> DEPARTMENT OF HEALTH AND HUMAN SERVICES
>
> FOOD AND DRUG ADMINISTRATION
>
> CENTER FOR FOOD SAFETY AND APPLIED NUTRITION
>
> **NUTRITION SUBCOMMITTEE MEETING**
>
> **TOTAL FAT AND TRANS FAT**
>
> Tuesday, April 27, 2004
>
> 12:30 p.m.
>
> Leows L\'Enfant Plaza Hotel
>
> 480 L\'Enfant Plaza
>
> Ballroom A and B
>
> Washington, D.C.
>
> PARTICIPANTS
>
> Norman I. Krinsky, Ph.D., Chair
>
> Jeanne Latham, Executive Secretary
>
> MEMBERS:
>
> Susan S. Baker, M.D., Ph.D.
>
> R. Jean Hine, Ph.D. (Consumer Representative)
>
> Guy Johnson, Ph.D. (Industry Representative)
>
> Susan T. Mayne, Ph.D.
>
> Suzanne Pelican, M.S., R.D.
>
> Barbara M. Shannon, Ph.D.
>
> TEMPORARY VOTING MEMBERS:
>
> Alice Lichtenstein, Ph.D.
>
> Eric Rimm, Ph.D.
>
> C O N T E N T S
>
> Welcoming Remarks, Virginia Wilkeneng, R.D. 4
>
> Conflict of Interest Statement, Jeanne Latham 6
>
> Background, Questions and Charges,
>
> Dr. Kathleen Ellwood 10
>
> Remarks by Chairperson and Member Introductions,
>
> Norman I. Krinsky, Ph.D. 20
>
> Public Comment:
>
> Robert Earl, National Food Processors
>
> Association 167
>
> Martin Hahn, Hogan and Hartson 175
>
> Subcommittee Discussion 195
>
> Public Comment:
>
> Mary Enig, Ph.D., Weston A. Price Foundation 200
>
> Subcommittee Discussion 215
>
> P R O C E E D I N G S
>
> **Welcoming Remarks**
>
> MS. WILKENENG: I would like to start the meeting. I am Virginia
> Wilkeneng, the Deputy Director in the Office of Nutritional Products,
> Labeling and Dietary Supplements. I am here to welcome the committee.
> This is the first meeting of the Nutrition Subcommittee of FDA\'s Food
> Advisory Committee. We thank you very much for your willingness to
> serve the agency in this way and for the service that you will be
> providing as you go through this meeting and future meetings.
>
> We thank you so much for helping us address some of the major issues
> of the day, in this particular case primarily health claims and
> nutrition labeling. In the case of health claims, we have been facing
> increasing issues of whether the total fat limitations we have on
> health claims is still relevant in light of the other limitations on
> saturated fat and cholesterol and we welcome your input on this.
>
> In the case of nutrition labeling, the issue of trans fat labeling has
> been one the agency has been dealing with for a great deal of time
> now. We do have our final regulations for putting the quantitative
> amount of trans fat on the label and you are starting to see those
> appear in the marketplace now. But our concern is how consumers will
> be able to put that information into action. They need some context
> for the numbers.
>
> Numerically, the amounts of trans fat in the label will be small
> numbers. Some of our research has shown that people react to the
> magnitude of the number. Whether it is grams of fat or milligrams of
> sodium or micrograms of other things, they can\'t be expected to know
> what amounts of those various nutrients are needed in a diet.
>
> For that reason, FDA established, with the new nutritional labeling
> regulations, daily values so there are to be percentages there so that
> the consumer doesn\'t need to know how much of any particular nutrient
> they need but can look at the percent DV and determine whether it is a
> high number or a low number and, therefore, know the magnitude of that
> nutrient in the serving of a food. So, we need some help with the
> trans fat in trying to figure out the best way possible to address
> those issues.
>
> So, I welcome you. I am a stand-in. You will see on your agenda that
> Dr. Laura Tarantino\'s name had been down here. She is our Acting
> Office Director. I expect many of you knew Dr. Christine Taylor who
> had been our director for a number of years since our Office was put
> together, and she has just recently, in fact this week, finally got to
> Geneva where she will now be in a two-year program with the World
> Health Organization. If you don\'t already know, I am happy to
> announce that starting next Monday we will have a new Office Director,
> Dr. Barbara Schnieman, from UC Davis, so she will be here to welcome
> you the next time you have a meeting but, in the meantime, thank you
> very much. We very much appreciate your service. I will turn it over
> to Jeanne Latham.
>
> **Conflict of Interest Statement**
>
> MS. LATHAM: Good morning. I am Jeanne Latham, the Executive Secretary
> for the FDA Nutrition Subcommittee of the Advisory Committee. I would
> like to welcome everyone, particularly our members and our temporary
> voting members. With that, I would like to read the conflict of
> interest statement into the meeting record.
>
> The following announcement addresses the issue of conflict of interest
> with respect to this meeting, and is made a part of the record to
> preclude even the appearance of such at this meeting.
>
> The authority to appoint temporary voting members is granted to the
> Center Director and, relying on that authority, Dr. Robert E.
> Brackett, Center Director of the Center for Food Safety and Applied
> Nutrition, has signed letters stating, by authority granted under the
> Food Advisory Committee Charter, that he appoints, Dr. Lichtenstein
> and Dr. Rimm as temporary voting members of the Nutrition Subcommittee
> of the Food Advisory Committee for the April 27th and 28th, 2004
> meeting on total fat and trans fat.
>
> All members and temporary voting members have been screened for
> financial conflicts of interest. Because of the breadth of topics to
> be discussed at this meeting, all of the members and temporary voting
> members have been screened for any and all financial interests
> associated with regulated industry. Based on this review, FDA has
> determined, in accordance with 18 USC Section 208(b)(3), to grant
> genera matters waivers to Dr. R.G. Hine, Dr. Norman Krinsky, Dr. Alice
> Lichtenstein, Dr. Jay Michael McGinnis, Dr. Susan T. Mayne, Ms. Susan
> Pelican and Dr. Eric Rimm that permits them to fully participate in
> the matters before the committee. Copies of the waiver statements may
> be obtained by submitting a written request to the agency\'s Freedom
> of Information Office, Room 12A-30 of the Parklawn Building.
>
> In an effort to enhance consistency within FDA, the agency has
> recently adopted a policy whereby all public commentors will be asked
> to report any personal financial interests that could be affected by
> the committee\'s deliberations. A copy of this policy was provided to
> all the individuals who registered to make a public comment. I believe
> that additional copies of the policy may be obtained at the
> registration desk.
>
> I have one additional administrative announcement. We have received
> six written submissions from individuals, some of whom were not able
> to appear at this meeting. The submissions are from Barbara Sakow, Dr.
> Mary Enig of the Western Price Foundation, Alison Krester, of the
> Grocery Manufacturers of America, two from Dr. Fred Kumerow at the
> University of Illinois Urbana, and Ann Beckman of Hogan and Hartson.
> The submissions have been provided to our members and copies are
> available at the registration desk.
>
> Thank you and, again, welcome to the committee members and everyone
> who has joined us today. I will turn the meeting over now to Dr.
> Kathleen Ellwood, FDA\'s Office of Nutritional Products Labeling and
> Dietary Supplements, the Center for Food Safety and Applied Nutrition,
> who will give us some background information and talk about questions
> and charges to the committee. Kathy?
>
> **Background, Questions and Charges**
>
> DR. ELLWOOD: I would like to thank the members of the committee for
> agreeing to serve on this committee and work with us on these
> important issues.
>
> I am going to go through and give you just a little bit of background
> as to why we are asking these questions. The first question is
> addressing the eligibility criterion the FDA has applied to most
> health claim regulations pertaining to heart disease risk. Foods
> bearing these claims must be low in total fat. We would like to know
> what the current evidence suggests in terms of total fat intake and
> risk of coronary heart disease. As you heard from Virginia Wilkeneng,
> we do have various disqualifying levels for many new trans and total
> fat is among those. Keep in mind that we still have low unsaturated
> fat and cholesterol.
>
> But as a background to this, I want to go through some of the health
> claims that do bear a low total fat criterion and some of the
> exemptions that we have made. Now, the first two that you see listed
> here are sat fat and the fruit and vegetable one. They came in under
> NLEA, the Nutritional Labeling and Education Act. The second one was a
> little bit of a modification for what Congress asked for. Then, the
> latter two were through the petition process. These are all health
> claims that meet significant scientific agreements so they are
> authorized.
>
> In the first health claim on saturated fat and cholesterol effect on
> heart disease, FDA concluded that the scientific evidence linking
> diets low in saturated fat and cholesterol to reduce the risk of CHD
> was strong. The agency also noted that while total fat was not as
> strongly or directly linked to increased risk of coronary heart
> disease as sat fat and cholesterol, it may have significant indirect
> effects.
>
> The justification was that low fat foods generally help individuals in
> reducing their intake of sat fat and cholesterol and that excess
> calories, of which fat contributes more per gram than the other energy
> nutrients, is associated with two health-related conditions that can
> be risk factors for heart disease.
>
> FDA concluded that the scientific evidence linking diets low in
> saturated fat and cholesterol to reduce risk of coronary heart disease
> was strong and, as such, the subject of the claim is dietary saturated
> fat and cholesterol and dietary total fat is addressed as an
> additional criterion that must be met by a food before it may use the
> dietary saturated fat and cholesterol health claim.
>
> But there was an exemption because it was noted that you can have
> diets with meat and poultry, as long as they were lean, as part of a
> healthful diet. Meats and poultry are recognized or regulated by FSIS.
> However, FDA put in a claim for game meats and fish, which we do
> regulate, that they meet the extra lean requirements for saturated
> fat, cholesterol and total fat or they were not as stringent as the
> definitions for low sat fat, low cholesterol and low total fat.
>
> Now, in the fruits, vegetables and grain products, the second health
> claim that I wanted to discuss, the low total fat criterion was
> included because low total fat is one of the characterizing features
> of diets rich in fiber containing fruits, vegetables and grain
> products. It is also a characteristic of dietary patterns which relate
> to lower heart disease risk and it facilitates the ability of
> consumers to achieve diets low in saturated fat and cholesterol. So,
> that remained a criterion.
>
> In the soy protein and coronary heart disease claim there was an
> exemption for a lower total fat criterion for food products consisting
> of or derived from whole soy beans as long as those products contained
> no other fat. The rationale for this was that whole soy beans are
> useful sources of soy protein and can be appropriately incorporated in
> a diet low in fat, saturated fat and cholesterol.
>
> For a more recent health claim, plant sterol and stanol esters and
> coronary heart disease, we have an interim final rule that came out in
> 2000. FDA required that foods bearing this health claim be low in
> saturated fat and low in cholesterol but not low in total fat. The
> rationale for this was that because the emphasis in the Dietary
> Guidelines for 2000 was on diets moderate in total fat and,
> additionally, there were a number of foods such as margarine and salad
> dressings that could be formulated to contain plant sterol or stanol
> esters by still qualifying as low saturated fat and low cholesterol.
>
> More recently, we just released a qualified health claim for walnuts
> and coronary heart disease. This health claim is not one through
> authorization, through a letter of enforcement discretion. We did not
> impose a requirement that a food meet the definition of a low fat food
> as walnuts are not because walnuts have a good ratio of unsaturated
> fat to saturated fat and they contain significant amounts of other
> substances, such as dietary fiber and phytosterols, which may reduce
> the risk of coronary heart disease. They are also exempt from the high
> fat disqualifying level which is 13 grams per reference amount
> customarily consumed.
>
> We have seen a lot of current scientific evidence in recent years and
> the shift that you need to look more at the type of fat, such as the
> Dietary Guidelines for Americans 2000 which I have mentioned, as well
> as the recent Institute of Medicine/National Academy of Sciences
> report, macronutrient report that was recently released, as well as
> the American Heart Association Dietary Guidelines and the National
> Cholesterol Education Program\'s ATP III report.
>
> Now I am going to shift to our second set of questions dealing with
> trans fatty acids, and our first one was that the dietary guidelines
> committee may suggest that less than 1 percent of energy should be
> obtained from trans fatty acids, and this calculates out to about 2
> grams per day for a 2,000 kilocalorie diet. We would like to know if
> the scientific evidence supports this level.
>
> It is very important to FDA that we set a dietary value so we can have
> a percent DV. If you have a percent DV it gives the consumer an idea
> as to how much there is of that nutrient. They can put it in the
> context of their total daily diet. For instance, if you have a 5
> percent daily value, that would be a low amount of that nutrient
> versus 20 percent which would be a high amount. So, it is a little bit
> more than just looking at a gram amount of a particular nutrient.
>
> The second question related to trans fatty acids we would like
> answered is, when compared to saturated fatty acids, are trans fatty
> acids considered to be more, less or similarly adverse with respect to
> coronary heart disease?
>
> A little bit of background on trans fat, in 1993 there was a final
> rule that came out entitled Food Labeling Mandatory Status of
> Nutrition Labeling and Nutrient Content Revision Format for Nutrition
> Label. In this, the agency required declaration of total fat and
> saturated fat in the nutrition label. At the same time, the agency
> said it was premature to include trans fatty acids in nutrition
> labeling because we lacked scientific agreement on the dietary
> implication of trans fat intake, but we also acknowledged that we
> would be revisiting this in the future as scientific evidence became
> more evident in this area.
>
> A final rule was released just last July. This was a partial response
> to a petition from the Center for Science in the Public Interest. But,
> at the same time, FDA was very aware of an increasing body of evidence
> that showed that dietary trans fatty acids raised blood cholesterol
> levels, specifically LDL cholesterol, thereby increasing the risk of
> coronary heart disease. Scientific evidence included authoritative
> statements from the Dietary Guidelines for Americans 2000.
>
> In this final rule the declaration of this nutrient must be on a
> separate line, immediately under the declaration for saturated fat,
> but it would not include a percent daily value. This is required for
> some of the other mandatory nutrients such as saturated fat. This
> final rule will go into effect as of January 1st, 2006.
>
> At the same time, an advance notice of proposed rule-making was
> released and this is a way for FDA to go out and ask several questions
> that we need to have addressed prior to going to a proposed rule. Some
> of the things we asked about trans fat statements were whether it
> should be alone or in combination with saturated fat and cholesterol,
> or should it be a footnote in the nutrition facts panel or disclosure
> statement in conjunction with claims. There are other issues on this
> but I am not going into those. I am going to just deal with the first
> statement here.
>
> Now, the use of a footnote\--we had several statements but
> essentially, due to several reports that have come out, trans fats
> should be kept as low as possible. But even coming up with a percent
> daily value would also help us in nutrient content and health claims.
>
> Some of the authoritative reports I have already discussed are the
> Dietary Guidelines 2000 that recommended that Americans cut back on
> trans fats, reducing fat intake; a recent report in the IOM/National
> Academy macronutrients report, as well as the NCEO ATP III report, all
> stating that trans fat should be kept as low as possible. The IOM/NAS
> report said it should be kept as low as possible while maintaining a
> nutritionally balanced diet. It may not provide a dietary reference
> intake for trans fat or information the agency needs to establish the
> daily reference value for nutrition labeling purposes. In addition, a
> more current report on guiding principles was just released suggesting
> that the saturated fat and trans fat be on separate lines but have a
> joint percent daily value.
>
> The authoritative body, as you all know, the Dietary Guidelines
> Committee, is currently meeting and, as of last month, discussed
> setting less than 1 percent of energy as what would be obtained from
> trans fatty acids. As I have said, this calculates out on a 2,000
> kilocalorie diet, which is what we base our daily values on, to be
> about 2 grams per day.
>
> So, what we would like for the committee to do is to provide a
> succinct reply to the three questions which we have proposed based on
> the most current scientific evidence and on what you will have heard
> during the deliberations of this meeting. And, we look forward very
> much to your deliberations. Thank you very much.
>
> **Remarks by Chairperson and Member Introductions**
>
> DR. KRINSKY: Thank you very much, Kathy, and this officially starts
> the meeting of the Subcommittee on Nutrition of the Food Advisory
> Committee. I would like to do a little housekeeping first of all. We
> have microphones in front of us and, as you will note, while I am
> speaking there is a red light on the microphone. That will indicate to
> me when you want to say something. There is a semicircle on the bottom
> that you push on or off and that will turn the mike on and off.
>
> I think it would be worthwhile at this time, since we know what our
> charge is, if we would just briefly introduce ourselves for the sake
> of the audience behind us. I would like to begin. I am Norman Krinsky
> and I am an Emeritus Professor of Biochemistry.
>
> I want to step back for a moment. I should have mentioned my name at
> the very beginning because this is being transcribed and the
> transcriber will find it most useful when you mention your name and
> then we will be able to write this down. So, Norman Krinsky. I am an
> Emeritus Professor of Biochemistry at Tufts University School of
> Medicine, in Boston, and a scientist at the Human Nutrition Research
> Center on Aging, also at Tufts University. My area of specialization
> is carotenoids, both chemistry, metabolism, action,
> function\--whatever they do in the human body, and also what their
> metabolites may be doing. Most of you know that the primary metabolite
> of the provitamin in carotenoids is vitamin A but there are other
> metabolites which have been becoming increasingly interesting with
> respect to what their functions may be. I am a member of the Food
> Advisory Committee of the FDA and I have also chaired two committees
> for the IOM/NAS, one the DRI committee on antioxidant vitamins, and
> the other a committee that was evaluating the scientific evidence for
> making claims. Let\'s go around from my right.
>
> DR. MAYNE: I am Susan Mayne. I am an Associate Professor of
> Epidemiology and Public Health at Yale University School of Medicine,
> and I am also the Associate Director of the Yale Cancer Center where I
> am responsible for cancer prevention and control at the Yale Cancer
> Center. My research interest is largely in nutritional epidemiology of
> cancer, with a broader interest in nutritional epidemiology of chronic
> disease. I have some specialized expertise in the antioxidant
> nutrients and the carotenoids, and I did serve on the DRI panel for
> antioxidant nutrients that Dr. Krinsky chaired. My background is in
> nutritional biochemistry and toxicology which later merged into
> epidemiology and clinical trials.
>
> DR. RIMM: I am Eric Rimm. I am an Associate Professor of Epidemiology
> and Nutrition at the Harvard School of Public Health. I have interests
> in nutrition and cardiovascular disease, specifically focusing on
> fatty acids, antioxidants, B vitamins, alcohol and a number of other
> interesting things related to cardiovascular disease, as well as
> obesity and diabetes. I also was on the DRI panel for macronutrients,
> and that is it.
>
> DR. SHANNON: I am Barbara Shannon. I am Professor Emeritus in
> Nutrition for the Pennsylvania State University and also Dean Emeritus
> of the College of Health and Human Development. My area is nutrition
> and education across the entire life span but most particularly
> nutrition and education in schools and cholesterol education in heart
> disease prevention.
>
> DR. HINE: My name is Jean Hine and I am from the Arkansas Cancer
> Research Center in Little Rock, where I am a Professor in the
> Department of Nutrition. My interests are in B vitamins, specifically
> folic acid and vitamin B-12, and more recently the effects of
> carbohydrates on development of cancers.
>
> DR. LICHTENSTEIN: My name is Alice Lichtenstein. I am a Professor of
> Nutrition Science and Policy at the Freedman School, Tufts University,
> and Director and Senior Scientist of the Cardiovascular Nutrition
> Laboratory at the USCA Human Nutrition Research Center on Aging at
> Tufts University. My primary interest is the effect of diet on
> cardiovascular disease risk factors in postmenopausal women and older
> males. As Dr. Rimm, I served on the IOM Macronutrients Panel. I also
> served on the 2000 Dietary Guidelines Committee and currently chair
> the nutrition committee of the Heart Association.
>
> DR. JOHNSON: My name is Guy Johnson. My background is nutrition and,
> after a brief stint in academia, I spent 20-some years with different
> food companies; 11 years with Gerber, 9 years with Pillsbury and, most
> recently, 2 years with Kellogg as VP of Nutrition for Kellogg USA. I
> saw the light a few years ago and decided to start my own consulting
> business so I have been deliriously happy helping a variety of
> interesting stakeholders address nutrition-related scientific,
> regulatory and communications issues, and I am very much looking
> forward to participating on this panel.
>
> DR. BAKER: My name is Susan Baker. I am a Professor of Pediatrics at
> the State University of New York at Buffalo and I am co-Division Chief
> of the Digestive Diseases and Nutrition Center at Buffalo Children\'s
> Hospital. I am a clinician. I am also a researcher. In the past my
> research has focused on the barrier function of the gastrointestinal
> tract and factors such as nutritional free radicals, and so on, that
> tend to disrupt it. More recently, we have had a big change in our
> laboratory and we are now looking at polymorphism in inflammatory
> mediators and the effect that it has on diseases in childhood. I also
> do a fair amount of clinical research, most recently in nutrition and
> CF, but my love is nutrition and pediatrics and that is where I
> continually try to focus myself. Thank you.
>
> MS. PELICAN: My name is Suzanne Pelican and I am a food and nutrition
> specialist with the University of Wyoming Cooperative Extension
> Service. I am also the co-principal investigator on a three-state
> project called \"Wellness in the Rockies.\" We are seeking to promote
> healthy weight among individuals of all ages using community and
> individual level approaches. We are looking to change people\'s
> attitudes and behaviors related to food, physical activity and body
> image. My area of work and training has been in nutrition education
> and public health. Prior to coming to University of Wyoming I worked
> for the Indian Health Service for the Navajo Nation for Pennsylvania
> State University and Colorado State University. Thank you.
>
> DR. KRINSKY: Thank you all for describing your interests and
> activities. I might point out that Michael McGinnis, whose name is at
> the table to my left, is not here today. He is not able to attend
> today but he will be here tomorrow but will not be in a position to
> vote on our actions because he will not be privy to the discussions
> that we have today.
>
> Speaking of voting, we have two temporary members of this committee,
> Eric Rimm and Alice Lichtenstein. They are voting members of this
> committee. We also have our consumer representative, Jean Hine. She
> also is a voting member. Guy Johnson is the industrial representative
> and he is a non-voting member. So, that sets us all straight, I hope,
> as far as who can vote and who can\'t vote. It is clear that we can
> all vote except for Guy.
>
> The issue that confronts us are the three separate questions, and we
> might as well begin with the very first one. The first one is what
> does the current evidence suggest in terms of total fat intake and
> risk of coronary heart disease?
>
> We have been supplied with readings, both in the notebook and readings
> that were sent to us later. There certainly is a long history of the
> relationship of fat intake and coronary heart disease. I think what
> this demonstrates is that we are beginning to get a little more
> sophisticated with respect to fat, that it is not a single entity but
> that it is composed of many different kinds of compounds. I think that
> is a general aspect of nutrition, that we deal with broad compounds
> and we see in many cases that we have to look at what the individual
> components are to see what their effects are on human nutrition.
>
> So, I would invite any comment with respect to total fat intake,
> particularly those of you that have had more direct experience than I.
> So, again, what does the current evidence suggest in terms of total
> fat intake and risk of coronary heart disease? Again, if you can give
> your name to begin with.
>
> DR. JOHNSON: Johnson. I just wanted to add one thing to the
> presentation that Dr. Ellwood made. Correct me if I am wrong, but I
> think there is another example of regulatory action that the agency
> has taken to provide more flexibility in a health claim with respect
> to fat, and that is the whole grain heart disease claim. It is a claim
> under the FDA Modernization Act. Originally the criteria for that
> health claim included a low fat criterion and, in response to a
> petition not too long ago, the agency relaxed that so that whole grain
> products that are not low fat are eligible to bear that claim as long
> as they meet the other criteria.
>
> DR. LICHTENSTEIN: I guess I will start the discussion off. I think the
> data support the impact of different fatty acids or classes of fatty
> acids in cardiovascular disease risk via effects on primarily lipids
> and lipoprotein levels and, to a lesser extent, on coagulation
> factors. But independent of the effect of low fat, high carbohydrate
> diets and triglyceride levels, I think the effect of the total fat
> content of the diet is far less, if not at all, relative to the
> individual fatty acids or classes.
>
> DR. KRINSKY: May I ask the question with respect to triglyceride
> levels and whether, in fact, that is a relative factor with respect to
> risk for coronary heart disease.
