyn and I have made our personal dreams a reality by building a summer camp for inner-city, financially disadvantaged children from Los Angeles. Camp Paintrock is a four year program that includes mentoring programs to assist youth in getting through high school, into college or trade schools, and eventually finding jobs. It is our goal that the students will obtain new skills such as: leadership, teamwork, responsibility, maturity, independence, and such core values as integrity, honesty, selflessness, and concern for others. We would welcome your visit to our ranch and camp in Wyoming, and would like to extend an open invitation to you. Thank you again for your kind words on our major initiatives, and we very much appreciate your using some of this information in future speeches! We are striving to live up to your expectations as a good corporate citizen to complement your efforts in leading constructive. solutions to support healthy and active lifestyles for all of our citizens. Sincerely, gott JRA/Iba C: Mr. John Downs Mr. Kevin Morris Mr. Clyde Tuggle Source: https://www.industrydocuments.ucsf.edu/docs/rfpj0226

What is the title of the series?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

SOFT DRINKS AND CAFFEINE

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

What is the fullform of ils?

tpjf0226

tpjf0226_p0, tpjf0226_p1, tpjf0226_p2

INTERNATIONAL LITIGATION SERVICES, international litigation services

From: Miyazaki, Masahiro i,fZão È-"^õ Sent: Monday, August 19, 2002 11:57 PM To: Kuroiwa, Takashi I ã-òl '[ Û '0 0,0,10"; Nishida, Takaharu/ã-0000] Û,0, Cc: Seita, Takeshi /^ã-òSJ"SJ"0 Subject: FW: Proposal for a study to explore the PPAR alpha effects of Act os Attachments: Takeda 00-2-8.doc Takeda 00-2-8.doc Original Message From: P. Collett [mailto:P.Collett@takeda-eurd.co.uk Sent: Friday, August 16, 2002 3:28 AM To: Miyazaki.Masahiro Cc: P.Collett; D.Eckland; Saito.Katsuhisa; g.belcher; y.wada Subject: FW: Proposal for a study to explore the PPAR alpha effects of Act os Miyazaki-san Clearly , in the light of recent events, this proposed study should be politely declined. Could you confirm with Mr Kuroiwa that this study is not wise. Philip Collett Original Message From: David Roberts Sent: Thursday, August 15, 2002 18:35 To: David Eckland; Ian Moules; Christopher Lee Cc: Glyn Belcher; Philip Collett Subject: Proposal for a study to explore the PPAR alpha effects of Actos David, Ian and Chris please be aware that this proposal from Bart Staels is with Osaka PPMD and maybe Miyasaki-san I am aware of your views David on the PPAR alpha message and just wanted to keep you in the loop. I would appreciate being able to discuss this proposal with you at some stage in the next few weeks cheers David Original Message--- 1 Confidential - Subject to Protective Order TAK-SEITAT-00061905 TAK-SEITAT-00061905P-0001 Source: https://www.indup378900007ts.ucsf.edu/docs/tpjf0226 From: Bart Staels [mailto:Bart.Staels@pasteur-lille.fr] To: NishidaTakaharu@takeda.co.jp - Subject: Dear Mr Nishida, It was a pleasure meeting you and discussing at recent meetings, such as the Prague symposium. As I indicated in one of our last discussions, it would be of major importance for the scientific support of Actos to demonstrate the effects of pioglitazone on PPARa in different physiological in vitro and in vivo models. Our laboratory has long-standing experience in profiling compounds with PPARa activity. We have recently profiled pioglitazone on our PPAR screening system and found it to activate PPARa with an EC50=2 microM and a maximal plateau activity comparable to Wy14643. These observations confirm that pioglitazone has stronger PPARa activity than the currently used fibrates! I have therefore taken the liberty to send you enclosed a project proposal which covers the different aspects that can be studied in our laboratory. I hope you will like, and discuss it wit the appropriate persons. I am always available for further discussions. Best regards, Bart Staels U545 INSERM - Dept.d'Atherosclerose Institut Pasteur de Lille 1, rue du Pr. Calmette B.P.245 59019 Lille Cedex France Tel: (33) 03 20 87 73 88 Fax: (33) 03 20 87 71 98 e-mail: Bart.Staels@pasteur-lille.fr 2 Confidential - Subject to Protective Order TAK-SEITAT-00061906 TAK-SEITAT-00061905P-0002 Source: https://www.indup3789-00002ts.ucsf.edu/docs/tpjf0226 de INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SEITAT-00061905P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 6th day of October 2013, in Aliso Viejo, California. Jacob Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. * 65 Enterprise Aliso Viejo, California 92658 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsTEAM.com www.ilsteAM.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source: https://www.indup'3788-00003ts.ucsf.edu/docs/tpjf0226

Who is the Managing Director of International Litigation Services, Inc?

tpjf0226

tpjf0226_p0, tpjf0226_p1, tpjf0226_p2

Joseph Thorpe, joseph thorpe

From: Miyazaki, Masahiro i,fZão È-"^õ Sent: Monday, August 19, 2002 11:57 PM To: Kuroiwa, Takashi I ã-òl '[ Û '0 0,0,10"; Nishida, Takaharu/ã-0000] Û,0, Cc: Seita, Takeshi /^ã-òSJ"SJ"0 Subject: FW: Proposal for a study to explore the PPAR alpha effects of Act os Attachments: Takeda 00-2-8.doc Takeda 00-2-8.doc Original Message From: P. Collett [mailto:P.Collett@takeda-eurd.co.uk Sent: Friday, August 16, 2002 3:28 AM To: Miyazaki.Masahiro Cc: P.Collett; D.Eckland; Saito.Katsuhisa; g.belcher; y.wada Subject: FW: Proposal for a study to explore the PPAR alpha effects of Act os Miyazaki-san Clearly , in the light of recent events, this proposed study should be politely declined. Could you confirm with Mr Kuroiwa that this study is not wise. Philip Collett Original Message From: David Roberts Sent: Thursday, August 15, 2002 18:35 To: David Eckland; Ian Moules; Christopher Lee Cc: Glyn Belcher; Philip Collett Subject: Proposal for a study to explore the PPAR alpha effects of Actos David, Ian and Chris please be aware that this proposal from Bart Staels is with Osaka PPMD and maybe Miyasaki-san I am aware of your views David on the PPAR alpha message and just wanted to keep you in the loop. I would appreciate being able to discuss this proposal with you at some stage in the next few weeks cheers David Original Message--- 1 Confidential - Subject to Protective Order TAK-SEITAT-00061905 TAK-SEITAT-00061905P-0001 Source: https://www.indup378900007ts.ucsf.edu/docs/tpjf0226 From: Bart Staels [mailto:Bart.Staels@pasteur-lille.fr] To: NishidaTakaharu@takeda.co.jp - Subject: Dear Mr Nishida, It was a pleasure meeting you and discussing at recent meetings, such as the Prague symposium. As I indicated in one of our last discussions, it would be of major importance for the scientific support of Actos to demonstrate the effects of pioglitazone on PPARa in different physiological in vitro and in vivo models. Our laboratory has long-standing experience in profiling compounds with PPARa activity. We have recently profiled pioglitazone on our PPAR screening system and found it to activate PPARa with an EC50=2 microM and a maximal plateau activity comparable to Wy14643. These observations confirm that pioglitazone has stronger PPARa activity than the currently used fibrates! I have therefore taken the liberty to send you enclosed a project proposal which covers the different aspects that can be studied in our laboratory. I hope you will like, and discuss it wit the appropriate persons. I am always available for further discussions. Best regards, Bart Staels U545 INSERM - Dept.d'Atherosclerose Institut Pasteur de Lille 1, rue du Pr. Calmette B.P.245 59019 Lille Cedex France Tel: (33) 03 20 87 73 88 Fax: (33) 03 20 87 71 98 e-mail: Bart.Staels@pasteur-lille.fr 2 Confidential - Subject to Protective Order TAK-SEITAT-00061906 TAK-SEITAT-00061905P-0002 Source: https://www.indup3789-00002ts.ucsf.edu/docs/tpjf0226 de INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SEITAT-00061905P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 6th day of October 2013, in Aliso Viejo, California. Jacob Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. * 65 Enterprise Aliso Viejo, California 92658 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsTEAM.com www.ilsteAM.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source: https://www.indup'3788-00003ts.ucsf.edu/docs/tpjf0226

Who seems to be following America's footsteps?

gfpj0226

gfpj0226_p0, gfpj0226_p1

Japan

December 22, 1978 Vice-Premier Teng Hsiao-Ping People's Republic of China c/o Mr. Chuai Tse-Min Liaison Office of the People' 8 Republic of China 2300 Connecticut Avenue, N.W. Washington, D.C. 20008 Dear Vice-Premier Teng: The Center for Science in the Public Interest is a non-profit citizens' group that advocates food and health policies that would benefit American consumers. We were deeply disturbed and disappéinted to learn that the People's Republic of China has signed an agreement with Coca-Cola that will result in the sale of Coca-Cola in your nation. Welcoming Coca-Cola to China is irrational in terms of both industrial development and health. Developing soft drink production and distribution facilities can be done by any nation, large or small, without resorting to the very symbol of bad nutrition and American imperialism for assistance. India recently forced Coca-Cola to leave the country, without any apparent harm to the economy. Public health experts in the United States have frequently pointed to China as a nation that has taken great pains to improve the health of its citizenry. I can think of few American food products that are more injurious to health than Coca-Cola. As has happened in the United States and other Western nations, people will be attracted to the sugary sweet taste and will drink Coca-Cola instead of eating nutritious foods. The Coca-Cola dilutes the general nutritional value of the diet. As your health experts will confirm, Coca-Cola contains no vitamins, no minerals, no protein. only sugar. The sugar will certainly promote tooth decay and obesity, and possibly diabetes. Furthermore, many doctors believe that the drug caffeine added to Coca-Cola is addictive and, in any case, promotes insomnia and anxiety. Though to be aimed at the tourist trade, it is safe to predict that the general public will soon gain access to it. We urge you to cancel the agreement with Coca-Cola. Doing so will promote China'e internal development, help prevent balance of trade problems in the future, and protect your citizens' health. Source: https://www.industrydocuments.ucsf.edu/docs/gfpj0226 Vice-Premier Teng Hsiao-Ping -2- December 22, 1978 People's Republic of China In addition, we urge you to send a team of public health specialists to the United States to discover the great harm that is caused by a diet high in sugar, salt, and fat. While Japan seems to be following America's footsteps down the road to bad health, China still has time to map out its future food policies in a rational way. And we believe that rational planning will not include a College of Dentistry in the basement of every Coca-Cola bottling plant. While Coca-Cola and its executives may be sweet while they are dickering for a lucrative contract, we guarantee you that in the long run they will cause tooth decay, sleeplessness, and headaches. We hope you will reconsider your decision and inform us of your thoughts on this matter. Sincerely, Michael F. Jacobson, Ph.D. Executive Director MFJ/jfc Source: https://www.industrydocuments.ucsf.edu/docs/gfpj0226

What is the Telephone Number given?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

301/436-2373

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

What is the full form of CFSAN?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

Center for Food Safety and Applied Nutrition

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

Which department is mentioned in the letter head?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

DEPARTMENT OF HEALTH & HUMAN SERVICES

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

Who is the President of Corn Refiners Association?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

Audrae Erickson

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

When was this letter received?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

07-03-2008

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

What is the date mentioned in the letter?

lhpj0226

lhpj0226_p0

July 28, 1972

Baxslift July 28, 1972 271 MADISON AVE. NEW YORK N.Y.10016 212 LE 2 - 0985 Michael F. Jacobson, Ph. D. Center for Science in the Public Interest 1346 Connecticut Avenue, N. W. Room 812 Washington, D. C. 20036 Dear Dr. Jacobson: Attached is a copy of the information on soft drinks produced by our Reader Panel studies. This should contain the information you require. Cordially, nirold RLG:jl Robert L. Goldsmith Att. Marketing Director THE NATIONAL MAGAZINE FOR ALL BOYS PUBLISHED BY THE BOY SCOUTS OF AMERICA Source: https://www.industrydocuments.ucsf.edu/docs/lhpj0226

What is the fulll form of FDA?

rxpj0226

rxpj0226_p0, rxpj0226_p1, rxpj0226_p2

FOOD & DRUG ADMINISTRATION, Food & Drug Administration

HFCS JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.02 ARVICAS DEPARTMENT OF HEALTH & HUMAN SERVICES Public Heallh Service de Food and Drug Administration - College Park, MD 20740- JUL 03 2008 Audrae Erickson President Corn Refiners Association 1701 Pennsylvania Avenue, N.W. Suite 950 Washington, DC 20006-5805 Dear Ms. Erickson: This is in follow up to the meeting of April 16, 2008, between the Corn Refiners Association and the Center for Food Safety and Applied Nutrition (CFSAN). The meeting was prompted by a Food Navigator-USA. com article on the use of the term "natural" on products containing high fructose com syrup (HFCS). You asked CFSAN to reconsider its position on whether the use of the term "natural" can be used to describe products containing HFCS. At the meeting Mr. Empie of Archer Daniels Midland Company described the manufacturing process used to make HFCS and following the meoting you sent CPSAN a written description of this production process. During the meeting, we stated that our longstanding policy on the use of the term "natural" is that "natural" means that nothing artificial (including artificial flavors) or synthetic (including all color additives regardless of source) has been included in or has been added to a food that would not normally be expected to be in the food. Additionally, we stated that we do not restrict the use of the term "natural" except on products that contain added color, synthetic substances and flavors as provided for in Title 21 of the Code of Federal Regulations (CFR), section 101.22. After reviewing the information about the HFCS production process that you provided, it is our understanding that the enzyme used to make HFCS is fixed to a column by the use of the synthetic fixing agent, glutaraldehyde. Any unreacted glutaraldehyde is remoyed by washing the column prior to the addition of the high dextrose equivalent com starch hydrolysate, which undergoes enzymatic reaction to produce HFCS. Because the glutaraldehyde does not come into contact with the high dextrose equivalent com starch hydrolysate, it would not bc considered to be included in or added to the HFCS. Therefore, we would not object to the use of the term "natural" on a product containing the HFCS produced by the manufacturing process described by Mr. Empie. However, we would object to the use of the term "natural" on a product containing HFCS that has a synthetic substance such as a synthetic fixing agent included in or added to it. We would also object to the use of the term "natural" on a product containing HFCS if the acids used to obtain the starch hydrolysate do not fit within our policy on "natural" as stated above. Received 07-03-2008 11:07am From-301 436 2639 To- Page 002 Source: :https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 436 2639 P.03 Page 2-Audre Bricson For your information, when we received an inquiry from Food Navigator-USA.com asking us whether a "natural" claim on a product containing HFCS and natural ingredients would be misleading to consumers, we reviewed our policy on the use of the term "natural". and our regulations on HFCS. In our response we stated our longstanding policy on the use of the term natural that we described above. We also described our regulation on HFCS (Title 21 of the Code of Federal Regulation (CFR), section 84.1866), which states that it is prepared from a high dextrose equivalent corn starch hydrolysate by partial enzymatic conversion of glucose (dextrose) to fructose using an insoluble glucose isomerase enzyme preparation listed at 21 CFR 184.1372. We indicated that, per 184.1372, the glucose isomerase enzyme preparation is fixed (rendered insoluble) using safe and suitable immobilization/fixing agents, including those listed in 21 CFR 173.357. We stated that the use of synthetic fixing agents in the enzyme preparation, which isithengused to produce HFCS, would not be consistent with our policy on the use of the term "natural." Consequently, we said that we would object to the use of the term "natural" on a product containing HFCS. In addition, we stated that the corn starch hydrolysate, which is the substrate used in the production of HFCS, may be obtained through the use of safe and suitable acids or enzymes. Depending on the type of acid(s) used to obtain the corn starch hydrolysate, this substrate itself may not fit within the description of "natural" and, therefore, we stated that HFCS produced from such corn starch hydrolysate would not qualify for a "natural" labeling term. Subsequently, we learned that in the process described by Mr. Empie none of the fixing agent (glutaraldehyde) would come in contact with the high dextrose equivalent com starch hydrolysate. Consistent with our policy on the use of the term "natural," WC have stated in the past that the determination on whether an ingredient would qualify for the use of the term "natural" is done on a case- by-case basis. Further, ingredients with the same common or usual name may be formulated in different ways, where a food containing the ingredient formulated one way may qualify for the use of term. "natural" and another food containing the ingredient with the same common or usual name, which has been formulated in a different way may not be eligible for the use of the term "natural." If we may be of further assistance, please let us know Sincerely yours. Gualdine a June Geraldine A. June Supervisor Product Evaluation and Labeling Team Food Labeling and Standards Staff Office of Nutrition, Labeling and Dietary Supplements Center for Food Safety and Applied Nutrition TOTAL P.03 Received 07-03-2008 11:07am From-301 436 2639 To= Page 003 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226 JUL-03-2008 10:26 FDA/CFSAN/ONPLDS 301 4362639 P.01 FDA CFSAN FOOD &s DRUG ADMIINISTRATION CENTER FOR FOOD SAFETY & APPLIED NUTRITION OFFICE OF NUTFTIONAL PRODUCTS, LABELING de DIETARY SUPPLEMENTS (HFS-800) 5100 Paint Branch Parkway College Park, MD 20740 TELEPHONE NUMBER: 301/436-2373 FAX NUMBER: 301/436-2636 DATE: 7/3/08 TO: audiae Enclsson FAX NUMBER: 202-331-2054 FROM: Catalin ALD-OUT COMMENTS: Received 07-03-2008 11:07am From-301 436 2630 To- Page 001 Source: https://www.industrydocuments.ucsf.edu/docs/rxpj0226

What are the scheduled public gatherings on?

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

on food labeling, food labeling

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

How much percent of consumers reads labels?

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

20%, 20 percent, 20

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

what is the main ingredient of soft drink?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

Carbonated Water, Carbonated water

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

What is are the words written in bold in second paragraph?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

Caffeine and Other Alleged Health Related Effects

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

What is the heading in right corner ?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

"Whats in Soft Drinks", "WHATS IN SOFT DRINKS"

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

What is the second reference mentioned?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

PepsiCo, Inc., The Physical or Technical Effect of Caffeine in Cola Beverages, Purchase, N.Y., July 20, 1981

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

Which university does the sixth reference mention?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

University of Florida

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

Which year is mentioned in the first reference?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

1983

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

who is marketing director?

lhpj0226

lhpj0226_p0

Robert L. Goldsmith, Robert l. goldsmith

Baxslift July 28, 1972 271 MADISON AVE. NEW YORK N.Y.10016 212 LE 2 - 0985 Michael F. Jacobson, Ph. D. Center for Science in the Public Interest 1346 Connecticut Avenue, N. W. Room 812 Washington, D. C. 20036 Dear Dr. Jacobson: Attached is a copy of the information on soft drinks produced by our Reader Panel studies. This should contain the information you require. Cordially, nirold RLG:jl Robert L. Goldsmith Att. Marketing Director THE NATIONAL MAGAZINE FOR ALL BOYS PUBLISHED BY THE BOY SCOUTS OF AMERICA Source: https://www.industrydocuments.ucsf.edu/docs/lhpj0226

What is the docket No?

xgpj0226

xgpj0226_p0, xgpj0226_p1, xgpj0226_p2, xgpj0226_p3, xgpj0226_p4, xgpj0226_p5, xgpj0226_p6, xgpj0226_p7, xgpj0226_p8, xgpj0226_p9

