Jump to content

Aspartame controversy: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Lead, the controversy did not end in the 1980s (look at e.g. ref 49 and 64 below)
(Username or IP removed)
→‎Reported effects: I have verified this Food Chemical News source. If you want the full-text, drop a note on my talk page. Please do diligence before removing high-quality sources.
Line 18: Line 18:


The debate over possible adverse health effects has focused{{Fact|date=November 2008}} mainly on four [[Metabolite#Metabolites|metabolites]] of aspartame: methanol, phenylalanine, aspartic acid, and aspartylphenylalanine diketopiperazine.
The debate over possible adverse health effects has focused{{Fact|date=November 2008}} mainly on four [[Metabolite#Metabolites|metabolites]] of aspartame: methanol, phenylalanine, aspartic acid, and aspartylphenylalanine diketopiperazine.

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. He stated that "there is still concern" about the substance and that "some people have an intolerance [to aspartame]".<ref>Food Chemical News, June 12, 1995, Page 27.</ref>


===Methanol and formaldehyde===
===Methanol and formaldehyde===

Revision as of 18:49, 14 November 2008

The artificial sweetener aspartame has been the subject of public controversy regarding its safety since the 1980s[1] and the circumstances around its approval, and its shelf stability.[2] Some studies recommended further investigation into any possible connection between aspartame and diseases such as brain tumors, brain lesions, and lymphoma.[3][4] These findings, combined with alleged conflicts of interest in the approval process, have been the focus of vocal activism regarding the possible risks of aspartame.[5]

The conspiracy theories, claims of aspartame dangers, and the source of those claims has been the subject of critical examination.[6] In 1987, the US Government Accountability Office concluded that the food additive approval process had been followed for aspartame.[7] Based on government research reviews and recommendations from advisory bodies such as the European Commission’s Scientific Committee on Food and the Food and Agriculture Organization/World Health Organization Joint Expert Committee on Food Additives, aspartame has been found to be safe for human consumption by more than ninety countries world-wide.[8][9] The U.S. Food and Drug Administration states that the safety of aspartame is "clear cut" and "one of the most thoroughly tested and studied food additives the agency has ever approved."[10]

Alleged conspiracy and dangers

An investigation by the Media Awareness Network[11] has been published which details the history behind the conspiracy theories and claims of aspartame dangers. They found the main activist and source of much of the material to be Betty Martini. This analysis says Ms. Martini constructed an apparently false story about "Nancy Markle", and has since spread the meme across the internet.[6] This conspiracy theory has been analyzed on several major internet conspiracy theory and urban legend websites.[12][13][14]

An Editor's Note from the Multiple Sclerosis Foundation sums up the story:

"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 has 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."[15]

FDA approval process

Some critics of Aspartame use have expressed concerns about its approval.[citation needed] Specifically, they note that the head of the FDA, Jere E. Goyan, was removed from his post on the first day of Ronald Reagan's presidency (1981). Goyan had refused to approve the use of aspartame due to studies documenting increase of cancers in rats.[citation needed] Reagan appointed Arthur Hull Hayes, MD as FDA Commissioner in April 1981. A FDA Public Board of Inquiry (PBOI), independent scientific advisors to the FDA, concluded in 1981 that aspartame did not cause brain damage but argued that there was not yet "sufficient scientific evidence" that aspartame did not cause brain tumors in rats; the PBOI recommended against approval of aspartame at that time, concluding that further study was needed.[16] However, Hayes approved aspartame as a food additive, citing newly available results from a recently-released Japanese brain tumor study, the results of which, the PBOI chairman later noted, would have resulted in an "unqualified approval" from the PBOI panel.[16] In November 1983, Hayes left the FDA and joined Searle's public-relations firm Burson-Marsteller as senior medical advisor.[17]

Reported effects

Some human and animal studies have found adverse effects associated with very high dosages of aspartame, or in certain susceptible groups.[18][19][20] and some have found no adverse effects.[21][22][23] It is not only the results of the research that have been questioned, but the design of the research that led to specific outcomes.[24]

The debate over possible adverse health effects has focused[citation needed] mainly on four metabolites of aspartame: methanol, phenylalanine, aspartic acid, and aspartylphenylalanine diketopiperazine.

