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    Aspartame Controversy, in Wikipedia democratic encyclopedia, 72
    references (including AspartameNM # 864 and 1173 by Murray), brief
    fair summary of much more research: Murray 2007.01.01

    "It is well known that formaldehyde (HCHO) and reactive oxygen species
    (ROS), such as free radicals, are cytotoxic as well as potentially
    Although the individual effects of these reactants on cells have been
    investigated, the cytotoxicity exerted by the coexistence of HCHO and
    reactive radicals is poorly understood."

    Toxicology. 2005 Jun 1; 210(2-3): 235-45.
    Cytotoxic effect of formaldehyde with free radicals via increment of
    cellular reactive oxygen species.
    Saito Y, Nishio K, Yoshida Y, Niki E.,,,
    [ included in Reference 50 of 72 in Aspartame Controversy, in
    Widipedia democratic encyclopedia ]

    [ Reference 21 is:
    Butchko, Tephly, McMartin: Alemany, aspartame formaldehyde adducts in
    rats: Murray 2002.09.08 ]

    [ Rich Murray: Without altering text, spacing has been added to
    increase readability. ]

    Aspartame controversy
    >From Wikipedia, the free encyclopedia
    Jump to: navigation, search
    * This page was last modified 21:18, 23 December 2006.

    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]


    * 1 Known effects
    o 1.1 Methanol and Formaldehyde
    o 1.2 Phenylalanine
    o 1.3 Aspartic acid
    o 1.4 Aspartylphenylalanine diketopiperazine
    o 1.5 Responses
    o 1.6 Recently-published research
    * 2 See also
    * 3 External links
    o 3.1 Films
    o 3.2 Pro-aspartame
    o 3.3 Anti-aspartame
    o 3.4 News & General Articles
    * 4 References

    [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,
    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).[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
    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

    There has been some concern that aspartame metabolism releases
    methanol.[citation needed]
    Methanol is quickly absorbed and distributed throughout the body.
    It is quickly broken down into formaldehyde, formic acid, and then
    shuttled into the energy production pathway.[citation needed]
    The blindness caused by methanol's toxicity is due to the peculiarities
    of methanol metabolism around the nerves in the eye rather than an
    inherit toxicity of the molecule itself.[citation needed]
    It is believed 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.[15] [16]

    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.[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, 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
    Tephly thinks that the by-product was not formaldehyde.
    The researchers have stated that the data in the experiment have proven
    it was formaldehyde.[21]

    [edit] Phenylalanine

    One of the functional groups in aspartame is phenylalanine,
    which is unsafe for those born with phenylketonuria.
    Phenylalanine is an amino acid commonly found in foods.
    Approximately 50% of aspartame (by mass) is broken down into
    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
    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.
    Note that many of the nutritional supplements suppliers who are
    denouncing aspartame as toxic also sell phenylalanine as a nutritional

    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
    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.[26][27]
    Other scientists think that a rise in blood plasma phenylalanine is
    negligible in typical use of aspartame[28] and
    their studies show no significant effects on neurotransmitter levels in
    the brain or changes in seizure thresholds.[29][30][31]
    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.[32]

    [edit] Aspartic acid

    Aspartic acid is an amino acid commonly found in foods.
    Approximately 40% of aspartame (by mass) is broken down into aspartic
    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
    Aspartic acid is in a class of chemicals known as excitatory amino
    acids, which also includes glutamate (found in MSG).
    At high levels, excitatory amino acids can be toxic and might be
    considered 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.[34][35]
    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.[36]
    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.[37]

    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.[38][39]
    While they agree that the combined effects of all food-based
    excitotoxins should be considered[40],
    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.[41][42]
    Other scientists think that primates are susceptible to excitotoxic
    damage[43] and that humans concentrate excitotoxins in the blood more
    than other animals.[44]
    Based on these findings, they think that humans are approximately 5-6
    times more susceptible to the effects of excitotoxins than are
    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,[46]
    the potential long-term neurodegenerative effects of small-to-moderate
    spikes on plasma excitotoxin levels[47], 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 [48][49] and
    that excitotoxins may potentiate formaldehyde damage.[50]

    [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. [51]
    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.[52][53]
    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. [54]
    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.[55]