78N-0158

Docket No. 78N-0158 Food and Drug Administration Hearings on Food Labeling Washington, D.C. September 27, 1978 Testimony of Agnes Molnar Nutritionist, Food Law Project Community Action for Legal Services 335 Broadway, NY 10013 Thank you for this opportunity to present my views on food labeling. I am here first as a consumer and a parent, concerned about my family's health, and second as a professional concerned about the eating habits of the public. I have a Master's degree in Nutrition in Public Health from Columbia University. I am presently employed by the Food Law Project of Community Action for Legal Services in New York City under a grant to improve New York City's school meals program. Before addressing the specific issues raised, I would like to state for the record that there is a serious omission in the topics under discussion at these hearings. The consumer knows practically nothing about what ingredients are in the foods eaten away from home. Restaurant and institutional food represent a large and growing proportion of our total food consumption, but often even the operators of these establishments do not know what is in the food they serve. To cite a recent personal experience, while evaluating the nutritional quality of the school breakfast program in New York City, I found my work hampered by a lack of information on the ingredients of the foods served in the schools. For example, I needed information on the ingredients of the waffles that are served in the school breakfast program. I called the Board of Education's Office of School Food Services but no one there had a list of the ingredients. I was told that the waffles must meet the required specifications but these spec- ifications do not include a list of ingredients. I also called local school districts that run their own breakfast program 1 Source: https://www.industrydocuments.ucsf.edu/docs/xgpj0226 and got the same answer. I did find out that the waffles are a product made by Kellogg's and are the same as the item sold in retail stores. I found the item in my supermarket and copied the list of ingredients from the package label. Upon analysis, I discovered that the Kelloga's item is nutritionally inferior to waffles made from an enriched mix to which milk is added. The Kellogg's product is higher in fat, lower in protein, and substantially lower in calcium. The problem is that not one person in the city's school food service is aware of this nutritional difference. Needless to say, the children and others who are consumers of institutional and restaurant food are equally unaware of the nutritionalaquality:of^the foods they eat. I strongly urge that the issue of ingredient labeling of foods consumed away from home be addressed in the very near future. Our food system has undergone rapid and drastic changes in one or two decades. One outcome of this change is that food labels must serve as substitutes for more traditional ways of learning about foods. Instead of imitating, and per- haps embellishing on the home-cooked meals that mom used to make, we make choices about what foods to eat from food adver- tising and we learn how to cook from reading the instructions on food packages. These are drastic changes with an unknown impact on our health. Historically, the knowledge of food has been handed down through the generations and has been a crucial part of the socialization process that enables a society to endure. Until now, each succeeding generation has learned 2 how to nourish itself without reading food labels. Today, we are increasingly being taught what to eat by the food in- dustry. Their teachings are not based on tradition, nor are they based on sound nutrition knowledge or practice. Their teachings are based on promoting foods that provide maximum profits for the producer. Unfortunately, the most profitable foods are also the most highly processed, and the most nu- tritionally unbalanced. Many of these products are barely recognizable as food and need labels to tell us what to do with them. To explainiwhat I mean more clearly, most of us recog- nize a potato as food when it is in raw, boiled or baked form. Contrast this with a box that contains a white powder and is called "instant mashed potato". We don't recognize this as food by its appearance, its smell, or its taste. This box of powder must have a label to identify it as an edible pro- duct. The fact that it is almost worthless nutritionally and does not compare with a real potato is not known by the con- sumer and is not so stated on the label. If the consumer is really to make a free and informed choice between a raw potato and instant mashed potatoes, that choice must be made based on all the facts and not on convenience alone. I am pleased to respond to the specific questions asked in the background information that has been prepared for these hearings. The information that is provided and the questions that have been asked are excellent and I will respond to them directly. I am submitting written comments in response to 3 Source:https://www.industrydocuments.ucsf.edu/docs/xgpj0226 most of the questions. I also want to highlight orally what I consider to be the more important aspects of labeling that need change. First, under ingredient labeling in response to question number 3, I believe that a quantitative ingredient label is tremendously important. The present method of listing ingred- ients in order of predominance does not indicate for example, whether a product has 30% or 50% sugar, although the place of sugar in the list of ingredients may be exactly the same. I have a cake mix label that begins with the following ingredients: sugar; enriched flour bleached; animal and/or vegetable short- ening; plus several other items. This cake mix might consist of 70% sugar, 20% flour, and 5% shortening. On the other hand, it might contain 40% sugar, 35% flour, and 20% shortening. The difference between the two products would be quite sub- stantial but the present label does not provide a clue as to the percent composition of the product. I would not be at allchagrined if consumers are discouraged from buying a product because the label identifies it as containing 70% sugar. Such consumer response might serve as an impetus to reduce the sugar content of the product. When we begin to label ingred- ients quantitatively, we will have achieved a major step in informing the consumer. Another important point is asked in question number 8 under Names of Ingredients. Spices, flavors, and colorings, although present in minute amounts, are the additives that are most 4 likely to cause allergic reactions in sensitive persons. Many allergic people find out through trial and error which foods cause reactions and they may never know which ingredient has adversely affected them. It appears that the numbers. of food allergies are increasing and that a dislosure of all ingredients on the label is necessary. On the other hand, many people probably avoid purchasing products under the mistaken notion that they contain unidentified harmful ingredients. Another item of importance is the need to identify the purpose or function of ingredients in a product. Only pre- servatives must now be so identified. Grouping ingredients according to their function, such as flavorings, colorings, or nutrients, would serve to reduce irrational fears of strange sounding chemical names and might cut down on manufacturer use of the more frivolous additives. I know that the name thiamin hydrochloride has frightened many consumers who may remember that hydrochloric acid is a potent and dangerous chemical. But thiamin hydrochloride as used in food is the nutrient, vitamin B-1. Fortification is one subject which disturbs me. I do not believe that fortification of foods is a desirable or effective way of maintaining or protecting our health. Overall, fort- ification should be allowed only as a replacement process for the nutrients that are lost in the refining or processing of foods. At best, this will only be a partial replacement, first because we don t know the full extent of the loss of nutrients- and second because we cannot replace all the known losses of nutrients with our present state of technology. 5 Our major successes in the area of fortification have been the enrichment of grains with some of the nutrients that are lost in refining, and the addition of vitamin D to milk. Although these were instituted long ago, as of now, we have no equally impressive results, such as the elimination of rickets through Vitamin-D fortification, or the elimination of pellagra through enrichment of grains with niacin. Promotion of fortified foods misleads consumers. For example, fortified breakfast cereals are promoted as nutritious foods, particularly to children who are the major consumers of these breakfast cereals. Nutritionally, these cereals are no better than sugar-coated vitamin pills. Interestingly, some who shout the loudest against the need for vitamin pills are the same people who laud the nutritive value of breakfast cereals. Consumers are misled into believing these foods are nutritionally complete. No mention is made of the dozens of vitamins and minerals that are not provided in these cereals, and no mention is made of the need to eat a variety of foods for a true nutritionally complete diet. 6 Therefore, my unequivocal answer to question number 1 is that the criteria for food fortification should be to pre- vent the occurrence of a real nutrient déficiency disease where the foods and the nutrients that are the cause of the deficiency are well understood. In addition, foods should not be fortified with nutrients that are not naturally found in that food. Fortification is appropriate only when it replaces the loss of a nutrient that is normally expected to be obtained from the food, such as the fortification of potatoes with vitamin C. When they are not unduly processed, potatoes are a naturally good source of vitamin C. Since French fries lose a great deal of their vitamin C content, the replacement of this nutrient is appro- priate and desirable. However, some French fried potatoes are now fortified with vitamin A as well as vitamin C. Vitamin A is not a nutrient that is found in white potatoes. This is a misuse of fortification. The reason that might be given for fortifying white potatoes is that a deficiency of this nutrient is prevalent in our population. If indeed, there is a deficiency of vitamin A in our population, the cause of that deficiency is certainly not due to the loss of vitamin A through the processing of white potatoes. The cause is more likely to be due to decreased consumption of foods such as liver, eggs, dark green leafy vegetables, carrots, and sweet potatoes and an increase in the consumption of French 7 fries. This change in dietary habits has more far-reaching consequences than just a vitamin A deficiency. French fries are a. highly processed, nutrient-poor, high-fat, high-sodium product, and should not be relied upon as a source of vitamin A. In comparison, dark green leafy vegetables, which are an excellent natural source of vitamin A also provide vitäminCC, calcium and other minerals, but contain no fat and little sodium. Clearly, this is much the better way to get our re- quirement of vitamin A. If nutrition policy is to serve the public wisely and well, the need to improve eating habits must be promoted rather than relying on the practice of fort- ifying foods to correct suspected deficiences of one or two nutrients. 8 The last item I want to comment on is the question of food standards under the section entitled "Safe and Suitable Ingredients". Standards of identity for certain foods such as ice cream or baked goods, have outlived their usefulness and now serve as a major impediment to full disclosure of ingredients in the foods we consume. I do not know which foods still re- quire standards. I do know that consumers need to be told what ingredients are in all the foods offered to them in the marketplace, whether those foods are covered by standards or not. In closing, I want to read a quote from one of the many books on nutrition written by Ronald Deutsch. In answer to some critics of the food industry, Mr. Deutsch says, "In a free society the public gets only what it asks for." I would like to reply, that before the public can ask for something, the public needs to know what it is already getting. Thank you. 9

who published the national magazine for all boys ?

lhpj0226

lhpj0226_p0

the boy scouts of america

Baxslift July 28, 1972 271 MADISON AVE. NEW YORK N.Y.10016 212 LE 2 - 0985 Michael F. Jacobson, Ph. D. Center for Science in the Public Interest 1346 Connecticut Avenue, N. W. Room 812 Washington, D. C. 20036 Dear Dr. Jacobson: Attached is a copy of the information on soft drinks produced by our Reader Panel studies. This should contain the information you require. Cordially, nirold RLG:jl Robert L. Goldsmith Att. Marketing Director THE NATIONAL MAGAZINE FOR ALL BOYS PUBLISHED BY THE BOY SCOUTS OF AMERICA Source: https://www.industrydocuments.ucsf.edu/docs/lhpj0226

With whom is the meeting being conducted?

gxpj0226

gxpj0226_p0, gxpj0226_p1, gxpj0226_p2

Sandy Douglas, Coca-Cola Co., Sandy Douglas

Coca-ColaF January 29, 2016 MFJ meeting with Sandy Douglas, Coca-Cola Co. Arti Arora, Senior Director Regulatory & Policy. Caren Pasquale Seckler, VP social commitment Jim O'Hara, CSPI He said that Coke has a five-point overall strategy: Shaping choice Innovation Clear facts (labeling?) Market responsibly (no logos on toys, etc.) Leading engagement (ABA's commitment to cut calories by 20%) His main point was to explain Coke's One Brand marketing strategy, which means including all brands in each ad. This includes significant packaging redesign, e.g., changing Diet Coke from silver with red trim to Coke red with silver trim. Indicated that this was going to happen for Coke Zero as well which is now black with red trim. Says it's a big deal. We shall see. His main point also was that Coke aims to reduce added sugars. It is making a big push to increase sales of 7.5- to 8.5-oz cans and bottles. He says they are higher priced now because relatively few bottlers have the ability to produce them, so shipping and other distribution costs are high. Coke wants to reduce the price differential. This faces significant hurdle with retailers who have relied on cheap soda as "loss leader". He hoped that the industry and health advocates could cooperate to push the moderation theme. And by industry, he meant the entire food and beverage industry, including supermarkets and restaurants. (I should talk with Larry Soler and others about that.) Moderation, he said, also represents a significant change in a 40-year-old business model where one and all were rewarded by increasing unit volume. Focus now is on generating revenue rather than volume. He said that in a recent period of time only one in four Americans had had a Coke. If that number can be hiked to one in two Americans, then theoretically that can bring down the per capita consumption but still drive revenue increase. 20% reduction in the UK from 2015 to 2020 (here is it 20% by 2025): He said that Britons believe EFSA's reassurances that aspartame is safe, whereas Americans don't believe U.S. government assurances. Apparently, Britons have been switching from full-calorie to diet soft drinks. Source: https://www.industrydocuments.ucsf.edu/docs/gxpj0226 He said that Coke is trying hard to move people in the three test markets (NYC, Little Rock, LA) to diet drinks, but most people are just not interested. Big challenge to reduce calories consumed by minorities. They plan to expand the study to an additional two or three cities. He said this is another example of testing "moderation" because these communities are high-volume consumers. How to reduce/shift consumption patterns. (We should check in with Brian Elbel about his evaluation which may be being funded by NYC.) He said that Diet Coke is not made with Coke's "secret formula," but that Coke Zero is. The latter tastes better. Relatively few people have tried Zero, but when they do, they like it. Caren said people don't understand "zero" means no added sugars. They may label it to say "Zero added sugars." Coke is working hard on new formulations with fewer calories. Marketing to kids: Coke (Caren) is taking a comprehensive look, including the 35% audience limit and theme parks. He said that Coke is reviewing its licensing contracts that result in Coke logos being used on toys. He said that Coke would like to get rid of Coke- emblazoned toys that don't have anything to do with Coca-Cola (such as baby bibs and toy trucks), but Coke would not stop selling or licensing toys/dolls/etc. with things like polar bears and Santa Claus, which are part of Coca-Cola iconography. Unclear the magnitude/scope of products that would be affected but suggested it was sizeable. He also said that Coke is trying to figure out how to stop Coke commercials from being run in movie theaters showing films aimed at young kids. What's happening with Disney? He couldn't discuss. He couldn't discuss pricing, such as when I asked him about trading higher volume for higher profits. Said repeatedly this was from lawyers. School scoreboards? Not at elementary schools, but would keep sponsoring them at middle and high schools. Coke will revise its branding at Boys & Girls Clubs and other community groups. Coke will continue to fund groups but will look to remove objectionable "branding" such as on uniforms. Again, unclear how extensive and how much real change. Added sugars: he assured us that Coke would not oppose FDA's proposal to list "added sugars" on Nutrition Facts panels. But Coke would like the %DV to include naturally occurring sugars, too. I explained that those sugars never posed a health problem and that people should be eating more of those sugars, because they occur in fruit and milk. He indicated they were prepared to accept whatever FDA ended up with and that the Coke Source: :ttps://www.industrydocuments.ucsf.edu/docs/gxpj0226 position has been communicated to the ABA and GMA (on which boards he sits) and he expects that they too will not object, e.g., sue. He said that he hasn't forgotten about our recommendation that sizes of containers be shrunk. We did not discuss FOP labels-like UK, Ecuador, or Chile. We did not discuss health notices (Excessive consumption of this beverage may increase your risk of obesity or other health problem) Reducing sugar content/sweetness levels (Tea line they are using stealth methods to cut total sweetness slowly) "Moderation" will be the message of Coke's Super Bowl advertising this year. Sought to put their Super Bowl advertising in a broad, progressive frame, i.e., the Hilltop ad was really anti-war, Big Mean Joe Green ad was really civil rights, the 2012 ad with the gay couple was an LGBT-rights ad especially in the context of the Moscow Olympics. Said we would both like and dislike it. Stay tuned. Source: https://www.industrydocuments.ucsf.edu/docs/gxpj0226

what is the title of the page?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

historical background

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

what are the common sources of caffeine consumed by humans?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

coffee beans, tea leaves, kola nuts and cocoa beans

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

What is the name of the person mentioned to Contact?

lzyj0226

lzyj0226_p0, lzyj0226_p1, lzyj0226_p2, lzyj0226_p3

Carlton, Carlton Curtis

The (ocneCola Company Media Relations Department P.O. Drawer 1734, Allanta, Ga. 30301 news Telephone (404) 676-2121 release FOR IMMEDIATE RELEASE Contact: Carlton Curtis 404/676-2678 COCA-COLA BEGINS 100TH YEAR WITH A NEW TASTE; FIRST CHANGE EVER IN SECRET FORMULA NEW YORK, April 23, 1985 -- Coca-Cola, the world's number one consumer product, will begin its 100th year with a new taste, representing the first change in the secret formula since Coca-Cola was created in 1886. "The best has been made even better, said Roberto C. Goizueta, chairman of the Board and chief executive officer of The Coca-Cola Company. "We have changed the taste of the most universally enjoyed consumer product around the world. "Consumers in blind taste tests all across the continent have told us they prefer the new taste of Coca-Cola to the original by an overwhelming majority," Mr. Goizueta said, "and there is an even wider margin when consumers are told, 'This is a new Coca-Cola. Mr. Goizueta added, "Some may choose to call this the boldest single marketing move in the history of the packaged goods business. We simply call it the surest move ever made, because the new taste of Coke was shaped by the taste of the consumer. Source: https://www.industrydocunfents.ucsf.edu/docs//zyj0226 Page 2 "The success of Coca-Cola has been built on a commitment to give consumers the best,' said Mr. Goizueta. "For 99 years, it has consistently delivered on the simple promise of refreshment and, as a result, has become a symbol of quality and synonymous with leadership. The new taste guarantees that Coca-Cola will continue to deserve this reputation for the next 100 years. " A legendary aspect of the product that will not change is the secrecy of the Coca-Cola formula. The original formula for Coca-Cola is one of the world's best-kept secrets, and the new formula will continue that tradition. Mr. Goizueta explained how the new taste was developed. "Just a few years back, we realized we needed a product worthy of the Coca-Cola name in the fast-growing low-calorie soft drink market. Our outstanding flavor researchers came through with flying colors when they created diet Coke. The success of diet Coke is already history -- the best diet soft drink ever created and now the number one low-calorie soft drink in the world. "In the process of perfecting diet Coke, our researchers first discovered a flavor complex, refined over time into a new cola formula, which we quickly realized was highly preferred over Coca-Cola itself, and, of course, over its primary competition. Page 3 "Our extensive data convinced us that this formula had achieved a new plateau of taste superiority,' said Mr. Goizueta. "That taste would have to be Coca-Cola. Coca-Cola could be nothing less. Any other decision would not have been trué to what Coca-Cola has come to mean over the past 99 years. "s Mr. Goizueta declined to describe the new taste of Coca-Cola. "I would not attempt to define the experience which each person will enjoy with the first sip of Coca-Cola with the new taste, said Mr. Goizueta. "The millions of people who have a special place in their hearts for the taste of Coca-Cola will find that they have been rewarded with an even better tasting Coke.' Every year Coca-Cola continues to set new soft drink sales records. In the United States, for-example, nearly 50 million people enjoy a serving of Coca-Cola on any given day. Around the world, Coca-Cola is consumed at the rate of over 270 million servings per day. The new taste of Coca-Cola will first be brought to consumers by Bottlers and fountain retailers in the United States and Canada. Concentrate and syrup are being shipped to U.S. and Canadian Bottlers and fountain retailers today, with widespread distribution of Coke and caffeine-free Coke with the new taste expected by May 8th, the beginning of the 100th year of Coca-Cola. Source: https://www.industrydocuefents.ucsf.edu/docs//zyj0226 Page 4 Within six weeks most of the United States and Canada will be introduced to the product's new taste. International distribution of Coca-Cola with the new taste will begin within a few months. Introductory dates for each market will be announced locally. Advertising for the new taste of Coca-Cola will begin immediately. After the introductory phase, which will take three to four weeks, a revised "Coke is it!' theme will be used for the campaign. Several executions with actor and comedian Bill-Cosby will be featured. Packaging for the new taste of Coke has been modified with striking silver accents featured on cans, non-returnable bottles and plastic bottles. The classic Coca-Cola Spencerian script of the trademarks and red background are unchanged. # # # Source: https://www.industrydocuments.ucsf.edu/docs//lzyj0226

Which year is COCA-COLA beginning with a new taste?

lzyj0226

lzyj0226_p0, lzyj0226_p1, lzyj0226_p2, lzyj0226_p3

100, 100th year, its 100th year

The (ocneCola Company Media Relations Department P.O. Drawer 1734, Allanta, Ga. 30301 news Telephone (404) 676-2121 release FOR IMMEDIATE RELEASE Contact: Carlton Curtis 404/676-2678 COCA-COLA BEGINS 100TH YEAR WITH A NEW TASTE; FIRST CHANGE EVER IN SECRET FORMULA NEW YORK, April 23, 1985 -- Coca-Cola, the world's number one consumer product, will begin its 100th year with a new taste, representing the first change in the secret formula since Coca-Cola was created in 1886. "The best has been made even better, said Roberto C. Goizueta, chairman of the Board and chief executive officer of The Coca-Cola Company. "We have changed the taste of the most universally enjoyed consumer product around the world. "Consumers in blind taste tests all across the continent have told us they prefer the new taste of Coca-Cola to the original by an overwhelming majority," Mr. Goizueta said, "and there is an even wider margin when consumers are told, 'This is a new Coca-Cola. Mr. Goizueta added, "Some may choose to call this the boldest single marketing move in the history of the packaged goods business. We simply call it the surest move ever made, because the new taste of Coke was shaped by the taste of the consumer. Source: https://www.industrydocunfents.ucsf.edu/docs//zyj0226 Page 2 "The success of Coca-Cola has been built on a commitment to give consumers the best,' said Mr. Goizueta. "For 99 years, it has consistently delivered on the simple promise of refreshment and, as a result, has become a symbol of quality and synonymous with leadership. The new taste guarantees that Coca-Cola will continue to deserve this reputation for the next 100 years. " A legendary aspect of the product that will not change is the secrecy of the Coca-Cola formula. The original formula for Coca-Cola is one of the world's best-kept secrets, and the new formula will continue that tradition. Mr. Goizueta explained how the new taste was developed. "Just a few years back, we realized we needed a product worthy of the Coca-Cola name in the fast-growing low-calorie soft drink market. Our outstanding flavor researchers came through with flying colors when they created diet Coke. The success of diet Coke is already history -- the best diet soft drink ever created and now the number one low-calorie soft drink in the world. "In the process of perfecting diet Coke, our researchers first discovered a flavor complex, refined over time into a new cola formula, which we quickly realized was highly preferred over Coca-Cola itself, and, of course, over its primary competition. Page 3 "Our extensive data convinced us that this formula had achieved a new plateau of taste superiority,' said Mr. Goizueta. "That taste would have to be Coca-Cola. Coca-Cola could be nothing less. Any other decision would not have been trué to what Coca-Cola has come to mean over the past 99 years. "s Mr. Goizueta declined to describe the new taste of Coca-Cola. "I would not attempt to define the experience which each person will enjoy with the first sip of Coca-Cola with the new taste, said Mr. Goizueta. "The millions of people who have a special place in their hearts for the taste of Coca-Cola will find that they have been rewarded with an even better tasting Coke.' Every year Coca-Cola continues to set new soft drink sales records. In the United States, for-example, nearly 50 million people enjoy a serving of Coca-Cola on any given day. Around the world, Coca-Cola is consumed at the rate of over 270 million servings per day. The new taste of Coca-Cola will first be brought to consumers by Bottlers and fountain retailers in the United States and Canada. Concentrate and syrup are being shipped to U.S. and Canadian Bottlers and fountain retailers today, with widespread distribution of Coke and caffeine-free Coke with the new taste expected by May 8th, the beginning of the 100th year of Coca-Cola. Source: https://www.industrydocuefents.ucsf.edu/docs//zyj0226 Page 4 Within six weeks most of the United States and Canada will be introduced to the product's new taste. International distribution of Coca-Cola with the new taste will begin within a few months. Introductory dates for each market will be announced locally. Advertising for the new taste of Coca-Cola will begin immediately. After the introductory phase, which will take three to four weeks, a revised "Coke is it!' theme will be used for the campaign. Several executions with actor and comedian Bill-Cosby will be featured. Packaging for the new taste of Coke has been modified with striking silver accents featured on cans, non-returnable bottles and plastic bottles. The classic Coca-Cola Spencerian script of the trademarks and red background are unchanged. # # # Source: https://www.industrydocuments.ucsf.edu/docs//lzyj0226

What is the date mentioned?