>
> DR. LICHTENSTEIN: Well, there is an inverse relationship between HDL
> cholesterol levels and triglyceride levels with rare exceptions,
> things like estrogen therapy which will increase triglycerides and not
> HDL cholesterol levels. Are you asking essentially is there an
> independent effect of triglyceride levels? I don\'t think it can be
> separated from the effect on HDL cholesterol levels. There are some
> data that would suggest that it is independent, but then there are
> other data to suggest that it is very difficult to control for one and
> not the other. Then, the other confounding factor is frequently, at
> least in a metabolic situation, that if you drop the fat content to
> the diet and the caloric density of the diet subjects tend to lose
> weight, at least in the short term. We are not clear about the long
> term. Then that complicates the effect of the macronutrient component
> of the diet on triglyceride levels because the weight loss itself will
> lower the triglyceride levels.
>
> DR. KRINSKY: I ask because it wasn\'t clear whether the trans fatty
> acids and saturated fatty acids, if they have an impact on
> triglycerides, whether that is going to be a direct relationship to
> altering the risk of coronary heart disease. Because I think basically
> what we are dealing with is what are the factors of trans and sat fat
> that impact on coronary heart disease. So, I gather with the
> triglycerides it is ambiguous. Thank you.
>
> DR. RIMM: I think one of the big issues that we stumbled over for a
> long time in the IOM committee was that by just talking about fat you
> miss what is being replaced in the diet, and that is if you move from
> a low fat diet to a high fat diet or, conversely, from a high fat diet
> to a low fat diet in an isocaloric situation, if you are putting in
> very refined carbohydrates you can say one thing, or if you are
> putting in whole grains or other carbohydrates which are absorbed more
> slowly then it makes it that much more difficult to interpret the
> effects of a high fat versus a low fat diet.
>
> But, in general, I think I concur completely with what Alice said,
> that the evidence suggests that the fatty acid component is much more
> important than the total amount of fat, and much of what we have
> struggled with is that in this country it is very hard to have a diet
> which is 60 percent of calories from fat and still be below the
> threshold for saturated fat and cholesterol.
>
> Obviously, that is an extreme but as you move down I think the
> challenge becomes, given the current food supply, can you eat 40
> percent of calories from fat and still stay below the saturated fat
> threshold and cholesterol threshold? So, given that, I think that
> there really is not strong evidence at all that variations in fat
> impact on coronary heart disease.
>
> DR. KRINSKY: Any other comments then? Alice?
>
> DR. LICHTENSTEIN: Just to follow-up on that, I think initially some of
> the reasoning behind recommending diets low in total fat, saturated
> fat and cholesterol was that if you decrease total fat, at least
> within the United States, you decrease saturated fat. There was a
> reassessment of that, at least during the deliberations of the 2000
> Dietary Guidelines Committee, because what happened as a result of
> that recommendation is that the low fat recommendation sort of took on
> a life of its own independent of the low saturated fat recommendation
> so that there was a proliferation of products that were low in total
> fat and had not been high in saturated far to begin with so that the
> adoption of a low fat diet using a lot of those products really
> resulted just in a net increase in carbohydrate intake, primarily
> refined carbohydrate intake and simple carbohydrates, and didn\'t have
> much of an impact on saturated fat.
>
> So, I think that some of the data that we have is partially confounded
> by that trend. I don\'t think it necessarily changes the conclusion
> that the total fat content of a diet doesn\'t seem to have a major
> effect on cardiovascular disease risk. But it needs to be taken into
> consideration because I think when you make recommendations they have
> to be scientifically sound but then one also needs to take into
> consideration how they are going to be interpreted by the public and
> by manufacturers.
>
> DR. KRINSKY: So, can we answer this first question with respect to
> total fat intake? If we are concerned about the component of the fat,
> how valid is the question with respect to coronary heart disease if it
> is not describing what the components are of the total fat? Because
> unless we assume that there is some given formula for total
> fat\--such-and-such percent sat, such-and-such percent
> polyunsaturated, such-and-such percent monounsaturated and trans, what
> is meant by total fat?
>
> DR. LICHTENSTEIN: What I think we have seen is that it de-emphasizes
> the components that probably have the major effect on cardiovascular
> disease which is saturated fat and trans fatty acids. Then we get into
> a situation where there are foods where perhaps there is adequate
> scientific data to make health claims as far as the examples that were
> given that actually required exemptions, so the bar was essentially
> higher for them.
>
> Another example would be something like salmon which is relatively
> high in fat but it is unsaturated fat, specifically a long chain of
> omega-3 fatty acids. So, the current emphasis on total fat really, I
> think, is diverting us from where probably the biggest bang for a
> health claim would be, and that would be the saturated fat and trans
> fatty acids.
>
> DR. RIMM: I think that if we look specifically at what the question
> asks, which is what I will try to do, the last line is what does the
> current evidence suggest in terms of total fat intake and risk of
> coronary heart disease? I think the current evidence from clinical
> trials that have been done and from prospective cohort studies\--all
> that evidence suggests that there is essentially no association within
> the range of what people eat. There have been two large clinical
> trials that have been done, one back in 1965 and one back in 1989,
> both of which altered fat intake and followed people for two to six
> years. There were secondary prevention trials. Both found no effect of
> change in fat of the diet.
>
> Subsequently, we and others have done prospective cohort studies
> looking across diets among men in the health professional follow-up
> study and nurses in the nurse health study, as well as a few other
> studies across a pretty wide range of diets in our cohort, ranging
> from 24 percent to 42 percent in calories from fat and within that,
> holding constant the composition, as we said, there really is no
> association between total fat and coronary heart disease.
>
> So, I think we really should be focusing on the composition, otherwise
> there may be more and more exemptions as more and more foods come up
> which, as you say, have higher monos and higher polys and lower sats
> and trans and would fit the definition and should be exempt.
>
> DR. JOHNSON: I wanted to also focus on the question that FDA asked.
> Primarily it is in the context of health claims. As those of us who
> lived through NLEA can attest, NLEA was spawned in the ocean where fat
> was public enemy number one and the dietary recommendations from the
> Heart Association and the dietary guidelines committee focused in on
> limiting total fat as part of a strategy to deal with that issue. Now
> we have a whole new chapter of the Heart Association, with guidelines
> written by the person sitting on my left I suspect, that came to the
> conclusion that heart disease risk can be perfectly well managed with
> a moderate fat diet assuming that it contained poly unsaturated and
> monounsaturated fatty acids. The dietary guidelines committee changed
> its tune. And, with respect to health claims there would still be a
> disqualifier level for total fat so that products that are very high
> in fat would be limited by that unless FDA granted them exclusion.
>
> So, there are still some controls on total fat with respect to health
> claims and it just seems to me that based on the information that has
> accumulated during the last 10 or 12 years, to have a carte blanche
> requirement that foods be low in fat in order to qualify for a health
> claim is based on yesterday\'s science.
>
> In addition, as has been pointed out, it is saturated fat and high
> levels of trans fat that are implicated in heart disease risk now and
> the agency can very easily control those as criteria for new health
> claims that come around. So, to me, this one is a slam dunk.
>
> DR. KRINSKY: Any other comments on total fat intake?
>
> MS. PELICAN: Suzie Pelican. Just to follow-up on Guy\'s slam dunk, it
> is really not necessarily a comment on the research but more looking
> in the future, and maybe this is beyond not only our committee\'s role
> but FDA\'s role, but thinking about such a change like this, would it
> be worthwhile to look at the kinds of changes that we might see in the
> food supply based on a change like this? Should we just kind of
> explore what that might mean for what we saw with, as I think Guy said
> NLEA, and saw this huge proliferation of low fat foods? Should we
> think at all that by dropping this requirement for total fat\--would
> that be worth exploring at all?
>
> DR. KRINSKY: Well, we know it has happened, the results of the low fat
> craze, if you will, and that is the present epidemic that we have of
> obesity. So, these recommendations have the most serious consequences.
> Alice?
>
> DR. LICHTENSTEIN: I think we have seen some of what will happen
> already because a lot of the products that were non-fat or low fat
> have actually gone off the market, in some cases due to consumer
> non-acceptance and in some cases because of some of the other diet
> trends that have occurred since that major proliferation. But I think
> if we look at what the consequences were and what types of foods came
> on the market, essentially if you take fat out of the diet or out of a
> food what are you putting in? Well, it appears that for a lot of those
> products it was sugar, and if it wasn\'t sugar it was refined
> carbohydrates. So, I think that is an important point to consider but
> I am not sure that, from what we have seen, it would be a disadvantage
> to drop those components of the diet. I think when the original low
> fat recommendations were made it was sort of envisioned that people
> would be eating a lot of fruits and vegetables, and legumes and whole
> grains. However, you know, we learned a lesson. We learned that
> although that may have been assumed and may have been what was
> intended, it turns out that is not exactly what happened. So, I think
> it is a point we need to really think about.
>
> DR. KRINSKY: That is \"the road to hell is paved with good
> intentions\" result. Certainly, the intention was laudable and the
> result is horrible, if you will, for the country.
>
> DR. LICHTENSTEIN: Unfortunate.
>
> DR. JOHNSON: I wanted to respond to Suzanne\'s question. I think that
> one ramification of what we are talking about would be to have the
> food industry focus in on cholesterol raising fatty acids and that
> would give them an incentive to develop products that are lower in
> those if there was more liberal use of health claims that provided
> some flexibility with respect to total fat.
>
> DR. LICHTENSTEIN: One other point that I think we learned from that
> lesson of just recommending low fat is that there was a certain
> perception of the consumer that low fat was synonymous with low
> calory, and that certainly was very dangerous because, with very rare
> exceptions, with something like whole milk and skim milk it definitely
> is not the case and, yet, there was a feeling that if it is low fat,
> non-fat, if that is what it says, it is good for me; I can eat lots of
> it. And, we see the consequences of it.
>
> Also, because I think the issue of overweight and obesity has really
> risen as far as a major health problem in the United States, in
> addition to perhaps putting less emphasis on the total fat content of
> the diet, I think what we really need to do is put a lot more emphasis
> on the caloric value of the specific foods and portions of the foods
> as presented on the food label. Because we are sort of seeing now that
> we have seen the pendulum swing towards the higher fat, higher protein
> foods, again to a certain extent the assumption is, well, these are
> the diet foods; these are lower in calories and, again, that is not
> the case. So, I think we have to perhaps recalibrate where we are
> putting the emphasis with respect to food health claims and nutrition
> education.
>
> DR. KRINSKY: The \"we\" is correct but the \"we\" is not around this
> table with respect to that kind of issue. The only calories that we
> are supposed to deal with is the percent trans of total calories. But
> your statement is heard and I hope it will be heard very widely. Thank
> you very much, Alice.
>
> DR. MAYNE: Just one comment, I know that we are talking about this in
> the context of cardiovascular but once foods make it on the
> marketplace we have to think about the global public health, not just
> cardiovascular disease. So, at some point I think the committee needs
> to think a little bit about the relationship between total fat intake
> in diabetes or total fat intake in cancer and total fat intake in
> other things because I think we get into trouble when we look at
> public health recommendations disease by disease rather than looking
> at the global burden of chronic disease.
>
> DR. KRINSKY: Well, let\'s go down that road a little bit. Can somebody
> give me the relationship between the total fat of the diet and its
> relationship to diabetes, cancer, rheumatoid arthritis\--you name it,
> whatever chronic disease?
>
> DR. MAYNE: As a cancer researcher, I think I will start with the
> cancer one, also the second leading cause of mortality in the U.S. It
> is still somewhat equivocal. The strongest evidence is thought to be
> related to things like breast cancer which was the primary rationale
> for launching the low fat diet part of the women\'s health initiative.
> As you know, that part of the trial is continuing so we don\'t have a
> final answer yet on whether a reduced fat diet will significantly
> impact on the incidence of breast cancer. We have some cohort studies,
> things like the nurses cohort and the pooling project which has pooled
> data from approximately seven different cohorts together and seems to
> not indicate a strong association between total fat intake and breast
> cancer risk. But the data is still somewhat equivocal and I think we
> just need to be a little cognizant.
>
> I think it is probably unlike cardiovascular disease but the type of
> fat is probably rather important. We have talked a little bit about
> omega-3, long chain omega-3 fatty acids. The evidence suggests, if
> anything, that they appear to be protective and not adverse in terms
> of cancer risk. That is pretty much a summary of where it is; the jury
> is still out at least until we have results. The only clinical trial
> is really the women\'s health initiative.
>
> There is one other secondary prevention trial under way, the WIN study
> which is looking at secondary intervention of breast cancer. No
> results are available yet.
>
> DR. RIMM: I think the evidence for diabetes also, if anything, points
> to specific fatty acids and not so much as that total fat may be an
> association for trans fat, independent of total fat. The one that we
> may argue the most about is looking at total fat and obesity. That
> maybe is what led to us to focusing on coronary heart disease because
> there have been so many trials on low fat diets and three months, six
> months, one year and two year loss of obesity. I think that area of
> trials is quite interesting and people argue both sides. I think part
> of the issue is that you have to follow long enough to see the
> long-term impact of a low fat diet. In some case people adapt to the
> low fat diet and in some cases people get fed up and can\'t stand the
> low fat diet. Short-term trials seem to show that low fat diets are
> pretty good at having people lose weight, much like the Atkins diet.
> In fact, after a year people were much better staying on the Atkins
> diet than they were on the low fat diet.
>
> But I think looking at a few of the longer studies, if you stay on a
> low fat diet your weight starts to creep up to your baseline weight.
> So, it is another area where I think that the evidence is not strong
> that total fat leads to increased obesity. I think, if anything, it is
> total calories and not total fat.
>
> DR. KRINSKY: I am sure your comment was not meant to be construed as
> an endorsement of any particular diet.
>
> DR. RIMM: No, it was not.
>
> DR. LICHTENSTEIN: I would agree with both of the prior speakers,
> especially because a lot of the relationships between diabetes,
> cancer, especially breast cancer, and dietary fat and just dietary
> calories\--really there is a lot of confounding because, from what I
> understand, women that are fatter are at increased risk of breast
> cancer because of increased estrogen production. So, there is sort of
> a biological basis for it, and the same thing with diabetes, we are
> seeing a tremendous increase in rates of type 2 diabetes which is tied
> to body weight.
>
> DR. KRINSKY: But is the body weight due to total dietary fat or total
> dietary calories?
>
> DR. LICHTENSTEIN: I would personally say that the data support
> calories as opposed to dietary fat, especially because there are so
> many different types of diets that could be low or high in fat, as the
> two examples that I used of a diet that is high in fruits, vegetables
> and whole grains, which I don\'t think anybody would argue against
> independent of the fat content, versus an extremely low fat diet that
> is made up primarily of diet soda and non-fat brownies and non-fat ice
> cream and potato chips made with olestra. They are just
> non-comparable.
>
> DR. KRINSKY: I think we have worked over the total fat issue. Do we
> have any other comments on it?
>
> \[No response\]
>
> We will return to this later on in our session but let\'s move on to
> our second question. The dietary guidelines committee may
> suggest\--now, I need some help with this, at what level are the
> dietary guidelines committee ready to suggest? Does somebody know?
>
> DR. JOHNSON: I have been attending the meetings and my understanding
> of where that recommendation is that the subcommittee that is working
> on fatty acid recommendations is deliberating that. The last sort of
> discussion about this topic was that 1 percent of energy as trans
> fatty acids as a limit was kind of a stake in the ground but they were
> going to talk about it more. So, this is certainly not a done deal at
> this point. I suspect there will be some more conversation about it.
>
> DR. KRINSKY: Thank you very much. But whether it is a done deal or not
> we have the question, and that is, the dietary guidelines committee
> may suggest that less than 1 percent of energy should be obtained from
> trans fatty acids, about 2 grams per day for a 2,000 kilocalorie diet.
> Does the scientific evidence support this level of less than 1 percent
> or 2 grams per day for trans fatty acids? Yes, go ahead.
>
> DR. LICHTENSTEIN: I am not sure actually that the scientific evidence
> is there. There are few dose-response studies on trans fatty acids and
> I am not aware of any that are really honed in on the range, let\'s
> say, between zero and 3 or 4 percent of calories to indicate that 1
> percent is more efficacious than 0.5 percent or 1.5 percent. But I am
> a little concerned because if you reduce the fatty acid content of the
> diet you, by definition, need to change the fats that are used to make
> the foods or create a lot of low fat foods. If you change the fats,
> then you have to ask, well, if you dramatically decrease the trans
> fatty acids what are the types of fats that are going to be
> substituted? If they are fats that are primarily unsaturated, well, I
> think it would be difficult to argue against doing that. If it is a
> tradeoff and you decrease the trans fatty acid content by half but you
> triple the saturated fatty acids, then the net effect may not be what
> is hoped for.
>
> DR. KRINSKY: That begins approaching our third question and that is
> the equivalency, if you would, of trans versus saturated fatty acids,
> equal, more or less, or not being able to measure it. Can you give
> some examples of studies where, in fact, the trans fat has been
> specifically altered?
>
> DR. LICHTENSTEIN: Well, I probably can\'t find it right now in the
> booklet but the first study was Mensick and Katan in 1990, [The New
> England Journal]{.underline} article, but that was not a
> dose-dependent study where dosage was assessed. There was one study
> published by Joe Judd, in [The American Journal of Clinical
> Nutrition]{.underline}, in 1994, but they looked at 3.8 percent
> calories per trans and 6.6 percent of calories per trans and
> statistically they couldn\'t distinguish between them with respect to
> the increase in LDL cholesterol levels, although they were
> significantly higher than in a diet that was high in oleic acid.
>
> Then, in 1999 we published a study in [The New England
> Journal]{.underline} where we didn\'t look specifically at trans fatty
> acids but looked at different types of hydrogenated fat that had
> different levels of trans fatty acids so they were diets that had 0.5,
> 0.9 or 1 of calories as trans fatty acids, 3.3 percent, 4.15, 6.72 and
> 1.25 was butter, and among the lower levels of trans fatty acids
> statistically for LDL cholesterol and for HDL cholesterol the
> differences were not statistically distinguishable. At the higher
> levels they were but that was up at 6.7 percent. And, I am not aware
> of any other studies that specifically looked at different levels of
> trans fatty acids within the same study.
>
> I think there is in the book a compilation of studies that was
> published by Ascherio in [The New England Journal of
> Medicine]{.underline} in 1999, where he looked at the relationship of
> LDL to HDL cholesterol levels with increasing levels of trans fatty
> acids but that was across studies, and there seemed to be a
> dose-dependent relationship but there was essentially one point under
> 1 percent and then a number of points at 3 percent and then above. So,
> there are just not a lot of data there as far as just the dose of
> trans fatty acids and change in lipoprotein levels.
>
> DR. KRINSKY: Is that that figure 8.4? What page number is that? It is
> section V, page 8-61.
>
> DR. LICHTENSTEIN: Yes, that is the one I am referring to. But,
> remember, that is the LDL/HDL cholesterol ratio. Some people feel that
> total HDL or LDL, THDL is the critical factor, whereas others\--for
> example, NCEP just looked at LDL cholesterol levels. So, you need to
> be somewhat careful about that but, yes, that is the figure I am
> referring to.
>
> DR. KRINSKY: Could you clarify for me the relative significance of the
> LDL/HDL ratio as opposed to the LDL cholesterol and the HDL total
> cholesterol?
>
> DR. LICHTENSTEIN: Right now I don\'t think we have enough data to
> determine whether the total to HDL or LDL to HDL ratios are different
> or equivalent. In the 1999 paper they used the LDL to HDL because they
> didn\'t have adequate data to look at the total to HDL cholesterol
> ratio, or that is what was told to me.
>
> Now, as far as looking at the ratio with respect to risk of
> cardiovascular disease versus looking at just LDL cholesterol level
> really depends on which side of the Atlantic you are on because it
> seems that on the other side of the Atlantic it is felt that the
> emphasis should be on the ratio, whereas on this side of the Atlantic
> we still feel the ratio should be\--and this is just sort of general
> and I am using it as an example, but NCEP decided to use as their
> criteria\--they rely more on the LDL cholesterol levels.
>
> DR. RIMM: I am not as much of an expert in this area as Alice, but I
> think part of the issue is that it is much easier to treat LDL than it
> is to treat the ratio. So, in epidemiological studies I think the
> ratio is more predictive of coronary outcomes than LDL is per se. If
> you go to your clinician and they measure your ratio, there are not
> clinical trials, thousands of clinical trials that have been done to
> lower someone\'s ratio. Essentially, there are thousands of clinical
> trials that have been shown to lower someone\'s LDL. So, I think that
> is part of the issue.
>
> I think that if you focused on the total to HDL ratio or the LDL to
> HDL ratio it would probably give you better guidance on the impacts of
> tans on lipids because we do know that trans impacts both LDL and HDL.
>
> DR. KRINSKY: Well, if trans impacts both LDL and HDL the guideline, as
> we all know, is that LDL is bad and HDL is good and what then does
> trans do to HDL in comparison to what it does to LDL?
>
> DR. LICHTENSTEIN: Well, it depends actually on the absolute levels.
> Just for the record, table 8.10, which is on page 8-60 of section V,
> has a summary of the studies where there were some kind of
> dose-dependent relationships with trans fatty acids. I think it is
> quite clear that trans raise LDL cholesterol levels. They probably
> raise them slightly less on a mole for mole basis than saturated fatty
> acids but, whereas saturated fatty acids raise HDL, trans fatty acids
> don\'t. However, you need also to take into consideration what the
> current levels of trans and saturated fatty acids are and what they
> potentially could be, and that is that the estimate of trans fatty
> acid intake in the United States now is between about 1.5 and 2.6
> percent of energy, and saturated fats are running between about 11-13
> percent of energy. So, if you look at the data on HDL given those
> relatively low levels, although at very high levels of trans they
> could not currently be achieved in the U.S. diet without extensive
> manipulation or somebody probably just eating out of fast food
> restaurants breakfast, lunch and dinner, there is not that much effect
> on HDL but you still do see the effect on LDL so the ratio is probably
> slightly worse with trans fatty acids but the LDL is probably not
> particularly worse or a little bit better. So, it is sort of a wash.
> Then you have to come down to trying to predict what the effect would
> be of having a specific recommendation for trans fatty acids, again,
> back to what would happen to the food supply for very little
> differences.
>
> DR. RIMM: I am sorry to go back to our meetings of the IOM but our
> charge for the macronutrient panel was to sort of take the best
> science and dictate what the science says and not necessarily make
> guidelines or give advice. It was to try to interpret the science. The
> interpretation of the science was that we could not come up with a
> health reason for having trans in the diet, and essentially that is
> what our final message was, that your trans should be as low as
> possible.
>
> So, I guess taking Ascherio\'s summary of all the trials that have
> been done on trans and LDL to HDL ratio, I guess we went down as far
> as there are data, getting down to the 1 percent level and realizing
> also that it would be very hard to have a diet in this country without
> having some trans because you get trans in ruminant animals. So, I am
> not quite sure beyond that where the exact 1 percent came from. Maybe
> Guy can provide guidance. Maybe it was sort of a place to start and to
> work forwards or backwards from that, and I don\'t know if there is
> going to be better evidence to say that 1.5 is better than 1 or 0.5 is
> better than 1. I think it should be as low as possible, especially for
> children where we don\'t have as good data and there is the potential
> likelihood that there may be much higher levels of trans consumption
> among children or individuals who are more likely to eat at fast food
> restaurants or large-scale donor purveyors. You know, the two largest
> sources of trans in our diet are from fried foods and from donuts. So,
> I think starting with 1 as a starting point is a good place to shoot
> for but I think the overall summary was that there was no reason to
> have trans in our diet, no health reasons to have trans in our diet.
>
> DR. LIECHTENSTEIN: I would agree with what Eric said, although I think
> part of the dilemma of the IOM committee was that we were asked to set
> an AI or an RDA for nutrients that were not essential, and that was
> somewhat new and I think the rubric that we were asked to use had
> really been developed for essential nutrients. Essentially, if trans
> fatty acids is an essential of saturated fatty acids, then it becomes
> very difficult to come up with any specific numbers and I think that
> is what the recommendation was, that for both saturated, trans and I
> also believe cholesterol the intake should be as low as possible
> because the data indicated that with any increase there was an
> increase in the indicators of risk.