    [edit] Responses

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

    * The American Cancer Society argues that "since aspartame is
    broken down into these components before it is absorbed into the blood
    stream, aspartame in its initial form does not have the opportunity to
    travel to target organs, including the brain, to cause cancer."[56]

    * The Feingold Association has stated that aspartame "is reported
    to cause a variety of neurological effects from headache to seizures
    and brain tumors."[57]

    * The American Heart Association concludes that "extensive
    investigation so far hasn't shown any serious side effects from

    * The Association for Consumers Action on Safety and Health issued
    a consumer alert related to the dangers of ingesting aspartame.[59]

    * The National Cancer Institute argues "there is no evidence that
    the regulated artificial sweeteners on the market in the United States
    are related to cancer risk in humans."[60]

    * The National Health Federation calls aspartame a "neurotoxic
    artificial sweetener."[61]

    * The Food and Drug Administration says that more than "100
    toxicological and clinical studies it has reviewed confirm that
    aspartame is safe for the general population."[62]

    * The UK Campaign for Truth in Medicine (consumer organization)
    says that "Aspartame is, by far, the most dangerous substance on the
    market that is added to foods."[63]

    [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,[64] 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.[65]
    The American Food & Drug Administration's (FDA) review of the Razzamini
    study is still pending.[66]

    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.[67]

    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.[68]
    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.[69]
    As the EFSA had already addressed this in their 04 May 2006 press
    release, no further press release was made.[70]

    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.[71]
    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
    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.[72]

    [edit] See also

    * Sugar substitute

    [edit] External links

    [edit] Films

    * Sweet Misery: A Poisoned World,
    Google video *[1]. Directed by Cori Brackett and J. T. Waldron,
    * David Icke on Aspartame
    * Sweet Misery Trailer

    [edit] Pro-aspartame

    * Aspartame Information Service
    * Aspartame Archives
    * Aspartame -- American Council on Science and Health
    * Sugar Substitutes (U.S. FDA web page)
    * U.S. FDA web page "FDA Consumer" magazine article, "Artificial
    Sweeteners: No Calories...Sweet!"
    * Update on Aspartame Safety; EC Scientific Committee on Food (263
    KB PDF)
    * Health Canada
    * Review of the EC Scientific Committee's 2002
    * American Heart Association
    * National Cancer Institute
    * Multiple Sclerosis Foundation
    * Site of the Calorie Control Council, which is, according to its
    website, a "non-profit association representing the low-calorie and
    reduced-fat food and beverage industry."

    [edit] Anti-aspartame

    * Aspartame Support Group
    * Aspartame Toxicity Information Center
    * Aspartame -- Dorway to Discovery
    * How Excitotoxins Were Discovered
    * Excitotoxins -- MSG and Aspartame
    * Aspartame -- Mission Possible News/Articles
    * Aspartame Consumer Safety Network
    * Aspartame -- The Secret Danger
    * Aspartame -- Former U.S. FDA Investigator
    * Sweet Poison
    * Update on Aspartame Safety; Response to EC Scientific Committee
    on Food
    * Responses to Aspartame and Its Effects on Health
    * Nutrapoison, Part One by Alex Constantine
    * Dangers of Aspartame Links Page

    [edit] News & General Articles

    * Deconstructing Dinner on Aspartame, featuring the European
    Ramazzini Foundation study, Kootenay Co-op Radio CJLY, Canada, October
    12, 2006
    * Safety of Artificial Sweetener Called Into Question by MP, The
    Guardian, UK, December 15, 2005
    * The Straight Dope on aspartame
    * Free E-course on Aspartame Dangers
    * The Lowdown on Sweet? -- article in New York Times
    * The Safety of Aspartame, The New York Times, USA, February 21,
    * Artificial Sweetener Given the All Clear, New Scientist, May 13,
    * Center for Disease Control Full Report on Aspartame Complaints
    * "Kiss My Aspartame" -- the Urban Legends Reference Pages

    [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

    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 Oct 24, 2005 from
    (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,

    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. ^ a b c NCBI, PubMed 3574137

    15. ^ NCBI, pubmed 12180494

    16. ^ sciencedirect article

    17. ^ about methanol

    18. ^ about methanol

    19. ^ ncbi, PubMed 9714421

    20. ^ NCBI, PubMed 12180494

    21. ^ healthgroups yahoo, message 864 [ aspartameNM ]

