critique of aspartame review by American Dietetic Association Feb 2004, Valerie B. Duffy & Madeleine

Discussion in 'Food and nutrition' started by Rich Murray, Apr 3, 2004.

  1. Rich Murray

    Rich Murray Guest

    April 1 2004 Hello Valerie Duffy, Madeleine Sigman-Grant,
    Maggie Powers,

    Despite the date, it is no joke that aspartame is 11%
    methanol, immediately released into the GI tract, and within
    hours converted by the liver into formaldehyde and formic
    acid-- potent cumulative toxins that attack every tissue and
    trigger hypersensitivity reactions.

    The exponentially ever expanding network of science makes it
    increasingly evident that this is so. The house of cards of
    three decades of denial is exceedingly unstable, liable to
    implosion this year. Indeed, this very communication is
    evidence of that.

    For five years, as a volunteer layman activist, concerned to
    serve the public welfare by supplying civil, lucid,
    detailed, long, referenced reviews of mainly mainstream
    scientific research, I have never had any genuine two-way
    communication with anyone on the pro-aspartame side. I now
    have an impulse to send this, sensing that female
    professionals can not help but act from the deepest core of
    their being to actually protect people.

    Here is an opportunity to alert families all over the world
    about an easily avoidable scourge. Here is an opportunity to
    mobilize responsible, capable, flexible, caring
    professionals to make the best of an increasingly difficult,
    rapidly unstable situation that affects hundreds of
    thousands of jobs, the fortunes of great corporations, and
    public trust in government worldwide. Why, like the heedless
    tobacco industry, continue to march blindly down a closed
    corridor that leads to decades of perilous, boring,
    humiliating, and exceedingly hazardous legal and financial
    difficulties, while needless disease , disability, and death
    wreck rampant and careless harm on individuals and

    Why not come clean, admit the disaster, apologize, warn the
    peoples of our single human family, cease production, sales,
    and distribution of aspartame and MSG, and set aside
    hundreds of billions of dollars into a fund to fairly
    recompense the hapless victims and to research alternatives,
    like stevia, that hold promise of being a wholly benign
    solution? Wouldn't this be fun? Wouldn't this set an
    outstanding historical precedent for dealing with similar
    situations, as serious, as simmering, just as ready to boil
    over? Why can't we cooperate reasonably, daringly, and
    creatively as free citizen souls of this wonderful, tortured
    single world polity? Wouldn't this be true democratic
    action? Wouldn't this be spiritual service?

    I say this to you now, and you do hear me. You must listen
    to the truth within yourself. Whatever you do, the fact
    stands and expands inevitably that this message is said
    widely, and heard widely. Truth can not be managed. It is
    essential that you scrutinize the evidence herein and
    rethink the entire situation. Your fate is in your own
    thinking, nowhere else.

    In mutual service, Rich Murray
    critique of aspartame review by American Dietetic
    Association Feb 2004, Valerie B. Duffy & Madeleine Sigman-
    Grant: Murray 4.3.4 rmforall

    Rich Murray, MA Room For All [email protected] 1943 Otowi
    Road, Santa Fe, New Mexico 87505 USA 505-501-2298

    [ My critical comments are in square brackets. I've copied
    parts of another recent critique after the end of this
    critique, and then supplied more references and links. I
    have spaced the lines to make the text a little easier to
    comprehend, without changing anything else. Two similar
    previous ADA position statements are referenced for 1998 and
    1993, both widely cited. I make a few comments about
    neotame, a derivative of aspartame. The journal letter by
    Anthony Kulczycki competently shows the flaws in the
    inadequate effort by Geha et al. I also draw attention to
    very interesting results by Yu F. Sasaki's team, which have
    aroused remarkably little comment: 24
    recent formaldehyde toxicity [Comet assay] reports: Murray
    12.31.2 rmforall
    Comet assay finds DNA damage from sucralose, cyclamate,
    saccharin in
    mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3 rmforall
    [Also borderline evidence, in this pilot study of 39
    food additives, using test groups of 4 mice, for DNA
    damage from for stomach, colon, liver, bladder, and
    lung 3 hr after oral dose of 2000 mg/kg aspartame-- a
    very high dose.]
    genotoxins, Comet assay in mice: Ace-K, stevia fine;
    aspartame poor; sucralose, cyclamate, saccharin bad: Y.F.
    Sasaki Aug 2002: Murray 1.27.3 rmforall [A detailed look at
    the data] ]

    American Dietetic Association, 120 South Riverside Plaza,
    Suite 2000, Chicago, IL 60606-6995 Phone: (800) 877-1600,
    ext. 5000 [email protected] J Am Diet Assoc.
    2004 Feb; 104(2): 255-75. Position of the American Dietetic
    Association: use of nutritive and nonnutritive sweeteners.
    American Dietetic Association.
    [ p. 275 lists 2 authors and 10 reviewers: ADA position
    adopted by the House of Delegates on October 18, 1992,
    and reaffirmed on September 6, 1996 and on June 22,
    2000. This position will be in effect until December
    31, 2009. ADA authorizes republication of the position
    statement/support paper, in its entirety, provided full
    and proper credit is given. Requests to use portions of
    the position must be directed to ADA Headquarters at
    312/899-0040, ext. 4835, or [email protected] .

    Authors: Valerie B. Duffy, PhD, RD (University of
    Connecticut, Storrs, CT) [ Valerie Duffy Assc. Prof.
    Organization: ALLIED HLTH DIETETICS Status: Faculty
    Building: KOONS HALL UBox: UNIT 2101 Email:
    [email protected] Web URL: M.UCONN.EDU/~VDUFFY/ Phone:
    860 486-1997 ]; Madeleine Sigman-Grant, PhD, RD (University
    of Nevada Cooperative Extension, Las Vegas, NV, [ MCH Nutrition Specialist
    and Professor, Cooperative Education, University of Nevada-
    Reno, 2345 Red Rock Street, Las Vegas, Nevada 89146-3160
    Phone 702-222-3130 [email protected] ]

    Reviewers: Margaret A. Powers, MS, RD, CDE, International
    Diabetes Center, Park Nicollet Institute, Minneapolis, MN,
    Diabetes Care and Education Dietetic Practice Group, [
    Maggie Powers, Powers and Associates Inc, "a health
    communications firm" , " Margaret is president of Powers
    and Associates, Inc., a national health and nutrition
    communications firm.", St. Paul, Minn. Minnesota Dietetic
    Association [email protected] , Maggie Powers 651-699-0031
    [email protected] ,
    Park Nicollet Institute, 3800 Park Nicollet Blvd.,
    Minneapolis, MN 55416 952-993-3350 , International
    Diabetes Center, 3800 Park Nicollet Boulevard, Minneapolis,
    Minnesota 55416-2699 Phone: 952-993-3393 Toll-free: 1-888-825-
    6315 Fax: 952-993-1302 [email protected] 1-888-637-
    2675. ] ; Denise Elmore, DTR, University of Texas MD
    Anderson Cancer Center, Houston, TX, Dietetic Technicians
    in Practice Dietetic Practice Group; Esther F. Myers, PhD,
    RD, FADA (American Diebetic Association, Chicago, IL);
    Diane Quagliani, MBA, RD (Quagliani Communications, Inc.,
    Western Springs,
    pA); Gita Patel, MS, RD, CDE, Nutrition Consultant, Etna,
    NH, Sports, Cardiovascular and Wellness Dietetic
    Practice Group; Marie Spano, MS, RD, Atlanta, GA.
    Sports, Cardiovascular and Wellness Dietetic Practice
    Group; Kimberly F. Stitzel, MS, RD (American Dietetic
    Association, Washington, DC); Sue Taylor, MS, RD
    (Kellen Company, Atlanta, GA); and [ADA] Association
    Positions Workgroup: Robert Earl, MPH, RD (chair);
    Sonja Connor, MS, RD. ]

