From: Jaffe, Lyle D
Sent: Tuesday, December 07, 2004 8:30 AM
To: Dockets, FDA
Subject: FW: The aspartame urban legend

-----Original Message-----
From: becky [mailto:becky@thefoodsyndicate.com]
Sent: Tuesday, December 07, 2004 8:19 AM
To: Bettym19@mindspring.com
Cc: inforeply@cdc.gov; RXH@CFSAN.FDA.GOV; DHATTAN@CFSAN.FDA.GOV;
LJAFFE@OC.FDA.GOV; randy.gordon@hs.utc.com
Subject: The aspartame urban legend

Dear Ms. Martini, 

I did research, and I draw conclusions different from yours. Below is small 
amount of the data I have read, which contains information both pro and con 
regarding aspartame. One of the articles is by Ellen Guthrie of Multiple 
Sclerosis Focus. Since you are so vehement about aspartame causing multiple 
sclerosis, I especially wanted to check out that claim because my brother, 
mother and both of my grandmothers had MS. 

My conclusion is that the data you cite, and that you have on your Web site, 
is not as convincing as the case for the safety of aspartame for the general 
public. I do not doubt that some people have problems with it, just like 
some people can't eat peanuts or shellfish without experiencing adverse 
reactions. 

I also have reservations about some of the medical doctors you cite. They 
have their own agendas, such as selling books, wholistic medicines and 
related products. You are doing a great job creating a hysteria and fear 
that drives people to buy their products and services. 

Just because you say something louder and longer doesn't make it true. 

This is the last e-mail I will send you personally. Do not send me any more 
e-mails or any other form of communication, because if you do I will 
consider it harrassment. 

Becky Billingsley
The Food Syndicate
www.TheFoodSyndicate.com
Food is Fun! 

20 Apache Trail
Myrtle Beach, SC 29588
843-293-1501 

British Medical Journal Editorial Concludes Aspartame Criticisms Are 
Unfounded (October 2, 2004)
Editorial
Aspartame and its effects on health
The sweetener has been demonised unfairly in sections of the press and 
several websites
The European population of 375 million consumes about 2000 tonnes annually 
of aspartame (NutraSweet, Canderel) an artificial sweetener, which contains 
two amino acidsaspartic acid and phenylalanine.1 It is 180-200 times 
sweeter than sucrose, and almost half a million extra tonnes of sugar would 
therefore be needed to generate the same sweetness. Was the world screaming 
for all this sweetness, and what has it done to us? Anyone searching the web 
on aspartame, launched in 1981 by Monsanto, the manufacturer of NutraSweet, 
will find a vast catalogue of frightening personal accounts attributing 
multiple health disasters to exposure to aspartame.1 Although no 
orchestrated public outcry about aspartame has taken place, much 
sensationalist journalism has been published mostly on websites (for 
example, www.holisticmed.com/aspartame/). In contrast, aspartame marketing 
implies that it embodies a healthy way of life and avoids obesity. Are these 
claims of hazards and benefits supported by evidence?
Evidence does not support links between aspartame and cancer, hair loss, 
depression, dementia, behavioural disturbances, or any of the other 
conditions appearing in websites. Agencies such as the Food Standards 
Agency, European Food Standards Authority, and the Food and Drug 
Administration have a duty to monitor relations between foodstuffs and 
health and to commission research when reasonable doubt emerges. Aspartame's 
safety was convincing to the European Scientific Committee on Food in 1988,2 
but proving negatives is difficult, and it is even harder to persuade vocal 
sectors of the public whose opinions are fuelled more by anecdote than by 
evidence. The Food Standards Agency takes public concerns very seriously and 
thus pressed the European Scientific Committee on Food to conduct a further 
review, encompassing over 500 reports, in 2002. It concluded from 
biochemical, clinical, and behavioural research that the acceptable daily 
intake of 40 mg/kg/day of aspartame remained entirely safeexcept for people 
with phenylketonuria.3
Does aspartame embody a healthy way of life and avoid obesity? In most 
Western countries sugar provides around 10% of total calories (about 200 
kcal (837 kJ), or 50 g daily). If this were entirely replaced by a 
non-nutritive, non-caloric sweetener such as aspartame then obesity could 
indeed be vanquishedassuming these calories are not replaced due to 
stimulation of appetite. We eat about 5 g aspartame annually, equivalent to 
another kg of sucrose, whose 4000 kcal (16 740 kJ) could generate 0.5 kg 
gain in weight. But evidence that aspartame prevents weight gain or obesity 
is generally inconclusive,4 5 although in children, the consumption of sugar 
sweetened soft drinks relates notably to increasing obesity, whereas 
increasing "diet" drinks or fruit juice is inversely related to weight 
gain.6
Dietary recommendations for the management of diabetes conclude that up to 
10% of total energy can safely come from sugars but that artificial 
sweeteners may help avoid weight gain.7 8 When sugar is consumed as a 
sweetener it is chemically identical with the sugar found in fruits, which 
we are promoting keenly, and its metabolic effects are no different if 
consumed in reasonable amounts even by people with diabetes.8 Most evidence 
points to fat as the main dietary culprit in obesity, and one 
counterargument to the use of artificial sweetener instead of sugar includes 
evidence that high sugar diets tend to be lower in fat.9 Displacing 
saturated fat would offer particular advantages by reducing risk of heart 
disease.10 Carried to extremes, large amounts of sucrose will increase 
triglycerides, a key component of the metabolic syndrome, and turn the 
tables back towards promoting heart disease. Its fructose component is 
responsible for this hazard.11
Artificial sweeteners are promoted to prevent dental caries, as sugars form 
the main substrate for mouth bacteria. However, avoiding sugar does not 
reduce dental caries dramatically in regions with high levels of caries.3 
The dominant factors are fluoride deficiency and prolonged exposure to sugar 
between meals. If children consume sweetened drinks between meals or suck on 
sweet foods, resulting in prolonged periods of exposure to sugar, then 
replacing the sugar with artificial sweeteners in such products has some 
rationale. Children exposed to heavily sweetened foods develop a "sweet 
palate," but those who take the plunge and take unsweetened drinks may 
prefer them, which seems a better solution.12
Why has aspartame been demonised by the world's press and countless 
websites? Monsanto was in the public eye, accused of enthusiastic 
dissemination of genetically modified plants and foods. People resent 
interference with foods, and synthetic food components are regarded with 
suspicion. However, aspartame comprises just two amino acids (aspartic acid 
and phenylalanine). Could this present a risk? Phenylalanine is a natural 
amino acid, and is toxic only in patients who have phenylketonuria.
Food labelling of sweetener is contentious. Six artificial sweeteners are 
permitted in Europe, each with an acceptable daily intake. Consumers cannot 
be expected to calculate cumulative daily intakes of each. Instead, 
manufacturers are encouraged to use cocktails of sweeteners so it becomes 
difficult for anyone to reach the acceptable daily intake of any sweetener 
individuallyadults need at least 10 cans of a drink fully sweetened with 
aspartame alone to reach the acceptable daily intake of 40 mg/kg/day. When 
using combinations of sweeteners, even high level consumers rarely exceed 10 
mg/day. Intakes over 1g/day were needed to alter brain neurotransmitters and 
provoke seizures in monkeys, and randomised controlled trials of high doses 
in humans have not shown any behavioural or other effects.13 14 The cynical 
conclusion is that there is probably too much sweetness and never enough 
light, and the public probably needs protection against misleading websites.
Michael E J Lean, professor
Division of Developmental Medicine, University of Glasgow, Royal Infirmary, 
Queen Elizabeth Building, Glasgow G31 2ER, (mcmn1h@clinmed.gla.ac.uk )
Catherine R Hankey, lecturer, University Department of Human Nutrition
Division of Developmental Medicine, University of Glasgow, Royal Infirmary, 
Queen Elizabeth Building, Glasgow G31 2ER 

