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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

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  • Rich Murray
    formaldehyde from many sources, including aspartame, is major cause of Allergic Contact Dermatitis, SE Jacob, T Steele, G Rodriguez, Skin and Aging 2005 Dec.:
    Message 1 of 1 , Mar 27, 2008
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      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"

      "We present a case of a medical student who presented with
      erythematous eczematoid plaques on her trunk and legs and
      fine vesiculation of her scalp, 3 weeks after starting anatomy class.

      Of note, she routinely washed her face and arms after leaving the
      anatomy lab, but remained in her scrubs for the rest of the day.

      Formaldehyde and Quaternium-15 positive reactions
      in the same patient."

      "Our patient underscores the importance of appropriate patch
      testing and education.
      Once we identified the allergy to formaldehyde and quaternium-15,
      we provided patient education materials regarding the common and
      not-so-common locations of these chemicals and cross-reactors.
      We also gave the patient information on avoidance
      and safe alternatives (see Table 5).

      Fortunately, with technical advances, this student completed the
      anatomy section via electronic learning tools.

      By avoiding formaldehyde, including anatomy lab, FRP
      in her shampoo and cosmetics,
      and aspartame in her diet, this patient dramatically improved.

      As with all contact dermatitides, the mainstay of treatment for
      allergic contact dermatitis is avoidance."


      http://www.skinandaging.com/article/5158Skin & Aging Journal
      Skin & Aging - ISSN: 1096-0120 - Volume 13 - Issue 12_2005 -
      December 2005 - Pages: 22 - 27

      Allergen Focus:
      Focus on T.R.U.E. Test Allergens #21, 13 and 18:
      Formaldehyde and Formaldehyde-Releasing Preservatives
      -- By Sharon E. Jacob, M.D., Tace Steele, B.A., [now MD]
      and Georgette Rodriguez, M.D., M.P.H.

      [ See also:

      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 ]


      Allergic Contact Dermatitis is an important disease with a high
      impact both in terms of patient morbidity and economics.

      The contact dermatitides include irritant contact dermatitis,
      contact urticaria and allergic contact dermatitis.

      Irritant contact dermatitis, the most common form, accounts for
      approximately 80% of environmental-occupational based
      dermatoses.

      Contact urticaria (wheal and flare reaction) represents an IgE and
      mast cell-mediated immediate-type hypersensitivity reaction
      that can lead to anaphylaxis,
      the foremost example of this would be latex hypersensitivity.
      While this is beyond the scope of this section, we acknowledge this
      form of hypersensitivity due to the severity of the potential reactions
      and direct the reader to key sources. 1,2

      Allergic contact dermatitis, on the other hand, is a delayed type IV
      hypersensitivity reaction. The primary focus of this section is to
      highlight the educational component of allergic contact dermatitis.

      Clinical Illustration

      We present a case of a medical student who presented with
      erythematous eczematoid plaques on her trunk and legs
      and fine vesiculation of her scalp,
      3 weeks after starting anatomy class.
      Of note, she routinely washed her face and arms after leaving the
      anatomy lab, but remained in her scrubs for the rest of the day.

      Formaldehyde and Quaternium-15 positive reactions
      in the same patient.

      History of Formaldehyde
      and the Formaldehyde-Releasing Preservatives

      The desire to improve one's appearance with topical applications
      dates back to the Egyptian Queen, Cleopatra, who was fond of
      using creams and make-up for skin beautification. 3

      What once was fit for a queen has become a $30 billion a year
      cosmetic industry. 4

      With the cosmetic boom came the concern of microorganisms
      in cosmetic creams introduced during manufacture or transferred
      to the product through use. 5

      A variety of reports of cosmetic contamination from
      Klebsiella pneumoniae have been reported.

      In addition, this bacterium has been linked to septicemia
      after contact with a contaminated hand cream dispenser. 6,7

      Consequently, considerable attention has been given to topical
      pharmaceutical preparations
      with effective methods of antimicrobial preservation.

      Preservatives are biocidal chemicals added to cosmetics,
      topical medicaments and foods to protect against spoilage,
      bacterial and fungal contamination, and biological degradation. 7

      The ideal preservative should be stable, antimicrobial, nontoxic,
      non-irritating and active over a broad range of pH values.

