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four Murray AspartameNM reviews in SE Jacob & SA Stechschulte debate with EG Abegaz & RG Bursey of Ajinomoto re migraines from formaldehyde from aspartame, Dermatitis 2009 May: TE Hugli -- folic acid with V-C protects: Rich Murray 2009.08.12

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  • Rich Murray
    four Murray AspartameNM reviews in SE Jacob & SA Stechschulte debate with EG Abegaz & RG Bursey of Ajinomoto re migraines from formaldehyde from aspartame,
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      four Murray AspartameNM reviews in SE Jacob & SA Stechschulte debate with EG Abegaz & RG Bursey of Ajinomoto re migraines from formaldehyde from aspartame, Dermatitis 2009 May: TE Hugli -- folic acid with V-C protects: Rich Murray 2009.08.12
      http://rmforall.blogspot.com/2009_08_01_archive.htm
      Wednesday, August 12, 2009
      http://groups.yahoo.com/group/aspartameNM/message/1582
      _____________________________________________________


      A medical layman, BS physics and history, MIT 1964, MA
      psychology, Boston University Graduate School 1967, retired after 19
      years as a home hospice care giver in Santa Fe, New Mexico, I have
      served over ten years as a volunteer information activist, accumulating
      a public archive of 1,583 conscientious, fair, civil, detailed reviews of
      mainly mainstream scientific and media reports re aspartame
      (methanol, formaldehyde, formic acid) toxicity and related issues.

      It may be helpful at this stage to "put words in the mouths"
      of responsible vested interests:

      "We believe in public service capitalism.

      We apologize for misleading and harming people.
      We share responsibility with many businesses and organizations
      worldwide for similar mistakes about many widely sold products.

      Rather than futilely resist and delay severe penalties and
      correction from legal and governmental actions, public service
      associations, corporate competition, aroused media, and an
      increasingly informed world public, while continuing to leave people
      at risk, we choose to take the creative intitiative to change ourselves
      immediately, setting a positive example for our world, that all people
      may cooperate for healthy food, drink, and environment.

      We cease production and distribution now of our harmful products.
      We make all our information conveniently available about our past
      stratagies and actions regarding research, development, testing,
      production, advertising, government, medicine, media, politics,
      handling of complaints -- all our staff must tell the truth, the whole
      truth, and nothing but the truth.

      We cooperate with true public service associations:

      1. Set up huge funds for aiding victims.
      2. Set up funds for independent robust research worldwide on all
      aspects of the problems.
      3. Persuade other corporations and groups to join vigorously in these
      endeavors.
      4. Set up funds for full and constant two-way feedback with all
      groups and people.
      5. Set up vigorous reforms for disfunctional political funding and
      influence on all levels.
      6. Set up thorough, accurate and full accounting for actual long-term
      costs to people and our world from our products.
      7. Base staff and corporate rewards on successful competiton
      focused on products that aid the evolution of people.
      8. Sustain genuine positive competition among businesses worldwide.
      9. Maintain complete transparency about all our strategies, policies,
      and actions."
      _____________________________________________________


      Formaldehyde, aspartame, migraines: a possible connection.
      Abegaz EG, Bursey RG.
      Dermatitis. 2009 May-Jun;20(3):176-7; author reply 177-9.
      No abstract available. PMID: 19470307

      Eyassu G. Abegaz *
      Robert G. Bursey
      Ajinomoto Corporate Services LLC, Scientific & Regulatory Affairs,
      1120 Connecticut Ave., N.W., Suite 1010, Washington, DC 20036
      * Corresponding author. Tel.: +1 202 457 0284;
      fax: +1 202 457 0107.
      abegazee@... (E.G. Abegaz),
      burseyb@... (R.G. Bursey)

      "For example, fruit juices, coffee, and alcoholic beverages produce
      significantly greater quantities of formaldehyde than aspartame-
      containing products. [6]"

      "[6] Magnuson BA, Burdock GA, Doull J, et al. Aspartame: a
      safety evaluation based on current use levels, regulations, and
      toxicological and epidemiological studies.
      Crit Rev Toxicol 2007;37:629-727"
      [ two detailed critiques of industry affiliations and biased science in
      99 page review with 415 references by BA Magnuson, GA Burdock
      and 8 more, Critical Reviews in Toxicology, 2007 Sept.: Mark D
      Gold 13 page: also Rich Murray 2007.09.15: 2008.03.24
      http://rmforall.blogspot.com/2008_03_01_archive.htm
      Monday, March 24, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1531

      "Nearly every section of the Magnuson (2007) review has research
      that is misrepresented
      and/or crucial pieces of information are left out.