>
> Specifically, we focused in this case on cardiovascular disease but I
> think we have hopefully learned a lesson, and that is that we have to
> take into consideration how it becomes interpreted and translated into
> the food supply since we certainly got a surprise with the low fat
> message. Certainly, I have responded to people saying, well, does that
> mean they are poisonous because we are recommending to consume them,
> you know, at levels as low possible? Well, no, that is not exactly
> what we are saying. We are saying that there is no reason to include
> them in the diet and then we just have to make some educated guess on
> what the impact will be of getting them as low as possible in the diet
> relative to what they would be replaced with.
>
> With respect to ruminant animals, if people adhere to the
> recommendation that saturated fat intake be as low as possible, then
> the trans from the ruminant animal fat will essentially come down. So,
> then it becomes translating the recommendation to minimize intake into
> one that doesn\'t result in an increase in saturated fat intake.
>
> DR. SHANNON: I wanted to ask a question to follow-up on that. You said
> our best guess as to how it will be interpreted. Are there people
> around the table who can give us a best guess or has that best
> guessing been done with regard to how lowering the trans fat
> recommendations are likely to affect the food supply?
>
> DR. JOHNSON: Clearly, the food industry has gotten the message about
> trans fats and there are earnest efforts under way to try and
> eliminate trans fats. Unfortunately, the technology to do that is
> still somewhat limited at this time. I am told there are four
> different approaches to reduce trans fats in foods. Let\'s see if I
> can remember them off the top of my head.
>
> One is to use naturale sources that don\'t contain trans fats but tend
> to have more saturated fats, like palm oil and that kind of thing.
>
> Another is to interesterify. What you do is to use sources of
> potentially totally hydrogenated fats which basically eliminate all
> the double bonds. So, if you eliminate all the double bonds you don\'t
> have any trans ones. Then you interesterify that with other sources of
> lipids so you get the functional attributes of hydrogenated fat that
> will allow you to have baked goods and things like that. That is a
> much more expensive process and it is still being developed.
>
> I am also told that there is an issue there because consumers, many of
> them, have been attuned to the word hydrogenated in the ingredient
> panel. So, if there is something that says hydrogenated fat, there are
> some people who will, you know, go to great lengths to avoid that.
> Peanut butter is an example. It is basically a trans fat saturated
> food. The nutrition fact panel is going to say zero gram trans fat but
> there is a little bit of hydrogenated fat to provide functionality of
> peanut butter and there are a lot of people who are avoiding peanut
> butter for that reason.
>
> So, my industry friends would love to see that issue addressed. It is
> not exactly our question but they would love to see some alternate
> nomenclature in the ingredient deck that would allow the use of
> totally hydrogenated fat in order to employ the interesterification
> technique without red flagging consumers. So, that is one.
>
> Another technique is use of different fats, like medium oleic, canola
> oil, and so forth, so that fats that have been bred to have a
> different fatty acid distribution that would provide the functionality
> for some things.
>
> The final one is genetically engineered fats. So, there are fats in
> the pipeline that alter the fatty acid content that would be a
> replacement for trans fats under some circumstances. But those are a
> ways off.
>
> I wanted to respond again. I think it was Dr. Rimm who had raised the
> issue about how the dietary guidelines committee had gotten to this
> thing. I am not a member of the committee but I have been attending
> the meetings so I know what the discussion was. When the fatty acid
> committee was making their report about where they are at in this
> recommendation for trans fats, an initial thing that they considered
> was to basically recommend that sources of trans from hydrogenated
> fats be discouraged or eliminated and that trans fats from natural
> sources be accommodated in the diet. The discussion around that point
> was, well, that may be laudable but it is not practical given the
> state of replacing trans fats. So, then the discussion was, well, I
> think that the current level of intake of somewhere around 6.2 percent
> of calories is one reasonable target to shoot for.
>
> I think that was based on more of an arbitrary thing than on hard
> science. Since then I have been given some information that is really
> interesting, put together by a guy named Ed Hunter at the University
> of Cincinnati. What he has done is take all of the studies in the
> figure that we have been looking at and look at the individual
> results, plotting percent energy as trans fats to changes in LDL and
> changes in HDL. What he did was he compared the control group and the
> trans fatty acid group from those studies, and the ones that were
> significant he gave a yellow dot and the ones that weren\'t
> significant he gave a black dot. Then he summarized them in a plot
> and, interestingly, the black dots or the level of trans fatty acids
> that resulted in insignificant intakes of LDL\--and nobody is arguing
> that trans fats raise LDL; they do. I mean, you can take that to the
> bank. But at low levels the increases were not statistically
> significant.
>
> DR. KRINSKY: I am sorry, what do you mean by low levels?
>
> DR. JOHNSON: Less than 1 percent of calories, and there was another
> study at around 3.8 percent. That might have been Judd too, I am not
> sure. But those two are the lowest two points that around 1 and a
> little over 3 were insignificant. His conclusion was that there really
> was no data to show that intakes of trans fatty acids up to 4 percent
> of total energy significantly increased LDL. That is just based on the
> data that we have and there is a gap there, as Dr. Lichtenstein
> pointed out.
>
> Then, if you look at HDL, which I think is really interesting, he did
> the same thing. What he found was that until you got up to like 6
> percent energy from trans or roughly twice of what the current intake
> is there was no significant impact on HDL. So, their conclusion is
> that really there isn\'t good data to suggest that 1 percent is any
> better than 2 percent, is any better than 3 percent\--hard data. So, I
> just thought I would pass that on because I thought it was a pretty
> interesting analysis.
>
> DR. KRINSKY: Then how does that jibe with the earlier statement that
> the lower the percent trans fatty acid the lower the risk for coronary
> heart disease? Am I misquoting you, Alice?
>
> DR. LICHTENSTEIN: Yes, I think so. I am not sure. Remember, the risk
> for heart disease that would be an association would be the epi data.
> In that case, pardon me, but I think you are guesstimating trans fatty
> acid. Essentially you are looking at dietary patterns and you are
> guesstimating it because you are relying on food frequency data and
> then you are relying on incomplete dietary tables. It certainly sort
> of points you in a direction to assess and it turns out that those
> data are very consistent with the clinical data.
>
> But as far as the actual clinical data, there just aren\'t a lot that
> are within that range of 0-3 percent, but in the data that I am aware
> of, which came from our group, it was between 0.55, which is about as
> low as you can get, up to 1.25 and there was no significant effect on
> LDL cholesterol. It wasn\'t until you got to the 3.3, and the Judd
> study was\--
>
> DR. KRINSKY: I am sorry, you are looking at table 8.10?
>
> DR. LICHTENSTEIN: Yes.
>
> DR. KRINSKY: And your butter is the one with 1.25 percent trans fatty
> acid?
>
> DR. LICHTENSTEIN: Yes.
>
> DR. KRINSKY: And the value\--
>
> DR. LICHTENSTEIN: In the original paper that was reported separately
> because the saturated fat was so different and the cholesterol was so
> different. So, it is the 0.55 and the 0.91, and that was relative to
> the next which was the 3.3. That is because we were looking at
> products that would be commonly available to the consumer.
>
> But there is one other issue and that does have to do with what would
> possibly be a substitute if you were going to try and get the trans
> fatty acids as low as possible. One of the issues that has come up is
> total hydrogenation so you end up primarily with standard stearic
> acids since most of the fatty acids in the vegetable oils are 18-0 and
> stearic acid does appear to have very little effect on lipoprotein
> levels and most of it is metabolized to oleic acid, which is a mono.
> But from a labeling perspective, it gets lumped with saturated fatty
> acids so from a manufacturer\'s perspective I would assume that there
> wouldn\'t be any advantage because their saturated fat would likely be
> very high. That comes then to a comment that somebody made about LDL
> raising fatty acids as opposed to trans or saturated fatty acids. And,
> it is difficult because we know with the other saturated fatty acids
> the magnitude of effect on LDL cholesterol is different. So, it would
> be quite complicated to think in terms of cholesterol raising fatty
> acids but, because of this anomaly of stearic acid and the potential
> advantage of stearic acid to substitute for trans fatty acids, it is
> something that ultimately we need to really think about.
>
> DR. RIMM: I have several comments, if I can remember them. It is an
> important issue that Guy and Alice have brought up that, you know, no
> single study will be able to shed light on differences between very
> small increments in trans, which is why I think that it was useful
> that the figure was put together where Alberto Ascherio put together
> all the trials that have been done to show that there was a dose
> response which would allow us to look across the whole range of the
> percentages of trans fatty acids. So, I think that does give us more
> information than any one study.
>
> Related to that and actually going back to Barbara\'s question that
> she put forward to Guy, you know, how would industry respond? I wish I
> knew more about how they responded in the Netherlands, and maybe you
> know more about this, but I heard they have essentially removed almost
> all of trans fatty acids from their diet there. I would assume that
> production methods aren\'t that much better in the Netherlands than
> they are here, but it does seem that we are much slower in adapting
> methods which could bring us foods that have a lower amount of trans
> fatty acids.
>
> I know that two years ago, or whatever, McDonald\'s announced that
> they were reducing almost all of their trans fatting acids out of
> their diet and they sort of rescinded that when they realized it was
> too hard to retrofit the oil that gets spread on their French fries.
>
> I am sure you know much more about this, Guy, than I do but I think we
> need to look carefully around the world and what other people are
> doing because I know that there are technologies out there, and the
> second method you described, maybe that is what they are doing in the
> Netherlands where they are essentially folding the fats together,
> esterification\--is that what it was called? Interesterification.
> Maybe that is what they are doing in the Netherlands to get rid of the
> trans in the diet. But I know that it is existing and I would hope
> that if we did make a statement about saying 1 percent of trans it
> would push industry to move that much quicker. You know, it may be our
> one effort to help things along.
>
> Finally, actually going back and thinking about the 1 percent and
> where the 1 percent guideline came from, part of it actually may have
> come from the nurses health study because the bottom 20 percent of the
> population of the nurses health study, their average intake was about
> 1 percent trans and those are the women that were at lowest risk of
> coronary heart disease. So, I think somewhere along the line someone
> may have been influenced by that although there are not many other
> studies where the lowest group has 1 percent energy from trans.
>
> DR. JOHNSON: I just want to respond to that a little bit. I am not an
> expert about what is going on in Finland but my understanding is that
> trans fatty acids have been such a bad word there that a lot of the
> margarines have used saturated fats to replace trans fatty acids. I
> don\'t think it had been the interesterification thing primarily. So,
> I think we need to be careful about that.
>
> With respect to the way that industry has responded, I think that the
> trans fatty acid rule that is out there requiring companies to list
> the grams of trans fatty acids has certainly elicited a big response.
> You have seen the snack food industry totally eliminate trans fatty
> acids. It is happening all over the place and I am almost wondering if
> by the time all of this gets done it will be a moot point because the
> industry is driven by consumers. Consumers have gotten the word about
> trans fatty acids and they will continue to get it. So, I do think the
> industry has been pretty responsive here.
>
> With respect to the company you mentioned, shame on them for making an
> announcement before they were sure they could do it. I\'ll bet you
> they won\'t do that again.
>
> DR. LICHTENSTEIN: As far as the trans fatty acid intake of Western
> European countries, there was a study, I think it may have been called
> the trans fat study. It involved 14 countries and it was published in
> the [European Journal of Clinical Nutrition]{.underline}, in 1990,
> volume 53, page 143. Their range was 0.5-2 percent of energy so it was
> lower than was estimated in the United States, or at least the 2.6
> percent.
>
> But as far as the Netherlands and Finland as far as really getting the
> trans down, I think we need to keep in mind that their food intake
> patterns are different. The major sources of their trans fatty acids
> are not from fast foods. A higher percentage from fast foods is in the
> United States. So, that allowed them to manipulate margarine and have
> a bigger impact on the trans fatty acid intake than we would be able
> to by just manipulating the margarine in this country.
>
> DR. KRINSKY: Can somebody tell me what the trans fatty acid
> consumption would be for a person who eats no hydrogenated fat
> containing trans fatty acid but will eat animal protein three or four
> times a week? Is there any idea of evaluating what percent of their
> fat will be trans fat or is it so small that it is insignificant with
> respect to what comes from hydrogenated fat? Is there data available?
>
> DR. LICHTENSTEIN: There are data available. You have to do the
> calculations. I think the best data on the distribution of the major
> sources of trans fatty acids in the U.S. diet actually come from the
> FDA web site. There is a great pie chart and you can actually see
> that. But that is for the whole conglomerate. I think we really need
> to keep in mind that you are describing one type of person. If you
> have somebody else who has lunch and dinner with commercially fried
> foods and baked foods that would be very different. The calculation
> certainly can be done and probably is represented in the range of
> intakes from the health professionals and the nurses.
>
> DR. KRINSKY: So, I don\'t even hear a consensus.
>
> DR. RIMM: The question was can you achieve 1 percent by just eating a
> normal diet with four servings of meat and would you still be below
> the 1 percent threshold? That is really probably the direct question
> you are getting at. I am sure there are some really smart people that
> are sitting behind me right now who probably could answer that
> question. She has probably looked at that much more than I have but I
> don\'t know if she is allowed to say anything or not. I would imagine
> it could be below 1 percent. Oh, it is already in the book we already
> read? Thank you, smart person!
>
> DR. KRINSKY: On page 8-45, it has been brought to my attention by a
> smart person that the middle paragraph which, in fact, I see has
> yellow marker in my particular copy meets 0.01-0.21 grams per serving.
> So, four servings of meat could contain close to a gram, and there are
> people who eat more than four servings of meat.
>
> DR. LICHTENSTEIN: That is less than half a percent. But you would hope
> people would be consuming fat-free milk.
>
> DR. KRINSKY: Hope burns eternal.
>
> DR. RIMM: The 1 percent DV is 2 g/2000 kg. So, you have to be below 2
> grams so you could achieve that easily.
>
> DR. HINE: I have to ask a question about serving sizes of meat. When
> people talk to me about meat, how many grams, how many ounces would
> this be a serving? It is a question I had when I read the information
> because 8 oz of meat is quite a bit more than 3 oz of meat.
>
> DR. LICHTENSTEIN: One would assume it would either be the serving size
> defined by the food pyramid or by the nutrient facts.
>
> DR. HINE: Can you tell us what that size is?
>
> DR. LICHTENSTEIN: No, I can\'t but I know the difference between the
> two systems.
>
> DR. RIMM: I think there is also some evidence out there to suggest
> that the trans fat achieved from hydrogenation has different health
> effects than necessarily the trans fat from milk or meat products.
> There is a case-control study that was done in Costa Rica looking at
> hydrogenated fats consumed in the diet and hydrogenated fats in the
> adipose and those hydrogenated fats that were made through
> hydrogenation of oils that were found in the adipose were much more
> strongly related to risk of non-fatal heart disease\--it was a
> case-control study\--were much more strongly related to risk of
> coronary heart disease than the naturally occurring trans fats that
> are found in ruminant animals. Now, that would require 15 more studies
> that Alice would need to do on LDL and HDL to show the differences,
> but I think there is some evidence to suggest that there are health
> differences.
>
> DR. LICHTENSTEIN: True, but you don\'t know what those two sources of
> trans fatty acids\--whether they deposit equally in the adipose
> tissue. There may be a selective metabolism of one isomer versus
> another isomer. We don\'t know. You can\'t get the purified isomers so
> it is really difficult to do those studies but, again, it raises an
> issue that needs to be considered and reconciled as some point.
>
> DR. KRINSKY: So, as I read this and hear you, we have the
> epidemiological evidence that the lower the trans fatty acid
> consumption is the safer the diet is with respect to coronary heart
> disease.
>
> DR. JOHNSON: I don\'t want to be imposing or passing myself off as an
> epidemiologist but through the wonders of the Internet I took a look
> at some of the epi studies that looked at trans fat intake and
> cardiovascular disease instance or mortality, and all of the ones that
> I could find that I had access to showed that the effect didn\'t
> become significant at the 95th percentile until the upper quintile of
> trans fatty acid intake.
>
> So, for instance, there was a case-control study reported just this
> year by Clifton. It was a small study, only 209 cases and 179 controls
> but the relative risk for heart disease instance in the quintiles is
> 1, 1, 1.3, 1.23 and then 2.25, with the upper quintile being
> significant.
>
> A case-control study reported by Mensick, in Boston, with heart
> patients, the same thing. After you controlled for all of the
> confounding variables, including high blood pressure, smoking, alcohol
> intake, family history, physical activity, MUFAs, PUFAs and saturated
> fats and cholesterol, the relative risk was 1, 0.81, 0.4 which,
> interestingly, was protective at intakes of 3.35 grams a day, 0.72 and
> then the upper quintile was significant at 2.03.
>
> The nurses health study and, Eric, correct me if I am misinterpreting
> this, but ultimately when the data on trans fatty acid intake were
> controlled for all of the variables that they could think of the
> relative risk was 1, 1.09, 1.16, 1.24 and 1.53 at intakes of 2.9 grams
> per day, and only the last one was significant.
>
> I won\'t bore you with the other one but there is another one that
> shows the same thing. To me, that kind of jibed with these
> intervention data that showed that there really wasn\'t a significant
> change in LDL or HDL at low levels of intake. So, I didn\'t think that
> the epidemiology gave us a lot of data at the lower intake but it
> certainly does show that there is a correlation at the higher intake,
> which I don\'t think is a point of contention.
>
> DR. LICHTENSTEIN: I would also like to point out that we are looking
> at associations there and that there are a lot of factors that covary
> with trans fatty intakes which are corrected but there could be
> residual confounding. I think those studies are important and they are
> all very consistent, and I think that is the important point, that
> trans fatty acids are associated with increased risk but I think you
> need to take into consideration that there are other confounders that
> may be operating there.
>
> I forgot the exact words you used but I am not sure that I would be as
> confident in those specific words but certainly we come down to there
> is no biological reason for people to consume trans fatty acid so you
> can\'t recommend them. By having a daily value, that really puts
> scientists in a difficult position because it implies that maybe there
> should be a certain minimum level the way there is for something like
> ascorbic acid, and that is just not the case.
>
> DR. KRINSKY: The question that we are dealing with is less than a
> certain percentage. That is not recommending that it should be a
> certain percentage, and maybe this question is really referring to the
> reality of the American diet and not to the scientific evidence with
> respect to what the exact relationship is between trans fatty acids
> and coronary heart disease risk. Because to get to zero trans fatty
> acids would eliminate meat products, animal products for example, and
> I don\'t think that we should be in a position to advocate that
> position at all. So, I wonder if, in fact, we are not in the same
> position that the dietary guidelines committee was in. That is, that
> there is a reality imposed upon the scientific evidence and that you
> can say you shouldn\'t do this but it is impossible to live in a world
> where you don\'t do that.
>
> DR. LICHTENSTEIN: Well, I don\'t think anyone is suggesting that there
> be zero trans fatty acids, just because of what you are saying. The
> IOM report was specifically very careful about the wording because it
> is essentially impossible to have nutritionally adequate diets without
> trans fatty acids. I guess what I am concerned about is what the
> general interpretation of the DV is and how it was originally defined,
> and that is the same concern that I had with the IOM committee where a
> system was set up for essential nutrients that below a certain level
> would cause deficiency and then you were imposing that system on
> nutrients that there is no biological requirement for. I think that is
> something we can\'t ignore.
>
> DR. KRINSKY: That is very similar to what we encountered with
> carotenoids for example. We were not able to find a biological basis
> for recommending an AI or minimum amount. Eric, I have a lot of
> trouble seeing your light. I don\'t want to prohibit you from using
> your computer.
>
> DR. RIMM: Sorry, I was too busy stewing over here over what Guy just
> said so I chose not to turn my light on. You know, I think it is true
> that any one study will not find highly significant associations
> between the second quintile and the first quintile. Usually, by
> definition, the variation between quintiles two, three and four is
> much less than quintiles one and quintiles five just because you have
> to cut the distribution that way.
>
> I think any one study when it is an association study is unlikely to
> find significant impacts in every increasing quintile. However, I
> think by putting together the intervention studies, it does suggest
> that there is an impact on LDL cholesterol across a range of trans
> fatty acids. I think now there is evidence that Alice has that it
> increases LDL; there is evidence to suggest that trans impacts on
> adipose-derived inflammatory markers. I mean, I think there is a whole
> number of other factors we haven\'t even started to address related to
> trans so I don\'t think we should get too lost in the fact that one
> single study may not find a highly significant impact of trans at any
> given level because there is measurement error and there is going to
> be random error so that studies will jump back and forth. But I think
> if you sort of take the totality of evidence it is a pretty strong
> suggestion of a dose response between increasing trans fat and
> increasing biological markers and increasing coronary heart disease.
>
> DR. MAYNE: I agree with Eric\'s comment. When you were reading the
> point estimates from the nurses health study, what epidemiologists
> tend to use is not necessarily each individual point estimate but we
> also do what is called a test for linear trend. So, while Q3 versus Q1
> may not be significant, if there is a linear relationship across those
> quintiles that is something we also look at, not just one quintile
> versus another. So, just be aware that we also consider the test for
> linear trend.
>
> Back to Dr. Lichtenstein\'s comments about how it seems awkward to use
> this, a non-essential nutrient that presumably has these adverse
> effects, using it in the setting of a daily value where I think we are
> struggling, I was struck that it would almost make more sense to set
> an upper limit for trans fatty acids rather than say this is your
> daily value of this. To many consumers, that kind of implies that it
> is a useful nutrient. So, in trying to communicate to consumers it is
> something we ought to think about\--would it be more useful to say the
> upper limit of trans fatty acids we recommend is no more than X grams
> per day, rather than trying to use a DV which I think is becoming
> confusing to the consumer?
>
> DR. LICHTENSTEIN: I guess the issue\--and I don\'t know if anyone from
> the FDA can respond\--with respect to the current regulations as far
> as labeling is does that help? Can we do that? I mean upper limits is
> a term set for the DRI but as far as the FDA, I am not sure they even
> recognize that term and that is a conundrum that we really face.
>
> DR. KRINSKY: That is what the FDA is there for, to deal with
> conundrums. You are absolutely right, Alice, that is, the UL is a DRI.
> It is an IOM/NAS term\--FNB/IOM/NAS term, to be more precise, and it
> is not an FDA term, if I am not mistaken. Is that correct? So, even
> though it is a very good idea and may, in fact, be more reflective of
> the way one should approach trans fatty acids, we may not be in a
> position to make that recommendation. So, there is DV. You don\'t have
> an upper DV, a UDV? No. May we create one?
>
> MS. PELICAN: I guess this is not the first time that we face this
> because I am looking at a label that I brought on the plane with me
> yesterday. We have cholesterol which in fact reflects the same kind of
> direction for sodium. You know, these tend to be nutrients for which
> we are trying to put an upper limit on. But I would agree, I have
> struggled with looking at the tans fat materials that we were given
> before the meeting. But I know on the same package\--and, you know,
> this is off fried chips which were pretty tasty on the plane\--this is
> like one of these products where I thought I am really looking forward
> to trans fat labeling to see how much trans fats are in some of these
> foods that I like in a serving. I guess one package has total fat as 7
> grams; saturated fat is 1 gram; and there is no trans fat, which kind
> of goes to what Guy is saying.
>
> You know, I think there are a lot of industry folks that are looking
> to eliminate trans fat. But it has\--and I think this is optional,
> voluntary labeling\--a double asterisk and at the bottom and it says
> intake of trans fat should be as low as possible. I am just wondering
> if we are kind of faced with what FDA was faced with 13 or 14 years
> ago of was there enough information at that point to label trans fats
> and they thought no. With all of our briefing materials we know that
> over time there has been enough information and I am just wondering if
> we would want to discuss the possibility of saying we don\'t have
> enough information but might recommend some kind of a statement like
> this, which I found informative but, again, we only have 275 million
> people reading the same food labels and we always have to think about
> how will the majority of people interpret that. But I did find this
> informative, both the label and the footnote.
>
> DR. KRINSKY: Thank you very much, Suzie. I just want to ask a
> question. How high can trans fat be to be declared zero percent trans
> fat, 0.5?