Competing interests: None declared.
References
1.	Aspartame Information Center. www.aspartame.org/ (accessed 28 Jul 2004).
2.	European Commission. Health and Consumer Protection Directorate-General, 
Scientific Committee on Food. Opinion of the scientific committee on food: 
update on the safety of aspartame. SCF, 10 December 2002. 
http://europa.eu.int/comm/food/fs/sc/scf/index_en.html (accessed 17 May 
2004).
3.	Navia JM. Carbohydrates and dental health. Amer J Clin Nutr 1994;59: 
719-27.
4.	Tordoff MG, Alleva AM. Effect of drinking soda sweetened with aspartame 
or high fructose corn syrup on food intake and body weight. Amer J Clin Nutr 
1990;51: 963-9.[Abstract]
5.	Drewnowski A. Review: intense sweeteners and energy density of foods: 
implications for weight control. Eur J Clin Nutr 1999;53: 
757-63.[CrossRef][ISI][Medline]
6.	Ludwig DS, Peterson, Gortmaker SL. Relation between consumption of sugar 
sweetened drinks and childhood obesity: a prospective, observational 
analysis. Lancet 2001;357: 505-8.[CrossRef][ISI][Medline]
7.	Nutrition Sub-Committee, British Diabetic Association. Dietary 
recommendations for people with diabetes. An update for the 1990's. J Hum 
Nutr Diet 1991;4: 393-412.[ISI]
8.	Diabetes and Nutrition Study Group (DNSG) of the European Association for 
the study of diabetes. Recommendations for the nutritional management of 
patients with diabetes mellitus. Eur J Clin Nutr 2000;54: 
353-5.[CrossRef][ISI][Medline]
9.	Bolton Smith C, Woodward M. Dietary composition and fat to sugar ratios 
in relation to obesity. Int J Obes 1994;18: 820-8.[ISI]
10.	Puska P, Vartiainen E, Tuomilehto J, Salomaa V, Nissinen A. Changes in 
premature deaths in Finland: successful long-term prevention of 
cardiovascular diseases. Bull WHO 1998;76: 419-2.[ISI][Medline]
11.	Hollenbeck CB. Dietary fructose effects on lipoprotein metabolism and 
risk for coronary artery disease. Am J Clin Nutr 1993;58: 
800s-809s.[Medline]
12.	Birch LL. Development of food preferences. Annu Rev Nutr 1999;19: 
41-62.[CrossRef][ISI][Medline]
13.	Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy 
MC. Effects of diets high in sucrose or aspartame on the behaviour and 
cognitive performance of children. N Eng J Med 1994;330: 
301-7.[Abstract/Free Full Text]
14.	Butchko HH, Stargel WW. Aspartame: scientific evaluation in the 
postmarketing period. Reg Toxic Pharma 2001;34: 221-233[CrossRef][ISI]
Rapid Responses to:
EDITORIALS:
Michael E J Lean and Catherine R Hankey
Aspartame and its effects on health
BMJ 2004; 329: 755-756 [Full text]
Rapid Responses: Submit a response to this article 

 

Rapid Responses published:
Fluoride Deficiency Non-Existent
Carol S. Kopf, BS, MA   (1 October 2004)
Aspartame Can Damage Your Health
Joseph M Mercola   (3 October 2004)
It's not just misleading websites that the public should be protected from
John P Briffa   (3 October 2004)
Aspartame Dangers ARE Real
Dr. Janet S Hull   (3 October 2004)
Aspartame - balanced and impartial editorials please
Ian J Gordon   (4 October 2004)
Re: Aspartame Can Damage Your Health
J. Dallas Van Wagoner, M.D.   (10 October 2004)
Re: Aspartame Can Damage Your Health
Carol Guilford   (10 October 2004)
Aspartame and its effects on health
Joanna Clarke   (11 October 2004)
Aspartame -safety in science
Nick Finer   (12 October 2004)
There's no place to hide
John P Briffa   (15 October 2004)
What Aspartame has in common with any artificial sweetener ("natural" or 
not) in effects on health
Tanya Zilberter, PhD   (15 October 2004)
Aspartame - the problems of population studies
Robert WJ Dingwall   (15 October 2004)
Re: Aspartame - the problems of population studies
Ellen C G Grant   (17 October 2004)
Independent Scientific Information
Mark D. Gold   (20 October 2004)
Lay-Observer's Response
Robert Park   (21 November 2004) 

Fluoride Deficiency Non-Existent	1 October 2004
	 

Carol S. Kopf, BS, MA,
writer
11756
Send response to journal:
Re: Fluoride Deficiency Non-Existent
Re: Aspartame and its effects on health BMJ 2004; 329: 755-756 by Lean and 
Hankey
Lean and Hankey state what so many assume, wrongly - that fluoride 
deficiency leads to tooth decay.
"...it must be acknowledged that a lack of fluoride does not cause dental 
caries," according to "Effective use of fluorides for the prevention of 
dental caries in the 21st century: the WHO approach," in Community Dentistry 
and Oral Epidemiology (2004;32:319-21).
The United States Centers for Disease Control says that fluoride's 
non-adverse effects occur topically after teeth erupt and that The 
prevalence of dental caries in a population is not inversely related to the 
concentration of fluoride in enamel, and a higher concentration of enamel 
fluoride is not necessarily more efficacious in preventing dental caries. 
(1)
Fluoride is not an essential nutrient. Optimal dosage is based on belief.(2)
References:
1) Recommendations for Using Fluoride to Prevent and Control Dental Caries 
in the United States, August 2001, 
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5014a1.htm
2) National Research Council (1993). Health Effects of Ingested Fluoride. 
National Academy Press, Washington DC. See page 30 
http://books.nap.edu/books/030904975X/html/30.html
Competing interests: None declared	
Aspartame Can Damage Your Health	3 October 2004
	 

Joseph M Mercola,
Medical director Optimal Wellness Center
Schaumburg, IL 60194
Send response to journal:
Re: Aspartame Can Damage Your Health
Your editorial fails to address the reasons why aspartame has been 
demonized. Since at least 2/3 of adults currently consume aspartame this 
is a serious issue.
Although aspartame contains two amino acids it is not a natural substance. 
It was originally developed as a drug to treat peptic ulcers. We were not 
designed to be exposed to large amounts of isolated free form amino acids. 
Free form aspartic acid is a damaging neuro excitotoxin mediated through 
NMDA receptors (1).
While it is true that phenylalanine is an essential amino acid it is rarely 
consumed in nature as a free from amino acid or in large doses. In 1987 it 
was calculated that nearly 4 million kg of phenylalanine were introduced 
annually into the food supply as aspartame. The consequences of flooding the 
brain with phenylalanine are profound as it serves as a precursor for two 
major neurotransmitters, dopamine and norepinephrine. The altered amino acid 
ratios can modify tryptophan concentrations and secondarily serotonin 
levels. This can lead to seizures, confusion, erratic behaviors, depression 
and other neuropsychiatric disturbances.
Interestingly, the FDA regards adverse reactions like seizures to products 
containing aspartame as only anecdotal idiosyncrasies that do not have to be 
reported because of aspartames Generally Recognized as Safe classification.
The methyl ester joining aspartic acid and phenylalanine is metabolized to a 
two potent neurotoxins methanol and formaldehyde. This is not insignificant 
as the digestion of aspartame yields 10% methanol by weight.
Additionally, the vast majority of the flawed scientific studies used to 
support the safety of aspartame products were funded by the manufacturer. 
The shortcomings variously pertain to the materials used, the amounts of 
administration, the nature of control subjects, the duration of such 
studies, the contents of presumed placebos and the arbitrary interpretation 
of results.
Obrenovitch TP Adv Exp Med Biol. 2003;527:147-54.
Competing interests: None declared	
It's not just misleading websites that the public should be protected from	3 
October 2004
	 

