Aspartame controversy

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Aspartame has been the subject of a vigorous public controversy regarding its safety and the circumstances around its approval. A few studies have recommended further investigation into the possible connection between aspartame and diseases such as brain tumors, brain lesions, and lymphoma.[1][2][3] These findings, combined with alleged conflicts of interest in the approval process, have engendered vocal activism regarding the possible risks of aspartame.[4][5]


Contents

[edit] Known effects

In 1995, FDA Epidemiology Branch Chief Thomas Wilcox reported that aspartame complaints represented 75% of all reports of adverse reactions to substances in the food supply from 1981 to 1995.[6] Concerns about aspartame frequently revolve around symptoms and health conditions that are allegedly caused by the sweetener. A total of 92 different symptoms and health conditions were reported by physicians and consumers.[7]

Questions have been raised about brain cancer, lymphoma, and genotoxic effects such as DNA-protein crosslinks, but these questions are primarily not based on reported case histories.

The sources for reported symptoms and health conditions that have raised questions include:

  1. Reports and analysis of case histories in scientific journals and at medical conferences
  2. Symptoms reported to the FDA and other governmental agencies
  3. Symptoms reported to non-governmental organizations, researchers, and physicians
  4. Reports of symptoms and health conditions in the media
  5. Self-reported cases on the Internet.

There is debate in the scientific and medical community as to whether these symptoms are or are not caused by short-term or long-term exposure to aspartame. Some human and animal studies have found adverse effects[8][9][10] and some have found no adverse effects.[11][12][13] It is not only the results of the research that have been questioned, but the design of the research that led to specific outcomes. For example, in human research of aspartame, the aspartame is usually provided in slow-dissolving capsules. But the concentration of aspartate in the blood from ingesting aspartame using slow-dissolving capsules is much lower than that from ingesting liquid aspartame (such as in carbonated beverages).[14]

Some human studies provide more than the daily allowance of aspartame, but in an encapsulated form. Based on the above-cited research, the equivalent amount of “real-world” aspartame in these human studies would be less. Other questions that have been raised about aspartame research involve the length of the studies, the number of test subjects, conflict of interest issues, and improper testing procedures.

The debate over possible adverse health effects has focused mainly on four chemical components of aspartame:

[edit] Methanol and formaldehyde

Approximately 10% of aspartame (by mass) is broken down into methanol in the small intestine. Most of the methanol is absorbed and quickly converted into formaldehyde. Opponents of aspartame's alleged health effects say that the metabolism of aspartame does not damage the body because: (a) the quantity of methanol produced is too small to disrupt normal physiologic processes; (b) methanol and formaldehyde are natural by-products of human metabolism and are safely processed by various enzymes; and (c) there is more methanol in some natural fruit juices and alcoholic beverages than is derived from aspartame ingestion.[15][16]

To counter these statements, aspartame detractors say that (a) fruit juices and alcoholic beverages contain protective chemicals such as ethanol that block conversion of methanol into formaldehyde, while beverages with aspartame contain no "protective factors"; (b) methanol and formaldehyde have been proven to cause chronic toxicity in humans; and (c) the low levels of methanol and formaldehyde in natural human metabolism are tightly-controlled, whereas increases in levels of methanol caused by aspartame ingestion are metabolized differently.[17][18]

In 1998, a team of scientists in Spain conducted an experiment on rodents to indirectly measure the levels of formaldehyde adducts in the organs after ingestion of aspartame. They did this by radiolabeling the methanol portion of aspartame. The scientists concluded that formaldehyde bound to protein and DNA accumulated in the brain, liver, kidneys and other tissues after ingestion of either 20 mg/kg or 200 mg/kg of aspartame.[19] However, representatives of the manufacturer of aspartame have argued that these scientists were not directly measuring formaldehyde, but simply measuring levels of some by-product of the methanol from aspartame.[20] Tephly thinks that the by-product was not formaldehyde. The researchers have stated that the data in the experiment proves it was formaldehyde.[21]

