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 alleged connections between aspartame and diseases such as brain tumors, brain lesions, and lymphoma.[1] [2] [3] These findings, combined with notable conflicts of interest in the approval process, have engendered vocal activism regarding the possible risks of aspartame.[4] [5]

Contents

[edit] Known effects

While it is well-known aspartame contains phenylalanine which is unsafe for those born with phenylketonuria, research has also indicated more recently that aspartame may be implicated in other public health issues and holds serious health risks.

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, although this does not mean physician-reported or self-reported health effects are a basis for drawing scientific conclusions.[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 biochemical changes from ingesting aspartame in slow-dissolving capsules are many times smaller than those from ingesting aspartame dissolved in liquids (such as carbonated beverages). [1]

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 involving 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. Some scientists think that the methanol cannot be a problem because: (a) there is not enough methanol absorbed to cause toxicity, (b) methanol and formaldehyde are already a by-product of human metabolism, and (c) there is more methanol in some alcoholic beverages and fruit juices than is derived from aspartame ingestion. [2] [3]

Other scientists think (a) fruit juices and alcoholic beverages always contain protective chemicals such as ethanol that block conversion of methanol into formaldehyde, but aspartame contains no protective factors, (b) the levels of methanol and particularly formaldehyde have been proven to cause chronic toxicity in humans,and (c) the low levels of methanol and formaldehyde in human metabolism are tightly-controlled such that significant increases from aspartame ingestion are not safe. [4], [5]

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. [6] However, it has been argued by Tephly that these scientists were not directly measuring formaldehyde, but simply measuring levels of some by-product of the methanol from aspartame. [7] Tephly thinks that the by-product was not formaldehyde. The researchers have stated that the data in the experiment have proven it was formaldehyde. [8]

[edit] Phenylalanine

Phenylalanine is an amino acid commonly found in foods. Approximately 50% of aspartame (by mass) is broken down into phenylalanine. 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. [9], [10] 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 case histories 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. [11], [12], [13] 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. [14], [15] Other scientists think that a rise in blood plasma phenylalanine is negligible in typical use of aspartame [16] and their studies show no significant effects on neurotransmitter levels in the brain or changes in seizure thresholds. [17], [18], [19] 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. [20]

[edit] Aspartic acid

Aspartic acid is an amino acid commonly found in foods. 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. [21], [22] Aspartic acid is in a class of chemicals known as excitotoxins. Abnormally high levels of excitotoxins have been shown in hundreds of animals 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. ISBN 0-89859-735-8, [23] 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 [24]. 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. [25]

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. [26], [27] While they agree that the combined effects of all food-based excitotoxins should be considered [28], 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. [29], [30] Other scientists think that primates are susceptible to excitotoxic damage [31] and that humans concentrate excitotoxins in the blood more than other animals. [32] Based on these findings, they think that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than are rodents. [33] 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 [34], the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels [35], 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 [36], [37] and that excitotoxins may potentiate formaldehyde damage. [38]

[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. [39] 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. [40], [41] 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. [42] 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. [43]

[edit] Responses

There have been more than 600 studies on aspartame and thousands of studies on aspartame breakdown products and metabolites. [citation needed]

[edit] Recently-published research

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. [52] 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 1,900 rats found evidence that aspartame caused leukemia and lymphoma cancer in female rats. The study showed that there was no statistically significant link between aspartame and brain tumors.

The study, published in the European Journal of Oncology, raised concerns about the levels of aspartame exposure. However, the European Food Safety Authority's (EFSA) review found that the European Ramazzini Foundation's conclusion that aspartame is a carcinogen was flawed and not supported by the data. [53] The American Food & Drug Administration's (FDA) review of the Razzamini study is still pending. [54]

A more recent analysis of the European Ramazzini Foundation data published in Environmental Health Perspectives found a link between life-long aspartame consumption in the rats and cancer of the kidney and peripheral nerves. [55]

A review of the Ramazzini study by the European Food Safety Authority (EFSA), published 04 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 is no reason to revise the previously established Acceptable Daily Intake levels for aspartame.[56] The European Ramazzini Foundation responded to the EFSA findings by stating that they thought 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. [57] As the EFSA had already addressed this in their 04 May 2006 press release, no further press release was made. [58]

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. [59] 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. The Ramazzini study simulated life-long consumption from childhood through old age (e.g., simulating 60 to 90 years of use). The new National Cancer Institute study looked at subjects who consumed diet drinks during a 12-month period from 1995 to 1996. 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 subjects with relatively short-term consumption of diet drinks. Finally, the questionnaire did not ask users to estimate aspartame consumption, only diet drink consumption. [60]

[edit] Films

[edit] See also

[edit] External links

[edit] Pro-aspartame

[edit] Anti-aspartame

[edit] News & General Articles

[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. http://www.ehponline.org/members/2005/8711/8711.pdf
  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. http://archive.gao.gov/d4t4/130780.pdf
  5. ^ Gordon, Gregory, United Press International Investigation, "NutraSweet: Questions Swirl," 1987. http://www.dorway.com/upipaper.txt
  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 Oct 24, 2005 from http://www.presidiotex.com/aspartame/Facts/92_Symptoms/92_symptoms.gif (This is 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
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