John P Briffa,
Doctor and Health Writer
Woolaston House, 25 Southwood Lane, Highgate, London N6 5ED
Send response to journal:
Re: It's not just misleading websites that the public should be protected 
from
I was surprised by much of the content of Professor Lean and Catherine 
Hankeys editorial on the effects of aspartame and health (1). It starts 
with an incomplete description of aspartames components: aspartame is not 
only composed of two amino acids (phenylalanine and aspartic acid) but 
methanol also. This is crucially important as methanol has toxic potential 
and may also be converted to formaldehyde within the body (2). It has been 
demonstrated in animals that low level ingestion of aspartame can lead to 
formaldehyde accumulation in the various parts of the body including the 
liver and brain (3). In addition, several human studies have found that 
chronic, low-level formaldehyde exposure has been linked with a variety of 
health issues including headaches (4,5,6), fatigue (4,5), chest tightness 
(4), dizziness, nausea and lack of concentration (6), seizures and 
neurobehavioural impairment (7). Long- term studies into the effects of 
ingestion of aspartame or its components in humans have not been done. Until 
they are, it seems premature to conclude that aspartame is safe.
Aspartames manufacturers and scientific advisors often defend aspartame by 
stating that it brings nothing new to the diet, as all of its constituents 
(including methanol) are found naturally in the diet. This defence is flawed 
in that it presupposes that naturally occurring food constituents can have 
no adverse effect on health. Also, it is possible that when found naturally 
in food (such as bananas and tomatoes), methanol may be ingested with other 
food elements that might protect against toxicity. While this notion may 
seem far-fetched to some, an example of it is known in the real World: two 
studies suggest that giving beta- carotene in supplement form may increase 
risk of lung cancer in smokers, although there appears to be no such 
association with dietary beta- carotene.
While the European Scientific Committee Foods 2002 report appears to 
exonerate aspartame, the Committee seems to have be ignorant of, ignored, or 
dismissed studies which show aspartame might have adverse effects on health. 
Such research includes an animal study in which aspartame disrupted brain 
chemistry (8). Also, in humans, aspartame was found to induce 
neurophysiological changes that might increase seizure risk (9). In 
addition, at least one study has linked aspartame use with depression in 
individuals susceptible to mood disorder (10). Other studies have linked 
aspartame ingestion with headaches (11,12). Other studies that attest to 
aspartames potential for harm can be found in an on-line review (13).
This review is particularly disconcerting as it shows a disparity in the 
findings of safety studies which appears to be related to source of study 
funding. In this review, studies in peer-reviewed medical or scientific 
journals were assessed for funding source and study outcome. Of 166 studies, 
74 had at least partial industry-related funding and 92 were 
independently-funded. While 100 per cent of industry-funded studies conclude 
aspartame is safe, 92 per cent of independently funded research identified 
aspartame as a potential cause of adverse effects.
Professor Lean and Ms Hankey speculate on the potential weight loss benefits 
of aspartame. Their assessment is largely theoretical based on the potential 
for the replacement of sugar with aspartame to bring about caloric deficit. 
They acknowledge that the evidence for the weight loss effects of aspartame 
is inconclusive. However, they fail to mention studies which have shown that 
aspartame ingestion may actually lead to increased food/calorie intake 
(14,15). The case for the benefits of aspartame use for weight loss seems to 
rest on one relatively short-term, unblinded clinical study in obese women 
(16). Men, children and individuals with less extreme weight problems (all 
groups of individuals who might be using aspartame for the purposes of 
weight loss) were not included in the study.
It is somewhat concerning that, to date, not one single double-blind 
placebo-controlled study designed to assess the effects of aspartame on 
weight has been published. Im left wondering why there is such enthusiasm 
from some quarters of the nutritional establishment for aspartame in the 
diet, bearing in mind the singular lack of evidence that it is efficacious 
for the purposes of weight loss.
It seems that the health-related benefits of aspartame are simply unproven, 
and that evidence exists which suggests that this novel chemical does have 
real potential for harm. The glaring disparity in results between 
industry-funded and independently-funded research is clearly of concern. 
Professor Lean and Ms Hankey conclude their editorial by suggesting that the 
public probably needs protection from misleading websites. However, by the 
same token, the public and members of the medical profession should probably 
be protected from misleading editorials too.
1. Michael Lean, Catherine Hankey. Aspartame and its effects on health BMJ 
2004;329:755-756 (2nd October 2004).
2. Kavet R, et al. The Toxicity of Inhaled Methanol Vapors. Critical Reviews 
in Toxicology 1990 21;1:21-50
3. Trocho C, et al. Formaldehyde Derived From Dietary Aspartame Binds to 
Tissue Components in vivo. Life Sciences 1998 63;5:337
4. Main DM, et al. Health Effects of Low-Level Exposure to Formaldehyde. 
Journal of Occupational Medicine 1983 25;896-900
5. Olsen JH, et al. Formaldehyde induced symptoms in day care centers. 
American Industrial Hygeine Association Journal 43;5 366-370
6. Burdach S, et al. Damages to health in schools. Complaints caused by the 
use of formaldehyde-emitting materials in school buildings. Fortschritte Med 
1980 98 11; 379-384
7. Kilburn KH, et al. Neurobehavioral and respiratory symptoms of 
formaldehyde and xylene exposure in histology technicians. Arch Env Health 
1985 40; 4; 229-233
8. Sharma RP, Coulombe RestioA Jr. Effects of repeated doses of aspartame on 
serotonin and its metabolite in various regions of the mouse brain. Food 
Chem Toxicol. 1987;25(8):565-568
9. Camfield, PR, et al., Aspartame exacerbates EEG spike-wave discharge in 
children with generalized absence epilepsy: a double-blind controlled study. 
Neurology, 1992;42:1000-1003
10. Walton RG, et al,. Adverse reactions to aspartame: double-blind 
challenge in patients from a vulnerable population. Biol Psychiatry. 
1993;34(1-2):13-17.
11. Van Den Eeden SK, et al. Aspartame Ingestion and Headaches: A 
Randomized, Crossover Trial. Neurology. 1994;44:1787- 1793
12. Lipton RB, et al. Aspartame as a dietary trigger of headache. Headache. 
1989;29(2):90-92
13. http://www.dorway.com/peerrev.html
14. Lavin JH, et al. The Effect of Sucrose- and Aspartame-Sweetened Drinks 
on Energy Intake, Hunger and Food Choice of Female, Moderately Restrained 
Eaters Int J Obes. 1997 21:37-42
15. Tordoff MG, Alleva AM. Oral stimulation with aspartame increases hunger. 
Physiol Behav 1990 47:555559
16. Blackburn GL, et al. The effect of aspartame as part of a 
multidisciplinary weight-control program on short- and long-term control of 
body weight. Am J Clin Nutr. 1997 65(2):409-418.
Competing interests: None declared	
Aspartame Dangers ARE Real	3 October 2004
	 

Dr. Janet S Hull,
Nutritionist/Environmental Engineer/Author
100 E. Louisiana St. Suite3 McKinney, TX 75069
Send response to journal:
Re: Aspartame Dangers ARE Real
RE: Aspartame and its effects on health
Thank you for bringing the aspartame issue to the attention of your readers. 
Nonetheless, the proper respect and recognition for the consumers who have 
suffered medically documented illnesses from aspartame, for the research 
scientists at universities in both the U.S. and the U.K. who have documented 
the damaging effects of aspartame, and for the mothers of children born with 
mental and physical deformities caused by aspartame during pregnancy  well, 
they were not properly mentioned in your article.
Yes, aspartame dangers are real and scientifically supported beyond any 
reasonable doubt. I provide scientific references and data in my book on 
aspartame dangers (Sweet Poison, New Horizon Press) citing scientific 
documentation that aspartame, indeed, causes holes in the brains of 
laboratory mice, mammary gland tumors and testicular tumors in rats, fetal 
deformities, and behavioral disorders. Dr. Russell Blaylock, M.D. is 
currently connecting aspartame to Multiple Sclerosis. The U.S. government 
agencies you cite in your article are clearly documented as denying 
aspartame approval TWICE before its questionable sanction in 1981.
Since aspartame came on the market over twenty years ago, many diseases such 
as MS, ALS, Parkinsons, Alzheimers, depression, aggression, and, now, 
obesity have become epidemic. The answer to these concerns is not more 
toxic brain chemical use as you suggest, but exactly the opposite - the 
answer is more public "caution" concerning the neuro-excitotoxins in 
aspartame and their damaging effects to the brain. Obesity among British and 
American children is horrifying and will only worsen if eating chemical 
foods and drinking non-nutritive colas is encouraged.
Before you publish your next article discrediting the many brilliant 
research scientists, doctors, and responsible consumers informing people of 
the dangers of aspartame and other chemical sweeteners  please, do more 
thorough research.
Competing interests: None declared	
Aspartame - balanced and impartial editorials please	4 October 2004
	 