      In addition to the misrepresentation of the research,
      readers (including medical professionals) are often not told that
      this review was funded by the aspartame manufacturer, Ajinomoto,
      and the reviewers had enormous conflicts of interest." ]
      _____________________________________________________


      http://www.medscape.com/viewarticle/579335

      Dermatitis. 2008; 19(3): E10-E11.
      © 2008 American Contact Dermatitis Society
      Formaldehyde, Aspartame, and Migraines: A Possible Connection
      Sharon E. Jacob; Sarah Stechschulte
      Published: 09/17/2008

      Abstract

      Aspartame is a widely used artificial sweetener that has been linked
      to pediatric and adolescent migraines.
      Upon ingestion, aspartame is broken, converted, and oxidized into
      formaldehyde in various tissues.
      We present the first case series of aspartame-associated migraines
      related to clinically relevant positive reactions to formaldehyde
      on patch testing.

      Case Series

      Six patients (ages 16 to 75 years) were referred for evaluation of
      recalcitrant dermatitis. By history, five of the patients were noted to
      have developed migraines following aspartame consumption; the
      sixth reported dermatitis flares associated with diet cola
      consumption of >2 liters/day.

      All six patients had current environmental exposures to formaldehyde
      or formaldehyde-releasing preservatives in their personal hygiene
      products and/or regular consumption of "sugar-free food" artificially
      sweetened with aspartame.

      Based on their histories and clinical presentations, these patients
      were patch-tested with the North American Contact Dermatitis
      Group 65-allergen Standard Screening Series and selected
      chemicals from the University of Miami vehicle, fragrance, bakery,
      and textile trays.

      All six patients had positive reactions to formaldehyde, and four had
      additional positive reactions to formaldehyde-releasing preservatives
      (FRPs). Expert counseling on allergen avoidance (including
      avoidance of formaldehyde, FRPs, and aspartame) and alternative
      product recommendations were provided to the patients.

      At their follow-up appointments (between 8 and 12 weeks), all the
      patients showed clearance of their dermatitis. Four patients (two
      inadvertently) resumed their consumption of aspartame and
      subsequently returned for an additional follow-up visit. Three of the
      first five patients had recurrences of both their migraines and their
      dermatitis; the sixth patient (who had no migraines) had a positive
      rechallenge dermatitis. These four patients were again counseled on
      avoidance regimen.

      Discussion

      Aspartame is a widely used artificial sweetener that has been linked
      to a multitude of ailments, particularly pediatric and adolescent
      migraines[1] ( Table 1 and Table 2 ).[2-4] Studies suggest that
      aspartame is a significant migraine trigger, especially when
      consumption is prolonged.[1]

      Upon ingestion, aspartame is broken down into aspartic acid,
      aspartic acid methyl ester, and phenylalanine in the gut wall.[5]

      The methyl ester is subsequently converted into methanol, which is
      oxidized to formaldehyde and formic acid in various tissues.[6]

      Formaldehyde is known to form chemical adducts with nucleic acids
      and proteins. These adducts have been found to be difficult to remove
      by normal metabolic pathways; hence, accumulation may occur.[6]

      To our knowledge, aspartame-associated migraines related to
      clinically relevant positive reactions to formaldehyde on patch testing
      have not previously been reported. In 2003, Hill and Belsito reported
      a case of a nonmigraine patient with chronic eyelid dermatitis that
      cleared when aspartame was discontinued. This case presented the
      possibility that formaldehyde from aspartame breakdown could trigger
      a systemic contact dermatitis in formaldehyde-sensitive patients.[7]

      Like Hill and Belsito's patient, our sixth patient (the only patient who
      did not have migraines) demonstrated a flare of his dermatitis with
      consumption of aspartame and clearance with avoidance of
      aspartame. Our five migraine cases suggest that aspartame-induced
      migraines may be a harbinger for formaldehyde sensitivity and an
      important historical point to be elucidated during the initial work-up
      of a patient with presumed allergic contact dermatitis.

      Although we recognize the limitations of drawing conclusions from a
      small sample of patients, we believe this observed association
      warrants further investigation. A larger case study with a
      double-blind placebo-controlled challenge study with aspartame
      capsules and placebo capsules (including nondermatitic control
      patients with aspartame-induced migraines) is needed to firmly
      establish the association between aspartame breakdown products,
      migraines, systemic contact dermatitis, and positive patch-test
      reactions to formaldehyde and FRPs.

      References

      1. Millichap JG, Yee MM. The diet factor in pediatric and
      adolescent migraine Pediatr Neurol 2003;28:9-15.

      2. The NutraSweet Company: statments. Available at:
      http://www.nutrasweet.com/articles/article.asp?Id=47
      (accessed July 19, 2007).

      3. Flintstones vitamins - the heading brand moms trust and kids love!
      Available at: http://www.bayercare.com/htm/flintfaq.htm
      (accessed February 6, 2007).

      4. US Food and Drug Administration: artificial sweeteners: no
      calories...sweet! Available at:
      http://www.fda.gov/fdac/features/2006/406_sweeteners.html
      (accessed July 19, 2007).

      5. Murray TG, Burton TC, Rajani C, et al. Methanol poisoning.
      A rodent model with structural and functional evidence for retinal
      involvement Arch Ophthalmol 1991;109:1012-6.