    Sweeteners elicit pleasurable sensations with (nutritive) or
    without (nonnutritive) energy. Nutritive sweeteners (eg,
    sucrose, fructose) are generally recognized as safe (GRAS)
    by the Food and Drug Administration (FDA), yet concern
    exists about increasing sweetener intakes relative to
    optimal nutrition and health. Dietary quality suffers at
    intakes above 25% of total energy (the Institutes of
    Medicine's suggested maximal intake level). In the United
    States, estimated intakes of nutritive sweeteners fall below
    this, although one in four children (ages 9 to 18 years) can
    surpass this level. Polyols (sugar alcohols), GRAS-affirmed
    or petitions filed for GRAS, add sweetness with reduced
    energy and functional properties to foods/beverages and
    promote dental health. Five nonnutritive sweeteners with
    intense sweetening power have FDA approval (acesulfame-K,
    aspartame, neotame, saccharin, sucralose) and estimated
    intakes below the Acceptable Daily Intake (level that a
    person can safely consume everyday over a lifetime without
    risk). By increasing palatability of nutrient-dense
    foods/beverages, sweeteners can promote diet healthfulness.
    Scientific evidence supports neither that intakes of
    nutritive sweeteners by themselves increase the risk of
    obesity nor that nutritive or nonnutritive sweeteners cause
    behavioral disorders. However, nutritive sweeteners increase
    risk of dental caries. High fructose intakes may cause
    hypertriglyceridemia and gastrointestinal symptoms in
    susceptible individuals. Thus, it is the position of The
    American Dietetic Association that consumers can safely
    enjoy a range of nutritive and nonnutritive sweeteners when
    consumed in a diet that is guided by current federal
    nutrition recommendations, such as the Dietary Guidelines
    for Americans and the Dietary References Intakes, as well as
    individual health goals. Dietetics professionals should
    provide consumers with science-based information about
    sweeteners and support research on the use of sweeteners to
    promote eating enjoyment, optimal nutrition, and health.
    Publication Types: Guideline PMID: 14760578
    /article.jhtml Valerie B. Duffy and G. Harvey Anderson,
    Position of The American Dietetic Association: Use of
    Nutritive and Nonnutritive Sweeteners, J. American Dietetic
    Assoc 98(5): 580-587 (May 1998)
    "Position of The American Dietetic Association: Use of
    Nutritive and Non-Nutritive Sweeteners," Journal of The
    American Dietetic Association, 93:
    7: 816-821, July 1993. Franz, M. J., Maryniuk, M. D.

    p. 263 "Aspartame, a dipeptide (L-a-aspartyl-L-phenylalanine
    methyl ester) is 160 to 220 times sweeter than sucrose.
    Intestinal esterases hydrolyze aspartame to aspartic
    acid, methanol, and phenylalanine (74). These components
    are found in much greater amounts in the normal diet in
    fruits, vegetables, meat, and milk. [ standard industry
    PR spin ] For example, a serving of nonfat milk provides
    about six times more phenylalanine and 13 times more
    aspartic acid, whereas a serving of tomato juice has
    about six time more methanol than an equal volume
    beverage sweetened 100% with aspartame (75). The amino
    acids are metabolized to provide 4 kcal/g. Thus, this
    sweetener does provide energy; however, because of the
    intense sweetness of aspartame, only minute amounts need
    to be added, and the amount of energy derived is

    [ To summarize the actual and simple reality:

    It is certain that high levels of aspartame use, above 2
    liters daily for months and years, must lead to chronic formaldehyde-
    formic acid toxicity, since 11% of aspartame (1,120 mg in
    2L diet soda, 5.6 12-oz cans) is 123 mg methanol (wood
    alcohol), immediately released into the body after drinking
    (unlike the large levels of methanol locked up in molecules
    inside many fruits), then quickly transformed into
    formaldehyde, which in turn becomes formic acid, both of
    which in time are partially eliminated as carbon dioxide
    and water.

    However, about 30% of the methanol remains in the body as
    cumulative durable toxic metabolites of formaldehyde and
    formic acid-- 37 mg daily, a gram every month. [Metabolism
    of aspartame in monkeys. Oppermann JA, Muldoon E, Ranney RE.
    [ an aspartame industry lab ]
    q. Nutrition 1973 Oct; 103(10): 1454-1459.] If 10% of the
    methanol is retained as formaldehyde, that would give 12
    mg daily formaldehyde accumulation, about 60 times more
    than the 0.2 mg from 10% retention of the 2 mg EPA daily
    limit for formaldehyde in water.

    Bear in mind that the EPA limit for formaldehyde in drinking
    water is 1 ppm, or 2 mg daily for a typical daily
    consumption of 2 L of water.
    RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking
    water July 1999
    5.30.2 rmforall

    This long-term low-level chronic toxic exposure leads to
    typical patterns of increasingly severe complex symptoms,
    starting with headache, fatigue, joint pain, irritability,
    memory loss, and leading to vision and eye problems, and
    even seizures. In many cases there is addiction. Probably
    there are immune system disorders, with a hypersensitivity
    to these toxins and other chemicals.

    J. Nutrition 1973 Oct; 103(10): 1454-1459. Metabolism of
    aspartame in monkeys. Oppermann JA, Muldoon E, Ranney RE.
    Dept. of Biochemistry, Searle Laboratories, Division of
    G.D. Searle and Co. Box 5110, Chicago, IL 60680 They
    found that about 70% of the radioactive methanol in
    aspartame put into the stomachs of 3 to 7 kg monkeys was
    eliminated within 8 hours, with little additional
    elimination, as carbon dioxide in exhaled air and as
    water in the urine. They did not mention that this meant
    that about 30% of the methanol must transform into
    formaldehyde and then into formic acid, both of which
    must remain as toxic products in all parts of the body.
    They did not report any studies on the distribution of
    radioactivity in body tissues, except that blood plasma
    proteins after 4 days held 4% of the initial methanol.
    This study did not monitor long-term use of aspartame.

    The low oral dose of aspartame and for methanol was 0.068
    mmol/kg, about 1 part per million [ppm] of the acute
    toxicity level of 2,000
    Ja/kg, 67,000 mmol/kg, used by McMartin (1979). Two L daily
    use of diet soda provides 123 mg methanol, 2 mg/kg for a
    60 kg person, a dose of 67 mmole/kg, a thousand times
    more than the dose in this study. By eight hours
    excretion of the dose in air and urine had leveled off at
    67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in
    the urine, so 68.7 % was excreted, and 31.3% was
    retained. [ This data is the average of 4 monkeys. ]

    In 1981, the FDA approved aspartame as a sweetener for a
    number of dry uses (eg, tabletop sweetener, cold breakfast
    cereal, gelatins and puddings) and in chewing gum. This
    approval was expanded in 1983 to include carbonated
    beverages. The Council on Scientific Affairs of the American
    Medical Association in 1985 concluded that, "Available
    evidence suggests that consumption of aspartame by normal
    humans is safe and not associated with serious adverse
    health effects." (76). [ Note the cautious qualifiers
    "available", "suggests", "normal", "serious". ] In 1996, the
    FDA approved aspartame as a "general purpose sweetener" for
    use in all foods and beverages. Aspartame is also approved
    for use in over 100 nations.

    Donald Rumsfeld, 1977 head of Searle Corp., got aspartame
    FDA approval: Turner: Murray 12.23.2 rmforall
    aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI
    reporter: Murray 7.10.0 rmforall
    aspartame history Part 1/4 1964-1976: Gold: Murray
    11.6.9: rmforall
    revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2
    rmforall ]

    The United Nations leads the world in demand for aspartame,
    accounting for up to 75% of sales. Although soft drinks
    account for above 70% of aspartame consumption, this
    sweetener is added to more than 6,000 foods, personal care
    products, and pharmarceuticals. Aspartame is available in
    liquid, granular, encapsulated, and powder forms to extend
    use in food and beverage products. Aspartame decomposes
    during excessive heating and loses its sweetening power.
    However, appropriate cooking methods can minimize losses of
    aspartame sweetness (77).