lzyj0226

lzyj0226_p0, lzyj0226_p1, lzyj0226_p2, lzyj0226_p3

April 23, 1985

The (ocneCola Company Media Relations Department P.O. Drawer 1734, Allanta, Ga. 30301 news Telephone (404) 676-2121 release FOR IMMEDIATE RELEASE Contact: Carlton Curtis 404/676-2678 COCA-COLA BEGINS 100TH YEAR WITH A NEW TASTE; FIRST CHANGE EVER IN SECRET FORMULA NEW YORK, April 23, 1985 -- Coca-Cola, the world's number one consumer product, will begin its 100th year with a new taste, representing the first change in the secret formula since Coca-Cola was created in 1886. "The best has been made even better, said Roberto C. Goizueta, chairman of the Board and chief executive officer of The Coca-Cola Company. "We have changed the taste of the most universally enjoyed consumer product around the world. "Consumers in blind taste tests all across the continent have told us they prefer the new taste of Coca-Cola to the original by an overwhelming majority," Mr. Goizueta said, "and there is an even wider margin when consumers are told, 'This is a new Coca-Cola. Mr. Goizueta added, "Some may choose to call this the boldest single marketing move in the history of the packaged goods business. We simply call it the surest move ever made, because the new taste of Coke was shaped by the taste of the consumer. Source: https://www.industrydocunfents.ucsf.edu/docs//zyj0226 Page 2 "The success of Coca-Cola has been built on a commitment to give consumers the best,' said Mr. Goizueta. "For 99 years, it has consistently delivered on the simple promise of refreshment and, as a result, has become a symbol of quality and synonymous with leadership. The new taste guarantees that Coca-Cola will continue to deserve this reputation for the next 100 years. " A legendary aspect of the product that will not change is the secrecy of the Coca-Cola formula. The original formula for Coca-Cola is one of the world's best-kept secrets, and the new formula will continue that tradition. Mr. Goizueta explained how the new taste was developed. "Just a few years back, we realized we needed a product worthy of the Coca-Cola name in the fast-growing low-calorie soft drink market. Our outstanding flavor researchers came through with flying colors when they created diet Coke. The success of diet Coke is already history -- the best diet soft drink ever created and now the number one low-calorie soft drink in the world. "In the process of perfecting diet Coke, our researchers first discovered a flavor complex, refined over time into a new cola formula, which we quickly realized was highly preferred over Coca-Cola itself, and, of course, over its primary competition. Page 3 "Our extensive data convinced us that this formula had achieved a new plateau of taste superiority,' said Mr. Goizueta. "That taste would have to be Coca-Cola. Coca-Cola could be nothing less. Any other decision would not have been trué to what Coca-Cola has come to mean over the past 99 years. "s Mr. Goizueta declined to describe the new taste of Coca-Cola. "I would not attempt to define the experience which each person will enjoy with the first sip of Coca-Cola with the new taste, said Mr. Goizueta. "The millions of people who have a special place in their hearts for the taste of Coca-Cola will find that they have been rewarded with an even better tasting Coke.' Every year Coca-Cola continues to set new soft drink sales records. In the United States, for-example, nearly 50 million people enjoy a serving of Coca-Cola on any given day. Around the world, Coca-Cola is consumed at the rate of over 270 million servings per day. The new taste of Coca-Cola will first be brought to consumers by Bottlers and fountain retailers in the United States and Canada. Concentrate and syrup are being shipped to U.S. and Canadian Bottlers and fountain retailers today, with widespread distribution of Coke and caffeine-free Coke with the new taste expected by May 8th, the beginning of the 100th year of Coca-Cola. Source: https://www.industrydocuefents.ucsf.edu/docs//zyj0226 Page 4 Within six weeks most of the United States and Canada will be introduced to the product's new taste. International distribution of Coca-Cola with the new taste will begin within a few months. Introductory dates for each market will be announced locally. Advertising for the new taste of Coca-Cola will begin immediately. After the introductory phase, which will take three to four weeks, a revised "Coke is it!' theme will be used for the campaign. Several executions with actor and comedian Bill-Cosby will be featured. Packaging for the new taste of Coke has been modified with striking silver accents featured on cans, non-returnable bottles and plastic bottles. The classic Coca-Cola Spencerian script of the trademarks and red background are unchanged. # # # Source: https://www.industrydocuments.ucsf.edu/docs//lzyj0226

what is widely distributed naturally occuring substance found in more than 60 plant species throughout he world?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

caffeine

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

Who said, "The best has been made even better"?

lzyj0226

lzyj0226_p0, lzyj0226_p1, lzyj0226_p2, lzyj0226_p3

Mr. Goizueta, Roberto C. Goizueta, chairman of the Board and Chief executive officer of The Coca-Cola Company, Roberto C. Goizueta

The (ocneCola Company Media Relations Department P.O. Drawer 1734, Allanta, Ga. 30301 news Telephone (404) 676-2121 release FOR IMMEDIATE RELEASE Contact: Carlton Curtis 404/676-2678 COCA-COLA BEGINS 100TH YEAR WITH A NEW TASTE; FIRST CHANGE EVER IN SECRET FORMULA NEW YORK, April 23, 1985 -- Coca-Cola, the world's number one consumer product, will begin its 100th year with a new taste, representing the first change in the secret formula since Coca-Cola was created in 1886. "The best has been made even better, said Roberto C. Goizueta, chairman of the Board and chief executive officer of The Coca-Cola Company. "We have changed the taste of the most universally enjoyed consumer product around the world. "Consumers in blind taste tests all across the continent have told us they prefer the new taste of Coca-Cola to the original by an overwhelming majority," Mr. Goizueta said, "and there is an even wider margin when consumers are told, 'This is a new Coca-Cola. Mr. Goizueta added, "Some may choose to call this the boldest single marketing move in the history of the packaged goods business. We simply call it the surest move ever made, because the new taste of Coke was shaped by the taste of the consumer. Source: https://www.industrydocunfents.ucsf.edu/docs//zyj0226 Page 2 "The success of Coca-Cola has been built on a commitment to give consumers the best,' said Mr. Goizueta. "For 99 years, it has consistently delivered on the simple promise of refreshment and, as a result, has become a symbol of quality and synonymous with leadership. The new taste guarantees that Coca-Cola will continue to deserve this reputation for the next 100 years. " A legendary aspect of the product that will not change is the secrecy of the Coca-Cola formula. The original formula for Coca-Cola is one of the world's best-kept secrets, and the new formula will continue that tradition. Mr. Goizueta explained how the new taste was developed. "Just a few years back, we realized we needed a product worthy of the Coca-Cola name in the fast-growing low-calorie soft drink market. Our outstanding flavor researchers came through with flying colors when they created diet Coke. The success of diet Coke is already history -- the best diet soft drink ever created and now the number one low-calorie soft drink in the world. "In the process of perfecting diet Coke, our researchers first discovered a flavor complex, refined over time into a new cola formula, which we quickly realized was highly preferred over Coca-Cola itself, and, of course, over its primary competition. Page 3 "Our extensive data convinced us that this formula had achieved a new plateau of taste superiority,' said Mr. Goizueta. "That taste would have to be Coca-Cola. Coca-Cola could be nothing less. Any other decision would not have been trué to what Coca-Cola has come to mean over the past 99 years. "s Mr. Goizueta declined to describe the new taste of Coca-Cola. "I would not attempt to define the experience which each person will enjoy with the first sip of Coca-Cola with the new taste, said Mr. Goizueta. "The millions of people who have a special place in their hearts for the taste of Coca-Cola will find that they have been rewarded with an even better tasting Coke.' Every year Coca-Cola continues to set new soft drink sales records. In the United States, for-example, nearly 50 million people enjoy a serving of Coca-Cola on any given day. Around the world, Coca-Cola is consumed at the rate of over 270 million servings per day. The new taste of Coca-Cola will first be brought to consumers by Bottlers and fountain retailers in the United States and Canada. Concentrate and syrup are being shipped to U.S. and Canadian Bottlers and fountain retailers today, with widespread distribution of Coke and caffeine-free Coke with the new taste expected by May 8th, the beginning of the 100th year of Coca-Cola. Source: https://www.industrydocuefents.ucsf.edu/docs//zyj0226 Page 4 Within six weeks most of the United States and Canada will be introduced to the product's new taste. International distribution of Coca-Cola with the new taste will begin within a few months. Introductory dates for each market will be announced locally. Advertising for the new taste of Coca-Cola will begin immediately. After the introductory phase, which will take three to four weeks, a revised "Coke is it!' theme will be used for the campaign. Several executions with actor and comedian Bill-Cosby will be featured. Packaging for the new taste of Coke has been modified with striking silver accents featured on cans, non-returnable bottles and plastic bottles. The classic Coca-Cola Spencerian script of the trademarks and red background are unchanged. # # # Source: https://www.industrydocuments.ucsf.edu/docs//lzyj0226

H ow many years of advertising is mentioned?

ztyj0226

ztyj0226_p0, ztyj0226_p1, ztyj0226_p2, ztyj0226_p3, ztyj0226_p4

95, 95 years

news Coker - COCA-COLA USA Public Relations Department P.O. Drawer 1734, Atlanta. Ga. 30301 Telephone (404)898-2121 CONTACT: Tony Tortorici FOR IMMEDIATE RELEASE 404/898-3696 PAUSE TO REFLECT 95 YEARS OF ADVERTISING FOR COCA-COLA ATLANTA, Feb. 4, 1982 "Coke is it!" is the new advertising theme for Coca-Cola and the descendant of a series of slogans which are as much a part of American life as Brand Coke itself. Unveiled this week at a Coca-Cola USA Bottlers' meeting in Atlanta, "Coke is it!" is a bold concept which succeeds "Have a Coke and a smile, II the main advertising theme for the product since 1979. The new theme breaks from tradition by placing more emphasis on the superiority of Coca-Cola in taste, total refreshment and as a thirst-quencher. The direct, positive statement "Coke is it!" -- appeals to the forthright stance of Americans in the 1980s. Throughout the history of Coca-Cola, the Company's advertising has accurately reflected attitudes of the times, often anticipating changing lifestyles and the national temperament. Since 1886, adver- tising for Coca-Cola has portrayed fluctuations in social climate, structure, values and politics. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -2- In the late 1880s, initial distribution of Coca-Cola began in the South. In tune with the temperance movement, Coke was the perfect answer -- a non-alcoholic beverage, "delicious and refreshing." At the time, Coke was only a fountain drink and the soda fountain was the American social institution -- a place to court a girl, or meet friends, always over a Coke. Magazine ads depicted corseted ladies and mustached gentlemen chatting with the "soda jerk" over their favorite fountain drink with its distinctive red-and-white sign on the mirror in the background. Along came the teens of the early twentieth century when baseball had become the national pastime. Of course, major league ball players were featured in advertising for Coca-Cola. They included such noted athletes as Ty Cobb, Rabbit Maranville, Walter Johnson, and Eddie Collins. Fashion, culture and technology went through a major revolution in the '20s, and Coke was in the forefront with flappers -- and a strange- looking machine called the automobile. Sports interests were broadening and suddenly golfers began showing up in ads for Coca-Cola. By the 1930s movies were enchanting the American public. Advertising for Coke featured major film stars of the period, all enjoying a refreshing, carbonated drink which, by now, everyone recog- nized as Coke. Some of them included Cary Grant, Claudette Colbert, Wallace Beery and Maurice Chevalier. The film industry's glorification of such stars as Jean Harlow reflect the public's new and more liberated willingness to admire openly the female form, so bathing beauties began sipping Coke by the sea in ads of the time. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -3- Depression years brought tightening of the budget and Coca-Cola offered not only a refreshing pause to keep you going but "The Biggest Nickel's Worth in the Store.' " Radio, an inexpensive form of entertainment, flourished in that Depression Era and the product Coca-Cola became one of the first com- merical sponsors, with such programs as "Refreshment Time" featuring Singing Sam, broadcast into living rooms each week all over the country. Later, Edgar Bergen and Charlie McCarthy, Spike Jones, Percy Faith and others were to entertain millions on radio for Coca-Cola. When the nation marched off to war in the '40s, Coca-Cola marched along. Robert W. Woodruff, then president of The Coca-Cola Company, announced the Company would "see that every man in uniform gets a bottle of Coca-Cola wherever he is and whatever it costs the Company. " The famous contour bottles were mobilized and more than five billion of them went to servicemente and women wherever they were stationed. On the homefront, ads for Coca-Cola featured wartime themes and as it drew to a close, smiling blondes in seamed stocking pulled wagon- - loads of bottled Coke down the street announcing, "He's Coming Home Tomorrow." The placid '50s replaced the soda fountain as the primary social gathering place with "drive-in" restaurants where Coca-Cola could be served curbside. Bowling began to appear in ads; slogans were, like the times, calm, unpretentious, straightforward. But those quiet, postwar years brought one of the most dynamic changes that media advertising for Coca-Cola would ever experience -- the black and white flickering of an uncertain new gadget called tele- vision. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -4- The first network TV show, a Thanksgiving special featuring Edgar Bergen and Charlie McCarthy, was sponsored by Brand Coca-Cola. At the same time, Company and agency ad executives decided it was time for a new look in print advertising, too, and they made the "drastic" change from graphics to photography, exclusively. "Rock and Roll" was in its embryonic stages with the pop music of the early 60s when major recording stars such as Ray Charles, Petula Clark and Connie Francis were featured in advertising for Coca-Cola. A new slogan announced "Things go better with Coke," and sales figures indicated most folks agreed. American youth yearned to return to basic values in the early '70s and advertising for Coca-Cola anticipated the American disenchantment which would occur with artificiality. The advertising theme for Coke emphasized the genuine, the basic, the authentic "It's the real thing" was born. The political uncertainty in the nation that followed presented a new creative challenge to advertising for Coca-Cola. The solution -- to remind Americans of the positive values in the country. "Look up America, said the new advertising for Coca-Cola and people smiled again. The advertising concept, "Coke adds life," continued the variation on a theme, that Coca-Cola adds a simple thing to the lives of Americans - enjoyment. Simple, but important - a break from the ordinary, to enjoy a product whose quality Americans know and on which they can depend. In 1979, "Have a Coke and a smile" further emphasized the reliability and the reward in drinking Coca-Cola. "Coke is it!" sums up these themes -- the quality, the enjoyment and, most of all, the anticipation and the reward for a good day's work. Americans in the 1980s are sharp and aggressive, looking for the best. As a refreshment, the theme states, "Coke is it!" AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -5- Advertising for Coke has been called innovative and revolutionary. Yet all of the themes, even in the 1980s, carry a basic message not so different from John Pemberton's first ad when he developed Coca-Cola in a kettle in his backyard. The red-and-white sign on the door of Jacobs' pharmacy read: "Drink Coca-Cola" and Pemberton's first newspaper ad in 1886 carried this message: "Coca-Cola. Delicious. Refreshing." "Coke is it!" simplifies these intrinsic qualities and promises the consumer that the most popular soft drink in the world is also the best. # # # AJT/RCW/1.19.9 Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226

What is the date mentioned?

ztyj0226

ztyj0226_p0, ztyj0226_p1, ztyj0226_p2, ztyj0226_p3, ztyj0226_p4

Feb 4, 1982, Feb. 4, 1982

news Coker - COCA-COLA USA Public Relations Department P.O. Drawer 1734, Atlanta. Ga. 30301 Telephone (404)898-2121 CONTACT: Tony Tortorici FOR IMMEDIATE RELEASE 404/898-3696 PAUSE TO REFLECT 95 YEARS OF ADVERTISING FOR COCA-COLA ATLANTA, Feb. 4, 1982 "Coke is it!" is the new advertising theme for Coca-Cola and the descendant of a series of slogans which are as much a part of American life as Brand Coke itself. Unveiled this week at a Coca-Cola USA Bottlers' meeting in Atlanta, "Coke is it!" is a bold concept which succeeds "Have a Coke and a smile, II the main advertising theme for the product since 1979. The new theme breaks from tradition by placing more emphasis on the superiority of Coca-Cola in taste, total refreshment and as a thirst-quencher. The direct, positive statement "Coke is it!" -- appeals to the forthright stance of Americans in the 1980s. Throughout the history of Coca-Cola, the Company's advertising has accurately reflected attitudes of the times, often anticipating changing lifestyles and the national temperament. Since 1886, adver- tising for Coca-Cola has portrayed fluctuations in social climate, structure, values and politics. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -2- In the late 1880s, initial distribution of Coca-Cola began in the South. In tune with the temperance movement, Coke was the perfect answer -- a non-alcoholic beverage, "delicious and refreshing." At the time, Coke was only a fountain drink and the soda fountain was the American social institution -- a place to court a girl, or meet friends, always over a Coke. Magazine ads depicted corseted ladies and mustached gentlemen chatting with the "soda jerk" over their favorite fountain drink with its distinctive red-and-white sign on the mirror in the background. Along came the teens of the early twentieth century when baseball had become the national pastime. Of course, major league ball players were featured in advertising for Coca-Cola. They included such noted athletes as Ty Cobb, Rabbit Maranville, Walter Johnson, and Eddie Collins. Fashion, culture and technology went through a major revolution in the '20s, and Coke was in the forefront with flappers -- and a strange- looking machine called the automobile. Sports interests were broadening and suddenly golfers began showing up in ads for Coca-Cola. By the 1930s movies were enchanting the American public. Advertising for Coke featured major film stars of the period, all enjoying a refreshing, carbonated drink which, by now, everyone recog- nized as Coke. Some of them included Cary Grant, Claudette Colbert, Wallace Beery and Maurice Chevalier. The film industry's glorification of such stars as Jean Harlow reflect the public's new and more liberated willingness to admire openly the female form, so bathing beauties began sipping Coke by the sea in ads of the time. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -3- Depression years brought tightening of the budget and Coca-Cola offered not only a refreshing pause to keep you going but "The Biggest Nickel's Worth in the Store.' " Radio, an inexpensive form of entertainment, flourished in that Depression Era and the product Coca-Cola became one of the first com- merical sponsors, with such programs as "Refreshment Time" featuring Singing Sam, broadcast into living rooms each week all over the country. Later, Edgar Bergen and Charlie McCarthy, Spike Jones, Percy Faith and others were to entertain millions on radio for Coca-Cola. When the nation marched off to war in the '40s, Coca-Cola marched along. Robert W. Woodruff, then president of The Coca-Cola Company, announced the Company would "see that every man in uniform gets a bottle of Coca-Cola wherever he is and whatever it costs the Company. " The famous contour bottles were mobilized and more than five billion of them went to servicemente and women wherever they were stationed. On the homefront, ads for Coca-Cola featured wartime themes and as it drew to a close, smiling blondes in seamed stocking pulled wagon- - loads of bottled Coke down the street announcing, "He's Coming Home Tomorrow." The placid '50s replaced the soda fountain as the primary social gathering place with "drive-in" restaurants where Coca-Cola could be served curbside. Bowling began to appear in ads; slogans were, like the times, calm, unpretentious, straightforward. But those quiet, postwar years brought one of the most dynamic changes that media advertising for Coca-Cola would ever experience -- the black and white flickering of an uncertain new gadget called tele- vision. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -4- The first network TV show, a Thanksgiving special featuring Edgar Bergen and Charlie McCarthy, was sponsored by Brand Coca-Cola. At the same time, Company and agency ad executives decided it was time for a new look in print advertising, too, and they made the "drastic" change from graphics to photography, exclusively. "Rock and Roll" was in its embryonic stages with the pop music of the early 60s when major recording stars such as Ray Charles, Petula Clark and Connie Francis were featured in advertising for Coca-Cola. A new slogan announced "Things go better with Coke," and sales figures indicated most folks agreed. American youth yearned to return to basic values in the early '70s and advertising for Coca-Cola anticipated the American disenchantment which would occur with artificiality. The advertising theme for Coke emphasized the genuine, the basic, the authentic "It's the real thing" was born. The political uncertainty in the nation that followed presented a new creative challenge to advertising for Coca-Cola. The solution -- to remind Americans of the positive values in the country. "Look up America, said the new advertising for Coca-Cola and people smiled again. The advertising concept, "Coke adds life," continued the variation on a theme, that Coca-Cola adds a simple thing to the lives of Americans - enjoyment. Simple, but important - a break from the ordinary, to enjoy a product whose quality Americans know and on which they can depend. In 1979, "Have a Coke and a smile" further emphasized the reliability and the reward in drinking Coca-Cola. "Coke is it!" sums up these themes -- the quality, the enjoyment and, most of all, the anticipation and the reward for a good day's work. Americans in the 1980s are sharp and aggressive, looking for the best. As a refreshment, the theme states, "Coke is it!" AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -5- Advertising for Coke has been called innovative and revolutionary. Yet all of the themes, even in the 1980s, carry a basic message not so different from John Pemberton's first ad when he developed Coca-Cola in a kettle in his backyard. The red-and-white sign on the door of Jacobs' pharmacy read: "Drink Coca-Cola" and Pemberton's first newspaper ad in 1886 carried this message: "Coca-Cola. Delicious. Refreshing." "Coke is it!" simplifies these intrinsic qualities and promises the consumer that the most popular soft drink in the world is also the best. # # # AJT/RCW/1.19.9 Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226

who is traditionally attributed to legendary for the first written mention of a coffee containing beverage tea?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

Chinese emperor Shen nung, chinese emperor shen nung, Shen nung

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

Whose name is mentioned to Contact?