      In 1938, the FDA passed the Food, Drug and Cosmetic Act
      requiring the cosmetic industry to prove product safety
      before marketing to consumers. 8

      Prior to that, products such as Lash-Lure
      (by the Los Angeles-based company)
      containing paraphenylenediamine had caused blindness,
      and a whitening foundation containing lead oxide
      had caused muscle paralysis. 9

      Soon thereafter, formaldehyde preservation of cosmetics was being
      streamlined for its many advantages.
      It was cheap and effective in eliminating a wide range of
      microorganisms and aggressively destroying degradation enzymes,
      thus slowing product decomposition.
      Formaldehyde remains a commonly used preservative in cosmetics
      today with an average concentration between 0.02% and 0.3%. 10

      How It Was Discovered

      A formaldehyde-based white brittle material, polyformaldehyde was discovered
      during the incomplete combustion of carbon in 1859
      by the Russian chemist, Alexander Mikhailovich Butlerov.
      This leader in isomer chemistry (and synthesizer of the first artificial
      sugar) has had a crater on the moon named after him to
      commemorate his work. 11,12

      Ten years after the polymer discovery, the German chemist,
      August Wilhem von Hofman, found that by passing methanol
      and air over a heated platinum spiral, he could create pure
      formaldehyde (a technique is still used today). 13

      In 1892, the year of Hofman's death, Friedrich August Kekule von Stradonitz,
      the scientist who introduced the concept of chemical
      bonds, isolated pure formaldehyde by the catalytic oxidation of
      methanol.

      First Commercial Uses

      One of the first mass commercial uses of formaldehyde was in
      medical embalming (a practice known to be utilized during the
      Civil War). 14

      Interestingly, formaldehyde use evolved with medical advancement.
      In 1883, Robert Koch made a landmark discovery with a weighty
      economic impact to the food industry.
      He found that the bacterium, Vibrio cholerae, the cause of cholera,
      could be transmitted via food and water.
      This discovery initiated the demand for government regulation
      of food industry sanitation and the necessitation of antimicrobial
      food additives. 8

      In 1900, San Franciscan Chinese immigrants suffered from an
      outbreak of the bubonic plague. The city board of health quarantined
      Chinatown and dusted the district with a mixture of lime and
      formaldehyde to control the spread of disease. 15

      In 1912, Dr. Harvey Wiley, Head of the Department of Chemistry
      in Washington D.C. (Predecessor to the Food and Drug
      Administration), founded the "poison squad".
      This squadron of volunteers ate food to test the safety of added
      preservatives (for example, borax, benzoic acid, sulfuric acid and
      formaldehyde).
      The poison squad was so popular with the public that minstrel
      shows sang about it:

      "Next week he'll give them mothballs, a la Newburgh or else plain;
      O, they may get over it, but they'll never look the same." 8

      After 5 years of experiments, vomiting and stomach pain,
      Dr. Wiley publicly resolved that preservatives in food and medications
      should "only be used when absolutely necessary,"
      despite big business fighting him "tooth and nail". 8

      In the 1950s, formaldehyde again made its mark in the medical
      news. Jonas Salk's team created a polio vaccine.
      This was made possible through the use
      of formaldehyde to kill the poliovirus. 15

      Success with Plastics

      Although the medical and food industries had mixed experiences
      with formaldehyde, the plastics industry thrived because of it.

      Prior to innovation of formaldehyde-derived plastics, the
      celluloid plastics had been highly flammable and not suitable for mass
      marketing. 16 At the turn of the century,
      the International Galalith Gesellschaft Hoff and Company
      compounded formaldehyde and fat-free milk curd to formulate
      a new synthetic plastic (casein-formaldehyde),
      which became a main constituent of buttons. 16,17

      The biggest landmark in formaldehyde-based plastics
      came in 1910.
      Leo H. Baekeland condensed phenol and formaldehyde to make
      the first non-flammable synthetic plastic, Bakelite, which had high
      utility as an electronics insulator. 10,18
      Bakelite sales skyrocketed, as it was marketed in toys,
      jewelry and cameras.
      The Bakelite Museum in England even boasts a Bakelite coffin! 19

      Its amber color contributed to its popularity in jewelry, but limited its
      potential when transparency was needed. 10
      During the Bakelite heyday, circa 1912, scientists, Daniel J. O'Conor
      and Herbert Faber, added formaldehyde to a urea polymer to
      develop a novel insulation substitute for mica, aka formica. 18

      The 1920s and '30s, saw the explosive age of the urea
      formaldehyde resins whose colorless properties allowed new lines
      of plastic products in bright colors, i.e the trendy plastic versions
      of marble dishes, bandalasta. 11,21

      Today, urea-formaldehyde resins and melamine-formaldehyde
      laminates dominate the commercial market.
      What began as a reach for a new plastic alternative and preservative
      has become a $500 billion industry,
      representing 5% of the United States' gross national product. 11

      Formaldehyde is used to make plywood, asphalt shingles, car gears
      and bearings.