>
> DR. LICHTENSTEIN: I think there is no one that has argued that we
> should encourage trans fatty acid intake or that we need trans fatty
> acids and I am just wondering if a way of getting around the issue of
> DVs\--we seem to accept it for saturated fat although there is no
> biological basis for recommending a minimum amount of saturated
> fat\--would be to just combine sats and trans with the DV that has
> already been established for saturated fatty acids. Since they both
> increase risk of cardiovascular disease, you may argue on a little bit
> more than the other but it may be compensated because you consume less
> of one than another but those, to me, sort of seem to be somewhat
> minor arguments. The major health advantage would be to minimize
> intake of both. So, what would the disadvantage be of just having one
> DV for trans and sats?
>
> DR. RIMM: There are about 20 pages of the Federal Register that are in
> our pamphlet which talk about why we don\'t want to do that. I
> think\--well, I don\'t even want to go into it because it looks like
> it has probably been discussed for four straight years at the FDA but
> there are a lot of reasons that they have already decided that that is
> not the case for at least putting it on the label. They decided to
> separate trans and sats on the label and I think they decided for a
> good reason. These are different chemicals; they have different
> biological effects; there are probably a lot of effects related to
> trans that we don\'t even know yet that probably don\'t impact sats.
> So, to then say, okay, let\'s separate the gram amount on the label
> but put together the DV values, to me, seems a little incongruent. I
> think if we think it is important enough to separate the trans from
> the sats, then we should probably separate the daily values also.
>
> DR. JOHNSON: My industry pals are divided on this issue. They are as
> confused as everybody else I think. However, the recent IOM report on
> applications suggests that they be combined. So, I think, like you
> say, Eric, it opens up a whole morass because then you get into the
> physiological versus the chemical differences and the stearic acid
> issue emerges and it all becomes very complicated.
>
> I wanted to respond to Suzanne\'s comment about the footnote. The
> footnote is another thing that my industry folks are not highly
> supportive of. It, again, was discussed in the Federal Register,
> whether by calling attention to any one item or multiple items in a
> footnote people who read that footnote assign it an unrealistic
> priority, I guess, and by putting that in the footnote\--some consumer
> research was done showing that when you put that footnote in people
> will make incorrect choices for things that are minimum in trans fatty
> acids but may have way more saturated fat. So, it kind of gives them a
> focus on trans fatty acid and dilutes the importance of saturated
> fats. So, there are some issues associated with that too.
>
> DR. LICHTENSTEIN: I understand that there couldn\'t potentially be
> biological differences between trans and saturated fatty acids but
> biological differences among saturated fatty acids, and I think the
> issue that has come up and gone down, come up and gone down still
> comes back to potentially looking at something like
> cholesterol-raising fatty acids. We knew and we explored and we wrote
> in the IOM report that there were a lot of different criteria that
> could be used to set an AI or a DA or DRI for any of the
> micronutrients, and what we did was go through them all and then chose
> the one that we felt either had the most evidence or was the most
> important as far as health outcomes.
>
> I think with respect to fatty acids, probably the most evidence is
> available for either LDL cholesterol or the ratio. But if we really
> want to see a decrease in trans fatty acid intake, and I think there
> is certainly good reason to want that, and if one alternative is to
> increase the saturated fatty acid intake, if that is actually really
> correct and will result in the expected outcome, then, again, maybe
> one needs to consider coming up with a different designation to put on
> the food label, and maybe that is close to erasing fatty acids.
>
> DR. KRINSKY: Would you also have cholesterol-lowering fatty acids as
> part of a label?
>
> DR. LICHTENSTEIN: You mean the unsaturated fatty acids?
>
> DR. KRINSKY: Yes.
>
> DR. LICHTENSTEIN: Right now I believe it is optional to include monos
> and polys so that is already in place. I certainly don\'t think that
> that should be eliminated. I think obviously it is something that
> should be considered and one would need to understand how the public
> would interpret that, as they would interpret cholesterol-raising
> fatty acids, but the bottom line within the nutrition facts panel is
> that you want to give consumers as much clear information that they
> can use to make educated decisions on what items they are going to
> purchase and, hopefully, that will be in favor of health promotion as
> opposed to the opposite. So, there has been a huge shift in what the
> consumer is aware of. There have been a lot of terms that weren\'t in
> the lay press ten years ago that are in the lay press now. I think
> there has been a lot more on the labeling and on regulations and
> health claims than there has been on education but ultimately I think
> we need to understand more about how the consumer is going to use this
> information and whether those types of designations would actually be
> useful in communicating any kind of information that the scientific
> community feels is important to communicate to the consumer because
> that is where the bottom line is.
>
> DR. KRINSKY: Does the consumer know the difference between cholesterol
> and LDL cholesterol?
>
> DR. SHANNON: That is the very point I was going to bring up. I think
> the consumer is aware of \"good cholesterol\" and \"bad cholesterol.\"
> If I am reading our material correctly, trans fats do lower good
> cholesterol. So, coming back to your point, Alice, if you are going to
> use this terminology of cholesterol-raising and cholesterol-lowering,
> what are you going to do with good versus bad? What kind of message
> are we sending to the consumer when we get into that?
>
> DR. LICHTENSTEIN: Well, within the context of the amounts of trans
> fatty acids that are currently consumed in the United States, the
> effect of HDL cholesterol is not significant. It is significant in the
> clinical trials where you artificially increase the trans fatty acid
> of the diet so that you are really pushing the system to understand
> what goes on and, in that case, clearly, there is a big difference
> between trans and saturated fatty acids and it is something that
> shouldn\'t be lost. But it appears that trans fatty acid intake in the
> U.S. has gone down with the introduction of the trans-free margarines.
> Although one company said they were going to eliminate trans and then
> didn\'t, another company actually has done this. So, at least you see
> industry going towards less trans.
>
> But what is on the label is not \"good cholesterol\" or \"bad
> cholesterol\" though, you are right, I mean I think it is what the
> consumer understands. What is on the label is the composition of the
> food and I think what we really need to understand is how best to
> communicate that information so that consumers will make the best
> choice, or how that information, by presenting it, will nudge industry
> into providing healthier alternatives. From what I understand, it is
> not clear whether the nutrient facts panel is most important because
> people are actually comparing and making a decision on this food or
> that food, or that industry wants their food to look pretty good on
> the nutrients facts label. And, that is fine. In either case it
> benefits the consumer and with nutrient labeling that is what we are
> talking about. That is very different than the guidelines or the IOM
> reports.
>
> DR. HINE: I have two questions that are unrelated to one another but
> the first one we have touched on already. First of all, what are the
> data about who reads food labels? That is question number one.
> Question number two is regarding differential effects of age, gender
> and ethnicity and the duration of the clinical trials and how the
> subjects were fed during those clinical trials.
>
> DR. LICHTENSTEIN: Well, I can certainly address the second question; I
> can\'t the first As far as the clinical trials, most of them were
> actually done with moderately hypercholesteremic individuals so the
> individuals would be candidates for dietary modification but not drug
> modification. So, a lot of the clinical trials were done in
> individuals with LDL cholesterol levels above about 130. Most of them
> were done with both males and females. There is very limited evidence
> that females might be slightly less responsive than males but that
> evidence is equivocal at this point.
>
> While most of the studies were done with older individuals, we know
> that women after menopause are at increased risk for cardiovascular
> disease. Their LDL cholesterol levels go up. So, if you use a minimum
> LDL cholesterol level most of the young females wouldn\'t qualify for
> the clinical trials anyway.
>
> As far as the duration of the feeding trials, most were done for at
> least four weeks. There certainly has been a lot of work on how long
> it takes for lipid levels to stabilize after you alter the fat content
> of the diet, and that certainly seems to be an adequate period of
> time. If you think about the half-life of lipoprotein particles, it
> certainly is more than adequate. But there are very good data that if
> you keep people on controlled trials for up to 24 weeks and monitor
> every 4 weeks you get a maximum effect at 4 weeks. If you are
> providing all the food so that you are reasonably assured that they
> are maintaining the diet, the line is straight. You don\'t see any
> going up or down.
>
> As far as the individual trials, I think most of the ones that are
> summarized in this book were controlled feeding trials where all the
> food was provided. I mean, there are a couple of studies, but they are
> so designated or separated out, where just the major fats were
> provided to the study subjects and they followed their habitual diet.
> But I think what we are talking about now is really the controlled
> clinical trials.
>
> I am not aware of any data on comparisons of young individuals versus
> older individuals, but I think that that probably is a moot point. I
> think what is critical is those individuals that are candidates for
> dietary modification or for pharmacological intervention. If you
> change the diet, can you have a clinically significant effect on the
> standard \"risk factors\" for cardiovascular disease? So, the studies
> that are summarized here pretty much meet those criteria.
>
> DR. HINE: You didn\'t mention ethnicity. Are there any data regarding
> that?
>
> DR. LICHTENSTEIN: With respect to trans fatty acids, not to my
> knowledge. I assume the NHANES data does break it down by ethnicity
> but not as far as the controlled feeding trials. They tend, by
> definition, to be small because they are extraordinarily expensive.
> The trials that are currently ongoing\--I think it is either a 15 or
> 20 percent minority representation and that is mandated by the NIH,
> but that wouldn\'t give you the power to actually look at response on
> the basis of ethnicity.
>
> DR. KRINSKY: With respect to Jean\'s first question, we only have an N
> of one, and that is Susan Pelican who reads the labels. I wonder if
> somebody from the FDA might have some information on the efficacy of
> labeling. Have any studies been carried out on the reading of your
> labels? If you have an answer, if you could use the podium we would
> appreciate it so that we and the audience can hear it, and if you
> could identify yourself for the recorder.
>
> MS. WILKENENG: Virginia Wilkeneng. I don\'t have any of the numbers
> with me but certainly the agency has done a lot of studies, as well as
> the food industry and groups such as the American Dietetic Association
> over the years since we implemented the new nutritional labeling
> regulations in \'93.
>
> Most of those studies show that the majority of consumers do look at
> the nutrition facts panel, particularly the first time they are buying
> a product. Of course, they are looking at different things. Some are
> looking at calories; others at fat; others at sodium, depending on
> what their personal needs are. But they look at that information and
> they tend to use it to compare products or just to find out
> information about that particular food. They don\'t particularly use
> it to add up numbers and plan a daily diet, but in making the
> purchasing decision all that research that has been done does show the
> majority of people are familiar with the nutrition label and look at
> it.
>
> DR. KRINSKY: Thank you very much. Jean?
>
> DR. HINE: How were the data collected, if you recall?
>
> MS. WILKENENG: Let\'s see, within the FDA studies we have done
> telephone surveys and we have done mall intercept surveys. I couldn\'t
> speak for ADA\'s studies and maybe the industry, when they come up and
> make some comments later, can indicate how some of their studies were
> done.
>
> DR. KRINSKY: Eric?
>
> DR. RIMM: I have a question for the FDA, as well as bringing us back
> to the original question here. The original question was does the
> scientific evidence support the level of 1 percent? I think what we
> are tripping over is 1.1 or 1 percent. I wonder if we could use the
> analogy of saturated fat or cholesterol. Right now there is a daily
> value for saturated fat. I don\'t know if it was in this packet or
> anywhere about how that was derived and why 1 gram less for saturated
> fat was okay and 2 grams more for saturated fat was not okay. Is there
> anybody who can give us some guidelines of how the exact daily value
> for saturated fat came to be?
>
> MS. WILKENENG: The current daily value for saturated fat was based on
> recommendations and dietary guidelines and other places for less than
> 10 percent of calories coming from saturated fat.
>
> DR. RIMM: Again, that was guidance, not necessarily hard science
> saying that 10 is that much worse than 9.9 or that much better than
> 10.1. So, it is somewhat of a guidance as opposed to taking the exact
> hard science and saying this is the threshold.
>
> MS. WILKENENG: Right, but we did have those recommendations in reports
> such as the Dietary Guidelines or American Heart Association and
> others. The exact recommendation is less than 10 percent. If you do
> the mathematics for a 2,000 calory diet it comes out to 22 grams. So,
> we rounded it out to meet the less than, and make it easier for
> consumers to use.
>
> DR. KRINSKY: Thank you. Alice?
>
> DR. LICHTENSTEIN: That is actually a really good point. My
> understanding is that less than 10 percent, less than 300 mg of
> cholesterol per day are actually somewhat historical and were
> established before the criteria for setting numbers was really as
> stringent or has come under as much scrutiny as now. It dates back to
> NCEP ATP I, and my understanding is that before that it is from the
> American Heart Association. I don\'t know which actually came first.
> The point is well taken. I am not sure, were it to be done today, that
> one would come up with those numbers but I know there have been
> efforts to try to trace back where they actually came from and it
> hasn\'t been solid.
>
> DR. KRINSKY: Well, historical is okay; hysterical though is to be
> avoided and I think that that is what we want to avoid with respect to
> trans fatty acids. We are asked for the scientific evidence and it is
> not clear that we have what people might define as scientific
> evidence, that is, rigorous studies that can help us come to a value
> of less than 1 percent, less than 1.1, less than 0.9. Alice?
>
> DR. LICHTENSTEIN: Well, there is one other factor, and that is I am
> not sure we are ever going to have that evidence because when you
> alter the trans fatty acid level of a diet, if you decrease one thing,
> if you are going to keep it isocaloric which you need to do so you
> don\'t have other confounding factors, you have to increase something
> else. And, if you increase carbohydrate or if you replace it with
> saturated fat or you replace it with mono or replace it with polys you
> are going to get slightly different results. So, it is almost as
> though we may be asking for something that probably we can\'t really
> deliver.
>
> DR. RIMM: I think we should also keep in mind what current health
> claims are allowed and that, in fact, we don\'t always have to have a
> ton of data and 16 clinical trials to make a point. Right now we have
> said that you can claim that fruits and vegetables or a whole grain
> product and, in fact, we don\'t have large long-term clinical trials
> showing that fruits and vegetables are better or that whole grains are
> better. You can say the same for exercising and you can say the same
> for smoking. So, I think we have to be a little bit careful about
> saying what is going to be the threshold before we set a number for
> trans. You know, I think if you ask can you eat meat and drink dairy
> products and still be well under the 1 percent, I think the answer is
> yes.
>
> DR. LICHTENSTEIN: Taken from the other perspective, we have something
> like fish which sometimes can be high in fat and high in omega-3 fatty
> acids and we have reasonably good data that that would be beneficial
> but we don\'t have a health claim for that.
>
> DR. KRINSKY: That is because of the PCBs. We are scheduled for a break
> at 2:45. It is now 2:40 and, with the committee\'s approval, I am
> going to call for a 15-minute break. I would just like to remind the
> committee not to have private meetings on this topic until we return
> because otherwise that will make the whole process invalid. So, we
> will reconvene at 2:56.
>
> \[Brief recess\]
>
> DR. KRINSKY: Thank you very much. I hope you are all refreshed and
> ready to continue the discussion. Let me just make the suggestion that
> when on occasion you want to make a point on some of the material that
> is in the notebook that was handed out to us, if you could just draw
> our attention to the section, the page number, paragraph, line, word,
> etc. so that we can all follow on it.
>
> We are still in the midst of deciding, since we can\'t change the
> world and change the definition of fatty acids that increase
> cholesterol levels although there is certain merit to that, we are
> still left with the situation dealing with the trans fatty acid. What
> I hear is that there is not adequate scientific evidence to set a
> figure for trans fatty acids in the diet as far as a high level or a
> low level, and that we are going to have to try to answer this, as
> they say, by flying by the seat of our pants, an expression that
> everyone understands and I have used frequently and I hope that you
> people understand what I mean.
>
> So, is there an argument with me when I say that there does not appear
> to be scientific evidence to support the level? Dr. Rimm?
>
> DR. RIMM: I am sorry, the argument is I guess I don\'t know what you
> mean by scientific evidence. We have scientific evidence to support a
> daily value for saturated fat at some level, which I guess was set
> based on the fact that 30 years ago HA flipped a coin and said let\'s
> take 10 percent of calories from fat. So, I think if that is our
> definition of scientific evidence, then I think we do have scientific
> evidence to suggest that at some level of tans fat there is harm.
>
> DR. KRINSKY: I am not sure that I agree that flipping of a coin is
> considered to be scientific evidence but, in fact, a claim has been
> made\--a statement has been made and there has been agreement at some
> point in the past as far as saturated fat is concerned. What that was
> based on or not based on I am not sure. We certainly have, in terms of
> the epidemiological data, associations between trans fatty acid levels
> and risk for coronary heart disease. Certainly, associations are
> considered scientific evidence. I will grant that to the
> epidemiologists, out of the kindness of my heart, but we don\'t have
> support from intervention studies for that particular figure. What I
> have heard is that there does not seem to be a great deal of
> difference between levels below 1 percent and levels above 1 percent
> with respect to LDL cholesterol levels or its effect on LDL
> cholesterol levels and that, in fact, this is not the easiest kind of
> experiment to run because it you alter the level of trans fatty acids
> you are altering something else, and that something else that you are
> altering may not be as important as the trans fatty acid but it has to
> be taken into consideration. So, I am in a bit of a dilemma and I am
> willing to be argued into any position; I am easy.
>
> DR. RIMM: Well, I don\'t want to rehash our discussion from before
> but, again, I think it would be very hard but there is no one trial
> that tested 1 percent, 2 percent, 3 percent, 4 percent of trans and
> looked at a change in something which we would deem scientifically
> important. But if you put all of the clinical trials together, all
> metabolic studies together they do suggest a trend that with
> increasing trans intake there are increasing levels of LDL or LDL to
> HDL ratio.
>
> Having said that, could we really set a level at 4 percent? I don\'t
> know if we could. Could we set it at 6 percent? If we can\'t set it at
> 1 percent, why do we think we can set it at 4 percent or 6 percent
> because there is not one trial that said, okay, 5 is worse than 4 and
> 4 is worse than 3. So, I think what we have to do is put all the
> evidence together and see what it shows us. It shows us that there is
> a pretty straightforward dose response. Obviously, there is some
> variability around that. So, I don\'t know how we will ever be able to
> specifically pick any point on that line.
>
> DR. JOHNSON: I think I agree with what Eric just said. I mean, it
> seems pretty clear, based on the intervention trials as well as the
> epi stuff, that at some point trans fatty acids raise LDL and lower
> HDL. The devil is in figuring out when that occurs and, based on the
> data that is available right now, I don\'t think there is evidence to
> set it at 1 percent, 2 percent, 4 percent or whatever. I don\'t think
> we are being asked to do that. The question says is there evidence to
> support 1 percent and in my mind the answer is a resounding no.
>
> DR. LICHTENSTEIN: I agree with the previous two speakers and I think
> were a level to be set one would have to take into consideration the
> balance of the diet and what is reasonable within the context of what
> is available in the United States. Having said that, given the range
> of dietary intakes, it would be pretty darned hard to do.
>
> DR. KRINSKY: Could you remind me what the dietary intake is for trans
> fatty acids in the U.S.?
>
> DR. RIMM: It was about 2.6 percent I think the last time it was
> measured. That includes hydrogenation, and donuts, and fast food
> restaurants. That is the average. But I think it is very easy to
> attain 1 percent.
>
> DR. KRINSKY: The question I want to know is whether that 2.6 percent
> has been changing with time.
>
> DR. LICHTENSTEIN: We don\'t have any data. I suspect it is and
> actually I think in some of your studies the average is lower than
> that. Isn\'t it closer to 2 or 2.1?
>
> DR. RIMM: Yes, right. For the nurses and the health professionals the
> average is in the low 2\'s.
>
> DR. KRINSKY: They are not normal!
>
> \[Laughter\]
>
> Well, no, they don\'t represent the average U.S.\--
>
> DR. RIMM: They represent a very wide range but, you are right, nurses
> and health professionals are not average; they are normal though.
>
> DR. LICHTENSTEIN: Also, the data were collected differently because
> that was food frequency. That was interpolated for food frequency
> whereas the 2.6 I think was from the NHANES data, or something like
> that, but we know that the food supply has changed.
>
> DR. RIMM: Right. So, it is already going down and we can maybe
> estimate that the average is around 2 right now. Although I don\'t
> know, you know, a few of the companies have taken trans out of their
> products but I don\'t know how quickly that is impacting on the
> overall diet considering that a lot of the trans comes from fried
> bakery products and from fast food potato products and I don\'t think
> those have changed that much yet, although, as you said, one fast food
> restaurant I think is attempting to take it out.
>
> DR. KRINSKY: So, it seems that in the last post-break conversation I
> have heard three people say that we don\'t have the scientific
> evidence to support this level. Although we may feel, which is not
> scientific, we may believe that this would be a good level for the
> U.S. population to achieve, as far as scientific evidence is
> concerned, it is at this stage lacking.
>
> DR. RIMM: I think the scientific evidence is as good as what we have
> for cholesterol and saturated fat.
>
> DR. KRINSKY: But we are not asked about cholesterol and saturated fat.
>
> DR. RIMM: But they are going to be on the same label.
>
> DR. KRINSKY: We are not even asked about the label\--well, yes, this
> does go to the labeling. I am sorry. This is something that has to be
> mulled over individually and maybe with a little re-reading of pages
> 8-40 to 8-50, or something of that nature, in tab 5\--and, as you
> know, we can\'t discuss this privately. We are not obligated to vote
> on this issue at this particular moment and I am not sure if we have
> any more discussion. Suzie?
>
> MS. PELICAN: Just to follow-up with this thought about saturated fat,
> kind of weighing that issue, is it appropriate for us to ask for any
> kind of summary? I mean, it seems like we have some good folks around
> the table here who have a sense that that saturated fat was
> historical, maybe just based on the best policy recommendations and
> not quite as much science maybe but it seems like we really don\'t
> have a sense around this table for being able to say firmly this is
> how that saturated fat DV or that 10 percent recommendation, which is
> historical, came about. Could we ask for that kind of research? Is
> that appropriate? That could be information that we could then have
> and discuss?
>
> DR. KRINSKY: It would be appropriate because the process is going to
> be the same and, Alice, you said you tried looking at how that figure
> came up?
>
> DR. LICHTENSTEIN: Indirectly because the Heart Association had been
> asked to justify the figure of that and the cholesterol so, of course,
> they bounced a telephone call to me and I then tried to get some
> information from them. I don\'t know, maybe the standing NCEP
> committee would have that. It may have come from data from other
> countries that had intakes of less than 10 percent of calories and
> less than 3 mg of cholesterol a day and they had better outcomes with
> respect to cardiovascular disease, but that is speculation. It is not
> something that I had the time to really pursue.
>
> DR. KRINSKY: Yes, but if it came from, say, other countries that had
> the dietary information, is that really comparable to what is going on
> here? Don\'t they have different life styles? How can you base
> whatever their health outcome might be solely and exclusively on the
> cholesterol level in the diet?
>
> DR. LICHTENSTEIN: I was just speculating on where it came from. It has
> to be at least 20, if not 30, years old and I think people thought
> about things differently then.
>
> DR. RIMM: Yes, I think at the DRI committee meeting Scott Rundy and
> Ron Krause were reflecting when they were discussing this for the HA
> 20 or 30 years ago, and I think there were just sort of a few people
> sitting in a room and picking a level which they thought seemed
> appropriate from the available evidence in the 1970s or 1960s before
> they actually spent a lot of time talking about LDL and HDL. At that
> time they were just talking about total cholesterol. So, I think it
> definitely is not based on as much fact as we have now.
>
> DR. LICHTENSTEIN: Also, keep in mind that when it was first proposed,
> it was proposed as a target for the population that had
> extraordinarily high risks for cardiovascular disease and very high
> intakes of saturated fat. It was not proposed to be used as criteria
> for labeling or anything like that. So, the whole basis for it was
> very different. It was a target.
>
> DR. KRINSKY: But targets tend to move and we have seen that with total
> plasma cholesterol recommendations. That is a moving target which has
> been moving down and down and soon will reach my level.
>
> DR. LICHTENSTEIN: Well, it has been a moving target for saturated fat
> because ATP I and ATP II had less than 10 percent of calories from
> saturated fat, whereas ATP III got rid of the step one diet and just
> now has the TLC diet, the therapeutic life style diet, and it is less
> than 7 percent of calories from saturated fat. So, that was the prior
> step two because they felt that the population had moved so close to
> the step one diet that that was no longer needed, that that should be
> considered the norm and then the TLC was the step two diet and, in the
> same way, to total fat was changed from the first two, ATP I and ATP
> II, less than 30 percent of calories from fat and ATP III is 25-35
> percent of calories as fat, again de-emphasizing the total fat.