    22. ^ ncbi, PubMed 1946186

    23. ^ ncbi PubMed 3319565

    24. ^ ncbi, PubMed 3352866

    25. ^ ncbi, PubMed 2442082

    26. ^, elsas

    27. ^, aspartame and pregnancy

    28. ^ ncbi PubMed 2215254

    29. ^ ncbi PubMed 2013754

    30. ^ ncbi PubMed 2379890

    31. ^ ncbi PubMed 2470165

    32. ^ ncbi PubMed 3351801

    33. ^ ncbi PubMed 3670074

    34. ^ ISBN 0-89859-735-8

    35. ^ holistic, msg-review

    36. ^ ncbi PubMed 5464249

    37. ^ ncbi PubMed 2294587

    38. ^ ncbi PubMed 810365

    39. ^ ncbi PubMed 827619

    40. ^ document

    41. ^ ncbi PubMed 903828

    42. ^ ncbi PubMed 2909831

    43. ^ ncbi PubMed 4626680

    44. ^ holistic stegink.jpg

    45. ^ ncbi PubMed 6152304

    46. ^ ncbi PubMed 1982368

    47. ^ ncbi PubMed 7854587

    48. ^ ncbi PubMed 12490131

    49. ^ ncbi pubmed 12112376

    50. ^ healthgroups @ yahoo: aspartameNM, message 1173

    51. ^ ACS article jf000640a43

    52. ^ a b ncbi PubMed 8939194

    53. ^ ncbi PubMed 8505016

    54. ^ ncbi PubMed 8990134

    55. ^ ncbi PubMed 8409113

    56. ^, aspartame

    57. ^, 06-2003

    58. ^, doc 4447

    59. ^ image on wikipedia

    60. ^, 3-19

    61. ^ The NHF, article 46

    62. ^ FDA, sugar

    63. ^ campaign for thruth, sugar body

    64. ^, aspartameGE2005.pdf

    65. ^ EFSA EU, press release 1472 EN

    66. ^ FDA, 2006 news topic 1369

    67. ^ ehp online, 2005, 8711.pdf

    68. ^ EFSA EU, afc_opinions, 1471 en

    69. ^, doc 292

    70. ^ EFSA EU, press release 1472 EN

    71. ^ Seattle PI, NWSource, 265559_soda

    72. ^ WNHO, diet questionnaire

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    50. ^ healthgroups @ yahoo: aspartameNM, message 1173
    five recent abstracts on formaldehyde damage to cells -- vitamin E and
    selenium protect, Yoshiro Saito and Yasukazu Yoshida et al, O'Brien PJ
    et al, Costa M et al: Murray 2005.06.07

    [ Herein I give selections from aspartameNM post #1173. ]

    [Rich Murray: Here is the abstract and four more that show that many
    groups are intensively studying cell damage and death from
    formaldehyde, and the role of chemicals that increase or decrease this
    damage from
    formaldehyde. ]

    "It is well known that formaldehyde (HCHO) and reactive oxygen species
    (ROS), such as free radicals, are cytotoxic as well as potentially
    Although the individual effects of these reactants on cells have been
    investigated, the cytotoxicity exerted by the coexistence of HCHO and
    reactive radicals is poorly understood."

    Toxicology. 2005 Jun 1; 210(2-3): 235-45.
    Cytotoxic effect of formaldehyde with free radicals via increment of
    cellular reactive oxygen species.
    Saito Y, Nishio K, Yoshida Y, Niki E.,,,