Ian J Gordon,
Physician in Occupational Medicine
Whiston Hospital, Merseyside L35 5DR
Send response to journal:
Re: Aspartame - balanced and impartial editorials please
I would like to ask why the editorial on aspartame went to such lengths to 
vindicate the substance without any balanced review of the numerous papers 
on its side effects. An editorial should impartially review all aspects of 
the current information on a subject and leave it to the reader to decide or 
research further. In fact the excellent rapid responses by Mercola, Biffra 
and Hull clearly state the other side of the coin. I am particularly 
concerned because of personal experience having had a severe episode of 
fortification spectra after trying aspartame sweeteners - the like of which 
I have never had in 37 years of being a migraine sufferer. What could the 
effect be in those with significant cerebrovascular disease? This substance 
was approved by the FDA in 1981 because of political armbending for 
industrial reasons - not because of safety. I would like to see another 
editorial to balance the one by Lean & Hankey as too many reports of adverse 
effects exist for this to be dismissed as hypochondriasis or peoples' 
resentment of food interference.
Competing interests: None declared	
Re: Aspartame Can Damage Your Health	10 October 2004
	 

J. Dallas Van Wagoner, M.D.,
Disabled Physician
929 W. Sunset Blvd #21,PMB 141, St. George, UT 84770 USA
Send response to journal:
Re: Re: Aspartame Can Damage Your Health
I became severely ill with chronic fatigue and severe depression in 1996. In 
2001 I read an article on aspartame and I stopped using it. I have gradually 
become much improved, and I am now able to function without constantly 
contemplating suicide.
There is more than enough evidence that aspartame is unsafe, but industry is 
too powerful and has too much money to allow the evidence to become known.
There have been studies in the US that have shown that artificial sweeteners 
actually contribute to weight gain now to weight loss. These studies seem to 
have been suppressed also. Amazing what money can do.
Before you publically support toxic agents you should do a more complete 
reveiw of the literature.
I am very dissapointed in the British Medical Journal. Of course that may be 
the British way of life.
I can be reached at lastcaldoc@aol.com.
Thank you
Competing interests: None declared	
Re: Aspartame Can Damage Your Health	10 October 2004
	 

Carol Guilford,
writer
Los Angeles, CA
Send response to journal:
Re: Re: Aspartame Can Damage Your Health
In 1995, the US FDA was forced to reveal under the Freedom of Information 
Act, 92 symptoms caused by aspartame.
Memory loss, seizures, death, bone and joint pain, change in vision, chane 
in heart rate.
To see a list go to www.dorway.com, www.presidiotex.com/aspartame or 
www.aspartamekills.com
Competing interests: None declared	
Aspartame and its effects on health	11 October 2004
	 

Joanna Clarke,
Microbiology Research Technician
Glasgow Royal Infirmary G4 0SF
Send response to journal:
Re: Aspartame and its effects on health
Dear Sir,
I agree with Professor Lean and Dr. Hankey that the proliferation of 
sensationalist websites attributing any and every symptom a person might 
have to the consumption of aspartame is not helpful. Such sites cloud the 
issue for people like myself who would like to see a rational approach and 
solution to the aspartame problem.
As one of the individuals who has a frightening personal account of 
multiple health disasters which disappeared when I removed aspartame from 
my diet (and which reappeared when inadvertently re-challenged), I can 
assure all readers that I do not have an opinion fuelled  by anecdote, 
nor by any website, but that I have experienced-based knowledge. Duty or 
not, the government bodies are not monitoring health- effects of aspartame: 
the necessary system for the reporting of such problems does not exist; the 
medical profession has not been alerted to the side-effects experienced from 
the many different forms of aspartame and so cannot contribute useful 
clinical information.
After my own bad experiences of aspartame, I started to invite people around 
me to talk about any awareness they had of ill-effects from the sweetener. I 
very easily contacted over thirty individuals (in Scotland) who told the 
same story of severe illness, of negligible help from medical professionals, 
and of finally discovering for themselves what was the cause. Consider the 
implications of this. If a private individual can trace thirty people just 
by asking around, the total number of aspartame survivors out there must 
be very large. Since, for every individual who has managed to work out their 
aspartame problem for themselves, there must be many more who have not, and 
the number of these sufferers must therefore be staggering.
Professor Lean concludes the public probably needs protection against 
misleading websites. I wholeheartedly agree, but, appearing beside the 
article in the British Medical Journal website is a link to a site claiming 
reliable and official information about aspartame. This website belongs to 
the makers, and global distributors, of aspartame. Like all commercial 
enterprises, it uses careful wording to appear to answer questions on safety 
and to give reassurances without actually acknowledging the problems which 
raised the safety questions in the first place. The site is clearly neither 
reliable nor official, it is a commercial PR exercise, and is using 
advertisement in a respected medical journal to camouflage its true nature..
The public definitely needs protection against ALL misleading websites.
Yours faithfully,
Joanna Clarke BSc. AIBMS MIBiol
Glasgow
Competing interests: None declared	
Aspartame -safety in science	12 October 2004
	 