>
> DR. KRINSKY: We have talked here and a number of you have raised the
> daily value and Suzie was good enough to give us a chart that she had
> taken with her off the airplane, with permission I assume. We have
> here a copy of a nutrition facts label and Virginia Wilkeneng is going
> to be willing to talk to us about deciphering this code. There are
> copies outside for the audience. I don\'t know if everyone in the
> audience has received a copy. It would only be fair to our audience if
> they could\--could somebody go\--they are doing it? Thank you. We will
> get you copies of this, although I am sure all of you at one point or
> another have seen a nutrition fact label but we are going to get the
> inside dope on it. Virginia?
>
> MS. WILKENENG: Let me give a little backup first. Within your packets
> is a copy of the Federal Register Notice, dated March 1. It is in tab
> 7, a little bit behind there. It is the announcement when we reopened
> the comment period on our ANPRM for trans fat labeling to try and deal
> with the idea of percent daily value for trans or perhaps the use of a
> footnote that would help consumers put the quantitative number into
> the context of how much they should eat in a day\'s time.
>
> In that Federal Register Notice we made mention of a recent NAS report
> that had been funded by FDA, USDA and Health Canada to give us some
> guiding principles on how all of the new National Academy dietary
> reference intake values should be used to update the daily values on
> the nutritional label.
>
> In regard to saturated fat and trans, that report had recommended that
> we perhaps reconsider the daily values and then put them together to
> have one joint daily value for saturated fat and trans. In our Federal
> Register Notice we were going out and asking for comments specifically
> on that recommendation, as well as in general any ideas that would
> help the agency address trans fat.
>
> Back when we first did the new nutrition facts label, we had some
> graphic artist that worked pro bono to help the agency design the
> nutrition facts panel. We think that was a very successful activity
> and we have even gotten presidential awards, all sorts of things, for
> the nutrition facts box and now you see it for all sorts of related
> things, that idea of the graphic.
>
> So, the graphic designer who did that, when he read the report that
> there be a joint daily value, felt some need to again get involved in
> the process and he put together this graphic that we have handed out
> to you just as a way to show how you could have a joint daily value
> with separate quantitative listings for saturated fat and trans. That
> is what this shows just to give you the idea of what it might look
> like to bring a halt to the line that divides them under the column
> for percent daily value.
>
> Again, I would just point out to the committee the importance that we
> place on the percent daily value information is a way to help
> consumers get a feeling for what those numbers, for whatever nutrient,
> represent in terms of dietary recommendations. In the case of the
> fats, fatty acids, cholesterol, sodium, generally those are maximum
> recommendations. So, our advice to consumers is don\'t go over 100
> percent of your daily value for those nutrients, whereas for the
> vitamins and minerals, the others that are helpful in a diet, we want
> them to reach at least 100 percent of the daily value.
>
> So, this would give them an impression in this particular label\--you
> know, we have jumbled with the numbers some because the graphic artist
> didn\'t have much concept of what the numbers were for trans fat, but
> if you had 1 gram of saturated fat and just 0.5 grams of trans fat in
> a serving of the product it would amount to 8 percent of the daily
> value so that they could know how that fits it in the context of the
> whole diet.
>
> If there are any questions on this particular rendition or anything
> else about the daily value, I would be glad to help. Yes?
>
> DR. RIMM: I have a few questions. The first one is the daily value is
> based on just summing up the total amount of saturated fat and trans
> fat in grams and then basing that on the total grams at the bottom,
> where you say 20 grams for 2,000 and 25 grams\--
>
> MS. WILKENENG: Actually, in this case we did that, yes. We summed them
> up and we used the 20 grams but were we to do this, we would need to
> go back and reassess the daily value for saturated fat as well as
> create one for trans fat. Now, the IOM report has recommended we do
> that through menu modeling and using food composition data tables. The
> biggest problem with that, as alluded to a little bit earlier, is that
> there aren\'t really good food composition data tables at this point
> in time.
>
> DR. RIMM: It is a moving target so any time a guy goes back and
> reconstitutes a potato chip we have to go back and measure it. So, it
> is a moving target. There are a number of foods that have been
> measured and I don\'t think we should completely throw our hands up. I
> think for trans the values are probably a lot better than zinc, for
> instance, but that is a separate issue.
>
> So, the proposal would be to have total fat, sat fat and trans fat in
> the bottom little section under the 2,000 and 2,500. You would
> actually have a separate line for trans fat saying you should have
> less than X number of grams.
>
> MS. WILKENENG: I would think that would be a logical outcome of it,
> yes.
>
> DR. RIMM: So, you actually could calculate a percent daily value for
> trans fat. You wouldn\'t necessarily have to sum them.
>
> MS. WILKENENG: Well, this bottom table gives consumers what the daily
> value is for those macronutrients.
>
> DR. RIMM: Correct.
>
> MS. WILKENENG: So, if we had a daily value for trans fat it could be
> added into that list.
>
> DR. LICHTENSTEIN: But from the way it is depicted here, there is a
> percent daily value for trans plus fats and it would appear that the
> value on the bottom would have to be trans plus fats because otherwise
> you would end up with individual daily values.
>
> DR. RIMM: That was my point that I was trying to communicate. Thank
> you, Alice.
>
> DR. LICHTENSTEIN: Anytime, Eric!
>
> MS. WILKENENG: That is certainly an option, yes. These are the types
> of things we hope people will comment on as a result of that ANPRM. I
> would let the committee know, if they are not aware of it, that
> because of the discussion of this committee we extended the comment
> period on that ANPRM until I believe June 15th.
>
> DR. RIMM: I also apologize, you can voluntarily put in polyunsaturated
> fat and monounsaturated fat, and is there a daily value that gets
> assigned to that also?
>
> MS. WILKENENG: No, there is not.
>
> DR. RIMM: Those are just separate as grams?
>
> MS. WILKENENG: The value lines are blank for mono and poly.
>
> DR. RIMM: I have only looked at a food label a thousand times but I
> just forget. Thank you.
>
> DR. KRINSKY: To follow-up on Eric\'s point, it seems to me that there
> is a conflict here between the total fat with saturated fat and trans
> fat underneath it in terms of the percent daily value and not having
> that trans fat on the bottom of the table because\--
>
> MS. WILKENENG: Oh, I think the bottom of the table would definitely
> need that.
>
> DR. KRINSKY: Would that have that? Okay.
>
> MS. WILKENENG: It is just that the artist didn\'t think about it; we
> didn\'t give him any guidance. This just came in as a comment.
>
> DR. KRINSKY: So, in our discussion here and with our question number
> two, if in fact we arrived at the conclusion that there was evidence
> that 2 grams of trans fatty acid would be the appropriate level, as
> this nutrition fact label is set up, if it had trans fat of 0.5 gram
> that would then be 25 percent of the daily value.
>
> MS. WILKENENG: If it was listed separately.
>
> DR. KRINSKY: If it were listed separately. Would that frighten the
> average consumer?
>
> MS. WILKENENG: That is an area that needs study.
>
> DR. LICHTENSTEIN: The question really is would it be useful. The way
> this mock label is set up, it looks to me like the logical thing would
> be to have a DV that was\--and I think this is what the assumption is,
> that the DV is 10 percent, that it is combined trans and sat. So,
> first of all, if it is under 0.5 grams it could be listed as zero. As
> you indicated if it was 2 grams it would be 25 percent and I don\'t
> think that would necessarily be useful information to the consumer
> relative to the 8 percent of saturated fat. So, again, one goes back
> to potentially combining them and then using a label something like
> this and communicating that you should pick the product that has the
> lowest number.
>
> DR. KRINSKY: But we can\'t combine it. That is what the Federal
> Register says?
>
> MS. WILKENENG: No, in terms of not combining them the discussions in
> the past Federal Registers is in regard to the quantitative amount,
> and that is why you see trans fat on a separate line under saturated
> fat. Our first proposals had put them all on one line using the term
> saturated fat.
>
> DR. MAYNE: I think the most compelling reason not to have the specific
> DV for trans fat is the measurement issues. If we can\'t measure any
> more precisely than, you know, less than 0.5 grams and we set it at 2,
> you are saying that we can\'t differentiate zero and 25 percent of a
> DV and that is extremely misleading to a consumer. So, I just don\'t
> think it is practical if you are talking about 2 grams as the limit
> there.
>
> DR. RIMM: I think we can differentiate it, it is just that the
> labeling laws allow anything less than 0.5 grams not to be put on the
> label. We definitely can measure 0.2 and 0.1.
>
> DR. MAYNE: Right, so then it would make no sense because manufacturers
> would make them all at 0.4 grams and then they would be exceeding
> their 2 grams and not realize they are consuming any at all. So, I
> don\'t think that would make any sense.
>
> DR. RIMM: Unless the daily value can be based on the true amount of
> trans fat. Even though the grams may say zero, the daily value could
> state 10 percent if it really was 0.3 grams but that is too much
> detail.
>
> DR. MAYNE: It confuses them even further.
>
> DR. LICHTENSTEIN: Again, it goes back to this is a reasonable proposal
> for presenting the information, at least at this point, and obviously
> none of this is chiselled in stone because nutrient facts panels do
> change if there are data to suggest that they should in the future.
>
> MS. WILKENENG: I think this format also clearly addresses your third
> question, whether trans fat and saturated fat have similar or
> different effects. If you are going to recommend that they have
> similar effects, this is reasonable. If they have different effects
> then perhaps it is not.
>
> DR. KRINSKY: Well, in the simplest world if they had identical
> effects, then they could be combined as sat and trans and we wouldn\'t
> have anything to worry about. So, we might at this point move into
> question three. I think you have already raised it for us, Virginia,
> and thank you very much, unless the committee has questions on the
> nutrition facts. Yes, Suzie?
>
> MS. PELICAN: It is not really a question, just a comment. I think Eric
> brought it up and Virginia kind of confirmed that we don\'t have
> anything in the DV column for monounsaturated and polys in the case of
> those foods that decide to declare them. So, there is a precedent for
> having no DV.
>
> DR. JOHNSON: I just wanted to touch on the analytical thing again. In
> a perfect world no doubt you can be precise in determining 0.4, 0.5,
> but in the reality of a food-based system there are manufacturing
> variabilities, there are variabilities in raw materials and all kinds
> of things like that, and the current label does have a window for
> compliance, which many of us feel is a challenge in and of itself, of
> 20 percent. So, I think when you get down to that level of half a gram
> or less it is tough to get much more precise than that.
>
> DR. KRINSKY: I really don\'t see why, Guy, because you are not dealing
> with an individual serving; you are dealing with a huge pot of product
> that is being produced. Certainly, industry can determine what the
> percent trans is in that pot and then break it down to the individual
> serving. No? Go ahead.
>
> DR. JOHNSON: I mean, there are just variabilities within any kind of
> system and processing, distribution, raw materials, analytical
> variability\--there are a lot of factors that enter into that.
>
> DR. KRINSKY: And you are allowed 20 percent over and under in the
> process?
>
> DR. JOHNSON: That is true.
>
> DR. KRINSKY: The whole thing would be simplified if trans was the same
> as sat. So, let us then move to the third question. The third question
> is when compared to saturated fatty acids, are trans fatty acids
> considered to be more, less or similarly adverse with respect to
> coronary heart disease?
>
> DR. LICHTENSTEIN: I will start the discussion. Probably they are not
> identical. We have just talked about some of the differences that are
> well established and some of the potential differences that there are.
> I think from a practical perspective what we also need to take into
> consideration is within the context of the quantities that they are
> likely to be consumed in, and how different are then saturated fatty
> acids.
>
> One could say that for practical purposes, because the intake is
> around 2 percent of energy so that if you break it down to a variety
> of foods, each food doesn\'t have that much but, you know,
> cumulatively it probably, from a biological perspective, would be
> difficult to distinguish between 2 percent trans and 6 percent sats or
> 3 percent trans and 5 percent sats as far as whatever biological
> measures we chose to use as the criteria.
>
> DR. KRINSKY: So, does that mean you couldn\'t differentiate 3 percent
> trans from 3 percent sat?
>
> DR. LICHTENSTEIN: Three percent trans and 3 percent sat you might be
> able to, but that is not what is likely to happen. We know that is not
> what is in the diet. What we know is that there is two to three times
> or four times more sat relative to trans so you are shifting in trans.
> Even if you cut your trans in half you are going from 2 percent to 1
> percent, whereas your saturated fat, if you went down an equivalent
> amount in weight the percent shift of the total is going to be
> smaller. So, again, it comes down to what you can measure with respect
> to your biological outcomes and, from a practical perspective, I am
> not sure that we have the data to really assign a relative factor to
> each so it may, to a certain extent, be a moot point if we go back to
> what we want to encourage people to do, minimize intake of both.
>
> DR. SHANNON: Could I ask a question here? If you did, like you say,
> cut trans in half and replaced that with a totally hydrogenated
> product what does that do? Do you have any sense of what that does in
> terms of raising the percent of saturated in the diet?
>
> DR. RIMM: It would all be saturated so if you take 2 percent and go
> down to 1 percent that 1 percent would no longer be trans, it would be
> all saturated. So, that would not increase your sats dramatically
> because your sats are at 10 percent and going to 11 percent so it
> would only be a small increase in overall sats. I think that is what
> you are asking.
>
> DR. SHANNON: That is what I am asking from a biological point of view.
>
> DR. LICHTENSTEIN: From a biological point of view, well, that is a
> unique example because in that case you are putting in a saturated
> fatty acid that is relatively neutral. If you are going to use your
> outcome measure to be some LDL cholesterol levels, it would probably
> have a very small biological outcome if those are the quantities you
> were talking about. You certainly could design a metabolic study where
> you had very high levels of trans; you cut it in half; you substitute
> stearic and you probably could see some beneficial effects
> biologically. But within the context of what is likely to happen with
> food, I don\'t think there is going to be that big an effect.
>
> DR. SHANNON: Then that is what I think is the most important thing for
> us to look at. When we are talking about similarity, what is likely to
> happen if we dropped the trans to the extreme of replacing it? Is it
> going to have a biological effect? If not, then perhaps we can
> consider them similar.
>
> DR. RIMM: I think we are not the first committee to ponder this.
> Obviously, when they spent four years trying to come up with a
> quantitative assessment for trans fat they spent a lot of time
> thinking about this and decided that biologically trans fat is very
> different from saturated fat so let\'s make a separate line for trans
> fat. I think that is one of the reasons that the trans fat line is now
> going to be in the labels.
>
> But I think in the paper we were given, Mensick does a meta-analysis
> of all the metabolic studies and it is very clear that the LDL or
> LDL/HDL raising effects of trans is about two- to three-fold that of
> saturated fat. If you look at the observational epidemiology, the
> risks associated with the 1 percent increment in trans is about three
> or four times that you would get for a 1 percent increase in saturated
> fat. If you look at the diabetes research, it seems that there is an
> impact for trans and not for sat. If you look at insulin sensitivity
> research, it suggests that there is an adverse effect for trans and
> maybe not necessarily for saturated fat. If you look at the
> inflammatory markers\--I mean, there are a lot of biological studies
> out there, some observational and some experimental, which would
> suggest that trans is very different from sat. You know, I don\'t know
> how important the small range that you are talking about is in our
> diet because there are people that have 1 percent of trans and there
> are people who have 6 percent of trans, and within that range I think
> there is a very big difference in the impact of trans\--than on
> saturated fat.
>
> DR. KRINSKY: So, in a normal American diet 2 to 3 percent trans; 2
> percent; 2.6?
>
> DR. LICHTENSTEIN: But that is probably high, probably closer to 2.
>
> DR. KRINSKY: We will round it off, 2 percent trans. If you drop that 2
> percent trans down to 1 percent and replace it with any saturated
> fatty acid will there be any biological effect? Any measurable change
> in CVD risk?
>
> DR. RIMM: Well, you are talking about the average if you took the top
> 25 percent.
>
> DR. KRINSKY: No, no, no. I am talking about\--
>
> DR. RIMM: A single 1 percent change?
>
> DR. KRINSKY: Yes.
>
> DR. RIMM: Again, if you are looking at the observational studies it
> would suggest that there is a slight difference. You know, we do it
> estimating on the whole range of the nurses health study, looking at a
> 1 percent change in trans versus\--exchanging it for 1 percent
> unsaturated fat and there would be a difference, small but there would
> be a difference.
>
> DR. LICHTENSTEIN: If you looked at the intervention data, no, there
> wouldn\'t be. Even if you look at things like glucose levels or
> insulin levels, even with LP(a) where some studies that show a change;
> some studies don\'t. But even those studies where we saw a change it
> is not in the range that would be physiologically relevant. It just
> turns out that in the intervention studies you see less of an effect
> than you do in the observational studies. So, in the interventional
> studies that magnitude of change is unlikely to have a measurable
> biological effect, at least in the short term. I think all bets are
> off in the long term.
>
> DR. RIMM: I think that is part of it. You are talking about short term
> where we are really only measuring one outcome. I think there are a
> lot of other things and if you put them altogether and measured
> insulin sensitivity, measured lipids\--if you put them altogether you
> would get a bigger difference than if you do if you have a four-week
> trial with a single outcome.
>
> DR. LICHTENSTEIN: Well, no, even with multiple outcomes in the same
> study you still get very little effect.
>
> DR. RIMM: I don\'t know if we know all the outcomes yet that are
> related to trans.
>
> DR. LICHTENSTEIN: We may not know all the outcomes related to sats.
>
> DR. KRINSKY: So, under some circumstances they are equivalent; under
> other circumstances they are not equivalent.
>
> DR. LICHTENSTEIN: Primarily under other circumstances where the intake
> levels are relatively low they are representative of the mean intake
> in the United States. If you go to higher levels, then I don\'t think
> one would be confident saying that. I think it is only in the context
> of the average current dietary intakes.
>
> DR. KRINSKY: And does that mean at the higher levels you are seeing
> more pronounced detrimental effects than you are at the lower levels?
> Is it a gradual change in risk as you go from 1 to 6 percent trans?
>
> DR. LICHTENSTEIN: Well, those data for the intervention studies are
> really just available for lipoprotein levels and a little bit for
> glucose insulin.
>
> DR. KRINSKY: When I say coronary vascular disease I mean the
> association with it.
>
> DR. LICHTENSTEIN: The epi data?
>
> DR. KRINSKY: Well, what you have, Alice, is change in LDL cholesterol.
> LDL cholesterol is associated with coronary vascular disease so even
> in the intervention trials aren\'t you, in fact, dealing with an
> association? You have data\--
>
> DR. LICHTENSTEIN: A relationship, yes. Well, we have relationship with
> glucose, with insulin, with Lp(a), with HDL primarily\--
>
> DR. KRINSKY: Right.
>
> DR. LICHTENSTEIN: \--with actually postprandial particles with
> triglyceride levels, and in that case it is hard to distinguish in the
> lower levels. You can certainly distinguish 6 percent from the 0.55
> percent, which is about the lowest that we ended up with in our
> experimental studies. But within that range of 0.55 and about 3, we
> weren\'t picking up statistically significant differences. In some
> cases there were small trends in LDL, not in HDL but in LDL.
>
> DR. KRINSKY: That is table 8-9? Is that the one you are quoting, page
> 8-59? No, no, no, it isn\'t. I am sorry, it is page 60, the next page.
> It is table 8-10.
>
> DR. LICHTENSTEIN: But those data are just for LDL, HDL and Lp(a).
>
> DR. KRINSKY: Right. I guess what I am trying to do is to relate these
> two worlds that I am hearing. I am hearing one world where the
> intervention trials are, in fact, getting hard data as far as LDL
> cholesterol is concerned as modified by the level of trans fatty acid,
> although that is not the only thing that is varying in those studies,
> it appears.
>
> DR. LICHTENSTEIN: It was for polys. That is because of the products
> that are currently available as far as spreads in the United States.
> It seems that that is what the effect is. If you hydrogenate, you
> decrease the polys and increase the trans.
>
> DR. KRINSKY: And in your studies, Eric, as you see a variation in the
> trans levels what is replacing it?
>
> DR. RIMM: Well, the way we modeled it is that you are reducing trans
> for carbohydrates so you are holding calories constant and you are
> moving trans down and carbohydrate up. Or, you can model it the other
> way. Statistically you can trade trans for sat also.
>
> DR. KRINSKY: So, are we dealing with apples and pears in terms of
> trying to compare these?
>
> DR. RIMM: No, I think that Alice has a dose response. If you put all
> the metabolic studies together there is a dose response between trans
> and LDL. If you look at our studies, as Susan was saying, there is a
> significant dose response between trans and coronary heart disease.
> The point is that if you are at 1 percent and 2 percent there is a
> difference but is it tangible? Well, I would argue that, of course,
> every little bit helps, and I think there is a pretty linear effect
> but no one has shown me that there is an absolute threshold effect
> based on the metabolic studies and I think if you put all the
> epidemiology together you are looking at ranges that are different in
> different countries and it would suggest there is a pretty linear
> association.
>
> DR. LICHTENSTEIN: That would actually argue to combine the two because
> if less than a half gram is considered zero trans you would actually
> lose those small effects, especially if it was cumulative over
> multiple foods throughout the day. Whereas, if it had to be added to
> the sats, then at least it would all be inclusive and you would hold
> together all those little potential dietary effects that might occur.
>
> DR. MAYNE: We have this Mensick review article from AJC and they
> specifically address this issue of isoenergetic replacement of trans
> AT-1 with saturated fats. The quote is that isoenergetic replacement
> of trans AT-1 constituting 1 percent of energy with saturated fats
> decreases total HDL cholesterol by 0.019, and those are the standard
> units. So, it is clear that there is an effect; that they are not
> comparable. Then, when they go on and look at the prediction on
> coronary heart disease risk, they find that they underestimate. With
> the LDL changes they underestimate the coronary-artery disease risk,
> saying that there may be other effects, like Eric was alluding to,
> that maybe trans fats may affect more than just the LDL cholesterol
> because the standard prediction equations underestimate the chronic
> disease risk.
>
> DR. KRINSKY: But that puts me in a bind because how do you evaluate
> the other effects of the trans?
>
> DR. RIMM: We do it the same way we do the lipids. We are just a year
> or two behind. I mean, I think there is a lot more data that will come
> out in insulin sensitivity or inflammation. There are already a number
> of association studies looking at trans and inflammation. So, I think
> it will just be a few more years until Alice has time to do some more
> trials to look at all these outcomes, unless she has some saved blood
> that we can look at.
>
> DR. JOHNSON: It seems to me that the meta-analysis, and so forth, are
> based on the studies that are there, most of which have been done at
> higher levels than are reflective of the current diet in the U.S. So,
> then you crunch the numbers and you come up with those things so I
> still think there really isn\'t hard evidence to show that at the
> levels that we are talking about in the diet there is a meaningful
> difference between trans and saturated fats. I think we also need to
> begin to feather in how this is going to be interpreted by the
> consumers. If we make a big difference between trans fats and
> saturated fats, and so forth, unless we really have to, I think we run
> the risk of really confusing people and pointing them in the wrong
> direction, emphasizing either trans or saturated fats unduly. So, we
> need to be cognizant of that I think.
>
> DR. KRINSKY: Let me just try to put this together. If we are dealing
> with low levels of trans fatty acids, then does that seem to be much
> of a change if we try to change the trans for the saturated? So, you
> go from 2 percent to 1 percent trans, it may be difficult to
> demonstrate that there is an increase, decrease or it looks as though
> it is equivalent. But if you are starting at 6 percent trans, then you
> can begin seeing a difference if you replace that with saturated fatty
> acids.
>
> So, in fact, maybe the thing that we should be doing here should be
> working even more energetically to try to get the trans level down to
> a level where there may not be much of a difference between trans and
> saturated fatty acids. That is, if we have people that are consuming 6
> percent trans fatty acids, then that may be a greater risk than a
> comparable level of saturated fatty acids\--they may be at greater
> risk than if they had a comparable level of saturated fatty acids.
> Whereas, if they are consuming 2 percent and they go to 1 percent it
> is going to be a little bit more difficult to evaluate the effect. Am
> I overstating the case? If I am, please correct me.
>
> DR. RIMM: Well, I think there is no question in getting someone to go
> from 6 percent to 1 percent. Even if they were switching to saturated
> fat I think there would be benefit because I think the trans is
> steeper than the saturated fat in terms of cholesterol and heart
> disease risk. So, sure, I think going from 2 to 1 is not as important
> as going from 6 to 1. But I think going from 2 to 1 is as important as
> going from 6 to 5. You know, the bigger the change, the better.