    Detailed studies have been conducted to determine how
    ingestion influences plasma levels of aspartic acid,
    phenylalanine, and methanol (or the byproduct formate). [
    Typical of industry PR spin, the alarming fact that
    formaldehyde is another inevitable byproduct is omitted. ]
    In studies with healthy adults (78), levels of plasma
    aspartate concentrations or blood levels of formate did not
    change with a bolus load up to four times the ADI for
    aspartame (ie, 200 mg/kg). [ The issue is not blood or
    plasma levels, but the cumulative levels of formaldehyde and
    formic acid toxic products in a variety of body tissues,
    resulting from long-term, heavy use (above 6 12-oz cans
    daily diet soda, about 2L) by many types of vulnerable
    persons. ] Plasma phenylalanine response to aspartame (as
    well as to other dietary sources of phenylalanine) varies in
    persons with phenylketonuria (PKU), a homozygous recessive
    inborn error of metabolism of which affected individuals
    cannot metabolize phenylalanine. In persons with this rare
    (frequency in approximately one in 10,000 whites) [ ie,
    1,000 in 10 million, 10,000 in 100 million, 30,000 in 300
    million ] inborn error, excess intake of this amino acid can
    cause higher plasma phenylalanine levels and its adverse
    effects (79). MNT involes the control of dietary sources of
    phenylalanine, including aspartame. The FDA requires that
    foods that contain aspartame have the prominent display of
    the following label: "PHENYLKETONURICS: CONTAINS

    Untreated individuals with PKU appear to tolerate the amount
    of phenylalanine in a diet soda sweetened with aspartame
    (approximately 104
    Jb/12 oz) (81). Heterozygotes for PKU do not show changes in
    cognitive performance or in electroencephalograms after
    12 weeks of consuming either 15 or 45 mg/kg bw/day of
    aspartame (82). [ milligrams per kilogram body weight per
    day ] In non-PKU individuals, single-bolus studies of
    aspartame (up to 50 mg/kg bw) or repeat dose studies show
    a plasma phenylalanine response near the normal
    postprandial range and considerably lower than that
    observed in PKU individuals or those with mild
    hyperphenylalanemia (78).

    Aspartame breaks down to diketopiperazine [ a potent
    carcincogen ] in liquid systems with excessive heat
    exposure. Animal toxicity studies show that, even if all
    aspartame were converted to diketopiperazine in beverages,
    the amount would be well below the FDA-established ADI of
    3,000 mg/kg bw/day for this compound (83).

    Some individuals report allergic reactions to aspartame,
    including edema of the lips, tongue, and throat;
    dermatologic reactions; and respiratory problems (84). [
    These are classic formaldehyde allergic reactions. It is
    typical that industry research never explores which
    breakdown products of aspartame might be causing allergic
    reactions. The disparaging term "some individuals" is used
    rather than give specific numbers. Russell M. Jaffe, MD,
    PhD found 20
    % of fibromyalgia patients were sensitive to aspartame: A Novel Treatment for
    Fibromyalgia Improves Clinical Outcomes in a Community-Based
    Study. Patricia A. Deuster, Russell M. Jaffe. Journal of
    Musculoskeletal Pain. 1998; Vol. 6(2): 133-149.

    "Using blood tests, the researchers ran a panel of 350
    antigens including environmental chemicals, food additives
    and preservatives, crustaceans, diary products, fish,
    fruits, grains, meats, mollusks, and oils."

    "Normal, healthy people react to only two or less of this
    panel. The greatest offenders were:

    MSG 42.5 % (17 out of 40 patients) Candida albicans 37.5 %
    Caffeine 37 % Chocolate/cocoa 37 % Food colorings 37 % Cola
    beverages 37 % Cow Dairy Products 25 % Sulfite/metabisulfite
    22.5% Xylene 22.5% Yogurt 22.5% Aspartames 20% BHA 20%
    Cadmium 20% Lead 20% Tylenol 20% Yeast 20% Sodium benzoate
    20% Orange 20% " [email protected] 800-525-7372
    Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer:
    Robert Swift, MD: [formaldehyde from methanol in aspartame]:
    Murray 1.16.4 rmforall
    hangovers from formaldehyde from methanol (aspartame?):
    Schwarcz: Linsley: Murray 1.18.4
    formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA:
    Gold: Murray: Wilson: CIIN: 12.12.2 rmforall

    Thrasher (2001): "The major difference is that the Japanese
    demonstrated the incorporation of FA and its metabolites
    into the placenta and fetus. The quantity of radioactivity
    remaining in maternal and fetal tissues at 48 hours was
    26.9% of the administered dose." [Ref. 14-16]

    Arch Environ Health 2001 Jul-Aug; 56(4): 300-11. Embryo
    toxicity and teratogenicity of formaldehyde. [100
    references] Thrasher JD, Kilburn KH.
    [email protected] Sam-1 Trust, Alto, New Mexico,
    y.html full text full text
    Jack Dwayne Thrasher, Alan Broughton, Roberta Madison.
    Immune activation and autoantibodies in humans with long-
    term inhalation exposure to formaldehyde. Archives of
    Environmental Health. 1990; 45: 217-223. "Immune activation,
    autoantibodies, and anti-HCHO-HSA antibodies are associated
    with long-term formaldehyde inhalation." PMID: 2400243

    Confirming evidence and a general theory are given by Pall
    testable theory of MCS type diseases, vicious cycle of
    nitric oxide & peroxynitrite: MSG: formaldehyde-methanol-
    aspartame: Martin L. Pall: Murray: 12.9.2 rmforall ]

    However, two double-blinded challenge studies report
    difficulty in recruiting individuals who claim an allergic
    respnse to aspartame and a failure to reproduce the allergic
    reactions in controlled experimental conditions (85, 86).
    [ Knumber of standard aspartame industry ploys apply here.
    Again and again, industry funded double-blind laboratory
    tests are used to justify ignoring negative clinical
    feedback. It happens to be very easy to conduct
    misleading double-blind laboratory studies: by using
    only healthy subjects, by using too few subjects to
    generate statistics that could detect effects rarer than
    1% incidence, by giving the aspartame in delayed release
    capsules, rather than in fast release beverages, by
    using one-time or limited duration exposures that can
    not detect long-term accumulation and gradual
    sensitivation, and, as always, failing to measure the
    actual disposition of the accumulation of toxic
    formaldehyde and formic acid products over time in many
    specific tissues. After the references for this ADA
    statement, I give the full text of a journal letter (Feb
    1995) by Prof. Anthony Kulczycki, Jr of Washington
    University School of Medicine, that gives a detailed
    critique of reference
    (86), the Geha study (1993) . In general, aspartame industry
    research and review papers barely mention that many
    competent negative laboratory studies do exist. Rich
    Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
    aspartame toxicity 6.4.1 rmforall four double-blind studies

    Headache 1988 Feb;28(1):10-4 The effect of aspartame on
    migraine headache. Koehler SM, Glaros A PMID: 3277925, UI:
    88138777 Shirley M. Koehler, PhD 904-858-7651
    [email protected]
    K.html#Koehler Alan Glaros [email protected] 816-235-2074

    They conducted a double-blind study of patients, ages 18-55,
    who had a medical diagnosis of classical migraines (normally
    having 1-3 migraines in 4-weeks), who were not on
    medications (other than analgesics), and who suspected that
    aspartame had a negative effect on their migraine headaches.
    The subjects were given 1200 mg daily, aspartame or placebo,
    for four weeks, about 17 mg/kg. The placebo group had no
    increase in headaches. Approximately half of the subjects (5
    of 11) who took aspartame had a large, statistically
    significant (p = 0.02), increase in migraine headache
    frequency, but not in intensity or duration, compared to
    baseline or placebo. Only 11 of 25 subjects completed the
    program: 8 dropped out, 4 began new medications, 2 had
    incomplete records. They were at home. Since 1/3 of the
    subjects dropped out, they may have been choosing to avoid
    headaches-- were they unpaid? To achieve statistical
    signifance with only 11 subjects hints that the incidence
    rate from aspartame is very high, about 1/2, for migraine
    cases who believe that they are hurt by aspartame.