      6. Trocho C, Pardo R, Rafecas I, et al. Formaldehyde derived from
      dietary aspartame binds to tissue components in vivo
      Life Sci 1998;63:337-49.

      7. Hill AM, Belsito DV. Systemic contact dermatitis of the eyelids
      caused by formaldehyde derived from aspartame?
      Contact Dermatitis 2003;49:258-9.


      formaldehyde, aspartame, and migraines, the first case series, Sharon
      E Jacob-Soo, Sarah A Stechschulte, UCSD, Dermatitis 2008 May:
      Rich Murray 2008.07.18
      http://rmforall.blogspot.com/2008_07_01_archive.htm
      Friday, July 18, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1553


      formaldehyde from many sources, including aspartame, is major
      cause of Allergic Contact Dermatitis, SE Jacob, T Steele, G
      Rodriguez, Skin and Aging 2005 Dec.: Murray 2008.03.27
      http://rmforall.blogspot.com/2008_03_01_archive.htm
      Thursday, March 27, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1533

      "For example, diet soda and yogurt containing aspartame
      (Nutrasweet), release formaldehyde in their natural biological
      degradation.

      One of aspartame's metabolites, aspartic acid methyl ester, is
      converted to methanol in the body, which is oxidized to
      formaldehyde in all organs, including the liver and eyes. 22

      Patients with a contact dermatitis to formaldehyde have been seen to
      improve once aspartame is avoided. 22

      Notably, the case that Hill and Belsito reported had a 6-month
      history of eyelid dermatitis that subsided after 1 week of avoiding
      diet soda. 22"


      Avoiding formaldehyde allergic reactions in children, aspartame,
      vitamins, shampoo, conditioners, hair gel, baby wipes, Sharon E
      Jacob, MD, Tace Steele, U. Miami, Pediatric Annals 2007 Jan.:
      eyelid contact dermatitis, AM Hill, DV Belsito, 2003 Nov.:
      Murray 2008.03.27
      http://rmforall.blogspot.com/2008_03_01_archive.htm
      Thursday, March 27, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1532
      _____________________________________________________


      Sharon E. Jacob, MD, Assistant Professor of Medicine
      (Dermatology)
      University of California, San Diego 200 W. Arbor Drive #8420,
      San Diego, CA 92103-8420 Tel: 858-552-8585 ×3504
      Fax: 305-675-8317 sjacob@...;

      Sarah A. Stechschulte, BA sstechschulte@...

      To the Editor,

      Thank you for the comments received regarding the potential
      association of aspartame consumption with migraine headaches and
      recurrent allergic contact dermatitis (ACD).
      While the commentary did not address the key issues of our
      observations [ie, that challenge results in a response and that a
      patch test challenge with formaldehyde was positive], we appreciate
      the opportunity to discuss this further.[1]
      Molecule for molecule, 11% of aspartame that is hydrolyzed
      becomes methanol (wood alcohol) in the blood.[2]
      The commentary authors' statement suggests that methanol
      metabolism is very rapid; however, the Environmental Protection
      Agency has reported methanol to in fact be a cumulative toxin.[3]
      It is true that methanol is generated from food, but the average intake
      of methanol from natural sources is reported to be about 10 mg/day,
      while a 12 ounce aspartame beverage generates 56 mg/L of
      methanol, or 22 mg per 12 ounces if fully hydrolyzed.[4]
      More than 30 years ago, Oppermann and colleagues reported that
      there was 31% retention of radioactive methanol in rats 8 hours after
      ingestion, retention levels confirmed by an expert review of modern
      studies by M Bouchard and colleagues in 2001.[5],[6]

      The administration of radiolabeled aspartame to experimental
      animals has been shown to result in the incorporation of a significant
      proportion of the label into proteins (thought to be the result of the
      formation of formaldehyde and formate adducts) at least six hours
      after aspartame ingestion.[7]
      In this study, the liver was found to retain more than 2% of the
      methanol carbon from a single dose of aspartame![7]
      Cumulative effects data obtained from the chronic administration
      model also have suggested that regular intake of aspartame may also
      result in a progressive accumulation of formaldehyde adducts.[7]

      Furthermore, it is important to note that the commentary authors'
      reference to the assumption that the incorporation of the methanol
      carbon to normal amino acid structures through the
      "essential one-carbon" tetrahydrofolate and S-adenosyl-methionine
      pathways from aspartame consumption is an assumption no longer
      maintained according to current data. [7]

      In their discussion, the commentary authors raised several false
      premises.
      For example, they concluded that aspartame does not cause
      allergic-type reactions, based on a study that demonstrated that
      aspartame and its conversion products were no more likely than
      placebo to cause urticaria, angioedema reactions, or both, which
      ignored delayed-type hypersensitivity reactions altogether.[8]
      It is important to recognize that ACD is an allergic-type reaction
      with an entirely different mechanism (type IV T-cell mediated
      reaction) from the type I reactions referenced.[9] And notably,
      aspartame has been previously associated with ACD.[10]

      Furthermore, if the incidence of this aspartame-mediated migraine
      response is one in a thousand, then a random study group size would
      need to be much larger than the ones cited by Schiffman and
      colleagues and Leon and colleagues. It is important to note that both
      Schiffman and colleagues (1987) and Leon and colleagues (1987),
      did not study the formaldehyde allergic patient[11],[12] and, that
      without knowing the true incidence of aspartame sensitivity in
      dermatitis patients, it is impossible to make any conclusion from
      these studies.