    It is well known that formaldehyde (HCHO) and reactive oxygen species
    (ROS), such as free radicals, are cytotoxic as well as potentially
    Although the individual effects of these reactants on cells have been
    investigated, the cytotoxicity exerted by the coexistence of HCHO and
    reactive radicals is poorly understood.
    The present study using Jurkat cells demonstrated that the coexistence
    of HCHO with water-soluble radical initiator,
    2,2'-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH)
    dramatically decreased cell viability,
    and that under such conditions scant cell death was observable induced
    by either of the reactants alone.
    Based on the results of phosphatidylserine exposure and caspase
    activation, this observed cell death, in fact,
    was apparently necrotic rather than apoptotic.
    To understand the mechanisms of the cell toxicity of HCHO and AIPH, we
    assessed two kinds of oxidative stress markers
    such as cellular glutathione (GSH) content and cellular ROS,
    and the DNA-protein cross-links,
    which formed as the result of HCHO treatment.
    A marked decrease in total cellular GSH was observed not only in the
    case of the coexistence conditions but also with AIPH alone.
    Dichlorodihydrofluorescein (DCF) assay revealed that cellular ROS were
    synergistically increased before cell death.
    The formation of DNA-protein cross-links was observed in the presence
    of HCHO and AIPH,
    and the extent was similar to HCHO alone.
    Co-incubation with semicarbazide, which inactivates HCHO,
    prevented this cell death induced by a combination of HCHO and AIPH.
    Semicarbazide also exhibited an inhibitory effect on the synergistic
    increment of cellular ROS and the formation of DNA-protein cross-links.
    These results suggest that the free radicals from AIPH induced GSH
    reduction, while HCHO resulted in the formation of DNA-protein
    eventuating in a synergistic, incremental increase of cellular ROS and
    cell death brought about by this combination.
    ************************************************** **************

    "The toxicity and carcinogenicity of formaldehyde (HCHO) has been
    attributed to its ability to form adducts with DNA and proteins."

    "This work demonstrates that DNA-protein cross-links can be formed in
    vitro following exposure to a variety of industrial compounds and that
    most cross-links are formed at cytotoxic concentrations."

    "At higher HCHO concentrations, lipid peroxidation ensued followed by
    cell death."

    "Antioxidants and iron chelators protected against HCHO cytotoxicity."

    Chem Biol Interact. 2001 Jan 30; 130-132(1-3): 285-96.
    The formaldehyde metabolic detoxification enzyme systems and molecular
    cytotoxic mechanism in isolated rat hepatocytes.
    Teng S, Beard K, Pourahmad J, Moridani M, Easson E, Poon R, O'Brien PJ.
    Faculty of Pharmacy, University of Toronto, 19 Russell St., Ont., M5S
    2S2, Toronto, Canada.
    416-978-2716 fax 416-978-8511, ]

    The toxicity and carcinogenicity of formaldehyde (HCHO) has been
    attributed to its ability to form adducts with DNA and proteins.
    A marked decrease in mitochondrial membrane potential and inhibition of
    mitochondrial respiration that was accompanied by reactive oxygen
    formation occurred when isolated rat hepatocytes were incubated with
    low concentrations of HCHO in a dose-dependent manner.
    Hepatocyte GSH was also depleted by HCHO in a dose-dependent manner.
    At higher HCHO concentrations, lipid peroxidation ensued followed by
    cell death.
    Cytotoxicity studies were conducted in which isolated hepatocytes
    exposed to HCHO were treated with inhibitors of HCHO metabolising
    There was a marked increase in HCHO cytotoxicity when either alcohol
    dehydrogenase or aldehyde dehydrogenase was inhibited.
    Inhibition of GSH-dependent HCHO dehydrogenase activity by prior
    depletion of GSH markedly increased hepatocyte susceptibility to HCHO.
    In each case, cytotoxicity was dose-dependent and corresponded with a
    decrease in hepatocyte HCHO metabolism and increased lipid
    Antioxidants and iron chelators protected against HCHO cytotoxicity.
    Cytotoxicity was also prevented, when cyclosporine or carnitine was
    added to prevent the opening of the mitochondrial permeability
    transition pore which further suggests that HCHO targets the
    Thus, HCHO-metabolising gene polymorphisms would be expected to have
    toxicological consequences on an individual's susceptibility to HCHO
    toxicity and carcinogenesis. PMID: 11306052
    ************************************************** **************

    "Chemicals such as cis-platinum, formaldehyde, chromate, copper, and
    certain arsenic compounds have been shown to produce DNA-protein
    cross-links in human in vitro cell systems at high doses, such as those
    in the cytotoxic range."

    J Toxicol Environ Health. 1997 Apr 11; 50(5): 433-49.
    DNA-protein cross-links produced by various chemicals in cultured human
    lymphoma cells.
    Costa M, Zhitkovich A, Harris M, Paustenbach D, Gargas M.
    Institute of Environmental Medicine, New York University Medical
    New York 10016, USA.