>
> DR. MAYNE: If you go back to the figure from Ascherio, the two
> regression lines there, it looks like the magnitude of the change is
> much greater if you go from 6 to 5 than if you go from 2 to 1 because
> they are not parallel lines. So, if you look at the total net change
> in LDL/HDL cholesterol, as Norman suggested, it would predict a much
> greater impact at higher levels of trans fatty intake if you agree
> with that line.
>
> DR. LICHTENSTEIN: I think the difference between those two lines is
> there was one study that was omitted for one of the lines because it
> was so out of range. So, I think you should look at the line that did
> not include that study because that was very unusual data.
>
> DR. RIMM: I think the line is estimated based on saturated fat change.
> The dotted line is saturated fat and the straight line is trans fat.
>
> DR. LICHTENSTEIN: Okay, I am sorry.
>
> DR. RIMM: There clearly are differences based on the estimate. The
> slope clearly is different. So, you can argue if you are way down at
> the 1 and 2 percent, you know, the slope is the same, there is going
> to be a difference but, obviously, the higher you get up the absolute
> difference will be greater.
>
> DR. KRINSKY: To get back to our question, when compared to saturated
> fatty acids at certain levels, because this is really the answer to
> this question is going to depend on the level of the trans fatty acid
> in the diet. So, can we modify our responses to the question by adding
> something to it? Are we allowed? Do we have dispensation? We are going
> to do it anyway. So, we can play around somewhat with this. I think
> the Ascherio figure really is a very important figure. What are the
> squares and the circles in that figure, please?
>
> DR. LICHTENSTEIN: I think they refer to the individual studies. The
> original figure was actually done in color. Oh, no, I am sorry, that
> is the controls versus the intervention. They were actually all color
> coded so you could match the study with the dots.
>
> DR. JOHNSON: Could I make just one observation about that figure? It
> is important to remember that what they are plotting here is the
> energy from saturated or trans fat versus the ratio of LDL to HDL
> cholesterol. If you look at the individual components, which my friend
> Ed Hunter at Cincinnati did, he showed that there is a clear
> relationship between trans fat intake and LDL over 4 percent of the
> diet, not under, but there are few points. When you look at HDL
> individually there is no effect in any of these studies until you get
> up to around 6 percent of the diet which is where the effect kicks in.
>
> So, I think it is important to recognize that the ratio here can be a
> bit misleading if you are simply looking at that and extrapolating it
> through the whole range and forcing it through the origin.
>
> DR. KRINSKY: If I follow Ed Hunter\'s argument I would ignore the
> percentage of energy from fat above 6 percent because if the HDL is
> not changing under those circumstances, if trans is not changing the
> HDL level, that ratio is the same as the effect on LDL if your
> denominator is constant. It looks to me, and I would need somebody who
> has had more experience in manipulating data, that is the
> epidemiologists, what those two lines looked like if you ignored
> everything above 6 percent energy. Again, I don\'t have the colored
> points so that makes it a little bit difficult to read this. For
> example, at 3 percent are those two points for trans fatty acids? At
> 3.5 percent are those two points\--so, that looks like there is, in
> fact, a real effect of trans fatty acid on LDL cholesterol from 6
> percent down.
>
> DR. LICHTENSTEIN: The question is between 1 and 2 percent and,
> remember, that is on the ratio. For LDL the effect of trans is less
> than for saturated fatty acids, it is just that there is an HDL effect
> also.
>
> DR. KRINSKY: But if we are told that there is no effect on HDL I am
> ignoring the ratio.
>
> DR. LICHTENSTEIN: But that is data are just plotting the ratio, this
> figure.
>
> DR. KRINSKY: But the denominator is constant.
>
> DR. LICHTENSTEIN: It is not. I don\'t think you can assume that. I
> think you have to look at the individual studies.
>
> DR. KRINSKY: I thought this is what Guy just said.
>
> DR. LICHTENSTEIN: Maybe you should reproduce that, or something.
>
> DR. JOHNSON: I would be happy to share this with the group.
>
> DR. KRINSKY: Whether the HDL is constant\--
>
> DR. JOHNSON: It is extracted from all of the studies that are
> published.
>
> DR. RIMM: I mean, if you look at the circles, regardless whether this
> is the ratio or LDL, the circles are the trans and the squares are the
> placebo group, the control group for that particular diet. The circles
> make a pretty nice, straight line with the exception of the one really
> high one, which is why I think people felt comfortable extrapolating
> down to zero, plus there is Alice\'s really low point, 0.5 percent.
> But if you look at just the circles it would suggest that there
> clearly are differences all the way down to the origin.
>
> DR. LICHTENSTEIN: But some of them must be for saturated. Some of
> those squares must be saturated fats because how would there be a line
> here for saturated fat?
>
> DR. RIMM: That is estimated based on all the other trials that have
> ever been done; that is not based on these eight trials. There have
> been a lot of trials done on saturated fat.
>
> DR. LICHTENSTEIN: But it says it represents the best fit regression
> for saturated fatty acids.
>
> DR. RIMM: This is just a meta-analysis of the trans studies, and that
> is the dark line. The dotted line is what you would expect if you took
> Mensick and Katan\'s review of all the 30 or 60 studies that have been
> done on saturated fat. So, you can see there are clear differences in
> the trend between trans and what would have been expected if you
> plotted all the saturated fat trials.
>
> DR. LICHTENSTEIN: Which Mensick and Katan review meta-analysis?
>
> DR. RIMM: Maybe it was the \'92 one, I believe, the first one.
>
> DR. KRINSKY: We are having a data searching pause.
>
> DR. JOHNSON: Dr. Lichtenstein has slides from her study that show that
> as you increase trans there is a clear impact on LDL but there isn\'t
> on HDL, and that is what my friend Dr. Hunter showed by looking at Dr.
> Lichtenstein\'s study as well as the other studies that were published
> in this document.
>
> DR. LICHTENSTEIN: It is on 8-60. So, it is one study. I mean, you
> know, I think we have to take that into consideration.
>
> DR. KRINSKY: And that study is included in this figure? We are trying
> to get the methods out of Ascherio\'s paper with respect to how the
> lines were established. Any luck, Eric? The pressure is on.
>
> DR. RIMM: As usual, Alice is right. The figure summarizes the
> randomized trials that directly compared the effects of trans fatty
> acids with isocaloric amounts of cis fatty acids. When the data are
> available, the figure also shows the effects of saturated fatty acids
> in the same studies. So, of those same studies that have looked at
> trans, some of them also looked at saturated fat and that is the four
> or five squares that are there. So, that is in the same studies.
>
> DR. LICHTENSTEIN: Right, but the data are incomplete because not all
> the studies looked at that.
>
> DR. RIMM: Correct. However, you can see that in most of them the
> saturated fat effect is much lower than the trans fat.
>
> DR. LICHTENSTEIN: Right, on the ratio but not on LDL and on LDL the
> trans tend to have less of an effect than the saturated fact, but it
> is compensated for because of the effects on HDL. So, at low levels,
> again, it seems sort of a wash.
>
> DR. KRINSKY: To get back to our question, you just said at low levels
> it seems like a wash.
>
> DR. LICHTENSTEIN: At 1 and 2 percent of energy. When you go higher the
> interpretation would be different.
>
> DR. KRINSKY: So, we could consider an approach to answering the
> question. That is, at low levels of trans it tends to be approximately
> equivalent to that of the saturated fatty acids. We may have to define
> what low levels mean but if you just accept that, for the moment at
> low levels there does not seem to be much difference between saturated
> and trans. But as we go to high levels we begin seeing a very distinct
> and presumably significant\--I don\'t want to use that term, we begin
> seeing a very marked difference between the trans fatty acids and the
> saturated fatty acids. In fact, the trans fatty acids are more adverse
> with respect to coronary heart disease, which very simply means that
> there should be recommendations that we have very low trans fatty
> acids in our diet.
>
> DR. LICHTENSTEIN: We do. That is the IOM report.
>
> DR. KRINSKY: I understand that, but now I am thinking right back to
> question two because question two is asking can we support the
> suggestion that a diet should contain less than 1 percent of its
> energy from trans fatty acids. If you look at figure 8.4, it seems
> that that would be a good thing to have.
>
> DR. RIMM: And that is just looking at the lipid effect. There are all
> sorts of other effects.
>
> DR. KRINSKY: But we are only asked with respect to\--yes, one and
> three are asking with respect to coronary heart disease and I know
> that there are other markers that are coming up and trans is having
> more and more effects and in the future it may be very profound, but
> the future lies before us and we are here today and tomorrow. So, we
> are going to have to evaluate what is available today and tomorrow,
> what is available to us, not what is available in unpublished or
> unstudied material.
>
> DR. JOHNSON: I was just going to reiterate the fact that all but one
> of these studies used levels of trans fatty acids over the mean
> intake. I mean, the fact that we would like to see trans fatty acid
> intake lowered doesn\'t mean that we have data to suggest that it
> would be a meaningful difference between saturated fat and trans fatty
> acid levels at usual dietary intakes. We just don\'t.
>
> DR. KRINSKY: I understand that and, you know, the usual dietary intake
> is between 2 and 2.6 grams of trans fatty acid per day.
>
> DR. LICHTENSTEIN: Percent of energy.
>
> DR. KRINSKY: Of energy, sorry. Thank you. But, in fact, we have a
> significant portion of the population that is consuming both more and
> less than that, and that portion of the population that is consuming
> more than 2 to 2.6 percent of energy\--if we look at this figure, is
> it risk? Is it increased risk? Now, do we then only think of the
> average intake of the population or do we think much more broadly,
> that, in fact, that average represents a very broad spectrum of
> intakes?
>
> DR. LICHTENSTEIN: Eric, do you remember what is the range in the
> nurses and health professionals? Because what we are looking at here
> are metabolic studies where it has been manipulated to be extremely
> high. It is hard to get 6 percent of energy. Do you remember what the
> range is?
>
> DR. RIMM: I think for the nurses the tenth percentile is 1-3.5
> percent, or something like that. In the health professionals the
> lowest quintile is 1.5 grams trans fatty acids per day. The highest
> quintile was 4.3.
>
> DR. LICHTENSTEIN: Which is 9 percent energy so we are switching units
> here.
>
> DR. RIMM: Right. In the health professional the lowest quintile is 1.3
> grams per day; the highest quintile is 2.9.
>
> DR. LICHTENSTEIN: So, that is 2 percent of energy.
>
> DR. KRINSKY: We may have some figures in one of our tables on page
> 8-67.
>
> DR. RIMM: Yes, so the nurses goes from 1.3 percent of energy up to 3.2
> percent of energy in the median of that first and fifth quintile. The
> health professionals is in grams so the two of them are difficult to
> interpret. So, it is 1.7 grams up to 6.5 grams, which would be about
> 0.5 percent up to 3.5 percent.
>
> DR. LICHTENSTEIN: I think for them it is probably a little bit lower
> because the males are consuming more than 2,000 calories.
>
> DR. RIMM: Right.
>
> DR. LICHTENSTEIN: So, it is probably closer to\--I don\'t know, 2, 2.5
> percent. So, that is what we are talking about for the current range
> on the basis of these data.
>
> DR. KRINSKY: But for the men there is like a four-fold range from the
> lowest\--
>
> DR. LICHTENSTEIN: That is grams. That is grams per day.
>
> DR. KRINSKY: It is four-fold\--
>
> DR. LICHTENSTEIN: Okay, it is still four-fold.
>
> DR. KRINSKY: Four-fold as opposed to the women that have about a
> 2.5-fold. So, that would indicate that you are going to have a higher
> percentage of men. If, in fact, the highest quintile of men is
> equivalent to 3.5 percent energy intake\--is that what somebody just
> said?
>
> DR. RIMM: Yes, the nurses are 3.2 percent in the highest quintile.
>
> DR. LICHTENSTEIN: We don\'t know what the men are because we don\'t
> know what the caloric intake is.
>
> DR. RIMM: The average caloric intake is about 2,100 kilocalorie for
> the men. For these men we estimated it was 2,100 kilocalorie. So, if
> they are an underestimate, then everything is an underestimate so they
> would be comparable. Dr. Krinsky is now doing a back of the envelope
> calculation.
>
> DR. KRINSKY: It looks like it is about 3.2071. So, it is similar to
> the 3.5\--it is between 3-3.5 percent energy intake.
>
> DR. RIMM: These are adults that are 40-75 male health professionals so
> we have to keep that in mind. So, again, I think the general
> population definitely at the high end will be much higher than these
> men and women, and I think that is who we want to be directing our
> message to. I think that the food label really needs to get out to
> people who are eating 5 and 6 percent of energy from trans.
>
> DR. KRINSKY: Kids, adolescents, college students. So, what is the
> message, Eric, that we want to get out to them?
>
> DR. RIMM: I think we need to make the point that trans is different
> than saturated fat and we have already put that on the quantitative
> label and I think we have to acknowledge the fact that it is important
> for people to understand that trans, maybe at very low levels, is not
> different than saturated fat but I think the biological effects of
> trans are different from saturated fat and the label should denote
> that.
>
> DR. JOHNSON: It sounds like we are in agreement that at high levels
> trans are different than saturated fat. I think the harder part of
> that question is should the label reflect that if most of the
> population is not going to benefit from that information.
>
> One of the things I am an advocate for is putting the E back in NLEA,
> and we need to remember that the trans fat message needs to be
> communicated by more than just the nutrition label. Particularly
> people that are consuming high amounts of trans I think should be
> given that information. I mean, that should be the target for
> educational efforts. I think we do a disservice if the bulk of the
> population need not be\--if that distinction is not significant.
>
> DR. KRINSKY: Well, I am not sure what position we are in to put out a
> message as you are suggesting, Guy. I think it is a very important
> message and it would be very useful, and I don\'t know whose
> responsibility that is. I don\'t know if it is the FDA\'s
> responsibility or who, but I think your point is very well taken that
> that message should come out. But how do we then try to reconcile that
> with trying to answer a question of this nature where the question is
> not addressing the educational value of this information? In fact, it
> is addressing the scientific aspects of this question and we are
> having a terrible time trying to answer it scientifically\--a
> difficult time trying to answer it scientifically because not so much
> that it varies but the difference may become insignificant at low
> levels of trans, whereas it may be very significant in terms of
> coronary heart disease risk at higher levels of trans.
>
> I am saying low and high and I am obviously not defining them. If any
> of you would like to define it, that would be fine. I can\'t define
> this. If we were to come out and try and answer this question by
> talking about high and low levels, I don\'t think that would be
> terribly useful for the FDA. I think it would be more useful if we
> could come out with some level and if I begin thinking about coming
> out with some level, then I begin thinking that this is a DV for trans
> fatty acids and maybe that is what direction we should go in. We
> can\'t go in that direction but we can make recommendations in that
> direction.
>
> DR. JOHNSON: Let me just say that I made the point about education
> because I don\'t think that should be lost. I think it is important
> and I think it is a shared responsibility not only with FDA and other
> government programs and the Dietary Guidelines but the industry plays
> a very active role in educating people about trans fatty acids. So, I
> think that is something that shouldn\'t be lost.
>
> With respect to where we are at, it seems like we all agree that at
> high levels, whatever that is, trans fatty acids are different than
> saturated fat. At low levels we don\'t have the data. So, the big
> question is where do you draw the line. The problem is that we really
> don\'t have good data. If you go back and look at the individual
> studies, HDL isn\'t impacted until you get something like 6 percent of
> calories and LDL is roughly the same between the two. So, that is one
> potential answer. But without good, solid kind of data at levels below
> the mean intake, we are kind of guessing.
>
> DR. KRINSKY: Could you hold up Alice\'s figure on LDL cholesterol as a
> function of trans fatty acid?
>
> DR. LICHTENSTEIN: Again, remember that was one study. That is not a
> compilation of studies.
>
> DR. KRINSKY: I understand that.
>
> DR. LICHTENSTEIN: A nice study, I must say.
>
> DR. KRINSKY: We will make the judgment call, if you don\'t mind! But
> as I look at that figure, Guy, there is a trend, isn\'t there? Even
> though there is not a significant difference, there is a trend. If you
> were to drop butter and do a trend analysis would it be significant?
>
> DR. LICHTENSTEIN: We just did an analysis of variance with all of the
> diets. I don\'t remember dropping the butter because that was just
> part of the experimental design but it certainly could be done. You
> can see a clear effect of HDL, with the butter being really high, and
> then at the highest level of trans, which was 20 percent of calories
> of stick margarine which was pushing the system.
>
> But getting back to the original questions, I don\'t think any of us
> are arguing that we should encourage the consumption of trans fatty
> acids and I don\'t think any of us arguing that if the intake was down
> to 1 percent of energy that that wouldn\'t be advantageous to the
> general population.
>
> So, in some senses it seems to me that the three questions are in one
> realm and then there is another realm which is how to deal with the
> label, and it seems sometimes that we are crossing over in that
> discussion or maybe you are bringing us back to it. Because when we
> started looking at the mock label, which is somewhere in my papers\--
>
> DR. KRINSKY: Actually, I think you brought up the DV for the label and
> I just thought that would be useful.
>
> DR. RIMM: Let me go back to a point I made before about what the
> threshold for what we call scientific evidence is for all the other
> things in this label because if you look at dietary fiber, there is a
> DV for dietary fiber and I am sure if you exchange 1 gram of dietary
> fiber for 1 gram of sugar you also would not see any biological
> difference. Yet, you know, I think there still is an accepted dose
> response between dietary fiber and LDL cholesterol if it is soluble
> fiber. So, I think maybe we are raising the bar too high for saturated
> fat compared to everything else in this label and that for most of
> these factors there is a dose response; there are metabolic studies
> where you can draw the line; but there are not 30,000 metabolic
> studies at all levels of sodium and all levels of fiber. So, I think
> we should just uphold the same\--of course, I don\'t know this for a
> fact but we should uphold the same evidence that we use for all these
> other factors that we do for trans fat and saturated fat.
>
> DR. LICHTENSTEIN: I am not sure the criteria for fiber was LDL
> cholesterol. I don\'t know if we could get Paula to comment, if she is
> allowed to. But it still doesn\'t diminish your point that we still
> have the saturated fat and the cholesterol where the data are not what
> we would expect them to be.
>
> MS. PELICAN: Just to follow-up on what Alice had said and also Guy, I
> think I really appreciate what Guy has said more than once about
> education, and I think Alice said, you know, somehow we are getting
> into kind of a grey area, kind of a difficult point, and I think this
> is sort of where the science meets education and I am one who doesn\'t
> think that the nutrition label itself is an education tool. It informs
> people but it needs to be used in the hands of educators, and I think
> our best role as this group is to give guidance on the science and
> then we have educators\--and I applaud FDA for this wonderful
> educational tool that in the hands of educators, with any number of
> programs, this can then be taken but we need to have this based on
> good science so that educators can interpret it correctly and help
> consumers interpret the foods they buy correctly.
>
> DR. RIMM: I think it really is meant to be an informative tool. So,
> the fact that we have grams of trans fat on there and grams of
> saturated fat is really quite a step forward and I applaud the FDA for
> being able to push that forward. My concern is that we need to inform
> people and educate them, and my concern is that forever people will
> think that a gram of trans fat is the same as a gram of saturated fat
> and I think the growing body of evidence would suggest that is not the
> case, that a gram of trans is probably worse than a gram of saturated
> fat. But we will have to leave it up to the educators to teach us
> that.
>
> DR. KRINSKY: Unless we had ULs for them, which we don\'t and we
> won\'t. I have a slight sense of wheel spinning, at least in my head.
> I have just been trying to find out whether it might not be worthwhile
> to see if we could move forward our public comment. I don\'t know if
> everybody is here for the public comment. We are trying to see if the
> speakers are ready so why don\'t we take a ten-minute break and
> reconvene at 4:35?
>
> \[Brief recess\]
>
> **Public Comment**
>
> DR. KRINSKY: Thank you, all. We are going to move into our public
> comment session and we have three speakers. I even have a list of them
> and they each have ten minutes and we are free to ask them any
> question that we want to. But before they begin, I have a statement
> that the FDA requires me to read. It deals with the disclosure of
> financial relationships for public commentors.
>
> Both the Food and Drug Administration and the public believe in a
> transparent process for information gathering and decision-making. To
> ensure such transparency at the open public hearing session of the
> advisory committee meeting, FDA believes that it is important to
> understand the context of an individual\'s presentation. For this
> reason, the FDA encourages you, the open public hearing speaker, at
> the beginning of your written or oral statement to advise the
> committee of any financial relationship that you may have with the
> sponsor, its product and, if known, its direct competitors. For
> example, this financial information may include the sponsor\'s payment
> of your travel, lodging or other expenses in connection with your
> attendance at the meeting. Likewise, FDA encourages you, at the
> beginning of your statement, to advise the committee if you do not
> have any such financial relationships. If you choose not to address
> this issue of financial relationships at the beginning of your
> statement it will not preclude you from speaking.
>
> So, I would like to call on Robert Earl, and if you could go to the
> podium, please, Mr. Earl. Robert Earl is the Senior Director of
> Nutrition Policy at the National Food Processors Association and he
> will cover the Association\'s position and principles about
> disqualifying levels of nutrients for health claims, and perspectives
> on data needs and utility of a DV for trans fat. Mr. Earl?
>
> MR. EARL: Thank you, Dr. Krinsky. Good afternoon to you and to members
> of the Nutrition Subcommittee and thank you for this opportunity to
> present the views of the National Food Processors Association on these
> important issues.
>
> The National Food Processors Association\--I think this next paragraph
> will cover the disclosure of all things financial related to my
> employment\--in the National Food Processors Association we are the
> voice of the 500 billion food processing industry on science and
> public policy issues involving food safety, food security, nutrition,
> technical and regulatory matters and consumer affairs. We have three
> scientific centers and one international office in Bangkok, Thailand.
> Our scientist and professional staff represent the food industry
> interests on government and regulatory affairs and provide research,
> technology assistance, education and communications, and crisis
> management support for the Association\'s U.S. and international
> members.
>
> Our members produce processed and packaged fruit, vegetable and grain
> products, meat, poultry and seafood products, snacks, beverages and
> juices, or provide supplies and services to food manufacturers.
>
> There are two topics before the subcommittee today, disqualifying
> levels for total fat and heart health claims and evidence supporting a
> daily value or DV for trans fatty acids. The National Food Processors
> Association has been active for over a decade regarding issues related
> to food nutrition labeling under the Nutrition Labeling and
> Educational Act. Under the NLEA implementing rules, the current health
> claim disqualifying level for total fat is predicated on the 2,000
> calory diet in which 3 percent of calories is derived from fat.
>
> As evidenced by the content of the report from the Institute of
> Medicine\'s dietary reference intake panel on macronutrients, the
> ongoing discussions of the dietary guidelines advisory committee
> preparing the edition for 2005 and evolving peer-reviewed scientific
> literature, we believe it is no longer prudent or acceptable for
> public health to advocate a one-size-fits all dietary pattern for
> protein, fat and carbohydrate. Existing national dietary guidelines
> advocating moderate in total fat diet and FDA believe the evidence is
> clear that ranges of fatty intake in varying ratios of protein to fat
> to carbohydrate can promote health, weight maintenance or weight loss
> among the public, assuming a wide variety of food choices to meet
> nutrient needs and balance between food intake and physical activity,
> with the negative energy balance required for weight loss.
>
> Based on this, NFPA believes that FDA should reconsider the total fat
> disqualifying level of heart health claims. The agency has already
> waived this criterion and replaced it with a disclosure statement for
> several heart health claims. Many of them were mentioned this morning
> and examples include health claims for stanol esters and sterolesters
> and the qualified health claims for walnuts and nuts. These actions
> acknowledge that a variety of fat levels in foods are acceptable in an
> overall dietary pattern, and that individual fat content of food is
> less important than the levels of saturated fat in reducing the risk
> of heart disease. The Institute of Medicine\'s dietary reference
> intake report on macronutrients also concurs that total dietary fat,
> within acceptable macronutrient distribution ranges, is not associated
> with chronic diseases, including heart disease.