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. He stated that "there is still concern" about the substance and that "some people have an intolerance [to aspartame]".[25]

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 and then to formic acid. Some research has indicated formaldehyde accumulation from aspartame ingestion.[26] However, the metabolism of aspartame does not damage the body because: (a) the quantity of methanol produced is too small to disrupt normal physiological processes; (b) methanol and formaldehyde are natural by-products of human metabolism and are safely processed by various enzymes; (c) there is more methanol in some natural fruit juices and alcoholic beverages than is derived from aspartame ingestion.[27][28] and (d) even large doses of pure methanol have been shown in non-human primate studies to lead to ample accumulation of formic acid (as formate), while no formaldehyde was detected.[29]

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.[26] However, these scientists were not directly measuring formaldehyde, but simply measuring levels of some by-product of the methanol from aspartame.[27]

Phenylalanine

One of the moieties of the aspartame molecule is phenylalanine, which is unsafe for those born with phenylketonuria, a rare genetic condition. Phenylalanine is one of the nine essential amino acids and is commonly found in foods. Approximately 50% of aspartame (by mass) is broken down into phenylalanine, which is considered 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.[30][31] Scientists have reported that a rise in blood plasma phenylalanine is negligible in typical use of aspartame[32] and their studies show no significant effects on neurotransmitter levels in the brain or changes in seizure thresholds.[33][34][35] 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.[36]

An alternative sweetener, neotame, has been developed apparently to solve the phenylalanine problem said to be associated with aspartame.

Aspartic acid

Food contains aspartic acid (aspartate), an amino acid in the structure of proteins. 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 can spike blood plasma levels of aspartate to very high levels.[30][37]

Aspartic acid belongs to a class of chemicals that, in high concentrations, act as an excitotoxin, inflicting damage on brain and nerve cells. Aspartate does not normally cross the blood-brain barrier in most parts of the brain without active uptake by transporters.[38] High levels of excitotoxins have been shown in 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.[39] John Olney found in 1970 that high levels of aspartic acid caused damage to the brains of infant mice.[40] Olney and consumer attorney James Turner filed a protest with the FDA to block the approval of aspartame. 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.[41]

Humans and other primates are not as susceptible to excitotoxins as rodents and therefore comparisons to human safety are problematic.[42][43] The measurements of the blood plasma levels of aspartic acid after ingestion of aspartame and monosodium glutamate do not indicate to human subject researchers a cause for concern.[citation needed][44][45] One group was concerned with potential effects in infants and young children,[46] the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels,[39] 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[47][48] and that excitotoxins may potentiate formaldehyde damage.

Aspartylphenylalanine diketopiperazine

Aspartylphenylalanine diketopiperazine, a 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.[49]

Concern among 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.[50][51] However, the nitrosation of aspartame or the DKP in the stomach likely does not produce chemicals that cause brain tumors. In addition, only a minuscule amount of the nitrosated chemical can be produced.[52] 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.[53]

Recently-published research

Mario Negri research institute

A 2007 study, published in Annals of Oncology of the European Society for Medical Oncology, reviewed Italian studies of instances 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".[54]

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.[50] The results of a large seven-year study into the long-term effects of eating aspartame in rats by the European Ramazzini Foundation Institute for cancer research in Bologna, Italy were released in July 2005. In the study of 1,800 rats, the research concluded 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,[55] published in Environmental Health Perspectives,[56] raised concerns about the levels of aspartame exposure. While a review by the American Food & Drug Administration's (FDA) of the Razzamini study was still pending,[57] the European Food Safety Authority (EFSA) issued a press release about the Ramazzini study on 5 May 2006.[58] It stated 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.[59] FDA later submitted its findings based on the evidence, and replied:[60]

Based on the available data... we have identified significant shortcomings in the design, conduct, reporting, and interpretation of this study. FDA finds that the reliability and interpretation of the study outcome is compromised by these shortcomings and uncontrolled variables, such as the presence of infection in the test animals.[60]

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.[citation needed] As the EFSA felt it had already addressed this in their 5 May 2006 press release, no further press release was made.[58]

The Guardian on 15 May 2006[61] 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.[62]
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'.