    Walton, RG, "Adverse reactions to aspartame: double-blind
    challenge in patients from a vulnerable population," 1993,
    with Robert Hudak and Ruth J. Green-Waite, Biological
    Psychiatry, 34 (1), 13-17. Ralph G. Walton, MD, Prof. of
    Clinical Psychology, Northeastern Ohio Universities, College
    of Medicine, Dept. of Psychiatry, Youngstown, OH 44501,
    Chairman, The Center for Behavioral Medicine, Northside
    Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown, OH
    44501 330-740-3621 [email protected]

    Eight depressed patients, ages 24-60, and five non-depressed
    controls, ages 24-56, employed at the hospital, were given
    for 7 days either aspartame or a placebo, and then after a 3
    day break, given the opposite. Each got 2100 mg aspartame
    daily, 30 mg/kg bodyweight, equal to 10-12 cans of diet soda
    daily, about a gallon. Despite the very small number of
    subjects, the results were dramatic and statistically
    significant. The eight depressed patients reported with
    aspartame, compared to placebo, much higher levels of
    nervousness, trouble remembering, nausea, depression,
    temper, and malaise. (For each symptom, p<0.01) The five
    normals did not report strong enough differences between
    aspartame and placebo to be significant. Initially, the
    study was to be on a group of 40, but was halted by the
    Institutional Review Board because of severe reactions among
    3 of the depressed patients.

    Again, statistical significance with only 8 depressed
    patients: "In this study, patients most often began to
    report significant symptoms after day 2 or 3." The incidence
    rate is very high, indeed, about 1/3. The most common
    symptoms are entirely typical of thousands of case

    Stephen K. Van Den Eeden, T.D. Koepsell, W.T.
    Longstreth, Jr,
    G. van Belle, J.R. Daling, B. McKnight, "Aspartame ingestion
    and headaches: a randomized crossover trial," 1994,
    Neurology, 44, 1787-93 Steven K. Van Den Eeden,PhD 550-450-
    2202 [email protected] Division of Research, Kaiser
    Permanente Medical Care Program 3505 Broadway, Oakland,
    CA 94611-5714

    In their introduction, they comment:

    "In addition, the FDA had received over 5,000 complaints as
    of July, 1991 in a passive surveillance system to monitor
    adverse side effects.
    (17) Neurologic problems constitute the primary complaints
    in these and several other case series, with headaches
    accounting for 18 to 45 %,depending on the case series
    reported. (17-19)"

    Subjects, ages 18-57, were recruited who believed they got
    headaches from aspartame, but were otherwise mentally and
    physically healthy. They were paid $ 15 total, and were at
    home. Of the 44 subjects, 32 contributed data to the 38-day
    trials: a week of inert placebo, a week of either aspartame
    or placebo, followed by a week of the opposite, and then
    this two-week cycle repeated. The daily dose was about 30
    mg/kg. "The proportion of days subjects reported having a
    headache was higher during aspartame treatment compared with
    placebo treatment (aspartame = 0.33, placebo = 0.24; p =
    0.04) (table 5)". Of the 12 subjects not included in the
    data, 7 reported adverse symptoms before withdrawing.

    Again, statistical significance with a moderate number of
    healthy subjects, willing to be recruited by a newspaper ad,
    who believed aspartame hurt them. The number of headaches
    for each subject for each treatment week are given: it
    appears that 4 subjects had the strongest increase in
    headaches from the run-in week or placebo week to their
    first week on aspartame, jumping from 0 to 5, 1 to 6, 1 to
    4, 0 to 5 headaches per week. So, about 4 of the 44 healthy
    people recruited for the study, who believed aspartame hurt
    them, had a stong increase in headaches from the first week
    of daily asparame exposure, while 7 reported adverse
    symptoms before leaving, a total of 11 out of 44, an
    incidence ratio of 1/4.

    This is sky high, if we consider that, if the incidence
    ratio for the about two hundred million users in the USA is
    1 of 100, that is 2 million cases. It is plausible that the
    incidence ratio lies between 1 and 10 out of 100 for
    continuous daily exposure. These three flames should have
    set off alarm bells, with extensive follow-up studies and
    much more careful study of thousands of case histories. But
    these little flares were adroitly smothered by thick
    blankets of industry funded fluff. Rich
    Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity
    6.4.1 rmforall two double-blind studies RTM: original documents and long reviews of flaws
    in aspartame toxicity research 7.31.2 rmforall
    "Scientific Abuse in Aspartame Research" Mark D. Gold

    "Survey of aspartame studies: correlation of outcome and
    funding sources," 1998, unpublished: Walton found 166 separate
    published studies in the peer reviewed medical literature,
    which had relevance for questions of human safety. The 74
    studies funded by industry all (100%) attested to
    aspartame's safety, whereas of the 92 non-industry funded
    studies, 84 (91%) identified a problem. Six of the seven non-
    industry funded studies that were favorable to aspartame
    safety were from the FDA, which has a public record that
    shows a strong pro-industry bias. Ralph G. Walton, MD, Prof.
    of Clinical Psychology, Northeastern Ohio Universities,
    College of Medicine, Dept. of Psychiatry, Youngstown, OH
    44501, Chairman, The Center for Behavioral Medicine,
    Northside Medical Center, 500 Gypsy Lane, P.O. Box 240
    Youngstown, OH 44501 330-740-3621 [email protected] ]

    The FDA increased the ADI for aspartame to its present level
    of 50 mg/kg bw/day when it was approve for use in carbonated
    beverages in 1983 (87). This ADI would approximate a 60-kg
    individual consuming 500 to 600 grams of sucrose per day
    over a lifetime based on sweetness of aspartame compared
    with that of sucrose (75). Postmarket assessment of
    aspartame conducted between July 1991 and June 1992 shows
    that daily intake of aspartaame is below this ADI (88):

    Aspartame eaters (at least 90th percentile of consumption)
    in the general population consume 6% of the ADI (3.0 mg/kg
    bw/day), those 0 to 5 years of age consume 0.4% (5.2 mg/kg
    bw/day), people with diabetes consume 6.6% (3.3 mg/kg
    bw/day), and women of childbearing age consume 8.4% (4.2
    mg/kg bw/day).

    As a tabletop sweetener, packets contain 35 to 40 mg of
    aspartame and are equivalent to the sweetness of 2 teaspoons
    of sugar. Consumers would need to contact individual
    companies to determine the amount of aspartame in each
    product. The amount in some common foods is as follows:

    up to 225 mg in a 12-oz diet soda, 100 mg in an 8-oz drink
    made from powder, 80 mg in an 8-oz yogurt or a 4-oz gelatin
    dessert, and up to 47 mg in frozen dairy products.

    To reach the ADI, an 18-kg child (nearly 40 pound) child
    would need to consume 900 mg of aspartame per day, which
    translates to 24 packets of sweetener (equivalent to 48
    teaspoons of sugar), four 12-oz cans of diet soda, or nine
    8-oz glasses of fruit drink made from a powder.