ztyj0226

ztyj0226_p0, ztyj0226_p1, ztyj0226_p2, ztyj0226_p3, ztyj0226_p4

Tony Tortorici, Tony tortorici

news Coker - COCA-COLA USA Public Relations Department P.O. Drawer 1734, Atlanta. Ga. 30301 Telephone (404)898-2121 CONTACT: Tony Tortorici FOR IMMEDIATE RELEASE 404/898-3696 PAUSE TO REFLECT 95 YEARS OF ADVERTISING FOR COCA-COLA ATLANTA, Feb. 4, 1982 "Coke is it!" is the new advertising theme for Coca-Cola and the descendant of a series of slogans which are as much a part of American life as Brand Coke itself. Unveiled this week at a Coca-Cola USA Bottlers' meeting in Atlanta, "Coke is it!" is a bold concept which succeeds "Have a Coke and a smile, II the main advertising theme for the product since 1979. The new theme breaks from tradition by placing more emphasis on the superiority of Coca-Cola in taste, total refreshment and as a thirst-quencher. The direct, positive statement "Coke is it!" -- appeals to the forthright stance of Americans in the 1980s. Throughout the history of Coca-Cola, the Company's advertising has accurately reflected attitudes of the times, often anticipating changing lifestyles and the national temperament. Since 1886, adver- tising for Coca-Cola has portrayed fluctuations in social climate, structure, values and politics. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -2- In the late 1880s, initial distribution of Coca-Cola began in the South. In tune with the temperance movement, Coke was the perfect answer -- a non-alcoholic beverage, "delicious and refreshing." At the time, Coke was only a fountain drink and the soda fountain was the American social institution -- a place to court a girl, or meet friends, always over a Coke. Magazine ads depicted corseted ladies and mustached gentlemen chatting with the "soda jerk" over their favorite fountain drink with its distinctive red-and-white sign on the mirror in the background. Along came the teens of the early twentieth century when baseball had become the national pastime. Of course, major league ball players were featured in advertising for Coca-Cola. They included such noted athletes as Ty Cobb, Rabbit Maranville, Walter Johnson, and Eddie Collins. Fashion, culture and technology went through a major revolution in the '20s, and Coke was in the forefront with flappers -- and a strange- looking machine called the automobile. Sports interests were broadening and suddenly golfers began showing up in ads for Coca-Cola. By the 1930s movies were enchanting the American public. Advertising for Coke featured major film stars of the period, all enjoying a refreshing, carbonated drink which, by now, everyone recog- nized as Coke. Some of them included Cary Grant, Claudette Colbert, Wallace Beery and Maurice Chevalier. The film industry's glorification of such stars as Jean Harlow reflect the public's new and more liberated willingness to admire openly the female form, so bathing beauties began sipping Coke by the sea in ads of the time. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -3- Depression years brought tightening of the budget and Coca-Cola offered not only a refreshing pause to keep you going but "The Biggest Nickel's Worth in the Store.' " Radio, an inexpensive form of entertainment, flourished in that Depression Era and the product Coca-Cola became one of the first com- merical sponsors, with such programs as "Refreshment Time" featuring Singing Sam, broadcast into living rooms each week all over the country. Later, Edgar Bergen and Charlie McCarthy, Spike Jones, Percy Faith and others were to entertain millions on radio for Coca-Cola. When the nation marched off to war in the '40s, Coca-Cola marched along. Robert W. Woodruff, then president of The Coca-Cola Company, announced the Company would "see that every man in uniform gets a bottle of Coca-Cola wherever he is and whatever it costs the Company. " The famous contour bottles were mobilized and more than five billion of them went to servicemente and women wherever they were stationed. On the homefront, ads for Coca-Cola featured wartime themes and as it drew to a close, smiling blondes in seamed stocking pulled wagon- - loads of bottled Coke down the street announcing, "He's Coming Home Tomorrow." The placid '50s replaced the soda fountain as the primary social gathering place with "drive-in" restaurants where Coca-Cola could be served curbside. Bowling began to appear in ads; slogans were, like the times, calm, unpretentious, straightforward. But those quiet, postwar years brought one of the most dynamic changes that media advertising for Coca-Cola would ever experience -- the black and white flickering of an uncertain new gadget called tele- vision. AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -4- The first network TV show, a Thanksgiving special featuring Edgar Bergen and Charlie McCarthy, was sponsored by Brand Coca-Cola. At the same time, Company and agency ad executives decided it was time for a new look in print advertising, too, and they made the "drastic" change from graphics to photography, exclusively. "Rock and Roll" was in its embryonic stages with the pop music of the early 60s when major recording stars such as Ray Charles, Petula Clark and Connie Francis were featured in advertising for Coca-Cola. A new slogan announced "Things go better with Coke," and sales figures indicated most folks agreed. American youth yearned to return to basic values in the early '70s and advertising for Coca-Cola anticipated the American disenchantment which would occur with artificiality. The advertising theme for Coke emphasized the genuine, the basic, the authentic "It's the real thing" was born. The political uncertainty in the nation that followed presented a new creative challenge to advertising for Coca-Cola. The solution -- to remind Americans of the positive values in the country. "Look up America, said the new advertising for Coca-Cola and people smiled again. The advertising concept, "Coke adds life," continued the variation on a theme, that Coca-Cola adds a simple thing to the lives of Americans - enjoyment. Simple, but important - a break from the ordinary, to enjoy a product whose quality Americans know and on which they can depend. In 1979, "Have a Coke and a smile" further emphasized the reliability and the reward in drinking Coca-Cola. "Coke is it!" sums up these themes -- the quality, the enjoyment and, most of all, the anticipation and the reward for a good day's work. Americans in the 1980s are sharp and aggressive, looking for the best. As a refreshment, the theme states, "Coke is it!" AJT/RCW/1.19.9 (more) Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226 -5- Advertising for Coke has been called innovative and revolutionary. Yet all of the themes, even in the 1980s, carry a basic message not so different from John Pemberton's first ad when he developed Coca-Cola in a kettle in his backyard. The red-and-white sign on the door of Jacobs' pharmacy read: "Drink Coca-Cola" and Pemberton's first newspaper ad in 1886 carried this message: "Coca-Cola. Delicious. Refreshing." "Coke is it!" simplifies these intrinsic qualities and promises the consumer that the most popular soft drink in the world is also the best. # # # AJT/RCW/1.19.9 Source: https://www.industrydocuments.ucsf.edu/docs/ztyj0226

who is the managing director of international litigation services ?

zpjf0226

zpjf0226_p0, zpjf0226_p1, zpjf0226_p2

Joseph Thorpe

From: Miyazaki, Masahiro Sent: Wednesday, July 31, 2002 05:14 PM To: Nonoyama, Takashi Sato, Keiichiro Kawana, Toshio /'ã- Ookubo, Hisao Nogami, Kenichiro òî-ñ. õ; Funatsu, Masami ã-òsJ"-"ú-{SJ"-,bfVfjfA,I; Ikeya, Kazuaki l'ã-òSJ"-"ú-{SJ",bS' Kubo, /^ã- Nishida, Takaharu/ã-'Û'Û,0,1-",0,c CC: Saito, Katsuhisa Seita, Subject: FW: Actos bladder issue Importance: High The teleconference with FDA is more serious than we had expected. It seems that the hypothesis that we built does not work anymore. For details, please read the e-mail below from Claire. The content of this matter is extremely sensitive, so please be sure to handle with care. Development Strategy Division, Miyazaki Original Message From: cthom [mailto:cthom@takedapharm.com Sent: Thursday, August 01, 2002 6:59 AM To: shamanaka; mbooth; rdaly; mkashiyae; d.eckland; Wada.Takashi; p.collett; g.belche; Miyazaki.Masahiro; Saito.Katsuhisa; Seita.Takeshi;Heya.Toshiro; tmuldoon Cc: cthom; WCheatham; ihoos; jpage; mramstack; aperez; melisseou; jhaskins Subject: Actos bladder issue Importance: High A teleconference was held with FDA this afternoon. What follows is an unofficial summary of the results. The FDA has 3 key issues with respect to the non-clinical data related to bladder tumors. 1. They requested us to propose a method by which to monitor bladder toxicity in patients in our long term phase 4 clinical trials (long term was defined as at least 1 year) 2. They indicated an inclination to rescind the written request for pediatric exclusivity based on their concern about bladder tumors. 3. They requested us to give some consideration to a label change that would reflect possible relatedness of tumor formation to mechanism (dual PPAR agonist) instead of the current language ("The relationship of these findings in male rats to humans is unclear. Underlying these issues is a fundamental belief by the agency that the "Cohen hypothesis" for bladder tumors in the pioglitazone rat studies is not relevant. The agency is no longer satisfied that the tumor formation is a species specific finding nor that the origin is related to calculi formation. FDA disclosed that they have received data from a dual PPAR agonist (the Novo Nordisk compound) in which bladder tumors were found (not gender or species specific) in the absence of calculi. Based on these data, FDA has drawn the conclusion that tumor formation must be the result of class pharmacology instead of mechanical origin (calculi irritation) The agency is also not convinced that our findings are isolated to the rat. They commented that our lack of findings in the mice, dog and monkey are unconvincing due to the limited duration of exposure and limited number of animals. In addition, FDA has further evidence from a bladder tumor promotion study in which pio was compared to another sponsor's compound and was shown to increase the formation of bladder tumors (have tumor promoting capabilities) Details on the design and results of this study could not be disclosed. We have been requested to respond to the FDA in writing within the next 3-4 weeks. We are Confidential - Subject to Protective Order TAK-SEITAT-00111731 TAK-SEITAT-00111731P-0001 Source: https://www.indup3790-000ts.ucsf.edu/docs/zpjf0226 currently pulling a detailed action plan together which we will share with you. This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. Confidential - Subject to Protective Order TAK-SEITAT-00111732 TAK-SEITAT-00111731P-0002 Source: https://www.indup3790-00002s.ucsf.edu/docs/zpjf0226 As INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SEITAT-00111731P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 28th day of August 2013, in Aliso Viejo, California. Joseph Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. * 65 Enterprise Aliso Viejo, California 92658 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsTEAM.com www.ilsteAM.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source: https://www.indup3790-00003s.ucsf.edu/docs/zpjf0226

What are mixed with α, γ?

xsjf0226

xsjf0226_p0, xsjf0226_p1, xsjf0226_p2, xsjf0226_p3, xsjf0226_p4, xsjf0226_p5

α, γ

From: Baron, David To: noyama_Takashi@takeda.co.jp'; Sato, Keiichiro (TPC); Saito, Katsuhisa CC: Thorn, Claire (TGRD); Kashiyae. Masalake (TGRD) Sent: 11/18/2002 6:20:11 PM Subject: Documents for Thursday Meeting Attachments; ACTOS and Rodent Bladder Cancer.ppt; Nonclincal Study Proposal.doc; Nonclincal White Paper WORKING doc: PPAR_bladder_prose doc; PPAR_bullets_11_14doc Attached is the agenda (PowerPoint) for Thursday's meeting at the O'Hare Hillon. Also included are supporting documents by Chris Durack and myself and Dr Chuck Aurant What we hope to accomplish at the meeting is to write collectively a 2-3 page summary of our position on bladder tumors to provide to the Agency next week and map out a supporting experimental strategy I look forward to seeing you in Chicago. Best regards, David Confidential - Subject to Protective Order TAK-BAROND-00000762 PENGAD Source: https://www.indug DOCUMENT PRODUCED IN NATIVE FORMAT ************* Confidential - Subject to Protective Order TAK-BAROND-00000763-R Source: https://www.indug5379000002ts.ucsf.edu/docs/xsjf0226 Draft Agenda Continental breakfast (8:00-9:00) Introductions (9:00-9:10) Purpose of meeting (9:10-9:15) Generation of response to FDA (9:15-12:00) Working lunch (12:00-1:00) Discussion of proposed experiments: (12:00-1:00) Feasibility Study conduct Timelines Future plans (1:00-1:30) Confidential - Subject to Protective Order TAK-BAROND-0000076 Source: https://www.indup537ac00003ts.ucsf.edu/docs/xsjf0226 Response Document Experiments already undertaken Proposal: high level "executive" summary Stand alone Bullet point organization Supplementary material Annotation of bullet points Annotated references TRE Confidential - Subject to Protective Order TAK-BAROND-0000076! Source: https://www.indup5370000004s.ucsf.edu/docs/xsjf0226 Response Document Introduction ACTOS male rat data summary Summary of presumed FDA data on mixed inhibitors Hypothesis for mechanism of action of ACTOS in male rats Cohen hypothesis revisited and updated Renal effects (urine electrolytes, osmolality, pH) Liver effects (urine protein composition) PPAR agonism: a, Y, mixed ac, Y Possible roles in bladder carcinogenesis Characterization of thiazolidinediones (pio VS. rosi) Confidential - Subject to Protective Order TAK-BAROND-00000761 Source: https://www.indup537ac00005s.ucsf.edu/docs/xsjf0226 Pakeda Executive Summary, cont. Proposed experiments Risk assessment for patients: o Are nongenotoxic rodent bladder tumorigens predictive of human risk? Conclusions Supplementary materials Confidential - Subject to Protective Order TAK-BAROND-0000076: Source: https://www.indup5370c00006ts.ucsf.edu/docs/xsjf0226

What are the renal effects mentioned?

xsjf0226

xsjf0226_p0, xsjf0226_p1, xsjf0226_p2, xsjf0226_p3, xsjf0226_p4, xsjf0226_p5

(urine electrolytes, osmolality, pH), urine electrolytes, osmolality, pH

From: Baron, David To: noyama_Takashi@takeda.co.jp'; Sato, Keiichiro (TPC); Saito, Katsuhisa CC: Thorn, Claire (TGRD); Kashiyae. Masalake (TGRD) Sent: 11/18/2002 6:20:11 PM Subject: Documents for Thursday Meeting Attachments; ACTOS and Rodent Bladder Cancer.ppt; Nonclincal Study Proposal.doc; Nonclincal White Paper WORKING doc: PPAR_bladder_prose doc; PPAR_bullets_11_14doc Attached is the agenda (PowerPoint) for Thursday's meeting at the O'Hare Hillon. Also included are supporting documents by Chris Durack and myself and Dr Chuck Aurant What we hope to accomplish at the meeting is to write collectively a 2-3 page summary of our position on bladder tumors to provide to the Agency next week and map out a supporting experimental strategy I look forward to seeing you in Chicago. Best regards, David Confidential - Subject to Protective Order TAK-BAROND-00000762 PENGAD Source: https://www.indug DOCUMENT PRODUCED IN NATIVE FORMAT ************* Confidential - Subject to Protective Order TAK-BAROND-00000763-R Source: https://www.indug5379000002ts.ucsf.edu/docs/xsjf0226 Draft Agenda Continental breakfast (8:00-9:00) Introductions (9:00-9:10) Purpose of meeting (9:10-9:15) Generation of response to FDA (9:15-12:00) Working lunch (12:00-1:00) Discussion of proposed experiments: (12:00-1:00) Feasibility Study conduct Timelines Future plans (1:00-1:30) Confidential - Subject to Protective Order TAK-BAROND-0000076 Source: https://www.indup537ac00003ts.ucsf.edu/docs/xsjf0226 Response Document Experiments already undertaken Proposal: high level "executive" summary Stand alone Bullet point organization Supplementary material Annotation of bullet points Annotated references TRE Confidential - Subject to Protective Order TAK-BAROND-0000076! Source: https://www.indup5370000004s.ucsf.edu/docs/xsjf0226 Response Document Introduction ACTOS male rat data summary Summary of presumed FDA data on mixed inhibitors Hypothesis for mechanism of action of ACTOS in male rats Cohen hypothesis revisited and updated Renal effects (urine electrolytes, osmolality, pH) Liver effects (urine protein composition) PPAR agonism: a, Y, mixed ac, Y Possible roles in bladder carcinogenesis Characterization of thiazolidinediones (pio VS. rosi) Confidential - Subject to Protective Order TAK-BAROND-00000761 Source: https://www.indup537ac00005s.ucsf.edu/docs/xsjf0226 Pakeda Executive Summary, cont. Proposed experiments Risk assessment for patients: o Are nongenotoxic rodent bladder tumorigens predictive of human risk? Conclusions Supplementary materials Confidential - Subject to Protective Order TAK-BAROND-0000076: Source: https://www.indup5370c00006ts.ucsf.edu/docs/xsjf0226

who were treated to a sweetened chocolate drink by aztec emporer montezuma?

pkpj0226

pkpj0226_p0, pkpj0226_p1, pkpj0226_p2, pkpj0226_p3, pkpj0226_p4, pkpj0226_p5, pkpj0226_p6, pkpj0226_p7

spanish conquerors, the Spanish conquerors

AIRRI 1 9987 Soft drinks are simple products. The main ingredient is carbonated WHAT'S IN water. Other ingredients are identified on the label in decreasing order of amount. SOFT The data included in this pamphlet are for those who want more detailed information. Values listed herein IS RINKS represent typical ranges for various categories of major, nationally distributed brands of soft drinks. More information about any of these ingredients may be obtained from the: National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202) 463-6750 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 12/86 (202) 463-6732 Soft Drink Ingredient Series Source: :ttps://www.industrydocuments.ucsf.edu/docs/pkpj0226 ARR11 1987 SOITDRINKS AND CAFFEINE I 1 Soft Drink Ingredient Series Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 Historical Background Caffeine is a widely-distributed, naturally-occurring substance found in more than 60 plant species throughout the world. Coffee beans, tea leaves, kola nuts, and cocoa beans are among the more common sources of caffeine con- sumed by humans. People the world over have enjoyed beverages made from these natural sources for thousands of years. Caffeine consumption dates back to prehistoric times. The first written men- tion of a caffeine-containing beverage, tea, is traditionally attributed to the legendary Chinese Emperor Shen Nung in 2737 B.C. Historians generally agree that coffee's consumption as a hot beverage dates from about 1000 A.D. and the coffee plant may have been cultivated in Ethiopia as early as 575 A.D. In 1519, the Spanish Conquerors were treated to a sweetened chocolate drink by the Aztec Emperor Montezuma. Small amounts of caffeine have been used as a flavor component in cola and pepper soft drinks since they originated in the mid-1880's.¹ Caffeine in Soft Drinks Grocery shelves today offer a wide vari- ety of soft drinks, each one formulated to meet particular consumer taste preferences. Some soft drinks contain Source: https://www.industrydocuments.ucsf.edu/docs/pkpj226 caffeine while others do not, depending associated with repetitive tasks and can on the overall taste desired. Cola and help prolong the length of time a person pepper soft drinks have customarily con- can endure physically demanding work.4 tained small amounts of caffeine, but In contrast, in some individuals, con- several brands of caffeine-free colas are sumption of more than 100 mg per day now in the marketplace to provide wider can contribute to postponed and/or choices for consumers. If a soft drink disturbed sleep. Some individuals also contains caffeine, its presence is noted in report irritability, heartburn, stomach the list of ingredients. upsets and increased heartbeat from Flavor chemists recognize caffeine as a valuable ingredient in flavoring formula- - large intakes of caffeine. However, the amounts derived from caffeine-containing tions because it provides a unique bitter soft drinks are, for most individuals, too taste that blends well with other flavors small to have any significant effect in and sweeteners. In some soft drinks, this regard. small amounts of caffeine in combination Ingested caffeine is rapidly absorbed by with other flavors are used to produce the body, metabolized primarily in the pleasing and distinctive overall tastes. 2 liver and totally eliminated, the rate of The Food and Drug Administration elimination depending on age, sex, and (FDA) regulations governing food ingre- other factors. Thus, caffeine does not ac- dients permit caffeine use as a flavor cumulate in the body and the effects component at levels up to six milligrams described above are reversible, disappear- per fluid ounce. (A milligram (mg) is a ing when consumption ceases. Neither metric weight unit with about 30,000 mg animal nor human studies have equal to one ounce.) However, caffeine demonstrated any lasting effects from levels used in caffeine-containing soft small amounts of caffeine.5 6 7 drinks generally fall between 2.5 and 4.9 Detectable effects of caffeine are mg per fluid ounce with approximately neither more intense nor are they pro- 18 mg per six ounce serving being a duced by smaller amounts in children typical value. than in adults. In general, children are less sensitive than adults to a given amount of caffeine since caffeine is eliminated from the body approximately twice as rapidly by children as by adults. 5 6 7 8 Caffeine and Health Scientific Safety Review At FDA's request, an independent group of scien- Characteristics of Caffeine Not only tific experts was assembled by the has caffeine been consumed by humans Federation of American Societies for Ex- for a very long time but it also has been perimental Biology (FASEB) to provide a studied extensively by scientists since it comprehensive evaluation of the health was first isolated in the laboratory in aspects of caffeine. The FASEB experts 1820. Caffeine is generally referred to as reviewed the world's scientific literature a mild stimulant³, but such effects are and concluded that: quite variable and highly dependent on no evidence in the avail- individual sensitivity and, as well, on the able information on caffeine amount of caffeine consumed. demonstrates a hazard to the For many individuals, caffeine can help public when it is used in cola- restore manual and mental performance type beverages at levels that which has been degraded by fatigue. Caf- are now current and in the feine can also help relieve the boredom manner now practiced. 9 Source: ittps://www.industrydocuments.ucsf.edu/docs/pkpj0226 FASEB recommended that additional tube study, were observed in the off- research be conducted on caffeine, spring.12 Amounts of caffeine that a however. Since that time, caffeine has human might normally consume have not been and continues to be the subject of shown adverse effects at equivalent doses extensive research efforts. in animal studies. In 1983, the Institute of Food Tech- Based on a review of existing birth nologists' Expert Panel on Food Safety defect studies, Professor J. G. Wilson, and Nutrition concluded that: Emeritus Professor of Research Pedi- There is no persuasive atrics at the University of Cincinnati, evidence that moderate concluded: amounts of caffeine are harm- existing information and ful to the average healthy data do not provide reason- adult all of the available able grounds to suspect data on moderate intake of adverse health effects from caffeine indicate that the continued use of caffeine- hazard to man, if any, is containing beverages during minimal. human pregnancy. 13 Animal Studies on Caffeine As part In September, 1983, FDA acknowledged of a routine investigation of caffeine, that the most recent caffeine research FDA in 1980 conducted a birth defects " has diminished our previous concern (teratology) study in which pregnant rats over low-dose teratogenic (i.e., birth were force-fed large doses of caffeine by defect) effects in rats."14 That position means of a stomach tube, throughout was reconfirmed by FDA in March, 1984. most of the pregnancy period. Only the Human Studies on Caffeine While highest doses produced any significant ef- the results of the animal studies are fects in the rat offspring. 10 However, for reassuring, even more reassuring are the all practical purposes, these doses are ir- results of investigations of human ex- relevant for humans since the doses periences regarding caffeine consumption would be equivalent, in a 110-pound per- in relation to birth defects. None of the son, to the instantaneous consumption of ten published scientific studies addressing from 40 to 60 quarts of caffeine- caffeine or coffee consumption and birth containing soft drink every day for defects, and involving over 40,000 several months! An expert government mothers, have shown any clear evidence panel reviewed the FDA study and stated of a relationship between caffeine con- that the results were inconclusive since sumption and birth defects. Among the the observed effects in the rat offspring more recent studies is a 1982 Harvard occurred only when the caffeine doses University study, involving 12,205 were so high as to adversely affect the women, which concluded that no health of the rat mothers. 11 Interestingly, consistent relationship between coffee when FDA scientists subsequently consumption and the occurrence of repeated the experiment in rats but ad- malformation" exists in the infants.15 A ministered the same high doses of caffeine Boston University research team recently to pregnant rats in their drinking water, studied 2,030 malformed infants in rela- more realistically reflecting the manner in tion to the caffeine intake of the mothers. which people consume caffeine, quite dif- They, too, concluded that the maternal ferent results were obtained. Under these caffeine intakes were not associated with conditions, but still with exceedingly high the common types of birth defects. 16 caffeine intake, none of the significant Thus, the more recent human studies birth defects, occurring in the stomach pertaining to caffeine consumption in Source: https://www.industrydocuménts.ucsf.edu/docs/pkpj0226 relation to birth defects reinforce the References broader conclusions from the scientific literature. No convincing evidence exists 1. Roberts, H. R. and J. J. Barone, that normal maternal caffeine consump- "Biological Effects of Caffeine: tion is associated with increased risk of History and Use," Food Technology, human birth defects. 37 No. 9, pp. 32-39, 1983. Caffeine and Other Alleged Health Related Effects At one time or another in recent years, caffeine has been alleged 2. PepsiCo, Inc., The Physical or to be connected with peptic ulcers, car- Technical Effect of Caffeine in Cola diovascular diseases, cancer, and Beverages, Purchase, N.Y., July 20, fibrocystic (benign) breast disease. 1981, However, extensive scientific research has failed to confirm such allegations. Some of these concerns were reviewed by the 3. Institute of Food Technologists' FASEB expert committee. More recently Expert Panel on Food Safety and the Expert Panel on Food Safety and Nutrition, "Caffeine," Food Nutrition convened by the Institute of Technology, 37, No. 4, pp. 87-91, Food Technologists also reviewed perti- 1983. nent scientific studies regarding the possible link between caffeine consump- tion and these health problems. The Panel concluded that the existing scien- 4. American Council on Science and tific evidence did not establish that caf- Health, The Health Effects of Caf- feine caused any of these ills. In all cases, feine, New York, N.Y., March they cited evidence to the contrary, and, 1981. in some cases unequivocally concluded that caffeine was not responsible for the health effect in question.3 5. Von Borstel, R. W., "Biological Effects of Caffeine: Metabolism," Food Technology, 37, No. 9, pp. 40-43, 1983. Conclusion A vast body of evidence exists which supports the conclusion that normal 6. Neims, A. H., The Comparative amounts of caffeine, especially the small Metabolism and Pharmacokinetics amounts found in some soft drinks, do of Caffeine in the Regulatory Con- not present a hazard to humans. text, University of Florida, July 18, 1981. More Information 7. Neims, A. H., and R. W. von Borstel, "Caffeine: Its Metabolism and For general information on caffeine and Biochemical Mechanisms of its use in soft drinks, please contact the Action," in Nutrition and the National Soft Drink Association, 1101 Brain, Vol. 6, R. J. Wurtman and Sixteenth Street, N.W., Washington, J. J. Wurtman, Eds., Raven Press, D.C. 20036 (202)463-6770. N.Y. 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 8. Dews, P. B., "Caffeine," in Annual 15. Linn, S., S. C. Schoenbaum, R. R. Review of Nutrition, Vol. 2, W. J. Monson, B. Rosner, P. G. Stub- Darby, H. P. Broquist and R. E. blefield, and K. J. Ryan, "No Olson, Eds., Annual Reviews, Inc., Association Between Coffee Con- Palo Alto, Calif., 1982. sumption and Adverse Outcomes of Pregnancy," New England Journal of Medicine, 306, No. 3, pp. 9. Federation of American Societies for 141-145, 1982. Experimental Biology, Evaluation of the Health Aspects of Caffeine as a Food Ingredient, Life Sciences 16. Rosenberg, L., A. A. Mitchell, S. Research Office, Bethesda, Md., Shapiro, and D. Slone, "Selected 1978. Birth Defects in Relation to ) Caffeine-Containing Beverages," Journal of the American Medical 10. Food and Drug Administration, Association, 247, No. 10, pp. Federal Register, Vol. 45, No. 205, 1429-1432, 1982. p. 69822, October 21, 1980. 11. Dixon, R. L., J. C. Dacre, D. G. Hoel, and M. C. Lowe, "An Analysis of FDA's Caffeine Teratogenicity Study," A Report to the Commis- sioner of Food and Drugs by the Caffeine Study Review Panel, May, 1981. 12. Collins, T. F. X., J. J. Welsh, T. N. Black, and D. I. Ruggles, "A Study of the Teratogenic Potential of Caf- feine Ingested in Drinking Water," Food Chemical Toxicology, 21, No. 6, pp. 763-777, 1983. 13. Wilson, J. G., Teratology and the Food and Drug Administration's Proposal to Remove Caffeine in Cola Beverages from the List of Substances Generally Recognized as Safe, University of Cincinnati, July 20, 1981. 14. Miles, C.I., "Biological Effects of Caffeine: FDA Status," Food Technology, 37, No. 9, pp. 48-50, 1983. Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226 National Soft Drink Association 1101 16th Street, N.W. Washington, D.C. 20036 (202)463-6770 Source: https://www.industrydocuments.ucsf.edu/docs/pkpj0226