    Chemicals such as cis-platinum, formaldehyde, chromate, copper, and
    certain arsenic compounds have been shown to produce DNA-protein
    cross-links in human in vitro cell systems at high doses, such as those
    in the cytotoxic range.
    Thus far there have only been a limited number of other chemicals
    evaluated for their ability to produce cross-links.
    The purpose of the work described here was to evaluate whether select
    industrial chemicals can form DNA-protein cross-links in human cells in
    We evaluated acetaldehyde, acrolein, diepoxybutane, paraformaldehyde,
    2-furaldehyde, propionaldehyde, chloroacetaldehyde, sodium arsenite,
    and a deodorant tablet [Mega Blue; hazardous component listed as
    Short- and long-term cytotoxicity was evaluated and used to select
    appropriate doses for in vitro testing. DNA-protein cross-linking was
    evaluated at no fewer than three doses and two cell lysate washing
    temperatures (45 and 65 degrees C) in Epstein-Barr virus (EBV) human
    Burkitt's lymphoma cells.
    The two washing temperatures were used to assess the heat stability of
    the DNA-protein cross-link, 2-Furaldehyde, acetaldehyde, and
    propionaldehyde produced statistically significant increases in
    DNA-protein cross-links at
    washing temperatures of 45 degrees C, but not 65 degrees C, and at or
    above concentrations of 5, 17.5, and 75 mM, respectively.
    Acrolein, diepoxybutane, paraformaldehyde, and Mega Blue produced
    statistically significant increases in DNA-protein cross-links washed
    at 45 and 65 degrees C at or above concentrations of 0.15 mM, 12.5 mM,
    0.003%, and
    0.1%, respectively.
    Sodium arsenite and chloroacetaldehyde did not produce significantly
    increased DNA-protein cross-links at either temperature nor at any dose
    Excluding paraformaldehyde and 2-furaldehyde treatments, significant
    increases in DNA-protein cross-links were observed only at doses that
    resulted in complete cell death within 4 d following dosing.
    This work demonstrates that DNA-protein cross-links can be formed in
    vitro following exposure to a variety of industrial compounds and that
    most cross-links are formed at cytotoxic concentrations. PMID: 9140463
    ************************************************** *****
    short aspartame (methanol, formaldehyde) toxicity research summary:
    Murray 2007.01.01

    "Of course, everyone chooses, as a natural priority,
    to actively find, quickly share, and positively act upon the facts
    about healthy and safe food, drink, and environment."

    Rich Murray, MA Room For All
    505-501-2298 1943 Otowi Road Santa Fe, New Mexico 87505
    group with 76 members, 1,395 posts in a public, searchable archive
    aspartame groups and books: updated research review of 2004.07.16:
    Murray 2006.05.11

    Coca-Cola carcinogenicity in rats, Ramazzini Foundation, F Belpoggi, M
    Soffritti, Annals NY Academy Sciences 2006 Sept, parts of 17 pages:
    Murray 2006.12.02

    Fiorella Belpoggi & Morando Soffritti of Ramazzini Foundation prove
    lifetime carcinogenicity of Coca-Cola, aspartame, and arsenic, Annals
    of the NY Academy of Sciences: Murray 2006.11.28 aspartame arsenic