    A comprehensive review of the safety of aspartame has
    recently been published (75). The review covers previous
    publications as well as new information that support the
    safety of aspartame as a food additive and negates claims of
    its association with a range of health problems includings
    brain tumors. The SCF (89) has also recently evaluated new
    scientific evidence. They conclude that current intakes in
    European countries are well below the ADI set of JECFA and
    SCF (40 mg/kg bw/day), that aspartame is not a carcinogen
    and is not associated with neurobehavioral disorders, and
    thus that there is no need to revise the risk assessment of,
    or ADI for, aspartame. [ You may not have noticed that the
    European ADI is 20% lower than the USA level, or known this: On
    4.10.2003 the European Union Parliament voted 440 to 20 to
    approve sucralose, limit cyclamates & reevaluate aspartame &
    stevia: Murray 4.12.3 rmforall safety
    of aspartame Part 1/2 12.4.2: EC HCPD-G SCF: Murray 1.12.3
    rmforall EU Scientific Committee on Food, a whitewash
    response.htm Mark Gold exhaustively critiques European
    Commission Scientific Committee on Food re aspartame
    (12.4.2): 59 pages, 230 references
    aspartame puts formaldehyde adducts into tissues, Part 1/2
    full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
    aspartame puts formaldehyde adducts into tissues, Part 2/2
    full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall Trocho C,
    Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez-Lopez
    JA, Alemany M ["Trok-ho"] Formaldehyde derived from dietary
    aspartame binds to tissue components in vivo. Life Sci 1998
    Jun 26; 63(5): 337-49. Departament de Bioquimica i Biologia
    Molecular, Facultat de Biologia, Universitat de Barcelona,
    Spain. Maria
    Alemany, PhD (male) [email protected]
    Murray: Butchko, Tephly, McMartin: Alemany: aspartame
    formaldehyde adducts in rats 9.8.2 rmforall Prof. Alemany
    vigorously affirms the validity of the Trocho study against
    criticism: Butchko, HH et al [24 authors], Aspartame: review
    of safety. Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt
    2): S1-93, review available for $35, [an industry paid
    organ]. Butchko: "When all the research on aspartame,
    including evaluations in both the premarketing and
    postmarketing periods, is examined as a whole, it is clear
    that aspartame is safe, and there are no unresolved
    questions regarding its safety under conditions of intended
    use." [ They repeatedly pass on the ageless industry deceit
    that the methanol in fruits and vegetables is as as
    biochemically available as that in aspartame-- see the 1984
    rebuttal by Monte, below. In the same report, Schiffman
    concludes on page S49, not citing any research after 1997,
    "Thus, the weight of the scientific evidence indicates that
    aspartame does not cause headache."
    Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
    [email protected] 919-684-3303, 660-5657
    Murray: Butchko, Tephly, McMartin: Alemany: aspartame
    formaldehyde adducts in rats 9.8.2 rmforall ] RTP
    ties to industry criticized by CSPI: Murray: 12.9.2
    rmforall ]

    [ The ADA article goes on to devote several long paragraphs
    to neotame, a derivative of aspartame, approved in
    Australia/New Zealand in summer 2000, and by the USA FDA in
    summer, 2002-- yet which has, as far as I can search out,
    never been put on the market anywhere in the world. Since it
    is 40 times sweeter than aspartame, 40 times less of it is
    necessary, and so it supplies 40 times less methanol,
    formaldehyde, and formic acid. However, of the "113
    preclinical, clinical, and special studies and an additional
    32 exploratory and screening studies", precisely no safety
    studies have been independenty funded and exactly one safety
    study has been published in a mainstream, peer-reviewed
    public access journal. The FDA has relied entirely on secret
    research by industry paid researchers. If the research was
    so good, and neotame is so safe and wonderful and worth
    billions of dollars of yearly business, why hasn't the
    industry sagely hastened to place their scores of studies in
    mainstream public research journals, and thereby boost the
    public reputations of their expensive scientists?
    FDA: objections to neotame approval (Section A) : Murray
    8.4.2 rmforall

    Regul Toxicol Pharmacol. 2003 Oct; 38(2): 144-56. Long-term
    food consumption and body weight changes in neotame safety
    studies are consistent with the allometric relationship
    observed for other sweeteners and during dietary
    restrictions. Flamm WG, Blackburn GL, Comer CP, Mayhew DA,
    Stargel WW. AAC Consulting Group, Vero Beach, FL, USA

    In long-term safety studies with neotame, a new high-
    intensity sweetener 7000-13,000 times sweeter than sucrose,
    the percent changes (%Delta) in body weight gain (BWG) in
    Sprague-Dawley rats were several-fold greater than the
    %Delta in overall food consumption (FC). This study
    investigates the question of whether the changes in BWG were
    adverse or secondary to small, long-term decrements in FC.
    The hypothesis tested in Sprague-Dawley rats was that the
    relationship between long-term %Delta in FC and %Delta in
    BWG is linear and in a ratio of
    1:1.The %Delta in FC were compared to %Delta in BWG after 52
    weeks on study in one saccharin (825 rats), two
    sucralose (480 rats), two neotame (630 rats), and five
    dietary restriction (>1000 rats) studies. Non-
    transformed plotting of data points demonstrated an
    absence of linearity between %Delta in FC and %Delta in
    BWG; however, log-log evaluation demonstrated a robust
    (R2=0.97) linear relationship between %Delta in FC and
    %Delta in BWG. This relationship followed the well-known
    allometric equation, y=bxa where x is %DeltaFC, y is
    %DeltaBWG, b is %DeltaBWG when DeltaFC=1, and a is the
    log-log slope. Thus, in Sprague-Dawley rats at week 52,
    the long-term relationship between %Delta in FC and
    %Delta in BWG was determined to be:
    %DeltaBWG=3.45(%DeltaFC0.74) for males and
    %DeltaBWG=5.28(%DeltaFC0.68) for females.

    sweeteners saccharin and sucralose versus dietary
    restriction, were not. The %Delta in BWG are allometrically
    consistent with the observed %Delta in FC for these high-
    intensity sweeteners, including neotame. BW parameters are
    not appropriate endpoints for setting no-observed-effect
    levels (NOELs) when materials with intense taste are admixed
    into food. An approach using objective criteria is proposed
    to delineate BW changes due to toxicity from those secondary
    to reduced FC. PMID: 14550756 ]

    [ cited references ]
    2. Ranney R, Oppermann J, Muldoon E, McMahon F. Comparative
    metabolism of aspartame in experimental animals and
    humans. J Toxicol Environ Health. 1976; 2: 441-1. [ Twenty-
    eight years ago, an aspartame industry lab proved 30%
    retention of toxic products (indubitably formaldehyde
    and formic acid) of methanol from a single low dose of
    aspartame in 4 monkeys. No humans were tested for
    methanol product retention in tissues, then or ever
    since. Obviously, this would be devastating to billions
    of dollars of yearly sales worldwide.

    3. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger
    C, Blackburn GL, de Sonneville LM, Geha RS, Hertelendy
    Z, Koestner A, Leon AS, Liepa GU, McMartin KE,
    Mendenhall CL, Munro IC, Novotny EJ, Renwick AG,
    Schiffman SS, Schomer DL, Shaywitz BA, Spiers PA, Tephly
    TR, Thomas JA, Trefz FK. Aspartame: Review of Safety.
    Regul Toxicol Pharmacol. 2002; 35: S1-S93. [ an industry
    funded and staffed organ ]

    4. Council on Scientific Affairs. Aspartame: Review of
    safety issues. JAMA. 1985; 254: 400-402. [ http://www.ama- American Medical
    Association Council on Scientific Affairs: no reports
    listed before 1994 ]

    5. Equal Sweetener. Available at: Accessed
    February 26, 2003.

    6. Stegink L, Filer L J. Effects of aspartame ingestion on
    plasma aspartate, phenylalanine, and methanol
    concentrations in normal adults.
    In: Tschanz C, Butchko H, Stargel W., Kotsonis F, eds. The
    Clinical Evaluation of A Food Additive. New York, NY:
    CRC Press; 1996. [ The term "food additive" is typical,
    because, unlike a "drug", the industry does not have to
    prove safety or collect complaints from users and
    physicians. As usual for industry studies, the amount of
    accumulation over long periods of exposure of toxic
    products of formaldehyde and formic acid in many
    specific tissues are not studied. ]

    79. Wolf-Novak LC, Stegink LD, Brummel MC, Persoon TJ, Filer
    LJ Jr, Bell EF, Ziegler EE, Krause WL. Aspartame
    ingestion with and without carbohydrate in
    phenylketonuric and normal subjects: effects on plasma
    concentrations of amino acids, glucose, and insulin.
    Metabolism. 1990; 39: 391-396.