[edit] Phenylalanine

One of the functional groups in aspartame is phenylalanine, which is unsafe for those born with phenylketonuria, a rare genetic condition. Phenylalanine is an amino acid commonly found in foods. Approximately 50% of aspartame (by mass) is broken down into phenylalanine, which is completely safe for everyone except sufferers of phenylketonuria. Because aspartame is metabolized and absorbed very quickly (unlike phenylalanine-containing proteins in foods), it is known that aspartame could spike blood plasma levels of phenylalanine.[22][23] The debate centers on whether a significant spike in blood plasma phenylalanine occurs at typical aspartame ingestion levels, whether a sudden influx of phenylalanine into the bloodstream adversely affects uptake of other amino acids into the brain and the production of neurotransmitters (since phenylalanine competes with other Large Neutral Amino Acids (LNAAs) for entry into the brain at the blood brain barrier), and whether a significant rise in phenylalanine levels would be concentrated in the brain of fetuses and be potentially neurotoxic.

Based on anecdotes from aspartame users, measuring levels of neurotransmitters in the brains of animals and measuring the potential of aspartame to cause seizures in animals, some scientists think that aspartame may affect neurotransmitter production.[24][25][26] They think that even a moderate spike in blood plasma phenylalanine levels from typical ingestion may have adverse consequences in long-term use. They are especially concerned that the phenylalanine can be concentrated in fetal brains to a potentially neurotoxic level.[27][28] However, other scientists think that a rise in blood plasma phenylalanine is negligible in typical use of aspartame[29] and their studies show no significant effects on neurotransmitter levels in the brain or changes in seizure thresholds.[30][31][32] In addition, they say that proven adverse effects of phenylalanine on fetuses has only been seen when blood phenylalanine levels stay at high levels as opposed to occasionally being spiked to high levels.[33]

An alternative sweetener, Neotame, has been developed apparently to solve the phenylalanine problem said to be associated with Aspartame (see Neotame).

[edit] Aspartic acid

Food contains aspartic acid as an amino acid bound to proteins. Natural food does not contain unbound free aspartic acid. Approximately 40% of aspartame (by mass) is broken down into aspartic acid. Because aspartame is metabolized and absorbed very quickly (unlike aspartic acid-containing proteins in foods), it is known that aspartame could spike blood plasma levels of aspartate to very high levels.[22][34] Aspartic acid belongs to a class of chemicals that in high concentrations act as an excitotoxin, inflicting damage on brain and nerve cells. High levels of excitotoxins have been shown in hundreds of animal studies to cause damage to areas of the brain unprotected by the blood-brain barrier and a variety of chronic diseases arising out of this neurotoxicity.[35][36] The debate amongst scientists has been raging since the early 1970s, when Dr. John Olney found that high levels of aspartic acid caused damage to the brains of infant mice.[37] Dr. Olney and consumer attorney, James Turner filed a protest with the FDA to block the approval of aspartame. The debate is complex and has focused on several areas: (a) whether the increase in plasma aspartate levels from typical ingestion levels of aspartame is enough to cause neurotoxicity in one dose or over time, (b) whether humans are susceptible to the neurotoxicity from aspartic acid seen in some animal experiments, (c) whether aspartic acid increases the toxicity of formaldehyde, (d) whether neurotoxicity from excitotoxins should consider the combined effect of aspartic acid and other excitotoxins such as glutamic acid from monosodium glutamate. The neuroscientists at a 1990 meeting of the Society for Neuroscience had a split of opinion on the issues related to neurotoxic effects from excitotoxic amino acids found in some additives such as aspartame.[38]