When it executed?

zpjf0226

zpjf0226_p0, zpjf0226_p1, zpjf0226_p2

28th day of August 2013

From: Miyazaki, Masahiro Sent: Wednesday, July 31, 2002 05:14 PM To: Nonoyama, Takashi Sato, Keiichiro Kawana, Toshio /'ã- Ookubo, Hisao Nogami, Kenichiro òî-ñ. õ; Funatsu, Masami ã-òsJ"-"ú-{SJ"-,bfVfjfA,I; Ikeya, Kazuaki l'ã-òSJ"-"ú-{SJ",bS' Kubo, /^ã- Nishida, Takaharu/ã-'Û'Û,0,1-",0,c CC: Saito, Katsuhisa Seita, Subject: FW: Actos bladder issue Importance: High The teleconference with FDA is more serious than we had expected. It seems that the hypothesis that we built does not work anymore. For details, please read the e-mail below from Claire. The content of this matter is extremely sensitive, so please be sure to handle with care. Development Strategy Division, Miyazaki Original Message From: cthom [mailto:cthom@takedapharm.com Sent: Thursday, August 01, 2002 6:59 AM To: shamanaka; mbooth; rdaly; mkashiyae; d.eckland; Wada.Takashi; p.collett; g.belche; Miyazaki.Masahiro; Saito.Katsuhisa; Seita.Takeshi;Heya.Toshiro; tmuldoon Cc: cthom; WCheatham; ihoos; jpage; mramstack; aperez; melisseou; jhaskins Subject: Actos bladder issue Importance: High A teleconference was held with FDA this afternoon. What follows is an unofficial summary of the results. The FDA has 3 key issues with respect to the non-clinical data related to bladder tumors. 1. They requested us to propose a method by which to monitor bladder toxicity in patients in our long term phase 4 clinical trials (long term was defined as at least 1 year) 2. They indicated an inclination to rescind the written request for pediatric exclusivity based on their concern about bladder tumors. 3. They requested us to give some consideration to a label change that would reflect possible relatedness of tumor formation to mechanism (dual PPAR agonist) instead of the current language ("The relationship of these findings in male rats to humans is unclear. Underlying these issues is a fundamental belief by the agency that the "Cohen hypothesis" for bladder tumors in the pioglitazone rat studies is not relevant. The agency is no longer satisfied that the tumor formation is a species specific finding nor that the origin is related to calculi formation. FDA disclosed that they have received data from a dual PPAR agonist (the Novo Nordisk compound) in which bladder tumors were found (not gender or species specific) in the absence of calculi. Based on these data, FDA has drawn the conclusion that tumor formation must be the result of class pharmacology instead of mechanical origin (calculi irritation) The agency is also not convinced that our findings are isolated to the rat. They commented that our lack of findings in the mice, dog and monkey are unconvincing due to the limited duration of exposure and limited number of animals. In addition, FDA has further evidence from a bladder tumor promotion study in which pio was compared to another sponsor's compound and was shown to increase the formation of bladder tumors (have tumor promoting capabilities) Details on the design and results of this study could not be disclosed. We have been requested to respond to the FDA in writing within the next 3-4 weeks. We are Confidential - Subject to Protective Order TAK-SEITAT-00111731 TAK-SEITAT-00111731P-0001 Source: https://www.indup3790-000ts.ucsf.edu/docs/zpjf0226 currently pulling a detailed action plan together which we will share with you. This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. Confidential - Subject to Protective Order TAK-SEITAT-00111732 TAK-SEITAT-00111731P-0002 Source: https://www.indup3790-00002s.ucsf.edu/docs/zpjf0226 As INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SEITAT-00111731P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 28th day of August 2013, in Aliso Viejo, California. Joseph Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. * 65 Enterprise Aliso Viejo, California 92658 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsTEAM.com www.ilsteAM.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source: https://www.indup3790-00003s.ucsf.edu/docs/zpjf0226

Where was the translation executed at?

zpjf0226

zpjf0226_p0, zpjf0226_p1, zpjf0226_p2

Aliso Viejo, California, In aliso Viejo, california

From: Miyazaki, Masahiro Sent: Wednesday, July 31, 2002 05:14 PM To: Nonoyama, Takashi Sato, Keiichiro Kawana, Toshio /'ã- Ookubo, Hisao Nogami, Kenichiro òî-ñ. õ; Funatsu, Masami ã-òsJ"-"ú-{SJ"-,bfVfjfA,I; Ikeya, Kazuaki l'ã-òSJ"-"ú-{SJ",bS' Kubo, /^ã- Nishida, Takaharu/ã-'Û'Û,0,1-",0,c CC: Saito, Katsuhisa Seita, Subject: FW: Actos bladder issue Importance: High The teleconference with FDA is more serious than we had expected. It seems that the hypothesis that we built does not work anymore. For details, please read the e-mail below from Claire. The content of this matter is extremely sensitive, so please be sure to handle with care. Development Strategy Division, Miyazaki Original Message From: cthom [mailto:cthom@takedapharm.com Sent: Thursday, August 01, 2002 6:59 AM To: shamanaka; mbooth; rdaly; mkashiyae; d.eckland; Wada.Takashi; p.collett; g.belche; Miyazaki.Masahiro; Saito.Katsuhisa; Seita.Takeshi;Heya.Toshiro; tmuldoon Cc: cthom; WCheatham; ihoos; jpage; mramstack; aperez; melisseou; jhaskins Subject: Actos bladder issue Importance: High A teleconference was held with FDA this afternoon. What follows is an unofficial summary of the results. The FDA has 3 key issues with respect to the non-clinical data related to bladder tumors. 1. They requested us to propose a method by which to monitor bladder toxicity in patients in our long term phase 4 clinical trials (long term was defined as at least 1 year) 2. They indicated an inclination to rescind the written request for pediatric exclusivity based on their concern about bladder tumors. 3. They requested us to give some consideration to a label change that would reflect possible relatedness of tumor formation to mechanism (dual PPAR agonist) instead of the current language ("The relationship of these findings in male rats to humans is unclear. Underlying these issues is a fundamental belief by the agency that the "Cohen hypothesis" for bladder tumors in the pioglitazone rat studies is not relevant. The agency is no longer satisfied that the tumor formation is a species specific finding nor that the origin is related to calculi formation. FDA disclosed that they have received data from a dual PPAR agonist (the Novo Nordisk compound) in which bladder tumors were found (not gender or species specific) in the absence of calculi. Based on these data, FDA has drawn the conclusion that tumor formation must be the result of class pharmacology instead of mechanical origin (calculi irritation) The agency is also not convinced that our findings are isolated to the rat. They commented that our lack of findings in the mice, dog and monkey are unconvincing due to the limited duration of exposure and limited number of animals. In addition, FDA has further evidence from a bladder tumor promotion study in which pio was compared to another sponsor's compound and was shown to increase the formation of bladder tumors (have tumor promoting capabilities) Details on the design and results of this study could not be disclosed. We have been requested to respond to the FDA in writing within the next 3-4 weeks. We are Confidential - Subject to Protective Order TAK-SEITAT-00111731 TAK-SEITAT-00111731P-0001 Source: https://www.indup3790-000ts.ucsf.edu/docs/zpjf0226 currently pulling a detailed action plan together which we will share with you. This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. Confidential - Subject to Protective Order TAK-SEITAT-00111732 TAK-SEITAT-00111731P-0002 Source: https://www.indup3790-00002s.ucsf.edu/docs/zpjf0226 As INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-SEITAT-00111731P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 28th day of August 2013, in Aliso Viejo, California. Joseph Hope Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. * 65 Enterprise Aliso Viejo, California 92658 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsTEAM.com www.ilsteAM.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source: https://www.indup3790-00003s.ucsf.edu/docs/zpjf0226

From whom has this email been sent?

xtjf0226

xtjf0226_p0, xtjf0226_p1, xtjf0226_p2, xtjf0226_p3

Kanayama Kiyoshi

From: Kanayama To: Spanheimer, Robert CC: Shepard, Kirk (TPI); Fuse, Touichirou (TPC) Sent: 10/27/2011 5:14:48 PM Subject: Re Potential Publication in Correspondence Section of The Lancel Dear Bob, Thank you for your response. Best, Kiyoshi On 2011/10/27, at 22:07, "Spanheimer, Robert" <bob.spanheimer@takeda.com> wrote: Dear Kiyoshi As noted below several letters were written to Lancet and the journal requested a response from the Proactive steering committee. The timeline for the response was short, I believe 4-5 days, and was to come from the Proactive steering committee. Because of the short timeline, the Proactive steering committee was contacted as well as key members of the Actos publication team to determine if we should respond, and then draft a response. The decision was we mustrespond, and Erland Erdmann(Chai of the committee) John Dormandy (lead author on the original publication), and Massimo Massi-Benedetti (safety officer of Proactive) and I wrote the response letter. The GMST for Actos as well as Alphonso Perez the GDT lead were informed. Bob From: Kanayama Kiyoshi@takeda.co.jp [mailto:Kanayama_Kiyoshi@takeda.co.jp] Confidential - Subject to Protective Order TAK-SPANHR-00005674 EXHIBIT is WIT: DATE: 10-23-13 Juliana Zajicek CSR Source: https://www.induptodorouoonts.ucsf.edu/docs/xtjf0226 Sent: Thursday, October 27, 2011 1:53 AM To: Spanheimer, Robert; Shepard, Kirk (TPI) Cc: Kanayama, Kiyoshi (TPC); Fuse, Touichirou (TPC) Subject: Potential Publication in Correspondence Section of The Lancet Dear Kirk and Bob, Thank you in London. Although I obtained the following information, I do not understand details well. 1 would appreciate it if you could inform me of the details by as soon as you can. Best Regards, Kiyoshi Kiyoshi Kanayama Vice President Pharmaceutical Information Services For Ethical Product Dep. Pharmaceutical Marketing Division Takeda Pharmaceutical Campany Limited 12-10, Nihonbashi 2-Chome,Chuo-ku,Tokyo,Japar Confidential - Subject to Protective Order TAK-SPANHR-00005675 Source: https://www.induptodocouoo2ts.ucsf.edu/docs/xtjf0226 EL:(03)3278-3889 FAX:(03)3278-2469 E-mail:Kanayama_Kiyoshi@takeda.co.jp From: Johnsen, Elissa (TPNA) [mailto:elissa.johnsen@takeda.com Sent: Thursday, October 27, 2011 7:35 AM To: Fuse A T GERHI Cc: Masuda Seizo/C CHERNE ma IR ) ; Tamamuro IR) Subject: Potential Publication in Correspondence Section of The Lancet Toi, As you may recall, a few months ago Takeda and the PROactive committee were contacted by The Lancet to respond to a letter submitted to The Lancet about a PROactive manuscript containing bladder cancer data. After evaluating the request, the committee and Takeda submitted a response letter to the publication. While we have not received notification as-authors, the CC team-has received word that the letters-will appear in the.Correspondence-section-of.thisweek's-publication (due-out on Friday, October 28th). 1 wanted to make you all aware of this, as given the continued high level of noise around this topic I believe we may get questions from the media once the letters are published. From a readiness standpoint, Bob Spanheimer is an author on the reply letter and has been the consistent global spokesperson on this topic I can work with him to respond to any inquiries we receive on this topic. Additionally, when we see the publication posted I will be sure to distribute a media monitoring flag immediately. In the meantime, since we have not received official notification / would recommend that we only verbally notify appropriate management that this may be on the horizon. Confidential - Subject to Protective Order TAK-SPANHR-00005676 Source: https://www.indup5040-00003t ts.ucsf.edu/docs/xtjf0226 Please let me know if you have any questions. Many thanks, Elli Elissa J. Johnsen Corporate Communications Takeda Pharmaceuticals North America, Inc. 224.554.3185 (work) 312.285.3203 (cell) Confidential - Subject to Protective Order TAK-SPANHR-00005677 Source: https://www.induptodo-ouoo4ts.ucsf.edu/docs/xtjf0226

Who are on the CC list?

xtjf0226

xtjf0226_p0, xtjf0226_p1, xtjf0226_p2, xtjf0226_p3

Shephard, Kirk (TPI); Fuse, Touichirou (TPC)

From: Kanayama To: Spanheimer, Robert CC: Shepard, Kirk (TPI); Fuse, Touichirou (TPC) Sent: 10/27/2011 5:14:48 PM Subject: Re Potential Publication in Correspondence Section of The Lancel Dear Bob, Thank you for your response. Best, Kiyoshi On 2011/10/27, at 22:07, "Spanheimer, Robert" <bob.spanheimer@takeda.com> wrote: Dear Kiyoshi As noted below several letters were written to Lancet and the journal requested a response from the Proactive steering committee. The timeline for the response was short, I believe 4-5 days, and was to come from the Proactive steering committee. Because of the short timeline, the Proactive steering committee was contacted as well as key members of the Actos publication team to determine if we should respond, and then draft a response. The decision was we mustrespond, and Erland Erdmann(Chai of the committee) John Dormandy (lead author on the original publication), and Massimo Massi-Benedetti (safety officer of Proactive) and I wrote the response letter. The GMST for Actos as well as Alphonso Perez the GDT lead were informed. Bob From: Kanayama Kiyoshi@takeda.co.jp [mailto:Kanayama_Kiyoshi@takeda.co.jp] Confidential - Subject to Protective Order TAK-SPANHR-00005674 EXHIBIT is WIT: DATE: 10-23-13 Juliana Zajicek CSR Source: https://www.induptodorouoonts.ucsf.edu/docs/xtjf0226 Sent: Thursday, October 27, 2011 1:53 AM To: Spanheimer, Robert; Shepard, Kirk (TPI) Cc: Kanayama, Kiyoshi (TPC); Fuse, Touichirou (TPC) Subject: Potential Publication in Correspondence Section of The Lancet Dear Kirk and Bob, Thank you in London. Although I obtained the following information, I do not understand details well. 1 would appreciate it if you could inform me of the details by as soon as you can. Best Regards, Kiyoshi Kiyoshi Kanayama Vice President Pharmaceutical Information Services For Ethical Product Dep. Pharmaceutical Marketing Division Takeda Pharmaceutical Campany Limited 12-10, Nihonbashi 2-Chome,Chuo-ku,Tokyo,Japar Confidential - Subject to Protective Order TAK-SPANHR-00005675 Source: https://www.induptodocouoo2ts.ucsf.edu/docs/xtjf0226 EL:(03)3278-3889 FAX:(03)3278-2469 E-mail:Kanayama_Kiyoshi@takeda.co.jp From: Johnsen, Elissa (TPNA) [mailto:elissa.johnsen@takeda.com Sent: Thursday, October 27, 2011 7:35 AM To: Fuse A T GERHI Cc: Masuda Seizo/C CHERNE ma IR ) ; Tamamuro IR) Subject: Potential Publication in Correspondence Section of The Lancet Toi, As you may recall, a few months ago Takeda and the PROactive committee were contacted by The Lancet to respond to a letter submitted to The Lancet about a PROactive manuscript containing bladder cancer data. After evaluating the request, the committee and Takeda submitted a response letter to the publication. While we have not received notification as-authors, the CC team-has received word that the letters-will appear in the.Correspondence-section-of.thisweek's-publication (due-out on Friday, October 28th). 1 wanted to make you all aware of this, as given the continued high level of noise around this topic I believe we may get questions from the media once the letters are published. From a readiness standpoint, Bob Spanheimer is an author on the reply letter and has been the consistent global spokesperson on this topic I can work with him to respond to any inquiries we receive on this topic. Additionally, when we see the publication posted I will be sure to distribute a media monitoring flag immediately. In the meantime, since we have not received official notification / would recommend that we only verbally notify appropriate management that this may be on the horizon. Confidential - Subject to Protective Order TAK-SPANHR-00005676 Source: https://www.indup5040-00003t ts.ucsf.edu/docs/xtjf0226 Please let me know if you have any questions. Many thanks, Elli Elissa J. Johnsen Corporate Communications Takeda Pharmaceuticals North America, Inc. 224.554.3185 (work) 312.285.3203 (cell) Confidential - Subject to Protective Order TAK-SPANHR-00005677 Source: https://www.induptodo-ouoo4ts.ucsf.edu/docs/xtjf0226

What is the email ID of Kanayama Kiyoshi?

xtjf0226

xtjf0226_p0, xtjf0226_p1, xtjf0226_p2, xtjf0226_p3

Kanayama_Kiyoshi@takeda.co.jp

From: Kanayama To: Spanheimer, Robert CC: Shepard, Kirk (TPI); Fuse, Touichirou (TPC) Sent: 10/27/2011 5:14:48 PM Subject: Re Potential Publication in Correspondence Section of The Lancel Dear Bob, Thank you for your response. Best, Kiyoshi On 2011/10/27, at 22:07, "Spanheimer, Robert" <bob.spanheimer@takeda.com> wrote: Dear Kiyoshi As noted below several letters were written to Lancet and the journal requested a response from the Proactive steering committee. The timeline for the response was short, I believe 4-5 days, and was to come from the Proactive steering committee. Because of the short timeline, the Proactive steering committee was contacted as well as key members of the Actos publication team to determine if we should respond, and then draft a response. The decision was we mustrespond, and Erland Erdmann(Chai of the committee) John Dormandy (lead author on the original publication), and Massimo Massi-Benedetti (safety officer of Proactive) and I wrote the response letter. The GMST for Actos as well as Alphonso Perez the GDT lead were informed. Bob From: Kanayama Kiyoshi@takeda.co.jp [mailto:Kanayama_Kiyoshi@takeda.co.jp] Confidential - Subject to Protective Order TAK-SPANHR-00005674 EXHIBIT is WIT: DATE: 10-23-13 Juliana Zajicek CSR Source: https://www.induptodorouoonts.ucsf.edu/docs/xtjf0226 Sent: Thursday, October 27, 2011 1:53 AM To: Spanheimer, Robert; Shepard, Kirk (TPI) Cc: Kanayama, Kiyoshi (TPC); Fuse, Touichirou (TPC) Subject: Potential Publication in Correspondence Section of The Lancet Dear Kirk and Bob, Thank you in London. Although I obtained the following information, I do not understand details well. 1 would appreciate it if you could inform me of the details by as soon as you can. Best Regards, Kiyoshi Kiyoshi Kanayama Vice President Pharmaceutical Information Services For Ethical Product Dep. Pharmaceutical Marketing Division Takeda Pharmaceutical Campany Limited 12-10, Nihonbashi 2-Chome,Chuo-ku,Tokyo,Japar Confidential - Subject to Protective Order TAK-SPANHR-00005675 Source: https://www.induptodocouoo2ts.ucsf.edu/docs/xtjf0226 EL:(03)3278-3889 FAX:(03)3278-2469 E-mail:Kanayama_Kiyoshi@takeda.co.jp From: Johnsen, Elissa (TPNA) [mailto:elissa.johnsen@takeda.com Sent: Thursday, October 27, 2011 7:35 AM To: Fuse A T GERHI Cc: Masuda Seizo/C CHERNE ma IR ) ; Tamamuro IR) Subject: Potential Publication in Correspondence Section of The Lancet Toi, As you may recall, a few months ago Takeda and the PROactive committee were contacted by The Lancet to respond to a letter submitted to The Lancet about a PROactive manuscript containing bladder cancer data. After evaluating the request, the committee and Takeda submitted a response letter to the publication. While we have not received notification as-authors, the CC team-has received word that the letters-will appear in the.Correspondence-section-of.thisweek's-publication (due-out on Friday, October 28th). 1 wanted to make you all aware of this, as given the continued high level of noise around this topic I believe we may get questions from the media once the letters are published. From a readiness standpoint, Bob Spanheimer is an author on the reply letter and has been the consistent global spokesperson on this topic I can work with him to respond to any inquiries we receive on this topic. Additionally, when we see the publication posted I will be sure to distribute a media monitoring flag immediately. In the meantime, since we have not received official notification / would recommend that we only verbally notify appropriate management that this may be on the horizon. Confidential - Subject to Protective Order TAK-SPANHR-00005676 Source: https://www.indup5040-00003t ts.ucsf.edu/docs/xtjf0226 Please let me know if you have any questions. Many thanks, Elli Elissa J. Johnsen Corporate Communications Takeda Pharmaceuticals North America, Inc. 224.554.3185 (work) 312.285.3203 (cell) Confidential - Subject to Protective Order TAK-SPANHR-00005677 Source: https://www.induptodo-ouoo4ts.ucsf.edu/docs/xtjf0226