      Specifically, p-tert-Butylphenol formaldehyde resin is used in
      bonded leather, construction materials and waterproof glues.

      In addition, fertilizers and photographic developers are also known to
      contain formaldehyde. 11

      A Powerful Allergen

      The rates of sensitization to formaldehyde have risen to 9.2%. 22,23

      Formaldehyde is second only to fragrances as the most common
      sources of cosmetic-associated contact dermatitis. 24

      To decrease sensitization and lower the concentration of
      formaldehyde, the formaldehyde-releasing-preservatives (FRPs)\
      are often used in place of frank formaldehyde, for example
      quaternium-15 (see Table 1). 7,22,25


      Herbert and Rietschel explain that if the concentration of
      formaldehyde that is released by FRPs is below the threshold
      of reactivity for virtually all formaldehyde-sensitive patients
      (somewhere between 30 and 250 ppm), there would not be
      an allergy to the FRP. 25

      Many cases of contact dermatitis to formaldehyde/FRPs present
      as eyelid dermatitis associated with the use of cosmetics
      (mascara, blush and foundation), shampoos, medical creams
      or nail hardeners, to name a few.

      Other important sources of exposure include permanent press clothing,
      cleaning agents, baby wipes, disinfectants, paper
      and even cigarette smoke. 22

      As is often the case in contact dermatitis, the distribution of the
      dermatitis can provide insight into the exposure.
      For example, patients sensitized to formaldehyde from adorned
      permanent-press clothing tend to present with a chronic dermatitis
      around their body folds, where the clothes rub against the skin. 22

      Patients sensitized to formaldehyde in clothing textiles have been found
      to become secondarily sensitized to quaternium-15, presenting with a
      diffuse nummular dermatitis or erythroderma. 24

      Systematized dermatitis is seen with both formaldehyde and the FRPs.

      Inhalation (smoking) and ingestion of formaldehyde containing foods
      are important systemic sensitization sources (see Table 2) .27-30


      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

      Formaldehyde-Releasing Preservatives

      The formaldehyde releasers are reversible polymers
      of formaldehyde. 31

      Formaldehyde is formed in different amounts based on the pH,
      temperature, and amount of water. 31,32
      The antibacterial effects are independent of the
      amount of formaldehyde released. 29

      An allergic reaction can be seen specifically to the FRP,
      formaldehyde or both. 31

      Quaternium-15, a colorless, odorless, biocidal FRP
      is highly water-soluble, stable, and active over a broad range of pH.

      It has broad antimicrobial activity, particularly Pseudomonas aeruginosa,
      yeasts, and molds. 22

      As the most common sensitizer among the formaldehyde-releasers,
      it is included on the T.R.U.E. test and has many alternative names
      (see Table 3). 23

      Occupational sources

      Occupation is one of the biggest risk factors
      for quaternium-15 exposure.
      Occupations such as hair dressing, painting, printing, textile dyeing,
      paper processing and working with disinfectants all have greater risks
      of developing allergies to quaternium-15, according to Haz-Map,
      an organization that evaluates occupational risks for exposures to
      hazardous chemicals.

      Formaldehyde is both an irritant and a contact allergen.

      Contact urticaria and anaphylaxis to formalin have been described
      in a patient after a root canal and in a hemodialysis patient,
      respectively
      (see list of systemic formaldehyde effects in Table 4). 28,33

      Garment industry workers, hemodialysis nurses, embalmers,
      pathologists, and dermatologists are at great occupational risk for
      occupational-based formaldehyde allergy.

      Due to the notoriety it has received as a potential carcinogen, irritant,
      and sensitizer, formaldehyde use in cosmetics
      has significantly decreased. Notably, formaldehyde is prohibited
      in cosmetics in Sweden and Japan. 22

      Testing for Allergy to Formaldehyde and FRPs

      Patch testing for formaldehyde, quaternium-15,
      and p-tert-Butylphenol formaldehyde resin allergy
      can be accomplished with the
      Thin-layer Rapid Use Epicutaneous (T.R.U.E.) test
      (sites 18, 21, and 13, respectively).

      The T.R.U.E. test is the commercially available, globally used,
      allergen screening system.

      While it is widely used, the discrepancy in allergen prevalence and
      uncertain relevance has led to scrutiny of its utility.

      The T.R.U.E test contains 23 allergens and one negative control.

      At best, the T.R.U.E test is a minimum screening tool because
      it tests only 23 of the more than 3,700 possible allergens
      that can cause allergic contact dermatitis.