    soft drinks and adolescent hyperactivity, mental distress, conduct
    problems, Lars Lien, Nanna Lien, Sonja Heyerdahl, Mayne Thoresen, Espen
    Bjertness 2006 Oct., A J Pub Health: Murray 2006.10.21
    healthy diet, vitamins, and fish oil help reduce depression and
    violence, studies by Joseph Hibbeln, Bernard Gesch, and Stephen
    Schoenthaler, articles by Felicity Lawrence in UK Guardian Unlimited
    and Pat Thomas in The Ecologist: Murray 2006.10.21
    11 members of New Mexico legislature sign letter to ban aspartame as a
    source of toxic methanol and formaldehyde, Stephen Fox, NM Senator
    Gerald Ortiz y Pino: Murray 2006.10.22
    47 UK Members of Parliament now support aspartame ban initiative of
    Roger Williams, MP: Murray 2006.10.16
    combining aspartame and quinoline yellow, or MSG and brilliant blue,
    harms nerve cells, eminent C. Vyvyan Howard et al, 2005, Felicity Lawrence: Murray 2005.12.21
    50% UK baby food is now organic -- aspartame or MSG
    with food dyes harm nerve cells, CV Howard 3 year study
    funded by Lizzy Vann, CEO, Organix Brands,
    Children's Food Advisory Service: Murray 2006.01.13
    all three aspartame metabolites harm human erythrocyte [red blood cell]
    membrane enzyme activity, KH Schulpis et al, two studies in 2005,
    Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
    Murray 2006.01.14
    toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
    JJ et al 2006 Aug: Murray 2006.09.06
    aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
    CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
    Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol
    in alcohol drinks: Murray 2006.09.29
    Bristol, Connecticut, schools join state program to limit artificial
    sweeteners, sugar, fats for 8800 students, Johnny J Burnham, The
    Bristol Press: Murray 2006.09.22
    Connecticut bans artificial sweeteners in schools, Nancy Barnes,
    New Milford Times: Murray 2006.05.25
    carcinogenic effect of inhaled formaldehyde, Federal Institute of Risk
    Assessment, Germany -- same safe level as for Canada:
    Murray 2006.06.02
    Home sickness -- indoor air often worse, as our homes seal in
    [one is formaldehyde, also from the 11% methanol part of aspartame],
    Megan Gillis, Murray 2006.06.01
    NIH NLM ToxNet HSDB Hazardous Substances Data Bank
    inadequate re aspartame (methanol, formaldehyde, formic acid):
    Murray 2006.08.19
    HSDB Hazardous Substances Data Bank: Aspartame

    ASPARTAME CASRN: 22839-47-0
    METHANOL CASRN: 67-56-1
    FORMIC ACID CASRN: 64-18-6
    DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
    ( becomes formaldehyde in body ): EU Scientific Committee on Foods
    2001.07.12: Murray 2004.01.22
    Aspartame Toxicity Information Center Mark D. Gold
    12 East Side Drive #2-18 Concord, NH 03301 603-225-2100
    "Scientific Abuse in Aspartame Research"
    safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
    Murray 2003.01.12 rmforall EU Scientific Committee on Food,
    a whitewash
    Mark Gold exhaustively critiques European Commission Scientific
    Committee on Food re aspartame ( 2002.12.04 ):
    59 pages, 230 references
    Russell L. Blaylock, MD discusses MSG, aspartame, excitotoxins
    with Mike Adams: Murray 2006.09.27
    Mike Adams interviews Randall Fitzgerald on "The Hundred Year Lie:
    How Food and Medicine are Destroying Your Health" 2006.06.21:
    Murray 2006.09.28
    ************************************************** *****
    RTM: Smith, Terpening, Schmidt, Gums:
    full text: aspartame, MSG, fibromyalgia 2002.01.17
    Jerry D Smith, Chris M Terpening,
    Siegfried OF Schmidt, and John G Gums
    Relief of Fibromyalgia Symptoms Following
    Discontinuation of Dietary Excitotoxins.
    The Annals of Pharmacotherapy 2001; 35(6): 702-706.
    Malcolm Randall Veterans Affairs Medical Center,
    Gainesville, FL, USA.
    BACKGROUND: Fibromyalgia is a common rheumatologic
    disorder that is often difficult to treat effectively.
    CASE SUMMARY: Four patients diagnosed with fibromyalgia
    syndrome for two to 17 years are described.
    All had undergone multiple treatment modalities with limited success.
    All had complete, or nearly complete,
    resolution of their symptoms within months after eliminating
    monosodium glutamate (MSG) or MSG plus aspartame from their diet.
    All patients were women with multiple comorbidities
    prior to elimination of MSG.
    All have had recurrence of symptoms whenever MSG is ingested.

    Siegfried O. Schmidt, MD Asst. Clinical Prof.
    Community Health and Family Medicine, U. Florida, Gainesville, FL
    Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
    ************************************************** *****
    Send blank post to: <br /> to join<br />free,open, list with searchable archives for toxicity issues.<br />Richard \"Rich\" T. Murray Room For All 1943 Otowi Road Santa Fe, NM 87505<br /> 505-501-2298