What is the subject of this email?

xtjf0226

xtjf0226_p0, xtjf0226_p1, xtjf0226_p2, xtjf0226_p3

Re: Potential Publicaton in Correspondence Section of The Lancet

From: Kanayama To: Spanheimer, Robert CC: Shepard, Kirk (TPI); Fuse, Touichirou (TPC) Sent: 10/27/2011 5:14:48 PM Subject: Re Potential Publication in Correspondence Section of The Lancel Dear Bob, Thank you for your response. Best, Kiyoshi On 2011/10/27, at 22:07, "Spanheimer, Robert" <bob.spanheimer@takeda.com> wrote: Dear Kiyoshi As noted below several letters were written to Lancet and the journal requested a response from the Proactive steering committee. The timeline for the response was short, I believe 4-5 days, and was to come from the Proactive steering committee. Because of the short timeline, the Proactive steering committee was contacted as well as key members of the Actos publication team to determine if we should respond, and then draft a response. The decision was we mustrespond, and Erland Erdmann(Chai of the committee) John Dormandy (lead author on the original publication), and Massimo Massi-Benedetti (safety officer of Proactive) and I wrote the response letter. The GMST for Actos as well as Alphonso Perez the GDT lead were informed. Bob From: Kanayama Kiyoshi@takeda.co.jp [mailto:Kanayama_Kiyoshi@takeda.co.jp] Confidential - Subject to Protective Order TAK-SPANHR-00005674 EXHIBIT is WIT: DATE: 10-23-13 Juliana Zajicek CSR Source: https://www.induptodorouoonts.ucsf.edu/docs/xtjf0226 Sent: Thursday, October 27, 2011 1:53 AM To: Spanheimer, Robert; Shepard, Kirk (TPI) Cc: Kanayama, Kiyoshi (TPC); Fuse, Touichirou (TPC) Subject: Potential Publication in Correspondence Section of The Lancet Dear Kirk and Bob, Thank you in London. Although I obtained the following information, I do not understand details well. 1 would appreciate it if you could inform me of the details by as soon as you can. Best Regards, Kiyoshi Kiyoshi Kanayama Vice President Pharmaceutical Information Services For Ethical Product Dep. Pharmaceutical Marketing Division Takeda Pharmaceutical Campany Limited 12-10, Nihonbashi 2-Chome,Chuo-ku,Tokyo,Japar Confidential - Subject to Protective Order TAK-SPANHR-00005675 Source: https://www.induptodocouoo2ts.ucsf.edu/docs/xtjf0226 EL:(03)3278-3889 FAX:(03)3278-2469 E-mail:Kanayama_Kiyoshi@takeda.co.jp From: Johnsen, Elissa (TPNA) [mailto:elissa.johnsen@takeda.com Sent: Thursday, October 27, 2011 7:35 AM To: Fuse A T GERHI Cc: Masuda Seizo/C CHERNE ma IR ) ; Tamamuro IR) Subject: Potential Publication in Correspondence Section of The Lancet Toi, As you may recall, a few months ago Takeda and the PROactive committee were contacted by The Lancet to respond to a letter submitted to The Lancet about a PROactive manuscript containing bladder cancer data. After evaluating the request, the committee and Takeda submitted a response letter to the publication. While we have not received notification as-authors, the CC team-has received word that the letters-will appear in the.Correspondence-section-of.thisweek's-publication (due-out on Friday, October 28th). 1 wanted to make you all aware of this, as given the continued high level of noise around this topic I believe we may get questions from the media once the letters are published. From a readiness standpoint, Bob Spanheimer is an author on the reply letter and has been the consistent global spokesperson on this topic I can work with him to respond to any inquiries we receive on this topic. Additionally, when we see the publication posted I will be sure to distribute a media monitoring flag immediately. In the meantime, since we have not received official notification / would recommend that we only verbally notify appropriate management that this may be on the horizon. Confidential - Subject to Protective Order TAK-SPANHR-00005676 Source: https://www.indup5040-00003t ts.ucsf.edu/docs/xtjf0226 Please let me know if you have any questions. Many thanks, Elli Elissa J. Johnsen Corporate Communications Takeda Pharmaceuticals North America, Inc. 224.554.3185 (work) 312.285.3203 (cell) Confidential - Subject to Protective Order TAK-SPANHR-00005677 Source: https://www.induptodo-ouoo4ts.ucsf.edu/docs/xtjf0226

What is the level of importance of the email send by Witte, Kimberly?

tsjf0226

tsjf0226_p0, tsjf0226_p1

High

1 Nathaniel M Osbome 08/06/99 11:34 AM To: Matthew W Beebe, Mitchell W Tull, Angela K Wade Subject: FW: SKB PROBLEMS fyi..nat Forwarded by Nathaniel M Osbome/AM/LLY on 08/06/99 11:34 AM "Daly, Rich" <rdaly@takedapharm.com> on 08/06/99 09:58:27 AM To: "Peters, Linda" <LPeters CC: Nathaniel M Osborne, "Orlando, Dan" <dorlando, "Blake, Bill" <bblake Subject: FW: SKB PROBLEMS Add this to the H&H conf call. rd > Original Message > From: Witte, Kimberly > Sent: Friday, August 06, 1999 9:26 AM > To: Daly, Rich > Cc: Graziano, Dave > Subject: FW: SKB PROBLEMS > Importance: High > > Rich, > > I am forwarding a message from Brian Chunn out of Champaign, IL. It seems > as though SKB is putting on some audio/teleconferences and giving out > incorrect information regarding Actos. The message from Brian is > self-explanatory. This is something that I wanted to bring to your > attention to see if there is anything that we could do. I appreciate your > attention to this as it is a big concern. Thanks so much Rich! Please > call me if you have any questions. > > Kim Witte > > Original Message > From: Chunn, Brian > Sent: Thursday, August 05, 1999 9:17 PM > To: Witte, Kimberly > Subject: SKB PROBLEMS > > Hi Kim! > I wanted to pass along a problem I came upon today while in Danville, IL. > I was in Dr. Sadiq's office who is one of my big targets (9A) and we were > discussing Actos. He proceeded to ask me if urinary bladder tumors were a > problem with the FDA. (This is the Doctor who asked me a month ago if > Actos caused Urinary bladder cancer) Knowing this woulds come up I was > prepared to discuss the portion of the PI on page 9 discussing tumors > found in rats, but no humans. When I asked where he had heard this > information, he proceeded to tell me it came from a Smith Kline Beecham > audio/tele conference. He mentioned the person he was discussing this > with mentioned that the tumors were why there was a delay in Actos coming > to market. I can't imagine this is fair balance. I am also running into > some smaller objections from Docs BEFORE I have even discussed Actos with > them. I'm not sure if these are also coming from SKB speakers or if it > is coming from the SKB reps locally. However, I do know the urinary > bladder tumor came from some form of an audio/tele conference from SKB. I > just need to find out if there is anything that can be done to stop their EXHIBIT Confidential - Subject to Protective Order LLY-CRCARCH-00008577 9 Beebe 11.12.13 > speakers from lying to Docs. If you could pass this along it would be > appreciated. > > Thanks ! > Brian Confidential - Subject to Protective Order LLY-CRCARCH-00008578 Source: https://www.indup5820-0000/2ts.ucsf.edu/docs/tsjf0226

What is the EXHIBIT number mentioned?

tsjf0226

tsjf0226_p0, tsjf0226_p1

9

1 Nathaniel M Osbome 08/06/99 11:34 AM To: Matthew W Beebe, Mitchell W Tull, Angela K Wade Subject: FW: SKB PROBLEMS fyi..nat Forwarded by Nathaniel M Osbome/AM/LLY on 08/06/99 11:34 AM "Daly, Rich" <rdaly@takedapharm.com> on 08/06/99 09:58:27 AM To: "Peters, Linda" <LPeters CC: Nathaniel M Osborne, "Orlando, Dan" <dorlando, "Blake, Bill" <bblake Subject: FW: SKB PROBLEMS Add this to the H&H conf call. rd > Original Message > From: Witte, Kimberly > Sent: Friday, August 06, 1999 9:26 AM > To: Daly, Rich > Cc: Graziano, Dave > Subject: FW: SKB PROBLEMS > Importance: High > > Rich, > > I am forwarding a message from Brian Chunn out of Champaign, IL. It seems > as though SKB is putting on some audio/teleconferences and giving out > incorrect information regarding Actos. The message from Brian is > self-explanatory. This is something that I wanted to bring to your > attention to see if there is anything that we could do. I appreciate your > attention to this as it is a big concern. Thanks so much Rich! Please > call me if you have any questions. > > Kim Witte > > Original Message > From: Chunn, Brian > Sent: Thursday, August 05, 1999 9:17 PM > To: Witte, Kimberly > Subject: SKB PROBLEMS > > Hi Kim! > I wanted to pass along a problem I came upon today while in Danville, IL. > I was in Dr. Sadiq's office who is one of my big targets (9A) and we were > discussing Actos. He proceeded to ask me if urinary bladder tumors were a > problem with the FDA. (This is the Doctor who asked me a month ago if > Actos caused Urinary bladder cancer) Knowing this woulds come up I was > prepared to discuss the portion of the PI on page 9 discussing tumors > found in rats, but no humans. When I asked where he had heard this > information, he proceeded to tell me it came from a Smith Kline Beecham > audio/tele conference. He mentioned the person he was discussing this > with mentioned that the tumors were why there was a delay in Actos coming > to market. I can't imagine this is fair balance. I am also running into > some smaller objections from Docs BEFORE I have even discussed Actos with > them. I'm not sure if these are also coming from SKB speakers or if it > is coming from the SKB reps locally. However, I do know the urinary > bladder tumor came from some form of an audio/tele conference from SKB. I > just need to find out if there is anything that can be done to stop their EXHIBIT Confidential - Subject to Protective Order LLY-CRCARCH-00008577 9 Beebe 11.12.13 > speakers from lying to Docs. If you could pass this along it would be > appreciated. > > Thanks ! > Brian Confidential - Subject to Protective Order LLY-CRCARCH-00008578 Source: https://www.indup5820-0000/2ts.ucsf.edu/docs/tsjf0226

Who is this Memo to?

sqjf0226

sqjf0226_p0, sqjf0226_p1

distribution, Distribution

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226

What is the date mentioned?

sqjf0226

sqjf0226_p0, sqjf0226_p1

JULY 19, 2002, July 19, 2002

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226

Whose signature is present at the bottom?

sqjf0226

sqjf0226_p0, sqjf0226_p1

MARLENE C. DUBAS, Marlene C. Dubas

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226

who are in the cc?

tzjf0226

tzjf0226_p0, tzjf0226_p1

johnston,Kendra; precurato-grubb, marti

From: Chen, Gigi To: "DCC WXA Dist Buffalo, NY CC: Johnston, Kendra; Precurato-Grubb, Marti Sent: 7/31/2007 11:48:09 AM Jubject: Article in today's USA Today regarding Avandia hearing Attachments: FDA Advised printed in USA Today July 31 07.doc Hello Buffalo Team & Marti, In case you did not see this in your travels today please find attached an article regarding the Avandia hearing in USA Today printed 7/31/07 (Today). Note the chart on the right hand side of the page stating *side effects" of TZD's. Jason, the article you sent all of us regarding the side effect of cancer was even listed! Obviously, not something we would bring up or mention on our sales calls but just something to be aware of in case it is mentioned out in the field! Also note the last sentence of the article: "Actos, the other drug in the same class as Avandia, does not appear to increase heart attack risk, he said", referencing David Graham's comment! Hope everyone is doing well! Gigi Gigi M. Chen, May Premier Sales Representative Buffalo North Tast 1.877.202.2720 ext. 14692 cellular: 716.725.7100 EXHIBIT 7 Confidential ww Subject to Protective Order TAK-CHENGI-00001696 P7141-00001 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226 D-TUESDAY, JULY 31, 2007 USA TODAY Keep diabetes drug Avandia on the market, FDA advised 'Black box' label cy usually follows them, trials of Avandia, He found that Therapies for type 2 diabetes Committee members vôted 20-3 Avandia patients were 43%imore for heart risk that Avandia increases heart risks, likely to have a lieart attack or be Type Name brands Sffect side effects But they also voied 22-1 that the hospitalized for blocked coromary NownLag, Lantus, that Loy blosd sugar, weight gain IS suggested drug's risk/bienefit profile merits 3 arteries than others la the thats. others by dojections contross staying on drugstore shelves. Glaxo has argued, that Nissen's Embera, - inhaled bigh pugar Mest panelists "who voted in fa- called a meta-analysis, is in Insuin by Nita Rubin vor of kepping Avandia on the mar hérently, fiawed, and that its lown Amary, (aw sugar, weight restriction ket suggested a variety of labeling research has labed to fmd secretions of blond frow in the heart (cardue (schemic risk) USA TODAY changes. including à "black box cantly. increased riskio theart Biguanides Glucophage, others Dectease the ampunt Lank acidas(s; The popular diabetes drig Avan- warning about its effect on heartat tacks in Avendia usersi Metformin of sugas abscribed shoud not be gives to people with lidney problems and released nemaio on the market tack risk and Before Nisser's study was post- by the lives lespite evidence) that it. can-in- tions" stating It should not be used ed, about million Americans with: Presuse; dyset Starch Nockers Costecistestinal effects the in high-risk patients) thôse) type erdiabetes took Avandia, that dow digestion such as Mouring gas, dianfae " nausex - (mendbers fof two Food %with , history of, cording to Glaxo, but that figuié has of Health and (Drugi Administra- disease or those who have, also about (900,000 Mare 8 tim advisory, commit- been long-teim users of insulin. than 18 million, Americans have SES incommended Monday. TWe welcome this- decision as type: d'abetes Prandin; Stasilx Stimulate Loss sugar; Their decision carnes after a day of positive for patients," said Ronald David Graham of the FDA's Office intealing to sdentists from the FDA Krail, (Glaxo's chief medical officer. on and Reulice hats effects nd' EAvandia maker GlaxisSmith- The committee recogrubed the de fold parielists Avandia shoud come meats Jine. The FDIA sought the advice of bilitating nature of this disease and nf the market The drug probably analogues Help régulate efferts ba advisory panels alter The New the importarce of multiple treat- caused 80,000. heart attacks and release in response is high sugar levels ingland journit of Medicine pasted ment aptions? deaths rince it came, 00 the LLS. pa that increases insalin Limited dirkal expesience becaus the drug was approved study May 21 that suggested In the New England fournal study, market in 1993 hie said. when blood suga. is high- in 2006. maker Merck apper resulatory frandia could Increase fieart attack Steven Nissen, chief of cardiovascui Actos, the other drug in the same tract infections, stuly ar hose, sere and headad sk Advisory panel recommenda- lar medicine ax the Cleveland Clinic, class as Avandia, does not apprar to às possible aide ons are not binding, but the agen pooled the: results of 42 clinical increase heart attack risk, he said. Secroe: TODAT MARKETPL ACE TODAY usitoday conte I Hours of operations Mon, 833 mm To adveruse call 1.800.397.0070 Tollfree In the U,S. enly NOTICES ANWOUNCEMENTS BUSINESS FRBINEHSHIPS TIGKETS NOTICES reccerch theelest < x Seet Buy or Yated " - LEGALADTICES com PUSLIG cosy a - Visgra, Calle, Loxtha and mare Catre Coropida thaty & - You can TEAM UP with us Ns per Stoc Sebs Codice YOUR and MISSING S THE STATES COURT FUR 350 Celebrity ATHLETESIS www.vlamedic.com Tha 338 - RISTRIC? CF ADOPTIONS -1-877-4-VIAGRA (668) TIT-VEGAS MORTRAGE, WC WIN WITH THE SUPER JUICE GIANTIII CASENO: P7141-00002 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226

Who is the 23rd Addressee mentioned in the list?

srjf0226

srjf0226_p15, srjf0226_p16, srjf0226_p17, srjf0226_p18

Senior Vice President, Accounting Center

Privileged and Confidential: Attorney - Client Communication and Attorney Work Product text messages; photographs or image files; databases and other structured data; data created, maintained, or accessed by any proprietary software application; and any other information that exists in electronic form regardless of how or where such information is stored, including without limitation, information stored at the office, at home, on computer servers or networks; on hard drives; on removable media such as floppy disks, CDs, DVDs, USB flash drives, memory sticks, thumb drives and cards, back-up tapes, and the like; or on home computers. II. GENERAL: To the extent that a document exists both electronically and in paper format, the electronic document must be retained, and the paper copy must also be retained to the extent that it is not an exact printout of the electronic document. All documents subject to this notice must continue to be maintained as they exist. This means that such documents must not be edited, marked upon, or otherwise altered in any manner whatsoever. If it is necessary, in the ordinary course of business, for you to edit, mark upon, or otherwise alter any document that is subject to this notice, then (1) a copy of such document should be created, (2) the original should be preserved in accordance with this notice, and (3) alterations can then be made to the copy. Any documents or information fitting the classifications set forth above that have been placed in off-site storage are also not to be destroyed at any time. III. WIIERE TO PRESERVE ACTOS® AND ACTOSO COMBINATION MEDICINES LEGAL HOLD DOCUMENTS: Each Takeda Employee and Contractor shall create an Outlook Subfolder for legal hold purposes entitled "Actos Legal Hold" and preserve the Responsive Documents in the form of e-mail which are or will be sent or received on or after September 2, 2011 in such Outlook Subfolder. The appendix attached hereto set forth how to create an Outlook Subfolder. Please make sure that such holder shall be created as subfolder of "Inbox." Paper documents and electronically stored information that may not be appropriate for storage in an Outlook Subfolder should be maintained pursuant to your department's filing systems. If you have questions regarding the manner in which electronically stored information trelating to ACTOS© or ACTOS combination medicines should be maintained, or if you need assistance in maintaining such information, please contact Mr. Hironao Ihara, Manager, MIS Planning, Corporate Strategy & Planning Department, (E-mail: hironao.ihara@takeda.com/l IP Phone: 702239 / T-net: 811-2450). IV. FORWARDTO RELEVANT PERSONNEL: If you believe anyone else in your division or department whom you believe has or might have Responsive Documents, please keep such person informed of this request by forwarding this 4 Confidential - Subject to Protective Order TAK-RIM30b6-00000828 Source: https://www.indup534500006t.ucsf.edu/docs/srjf0226 Privileged and Confidential: Attorney - Client Communication and Attorney Work Product legal hold. In the case of forwarding, please copy the personnel in theLegal Department as set forth below. V. CONTACT INFORMATION: If you have any questions or need any assistance with respect to the retention of ACTOS®, ACTOS® combination medicines, and PPAR alpha/gamma agonists-related materials, please contact the below personnel. Thank you for your continuing cooperation in this important matter. [Contact Information] Legal Department (IP Licensing and R&D Contracts) Senor Directors, Kazuyuki Kisaka E-mail: kazuyuki.kisaka@takeda.com IP Phone: 700729 / T-net: 811-2145 Legal Department (IP Licensing and R&D Contracts) Manager, Yukari Maei E-mail: yukari.mael@takeda.com IP Phone: 706440/T-net: 811-2557 List of Addressees: Senior Vice President, Office of the Corporate Auditors Senior Vice President, Corporate Strategy Department Senior Vice President, Corporate Finance & Controlling Department Senior Vice President, Human Resources Department Senior Vice President, Office of the President & CEO Senior Vice President, Corporate Communications Department Senior Vice President, Global Licensing & Business Development Department Senior Vice President, Administrative Management Department Pharmaceutical Affairs Senior Vice President, Auditing Department Senior Vice President, Environment & Safety Department Senior Vice President, Global Quality Assurance Department Senior Vice President, Pharmaceutical Research Division Senior Vice President, Chemistry, Manufacturing and Controls Center Senior Vice President, Pharmaceutical Development Division Senior Vice President, Intellectual Property Department Senior Vice President, Vaccine Business Division Senior Vice President, CMSO Office Senior Vice President, Pharmaceutical Production Division Senior Vice President, Pharmaceutical Marketing Division Senior Vice President, Division of North Asia President, Consumer Healthcare Company Senior Vice President, General Affairs & Personnel Center Senior Vice President, Accounting Center 5 Confidential - Subject to Protective Order TAK-RIM30b6-00000829 Source: https://www.indup'534s000a7ts.ucsf.edu/docs/srjf0226 Privileged and Confidential: Attorney - Client Communication and Attorney Work Product Copy to: Senior Directors and Directors of relevant departments, divisions Special note to Senior Directors of relevant divisions or center who are responsible for administrative operation of the divisions or center; We identified and list certain departments within your division or department which we believe have or might have Responsive Documents in accordance with the Rules of Organizations and Operations and are sending this legal hold to each of those departments. If you believe any other departments have or might have Responsive Documents, please forward this legal hold to such departments. In such case, please inform us of the departments to which you forwarded this legal hold. 6 Confidential - Subject to Protective Order TAK-RIM30b6-00000830 Source: https://www.indup534s-0008ts.ucsf.edu/docs/srjf0226 Privileged and Confidential: Attorney - Client Communication and Attorney Work Product Appendix How to create "Actos Legal Hold" Stepl: Select "New-Folder" in the Oul-Shift+! E Step2: At the Create New Folder window, enter "Actos Legal Hold" as the folder name, select "Inbox" as the place and push "OK" button. the Actov Legal Hokd l's the the As the result of above operation, you can find the "Actos Legal Hold" folder as follows. b u E PIV. 0 is a --- n. Actos Legal Hold 7 Confidential - Subject to Protective Order TAK-RIM30b6-00000831 Source: https://www.indup5345-0009ts.ucsf.edu/docs/srjf0226