      We absolutely recognize the need to further study the
      biochemistry of these reactions and that there is speculation and
      concern about aspartame's being a sufficient source of formaldehyde
      to evoke the response, especially when wine and many foods contain
      methanol and methyl esters.
      This being said, we believe the dose may be critical and question the
      effect of ingestion of aspartame as a bolus, as foods are generally
      more slowly metabolized.
      Last, the dose levels of aspartame needed to provoke a response in
      an exquisitely sensitized person may be very low, making half-life
      and metabolic rate less meaningful.

      Thank you for this opportunity for intellectual discourse.
      We still maintain that a larger case study including aspartame-induced
      migrainous non-dermatitis control patients is necessary to establish
      the association presented in our study, and we would like to perform
      an aspartame-formaldehyde challenge to show repeatable responses.
      Alternatively, we would like to challenge individuals known to have
      formaldehyde sensitivity with aspartame and demonstrate a response
      as an indirect proof of principle.

      Acknowledgments

      We acknowledge Tony E. Hugli, PhD, of the Torrey Pines Institute
      for Molecular Studies, for his provocative academic discourse on
      the metabolism of aspartame as we work toward better
      understanding this observed phenomenon.

      Sarah A. Stechschulte, BA
      Sharon E. Jacob, MD
      University of California, San Diego--Rady Children's Hospital,
      San Diego, CA.

      References

      [1] Jacob SE, Stechschulte S. Formaldehyde, aspartame, migraines:
      a possible connection. Dermatitis 2008;19E10-E1.

      [2] Staples RE. Teratogenicity of Formaldehyde.
      In: Gibson JE, editor, Formaldehyde Toxicity. Newport. Australia:
      Hemisphere Publishing Company. 1983. p. 51-60.

      [3] Cleland JG, Kingsbury GL. Multimedia environmental goals for
      environmental assessment. U.S. Environmental Protection Agency;
      1977 Nov. EPA-600/7-77-136b, E-28.

      [4] Monte WC. Aspartame: methanol and the public health.
      J Appl Nutr 1984;36(1). Available at:
      http://groups.yahoo.com/group/aspartameNM/message/870
      (accessed February 11, 2009).

      [5] Oppermann JA, Muldoon E, Ranney RE. Metabolism of
      aspartame in monkeys. Nutrition 1973;103:1454-9.

      [6] Bouchard M, Brunet RC, Droz PO, Carrier G. A biologically
      based dynamic model for predicting the disposition of methanol
      and its metabolites in animals and humans.
      Toxicol Sci 2001;64:169-84.

      [ http://groups.yahoo.com/group/aspartameNM/message/1143
      antiseptic? antifungal? antiviral? methanol (formaldehyde, formic
      acid) disposition: Bouchard M et al, full plain text, 2001: substantial
      sources are degradation of fruit pectins, liquors, aspartame, smoke:
      Murray 2005.01.05 rmforall

      "Exposure to methanol also results from the consumption of certain
      foodstuffs (fruits, fruit juices, certain vegetables, aspartame
      sweetener, roasted coffee, honey) and alcoholic beverages (Health
      Effects Institute, 1987; Jacobsen et al., 1988)." [ It's unusual for a
      mainstream journal article to mention"fruits, fruit juices, certain
      vegetables, aspartame sweetener" and "alcoholic beverages" to be
      methanol sources.]... little is known about the chronic effects of low
      exposure doses... Systemic methanol is extensively metabolized by
      liver alcohol dehydrogenase [ ADH ] and catalase-peroxidase
      enzymes to formaldehyde, which is in turn rapidly oxidized to formic
      acid by formaldehyde dehydrogenase enzymes... Formaldehyde, as it
      is highly reactive, forms relatively stable adducts with cellular
      constituents... Primates and humans appear to be more susceptible to
      the acute toxicity of methanol than rodents... Although methanol has
      been reported to be metabolized mainly in the liver, pulmonary
      metabolism is also likely to occur. Indeed, the catalase-peroxidase
      system responsible for a major fraction of methanol metabolism in
      rats is widely distributed in mammalian tissues... The model
      included a constant background whole body methanol burden of
      2133 µmol, which corresponds to the mean blood concentration of
      .5 mg/L of methanol measured by Osterloh et al. (1996) in control
      subjects at the end of an 8-h frequent blood sampling period... once
      formed, a substantial fraction of formaldehyde is converted to
      unobserved forms. This pathway contributes to a long-term
      unobserved compartment. The latter, most plausibly, represents
      either the formaldehyde that ( directly or after oxidation to formate )
      binds to various endogenous molecules (Heck et al., 1983; Røe,
      1982)... That substantial amounts of methanol metabolites or
      by-products are retained for a long time is verified by Horton et al.
      (1992) who estimated that 18 h following an iv injection of 100
      mg/kg of 14C-methanol in male Fischer-344 rats, only 57% of
      the dose was eliminated from the body. From the data of
      Dorman et al. (1994) and Medinsky et al. (1997), it can further
      be calculated that 48 h following the start of a 2-h inhalation
      exposure to 900 ppm of 14C-methanol vapors in female
      cynomolgus monkeys, only 23% of the absorbed 14C-methanol
      was eliminated from the body. These findings are corroborated by
      the data of Heck et al. (1983) showing that 40% of a
      14C-formaldehyde inhalation dose remained in the body 70 h
      postexposure... Experimental studies on the detailed time profiles
      following controlled repeated exposures to methanol are lacking...
      Thus, in monkeys and plausibly humans, a much larger fraction of
      body formaldehyde is rapidly converted to unobserved forms rather
      than passed on to formate and eventually CO2."