>
> NFPA believes it is appropriate to reconsider total fat disqualifying
> criteria for heart health claims because the nutrition label clearly
> discloses amounts of total fat and other nutrients. NFPA has long
> advocated disclosure of information over criteria that would prohibit
> speech. NFPA advocates a how to eat appropriate to diet and health
> rather than a good food, bad food appropriate that would stigmatize
> moderate fat foods that can contribute to overall health and dietary
> patterns that prevent chronic disease. NFPA believes that total
> disqualifying levels for heart disease health claims should be
> converted to a disclosure.
>
> The second topic of this subcommittee\'s meeting relates to the
> ability of the agency to proceed with establishing a daily value for
> trans fat for food labeling. Given the needs for harmony and
> coordinating mandatory food label changes, we question whether
> sufficient data exists to introduce a daily value for trans fat to the
> nutrition facts panel. It is unclear that sufficient data exists about
> current trans fat content of food and food consumption patterns to
> make meaningful estimates to establish a daily value. Studies of
> dietary intake of trans fat conclude that trans fat consumption is far
> below the consumption of saturated fat as a percentage of energy.
>
> FDA should also not proceed rapidly or piecemeal with further required
> changes to the nutrition label following implementation of the trans
> fat quantitative declaration final rules. NFPA believes that it is
> important to avoid the prospect of several sequential mandatory
> nutrition label revisions within the span of a few years as frequent
> changes to the nutrition label structure could undermine consumer
> confidence in the label.
>
> Careful consideration and coordination of mandatory label changes are
> essential because contextual information on trans fat related to
> information about saturated fat and cholesterol which, in turn,
> relates to the future prospect of daily values for other fatty acids.
>
> The nutrition label should not be a field for experimentation but
> should be a tool for conveying reliable information to consumers. NFPA
> believes that consideration of a daily value for trans fat should be
> coordinated into the future single set of changes to all daily values
> that FDA plans to initiate in the near future.
>
> An additional comment is that this would also allow to take advantage
> of future data from food composition databases and also information
> from the ongoing data collection of food consumption and health
> indices from the integrated USDA and National Center for Health
> Statistics survey that was formerly best known as the NHANES survey.
>
> Further, we believe that there is a paucity of data to demonstrate
> that daily values are either understood or widely used by consumers in
> assembling foods for a dietary pattern. A strategy should be developed
> for educating consumers about daily values. NFPA has been a leader in
> food label education and continues to believe in the nutrition label
> and the E in the NLEA, education. More educational opportunities need
> to be provided by the Dietary Guidelines for Americans, the food guide
> pyramid, and these are all critical for consumer understanding about
> the contributions of foods to diet and health.
>
> FDA appears poised to recommit to consumer education about food and
> nutrition labeling, as is mentioned and evidenced in its \"Calories
> Count\" report. NFPA concurs that further education about the
> understanding and use of daily values is warranted.
>
> In summary, we offer these comments to remind the subcommittee that
> your scientific considerations do not exist in a vacuum. They would be
> applied in nutrition laboratory. Because of this application, the
> practical effects of your deliberations should also be considered.
>
> A couple of other points based on some of the discussion that we heard
> this afternoon, some of the discussion related to the pros and cons
> and related to positive and negative nutrients on the nutrition facts
> panel and the use of daily values and now considering the dietary
> reference intakes for labels. One thing to remember is that ULs are
> upper levels, not limits, and that risk begins at the establishment
> level of the upper level, and that daily values for saturated fat,
> cholesterol and sodium are upper targets currently on the label. And,
> these are amounts that are recommended, as this discussion has
> evidenced, not to exceed in planning an overall daily diet.
>
> Another point is that perhaps the subcommittee might benefit from some
> glance back in history to the proposed rule for daily values from 1991
> and the final rules for daily values, to look back at what were the
> considerations in picking the numbers and how the agency proceeded
> forward when there was not information in the form of an RDA to create
> the daily values on the label.
>
> Dr. Lichtenstein is correct that the source of the 10 percent daily
> value for saturated fat on the label is from the ATP report by the
> National Heart, Lung and Blood Institute. But if I recall correctly,
> that value is still for the normal population and primary prevention I
> think is still 10 percent for saturated fat and 300 mg for
> cholesterol, with the lower numbers you mentioned that were relevant
> for those who had had heart disease events, stroke or something else
> and were on a different level of dietary intervention.
>
> With those comments, thank you very much for the opportunity to
> comment on the important issues before you.
>
> DR. KRINSKY: Mr. Earl, thank you very much for your very timely
> presentation. Are there any questions from the members of the
> committee?
>
> DR. RIMM: If we are looking at our made-up label here, are you
> advocating to remove anything related to the daily value assigned to
> trans fat and essentially you would like to leave the daily value for
> saturated fat and leave a line blank next to the trans fat?
>
> MR. EARL: Well, at present the final rule allows you to have the
> quantitative listing of trans fat on a separate line and, given the
> discussions of the subcommittee this afternoon and the level of
> evidence related to developing a daily value, it may be prudent to
> wait and roll that into the entire portfolio of daily value revisions
> that the agency is about to embark on and as further science unfolds
> related to diet and health food composition and food consumption
> patterns.
>
> DR. RIMM: What we have in front of us is what is proposed currently.
> Is that correct?
>
> MR. EARL: I believe what is on the label as was described by Virginia
> Wilkeneng was relating to what the Institute of Medicine\'s diet
> reference intakes in food labeling and fortification reports laid out
> as one of its principles, not as what the final rule states for
> labels.
>
> DR. KRINSKY: Any other questions or comments? If not, thank you very
> much, Mr. Earl.
>
> MR. EARL: Thank you.
>
> DR. KRINSKY: Our next presenter is Mr. Martin Hahn, of Hogan and
> Hartson and he will be speaking on behalf of his client, GFA Brands.
> We have a handout that was supplied by Mr. Hahn and he is going to
> summarize the scientific evidence establishing the importance of
> considering the blend of fatty acids in the total diet when
> considering risk factors for heart disease.
>
> MR. HAHN: Well, I certainly want to thank you for the opportunity to
> make these comments today. I noticed that I was very transparent
> saying that I was here on behalf of GFA brands. I was less transparent
> in saying that I am an attorney with Hogan and Hartson so thank you
> for clarifying that. For purposes of the FDA guidelines, I can assure
> you that I do have a financial relationship and I am being paid for
> being here today.
>
> \[Laughter\]
>
> That is just in case there was any doubt! A little bit about GFA, GFA
> is a manufacturer of many fat-containing products including buttery
> spreads, cheese products, microwave popcorn and other foods. Their
> entire product line is based on the research that is out of Brandyce
> University, by Dr. Casey Hayes who has done a lot of research on the
> importance of balancing the various fatty acids that are in the diet.
>
> The presentation today is based on materials that Dr. Hayes has
> prepared I have to say it is a little bit intimidating for someone who
> has legal training and, although I have a degree in food technology
> and took basic biochem and nutrition classes, the area of expertise of
> this group that I am addressing far surpasses what I am accustomed to
> so I ask you to bear with me. I will try my best to answer any
> questions that you do have but when it comes to questions about
> specific studies, I have not read all the studies in detail and,
> unfortunately, Dr. Hayes could not be here to present this
> presentation so I am standing in his place.
>
> I wanted to address the questions that were raised, and to address the
> first question\--it was a very fascinating debate to date and I think
> the debate really underlines the complication of trying to address
> this whole trans fatty acids issue. But we believe, based on the
> science that is out there, that trans fatty acids are considered more
> adverse with respect to coronary heart disease risk factors than
> saturated fat, particularly when you look at comparing comparable
> levels and higher levels of trans fatty acids in the diet. We think
> that that biological activity is something that this group needs to
> consider when addressing that question.
>
> With regard to question one, we also think that coronary heart disease
> risk factors can\--the data will show that it is appropriate to
> include or allow products that may not be low in total fat or low in
> saturated fat to be eligible for health claims regarding coronary
> heart disease, and a lot of what we are going to focus on today is
> some of the research that talks about the importance of balancing the
> fatty acids in the diet. When we are talking about the correct
> balance, the balance that we are talking about and the numbers you are
> going to see throughout the presentation is, first, the percent energy
> of saturated fatty acids, followed by percent energy of
> monounsaturated fatty acids, followed by percent energy of
> polyunsaturated fatty acids, and the correct balance that we are
> looking for is a balance in the relationship of 1:1:1.
>
> Let\'s first address the trans fatty acids issue. Here is a graph that
> was based on research out of [The New England Journal of
> Medicine]{.underline} that tried to quantify the risk associated with
> coronary heart disease with trans fatty acids. You can see they have
> 132 percent; saturated fats; monounsaturated fats; and poly
> unsaturated fatty acids. I am not going to spend a lot of time on
> this, I just thought it was relevant to illustrate the point that
> trans fatty acids can, in fact, have a very important role in CHD risk
> factors.
>
> I did, however, want to spend a little bit of time on a study by
> Sandram that evaluated trans fatty acids head-to-head with saturated
> fatty acids and compared the effect that trans fatty acids and
> saturated fatty acids have on the cholesterol profile. It also
> addresses one of the questions on this slide as well as other ones, of
> what happens when you substitute trans fatty acids and you replace
> them with saturated fatty acids. I would say it will depend in part on
> which saturated fatty acid is being replaced and what is the level of
> polyunsaturated fatty acids and monounsaturated fatty acids in that
> food.
>
> When you look at this particular slide you will see that the trans
> fatty acid had the worst impact on LDL and depressed the HDL. It also
> shows that different saturated fatty acids have different effects on
> cholesterol profiles. If you look at what we would pretty much
> categorize as the control here, when you look at a product that has a
> 1-carbon chain saturated fatty acid, if you look at the numbers here,
> they are the ratio of LDL to HDL. So, you can see that total
> cholesterol remains about the same. The ratio to LDL and HDL remains
> about the same as well.
>
> When you start looking at what happens with diets when you have a 12-
> and 14-carbon saturated fatty acid, you start to see a gradual
> decrease in the HDL and increase in the LDL. The ratio starts going
> up. Then when you look at the trans fat diet\--and I will note that
> this number is a diet that contained 7 percent trans fatty acids so it
> is a relatively high trans fatty acid diet but, certainly based on the
> nurses survey or the professional survey, a diet that could be typical
> for those on the higher end of the trans fatty acid consumption. Here
> you can see how the trans fats definitely are depressing the HDL and
> increasing the LDL level.
>
> In conclusion, when we look at the effect of trans fatty acids, as has
> been echoed by many of the people today, we really do believe that
> trans fats have been shown to be biochemically different and have a
> more adverse effect on coronary heart disease risk factors.
>
> I want to then look at the importance of balancing the fatty acids and
> considering the various ratios of saturated fat to polyunsaturated fat
> to monounsaturated fat. Here is a diet that looked at what happens
> when you start removing saturated fat from the diet. They did it in
> two steps. They removed 4.5 percent energy in the form of saturated
> fat at each step and then they evaluated what happened to the blood
> cholesterol profiles in these individuals.
>
> It shows that a progressive removal of saturated fatty acid does
> decrease LDL by 12 percent, but it also decreases HDL proportionately.
> So, what you end up with is you may have a decrease in total
> cholesterol as you increase the saturated fatty acid content but today
> it is important to focus on the HDL/LDL ratio. You can see that, yes,
> total cholesterol goes down but so does LDL and so does HDL, and the
> ratio of LDL to HDL remains relatively constant throughout those
> diets.
>
> With the fatty acid balance we can selectively lower the LDL but not
> the HDL which is, of course, a goal. We are trying to increase that
> ratio of HDL to LDL. Here is a study that shows that by balancing the
> ratio you can, in fact, have a positive effect on the coronary heart
> disease risk factors.
>
> Taking a look here, the regular fat diet, 37 percent energy, and here
> you see that 18 percent of the energy is from saturated fats whereas
> only 6 percent is from polyunsaturated fats. When you balance the
> ratio so we have 12:12:12 balanced saturated fat, monounsaturated fat
> and polyunsaturated fat, you can see a reduction in total cholesterol.
> The asterisk means it is statistically significant. A statistically
> significant reduction in LDL. HDL remains the same and, importantly,
> that HDL/LDL ratio improves.
>
> We believe that saturated fatty acids and polyunsaturated fatty acids
> are required for the best LDL/HDL ratio. Here is a study that
> evaluates three different fat blends in 23 young men with normal
> cholesterol. One was a balanced fat, one was a high monounsaturated
> fatty acid blend and one was a high saturated fatty acid blend with
> low polyunsaturated fatty acids. Although all three of these diets
> yield about the same total cholesterol, the balanced diet produced the
> highest HDL and the lowest LDL.
>
> Here you can see the balanced diet. It says the AHA because this is
> based on the former American Heart Association\'s step one
> recommendation. We are not exactly at 1:1:1 here but when you compare
> that to the other diets that are here you are certainly seeing that
> that is by far the most balanced of the diets, and the diet that has
> the best HDL to LDL ratio.
>
> Other research has pointed to the fact that fatty acid balance can
> actually be as critical or as important as the total amount of fat in
> the diet. Here is a study that evaluated the lipoprotein profiles in
> 22 nuns with mildly elevated total cholesterol. There were three
> dietary fat mixes for six weeks each were consumed. The three diets
> included a high level saturated fat with 42 percent energy, a high fat
> with a balanced polyunsaturated and saturated fatty acid ratio, and
> then we had a moderate fat diet, one that goes under 32 percent of
> energy from fat.
>
> What this study showed is that by balancing the polys and the
> saturated fats you can, in fact, improve the LDL/HDL ratio even in
> these relatively high fat diets. The study also shows that a moderate
> fat diet did not further improve total cholesterol.
>
> Once again, here is the high fat diet. When you go to the 42 percent
> energy, one that is balanced with the polys and the saturated fats
> that are 1:1 in the monos and saturated slightly higher, you can see a
> statistically significant improvement in the LDL/HDL ratio. Total
> cholesterol goes down. Interestingly, when we look at a moderate fat
> diet with 32 percent energy from fat, once again the polys and the
> saturated fats are balanced and you can see a very limited difference
> in terms of the cholesterol profile.
>
> The research conducted by Dr. Hayes and others, and these are just a
> few of the numerous studies that are out there, points to the fact
> that not all saturated fats are in fact the same. Typically, those
> saturated fatty acids in the 12- and 14-chain saturated fatty acids
> have a tendency to raise LDL the most. When you start looking a
> palmitic acid, which is the 16-carbon saturated fat, it has more of an
> intermediate effect and, when combined with a proper balance of
> polyunsaturated fats and monounsaturated fats, has been most
> successful in improving cholesterol profiles.
>
> This is a slide that Dr. Hayes asked that I put on and display before
> this group. It is new research, as of yet unpublished. The preliminary
> results have been made public but one of the points that Dr. Hayes
> wanted to make is that there is a need for trans fats and saturated
> fats in the food supply. It is important to have a solid fat when you
> are making various types of foods. As you move away from saturated
> fats, as you move to trans fats one of the things that people are
> starting to look into is the interesterification effect because it
> also allows you to have a solid fat at room temperature.
>
> Here is a study that just evaluated the biological effects of these
> various diets. Once again, it is an unpublished study but it did show
> that use of these interesterified fats started to show some adverse
> effects in terms of fasting blood glucose level. So, it was just
> something that we do think that the industry and the agency needs to
> be aware of because as we start looking for replacements for trans
> fats or saturated fats some of the alternatives may not necessarily
> put us in a better place than where the trans fats have us today. That
> would apply to some of the saturated fats as well.
>
> In conclusion, I think the data that we have presented here shows that
> the right type of saturated fats, when balanced with polyunsaturated
> and monounsaturated fats, can in fact improve the cholesterol profile.
> Because of that, we think it is important that when the agency is
> looking at coronary heart disease health claims that they should
> continue to allow for the use of CHD health claims on products that
> exceed the low fat definition.
>
> We also believe that flexibility is warranted for products that may
> exceed definition of low unsaturated fat because when products are
> formulated to have the correct balance of fact you can, in fact, have
> a powerful effect on the overall blood lipid profile.
>
> Finally, we believe that the data does show that trans fats have been
> shown to be more adverse with respect to coronary heart disease risk
> factors, particularly when compared to the palmitic acid saturated
> fatty acid.
>
> If there are any questions, I would be more than happy to try to
> answer them for you.
>
> DR. KRINSKY: Thank you very much for your presentation. Do we have
> questions? Alice?
>
> DR. LICHTENSTEIN: Yes, I have a question. Not all saturated fatty
> acids are created equal and their palmitic is intermediate relative to
> 12-0 and 14-0. I am just looking at a meta-analysis that was recently
> published and that doesn\'t seem to be consistent with the aggregate
> data and I was just wondering if you have any comments.
>
> MR. HAHN: Unfortunately, I cannot comment on that recent
> meta-analysis, sorry.
>
> MS. PELICAN: Could you tell us a little bit more about the study that
> is unpublished, by Sandram, in terms of number of subjects and sort of
> the makeup of those folks?
>
> DR. HAHN: I don\'t have any details in terms of the number of
> subjects. These are only the preliminary results and he is waiting
> until the study is published. When everything is finalized he will be
> able to get it published.
>
> DR. RIMM: Guy, do you know about any other studies that are similar to
> what he talked about with the interesterification causing adverse
> outcomes?
>
> DR. JOHNSON: No.
>
> DR. LICHTENSTEIN: There is one study that was published by Judd that
> did not make that observation with interesterified fatty acids. I am
> just wondering about that study that you mentioned, with Sandram, with
> the saturated relative to trans, their results were quite different
> than any others as far as the magnitude of the change. Although I
> guess you may not be the right person to ask, was there any
> explanation for that because from the data that we have on page 8-61,
> that is the one that showed the unusually large differential effect
> which is not consistent with any of the other data.
>
> MR. HAHN: That was 7 percent energy from trans fatty acids, if that is
> the study that you are referring to.
>
> DR. LICHTENSTEIN: Absolutely, but there are similar studies with 6, 8,
> 10 percent and you still didn\'t see that level of difference.
>
> MR. HAHN: When compared to diets with saturated fats?
>
> DR. LICHTENSTEIN: Yes.
>
> DR. KRINSKY: If there are no other question, thank you very much, Mr.
> Hahn.
>
> MR. HAHN: Thank you.
>
> We are in the process of trying to determine whether our third
> speaker, Dr. Enig, is out in the hallway waiting to come in. Since we
> don\'t know if she is here, if she is here, she has not made her
> appearance in this room, we will defer her presentation and we can
> continue with our discussion.
>
> **Subcommittee Discussion (Continued)**
>
> DR. KRINSKY: On trans versus sat, would anybody like to comment on
> whether we can determine these differences in the isolation of other
> dietary changes, if we change trans for saturated fatty acids. For
> example, Alice, in your studies, were those the only variable in the
> groups prior to the butter group?
>
> DR. LICHTENSTEIN: Yes. It turns out they were and the difference,
> though, was dictated by the products that were available. But it turns
> out that the monos were essentially the same. The sats were
> essentially the same except for the butter, so it was a poly-trans
> difference.
>
> DR. KRINSKY: In this study, although it is only one study, the change
> in the LDL cholesterol was not significant as you went up to what
> percent trans?
>
> DR. LICHTENSTEIN: It was at the lower levels. I think by 3 percent it
> was significant.
>
> DR. KRINSKY: By 3 percent.
>
> DR. LICHTENSTEIN: But certainly there was a trend there.
>
> DR. KRINSKY: So what we are left with with Question 3, I think one
> thing that I have used in the past is whenever things get sticky and
> tacky is maybe to divide the question and let\'s see whether we can\'t
> come up with some kind of division of this question so that we might
> be able to come up with a reasonable answer.
>
> DR. LICHTENSTEIN: I don\'t think we are necessarily disagreeing that
> they are not different. I think they are different. I think the only
> issue, perhaps, and maybe that oversteps the question, is whether, at
> the current levels of intake, they are different enough to make the
> distinction. That is really not what the question is. The question is
> do they have different biological effects or not. From my perspective,
> the data is yes; they do have different biological effects.
>
> DR. KRINSKY: But the question is not just different biological effects
> but adverse with respect to coronary heart disease.
>
> DR. LICHTENSTEIN: Using the data that is most prevalent which is
> lipoprotein levels, yes, because of differential effects on HDL
> cholesterol. Then the other potential effects, I think the data are
> scarcer and somewhat less consistent although\--and we are somewhat
> constrained because of the paucity of data.
>
> DR. KRINSKY: So a response to the question that trans fatty acids are
> more adverse\--that is, consumption of trans fatty acids are more
> adverse with respect to coronary heart disease would be a reasonable
> response to this question.
>
> DR. LICHTENSTEIN: Qualifying on the basis of the total-to-HDL ratio.
>
> DR. KRINSKY: The LDL-to-HDL ratio.
>
> DR. LICHTENSTEIN: Either LDL-to-HDL or total-to-HDL.
>
> DR. KRINSKY: Okay. We do have Dr. Enig here.
>
> Would you be prepared to speak now, or would you like a moment?
>
> So we seem to be moving towards agreement at some level with respect
> to this question, with the adverse effect of trans versus saturated
> fatty acid. Then we come into the fact that just that statement, by
> itself, is not going to be the most useful statement for the public
> interest. I think that we would should not neglect the fact that we
> are an advisory committee to the FDA and the FDA is really responsible
> to the public.
>
> So would you like to comment on that, Guy?
>
> DR. JOHNSON: I was going to clarify what the consensus that was
> emerging is, and that is that trans fatty acids do have a different
> effect than saturated fats based on the big caveat that the HDL fact
> is taken into account. That means at higher levels. That is where, I
> think, we are struggling, is kind of where is the dividing line and is
> that significant from a public-health perspective based on current
> intake levels.
>
> DR. KRINSKY: Anybody have a level that they would like to propose?
> Does anybody have the temerity to say 2 grams per day about that would
> be adverse?
>
> DR. JOHNSON: See, I just don\'t think we have the data to do that. You
> can look at this HDL stuff and say it is 6 percent. You can say, well,
> one molecule is undesirable. So it is just kind of looking at the
> limited data we have and reacting with our own perspectives, I think.
> That is the problem.
>
> I guess if you had a nice randomized, double-blind, placebo-controlled
> trial for every answer, you wouldn\'t need committees like this. I
> think that is where we are at.
>
> DR. KRINSKY: We need a committee to verify that the data that was
> being presented was, in fact, valid data. but we may have an
> opportunity to hear a little bit more.
>
> I would like to introduce Dr. Mary Enig. Dr. Enig is the Vice
> President and Science Advisor of the Weston A. Price Foundation. She
> is going to talk to us about the second and third questions, n the
> level of trans fat in the diet and the health effect of trans fat on
> risk levels of coronary heart disease.
>
> **Public Comment** **(Continued)**
>
> Do you have a Powerpoint presentation?
>
> DR. ENIG: No, I didn\'t bring one because, given ten minutes, there
> was hardly very much that you can put into a Powerpoint presentation.
>
> DR. KRINSKY: Oh; you can actually get much more in than talking. You
> can have your slide in a very minute font and really present an
> immense amount of material. But we are grateful that you have not
> tried to do that.
>
> DR. ENIG: I remember very distinctly that Dave Kritchevsky indicated
> that he didn\'t bring any slides to the Cholesterol Consensus
> Conference because, if he did, he wouldn\'t have enough time to even
> say what he wanted to say. So\--
>
> DR. KRINSKY: May I interrupt you for a moment, Dr. Enig. I read a
> disclaimer about your financial relationship to the Foundation and to
> sponsors, but have you presented before the FDA?
>
> DR. ENIG: Yes; I have.
>
> DR. KRINSKY: So you have had this disclaimer read to you?
>
> This is not a new disclaimer, is it?
>
> MS. LATHAM: It is relatively new.
>
> DR. KRINSKY: I am going to give you the privilege of listening to this
> before you start your talk.
>
> DR. ENIG: Sure.
>
> DR. KRINSKY: Both the Food and Drug Administration and the Public
> believe in a transparent process for an information-gathering decision
> making. To ensure such transparency at the Open Public Hearing session
> of the advisory committee, FDA believes that it is important to
> understand the context of an individual\'s presentation.
