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 acids—aspartic 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 safe—except 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 vanquished—assuming 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 individually—adults 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 aspartame’s 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 Hankey’s editorial on the effects of aspartame and health (1). It starts with an incomplete description of aspartame’s 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. Aspartame’s 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 Food’s 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 aspartame’s 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. I’m 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 47:555–559 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, Parkinson’s, Alzheimer’s, 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 Hankey’s 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 Finer’s riposte (1) to the rapid responses relating to Lean and Hankey’s 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 Finer’s 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, there’s 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, BBC’s Panorama programme did a good job of exposing the food industry’s 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? Finer’s 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 Finer’s comments (or rather, lack of them) regarding aspartame’s 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 Hankey’s 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 aspartame’s 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 aspartame’s supposed health benefits? The bias that pervades this area seems neatly mirrored in the electronic responses to Lean and Hankey’s 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 aspartame’s 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 Finer’s 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. I’ll 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 Finer’s 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. It’s 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