In response to criticism, the Ramazzini Foundation conducted a new study entitled "Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal Life Increases Cancer Effects in Rats", confirming the carcinogenic effects of aspartame from previous studies.[63][64] The Foundation stated: "The results of this carcinogenicity bioassay not only confirm, but also reinforce the first experimental demonstration of APM's multipotential carcinogenicity at a dose level close to the acceptable daily intake (ADI) for humans. Furthermore, the study demonstrates that when lifespan exposure to APM begins during fetal life, its carcinogenic effects are increased."[65]

In August 2007, the New Zealand Food Safety Authority (NZFSA) published a press release commenting upon the Italian study:

These studies were conducted in a way that could not possibly have provided any information about the toxicity of aspartame – or in fact anything else in the rats’ diet. The animals used were allowed to live until they died naturally, meaning that all the study did was show the results of ageing, which as we all know is a natural process that leads, inevitably, to death.
In fact, the only conclusion that can be drawn from the results is that aspartame appears to be safe because the studies showed that those rats fed it (even at very high doses) lived as long (if not longer) as untreated rats, despite consuming up to more than 100 times the ADI every day of their lives. If aspartame was as horrendously toxic as is being claimed, it would be logical to expect the rats dosed with it to have shortened life-spans. The conclusions drawn by the researchers were clearly not backed up by their own data.[66]

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.[67] 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."

Postulated conflict of interest prior to 1996

In 1996, Ralph G. Walton, then Professor of Clinical Psychiatry, Northeastern Ohio Universities College of Medicine, made a private survey of 166 studies of aspartame in peer reviewed medical literature prior to 1996. According to Walton's review, 74 studies had Nutrasweet industry related funding and 92 were independently funded. 100% of the industry funded research attested to aspartame's safety, whereas 92% (85 of 92) of the independently funded (private and personal) research identified a problem.[citation needed]

In a rebuttal to Walton's review, the 'Aspartame Information Service' (a service provided by Ajinomoto, a producer of aspartame and supplier to well known food and drink makers), states that of the 85 studies:[68]

  • 10 studies actually involve aspartate and not aspartame and are irrelevant to aspartame safety.
  • 18 of the studies do not draw any negative conclusions about aspartame.
  • 5 are reviews, not peer-reviewed studies.
  • 2 are reports, not peer-reviewed studies.
  • 5 are anecdotes, based on observations of patients.
  • 11 are conference proceedings, not peer-reviewed studies.
  • 19 are letters to medical journals.
  • 3 are different reports of the same study.
  • 2 are exact duplicates of other documents appearing in the list.
  • 3 are different reports of the same allegations.

This totals 78 of 85 studies, leaving 7 independently funded studies that found a problem with aspartame, that the Aspartame Information Service did not find issue with.