Some scientists think that humans and other primates are not as susceptible to excitotoxins as rodents and therefore there is little concern with aspartic acid from aspartame.[39][40] While they agree that the combined effects of all food-based excitotoxins should be considered,[41] their measurements of the blood plasma levels of aspartic acid after ingestion of aspartame and monosodium glutamate demonstrate that there is not a cause for concern.[42][43] Other scientists think that primates are susceptible to excitotoxic damage[44] and that humans concentrate excitotoxins in the blood more than other animals.[45] Based on these findings, they think that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than are rodents.[46] While they agree that typical use of aspartame does not spike aspartic acid to extremely high levels in adults, they are particularly concerned with potential effects in infants and young children,[47] the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels,[48] and the potential dangers of combining formaldehyde exposure from aspartame with excitotoxins given that chronic methanol exposure increases excitoxin levels in susceptible areas of the brain[49][50] and that excitotoxins may potentiate formaldehyde damage.[51]

[edit] Aspartylphenylalanine diketopiperazine

This type of diketopiperazine (DKP) is created in products as aspartame breaks down over time. For example, researchers found that 6 months after aspartame was put into carbonated beverages, 25% of the aspartame had been converted to DKP.[52] Concern amongst some scientists has been expressed that this form of DKP would undergo a nitrosation process in the stomach producing a type of chemical that could cause brain tumors.[53][54] Other scientists think that the nitrosation of aspartame or the DKP in the stomach would not produce a chemical that would cause brain tumors. In addition, only a minuscule amount of the nitrosated chemical would be produced.[55] There are very few human studies on the effects of this form of DKP. However, a (one-day) exposure study showed that the DKP was tolerated without adverse effects.[56]

[edit] Recently-published research

[edit] Mario Negri research institute

A 2007 study, published in Annals of Oncology of the European Society for Medical Oncology, reviewed Italian studies of incidences of cancer from 1991 and 2004 and concluded a "lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms".[57]

[edit] Ramazzini Foundation

Since the FDA approved aspartame for consumption in 1981, some researchers have suggested that a rise in brain tumor rates in the United States may be at least partially related to the increasing availability and consumption of aspartame.[53] The results of a large seven-year study into the long-term effects of eating aspartame in rats by the European Ramazzini Foundation for cancer research in Bologna, Italy were released in July 2005. The study of 1,800 rats demonstrates that aspartame administered at varying levels in feed causes a statistically significant increase of lymphomas-leukemias and malignant tumors of the kidneys in female rats and malignant tumors of peripheral nerves in male rats. The study showed that there was no statistically significant link between aspartame and brain tumors.

The Ramazzini study,[58][59] published in Environmental Health Perspectives, raised concerns about the levels of aspartame exposure. While a review by the American Food & Drug Administration's (FDA) review of the Razzamini study is still pending,[60] the European Food Safety Authority's (EFSA) issued a press release about the report fairly promptly.

The EFSA's press release about the Ramazzini study,[61] published on 5 May 2006, concluded that the increased incidence of lymphomas/leukaemias reported in treated rats was unrelated to aspartame, the kidney tumors found at high doses of aspartame were not relevant to humans, and that based on all available scientific evidence to date, there was no reason to revise the previously established Acceptable Daily Intake levels for aspartame.[62] The European Ramazzini Foundation responded to the EFSA press release, standing by their results and stating that they considered the 16% increase in incidence of lymphoma and leukemia between the aspartame group and control group signified that these cancers were caused by aspartame ingestion.[63] As the EFSA felt it had already addressed this in their 5 May 2006 press release, no further press release was made.[64] An open letter to the European Union Food Safety Authority, subsequently posted on the website of the World Natural Health Organization on 29 December 2006 states that the EFSA's published conclusion regarding the Ramazzini study's raw data "is bizarre", and also draws attention to conflicts of interest regarding members of the EFSA's panel:

“ The Guardian on 15 May 2006[65] quoted EFSA Executive Director, Dr Herman Koeter: "Dr Koeter said, he wanted to clear up misunderstandings about "conflicts of interest" among his advisory panel overseeing the review. MEPs complained last month that the scientist who chairs the advisory panel, Dr Susan Barlow, works for the International Life Sciences Institute, a body funded by sweetener manufacturers and major aspartame users such as Coca Cola, PepsiCo and Nestle, and Monsanto.[66]

The European commission was also told by MEPs of other "conflicts of interest". One scientist involved in the review had declared a research grant from Ajinomoto, the leading Japanese manufacturer of aspartame, they said. Other panel members listed links with food processors such as Nestlé in their declarations of interest.