      If we assume 30% retention of durable cumulative toxic products of
      formaldehyde and formic acid, then a 12-oz can diet drink gives 200
      mg aspartame, 22 mg methanol, and 7 mg formaldehyde and formic
      acid at 30% cumulative retention . We may add that well known
      sources of formaldehyde include both wood and tobacco smoke,
      and, notoriously, mobile homes. Two teams give evidence that
      formaldehyde and formic acid from methanol in ethanol drinks
      (often far above the 100 mg/L methanol in red wines, two times the
      level in aspartame drinks) are the main cause of the many symptoms
      of "morning after" hangovers.

      http://groups.yahoo.com/group/aspartameNM/message/1495
      folic acid prevents neurotoxicity from formic acid, made by body
      from methanol impurity in alcohol drinks [ also 11 % of aspartame ],
      BM Kapur, PL Carlen, DC Lehotay, AC Vandenbroucke,
      Y Adamchik, U. of Toronto, 2007 Dec., Alcoholism Cl. Exp. Res.:
      Murray 2007.11.27

      Furthermore, BM Kapur et al, 2007 give evidence that formic acid
      from methanol in ethanol drinks is a major cause of Fetal Alcohol
      Syndrome, readily preventable by adequate levels of folic acid,
      which expedites the safe metabolism of formaldehyde, in most
      people.
      "Methanol is endogenously formed in the brain and is present as a
      congener in most alcoholic beverages.
      Because ethanol is preferentially metabolized over methanol
      (MeOH) by alcohol dehydrogenase, it is not surprising that
      MeOH accumulates in the alcohol-abusing population.
      This suggests that the alcohol-drinking population will have higher
      levels of MeOH's neurotoxic metabolite, formic acid (FA).
      FA elimination is mediated by folic acid.
      Neurotoxicity is a common result of chronic alcoholism.
      This study shows for the first time that FA, found in chronic
      alcoholics, is neurotoxic and this toxicity can be .mitigated by
      folic acid administration." ...
      "MeOH concentrations between 4 and 4500 mg/l can be present
      in various alcoholic beverages (Sprung et al., 1988)."


      A variety of mutations, as well as aspirin and many painkillers,
      impede folic acid. However, fruits and vegetables give enough folic
      acid to mitigate harm from their methanol. Then again, formaldehyde
      may in many people treat infections by fungi, bacteria, and virusus.
      All these unexamined co-factors have confused attempts to study
      aspartame toxicity for three decades.


      http://groups.yahoo.com/group/aspartameNM/message/1490
      details on 6 epidemiological studies since 2004 on diet soda
      (mainly aspartame) correlations, as well as 14 other mainstream
      studies on aspartame toxicity since summer 2005:
      Murray 2007.11.27

      A widely proclaimed NIH-AARP mass survey by U Lim et al. 2006,
      while failing to show specific cancers with feeble diet drink
      consumption data for a year for seniors, did find that 4% of a
      half-million seniors drank 3 and more cans daily diet soda
      [ 12-oz can gives 200 mg aspartame, 22 mg methanol,
      7 mg formaldehyde and formic acid at 30% cumulative retention ]

      aspartame mg/d
      0 ---- under 100 - 100-200 - 200-400 - 400-600 - 600-1200 -
      cohort %
      46 ------- 25 ------ 13 ------- 7 --------- 5 ------ about 3 ----

      over 1200 mg/d
      under 1%

      This is the first good data about the percentage of aspartame users
      who use over 3 cans daily, averaging 5 cans daily at 200 mg per 12
      oz can diet soda.
      About 4% of 473,984 is 19,000 people, with a peak intake of 17
      cans daily, and average 5 cans daily.
      It would be worthwhile to investigate a wide variety of symptoms for
      the 0.1 % of highest level users, about 500 people.
      For about 200 million USA aspartame users, this would be 200,000
      people.