Nick Finer,
Senior Research Associate and Consultant in Obesity Medicine
University of Cambridge and Addenbrooke's Hospital
Send response to journal:
Re: Aspartame -safety in science
Lean and Hankeys editorial on aspartame succinctly outlined the substantial 
evidence that supports the safety of aspartame. They also address the 
evidence that suggests aspartame may usefully protect consumers from some of 
the environmental pressures that have been firmly implicated in the current 
epidemic of obesity and diabetes. Lean and Hankey also drew attention to the 
extraordinary opinions paraded on web- sites that border from the merely 
uninformed and un-evidenced, to the frankly bizarre.
It is not surprising therefore that this editorial has excited responses 
from excited nutritionists, wellness experts and journalists. It is not 
possible to refute each of the issues raised in the space of a rapid 
response letter, but it is worth dissecting some of statements to illustrate 
the often simplistic and selective approach to evidence that detractors use.
Joseph Mercola uses emotive and ill-defined terms such as natural 
substances to imply that natural is good and unnatural is bad. Digitalis, 
bacterial contamination and aflatoxins are all natural but I would rather my 
food was free of them. He talks about flooding the brain with amino acids, 
something for which there is simply no evidence. His statement pre-supposes 
that aspartame causes excessive rises in plasma phenylalanine that then 
crosses the blood brain barrier to enter the brain. Plasma phenylalanine 
levels rise to between 80 and 120 mmol/L after a protein meal such as a 
glass of the natural substance milk. This is about the same as after a 
dose of 34 mg/kg bw aspartame (equivalent to about 28 cans of 
aspartame-sweetened drink consumed all in one go) (1). Current data (2) show 
that average daily intake of aspartame in adults is between 0.05 and 0.4 
mg/kg bw/day and maximum values between 1 and 2.75 mg/kg bw/day. In French 
young diabetics mean consumption of aspartame was estimated at 1.9 mg/kg 
bw/d (less than 5% of the ADI) and maximum intake was 15.6 mg/kg bw/d (40% 
of the ADI). It is thus unclear on what data Dr Mercola has based his 
statement.
Dr Briffa and others raise the issue of the small amounts of methanol 
produced by aspartame metabolism. It is the metabolite formate, not methanol 
itself that can cause toxicity in man. In order for the body to accumulate a 
significant amount of formate, a human must consume 200 to 500 mg of 
methanol per kg of body weight (3), an amount that corresponds to drinking 
600 to 1700 cans of diet soft drink at once. Researchers have studied 
whether methanol levels in the blood rise significantly when humans consume 
aspartame. In one study, subjects were given 34 mg- aspartame/kg body 
weight. Blood levels did not rise detectably (4) Another experiment showed 
that blood methanol levels did not rise even when subjects consumed 200 
mg-aspartame/kg body weight (5). In long term studies, researchers found 
that when humans consume aspartame, the resulting formate production is 
balanced by excretion, so that blood levels of formate do not change [Leon 
and others, 1989].
Briffa goes on to quote a study by Trocho et al (7) as evidence for 
formaldehyde accumulation in animals with low level of ingestion of 
aspartame, but not that from Tephly (8) who questions these conclusions in 
a letter published to the journal editor and outlines previous research on 
methanol toxicity in monkeys not discussed by Trocho et al. relevant to the 
question of methanol toxicity. Tephly cites previous studies in monkeys that 
show high levels and rapid rise of blood formate following administration of 
methanol or formaldehyde. This study and a human case study of formaldehyde 
intoxication provide evidence for a half-life of 1.5 minutes for 
formaldehyde and its rapid conversion to formate. He also questions the use 
of rodents to study methanol toxicity as primates metabolize methanol and 
formate by different enzymatic pathways. More importantly he also describes 
the normal disposition of formaldehyde to formate and it's inclusion into 
the one-carbon folate pool eventually leading to S-adenosylmethionine (SAM), 
often referred to as the universal methyl donor. Tephly reports that the 
appearance of around 1% of the radio-labelled carbon in protein, DNA or RNA 
could be explained by the very rapid flux of the carbon through SAM or other 
folate dependant reactions into these molecules and tissues. He stresses 
that this flux of carbon derived from methanol from any source (fruit juice, 
pectin or aspartame) is a result of normal biochemistry and is not a toxic 
event.
On the issue of research sponsorship and whether this biases the research. 
It seems entirely appropriate that companies should respond to concerns over 
their products safety by commissioning research. The only issue is the 
quality of that research of which a good test is whether it has been 
accepted for publication in peer reviewed journals. It is a dangerous game 
to assume that non-industry researchers or commentators do not have 
conflicts; they may be renewing grants, writing books or newspaper articles 
or trying to attract patients to their practice for personal income. Amongst 
the 74 studies Dr Briffa quotes as non-industry supported by are several 
papers from the MIT group. It is curious that their recent publication (9) 
that concluded Large daily doses of aspartame had no effect on 
neuropsychologic, neurophysiologic, or behavioral functioning in healthy 
young adults is omitted. This study was jointly funded by both NutraSweet 
and The Center for Brain Science. Would this, coming from a laboratory and 
clinical research centre at the heart of raising dangers about aspartame be 
regarded as industry sponsored or non-industry sponsored?
Those wishing authoritative recent reviews would do well to read the 
Opinion of the Scientific Committee on Food: Update on the Safety of 
Aspartame (10) and the 2002 issue of Regulatory Toxicology and Pharmacology 
(11).
(1) Stegink LD et al. Effect of aspartame and aspartate loading upon plasma 
and erythrocyte free amino acid levels in normal adult volunteers. J Nutr. 
1977, 107: 1837-1845.
(2) French Food Safety Agency Report 2002. 
http://www.aspartame.org/pdf/AFSSA-Eng.pdf.
(3) Food and Drug Administration, Federal Register, 984.
(4) Stegink LD et al. Effect of repeated ingestion of aspartame-sweetened 
beverage on plasma amino acid, blood methanol and blood formate 
concentrations in normal adults. Metabolism 1989, 38:357-363.
(5) Stegink LD, Filer LJ. Effects of aspartame ingestion on plasma 
aspartate, phenylalanine and methanol concentrations in potentially 
sensitive populations. In: The clinical evaluation of a food additive. 
Assessment of Aspartame. Tschanz C, Butchko HH, Stargel WW, Kotsonis FN, 
Edts, 1996(a), pp 87-113, CRC Press, Boca Raton, New York, London, Tokyo.
(6) Leon AS et al. Safety of Long-term Large Doses of Aspartame. Arch Intern 
Med. 1989;1 49:2318-2324
(7)Trocho et al. Formaldehyde derived from dietary aspartame binds to tissue 
components in vitro. Life Sci. 1998, 63 (5), 337-349.
(8)Tephly TR. Comments on the purported generation of formaldehyde and 
adduct formation from the sweetener aspartame. Life Sci., 1999, 65(13), 
157-160
(9) Spiers PA, Sabounjian L, Reiner A, Myers DK, Wurtman J, Schomer DL. 
Aspartame: neuropsychologic and neurophysiologic evaluation of acute and 
chronic effects. Am J Clin Nutr. 1998 Sep;68(3):531-7
(10) Opinion of the Scientific Committee on Food: Update on the Safety of 
Aspartame. SCF/CS/ADD/EDUL/222 Final. Brusssels Dec 2002. 
http://www.food.gov.uk/multimedia/pdfs/aspartameopinion.pdf
(11) Butchko HH et al. Aspartame: Review of safety. Regul Toxicol Pharmacol. 
2002;35:S1-S93.
Competing interests: Medical Adviser to Ajinomoto	
There's no place to hide	15 October 2004
	 