But to say that these scientists therefore have a conflict of interest was a misunderstanding, Dr Koeter explained to the Rome conference. "The expertise required (to judge any new study on whether aspartame causes cancer) almost inevitably means having a previous involvement." Eliminate the scientists who had worked in the area before or who had worked for industry and there would be no scientists left, he said. The panel had been "fully impartial".

He insults our intelligence. Are we to believe there are no scientists in Europe capable of conducting this study except those paid by the aspartame industry? The one thing Dr Koeter didn't get from the advisory panel was impartiality.[67]

 ”

[edit] National Cancer Institute

A study published in April 2006 sponsored by the National Cancer Institute involved 340,045 men and 226,945 women, ages 50 to 69, found no statistically significant link between aspartame consumption and leukemias, lymphomas or brain tumors.[68] The study used surveys filled out in 1995 and 1996 detailing food and beverage consumption. The researchers calculated how much aspartame they consumed, especially from sodas or from adding the sweetener to coffee or tea. The researchers report, "Our findings from this epidemiologic study suggest that consumption of aspartame-containing beverages does not raise the risk of hematopoietic or brain malignancies."

Critics of this study point out that while the study looked at humans, it did not look at life-long aspartame consumption as did the Ramazzini study on rats. The Ramazzini study simulated life-long consumption from childhood through old age (simulating 60 to 90 years of use). However the new National Cancer Institute study simply looked at subjects who consumed diet drinks during a twelve-month period from 1995 to 1996, without determining aspartame intake prior to the start of the study. Neurosurgeon Dr Russell Blaylock, commenting on the NCI study, remarked that "The greatest risk of leukemia and lymphoma would be in a younger population (young children and adolescents) and they would need to be exposed regularly from early in life."[69] Given that aspartame has only been publicly available for about a quarter of a century (in France from 1979, the USA since 1982, and the UK since 1983),[70] not one of the people examined in the NCI study could have ingested any aspartame product during their formative growth years, until they were at least into their mid-twenties.

The Ramazzini study had the disadvantage of being an animal study but looked at life-long consumption of aspartame. The National Cancer Institute study was a human study, but only looked at a limited range of older subjects with relatively short-term consumption of diet drinks. Finally, the questionnaire did not ask users to estimate aspartame consumption, only diet drink consumption.[71]

[edit] FDA approval process

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The first day Ronald Reagan was president of the U.S. (1981), he fired the head of the FDA who would not approve legalization of aspartame, due to the brain cancer in rats issue. Reagan hired Arthur Hayes MD (FDA Commissioner 1981-1983), who legalized aspartame a year later. Secretary of Defense and Reagan supporter Donald Rumsfeld was president and later CEO of G. D. Searle & Company from 1977 to 1985.[72][73] Arthur Hull Hayes MD was a defense contractor before he was head of the FDA. In November 1983 Hayes was under fire for accepting corporate gifts. He quit and joined Searle's public-relations firm as senior medical advisor. Searle lawyer Robert Shapiro renamed aspartame NutraSweet. Monsanto purchased Searle. Rumsfeld received a $12 million bonus. Shapiro later became Monsanto president.

Several members of the FDA board left their jobs after Stevia (aspartame's main competitor then) was banned in 1991. They were all hired at Nutrasweet in higher paying jobs, according to national records. Dr. Michael Friedman quit the FDA when Jane Henney was selected to become the permanent FDA commissioner (1999). Friedman elected to sign on with G. D. Searle as a senior vice president at a purported $500,000 a year. He later accepted a position with Monsanto.