What are the timings for Continental Breakfast?

xsjf0226

xsjf0226_p0, xsjf0226_p1, xsjf0226_p2, xsjf0226_p3, xsjf0226_p4, xsjf0226_p5

8:00-9:00

From: Baron, David To: noyama_Takashi@takeda.co.jp'; Sato, Keiichiro (TPC); Saito, Katsuhisa CC: Thorn, Claire (TGRD); Kashiyae. Masalake (TGRD) Sent: 11/18/2002 6:20:11 PM Subject: Documents for Thursday Meeting Attachments; ACTOS and Rodent Bladder Cancer.ppt; Nonclincal Study Proposal.doc; Nonclincal White Paper WORKING doc: PPAR_bladder_prose doc; PPAR_bullets_11_14doc Attached is the agenda (PowerPoint) for Thursday's meeting at the O'Hare Hillon. Also included are supporting documents by Chris Durack and myself and Dr Chuck Aurant What we hope to accomplish at the meeting is to write collectively a 2-3 page summary of our position on bladder tumors to provide to the Agency next week and map out a supporting experimental strategy I look forward to seeing you in Chicago. Best regards, David Confidential - Subject to Protective Order TAK-BAROND-00000762 PENGAD Source: https://www.indug DOCUMENT PRODUCED IN NATIVE FORMAT ************* Confidential - Subject to Protective Order TAK-BAROND-00000763-R Source: https://www.indug5379000002ts.ucsf.edu/docs/xsjf0226 Draft Agenda Continental breakfast (8:00-9:00) Introductions (9:00-9:10) Purpose of meeting (9:10-9:15) Generation of response to FDA (9:15-12:00) Working lunch (12:00-1:00) Discussion of proposed experiments: (12:00-1:00) Feasibility Study conduct Timelines Future plans (1:00-1:30) Confidential - Subject to Protective Order TAK-BAROND-0000076 Source: https://www.indup537ac00003ts.ucsf.edu/docs/xsjf0226 Response Document Experiments already undertaken Proposal: high level "executive" summary Stand alone Bullet point organization Supplementary material Annotation of bullet points Annotated references TRE Confidential - Subject to Protective Order TAK-BAROND-0000076! Source: https://www.indup5370000004s.ucsf.edu/docs/xsjf0226 Response Document Introduction ACTOS male rat data summary Summary of presumed FDA data on mixed inhibitors Hypothesis for mechanism of action of ACTOS in male rats Cohen hypothesis revisited and updated Renal effects (urine electrolytes, osmolality, pH) Liver effects (urine protein composition) PPAR agonism: a, Y, mixed ac, Y Possible roles in bladder carcinogenesis Characterization of thiazolidinediones (pio VS. rosi) Confidential - Subject to Protective Order TAK-BAROND-00000761 Source: https://www.indup537ac00005s.ucsf.edu/docs/xsjf0226 Pakeda Executive Summary, cont. Proposed experiments Risk assessment for patients: o Are nongenotoxic rodent bladder tumorigens predictive of human risk? Conclusions Supplementary materials Confidential - Subject to Protective Order TAK-BAROND-0000076: Source: https://www.indup5370c00006ts.ucsf.edu/docs/xsjf0226

what is the "subject" of this letter?

tzjf0226

tzjf0226_p0, tzjf0226_p1

"article in todays USA Today regarding Avandia hearing"

From: Chen, Gigi To: "DCC WXA Dist Buffalo, NY CC: Johnston, Kendra; Precurato-Grubb, Marti Sent: 7/31/2007 11:48:09 AM Jubject: Article in today's USA Today regarding Avandia hearing Attachments: FDA Advised printed in USA Today July 31 07.doc Hello Buffalo Team & Marti, In case you did not see this in your travels today please find attached an article regarding the Avandia hearing in USA Today printed 7/31/07 (Today). Note the chart on the right hand side of the page stating *side effects" of TZD's. Jason, the article you sent all of us regarding the side effect of cancer was even listed! Obviously, not something we would bring up or mention on our sales calls but just something to be aware of in case it is mentioned out in the field! Also note the last sentence of the article: "Actos, the other drug in the same class as Avandia, does not appear to increase heart attack risk, he said", referencing David Graham's comment! Hope everyone is doing well! Gigi Gigi M. Chen, May Premier Sales Representative Buffalo North Tast 1.877.202.2720 ext. 14692 cellular: 716.725.7100 EXHIBIT 7 Confidential ww Subject to Protective Order TAK-CHENGI-00001696 P7141-00001 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226 D-TUESDAY, JULY 31, 2007 USA TODAY Keep diabetes drug Avandia on the market, FDA advised 'Black box' label cy usually follows them, trials of Avandia, He found that Therapies for type 2 diabetes Committee members vôted 20-3 Avandia patients were 43%imore for heart risk that Avandia increases heart risks, likely to have a lieart attack or be Type Name brands Sffect side effects But they also voied 22-1 that the hospitalized for blocked coromary NownLag, Lantus, that Loy blosd sugar, weight gain IS suggested drug's risk/bienefit profile merits 3 arteries than others la the thats. others by dojections contross staying on drugstore shelves. Glaxo has argued, that Nissen's Embera, - inhaled bigh pugar Mest panelists "who voted in fa- called a meta-analysis, is in Insuin by Nita Rubin vor of kepping Avandia on the mar hérently, fiawed, and that its lown Amary, (aw sugar, weight restriction ket suggested a variety of labeling research has labed to fmd secretions of blond frow in the heart (cardue (schemic risk) USA TODAY changes. including à "black box cantly. increased riskio theart Biguanides Glucophage, others Dectease the ampunt Lank acidas(s; The popular diabetes drig Avan- warning about its effect on heartat tacks in Avendia usersi Metformin of sugas abscribed shoud not be gives to people with lidney problems and released nemaio on the market tack risk and Before Nisser's study was post- by the lives lespite evidence) that it. can-in- tions" stating It should not be used ed, about million Americans with: Presuse; dyset Starch Nockers Costecistestinal effects the in high-risk patients) thôse) type erdiabetes took Avandia, that dow digestion such as Mouring gas, dianfae " nausex - (mendbers fof two Food %with , history of, cording to Glaxo, but that figuié has of Health and (Drugi Administra- disease or those who have, also about (900,000 Mare 8 tim advisory, commit- been long-teim users of insulin. than 18 million, Americans have SES incommended Monday. TWe welcome this- decision as type: d'abetes Prandin; Stasilx Stimulate Loss sugar; Their decision carnes after a day of positive for patients," said Ronald David Graham of the FDA's Office intealing to sdentists from the FDA Krail, (Glaxo's chief medical officer. on and Reulice hats effects nd' EAvandia maker GlaxisSmith- The committee recogrubed the de fold parielists Avandia shoud come meats Jine. The FDIA sought the advice of bilitating nature of this disease and nf the market The drug probably analogues Help régulate efferts ba advisory panels alter The New the importarce of multiple treat- caused 80,000. heart attacks and release in response is high sugar levels ingland journit of Medicine pasted ment aptions? deaths rince it came, 00 the LLS. pa that increases insalin Limited dirkal expesience becaus the drug was approved study May 21 that suggested In the New England fournal study, market in 1993 hie said. when blood suga. is high- in 2006. maker Merck apper resulatory frandia could Increase fieart attack Steven Nissen, chief of cardiovascui Actos, the other drug in the same tract infections, stuly ar hose, sere and headad sk Advisory panel recommenda- lar medicine ax the Cleveland Clinic, class as Avandia, does not apprar to às possible aide ons are not binding, but the agen pooled the: results of 42 clinical increase heart attack risk, he said. Secroe: TODAT MARKETPL ACE TODAY usitoday conte I Hours of operations Mon, 833 mm To adveruse call 1.800.397.0070 Tollfree In the U,S. enly NOTICES ANWOUNCEMENTS BUSINESS FRBINEHSHIPS TIGKETS NOTICES reccerch theelest < x Seet Buy or Yated " - LEGALADTICES com PUSLIG cosy a - Visgra, Calle, Loxtha and mare Catre Coropida thaty & - You can TEAM UP with us Ns per Stoc Sebs Codice YOUR and MISSING S THE STATES COURT FUR 350 Celebrity ATHLETESIS www.vlamedic.com Tha 338 - RISTRIC? CF ADOPTIONS -1-877-4-VIAGRA (668) TIT-VEGAS MORTRAGE, WC WIN WITH THE SUPER JUICE GIANTIII CASENO: P7141-00002 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226

who is writing this letter?

tzjf0226

tzjf0226_p0, tzjf0226_p1

CHEN, GIGI, chen, gigi, gigi m. chen, MBA

From: Chen, Gigi To: "DCC WXA Dist Buffalo, NY CC: Johnston, Kendra; Precurato-Grubb, Marti Sent: 7/31/2007 11:48:09 AM Jubject: Article in today's USA Today regarding Avandia hearing Attachments: FDA Advised printed in USA Today July 31 07.doc Hello Buffalo Team & Marti, In case you did not see this in your travels today please find attached an article regarding the Avandia hearing in USA Today printed 7/31/07 (Today). Note the chart on the right hand side of the page stating *side effects" of TZD's. Jason, the article you sent all of us regarding the side effect of cancer was even listed! Obviously, not something we would bring up or mention on our sales calls but just something to be aware of in case it is mentioned out in the field! Also note the last sentence of the article: "Actos, the other drug in the same class as Avandia, does not appear to increase heart attack risk, he said", referencing David Graham's comment! Hope everyone is doing well! Gigi Gigi M. Chen, May Premier Sales Representative Buffalo North Tast 1.877.202.2720 ext. 14692 cellular: 716.725.7100 EXHIBIT 7 Confidential ww Subject to Protective Order TAK-CHENGI-00001696 P7141-00001 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226 D-TUESDAY, JULY 31, 2007 USA TODAY Keep diabetes drug Avandia on the market, FDA advised 'Black box' label cy usually follows them, trials of Avandia, He found that Therapies for type 2 diabetes Committee members vôted 20-3 Avandia patients were 43%imore for heart risk that Avandia increases heart risks, likely to have a lieart attack or be Type Name brands Sffect side effects But they also voied 22-1 that the hospitalized for blocked coromary NownLag, Lantus, that Loy blosd sugar, weight gain IS suggested drug's risk/bienefit profile merits 3 arteries than others la the thats. others by dojections contross staying on drugstore shelves. Glaxo has argued, that Nissen's Embera, - inhaled bigh pugar Mest panelists "who voted in fa- called a meta-analysis, is in Insuin by Nita Rubin vor of kepping Avandia on the mar hérently, fiawed, and that its lown Amary, (aw sugar, weight restriction ket suggested a variety of labeling research has labed to fmd secretions of blond frow in the heart (cardue (schemic risk) USA TODAY changes. including à "black box cantly. increased riskio theart Biguanides Glucophage, others Dectease the ampunt Lank acidas(s; The popular diabetes drig Avan- warning about its effect on heartat tacks in Avendia usersi Metformin of sugas abscribed shoud not be gives to people with lidney problems and released nemaio on the market tack risk and Before Nisser's study was post- by the lives lespite evidence) that it. can-in- tions" stating It should not be used ed, about million Americans with: Presuse; dyset Starch Nockers Costecistestinal effects the in high-risk patients) thôse) type erdiabetes took Avandia, that dow digestion such as Mouring gas, dianfae " nausex - (mendbers fof two Food %with , history of, cording to Glaxo, but that figuié has of Health and (Drugi Administra- disease or those who have, also about (900,000 Mare 8 tim advisory, commit- been long-teim users of insulin. than 18 million, Americans have SES incommended Monday. TWe welcome this- decision as type: d'abetes Prandin; Stasilx Stimulate Loss sugar; Their decision carnes after a day of positive for patients," said Ronald David Graham of the FDA's Office intealing to sdentists from the FDA Krail, (Glaxo's chief medical officer. on and Reulice hats effects nd' EAvandia maker GlaxisSmith- The committee recogrubed the de fold parielists Avandia shoud come meats Jine. The FDIA sought the advice of bilitating nature of this disease and nf the market The drug probably analogues Help régulate efferts ba advisory panels alter The New the importarce of multiple treat- caused 80,000. heart attacks and release in response is high sugar levels ingland journit of Medicine pasted ment aptions? deaths rince it came, 00 the LLS. pa that increases insalin Limited dirkal expesience becaus the drug was approved study May 21 that suggested In the New England fournal study, market in 1993 hie said. when blood suga. is high- in 2006. maker Merck apper resulatory frandia could Increase fieart attack Steven Nissen, chief of cardiovascui Actos, the other drug in the same tract infections, stuly ar hose, sere and headad sk Advisory panel recommenda- lar medicine ax the Cleveland Clinic, class as Avandia, does not apprar to às possible aide ons are not binding, but the agen pooled the: results of 42 clinical increase heart attack risk, he said. Secroe: TODAT MARKETPL ACE TODAY usitoday conte I Hours of operations Mon, 833 mm To adveruse call 1.800.397.0070 Tollfree In the U,S. enly NOTICES ANWOUNCEMENTS BUSINESS FRBINEHSHIPS TIGKETS NOTICES reccerch theelest < x Seet Buy or Yated " - LEGALADTICES com PUSLIG cosy a - Visgra, Calle, Loxtha and mare Catre Coropida thaty & - You can TEAM UP with us Ns per Stoc Sebs Codice YOUR and MISSING S THE STATES COURT FUR 350 Celebrity ATHLETESIS www.vlamedic.com Tha 338 - RISTRIC? CF ADOPTIONS -1-877-4-VIAGRA (668) TIT-VEGAS MORTRAGE, WC WIN WITH THE SUPER JUICE GIANTIII CASENO: P7141-00002 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226

when was this letter sent?

tzjf0226

tzjf0226_p0, tzjf0226_p1

7/31/2007 11:48:09 am, 7/31/2007 11:48:09 AM

From: Chen, Gigi To: "DCC WXA Dist Buffalo, NY CC: Johnston, Kendra; Precurato-Grubb, Marti Sent: 7/31/2007 11:48:09 AM Jubject: Article in today's USA Today regarding Avandia hearing Attachments: FDA Advised printed in USA Today July 31 07.doc Hello Buffalo Team & Marti, In case you did not see this in your travels today please find attached an article regarding the Avandia hearing in USA Today printed 7/31/07 (Today). Note the chart on the right hand side of the page stating *side effects" of TZD's. Jason, the article you sent all of us regarding the side effect of cancer was even listed! Obviously, not something we would bring up or mention on our sales calls but just something to be aware of in case it is mentioned out in the field! Also note the last sentence of the article: "Actos, the other drug in the same class as Avandia, does not appear to increase heart attack risk, he said", referencing David Graham's comment! Hope everyone is doing well! Gigi Gigi M. Chen, May Premier Sales Representative Buffalo North Tast 1.877.202.2720 ext. 14692 cellular: 716.725.7100 EXHIBIT 7 Confidential ww Subject to Protective Order TAK-CHENGI-00001696 P7141-00001 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226 D-TUESDAY, JULY 31, 2007 USA TODAY Keep diabetes drug Avandia on the market, FDA advised 'Black box' label cy usually follows them, trials of Avandia, He found that Therapies for type 2 diabetes Committee members vôted 20-3 Avandia patients were 43%imore for heart risk that Avandia increases heart risks, likely to have a lieart attack or be Type Name brands Sffect side effects But they also voied 22-1 that the hospitalized for blocked coromary NownLag, Lantus, that Loy blosd sugar, weight gain IS suggested drug's risk/bienefit profile merits 3 arteries than others la the thats. others by dojections contross staying on drugstore shelves. Glaxo has argued, that Nissen's Embera, - inhaled bigh pugar Mest panelists "who voted in fa- called a meta-analysis, is in Insuin by Nita Rubin vor of kepping Avandia on the mar hérently, fiawed, and that its lown Amary, (aw sugar, weight restriction ket suggested a variety of labeling research has labed to fmd secretions of blond frow in the heart (cardue (schemic risk) USA TODAY changes. including à "black box cantly. increased riskio theart Biguanides Glucophage, others Dectease the ampunt Lank acidas(s; The popular diabetes drig Avan- warning about its effect on heartat tacks in Avendia usersi Metformin of sugas abscribed shoud not be gives to people with lidney problems and released nemaio on the market tack risk and Before Nisser's study was post- by the lives lespite evidence) that it. can-in- tions" stating It should not be used ed, about million Americans with: Presuse; dyset Starch Nockers Costecistestinal effects the in high-risk patients) thôse) type erdiabetes took Avandia, that dow digestion such as Mouring gas, dianfae " nausex - (mendbers fof two Food %with , history of, cording to Glaxo, but that figuié has of Health and (Drugi Administra- disease or those who have, also about (900,000 Mare 8 tim advisory, commit- been long-teim users of insulin. than 18 million, Americans have SES incommended Monday. TWe welcome this- decision as type: d'abetes Prandin; Stasilx Stimulate Loss sugar; Their decision carnes after a day of positive for patients," said Ronald David Graham of the FDA's Office intealing to sdentists from the FDA Krail, (Glaxo's chief medical officer. on and Reulice hats effects nd' EAvandia maker GlaxisSmith- The committee recogrubed the de fold parielists Avandia shoud come meats Jine. The FDIA sought the advice of bilitating nature of this disease and nf the market The drug probably analogues Help régulate efferts ba advisory panels alter The New the importarce of multiple treat- caused 80,000. heart attacks and release in response is high sugar levels ingland journit of Medicine pasted ment aptions? deaths rince it came, 00 the LLS. pa that increases insalin Limited dirkal expesience becaus the drug was approved study May 21 that suggested In the New England fournal study, market in 1993 hie said. when blood suga. is high- in 2006. maker Merck apper resulatory frandia could Increase fieart attack Steven Nissen, chief of cardiovascui Actos, the other drug in the same tract infections, stuly ar hose, sere and headad sk Advisory panel recommenda- lar medicine ax the Cleveland Clinic, class as Avandia, does not apprar to às possible aide ons are not binding, but the agen pooled the: results of 42 clinical increase heart attack risk, he said. Secroe: TODAT MARKETPL ACE TODAY usitoday conte I Hours of operations Mon, 833 mm To adveruse call 1.800.397.0070 Tollfree In the U,S. enly NOTICES ANWOUNCEMENTS BUSINESS FRBINEHSHIPS TIGKETS NOTICES reccerch theelest < x Seet Buy or Yated " - LEGALADTICES com PUSLIG cosy a - Visgra, Calle, Loxtha and mare Catre Coropida thaty & - You can TEAM UP with us Ns per Stoc Sebs Codice YOUR and MISSING S THE STATES COURT FUR 350 Celebrity ATHLETESIS www.vlamedic.com Tha 338 - RISTRIC? CF ADOPTIONS -1-877-4-VIAGRA (668) TIT-VEGAS MORTRAGE, WC WIN WITH THE SUPER JUICE GIANTIII CASENO: P7141-00002 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226

who is the premier sales representative ?

tzjf0226

tzjf0226_p0, tzjf0226_p1

gigi m.chen, gigi m. chen, MBA

From: Chen, Gigi To: "DCC WXA Dist Buffalo, NY CC: Johnston, Kendra; Precurato-Grubb, Marti Sent: 7/31/2007 11:48:09 AM Jubject: Article in today's USA Today regarding Avandia hearing Attachments: FDA Advised printed in USA Today July 31 07.doc Hello Buffalo Team & Marti, In case you did not see this in your travels today please find attached an article regarding the Avandia hearing in USA Today printed 7/31/07 (Today). Note the chart on the right hand side of the page stating *side effects" of TZD's. Jason, the article you sent all of us regarding the side effect of cancer was even listed! Obviously, not something we would bring up or mention on our sales calls but just something to be aware of in case it is mentioned out in the field! Also note the last sentence of the article: "Actos, the other drug in the same class as Avandia, does not appear to increase heart attack risk, he said", referencing David Graham's comment! Hope everyone is doing well! Gigi Gigi M. Chen, May Premier Sales Representative Buffalo North Tast 1.877.202.2720 ext. 14692 cellular: 716.725.7100 EXHIBIT 7 Confidential ww Subject to Protective Order TAK-CHENGI-00001696 P7141-00001 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226 D-TUESDAY, JULY 31, 2007 USA TODAY Keep diabetes drug Avandia on the market, FDA advised 'Black box' label cy usually follows them, trials of Avandia, He found that Therapies for type 2 diabetes Committee members vôted 20-3 Avandia patients were 43%imore for heart risk that Avandia increases heart risks, likely to have a lieart attack or be Type Name brands Sffect side effects But they also voied 22-1 that the hospitalized for blocked coromary NownLag, Lantus, that Loy blosd sugar, weight gain IS suggested drug's risk/bienefit profile merits 3 arteries than others la the thats. others by dojections contross staying on drugstore shelves. Glaxo has argued, that Nissen's Embera, - inhaled bigh pugar Mest panelists "who voted in fa- called a meta-analysis, is in Insuin by Nita Rubin vor of kepping Avandia on the mar hérently, fiawed, and that its lown Amary, (aw sugar, weight restriction ket suggested a variety of labeling research has labed to fmd secretions of blond frow in the heart (cardue (schemic risk) USA TODAY changes. including à "black box cantly. increased riskio theart Biguanides Glucophage, others Dectease the ampunt Lank acidas(s; The popular diabetes drig Avan- warning about its effect on heartat tacks in Avendia usersi Metformin of sugas abscribed shoud not be gives to people with lidney problems and released nemaio on the market tack risk and Before Nisser's study was post- by the lives lespite evidence) that it. can-in- tions" stating It should not be used ed, about million Americans with: Presuse; dyset Starch Nockers Costecistestinal effects the in high-risk patients) thôse) type erdiabetes took Avandia, that dow digestion such as Mouring gas, dianfae " nausex - (mendbers fof two Food %with , history of, cording to Glaxo, but that figuié has of Health and (Drugi Administra- disease or those who have, also about (900,000 Mare 8 tim advisory, commit- been long-teim users of insulin. than 18 million, Americans have SES incommended Monday. TWe welcome this- decision as type: d'abetes Prandin; Stasilx Stimulate Loss sugar; Their decision carnes after a day of positive for patients," said Ronald David Graham of the FDA's Office intealing to sdentists from the FDA Krail, (Glaxo's chief medical officer. on and Reulice hats effects nd' EAvandia maker GlaxisSmith- The committee recogrubed the de fold parielists Avandia shoud come meats Jine. The FDIA sought the advice of bilitating nature of this disease and nf the market The drug probably analogues Help régulate efferts ba advisory panels alter The New the importarce of multiple treat- caused 80,000. heart attacks and release in response is high sugar levels ingland journit of Medicine pasted ment aptions? deaths rince it came, 00 the LLS. pa that increases insalin Limited dirkal expesience becaus the drug was approved study May 21 that suggested In the New England fournal study, market in 1993 hie said. when blood suga. is high- in 2006. maker Merck apper resulatory frandia could Increase fieart attack Steven Nissen, chief of cardiovascui Actos, the other drug in the same tract infections, stuly ar hose, sere and headad sk Advisory panel recommenda- lar medicine ax the Cleveland Clinic, class as Avandia, does not apprar to às possible aide ons are not binding, but the agen pooled the: results of 42 clinical increase heart attack risk, he said. Secroe: TODAT MARKETPL ACE TODAY usitoday conte I Hours of operations Mon, 833 mm To adveruse call 1.800.397.0070 Tollfree In the U,S. enly NOTICES ANWOUNCEMENTS BUSINESS FRBINEHSHIPS TIGKETS NOTICES reccerch theelest < x Seet Buy or Yated " - LEGALADTICES com PUSLIG cosy a - Visgra, Calle, Loxtha and mare Catre Coropida thaty & - You can TEAM UP with us Ns per Stoc Sebs Codice YOUR and MISSING S THE STATES COURT FUR 350 Celebrity ATHLETESIS www.vlamedic.com Tha 338 - RISTRIC? CF ADOPTIONS -1-877-4-VIAGRA (668) TIT-VEGAS MORTRAGE, WC WIN WITH THE SUPER JUICE GIANTIII CASENO: P7141-00002 Source: https://www.industrydocuments.ucsf.edu/docs/tzjf0226

what is the title of this page?

xsjf0226

xsjf0226_p0, xsjf0226_p1, xsjf0226_p2, xsjf0226_p3, xsjf0226_p4, xsjf0226_p5

Executive Summary, cont., executive summary, cont.