    80. Food and Drug Administration. Food additives permitted
    for direct addition to food for human consumption:
    Aspartame. 2002. 21CFR172.804.

    81. Mackey S, Berlin CJ. Effect of dietary aspartame on
    plasma concentrations of phenylalanine and tyrosine in
    normal and homozygous phenylketonuric patients. Clin
    Pediatr. 1992; 31: 394-399.

    82. Trefz F, De Sonneville L, Matthis P, Benninger C, Lanz-
    Englert B, Bickel H. Neuropsychological and biochemical
    investigations in heterozygotes for phenylketonuria
    during ingestion of high dose aspartame (a sweetener
    containing phenylalanine) Hum Genet. 1994. 93: 369-374.

    83. Food and Drug Administration. Food additives permitted
    for direct addition to food for human consumption:
    Aspartame. Federal Register. 1983; 48: 31376-31382.

    84. Health Hazard Evaluation. Summary of Adverse Reactions
    Attributed to Aspartame. Washington, DC: US Dept of
    Health and Human Services; April 20, 1995.

    85. Garriga M, Berkebile C, Metcalfe D. A combined single-
    blind, double-blind, placebo-controlled study to
    determine the reproducibility of hypersensitivity
    reactions to aspartame. J Allergy Immunol. 1991;
    87: 821-827.

    86. Geha R, Buckley C, Greenberger P, Patterson R, Polmar S,
    Saxon A, Rohr A, Yang W, Drouin M. Aspartame is no more
    likely than placebo to cause uticaria/angioedema:
    Results of a multi-center, randomized, double-blind, placebo-
    controlled crossover study. J Allergy Clin Immunol.
    1993: 92;513-520. [ Typically, this industry funded
    study manages to avoid the deadly words, "formaldehyde"
    and "formic acid", the most potent allergens produced in
    the body from the 11% methanol component of aspartame.
    It is surely fruitless to attempt to study allergies
    while ignoring the most potent allergens. ]

    87. Food and Drug Administration. Food additives permitted
    for direct addition to food for human consumption:
    Aspartame. 1984; 49: 6672-6677.

    88. Food and Drug Administration. Food additives permitted
    for direct addition to food for human consumption:
    Aspartame. 1996; 61(126)(21CFR Part 172): 33654-33656.

    89. Scientific Committeee on Food. Opinion of the Scientific
    Committee on Food: Update on the Safety of Aspartame.
    Brussels: European Commission; Deacember 2 2002.
    SCF/CS/ADD/EDUL/222 Final.

    [ Geha et al. (1993) used monocrystalline cellulose in
    gelatin capsules as their placebo. A recent study suggests
    that an inhaled cellulose powder extract may prevent
    classic hay fever attacks. Another study find
    hypersensitivity reactions in patients [ blood ] dialysed
    with cellulose or synthetic membranes". There are scores of
    studies on gelatin allergy.

    Adv Ther. 2003 Jul-Aug; 20(4): 213-9. Use of cellulose
    powder for the treatment of seasonal allergic rhinitis.
    Josling P, Steadman S. Herbal Health Centre, Battle, UK.

    This study was designed to determine whether a unique
    cellulose powder extract could prevent the classic hay
    fever attack from occurring among volunteers who have
    suffered for some years. Nasaleze enhances nasal mucus,
    which allows the filtration of allergens, to ensure that
    only clean air reaches the lungs. One hundred two
    volunteers were recruited and, using a simple 5-point
    scoring system to grade their general well-being and
    severity of any hay fever attacks, the overall average
    score was 3.85, indicating that Nasaleze was able to
    control hay fever very well. Rapid relief of symptoms was
    also demonstrated, sometimes within minutes after
    inhalation. Overall, 77% of volunteers reported a
    significant reduction in the number of challenges
    throughout the study period and most graded Nasaleze as
    more effective and reported fewer side effects than with a
    wide range of chemical treatments. Publication Types:
    Clinical Trial PMID: 14669817

    Nephrologie. 1996; 17(3): 163-70. [Risk factors for acute
    hypersensitivity reactions in hemodialysis] [Article in
    French] Simon P, Potier J, Thebaud HE. CH La Beauchee,

    The aim of this prospective study was to evaluate the
    prevalence of anaphylactoid reactions (AR) in patients
    dialysed with cellulose or synthetic membranes and the
    possible link with ACE inhibitors.... PMID: 9064565

    Biologicals. 2003 Dec; 31(4): 245-9. Removal of gelatin from
    live vaccines and DTaP-an ultimate solution for vaccine-
    related gelatin allergy. Kuno-Sakai H, Kimura M. Department
    of Public Health and Social Medicine, School of Medicine,
    Tokai University, 143 Shimokasuya, Isehara City, Kanagawa,
    259-1193, Japan.

    From the early 1990s infants started to receive acellular
    pertussis vaccine combined with diphtheria and tetanus
    toxoids (DTaP) before live vaccines such as measles,
    rubella, and mumps vaccines, which contained gelatin as a
    stabilizer. Then, an increasing number of cases of
    anaphylactic/allergic reactions to those live vaccines were
    reported. Almost all these cases had a previous history of
    receiving three or four doses of DTaP containing
    gelatin.Anaphylactic/allergic reactions to live measles
    vaccine were analyzed using information obtained from the
    Reporting System, a retrospective study, as well as from the
    Monitoring System, a prospective study. Dramatic decreases
    in anaphylactic/allergic reactions to live measles vaccines
    were observed immediately after each manufacturer marketed
    gelatin-free or gelatin (hypo-allergic)-containing live
    measles vaccine, and since the end of 1998 reports on
    anaphylactic/allergic reactions to live measles vaccine have
    almost ceased. PMID: 14624794

    Clin Exp Allergy 2000 May; 30(5): 739-43. Why do some
    dietary migraine patients claim they get headaches from
    placebos? Strong FC 3rd Departamento de Ciencia de Alimentos
    Faculdade de Engenharia de Alimentos Universidade Estadual
    de Campinas, SP, Brasil
    rsidade/universidade.html and Department of Chemistry,
    Bucknell University 570-577-2000 Lewisburg,
    PA, USA. Strong Frederick C [email protected]
    c/o C H Clapp Chemistry Dept, Graduate/Special, guest