[edit] Books

  • Dr Joseph Mercola and Dr Kendra Pearsall, Sweet Deception: Why Splenda, NutraSweet, and the FDA May Be Hazardous to Your Health, (Nelson Books, November 2006). ISBN 0-78522-179-4 and ISBN-13 978-0785221791
  • Miladie L. Dillard, Food Sweeteners - Aspartame and Its Adverse Reactions, Strange Symptoms, Illness Behavior and Controversy: Index of New Information With Authors and Subjects, (Abbe Pub Assn of Washington DC, Reprint edition, March 1997). ISBN 1-55914-850-0 and ISBN-13 978-1559148504.
  • Christian Tschanz (Editor), Harriett H. Butchko (Editor), W. Wayne Stargel (Editor), Frank N. Kotsonis (Editor), The Clinical Evaluation of a Food Additive: Assessment of Aspartame, (CRC, June 1996). ISBN 0-84934-973-7 and ISBN-13 978-0849349737.

[edit] References

  1. ^ Olney, J.W., N.B. Farber, E. Spitznagel, L.N. Robins, 1996. "Increasing Brain Tumor Rates: Is There a Link to Aspartame?" Journal of Neuropathology and Experimental Neurology, Volume 55, pages 1115-1123.
  2. ^ Soffritti, Morando, et al., "First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats." Environmental Health Perspectives, Volume 114(3): 379-385, 2006.
  3. ^ Roberts, H.J., "Does Aspartame Cause Human Brain Cancer," Journal of Advancement in Medicine, Volume 4(4):231-241, 1991.
  4. ^ GAO 1986. "Six Former HHS Employees' Involvement in Aspartame's Approval." United States General Accounting Office, GAO/HRD-86-109BR, July 1986.
  5. ^ Gordon, Gregory, United Press International Investigation, "NutraSweet: Questions Swirl." 1987.
  6. ^ Food Chemical News, June 12, 1995, Page 27.
  7. ^ Department of Health & Human Services (DHHS). (1993, April 1) Adverse Reactions Associated with Aspartame Consumption (HFS-728). Chief, Epidemiology Branch. Retrieved October 24, 2005. an image of part of the document
  8. ^ Walton RG, Hudak R, Green-Waite RJ, "Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population," Biological Psychiatry, Vol. 34, Pages 13-17, 1993
  9. ^ Koehler SM, Glaros A, "The effect of aspartame on migraine headache," Headache, Volume 28, pages 10-14, 1988
  10. ^ Smith JD, Terpening CM, Schmidt SO, Gums JG, "Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins," The Annals of Pharmacotherapy, Volume 35, pages 702-706, 2001
  11. ^ Spiers PA, Sabounjian L, Reiner A, Myers DK, Wurtman J, Schomer DL, "Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects," American Journal of Clinical Nutrition, Volume 68, pages 531-537, 1998
  12. ^ Schiffman SS, Buckley CE 3rd, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS, "Aspartame and susceptibility to headache," New England Journal of Medicine, Volume 317, pages 1181-1185, 1987
  13. ^ Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S, "Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study," Journal of The National Cancer Institute, Volume 89, pages 1072-1074, 1997
  14. ^ Stegink LD, Filer LJ Jr, Bell EF, Ziegler EE. Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. Metabolism. Volume 36, Issue 5, Pages 507-512. PMID 3574137. 1987 Retrieved on January 31, 2007.
  15. ^ PMID 12180494
  16. ^ sciencedirect article
  17. ^ "Aspartame: Methanol and the Public Health" Journal of Applied Nutrition Vol. 36(1) on dorway.com
  18. ^ holisticmed.com about methanol
  19. ^ PMID 9714421
  20. ^ PMID 12180494