John P Briffa,
Doctor and Writer
Woolaston House, 25 Southwood Lane, Highgate, London N6 5ED
Send response to journal:
Re: There's no place to hide
I read with interest Dr Finers riposte (1) to the rapid responses relating 
to Lean and Hankeys editorial (2). It is clearly an attempt to discredit 
detractors and allay fears about aspartame. In his response, Dr Finer 
strives to cast doubt on the validity of the criticisms of aspartame, and 
states that "it is worth dissecting some of [sic] statements to illustrate 
the often simplistic and selective approach to evidence that detractors 
use". It seems only reasonable that Dr Finers response should be subjected 
to the same scrutiny.
Dr Finer dismisses much of the evidence which shows aspartame has the 
potential for harm by saying that the "issue is the quality of that research 
of which a good test is whether it has been accepted for publication in peer 
reviewed journals". Earlier in his response, however, he cites a study that 
is not published in a peer-reviewed journal (3). Also, I feel compelled to 
remind Dr Finer that of the 92 independently funded aspartame safety studies 
referred to in the on-line review referred to in my earlier response (4) (92 
per cent of which suggested that aspartame has the potential to cause harm), 
ALL were published in peer-reviewed journals (5).
The quality of some of the science that Dr Finer uses to make his case is 
also leaves a lot to be desired. For instance, he cites one study (6) which 
involved giving aspartame to just 6 (six) healthy young adults for just 1 
(one) day (when it is the chronic, long-term exposure to the constituents of 
aspartame and its metabolites that is consistently raised as the real 
concern). Another study that Dr Finer cites (7) is also critically flawed. 
This study assessed the effects of aspartame on healthy subjects who may not 
be representative of individuals sensitive to aspartame or its metabolites. 
Although 24 weeks in duration, this study does not preclude health hazards 
that may come from consuming aspartame in the long term. It should be noted 
that some individuals may be able to ingest aspartame without 
clinically-obvious adverse effects for many months or years (8). Also, in 
the Leon study (7), aspartame was given in slow-dissolving capsules i.e. in 
a way that is not bioequivalent to aspartame ingested via food products, 
particularly beverages. This study still actually turned up a greater than 
50 per cent increase in adverse reactions in the aspartame group. However, 
because the researchers split the reactions into 14 small sub-categories, 
the chances of seeing statistically significant differences in any one 
sub-category were very low.
It seems utterly ironic to me that Dr Finer should emphasise the importance 
of quality research, only for him to use such poor science in an attempt to 
vindicate aspartame. And it appears somewhat hypocritical that Dr Finer 
should accuse others of using a "simplistic and selective" approach to the 
evidence they use.
Dr Finer seems dismissive of the potential for bias related to industry 
funding in the area. Is he really blissfully unaware of the very real issues 
that may pervert scientific objectivity, including publication bias? Maybe 
he is ignorant of the published research which shows that pharmaceutical 
industry funding can have a significant impact on the apparent outcome of 
research (9). It may enlighten Dr Finer to know that the authors of this 
study concluded that "systematic bias favours products which are made by the 
company funding the research". It seems that in the area of industry-related 
research, theres an element of he who pays the piper, calls the tune. And 
let us not imagine for one moment that the food industry is not capable of 
underhand and cynical practices. Only this week, BBCs Panorama programme 
did a good job of exposing the food industrys attempts to influence the 
"official" findings of diet-related reports and food policy, as well as its 
ability to coerce and corrupt at the highest level (10).
It is perhaps worthy of note that the lead author of the editorial, 
Professor Michael Lean, is not only Professor of human nutrition at the 
Unversity of Glasgow, but also the Chairman of the Advisory Committee on 
Research (ACR) that advises the Food Standards Agency (FSA) - the 
organisation that plays a leading role in dictating food policy in the UK. 
Personally, I am concerned that several members of the ACR have personal 
interests in food companies or trade organisations that promote specific 
foodstuffs (11). I am also perplexed at how Professor Lean (and his co- 
author) managed to write an editorial that seemed to take aspartame's safety 
so unquestioningly, in the face of considerable scientific evidence to the 
contrary.
In his response, Finer cites another study that appears to exonerate 
aspartame (12). He seems at great pains to point out that this study was 
partly funded by the aspartame industry, and questions whether this study 
should be regarded as industry funded or not. Does he really need someone to 
answer this question for him? Finers own observations here are utterly 
consistent with the findings of the on-line review that shows that 
industry-funded (either whole or in part) research ALWAYS finds in favour of 
aspartame (5).
Still further cause for concern comes from Dr Finers comments (or rather, 
lack of them) regarding aspartames role in weight loss. He congratulates 
Lean and Hankey on addressing "the evidence that suggests aspartame may 
usefully protect consumers from some of the environmental pressures that 
have been firmly implicated in the current epidemic of obesity and 
diabetes". Dr Finer fails to acknowledge, however, that Lean and Hankeys 
appraisal in this respect was theoretical. I wonder what Dr Finer thinks of 
the glaring lack of evidence that aspartame ingestion is effective for 
weight loss. Perhaps he could explain his appetite for aspartame, bearing in 
mind the fact that not one single double-blind placebo-controlled study that 
attests to aspartames efficacy and a weight loss aid has been published? I 
note that Professor Lean is quoted on the FSA website as saying: "Very 
important policy decisions are being made by the FSA and it is in the public 
interest that that these are based on top quality research." Maybe he too 
would like to comment on the dearth of "top quality research" that exists in 
support of aspartames supposed health benefits?
The bias that pervades this area seems neatly mirrored in the electronic 
responses to Lean and Hankeys editorial. It is perhaps worth noting that, 
to date, all but one of the rapid responses that pertain to aspartame have 
been critical of the review and/or aspartame. Some may take a rather cynical 
view of the fact that the only individual who has leapt to aspartames 
defence is in the pay of its manufacturer (Ajinomoto).
Dr Finer claims not to be surprised that there have been responses from 
"excited nutritionists, wellness experts and journalists". Dr Finers use of 
the adjective "excited" seems inappropriate to me. Perhaps this was an 
attempt by him to portray genuinely concerned individuals as somewhat 
hysterical? Also, perhaps Dr Finer could explain why he chose to refer to 
the responses from "nutritionists, wellness experts or journalists" when, in 
fact, the majority of responses, to date, have come from doctors. I wonder 
whether Dr Finer calculated that this omission might somehow make it easier 
for him to dismiss the "detractors".
Dr Finer does make one valid point, though: that some individuals critical 
of aspartame have their own agendas. Ill tell him what mine is: that people 
should have access to balanced information about aspartame, including the 
knowledge that:
a. aspartame has not been proven to help weight loss.
b. a considerable body of evidence exists which shows that this synthetic 
chemical has potential for adverse effects on human health.
c. there is a glaring disparity between the findings of industry- funded and 
non-industry funded research.
Dr Finers soothing reassurances do not change these basic facts. While he 
may believe that there is safety in science, a closer, more impartial look 
at the research into aspartame reveals that, in reality, there is no place 
to hide.
References:
1. Finer, N. Aspartame - safety in science. Rapid response published 12th 
October 2004.
2. Lean MJ, Hankey C. Aspartame and its effects on health. BMJ 2004 
328:755-756
3. Stegink LD, Filer LJ. Effects of aspartame ingestion on plasma aspartate, 
phenylalanine and methanol concentrations in potentially sensitive 
populations. In: The clinical evaluation of a food additive. Assessment of 
Aspartame. Tschanz C, Butchko HH, Stargel WW, Kotsonis FN, Edts, 1996(a), pp 
87-113, CRC Press, Boca Raton, New York, London, Tokyo.
4. Briffa J. Its not just misleading websites that the public should be 
protected from. BMJ Rapid response published 3rd October 2004.
5. http://www.dorway.com/peerrev.html
6. Stegink LD, et al. Effect of repeated ingestion of aspartame- sweetened 
beverage on plasma amino acid, blood methanol and blood formate 
concentrations in normal adults. Metabolism 1989, 38:357-363.
7. Roberts. Reactions Attributed to Aspartame-Containing Products: 551 Cases 
Journal of Applied Nutrition 1988 40; 85-94
8. Leon AS, et al. Safety of Long-term Large Doses of Aspartame. Arch Intern 
Med. 1989;1 49:2318-2324
9. Lexchin J, et al. Pharmaceutical industry sponsorship and research 
outcome and quality: systematic review. BMJ 2003 326(7400):1167-1170.
10. Panorama: The Trouble With Sugar BBC1 aired 10th October 2004
11. http://www.food.gov.uk/multimedia/pdfs/acr051_6.pdf
12. Spiers PA, et al. Aspartame: neuropsychologic and neurophysiologic 
evaluation of acute and chronic effects. Am J Clin Nutr. 1998 68(3):531-537
Competing interests: None declared	
What Aspartame has in common with any artificial sweetener ("natural" or 
not) in effects on health	15 October 2004
	 

Tanya Zilberter, PhD,
Health educator, writer: dietandbody.com, bantadiet.com
Stockholm, Sweden, 13542
Send response to journal:
Re: What Aspartame has in common with any artificial sweetener ("natural" or 
not) in effects on health
In 1974, Drs Fischer, Hommel, Fiedler, and Bibergeil published an article 
titled "Reflex mechanism on insulin secretion." It's been followed by 
research data showing the details of insulin secretion time course.
The insulin level rises already in the first minute after the start of a 
carbohydrate-rich meal, whereas the glucose level begins to increase only in 
the third minute. This early rise in insulin level is observed also when 
either carbohydrate-free food or even artificial food without any caloric 
value is offered. The phenomenon is now well-researched under the name 
"cephalic phase of insulin release" though it is amazing how little it 
influenced the art and science of dietetics and the current discussion.
It usually comes without questioning that it's carbohydrate- containing food 
absorbed into the circulation that stimulate the pancreatic beta-cells to 
secrete insulin. However, careful analysis of the time course of insulin 
secretion during carbohydrate ingestion has shown that insulin secretion can 
start even before glucose is actually absorbed. This so-called early insulin 
response is elicited by stimulation not only of taste buds but also through 
sight and smell of the food or even by meal anticipation.
Why any sweet taste, coming with any artificial sweetener, raises glucose 
concentration in the blood *before* the food has a chance to be digested? 
Because your body knows that eventually, it will have all the carbs you've 
swallowed and it doesn't wait until it that happens and borrows real 
carbohydrates from its carbohydrate depots. When the sweet-tasted food is 
real, the carbohydrates eventually do get into the blood. And if they're 
not?
Being fooled, your body reacts rather vindictively: it forces you to * want* 
more sweets plus next time, you consume more calories with any food, 
including the innocent protein food -- to convert it into glucose in process 
of gluconeogenesis. So, you'd be better off without artificial sweeteners, 
Aspartame or not.
Sources
Endocrinol Exp 1974 Jun;8(2):137-46
Am J Physiol 1975 Oct;229(4):1019-22
Physiol Behav 1990 Jun;47(6):1295-7
Am J Physiol Endocrinol Metab 278(4):E603-E610
dietandbody.com/article1082.html
Competing interests: None declared	
Aspartame - the problems of population studies	15 October 2004
	 