See also

References

  1. ^ Humphries P, Pretorius E, Naudé H (2008). "Direct and indirect cellular effects of aspartame on the brain". European journal of clinical nutrition. 62 (4): 451–62. doi:10.1038/sj.ejcn.1602866. PMID 17684524. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Carole Sugarman (July 3, 1983), Controversy Surrounds Sweetener Aspartame Approval & The Soft Drink Industry Aspartame Controversy, Washington Post, pp. D1-2
  3. ^ 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.
  4. ^ 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.
  5. ^ GAO 1986. "Six Former HHS Employees' Involvement in Aspartame's Approval." United States General Accounting Office, GAO/HRD-86-109BR, July 1986.
  6. ^ a b Deconstructing Web Pages - An exercise deconstructing a web page to determine its credibility as a source of information, using the aspartame controversy as the example.
  7. ^ "U.S. GAO - HRD-87-46 Food and Drug Administration: Food Additive Approval Process Followed for Aspartame, June 18, 1987". Retrieved 2008-09-05.
  8. ^ Health Canada: "Aspartame - Artificial Sweeteners". Retrieved 2008-11-08.
  9. ^ Food Standards Australia New Zealand: "Food Standards Australia New Zealand: Aspartame (September 2007)". Retrieved 2008-11-08.
  10. ^ FDA Consumer magazine November - December 1999
  11. ^ Media Awareness Network website.
  12. ^ Kiss My Aspartame. False. Snopes.com
  13. ^ The World's Best Ant Poison. False. Snopes.com
  14. ^ About.com, Urban legends
  15. ^ Examining the Safety of Aspartame, Multiple Sclerosis Foundation
  16. ^ a b FDA Statement on Aspartame, November 18, 1996
  17. ^ Six Former HHS Employees' Involvement in Aspartame's Approval, United States General Accounting Office, GAO/HRD-86-109BR, July 1986.
  18. ^ 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
  19. ^ Koehler SM, Glaros A, "The effect of aspartame on migraine headache," Headache, Volume 28, pages 10-14, 1988
  20. ^ 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
  21. ^ 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
  22. ^ 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
  23. ^ 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
  24. ^ 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.
  25. ^ Food Chemical News, June 12, 1995, Page 27.
  26. ^ a b Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernández-López JA, Alemany M (1998). "Formaldehyde derived from dietary aspartame binds to tissue components in vivo". 63 (5): 337–349. PMID 9714421. {{cite journal}}: Cite has empty unknown parameter: |month= (help); Cite journal requires |journal= (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "PubMed9714421" was defined multiple times with different content (see the help page).
  27. ^ a b Butchko HH, Stargel WW, Comer CP; et al. (2002). "Aspartame: review of safety". Regul. Toxicol. Pharmacol. 35 (2 Pt 2): S1–93. doi:10.1006/rtph.2002.1542. PMID 12180494. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Abel Lajtha, Margaret A. Reilly and David S. Dunlop (June 1994). "Aspartame consumption: lack of effects on neural function". The Journal of Nutritional Biochemistry. 5 (6). Elsevier Science Inc.: 266–283. doi:10.1016/0955-2863(94)90032-9.
  29. ^ McMartin KE, Martin-Amat G, Noker PE, Tephly TR (1979). "Lack of a role for formaldehyde in methanol poisoning in the monkey". Biochem. Pharmacol. 28 (5): 645–9. doi:10.1016/0006-2952(79)90149-7. PMID 109089. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ 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. doi:10.1016/0026-0495(87)90052-7. PMID 3574137.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "PubMed3574137" was defined multiple times with different content (see the help page).
  31. ^ 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.
  32. ^ Stegink LD, Filer LJ, Bell EF, Ziegler EE, Tephly TR, Krause WL (1990). "Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria". Metabolism: clinical and experimental. 39 (10): 1076–81. PMID 2215254. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ Koeppe RA, Shulkin BL, Rosenspire KC; et al. (1991). "Effect of aspartame-derived phenylalanine on neutral amino acid uptake in human brain: a positron emission tomography study". Journal of neurochemistry. 56 (5): 1526–35. doi:10.1111/j.1471-4159.1991.tb02047.x. PMID 2013754. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Romano M, Diomede L, Guiso G, Caccia S, Perego C, Salmona M (1990). "Plasma and brain kinetics of large neutral amino acids and of striatum monoamines in rats given aspartame". Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 28 (5): 317–21. doi:10.1016/j.asr.2007.02.043. PMID 2379890. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ Dailey JW, Lasley SM, Mishra PK, Bettendorf AF, Burger RL, Jobe PC (1989). "Aspartame fails to facilitate pentylenetetrazol-induced convulsions in CD-1 mice". Toxicology and applied pharmacology. 98 (3): 475–86. doi:10.1016/0041-008X(89)90176-2. PMID 2470165. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ London RS (1988). "Saccharin and aspartame. Are they safe to consume during pregnancy?". The Journal of reproductive medicine. 33 (1): 17–21. PMID 3351801. {{cite journal}}: Unknown parameter |month= ignored (help)
  37. ^ Stegink LD, Filer LJ, Baker GL (1987). "Plasma amino acid concentrations in normal adults ingesting aspartame and monosodium L-glutamate as part of a soup/beverage meal". Metabolism: clinical and experimental. 36 (11): 1073–9. PMID 3670074. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Smith, QR (2000). "Transport of glutamate and other amino acids at the blood-brain barrier". The Journal of nutrition. 130 (Supplement 4S). The American Society for Nutritional Sciences: 1016S–1022S. PMID 10736373. Retrieved 2007-01-31.
  39. ^ a b Olney, J. (1994). "Excitotoxins in Foods". Neurotoxicology. 15 (3): 535–544. PMID 7854587. Cite error: The named reference "PubMed7854587" was defined multiple times with different content (see the help page).