      Krob et al. recently demonstrated that nickel, thimerosal, cobalt,
      fragrance and balsam of Peru are the most prevalent allergens
      detected by the T.R.U.E. test, yet a significant number of relevant
      allergens, not present on the T.R.U.E. test, are potentially missed
      by this screening tool used alone. 34

      Value of this Patient Case

      Our patient underscores the importance of appropriate
      patch testing and education

      Once we identified the allergy to formaldehyde and quaternium-15,
      we provided patient education materials regarding the common and
      not-so-common locations of these chemicals and cross-reactors.

      We also gave the patient information on avoidance
      and safe alternatives (see Table 5).

      Fortunately, with technical advances, this student completed the
      anatomy section via electronic learning tools.

      By avoiding formaldehyde, including anatomy lab,
      FRP in her shampoo and cosmetics,
      and aspartame in her diet,
      this patient dramatically improved.

      As with all contact dermatitides, the mainstay of treatment
      for allergic contact dermatitis is avoidance.

      References:

      1. Valks R, Conde-Salazar L, Cuevas M.
      Allergic contact urticaria from
      natural rubber latex in healthcare and non-healthcare workers.
      Contact Dermatitis 2004; 50(4): 222-4.

      2. Warshaw E. Latex allergy.
      Skinmed. 2003; 2(6): 359-66.

      3. Mehta, Surjit S, Surjit R, Belum SN.
      Cosmetic dermatitis current perspectives.
      International Journal of Dermatology 2003; 42(7): 533-542.

      4. Geist I.
      Movers & Shakers Ron's $70 Million Sale.
      Forbes Accessible on the Internet at:
      www.forbes.com/realestate/2004/11/05/cx_cd_1105movers.html

      5. Behravan, J., Bazzaz, Fazly & Malaekeh, P.
      Survey of bacteriological contamination
      of cosmetic creams in Iran (2000).
      International Journal of Dermatology 2005; 44(6): 482-485.

      6. Morse LJ, Williams HL, Grenn FP, et al.
      Septicemia due to Klebsiella pneumoniae
      originating from a hand cream dispenser.
      New Engl J Med 1967; 277: 472-473.

      7. Sasseville, D.
      Hypersensitivity to preservatives.
      Dermatologic Therapy 2004; 17: 251-263.

      8. US Food and Drug Administration.
      History of the FDA: The 1938 Food, Drug, and Cosmetic Act
      Accessible on the Internet at:
      http://www.fda.gov/oc/history/historyoffda/section2.html

      9. Brief History of Beauty and Hygiene Products.
      Accessible on the Internet at:
      http://scriptorium.lib.duke.edu/adaccess/cosmetics-history.html

      10. Cahill J, Nixon R
      Allergic contact dermatitis to quaternium-15 in a moisturizing lotion.
      Australasian Journal of Dermatology. 2005; 46(4): 284-285.

      11. Formaldehyde Council.
      Formaldehyde: A Brief History and Its Contributions to Society
      and the U.S. Economy. Accessible on the Internet at: www.formaldehyde.org
      2005.

      12. Biography.ms.
      Aleksandr Mikhailovich Butlerov. Accessible on the Internet at:
      http://aleksandr-butlerov.biography.ms/

      13. Formaldehyde its history, chemistry and uses.
      Accessible on the Internet at:
      www.chm.bris.ac.uk/webprojects2002/robson/Home%20page.htm

      14. Bedino JH.
      Formaldehyde Embalming Sprays: A Modern Myth.
      In: The Expanding Encyclopedia of Mortuary Practices.
      Champion Company; Springfield, OH: 2001.

      15. Chase M.
      The Barbary Plague.
      Random House; New York, NY: 2003.

      16. British Plastics Federation.
      History of Plastics. Accessible on the Internet at:
      http://www.bpf.co.uk/bpfindustry/History_of_Plastics.cfm.

      17. Plastics Historical Society.
      Casein.
      Accessible on the Internet at:
      http://www.plastiquarian.com/casein2.htm

      18. Cook P, Sleeker C.
      Bakelite, An Illustrated Guide to Collectible Bakelite Objects.
      Chartwell Books; Secaucus, New York: 1992.

      19. Bakelite Museum. Accessible on the Internet at:
      http://www.bakelitemuseum.co.uk/

      20. Wikedia.
      Formica (plastic).
      Accessible on the Internet at:
      http://en.wikipedia.org/wiki/Formica_(plastic)

      21. The Bandalasta Web site.
      Accessible on the Internet at:
      http://www.bandalasta.com/

      22. Hill AM, Belsito DV.
      Systemic contact dermatitis of the eyelids
      caused by formaldehyde derived from aspartame.
      Contact Dermatitis. 2003; 49(5): 258-259.