Robert WJ Dingwall,
Professor
University of Nottingham NG7 2RD
Send response to journal:
Re: Aspartame - the problems of population studies
It seems to me that there is a wider problem revealed by this debate, namely 
the extent to which safety testing relies on population-level studies which 
have not, thus far, paid much attention to the distribution of harmful 
effects and the possibility that some genotypes are more sensitive than 
others. Anecdotally, aspartame seems to be capable of triggering me into 
migraine-like reactions, like those that I experience from exposure to 
monosodium glutamate, cheap red wine and other known triggers. People like 
me seem to be a relatively small proportion of the population but can 
certainly experience serious adverse effects from substances that are 
considered to be safe in population studies and are widely employed by the 
food industry. Our sensitivity almost certainly has a genetic basis, 
although I am not aware of any work that identifies specific alleles or even 
proposes a plausible mechanism that might precipitate such reactions. I 
suspect that a new generation of food safety studies needs to be considered 
to take account of genetic variation and that we should be moving towards a 
situation where it is easier for those of us at-risk to identify ourselves 
and to determine from product and menu labelling that we should not consumer 
certain products, both natural and synthetically enhanced, that contain 
known triggers of adverse reactions when encountering our metabolism. This 
does not necessarily imply that products like aspartame are not safe for 
mass consumption - but I would personally prefer to avoid a couple of hours 
intense pain and vomiting if I inadvertently consume more than a fairly 
small amount.
Competing interests: None declared	
Re: Aspartame - the problems of population studies	17 October 2004
	 

Ellen C G Grant,
physcian and medical gynaecologist
20 Coombe Ridings, Kingston-upon-Thames, KT2 7JU
Send response to journal:
Re: Re: Aspartame - the problems of population studies
It is not only genetics which determines susceptibility to have migraine 
attacks triggered by common foods and chemicals like aspartame.
Women are more reactive in the premenstrual phase of the menstrual cycle. 
While the pre-trial incidence of migraine was 9%, first year exposures to 
some trial combinations of exogenous progesterones and oestrogens induced 
migraine in 40 to 60% of women.1
Also common nutritional deficiencies of zinc and /or magnesium increase the 
susceptibility in many of us. Among couples complaining of unexplained 
infertility or recurrent miscarriages, individuals who also suffered from 
headaches or migraine attacks had lower levels of these essential minerals 
than headache-free couples.2
Neil Ward and colleagues found that intake of the food additive tartrazine 
reduced serum and salivary zinc concentrations and increased urinary zinc 
content with a corresponding deterioration in behaviour/emotional responses 
of hyperactive children compared with controls.3
A similar sudden loss of in zinc, especially in individuals who are already 
zinc deficient, may help to explain the different individual responses to 
aspartame.
1.Grant ECG. Relation between headaches from oral contraceptives and 
development of endometrial arterioles. BMJ 1968;3:402-5.
2.Grant ECG. The pill, hormone replacement therapy, vascular and mood 
over-reactivity , and mineral imbalance .J Nutr Environ Med 1998;8:105- 116.
3. Ward NI, Soulsbury KA, Zettel VH, et al. The influence of the chemical 
additive tartrazine on the zinc-status of hyperactive children  a 
double-blind placebo-controlled study. J Nutr Med 1990;1:51-57.
Competing interests: None declared	
Independent Scientific Information	20 October 2004
	 

Mark D. Gold,
Health / Medical Writer
12 East Side Dr., Suite 2-18, Concord, NH 03301 USA
Send response to journal:
Re: Independent Scientific Information
In their editorial, "Aspartame and its effects on health" (1), Professor 
Lean and Catherine Hankey described my web page as "sensationalist 
journalism." That web page contains nearly 400 pages of referenced 
discussion related to the toxicity of aspartame and its metabolites. In 
addition, there are several hundred pages of reports from individuals 
detailing their experience of aspartame toxicity. I would invite healthcare 
professionals to peruse a portion the scientific sections that address both 
independent and aspartame industry-funded research in detail:
http://www.holisticmed.com/aspartame/abuse/
http://www.holisticmed.com/aspartame/scf2002.html
http://www.holisticmed.com/aspartame/aspfaq.html
In addition, there are numerous reasoned articles written by independent 
researchers and phsycians that have been reproduced on the web:
http://www.dorway.com/doctors.html
Citations in the editorial that related to aspartame and health effects 
included a web page published by an aspartame industry-funded public 
relations organization (2) and a published review written by NutraSweet 
company employees and others who have received funding from the manufacturer 
(3). In is not surprising, therefore, that the authors erroneously stated 
that "aspartame comprises just two amino acids" and implied that the 
evidence does not support the link between aspartame and health effects. On 
the other hand, evidence from independent research and published case 
reports (as detailed on the above-mentioned web pages) demonstrates that 
aspartame can cause a wide range of adverse health effects.
Addressing the response by Dr. Finer, Medical Advisor to Ajinomoto 
(aspartame manufacturer), he states that:
1) Individuals must consume 200 to 500 mg/kg of methanol in order to cause 
toxicity. Kavet (4) estimated that as little as a single dose of 300 mg/kg 
of methanol can be lethal. Dr. Finer's comments related only to single, 
lethal doses of methanol and not to chronic methanol and formaldehyde 
toxicity.
2) Various manufacturer-sponsored studies of aspartame ingestion showed no 
rise in plasma methanol levels. The methanol technique used in the studies 
was a technique developed in 1969 (5) and incapable of reading rises in 
plasma methanol less than 350 to 600%. Tephly (6) and other aspartame 
manufacturer sponsored researchers involved in plasma methanol measurements 
have refused to use sensitive testing methods despite their availability for 
many years (7-9).
3) Dr. Briffa cited a study by Trocho et al. (10), that showed an 
accumulation of significant levels formaldehyde adducts in various organs 
and tissues (brain, liver, etc.) after ingestion of relatively small amounts 
of aspartame. However, Dr. Briffa did not cite the letter by, Tephly (11), a 
researcher involved in many of the aspartame manufacturer- funded studies 
related to methanol and formate. However, the issues raised by Tephly (such 
as items #1 and #2 above) have been refuted in numerous forums and by using 
the data in the Trocho et al. study itself:
"The 'alternative' point expressed by Tephly, suggesting that aspartame 
methanol-label goes all the way into formic acid and the C1 pathway was 
thoroughly refuted by us, using experimental data. There was no labelled 
methionine nor thymine in protein and DNA respectively in the rat protein we 
recovered from rats treated with aspartame. This means-- unequivocally-- 
that the label present in DNA and protein adducts was NOT incorporated into 
amino acids or nucleic acid bases. The only explanation for our data was 
that the label was in the form of formaldehyde adducts." (12)
Dr. Finer did not discuss in detail other issues related to aspartame and 
formaldehyde typically mentioned by the manufacturer: methanol in fruits, 
formaldehyde in foods, long-term studies on non-human primates and 
production of formaldehyde and methanol in the body. The above-mentioned web 
pages addresses all of these issues as well as various industry-sponsored 
double-blind studies often cited by the manufacturer.
Dr. Finer is correct about me being an "excited" responder to the editorial. 
I am excited that busy healthcare professionals are finding the time to look 
at the independent research and, based on case reports received, are 
beginning to warn their patients off of aspartame. I am also excited that 
the World Health Organization's recent approval of the sweetener stevia (13) 
allows diabetics and others in Europe a healthier, time-tested alternative.
1. Michael Lean, Catherine Hankey. Aspartame and its effects on health BMJ 
2004;329:755-756 (2nd October 2004).
2. Aspartame Information Center. http://www.aspartame.org/ Web site owned by 
the Calorie Control Council. "It represents 60 manufacturers and suppliers 
of low-calorie, low-fat and light foods and beverages, including the 
manufacturers and suppliers of more than a dozen different dietary 
sweeteners, fat replacers and other low-calorie ingredients." 
http://www.caloriecontrol.org/aboutCCC.html (accessed 19 Oct 2004).
3. Butchko HH, Stargel WW. Aspartame: scientific evaluation in the 
postmarketing period. Reg Toxic Pharma 2001;34: 221-233.
4. Kavet R, et al. The Toxicity of Inhaled Methanol Vapors. Critical Reviews 
in Toxicology 1990 21;1:21-50.
5. Baker, R.N., A.L. Alenty, J.F. Zack. Simultaneous determination of lower 
alcohols, acetone and acetaldehyde in blood by gas chromatography. Journal 
of Chromatographic Science, 1969; 7:312-314.
6. Stegink, Lewis D., Tephly, Thomas R., et al. Repeated ingestion of 
aspartame-sweetended beverages: further observations in individuals 
heterozygous for phenylketonuria. Metabolism, 1990; 39(10):1076-1081.
7. d'Alessandro, Alessandra, et al. Formate in serum and urine after 
controlled methanol exposure at the threshold limit value. Environmental 
Health Perspectives, 1994; 102(2): 178-181.
8. Davoli, E., et al. Trace analysis of methanol in rat serum by headspace 
high resolution gas chromatography/selected ion monitoring," Journal of 
Chromatographic Science, 1986; 24:113-116.
9. Cook, M.R., F.J. Bergman, et al. Effects of methanol vapor on human 
neurobehavioral measures. Research Report No. 42 (Peer Reviewed), Health 
Effects Institute, 141 Portland Street, Suite 7300, Cambridge, MA 02139, 
+1-617-621-0266, August 1991.
10. Trocho C, et al. Formaldehyde derived from dietary aspartame binds to 
tissue components in vivo. Life Sciences 1998 63;5:337.
11. Tephly TR. Comments on the purported generation of formaldehyde and 
adduct formation from the sweetener aspartame. Life Sci., 1999, 65(13), 
157-160.
12. Alemany 2002. Letter from Dr. Mari Alemany to Rich Murray, September 8, 
2002. http://groups.yahoo.com/group/aspartameNM/message/864 .
13. Joint FAO/WHO Expert Committee on Food Additives, 63rd Meeting, Geneva, 
8-17 June 2004: 
http://www.who.int/ipcs/publications/jecfa/en/Summary63final.pdf
Competing interests: None declared	
Lay-Observer's Response	21 November 2004
	 