    BACKGROUND: In six double-blind studies involving 182 tests
    of dietary migraine patients sensitive to tyramine and beta-
    phenylethylamine, 18% reported headaches from placebos which
    were all concealed in gelatin capsules. OBJECTIVE: The
    purpose of this research was to test a hypothesis: gelatin
    is partially hydrolysed animal protein; (partially)
    hydrolysed vegetable protein (PHVP) is known to cause
    migraine; perhaps the gelatin caused some of the headaches.
    METHOD: The author tested this hypothesis on himself because
    he suffers from dietary migraine. He proved this in a double-
    blind test with tyramine hydrochloride (TYH). The amount
    required for the test was so small (1 mg) that it was
    tasteless and capsules were unnecessary. The author then
    undertook tests with a capsule, PHVP, monosodium glutamate
    (MSG) aspartame (a dipeptide) and TYH, adjusting quantities
    to give a moderate headache. Samples were mixed with foods
    to simulate normal eating: the capsule with potato chips,
    aspartame with orange juice and the rest with cottage cheese
    or ricotta cheese. Times were measured from ingestion (1) to
    start of the headache and (2) to maximum headache intensity.
    Each experiment was repeated three times. The headaches were
    relieved with caffeine. RESULTS: Of eight double-blind test
    samples, the author identified correctly the two placebos
    and five of the six samples containing tyramine. Quantities
    giving moderate headaches were: 1 gelatin capsule, 400 mg
    MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical
    times for the three repetitions of the two time periods were
    8, 9 and 11 and 17, 19 and 22 min. CONCLUSIONS: Capsules may
    give headaches to dietary migraine patients that are similar
    to those from foods. This would explain some of the
    headaches of patients from placebos. The double-blind test
    and the repeatability of the time measurements demonstrated
    the validity of the experiments. PMID: 10792367 ]

    J Allergy Clin Immunol. 1995 Feb; 95(2): 639-640. Aspartame-
    induced hives. Anthony Kulczycki, Jr., MD
    [email protected] Assc. Prof. of Medicine Division of
    Allergy and Immunology, Department of Medicine Washington
    University School of Medicine Box 8122, 660 South Euclid
    Avenue, St. Louis, MO 63110.

    Correspondence: To the Editor:

    The failure by Geha et al. (J Allergy Clin Immunol 1993; 92:
    513-20) to find more than two subjects with aspartame-
    induced hives may have resulted from flaws in study design.
    After reviewing their study protocol in 1986 to 1987, I
    declined to take part because I identified the defects
    numbered below.

    My perspective is based on my own additional experience with
    aspartame-induced hives, summarized as follows.

    During 1986, after reporting two index cases (1), I was
    contacted by 88 individuals in the St. Louis area who had
    heard a direct televised appeal for subjects and had
    suspected that their chronic urticaria or angioedema might
    be due to aspartame. By contrast, indirect attempts to
    recruit subjects (i.e., appeals to local allergists) yielded
    no referrals during the same period. Few of my telephone
    respondents had consulted an allergist.

    Seventy-five of the individuals who telephoned were willing
    to avoid aspartame for 2 weeks; 50 experienced complete
    resolution of hives upon aspartame avoidance; 22 were
    willing to openly rechallenge themselves with aspartame,
    and each re-experienced allergic skin reactions. With
    resources to study only six of these individuals, I found
    four of them (all women) who experienced hives after double-
    blind, placebo-controlled challenges with aspartame. One
    subject (age 40) had a reaction 3 hours after challenge,
    which was similar to the initial cases (1); one subject
    (age 26) had an immediate reaction and a delayed reaction
    12 hours after challenge; one subject (age 29) had an
    "immediate reaction" 2.5 hours after challenge and
    subsequent delay outbreaks of hives at 9, 23, 30, and 43
    hours, which required treatment; and one subject (age 43)
    had only a delayed reaction at 22 hours after challenge; no
    subjects reacted to placebo. Thus it should not be
    surprising that the subjects B01 and F03 in the study by
    Geha et al. experienced delayed reactions to aspartame.
    Allergists need to recognize that aspartame-induced hives
    can be acute, delayed, or chronic. [ As in the case of morning-
    after hangovers from the formaldehyde produced from the
    methanol impuritities in wines and dark liquors, it takes
    some hours for the liver to process the aspartame-derived
    methanol into formaldehyde and formic acid.
    Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer:
    Robert Swift, MD: [formaldehyde from methanol in aspartame]:
    Murray 1.16.4 rmforall
    hangovers from formaldehyde from methanol (aspartame?):
    Schwarcz: Linsley: Murray 1.18.4 ]

    The defects I identified in the study by Geha et al. are the

    1. Subject recruitment methods.

    There are two types of recruiting: direct appeals to
    subjects and indirect appeals through physicians. Indirect
    recruiting is less successful when subjects rarely visit
    physicians and when physicians are not actively looking for
    a given disorder. Geha et al. relied primarily on indirect
    types of recruiting and garnered only 86 referrals. I found
    that direct appeals to patients via television were
    essential for adequate recruitment of aspartame-allergic
    subjects. From my perspective, the recruiting efforts of
    Geha et al were inadequate to address the problem of aspartame-
    induced hives, and therefore their conclusion that "the
    incidence (of aspartame-induced urticaria) is "rare" is

    There remains no study that adequately defines the incidence
    of aspartame-induced hives in the population. [ Indeed, the
    Geha study is widely used by the aspartame industry to deny
    the validity of hundreds of cases of allergic and
    dermatological reactions, disparaging dismissed as
    "anecdotal reports". ]

    2. Convenience, compensation, and safety for subjects.

    Geha et al. note that 32 of the individuals contacted
    "decline to participate". Their study design probably tended
    to discourage the participation of the subjects who were
    most likely to be allergic to aspartame. Why? The more a
    potential subject finds that aspartame consumption
    correlates with hives, the less motivation the potential
    subject has to learn about the cause of his or her hives and
    to participate in an inconvenient, 5-day hospital stay,
    especially if compensation is inadequate. The more uncertain
    the correlation, the more likely a potential subject might
    be to welcome an extensive evaluation. (The authors should
    disclose the financial compensation to subjects; it may have
    been inadequate to encourage sufficient subject
    participation.) Also, subjects with more severe or delayed
    symptoms would be more likely to decline to participate
    because of the potential for a severe reaction. Having once
    experienced that one diet soda could produce severe or
    delayed allergic reactions, some of the potential subjects
    most sensitive to aspartame may have been unwilling to
    participate out of concern for their safety. (The study
    required ingestion of the equivalent of over six cans of
    diet soda.) Obviously, the nine enrolled subjects in the
    study by Geha et al who had required no medications did not
    have severe urticaria or angioedema.

    My challenge procedures were more conveniently designed.
    They involved two 4-hour outpatient visits, usually on
    Saturdays, with 50 mg of aspartame. [ 2 oz diet soda
    equivalent ] The six subjects that I found to have positive
    responses to aspartame were unwilling to be referred to the
    Geha et al. study because they believed it would be too
    inconvenient and possibly unsafe.

    Thus several aspects of the Geha et al. study design may
    have contributed to selectively discourage the participation
    of the subjects likely to be allergic to aspartame.

    3. Inclusion or exclusion criteria and challenge design.

    Avoiding "confounding (but unspecified) medication within
    three weeks" is not adequate preparation for aspartame
    challenges. The national task force recommendation to avoid
    astemizole for at least 6 weeks, and also tricyclic
    antidepressants, before skin testing (2) should clearly
    apply to this type of challenge study. Because astemizole,
    which can suppress responses to skin tests (and presumably
    challenges) for possibly up to 12 weeks, has been commonly
    used in treatment of chronic urticaria, prior astemizole use
    might explain some of the negative aspartame challenge
    results. Withdrawal from the astemizole might account for
    one or both of the "positive" placebo challenge results. I
    ask the authors, "How many subjects had taken astemizole
    during the 12 weeks before their challenges?" (Also, what
    justifies the authors' apparent assumption that "a positive
    histamine skin test" will guarantee a positive challenge?)

    Although five subjects in the "population identified as
    alleged responders" by Geha et al. had food-induced hives
    and seven subjects had allergic respiratory problems,
    apparently no effort was made to limit the subjects'
    diets or to exclude other recognized causes of chronic
    urticaria (3).

    Because of these deficiences in study design, I am
    concedrned that the NutraSweet Company-sponsored study by
    Geha et al. does not accurately reflect the incidence of aspartame-
    induced hives. I hope that, from among the dozens of
    allergist who have cases of aspartame-induced hives,
    additional studies will be forthcoming.