>
> For this reason, FDA encourages you, the Open Public Hearing
> speaker\--that is a general \"you.\" I am not directing this
> specifically at you\--the Open Public Hearing speaker, at the
> beginning of your written or oral statement, to advise the committee
> of any financial relationship that you may have with the sponsor, its
> product and, if known, its direct competitors.
>
> For example, this financial information may include the sponsor\'s
> payment of your travel, lodging or other expenses in connection with
> your attendance at the meeting. Likewise, FDA encourages you at the
> beginning of your statement to advise the committee if you do not have
> any such financial relationships. If you choose not to address this
> issue of financial relationships at the beginning of your statement,
> it will not preclude you from speaking.
>
> So you are free to speak to us.
>
> DR. ENIG: My response to that is that I am a member of Weston A. Price
> Foundation, a volunteer member. It is, I guess you could call it,
> like, a volunteer organization. I am the science advisor because I am
> one of the few people who actually happens to have the type of
> scientific training that is needed by the organization to be able to
> make sure that the information that we are putting out for the public
> is accurate.
>
> My expertise happens to come from many years of being at the
> University of Maryland in the Lipid Research Group working on trans
> fatty acids, saturated fatty acids, other types of lipids. Since I
> left the University of Maryland, which was in the 1990s, I have
> followed the literature extremely closely. I have gone to meetings
> even though I, myself, have been the one that sponsored the expense.
>
> I just went to the Trans Fatty Acid meeting in the Chicago area in
> February that was put on by the American Oil Chem Society. I sponsored
> myself, I guess you could say. At that time, I noticed that there was
> an awful lot of spinning being done, that the information that was
> being put together, some of it extremely interesting, was either
> incomplete or else it was just with a little spin here and a little
> spin there, and that included the amounts of trans that are actually
> in the diet.
>
> I happen to know from my contacts with the people in Canada, that the
> amounts that I predicted as probably being in the diet were exactly
> the same as the amounts that they ended up predicting that some of my
> colleagues at the University of Maryland also came up with the same
> amounts in the diet that the people in Canada did.
>
> You don\'t have a lot of trans fatty acids in the diet of a
> formula-fed infant. You may have a tremendous amount of trans fatty
> acids in the diet of a nursed infant if the mother takes in 30 grams
> of trans, as the Canadians found she did. They ended up discovering,
> both in Canada, research from Sheila Innis, and in research in Holland
> with Hornstra, that these infants, as they had more trans in their
> diets, ended up with visual-acuity problems.
>
> So, as we have gone from the 1970s, when I first became concerned and
> interested and first reported to the FDA that there were potential
> problems with the trans fatty acids, we have ended up seeing not only
> that there definitely is an effect, if you want to consider an
> increase in LDL as an effect on the heart-disease issues or a decrease
> in HDL, an increase in lipoprotein (a); in other words, all of the
> things that the clinicians say are not good the trans fatty acids
> cause.
>
> When you look at the research, you also discover that the saturated
> fats do exactly the opposite. So I have been following this in the
> literature. We will have a couple of people following things at the
> University of Maryland and I have, as I said, been in touch with
> people in Canada and, to a certain extent, also in Europe. Gradually,
> more and more of the health problems that we didn\'t even predict have
> cropped up.
>
> One particular one, Europe has discovered and reported, and I think
> there has been some reporting in this country, that you see asthma
> increasing from the trans fatty acids in children.
>
> Well, that is not surprising because the children who are consuming
> partially hydrogenated vegetable fats in their crackers and cookies
> are probably not getting enough of the carbohydrates to make their own
> saturates and they are not getting enough saturates in the foods that
> they are eating because they have been replaced by the trans. They
> need saturates in their lungs for lung surfactant. I think Alice and I
> had a discussion on that a couple of years ago, as a matter of fact,
> at the American Heart Association meeting.
>
> So the trans are very definitely a problem and the amounts that were
> taken in can range anywhere from, I guess, 2 grams for people who are
> not taking in very much to 40 grams. In Canada, they have verified
> this. In Scotland, they have verified this. At the University of
> Maryland, we verified this.
>
> I actually had a student that I was teaching who had to put down all
> of what he ate and then do the calculations, come up with over 100
> grams of trans fatty acids. So I have no difficulty thinking that
> there are a lot of diets out there that have a large amount of trans
> fatty acids.
>
> My own personal feeling is that, except for the ruminant trans, which
> are a totally different type of fatty acid, react differently in the
> body, and that research has been done and the committee had a note
> from Dr. Kummerow to make sure that that was kept separate. Except of
> that, my feeling is 0 is the amount because we have no need for trans
> fatty acids in our tissues. We have no need for trans fatty acids in
> our phospholipids. We have no need for trans fatty acids in our lungs.
>
> We have gotten along very well without the trans fatty acids for many
> years. The only people who didn\'t get along very well without the
> trans fatty acids were the industry because they had more expense with
> the more saturated animal fats. So, as far as I am concerned, we can
> have a 0 on that. But then, of course, you can\'t do some of your
> menu-modeling if you have got 0.
>
> Now, with respect to the saturates, I was around when the
> anti-saturate agenda started. I think that almost all of the
> researchers who say that saturates are bad have never read the
> original literature. They just simply don\'t know who did what, who
> pulled what. I happen to have known, for quite a long time, and I just
> recently started to see some of the research coming out where, in
> fact, the saturates were showing up good.
>
> But the people who were writing the papers sort of tucked that under
> the bottom of some of the tables and graphs and so forth. There are
> three papers that came out from\--it is Dreon, et al., so that is
> Krauss\'s group out in California\--where they lowered the total
> amount of fat in the diet in their cohort that they were studying.
> What did they end up getting? They ended up getting things going the
> wrong direction.
>
> They ended up with the LDL going from the light and fluffly LDL that
> everybody has now decided is okay and they are not quite sure what
> they are going to do with reporting it to the public, and they got an
> increase in the small, dense LDL. Then they did the same thing with
> saturated fat. They lowered the saturated fat and they also got the
> wrong kind of a response.
>
> Then they looked at some of the children of the people that they were
> studying and they discovered, in fact, that the children who should
> have been like the (a) type became a (b) type, who should have been
> like the (b) type became an (a) type. So, removing saturated fatty
> acids from somebody\'s diet does not do something good.
>
> DR. KRINSKY: You have about one more minute of your time.
>
> DR. ENIG: I had sort of prepared just three comments to the three
> questions. I think I have actually more or less covered them. What I
> wanted to say was basically that the current scientific evidence
> indicates that the idea of lowering total unsaturated fat is going to
> be counterproductive in the long term because there are enough people
> like myself and others, and especially in Europe, who are very, very
> much aware of this.
>
> Then, the scientific evidence supports a level below 1 percent of the
> energy, although I said, of course, 0, for the commercially produced
> trans fatty acids. But, as pointed out by others, Dr. Kummerow today,
> this should not apply to ruminant trans fatty acids.
>
> Then, the third thing was a comment that, compared to saturated fatty
> acids, which have no adverse effects with respect to coronary heart
> disease, the commercially produced trans fatty acids are more adverse
> in their effects and ruminant trans are not a problem.
>
> I will be happy to take any questions.
>
> DR. KRINSKY: Thank you very much, Dr. Enig. Do we have some questions
> for Dr. Enig, please?
>
> DR. RIMM: I am not sure, at the beginning, did you mean to imply that
> our estimates, our food-composition estimates of trans fatty acids
> greatly underestimate what we are really eating? Before you came in,
> we had discussed that, on average, in this country, or at least five
> years ago, consumed 2.6 percent of energy from trans. Do you think
> that is a dramatic underestimate based on our food-composition tables?
>
> DR. ENIG: I think it is because if you go in and take a look at how
> much an infant is taking in, or a child is taking in, and do the
> weighted average of some things of that sort, you will get a totally
> different amount. The amounts that people come up with when they start
> doing the types of analysis depend on what they want to find as an
> answer.
>
> I spent years, literally starting in the late \'70\'s, having this
> happen to my work from what the industry wanted reported. All I can
> tell you is, right now, today, after having provided some information
> to people in Europe, didn\'t tell them how they should think, didn\'t
> tell them what they should do, but I gave them the type of information
> that they wouldn\'t have otherwise had access to and they could run
> with that.
>
> Denmark has said, \"It is going to go out of our food supply and
> anybody that puts it in,\" this is the commercial trans,\" is going to
> go to jail.
>
> DR. RIMM: What have they done instead? In Denmark, what have they done
> instead to create foods that need to have solid components?
>
> DR. ENIG: They have replaced the partially hydrogenated vegetable fats
> with the normal saturated animal and tropical-oils fats; in other
> words, there exists in the world, and have existed in the world since
> the beginning of who knows how long, certainly the beginning of this
> century, adequate amounts of these types of fats, and we never had any
> of the problems that we have been having when they were being used.
>
> DR. SHANNON: Dr. Enig, is it your position that all saturated fats are
> appropriate in the diet and that we should not be concerned with
> reducing saturated fats of any kind?
>
> DR. ENIG: Basically, that is what my position is. If you are talking
> about palmitic acid, palmitic acid is very essential, dipalmitoyl(?)
> phosphotidalcholine is what the lung surfactant is. Palmitic acid is
> absolutely essential for growth in infants and children. Myristic acid
> is what the body uses to do what is called myristilation(?); in other
> words, it attaches myristic acid to a type of protein, protein
> molecule, and that is used as a messenger type of protein.
>
> You really don\'t very much in the way of myristic acid until you have
> animal fats in the diet. It is almost nonexistent the vegetable fats.
> Lauric acid, which the body needs, used to get small amounts of it on
> a regular basis, is made by the mammary gland because infants need it
> for their development. You can get it in coconut oil or palm-kernel
> oil, and you can get some of it in milk fat. But you don\'t get it in
> any of the other vegetable oils although there were some attempts to
> make, to grow, a vegetable oil that would have it because the company
> recognized that it was something that was going to be a product down
> the road to be making money from. And then they ran into trouble
> growing it.
>
> Stearic acid, everybody who has been anti-saturate for as long as I
> can remember, is something that everybody says, oh; well stearic acid
> is not a problem. Stearic acid is found in very small amounts in most
> fats and oils except cocoa butter and some of the animal fats.
>
> DR. KRINSKY: Dr. Baker?
>
> DR. BAKER: Thank you so much for mentioning children. I have been
> waiting to hear their name brought up and I actually had some
> comments. What I really like, in your handout, do you have references,
> or will you share with us the calculations that you have done on their
> intake and outcomes that you know about? I would really love to see
> that.
>
> DR. ENIG: I have a paper from 1990 published in the Journal of the
> American College of Nutrition.
>
> DR. BAKER: On trans fats?
>
> DR. ENIG: On trans fat, and so forth. I had another one that was
> published in Cereal Foods World.
>
> DR. BAKER: Okay. Is that part of your handout? Do you reference it? We
> could find it.
>
> DR. ENIG: I don\'t know if it is in the references that we put
> together, the ones that I put together. No; I don\'t have that, but I
> can certainly, if you want me to put together that particular
> information, I can certainly do that and\--
>
> DR. BAKER: Just the references. Thank you so much.
>
> DR. KRINSKY: Any other questions? If not, thank you very much, Dr.
> Enig.
>
> DR. ENIG: My pleasure.
>
> **Committee Discussion (Continued)**
>
> DR. KRINSKY: We return to our committee discussion. We are on Question
> 3. We are dealing with a quantitative issue that may be irresolvable
> unless we go to nonquantitative terms like big and little, unless
> somebody can help me. Can we get anything semi-quantitative,
> qualitative\--qualitative we can talk about the fact that trans fatty
> acids can increase the risk of coronary heart disease and are
> detrimental. But how much?
>
> Do you know how much Eric?
>
> DR. RIMM: I think we actually all did sort of agree that trans fat can
> be more detrimental than saturated fatty acid. The only issue is that
> Guy had the caveat that it has to be at high enough intake.
>
> But the answer to the question is, is trans more adverse than
> saturated fat. The answer to that would be Yes. There are caveats for
> everything we are going to discuss here, and I am sure there\'s
> caveats for everything that is currently on the Nutrition Facts label.
> But, based on what we discussed and based on the published evidence,
> it would suggest that it is more detrimental.
>
> DR. KRINSKY: Does anybody feel an obligation to come up with when does
> it become more detrimental? At what level of intake does it become
> more detrimental or is it more detrimental at all levels of intake.
>
> DR. MAYNE: It seems to me that it is a continuum, so I would be more
> comfortable saying something to the effect that saturated fatty acids
> are considered to be more adverse\--I\'m sorry; trans fatty acids are
> considered to be more adverse when compared to saturated fatty acids
> with respect to coronary heart disease, and then say this is
> particularly true in looking at LDL, HDL ratios as the outcome of the
> interest and the difference is more noted, or more magnified as intake
> levels increase.
>
> I think we are all in agreement with that because it is a continuum
> and I am not really comfortable setting thresholds because the data
> doesn\'t look like a threshold to me.
>
> DR. HINE: To further muddy the waters, I raise the question of
> duration of exposure because, as pointed out by Susan Baker, the issue
> of children who are now exposed to a lot more trans fatty acids than
> many of this in this room have been exposed to. I think that is an
> important scientific question as well.
>
> DR. RIMM: I will third that motion. I think, in addition to being
> concerned about trans in children, I think that when we looked at our
> nurses\' data and you looked at trans intake at baseline, at estimated
> baseline, we found some increased risk of coronary disease. But, if
> you updated their diets every four years so you had a better, tighter
> estimate, you got a stronger relative risk which suggests that there
> probably is a long-term effect that becomes to accumulate that maybe
> you can\'t capture in a four-week metabolic-ward study.
>
> DR. JOHNSON: I am not sure, based on the data that we have, I can buy
> the continuum conclusion since there just aren\'t any datapoints at
> levels around the mean intake or below, other than 1. So it is
> anybody\'s guess as to what is going on there. We don\'t know whether
> there is a threshold or not. The HDL data would suggest that there is
> but it is not at the level where we really are interested. So we just
> don\'t have the data, I don\'t think.
>
> DR. MAYNE: Can I respond to that? Susan Mayne. True. Clearly, we are
> lacking datapoints. We all agree on that. But I think the more
> conservative estimate is to assume a linear relationship. I think it
> would be erroneous to assume a less conservative relationship, given
> the lack of data. So, given that we are trying to protect the
> consumer, I am much more comfortable assuming a linear relationship
> based on a lack of data than assuming a threshold when there is really
> no evidence.
>
> In my view of that data, there is no evidence for a threshold effect
> there.
>
> DR. JOHNSON: Then we get into sort of a philosophical thing and maybe
> it comes a consumer research issue because it is a conservative
> estimate. Maybe your position is conservative under the assumption
> that we should alert consumers to potential increased adverse effects
> for trans fatty acids, regardless of whether there is a threshold or
> not, on the assumption that that is going to help them make the
> appropriate changes in their diet.
>
> However, we are doing a disservice by making that point. We are giving
> people an unrealistic perspective on trans fatty acids and, perhaps,
> encourage them, unwittingly, perhaps, to focus on trans rather than
> saturated. We all know that saturated fats are present in the diet at
> much higher levels and we don\'t want them to make trade-offs based on
> what could be a false distinction between the two at the levels where
> people really are now.
>
> That wasn\'t very articulate, but I think you know what I am trying to
> say.
>
> DR. KRINSKY: Would there be any damage if somebody moved from a 2
> percent intake of trans fatty acid to 1 percent with the substitution
> of a saturated fatty acid?
>
> DR. LICHTENSTEIN: Unlikely.
>
> DR. KRINSKY: Unlikely?
>
> DR. LICHTENSTEIN: Or, no.
>
> DR. KRINSKY: So we don\'t have any threshold data. That is for sure.
> The linear data, certainly it looks linear from the Ascherio plot that
> we had presented to us. And, if that is the case\--well, let me back
> off for a second. Can you present an argument that there may be a
> threshold because I would assume that we either have a linear response
> or a threshold response. Do we have any indication whatsoever that
> there is a threshold that, below a certain level, there is no effect.
>
> Now, I know that is dangerous because the ability to measure these
> effects get more and more constrained as you go to lower and lower
> levels.
>
> DR. LICHTENSTEIN: That is what the IOM committee came\--the decision
> they came to is that, because there is no advantage to consumer trans
> fatty acids, you can\'t come up with any sort of lower limit because
> the lower you go, it appears, the better off you are.
>
> DR. KRINSKY: I know that Guy is concerned about the educational
> aspect, or the information aspect, of transmitting that to the public,
> that the lower you go in trans fatty acid, the better off you are
> going to be, and how that will be resolved in terms of dietary
> selections as they look at the nutrition label.
>
> DR. LICHTENSTEIN: I mean, that is something that I brought up at the
> beginning. I don\'t want to really repeat a lot, but the issue becomes
> how do you communicate it to the consumer. From my perspective, what
> you want to communicate is that you would minimize your intake of
> trans and saturated fatty acids. You need to do that in the most
> direct way possible.
>
> If you communicate to them that you have got to keep track and balance
> your sats and trans, I don\'t know what they are going to do with
> that. I mean, that is what we need consumer, I guess, research for.
> But I tend to be minimalist when it comes to communicating
> information.
>
> DR. JOHNSON: Can I respond to your question about is there any
> evidence for a threshold. I feel like I am beating a dead horse and
> forgive me if I am, but you could answer that question yes, if you
> take studies, as my friend did, in the Ascherio plot and, instead of
> plotting the percent intake, energy intake, of trans and saturated
> fats versus the ratio of LDL to HDL, you tease those out, and you
> simply look in the papers and see which changes in the trans group
> compared to the control group were significant, statistically
> significant.
>
> He is not doing any statistical smoke in mirrors here. He is just
> saying, was it significant or not. And, when you put points on that
> dot, you see that the studies below the current mean intake of trans
> fats did not raise LDL statistically significantly. Maybe we don\'t
> know if that is biologically significant or not, but statistically,
> they didn\'t. If you look at the changes in HDL, there were none of
> the studies up until over 4 percent of energy and then only one was
> statistically significant when they looked at trans diets versus the
> control diet with respect to HDL.
>
> So it looks like there is a threshold there.
>
> Then, and I apologize to Eric again, but you look at the epi studies
> and they all\--maybe this isn\'t fair, but they all show
> nonsignificant relative risks until you get to the upper quintile.
> Now, maybe that is unfair and maybe not, and I understand how you are
> unlikely to get a nice quantitative dose response in each one of those
> quintiles, but the fact of the matter is, they weren\'t significant.
>
> You can assume that there is a trend there, but it is an assumption.
> So I am coming back to the fact that there is some evidence for a
> threshold if we are looking for that. Is it iron-clad? No; but there
> is some evidence that certainly injects some doubt into the conclusion
> that there isn\'t.
>
> MS. PELICAN: Pelican. Guy, just to follow up on that. If you were to,
> assuming that you have said that you think there is a threshold, what
> would you suggest if the threshold could lend itself to a D.V.; what
> would you see that D.V. being?
>
> DR. JOHNSON: I am not comfortable coming up with a number. The IOM
> couldn\'t come up with a number. I am certainly not going to do one.
> If you look at the HDL data, you would say 5 to 6 percent. But I am
> not going to say that there is enough data to put that on the
> Nutrition Facts panel as a daily value.
>
> That decision is a profound one that is going to have to be defended.
> I just think we need a more thorough assessment of all this. Maybe we
> need new data. I just don\'t think we are at the point where we can
> bet on the outcome with the Nutrition Facts panel.
>
> DR. KRINSKY: Eric, can you respond, again, to the quintilization of
> the data for the epidemiological surveys?
>
> DR. RIMM: Yes. I mean, we are sort of getting down to
> mincing\--fighting over small words here. I think the fact of the
> matter is that Guy agrees with Question 3, that trans fat is worse
> than saturated fat. Now, he may think there is a threshold or maybe
> there are other subtle things in there, but, the fact of the matter is
> I think everybody agrees that trans fat is worse than saturated fat.
>
> Dr. Enig has done some of the premiere research on this area and
> thinks it should be 0 percent from hydrogenated oils. Maybe some of us
> think that. Obviously, there is going to be some cutoff above that if
> there is any cutoff at all.
>
> But, again, no single study, I think, should be used to summarize the
> data, no single metabolic study, no single observational
> epidemiological study should be used. But if you take the four or five
> large observational studies on trans fatty acid and coronary heart
> disease\--that is not just from here. It is from Costa Rica. It is
> from the Netherlands as well as several from the U.S. and
> Finland\--and plot them, rather than just doing it be quintiles, if
> you actually plotted by the median of each quintile so the fifth
> quintile would end up being further out because of the fact there is a
> much wider range in that highest quintile, and draw a line, you are
> not too far off. You are not exaggerating too far off to say that
> there is a linear association as you go up with intake.
>
> I don\'t think anybody would be surprised that the second quintile is
> significantly different than the first quintile. The studies aren\'t
> powered to do that. There are not enough cases to do that. You would
> need to have 3 million people to follow for a long time.
>
> So that is why we use an estimate dose response and to a test for
> trend rather than counting on each quintile being significant
> different from the first. So I think that if each one of the studies
> had found the relative risk of 1, 1, 1, 1, 1 and 1.7 in the highest
> quintile, we would be concerned. But, in fact, that is not what we see
> for the dietary data and that is not what we see for the data where
> trans fatty acids are isolated from adipose.
>
> I think, if you were to say, I am definitely sure about one, no one
> would say that. I am definitely sure that there is a threshold. No one
> would say that. But I think the evidence would support that there is
> more of a dose response. I think there is more evidence to support
> there is a dose response than there is evidence to support there is a
> threshold.
>
> DR. KRINSKY: We all have the opportunity to express our opinions. As a
> matter of fact, one policy that the FDA\--some of the advisory
> committees have done\--I don\'t know whether, in fact, we are
> obligated to, is that when the time comes for voting, the members have
> to tell why they say yes or no so that there is some support in the
> record of the position that the individual members of committee take.
>
> But I am not sure that, at this time\--no; I am sure. At this time, I
> think, in fact, we can take a vote on Question 3 as it is formulated
> to us. That formulation is, as we all have in front of us, when
> compared to saturated fatty acids, are trans fatty acids considered to
> be more, less or similarly adverse with respect to coronary heart
> disease.
>
> I will start out by asking for a show of hands for those that feel
> that trans fatty acids are more adverse.
>
> (Show of hands.)
>
> Thank you. Trans fatty acids are less adverse?
>
> (No response.)
>
> And trans fatty acids are similarly adverse.
>
> (No response.)
>
> Guy you don\'t like the question?
>
> DR. JOHNSON: I am not allowed to vote.
>
> DR. KRINSKY: Oh; sorry. Look what I just gave you, the opportunity.
>
> Well, with that momentous vote, I think that it is, in fact, time to
> adjourn our meeting until tomorrow morning where we will have an
> opportunity to go back to Question 2 and even vote on Question 1 which
> we didn\'t vote on.
>
> I just want to remind the committee that the meeting tomorrow
> meeting\--the official meeting will begin at 8:00 in the Monet Room.
> The Monet Room is up on the second floor.
>
> DR. LICHTENSTEIN: Can I just ask the Chair a question?
>
> DR. KRINSKY: You certainly may.
>
> DR. LICHTENSTEIN: Why don\'t we vote on Question 1 since the
> discussion is sort of fresh in our heads? Is there a reason for
> waiting until tomorrow for Question 1?
>
> DR. KRINSKY: No. Do you feel that we are prepared to vote on Question
> 1? Yes; as a matter of fact, considering the discussion, what does the
> current evidence suggest\--okay. The question is, what does the
> current evidence suggest in terms of total fat intake and risk of
> coronary heart disease.
>
> That is not a yes or no. So I think the question will have to be
> rephrased to give it a yes or no answer. That is going to be done by
> the Chair and the Exec Secretary between now and 8:00 tomorrow
> morning. At 8:00 tomorrow morning, this committee reconvenes in the
> Monet Room. But, prior to that, from 7:15 to 8:00 a.m., you will be
> eligible to receive a continental breakfast in the Montcalm Room.
>
> I hope to see all of you before 8:00 eating our high trans foods in
> the Montcalm Room.
>
> Thank you all for your attendance and thank you all for your patience.
>
> (Whereupon, at 6:00 p.m., the meeting was recessed, to resume on April
> 28, 2004, at 8:00 a.m.)