Robert Park,
Retired Prison Governor
Prison Service, Scotland, UK. DD8 4TP
Send response to journal:
Re: Lay-Observer's Response
As a lay-person I found this article, and especially its response, both 
interesting and informative. I have some anecdotal evidence from my own life 
that indicates that soft-drinks may indeed be harmful, and also, that 
saturated animal fat, in the absence of carbohydrate, is probably beneficial 
to one's health. The free speech, however, of the Internet may be 
problematic to some while others will find it fascinating and informative. 
Obviously the Internet has become a Cyclopean and illustrious world library 
which has the capacity to educate both professional and lay person alike. As 
a rapid global communicator it has manifestly become the greatest political 
tool devised. It is not, however, a respecter of rank. It may appear a 
threat to some, but, when it does, they may wish to question their motives. 
I am glad to have witnessed this argument and to have observed the frankness 
of its contributers and that of the authors of the responses. If I may take 
the liberty here in quoting this rather interesting but cynical-like truism: 
"Some people must think I am a mushroom. They keep me in the dark, and feed 
me with bull" Surely the liberty of the Internet will aid in resolving this 
minor but not inconsequential human quandary? The Internet appears to 
possess the capacity to expose publicly, scoundrels, and the frailties in 
argument, which has to be to the benefit of the individual. One learns so 
much from it. I now feel better informed!
Competing interests: None declared	 

 

 

 

 

 

Examining the Safety of Aspartame
Written by Ellen Guthrie, Pharm.D.
For several years, an alarming and controversial report has been circulating 
on the Internet, claiming that the artificial sweetener aspartame can cause 
multiple sclerosis and a host of other ailments. Certain versions of the 
report even claim that MS symptoms will disappear if intake of aspartame is 
halted. MSFocus frequently receives letters questioning the truth of these 
allegations. Ellen Guthrie, Pharm.D. now explores the question, is aspartame 
safe?
Clinically speaking, we can never say that anything (drug, additive, food, 
device, etc.) is 100 percent safe. We can, however, examine the data and 
research and differentiate fact from fiction. The Internet is an excellent 
source of information, but this information is only as reliable as the 
person posting the information and only as accurate as the data that backs 
it up.
In 1965, chemist James Schlatter accidentally discovered the high-intensity 
sweetener known as aspartame. Before its approval in the early 1980's by the 
U.S. Food and Drug Administration (FDA), aspartame underwent extensive 
scientific studies that demonstrated its safety in both animals and humans. 
Since its approval, some 20 years ago, aspartame has been consumed in more 
than 6000 products by hundreds of millions of people in hundreds of 
countries throughout the world. Aspartame is the ingredient that makes many 
foods (primarily colas) "light," "low-calorie," or "diet." Since it is 
impossible to detect all side effects in pre-marketing studies, aspartame 
has undergone extensive post-marketing surveillance to ensure that the 
additive is safe.
The metabolism of aspartame in the human body and the proposed toxicities 
from its metabolic components have concerned a lot of people and have been 
the emphasis of many post-marketing surveillance studies. Aspartame is 
metabolized by digestive enzymes and peptides to three common dietary 
components: amino acids, aspartic acid, and phenylalanine. Minute amounts of 
methanol can also be detected. Eating foods such as meat, dairy, fruits, and 
vegetables will also produce these same components, but in greater amounts 
than aspartame. For example, a glass of milk has 6 times more phenylalanine 
and 13 times more aspartic acid and a glass of tomato juice provides 6 times 
more methanol than a beverage the same size sweetened with 100 percent 
aspartame. Interestingly enough, it is impossible for humans to digest 
enough aspartame to raise the levels of these metabolic components to a 
dangerous level.
Anecdotal reports claiming that aspartame caused health problems increased 
in the days and weeks after aspartame was approved for use in carbonated 
beverages in 1983. These reports prompted the FDA to request an 
investigation by the Centers for Disease Control (CDC). The CDC analyzed 
more than 500 reports and the problems associated with aspartame were 
divided into two categories. Two-thirds of the people experienced 
neurological problems while one-quarter of the people experienced 
gastrointestinal problems. The neurological symptoms consisted of headaches, 
mood alterations, insomnia, dizziness, and fatigue. The gastrointestinal 
symptoms included abdominal pain, nausea, diarrhea, and vomiting. The CDC 
concluded, "The majority of symptoms were mild and are symptoms that are 
common in the general populace." The CDC also noted that there was no 
evidence supporting the claim that aspartame could cause certain diseases 
(i.e. multiple sclerosis, lupus, etc.).
While nothing can be considered 100 percent safe, aspartame has undergone 
extensive testing. With the exception of a few very mild side effects, 
aspartame appears to be quite safe. Those individuals, who experience 
problems after consuming aspartame, should eliminate foods and beverages 
that contain this sweetener from their diet.
Editor's Note:
The report claiming aspartame causes MS, often referred to as the Nancy 
Merkle hoax, is believed to have been circulating since 1995. The message is 
attributed to "Nancy Merkle," yet no one by that name is known to exist, nor 
has anyone come forward claiming to be the author. No credentials, research 
or sources are cited. This hoax first came to the attention of the Multiple 
Sclerosis Foundation in 1998, when those circulating it added the false 
claim that the MSF was suing the U.S. Food and Drug Administration to halt 
the sale and use of aspartame. The MSF neither condemns nor endorses 
aspartame, and has never filed suit against the FDA.
For more information about the Nancy Merkle hoax and the scientific facts 
about aspartame, visit the following hoax and urban legend sites:
	Urban Legends
	Snopes
	Scambusters