    Anthony Kulczycki, Jr, MD


    4. Kulczycki A. Aspartame-induced urticaria. Ann Intern
    Med. 1986; 104: 207-208.

    5. Bernstein IL. Proceedings of the Task Force on
    guidelines for standardizing old and new technologies
    used for the diagnosis and treatment of allergic
    diseases. J Allergy Clin Immnol. 1988; 82: 494.

    6. Kulczycki A, Atkinson JP. Urticaria and angioedema.
    Io: Korenblat PE, Wedner HJ, eds. Allergy: theory and
    practice. 2 ed. Philadelphia: WB Saunders Co.,
    1992, 217-228.
    eyelid contact dermatitis by formaldehyde from
    aspartame, AM Hill & DV Belsito, Nov 2003: Murray 3.30.4
    rmforall [ 150 KB ]

    Rich Murray, MA Room For All [email protected] 1943 Otowi
    Road, Santa Fe, New Mexico 87505 USA 505-986-9103

    [ Comments by Rich Murray are in square brackets. To
    increase the readability of the dense, specialized,
    condensed text of a brief scientific letter (usually not
    peer reviewed), I have added spacing without altering text,
    while correcting minor typos.

    I then offer some critical analyses and extensions of the
    references, since the relevant scientific literature is
    contaminated by long-term, systematic influence by corporate
    vested interests. ]

    "A 60-year-old Caucasian woman presented with a 6-month
    history of eyelid dermatitis...

    By strictly avoiding formaldehyde and all formaldehyde
    releasers for the next 3 weeks, she improved only slightly.

    Her problem, however, was subsequently solved when a local
    pharmacist advised her to avoid aspartame.

    She had begun using an aspartame-based artificial sweetener
    5 months prior to the onset of her dermatitis. [ 12 months
    of low-level aspartame use until stopping. ]

    Within 1 week of discontinuing the aspartame, her eyelid
    dermatitis resolved completely and has not recurred over 18
    months without specific treatment....

    Our patient was consuming an average of 80 mg (1.13
    mg/kg) of aspartame daily, well below the levels
    previously studied."

    [ Jpacket of tabletop sweetener gives 37 mg aspartame,
    while a 12 oz diet soda gives 200 mg aspartame. An
    aspartame reactor can have immediate strong symptoms
    from an under-the-tongue wafer with 4 mg aspartame.
    (Appendix A, for comments, abstracts, and links.) ]

    Contact Dermatitis. 2003 Nov; 49(5): 258-9. Systemic contact
    dermatitis of the eyelids caused by formaldehyde derived
    from aspartame? Hill AM, Belsito DV. [email protected]
    Division of Dermatology, University of Kansas Medical
    Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
    PMID: 14996049

    K. Michele Hill and Donald V. Belsito Division of
    Dermatology, University of Kansas Medical Center 3901
    Rainbow Blvd., Kansas City, KS 66160, USA [ (Appendix B,
    for more abstracts by Donald V. Belsito, selections, and
    institutions) ]

    Key Words: allergic contact dermatitis; aspartame; eyelids;
    formaldehyde; systemic contact dermatitis.

    Formaldehyde is a common and ubiquitous contact allergen.
    Sources of exposure include hair and skin care products,
    cosmetics, topical medications, permanent press clothing,
    cleaning agents, disinfectants, paper and even smoke. [
    Also, new buildings, mobile homes, furniture, carpets,
    drapes, particleboard, medical facilities, methanol,
    aspartame, dimethyl dicarbonate, dark wines and liquors ]

    Sensitization is reported in between 2.2 and 9.6% of
    patients patch tested (1,2). [ (Appendix C, for abstracts on
    rates of formaldehyde sensitivity in control groups, as a
    possible first estimate of the impact of widespread exposure
    to aspartame since 1981.) ]

    Case Report

    A 60-year-old Caucasian woman presented with a 6-month
    history of eyelid dermatitis. A corticosteroid-containing
    opthalmologic ointment improved but did not clear the rash.
    She failed to improve when she discontinued the use of all
    eyelid cosmetics and nail polishes for 2 months. She had had
    a facial dermatitis in 1995, for which she had been patch
    tested and found to be allergic to formaldehyde, quaternium-
    15 and fragrances. She had also had incidental, non-relevant
    reactions to neomycin and ethylenediamine. Her dermatitis
    had resolved with a change to formaldehyde-, quaternium-15
    and fragrance-free facial and nail cosmetics.

    There was no personal or family history of atopy or
    psoriasis. Her only oral medication was celecoxib that she
    had taken for years prior to the onset of her blepharitis.
    She had also taken multivitamins, calcium and flaxseed oil
    for many years. She worked as a homemaker and library
    volunteer. [ It is relevant as to whether she had the
    standard urban diet with high protein and animal fats,
    meats, milk products, some inorganic fruits and vegetables,
    high sugars, and processed foods. Mercury dental amalgams
    and mercury contaminated fish could also play a role. Was
    her water fluoridated or otherwise contaminated? Were there
    toxic mold exposures in her environment? Was she exposed to
    pesticides in her area? ]

    Her eyelid dermatitis was kept clear with tacrolimus 0.03%
    ointment X2 daily. She underwent patch testing to the North
    American Contact Dermatitis Group standard tray, the
    University of Kansas' supplemental standard tray, and to her
    cosmetics, cleansers, skin and hair care products and
    topical medications. She had relevant positive reactions at
    days 2 and 4 to formaldehyde (++), quaternium-15 (++),
    diazolidinyl urea (+), DMDM hydantoin (+) and imidazolidinyl
    urea (++), her hair care products and cleansers containing
    multiple sources of these allergens.

    She was extensively instructed in avoidance of formaldehyde
    and formaldehyde releasers, as well as that of her multiple,
    currently non-relevant allergens, including fragrance,
    benzalkonium chloride, neomycin, bacitracin, p-
    phenylenediamine and black rubber mix. [ As a medical
    layman, I'm disturbed to see all these chemicals that I know
    nothing about. ]

    By strictly avoiding formaldehyde and all formaldehyde
    releasers for the next 3 weeks, she improved only slightly.

    Her problem, however, was subsequently solved when a local
    pharmacist advised her to avoid aspartame.

    She had begun using an aspartame-based artificial sweetener
    5 months prior to the onset of her dermatitis. [ 12 months
    of low-level aspartame use until stopping. Aspartame
    reactors discover this possibiliy usually from the Net,
    alternative medicine providers, media, nurses, friends, and
    pharmacists, rarely from physicians. ]

    Within 1 week of discontinuing the aspartame, her eyelid
    dermatitis resolved completely and has not recurred over 18
    months without specific treatment. [ This quick healing
    response is typical of cases of low-level use with few
    symptoms. Long-term heavy users , above 2 L, about 6 12-oz
    cans daily for years, often have severe craving and
    withdrawal symptoms for weeks, with gradual recovery for
    months. H. J. Roberts, MD has summarized over 1200 cases.
    (Appendix H) Three recent case reports are added here.
    (Appendix I) ]

    Unfortunately, she refused to undergo rechallenge with the
    sweetener. [ This is usually the case. Commonly, there is
    inadvertent reexposure, with immediate painful symptoms,
    even with low doses. ]


    The artificical sweetener, aspartame, is consumed by 54% of
    adults in the USA (3).

    It has been reported to cause dry eyes and difficulty in
    wearing contact lenses (3) but never allergic contact
    dermatitis. [ Reference (3) is given in full here. (Appendix
    H) Roberts H J. Dry eyes from use of aspartame (Nutrasweet):
    Associated insights concerning the Sjogren syndrome. The
    Townsend Letter for Doctors, January 1994. Appendix H also
    quotes several cases of eyelid dermatitis from his review