  21. ^ Personal communication from Dr. Mari Alemany (lead author of the study) to Rich Murray at healthgroups yahoo, message 864
  22. ^ a b Stegink L, Filer L, Bell E, Ziegler E (1987). "Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence". Metabolism 36 (5): 507-12. PMID 3574137. 
  23. ^ Møller S (1991). "Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man". Pharmacol Toxicol 68 (5): 408-12. PMID 1946186. 
  24. ^ Maher T, Wurtman R. "Possible neurologic effects of aspartame, a widely used food additive". Environ Health Perspect 75: 53-7. PMID 3319565. 
  25. ^ Pinto J, Maher T (1988). "Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice". Neuropharmacology 27 (1): 51-5. PMID 3352866. 
  26. ^ Sharma R, Coulombe R (1987). "Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain". Food Chem Toxicol 25 (8): 565-8. PMID 2442082. 
  27. ^ dorway.com, elsas
  28. ^ trustedhands.com, aspartame and pregnancy
  29. ^ ncbi PubMed 2215254
  30. ^ ncbi PubMed 2013754
  31. ^ ncbi PubMed 2379890
  32. ^ ncbi PubMed 2470165
  33. ^ ncbi PubMed 3351801
  34. ^ ncbi PubMed 3670074
  35. ^ ISBN 0-89859-735-8
  36. ^ holistic med.com, msg-review
  37. ^ ncbi PubMed 5464249
  38. ^ ncbi PubMed 2294587
  39. ^ ncbi PubMed 810365
  40. ^ ncbi PubMed 827619
  41. ^ nlm.nih.gov document
  42. ^ ncbi PubMed 903828
  43. ^ ncbi PubMed 2909831
  44. ^ ncbi PubMed 4626680
  45. ^ holistic med.com stegink.jpg
  46. ^ ncbi PubMed 6152304
  47. ^ ncbi PubMed 1982368
  48. ^ ncbi PubMed 7854587
  49. ^ ncbi PubMed 12490131
  50. ^ ncbi pubmed 12112376
  51. ^ healthgroups @ yahoo: aspartameNM, message 1173
  52. ^ ACS article jf000640a43
  53. ^ a b ncbi PubMed 8939194
  54. ^ ncbi PubMed 8505016
  55. ^ ncbi PubMed 8990134
  56. ^ ncbi PubMed 8409113
  57. ^ Gallus S; Scotti L, Negri E, Talamini R, Franceschi S, Montella M, Giacosa A, Dal Maso L, La Vecchia C. (January 2007). "Artificial sweeteners and cancer risk in a network of case–control studies". Annals of Oncology 18 (1): 40-44. DOI:10.1093/annonc/mdl346. Retrieved on 2007-03-01. 
  58. ^ Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, and Luca Lambertini, "Aspartame induces lymphomas and leukaemias in rats (L’aspartame induce linfomi e leucemie nei ratti)", Eur. J. Oncol. 10 (2005), nbr. 2, pp. 107-116.
  59. ^ Abstract: Soffritti et al., "Aspartame induces lymphomas and leukaemias in rats", Eur. J. Oncol. 10 (2005), nbr. 2, pp. 107-116.
  60. ^ FDA, 2006 news topic 1369
  61. ^ EFSA EU, press release 1472 EN
  62. ^ EFSA EU, afc_opinions, 1471 en
  63. ^ raazzini.it, doc 292
  64. ^ EFSA EU, press release 1472 EN
  65. ^ Felicity Lawrence. Food safety authority says aspartame not linked to cancer. Guardian Unlimited. Retrieved on December 31, 2006.
  66. ^ List of International Life Sciences Institute members. Retrieved on December 31, 2006.
  67. ^ Dr Betty Martini (2006-12-29). Open Letter to EU Food Safety Authority about Aspartame. Retrieved on March 5, 2007.
  68. ^ Seattle PI, NWSource, 265559_soda
  69. ^ Dr Russell Blaylock (2006-04-12). Aspartame Is Still Hazardous. Retrieved on December 31, 2006.
  70. ^ http://www.canderel.uk.com/uk/corporate/historical.asp
  71. ^ WNHO, diet questionnaire
  72. ^ [1]
  73. ^ [2]

[edit] See also

[edit] External links

[edit] pro-aspartame

[edit] anti-aspartame

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