      The highest level 3400 mg aspartame [ 17 12-oz cans ] gives
      11% = 374 mg methanol, 48 times the recommended daily limit of
      consumption of 7.8 mg as recommended by the
      Environmental Protection Agency (EPA).3

      At 30% retention of cumulative toxic products of formaldehyde and
      formic acid, these would be 125 mg, 60 times higher than the 1999
      EPA alarm level for formaldehyde in daily drinking water of
      1 ppm = 2 mg for average daily drinking water of 2 L daily. ]

      [7] Trocho C, Pardo R, Rafecas I, Virgili J, et al. Formaldehyde
      derived from dietary aspartame binds to tissue components in vivo.
      Life Sci. 1998;63:337-49. Available at:
      http://groups.yahoo.com/group/aspartameNM/message/925
      (accessed February 11, 2009).

      [Extract from aspartameNM #925:
      McMartin (1979) admitted one datum that showed accumulation of
      formaldehyde in the midbrain from an acute toxicity dose of
      methanol, and widespread accumulation of formic acid in five tissues.
      He wrote: "It is now generally accepted that the toxicity of methanol
      is due to the formation of toxic metabolites (1,2), either formaldehyde
      or formic acid."

      Biochemical Pharmcacology 1979: 28; 645-649.
      Lack of a role for formaldehyde in methanol poisoning in the monkey.
      Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
      and Thomas R. Tephly
      The Toxicology Center, Dept. of Pharmacology,
      University of Iowa, Iowa City, Iowa 52242

      Abstract [not given in PubMed]:
      Methanol was administered [by nasogastric tube] either to untreated
      cynomolgus monkeys [2-3.5 kg] or to a folate-deficient cynomolgus
      monkey which exhibits exceptional sensitivity to the toxic effects of
      methanol.
      Marked formic acid accumulation in the blood and in body fluids and
      tissues was observed.
      No formaldehyde accumulation was observed in the blood and no
      formaldehyde was detected in the urine, cerebrospinal fluid, vitreous
      humor, liver, kidney, optic nerve, and brain in these monkeys at a
      time when marked metabolic acidosis and other characteristics of
      methanol poisoning were observed.
      Following intravenous infusion into the monkey, formaldehyde was
      rapidly eliminated from the blood with a half-life of about 1.5 min
      and formic acid levels promptly increased in the blood.
      Since formic acid accumulation accounted for the metabolic acidosis
      and since ocular toxicity essentially identical to that produced in
      methanol poisoning has been described after formate treatment, the
      predominant role of formic acid as the major metabolic agent for
      methanol toxicity is certified.
      Also, results suggest that formaldehyde is not a major factor in the
      toxic syndrome produced by methanol in the monkey. [End]

      So, this is an acute toxicity study, with little relevance for chronic
      long-term, low-level exposure.
      None of the five tissues showed any formaldehyde in this study,
      except the midbrain, 0.14 mmol/kg wet weight tissue [units
      converted from their 0.14 micromole/gm]-- just 1.5 times the
      detection limit of .09 mmol/kg wet tissue weight (given on p. 648).
      It is reasonable to surmise that more sensitive assays would have
      found formaldehyde and formate bound to and reacted with a variety
      of cellular substances in all tissues, as later found by Trocho (1998).]

      [8] Geha R, Buckley CE, Greenberger P, et al. Aspartame is no more
      likely than placebo to cause urticaria/angioedema: results of a
      multicenter, randomized, double-blind, placebo-controlled, crossover
      study. J Allergy Clin Immunol 1993;92:513-20.

      [9] Fisher AA. Contact dermatitis.
      Philadelphia, Lea & Febiger, 1967.

      [10] Hill AM, Belsito DV. Systemic contact dermatitis of the
      eyelids caused by formaldehyde derived from aspartame?
      Contact Dermatitis. 2003;49:258-9.
      [ http://groups.yahoo.com/group/aspartameNM/message/1067
      eyelid contact dermatitis by formaldehyde from aspartame, AM Hill
      & DV Belsito, Nov 2003: Murray 3.30.4 rmforall [ 150 KB ] ]

      [11] Schiffman SS, Buckley CE, Sampson HA, et al. Aspartame
      and susceptibility to headache. N Engl J Med 1987;317:1181-5.
      Available at:
      http://groups.yahoo.com/group/aspartameNM/message/623
      (accessed February 11, 2009).

      [12] Leon AS, Hunninghake DB, Bell C, et al. Safety of long term
      large doses of aspartame. Arch Intern Med 1989;149:2318-24.
      Available at:
      http://groups.yahoo.com/group/aspartameNM/message/622
      (accessed February 11, 2009).