From: Baron, David To: noyama_Takashi@takeda.co.jp'; Sato, Keiichiro (TPC); Saito, Katsuhisa CC: Thorn, Claire (TGRD); Kashiyae. Masalake (TGRD) Sent: 11/18/2002 6:20:11 PM Subject: Documents for Thursday Meeting Attachments; ACTOS and Rodent Bladder Cancer.ppt; Nonclincal Study Proposal.doc; Nonclincal White Paper WORKING doc: PPAR_bladder_prose doc; PPAR_bullets_11_14doc Attached is the agenda (PowerPoint) for Thursday's meeting at the O'Hare Hillon. Also included are supporting documents by Chris Durack and myself and Dr Chuck Aurant What we hope to accomplish at the meeting is to write collectively a 2-3 page summary of our position on bladder tumors to provide to the Agency next week and map out a supporting experimental strategy I look forward to seeing you in Chicago. Best regards, David Confidential - Subject to Protective Order TAK-BAROND-00000762 PENGAD Source: https://www.indug DOCUMENT PRODUCED IN NATIVE FORMAT ************* Confidential - Subject to Protective Order TAK-BAROND-00000763-R Source: https://www.indug5379000002ts.ucsf.edu/docs/xsjf0226 Draft Agenda Continental breakfast (8:00-9:00) Introductions (9:00-9:10) Purpose of meeting (9:10-9:15) Generation of response to FDA (9:15-12:00) Working lunch (12:00-1:00) Discussion of proposed experiments: (12:00-1:00) Feasibility Study conduct Timelines Future plans (1:00-1:30) Confidential - Subject to Protective Order TAK-BAROND-0000076 Source: https://www.indup537ac00003ts.ucsf.edu/docs/xsjf0226 Response Document Experiments already undertaken Proposal: high level "executive" summary Stand alone Bullet point organization Supplementary material Annotation of bullet points Annotated references TRE Confidential - Subject to Protective Order TAK-BAROND-0000076! Source: https://www.indup5370000004s.ucsf.edu/docs/xsjf0226 Response Document Introduction ACTOS male rat data summary Summary of presumed FDA data on mixed inhibitors Hypothesis for mechanism of action of ACTOS in male rats Cohen hypothesis revisited and updated Renal effects (urine electrolytes, osmolality, pH) Liver effects (urine protein composition) PPAR agonism: a, Y, mixed ac, Y Possible roles in bladder carcinogenesis Characterization of thiazolidinediones (pio VS. rosi) Confidential - Subject to Protective Order TAK-BAROND-00000761 Source: https://www.indup537ac00005s.ucsf.edu/docs/xsjf0226 Pakeda Executive Summary, cont. Proposed experiments Risk assessment for patients: o Are nongenotoxic rodent bladder tumorigens predictive of human risk? Conclusions Supplementary materials Confidential - Subject to Protective Order TAK-BAROND-0000076: Source: https://www.indup5370c00006ts.ucsf.edu/docs/xsjf0226

what is the first point under the title-executive summary, cont.

xsjf0226

xsjf0226_p0, xsjf0226_p1, xsjf0226_p2, xsjf0226_p3, xsjf0226_p4, xsjf0226_p5

Proposed experiments, proposed experiments

From: Baron, David To: noyama_Takashi@takeda.co.jp'; Sato, Keiichiro (TPC); Saito, Katsuhisa CC: Thorn, Claire (TGRD); Kashiyae. Masalake (TGRD) Sent: 11/18/2002 6:20:11 PM Subject: Documents for Thursday Meeting Attachments; ACTOS and Rodent Bladder Cancer.ppt; Nonclincal Study Proposal.doc; Nonclincal White Paper WORKING doc: PPAR_bladder_prose doc; PPAR_bullets_11_14doc Attached is the agenda (PowerPoint) for Thursday's meeting at the O'Hare Hillon. Also included are supporting documents by Chris Durack and myself and Dr Chuck Aurant What we hope to accomplish at the meeting is to write collectively a 2-3 page summary of our position on bladder tumors to provide to the Agency next week and map out a supporting experimental strategy I look forward to seeing you in Chicago. Best regards, David Confidential - Subject to Protective Order TAK-BAROND-00000762 PENGAD Source: https://www.indug DOCUMENT PRODUCED IN NATIVE FORMAT ************* Confidential - Subject to Protective Order TAK-BAROND-00000763-R Source: https://www.indug5379000002ts.ucsf.edu/docs/xsjf0226 Draft Agenda Continental breakfast (8:00-9:00) Introductions (9:00-9:10) Purpose of meeting (9:10-9:15) Generation of response to FDA (9:15-12:00) Working lunch (12:00-1:00) Discussion of proposed experiments: (12:00-1:00) Feasibility Study conduct Timelines Future plans (1:00-1:30) Confidential - Subject to Protective Order TAK-BAROND-0000076 Source: https://www.indup537ac00003ts.ucsf.edu/docs/xsjf0226 Response Document Experiments already undertaken Proposal: high level "executive" summary Stand alone Bullet point organization Supplementary material Annotation of bullet points Annotated references TRE Confidential - Subject to Protective Order TAK-BAROND-0000076! Source: https://www.indup5370000004s.ucsf.edu/docs/xsjf0226 Response Document Introduction ACTOS male rat data summary Summary of presumed FDA data on mixed inhibitors Hypothesis for mechanism of action of ACTOS in male rats Cohen hypothesis revisited and updated Renal effects (urine electrolytes, osmolality, pH) Liver effects (urine protein composition) PPAR agonism: a, Y, mixed ac, Y Possible roles in bladder carcinogenesis Characterization of thiazolidinediones (pio VS. rosi) Confidential - Subject to Protective Order TAK-BAROND-00000761 Source: https://www.indup537ac00005s.ucsf.edu/docs/xsjf0226 Pakeda Executive Summary, cont. Proposed experiments Risk assessment for patients: o Are nongenotoxic rodent bladder tumorigens predictive of human risk? Conclusions Supplementary materials Confidential - Subject to Protective Order TAK-BAROND-0000076: Source: https://www.indup5370c00006ts.ucsf.edu/docs/xsjf0226

What is the full form of FDA?

hsjf0226

hsjf0226_p0, hsjf0226_p1

Food and Drug Administration

Received: 3703 1.6 3014439282 T REGULATORY AFFAIRSE Page 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P001/002 EXHIBIT 105 Food and Drug Administratio Center for Drug Evaluation Office of Drug Evaluation ODE Il FACSIMILE TRANSMITTAL SHEET DATE: January 3, 2003 To: Jane: Hasking From: Jena Weber gib Regulatory Manager Project Manager Company: Takeda Pharmaceuticals North Division of Metabolic and Endocrine Drug America, Inc. Products, HFD-510 Fax number: 847-383-3143 Fax number: 301-443-9282 Phone number: 847-383-3243 Phone number: 301-827-6422 Subject: Reference NDA 21-073 (Actos); labeling change to PRECAUTIONS section, Carchnogenesin, Mutagenests, Impairment of Fertility subacction of the package insert as recommended by executive Carcinogenicity Assessment Committee (eCAC), convened December 17, 2002. Total no. of pages including cover: I Comments - Committee Concludions: Data from the 2-year rat caroinogenicity studies with several PPAR agonists demonstrate this class of compounds is clearly associated with marked increases in the incidence of bladder and/or renal epithelial cell tumors in rats of borh sexes. The available mechanistic studies have failed to correlate the tumors in rats with changes in urine pH, osmolarity, changes in electrolyte concentrations, microcrystalluria or calculi. The Committee concluded these data suggeat a potential clinical safety concom and agrees with the Division's recommendation for a proposed labeling change as follows: A two-year carcinagenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human onal dose of 45 mg basod ou mg/m ). Drug-induced tumors were not observed in any organ except for the vrinnry bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 thg/kg/day and mpove (approximately cqual to the maximum recommended human onal dose based on mg/ra ). The of-thase A two-year carcinogenicity study was conducted in maie and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m ). No drug-induced turnors were observed in any organ. Document to be mailed: YES NO THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT 13 ADDRESSED AND MAY CONTAIN INFORMATION THAT (a PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER APPLICABLE LAW, RECEIVED REGULATORY AFFAIRS DEPARTMENT JAN 03 2003 Takeda Pharmaceuticals North America, Inc. Confidential - Subject to Protective Order TAK-THOMCL-00032194 Produced in MDI on 02/21 Source: https://wwww.indup5370c0000ts.ucsf.edu/docs/hsjf0226 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P002/002 This Is a representation of an electronic record that was signed electronically and this page la the manifestation of the electronic signature. 181 Jena Weber 1/3/03 01:48:27 PM aso David Orloff 1/3/03 01:55:38 PM MEDICAL OFFICER Confidential - Subject to Protective Order TAK-THOMCL-00032195 Source: ttps://www.indup5370-00002 s.ucsf.edu/docs/hsjf0226

What is the date mentioned?

hsjf0226

hsjf0226_p0, hsjf0226_p1

January 3, 2003

Received: 3703 1.6 3014439282 T REGULATORY AFFAIRSE Page 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P001/002 EXHIBIT 105 Food and Drug Administratio Center for Drug Evaluation Office of Drug Evaluation ODE Il FACSIMILE TRANSMITTAL SHEET DATE: January 3, 2003 To: Jane: Hasking From: Jena Weber gib Regulatory Manager Project Manager Company: Takeda Pharmaceuticals North Division of Metabolic and Endocrine Drug America, Inc. Products, HFD-510 Fax number: 847-383-3143 Fax number: 301-443-9282 Phone number: 847-383-3243 Phone number: 301-827-6422 Subject: Reference NDA 21-073 (Actos); labeling change to PRECAUTIONS section, Carchnogenesin, Mutagenests, Impairment of Fertility subacction of the package insert as recommended by executive Carcinogenicity Assessment Committee (eCAC), convened December 17, 2002. Total no. of pages including cover: I Comments - Committee Concludions: Data from the 2-year rat caroinogenicity studies with several PPAR agonists demonstrate this class of compounds is clearly associated with marked increases in the incidence of bladder and/or renal epithelial cell tumors in rats of borh sexes. The available mechanistic studies have failed to correlate the tumors in rats with changes in urine pH, osmolarity, changes in electrolyte concentrations, microcrystalluria or calculi. The Committee concluded these data suggeat a potential clinical safety concom and agrees with the Division's recommendation for a proposed labeling change as follows: A two-year carcinagenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human onal dose of 45 mg basod ou mg/m ). Drug-induced tumors were not observed in any organ except for the vrinnry bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 thg/kg/day and mpove (approximately cqual to the maximum recommended human onal dose based on mg/ra ). The of-thase A two-year carcinogenicity study was conducted in maie and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m ). No drug-induced turnors were observed in any organ. Document to be mailed: YES NO THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT 13 ADDRESSED AND MAY CONTAIN INFORMATION THAT (a PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER APPLICABLE LAW, RECEIVED REGULATORY AFFAIRS DEPARTMENT JAN 03 2003 Takeda Pharmaceuticals North America, Inc. Confidential - Subject to Protective Order TAK-THOMCL-00032194 Produced in MDI on 02/21 Source: https://wwww.indup5370c0000ts.ucsf.edu/docs/hsjf0226 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P002/002 This Is a representation of an electronic record that was signed electronically and this page la the manifestation of the electronic signature. 181 Jena Weber 1/3/03 01:48:27 PM aso David Orloff 1/3/03 01:55:38 PM MEDICAL OFFICER Confidential - Subject to Protective Order TAK-THOMCL-00032195 Source: ttps://www.indup5370-00002 s.ucsf.edu/docs/hsjf0226

who is writing this letter?

sqjf0226

sqjf0226_p0, sqjf0226_p1

Marlene Dubas, marlene dubas

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226

who is in the cc?

sqjf0226

sqjf0226_p0, sqjf0226_p1

tom muldoon, Tom Muldoon

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226

Who is the sender of this fax?

hsjf0226

hsjf0226_p0, hsjf0226_p1

Jena Weber

Received: 3703 1.6 3014439282 T REGULATORY AFFAIRSE Page 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P001/002 EXHIBIT 105 Food and Drug Administratio Center for Drug Evaluation Office of Drug Evaluation ODE Il FACSIMILE TRANSMITTAL SHEET DATE: January 3, 2003 To: Jane: Hasking From: Jena Weber gib Regulatory Manager Project Manager Company: Takeda Pharmaceuticals North Division of Metabolic and Endocrine Drug America, Inc. Products, HFD-510 Fax number: 847-383-3143 Fax number: 301-443-9282 Phone number: 847-383-3243 Phone number: 301-827-6422 Subject: Reference NDA 21-073 (Actos); labeling change to PRECAUTIONS section, Carchnogenesin, Mutagenests, Impairment of Fertility subacction of the package insert as recommended by executive Carcinogenicity Assessment Committee (eCAC), convened December 17, 2002. Total no. of pages including cover: I Comments - Committee Concludions: Data from the 2-year rat caroinogenicity studies with several PPAR agonists demonstrate this class of compounds is clearly associated with marked increases in the incidence of bladder and/or renal epithelial cell tumors in rats of borh sexes. The available mechanistic studies have failed to correlate the tumors in rats with changes in urine pH, osmolarity, changes in electrolyte concentrations, microcrystalluria or calculi. The Committee concluded these data suggeat a potential clinical safety concom and agrees with the Division's recommendation for a proposed labeling change as follows: A two-year carcinagenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human onal dose of 45 mg basod ou mg/m ). Drug-induced tumors were not observed in any organ except for the vrinnry bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 thg/kg/day and mpove (approximately cqual to the maximum recommended human onal dose based on mg/ra ). The of-thase A two-year carcinogenicity study was conducted in maie and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m ). No drug-induced turnors were observed in any organ. Document to be mailed: YES NO THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT 13 ADDRESSED AND MAY CONTAIN INFORMATION THAT (a PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER APPLICABLE LAW, RECEIVED REGULATORY AFFAIRS DEPARTMENT JAN 03 2003 Takeda Pharmaceuticals North America, Inc. Confidential - Subject to Protective Order TAK-THOMCL-00032194 Produced in MDI on 02/21 Source: https://wwww.indup5370c0000ts.ucsf.edu/docs/hsjf0226 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P002/002 This Is a representation of an electronic record that was signed electronically and this page la the manifestation of the electronic signature. 181 Jena Weber 1/3/03 01:48:27 PM aso David Orloff 1/3/03 01:55:38 PM MEDICAL OFFICER Confidential - Subject to Protective Order TAK-THOMCL-00032195 Source: ttps://www.indup5370-00002 s.ucsf.edu/docs/hsjf0226

What is the total no of pages in the fax including cover?

hsjf0226

hsjf0226_p0, hsjf0226_p1

1

Received: 3703 1.6 3014439282 T REGULATORY AFFAIRSE Page 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P001/002 EXHIBIT 105 Food and Drug Administratio Center for Drug Evaluation Office of Drug Evaluation ODE Il FACSIMILE TRANSMITTAL SHEET DATE: January 3, 2003 To: Jane: Hasking From: Jena Weber gib Regulatory Manager Project Manager Company: Takeda Pharmaceuticals North Division of Metabolic and Endocrine Drug America, Inc. Products, HFD-510 Fax number: 847-383-3143 Fax number: 301-443-9282 Phone number: 847-383-3243 Phone number: 301-827-6422 Subject: Reference NDA 21-073 (Actos); labeling change to PRECAUTIONS section, Carchnogenesin, Mutagenests, Impairment of Fertility subacction of the package insert as recommended by executive Carcinogenicity Assessment Committee (eCAC), convened December 17, 2002. Total no. of pages including cover: I Comments - Committee Concludions: Data from the 2-year rat caroinogenicity studies with several PPAR agonists demonstrate this class of compounds is clearly associated with marked increases in the incidence of bladder and/or renal epithelial cell tumors in rats of borh sexes. The available mechanistic studies have failed to correlate the tumors in rats with changes in urine pH, osmolarity, changes in electrolyte concentrations, microcrystalluria or calculi. The Committee concluded these data suggeat a potential clinical safety concom and agrees with the Division's recommendation for a proposed labeling change as follows: A two-year carcinagenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human onal dose of 45 mg basod ou mg/m ). Drug-induced tumors were not observed in any organ except for the vrinnry bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 thg/kg/day and mpove (approximately cqual to the maximum recommended human onal dose based on mg/ra ). The of-thase A two-year carcinogenicity study was conducted in maie and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m ). No drug-induced turnors were observed in any organ. Document to be mailed: YES NO THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT 13 ADDRESSED AND MAY CONTAIN INFORMATION THAT (a PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER APPLICABLE LAW, RECEIVED REGULATORY AFFAIRS DEPARTMENT JAN 03 2003 Takeda Pharmaceuticals North America, Inc. Confidential - Subject to Protective Order TAK-THOMCL-00032194 Produced in MDI on 02/21 Source: https://wwww.indup5370c0000ts.ucsf.edu/docs/hsjf0226 01/03/03 16:13 DMEDP-CDER-FDA 8473833143 NO.006 P002/002 This Is a representation of an electronic record that was signed electronically and this page la the manifestation of the electronic signature. 181 Jena Weber 1/3/03 01:48:27 PM aso David Orloff 1/3/03 01:55:38 PM MEDICAL OFFICER Confidential - Subject to Protective Order TAK-THOMCL-00032195 Source: ttps://www.indup5370-00002 s.ucsf.edu/docs/hsjf0226

Which all compaies are added as defendants in a lawsuit?

sqjf0226

sqjf0226_p0, sqjf0226_p1

Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc.

EXHIBIT Takeda 40 TO: Sam Hamanaka DATE: July 19, 2002 Mark Booth Wendell Cheatham Rich Daly Terry Fukumoto Dean Hart Masatake Kashiyae Curtis Rhine Lori Smith Claire Thom Lee Voight Chuck Whitmer FROM: Marlene Dubas CC: Tom Muldoon RE: Preservation of Documents And Electronic Data relating to Actos MEMO: A motion has been filed to add Takeda Pharmaceuticals North America, Inc. and Takeda Pharmaceuticals America, Inc. as defendants in a lawsuit. The plaintiff in this lawsuit seeks damages for personal injury and wrongful death allegedly resulting from the use of certain prescription drugs, including Actos. To be able to respond to discovery requests from the plaintiff, if that becomes necessary, we must take steps to preserve any documents that may be called for in this lawsuit. Until further notice, you are instructed to preserve any and all documents and electronic data which discuss, mention, or relate to Actos. This means do not destroy, delete, throw away or otherwise discard any such documents or electronic data. This includes correspondence, records, and data, contained in your paper and electronic files, regardless of form and including email correspondence and attachments and electronic data. Continued Confidential - Subject to Protective Order TAK-RIM30b6-00000653 Source: https://www.indup53090007ts.ucsf.edu/docs/sqjf0226 Memo to: Distribution July 19, 2002 Page 2 Action Steps: Please interpret this directive in its broadest sense to prevent the deletion or destruction of any recorded information and data relating in any way to Actos. Please take steps immediately to preserve such documents and data within your department. Please distribute this memo to members of your group and advise them of the importance of following these instructions. If you have any questions regarding the implementation of this directive, please contact me. Marlene Charra Marlene C. Dubas Confidential - Subject to Protective Order TAK-RIM30b6-00000654 Source: https://www.indup5309-00002s.ucsf.edu/docs/sqjf0226