  40. ^ Olney JW, Ho OL (1970). "Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine". Nature. 227 (5258): 609–11. doi:10.1038/227609b0. PMID 5464249. {{cite journal}}: Unknown parameter |month= ignored (help)
  41. ^ Barinaga M (1990). "Amino acids: how much excitement is too much?". Science (New York, N.Y.). 247 (4938): 20–2. PMID 2294587. {{cite journal}}: Unknown parameter |month= ignored (help)
  42. ^ Abraham R, Swart J, Golberg L, Coulston F (1975). "Electron microscopic observations of hypothalami in neonatal rhesus monkeys (Macaca mulatta) after administration of monosodium-L-glutamate". Experimental and molecular pathology. 23 (2): 203–13. doi:10.1016/0014-4800(75)90018-0. PMID 810365. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  43. ^ Reynolds WA, Butler V, Lemkey-Johnston N (1976). "Hypothalamic morphology following ingestion of aspartame or MSG in the neonatal rodent and primate: a preliminary report". Journal of toxicology and environmental health. 2 (2): 471–80. PMID 827619. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ Stegink LD, Filer LJ, Baker GL (1977). "Effect of aspartame and aspartate loading upon plasma and erythrocyte free amino acid levels in normal adult volunteers". The Journal of nutrition. 107 (10): 1837–45. PMID 903828. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  45. ^ Stegink LD, Filer LJ, Baker GL; et al. (1989). "Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria". Metabolism: clinical and experimental. 38 (1): 78–84. PMID 2909831. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Olney JW (1990). "Excitotoxin-mediated neuron death in youth and old age". Progress in brain research. 86: 37–51. doi:10.1016/S0079-6123(08)63165-9. PMID 1982368.
  47. ^ González-Quevedo A, Obregón F, Urbina M, Roussó T, Lima L (2002). "Effect of chronic methanol administration on amino acids and monoamines in retina, optic nerve, and brain of the rat". Toxicology and applied pharmacology. 185 (2): 77–84. doi:10.1006/taap.2002.9477. PMID 12490131. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ Izumi Y, Shimamoto K, Benz AM, Hammerman SB, Olney JW, Zorumski CF (2002). "Glutamate transporters and retinal excitotoxicity". Glia. 39 (1): 58–68. doi:10.1002/glia.10082. PMID 12112376. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ Wing Sum Tsang, Margaret A. Clarke, and Frederick W. Parrish (1985). "Determination of aspartame and its breakdown products in soft drinks by reverse-phase chromatography with UV detection". Journal of Agricultural and Food Chemistry. 33: 734–738. doi:10.1021/jf00064a043.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ a b Olney JW, Farber NB, Spitznagel E, Robins LN (1996). "Increasing brain tumor rates: is there a link to aspartame?". Journal of neuropathology and experimental neurology. 55 (11): 1115–23. doi:10.1097/00005072-199611000-00002. PMID 8939194. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  51. ^ Shephard SE, Wakabayashi K, Nagao M (1993). "Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation". Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 31 (5): 323–9. PMID 8505016. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  52. ^ Flamm WG (1997). ""Increasing brain tumor rates: is there a link to aspartame?"". Journal of neuropathology and experimental neurology. 56 (1): 105–6. doi:10.1097/00005072-199701000-00014. PMID 8990134. {{cite journal}}: Unknown parameter |month= ignored (help)
  53. ^ Geha R, Buckley CE, Greenberger P; et al. (1993). "Aspartame is no more likely than placebo to cause urticaria/angioedema: results of a multicenter, randomized, double-blind, placebo-controlled, crossover study". The Journal of allergy and clinical immunology. 92 (4): 513–20. doi:10.1016/0091-6749(93)90075-Q. PMID 8409113. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  54. ^ Gallus S (2007). "Artificial sweeteners and cancer risk in a network of case–control studies" (abstract page). Annals of Oncology. 18 (1): 40–44. doi:10.1093/annonc/mdl346. PMID 17043096. Retrieved 2007-03-01. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)
  55. ^ Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, and Luca Lambertini (2005). "Aspartame induces lymphomas and leukaemias in rats (L'aspartame induce linfomi e leucemie nei ratti)" (PDF). Eur. J. Oncol. 10 (2): 107–116.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  56. ^ Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A (2006). "First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats". Environmental health perspectives. 114 (3): 379–85. PMC 1392232. PMID 16507461. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ FDA Statement on European Aspartame Study, May 8, 2006
  58. ^ a b EFSA EU, press release 1472 EN
  59. ^ EFSA EU, afc_opinions, 1471 en
  60. ^ a b FDA reviews Italian aspartame study
  61. ^ Felicity Lawrence. "Food safety authority says aspartame not linked to cancer". Guardian Unlimited. Retrieved 2006-12-31.
  62. ^ "List of International Life Sciences Institute members" (PDF). Retrieved 2006-12-31.
  63. ^ http://www.ramazzini.it/fondazione/newsDetail.asp?id=15 New aspartame data to be presented at Mount Sinai School of Medicine in NYC, USA, April 13, 2007
  64. ^ Soffritti, M. et. al (2007) "Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal Life Increases Cancer Effects in Rats", Environmental Health Perspectives (115:6) June 2007
  65. ^ Ramazzini APM study (Environmental Health Perspectives 114:379-385, 2006): First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats
  66. ^ Food Safety Authority challenges activists’ views on aspartame
  67. ^ Seattle PI, NWSource, 265559_soda
  68. ^ "Aspartame Information replies to the New York Times". Aspartame Information Service. 2006-02-16.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Aspartame_controversy&oldid=251814867"