      [ http://groups.yahoo.com/group/aspartameNM/message/846
      RTM: aspartame in Merck Maxalt-MLT worsens migraine,
      AstraZeneca Zomig, Eli Lilly Zyprexa,
      J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
      Pfizer Cool Mint Listerine Pocketpaks 7.16.2 rmforall
      Migraine MLT-Down: an unusual presentation of migraine
      in patients with aspartame-triggered headaches.
      Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
      [Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
      while 12 oz diet soda has 200 mg.]
      Headache Institute, St. Lukes-Roosevelt Hospital Center,
      New York, NY
      Department of Neurology newmanache@...
      Albert Einstein College of Medicine, Bronx, NY
      Innovative Medical Research RLipton@...

      http://groups.yahoo.com/group/aspartameNM/message/855
      RTM: Blumenthall & Vance:
      aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
      Harvey J. Blumenthal, MD, Dwight A Vance, RPh
      Chewing Gum Headaches.
      Headache 1997 Nov-Dec; 37(10): 665-6.
      Department of Neurology,
      University of Oklahoma College of Medicine, Tulsa, USA.
      neurotulsa@...
      Aspartame, a popular dietetic sweetener, may provoke headache
      in some susceptible individuals. Herein, we describe three cases of
      young women with migraine who reported their headaches could be
      provoked by chewing gum sweetened with aspartame.
      [6-8 mg aspartame per stick chewing gum] ]


      [ http://www.thetruthaboutstuff.com/review1.shtml plain text
      Review 1 - Published November 2007
      Monte WC. 2007, Is your Diet Sweetener killing you?
      Fitness Life. 2007 Nov; 33:31-33.
      http://www.fitnesslife.co.nz/
      www.fitnesslife.co.nz/contactus/contactus.htm

      NZ's best selling health & fitness magazine

      role of formaldehyde, made by body from methanol from foods and
      aspartame, in steep increases in fetal alcohol syndrome, autism,
      multiple sclerosis, lupus, teen suicide, breast cancer, Nutrition Prof.
      Woodrow C. Monte, retired, Arizona State U., two reviews, 190
      references supplied, Fitness Life, New Zealand 2007 Nov, Dec:
      Murray 2007.12.26
      http://rmforall.blogspot.com/2007_12_01_archive.htm
      Wednesday, December 26 2007
      http://groups.yahoo.com/group/aspartameNM/message/1498
      full text, references

      http://www.thetruthaboutstuff.com/review2.shtml plain text

      Sweet Misery: A Poisoned World

      Review 2 - Published December 2007

      Monte WC. 2007, A Deadly Experiment --
      (Fitness Life. 2007 Dec;34:38-42.)

      The abstracts and texts of all 190 references are given in pdf form:
      http://www.thetruthaboutstuff.com/articles.shtml

      USA Fetal Alcohol Syndrome rates per 10,000 births
      and aspartame consumption 1980-1995
      1984 --- 1.8 cases per 10,000 births
      1993 --- 6.8
      http://www.thetruthaboutstuff.com/charts/FAS%20USA.pdf

      Methyl alcohol ingestion as a model etiologic agent in multiple
      sclerosis, WC Monte, D Glanzman, C Johnston; Methanol
      induced neuropathology in the mammalian central nervous system,
      Woodrow C. Monte, Renee Ann Zeising, both reports
      1989.12.04: Murray 2007.12.28
      http://rmforall.blogspot.com/2007_12_01_archive.htm
      Friday, December 28 2007
      http://groups.yahoo.com/group/aspartameNM/message/1499
      full text

      old tiger roars -- Woodrow C Monte, PhD -- aspartame causes
      many breast cancers, as ADH enzyme in breasts makes methanol
      from diet soda into carcinogenic formaldehyde -- same in dark wines
      and liquors, Fitness Life 2008 Jan.: Murray 2008.02.11
      http://rmforall.blogspot.com/2008_02_01_archive.htm
      Monday, February 11, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1517
      full text, confirming abstracts ]
      _____________________________________________________



      Tony E. Hugli has 226 items in PubMed.

      http://www.zoominfo.com/people/Hugli_Tony_583089966.aspx

      www.dermazaide.com/partnership.htm - [Cached Version]
      Last Visited: 7/4/2009

      # If you represent a skin care development and marketing company
      and would like to learn more about partnership opportunities please
      contact: Dr. Tony Hugli, CEO, HealthAide, Inc. (858) 455-3892
      tony@...

      # New company explores novel therapeutic uses for... --
      [Cached Version] Published on: 8/27/2004 Last Visited: 6/29/2005

      According to HealthAide CEO Dr. Tony E. Hugli, the company will
      investigate a wide variety of health and medical applications for the
      sweetener ."Many of the applications that we have planned are
      enhancements of existing brand-name products that are already
      generating multi-million dollar annual sales," he said. ...
      CEO Hugli expects that this edge will translate into dollars and cents
      on the company's bottom line."HealthAide will have very low
      overhead and operational expenses, which affords us the opportunity
      to become profitable sooner than is normally expected," he said.

      HealthAide's management team consists of:
      CEO: Dr. Tony E. Hugli,
      Scientific Director, California Toxicology Research Institute

      # View Online Source
      Scientific Advisory Board - Antigen Express - [Cached Version]
      Published on: 3/25/2006 Last Visited: 6/25/2009
      Tony Hugli, Ph.D. Director,
      Department of Immunological Toxicology,
      Califormia Toxicology Research Institute

      http://www.faqs.org/patents/app/20090036528

      Patent title: Multifunctional and combinational application
      aspartame and or futhan
      Inventors: Tony E. Hugli, John E. Adams
      Agents: Martin G. Ozinga;Phillips Murrah, P.C.
      Assignees:
      Origin: OKLAHOMA CITY, OK US
      IPC8 Class: AA61K3124FI
      USPC Class: 514542

      Abstract:
      The present invention is an application, composition, and method of
      using a pharmaceutically effective amount of aspartame or its primary
      metabolite aspartyl-phenylalanine in systematic and periodic
      application or dose as an aspirin (NSAID) substitute, treatment for
      osteoporosis, and or topical treatment for Rosacea.

      Claims:
      1. A method for treating rosacea in a patient comprising administering
      to a patient suffering from rosacea a pharmaceutically effective amount
      of aspartame.

      2. A method for treating osteoporoses in a patient comprising
      administering to a patient suffering from osteoporoses a
      pharmaceutically effective amount of aspartame.

      3. A method of substituting aspartame for aspirin in a patient
      comprising administering to a patient a pharmaceutically effective
      amount of aspartame instead of aspirin.
      Description:
      CROSS-REFERENCE TO RELATED APPLICATIONS

      [0001] Priority is claimed from provisional patent applications
      U.S. Ser. No. 60/964,987, filed on Aug. 16, 2007,
      and U.S. Ser. No. 60/962,651, filed on Jul. 31, 2007
      and incorporated by reference herein.

      BACKGROUND OF THE INVENTION

      [0002] 1. Field of the Invention

      [0003] In general, the present invention is an application,
      composition, and method of using the dipeptide ester aspartame.

      More in particular, the present invention is a systematic and
      periodic application of aspartyl-phenylalanyl methyl ester,
      hereinafter referred to generally as aspartame, as a topical
      formulation and/or an oral formulation for applications utilizing
      aspartame beneficial analgesia, anti-inflammatory, osteoporosis,
      anti-platelet blood thinning effects and combinations thereof.

      It is understood that the current invention may provide a
      pharmaceutically effective amount of aspartame or its primary
      metabolite aspartyl-phenylalanine as an aspirin (NSAID)
      substitute as well as enhance calcium solubility, bio-availability,
      absorption, mineral transfer and bone growth for animals and
      humans as will be described in greater detail below.

      It is also contemplated a pharmaceutically effective amount of
      aspartame may be utilized for a topical application for rosacea
      in specific......

      Addressing the Potential Side Effects of Aspartame

      [0092] Besides addressing the very real problem of Phenylketouria,
      and indicating that Aspartame should not be used by individuals with
      this condition, there is a major problem associated with claims of
      Aspartame being dangerous. The main danger that is cited is that the
      breakdown product methanol can be converted (oxidized) to
      formaldehyde and large quantities of formaldehyde can be toxic.
      These are not biochemically sound assertions and clinical studies
      have widely refuted these claims, however the damage has been
      done in terms of the general public's perception of the compound.

      [0093] The body has several metabolic pathways to deal with both
      methanol and formaldehyde, which is found in many foods and are
      essential at normal dietary levels. A major pathway is called the
      "single carbon metabolism pathway" and it is an essential pathway
      for building both protein (i.e. certain amino acids) and nucleic acids.
      In fact, when the single carbon pathway dysfunctions humans become
      anemic.

      [0094] The single carbon pathway actually utilizes formaldehyde
      that is primarily made in the body.
      The process involves a vitamin called Folic Acid.
      The folic acid is reduced to Tertrahydrofolic Acid by reducing agents
      such as ascorbic acid or Vitamin C. See FIG. 4.
      In the tetrahydrofolic acid, this compound chemically reacts with
      formaldehyde at two sites, the N5 and N10 positions.
      This effectively removes formaldehyde from the body or from
      embodiment of the invention and the body uses it either for the
      metabolism of other body molecules or it is excreted.
      In either case, this is a method to detoxify both methanol and
      formaldehyde.

      [0095] It is therefore contemplated the above embodiments may
      utilize the addition of ascorbic acid (vitamin C) and folic acid along
      with aspartame.
      It is contemplated this may keep the levels of methanol and
      formaldehyde low and avoid any side effects from the normal
      breakdown of dipeptide ester.
      Since both of these ingredients are inexpensive, it may be a
      convenient way to effectively neutralize the urban myths about
      aspartame being potentially dangerous......
      _____________________________________________________


      "Of course, everyone chooses, as a natural priority, to enjoy
      peace, joy, and love by helping to find, quickly share, and positively
      act upon evidence about healthy and safe food, drink, and
      environment."

      Rich Murray, MA Room For All rmforall@...
      505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

      http://RMForAll.blogspot.com new primary archive

      http://groups.yahoo.com/group/aspartameNM/messages
      group with 141 members, 1,583 posts in a public archive

      http://groups.yahoo.com/group/aspartame/messages
      group with 1207 members, 23,863 posts in a public archive
      _____________________________________________________

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