      23. Marks JG, Belsito DV, DeLeo VA, et al.
      North American Contact Dermatitis Group
      patch-test results, 1998-2000.
      J Am Acad Dermatol 1998; 38: 9118.

      24. Adams R M, Maibach H I.
      A five-year study of cosmetic reactions.
      J Am Acad Dermatol 1985; 13: 1062-1069.

      25. Herbert, Courtney & Rietschel, Robert L.
      Formaldehyde and formaldehyde releasers:
      How much avoidance of cross-reacting agents is required?
      Contact Dermatitis 2004; 50(6): 371-373.

      26. Fowler JF, Jr, Skinner SM, Belsito DV.
      Allergic contact dermatitis from
      formaldehyde resins in permanent-press clothing.
      An underdiagnosed cause of generalized dermatitis.
      J Am Acad Dermatol 1992; 27: 962-968.

      27. Restani P, Campagner P, Fiecchi A, et al.
      Identification of spinacine as the principal reaction product of
      gamma-casein with formaldehyde in cheese.
      Food Chem Toxicol. 1988; 26(5): 441-6.

      28. Food Standards Agency.
      Analysis of formaldehyde in shiitake mushrooms
      (2004) Accessible on the Internet at:
      www.food.gov.uk/science/research/researchinfo/
      foodcomponentsresearch/phytoestrogensresearch/
      t05-t06programme/t05t06projectlist/t05027project/

      29. Food and environmental Hygiene department.
      The Government of Hong Kung
      special administration region. Accessible on the Internet at:
      www.fehd.gov.hk/safefood/report/formaldehyde/formaldehyde.html

      30. Agency for Toxic Substances and Disease Registry.
      Medical Management Guidelines (MMGs) for Formaldehyde
      (HCHO) on the Internet at:
      http://www.atsdr.cdc.gov/MHMI/mmg111.html

      31. Andersen K, White I, Goossens A.
      Allergens from the Standard Series.
      In: Rycroft R, Menne T, Frosch P, Lepoittevin JP (eds)
      Textbook of Contact Dermatitis. 3rd ed.
      Springer-Verlag: New York: 2001.

      32. De Groot A, White I.
      Cosmetics and Skin Care Products.
      In: Rycroft R, Menne T, Frosch P, Lepoittevin JP (eds)
      Textbook of Contact Dermatitis. 3rd ed.
      Springer-Verlag: New York: 2001.

      33. Kitagawa T, Katoh N, Yasuno H, Wakamori T.
      A case of contact urticaria syndrome due to formalin
      in root-canal dental paste (2001). Accepted for publication:
      Accessible at:
      http://www.fujita-hu.ac.jp/JSCD/all_folder/pdf/83-14601.pdf

      34. Krob HA, Fleischer AB, D'Agostino R, et al.
      Prevalence and relevance of contact dermatitis allergens:
      a meta-analysis of 15 years of published T.R.U.E. test data.
      J Am Acad Dermatol. 2004; 51(3): 349-53.

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      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.: eye 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
      ____________________________________________________


      "It is generally recommended that exposure to products containing
      formaldehyde, FRP's, and aspartame (NutraSweet) be avoided
      in children."

      "Through metabolism, aspartame is converted metabolically
      in the liver to methanol,
      which is in turn metabolized to formaldehyde. 8"


      www.pediatricannalsonline.com/showPdf.asp?rID=21306

      Avoiding formaldehyde allergic reactions in children
      Pediatric Annals. 2007 Jan.; 36(1): 55-6. PMID: 17269284

      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@...;

      Tace Steele, BA

      http://www.aad.org/ American Academy of Dermatology
      over 16,000 members
      ____________________________________________________


      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."


      [ See also:

      http://groups.yahoo.com/group/aspartameNM/message/1453
      Souring on fake sugar (aspartame), Jennifer Couzin,
      Science 2007.07.06: 4 page letter to FDA from 12 eminent
      USA toxicologists re two Ramazzini Foundation cancer studies
      2007.06.25: Murray 2007.07.18


      http://groups.yahoo.com/group/aspartameNM/message/957
      safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
      Murray 2003.01.12 EU Scientific Committee on Food, a whitewash

      http://groups.yahoo.com/group/aspartameNM/message/1045
      http://www.holisticmed.com/aspartame/scf2002-response.htm
      Mark Gold exhaustively critiques European Commission Scientific
      Committee on Food re aspartame ( 2002.12.04 ):
      59 pages, 230 references

      bias, omissions, incuriosity = opportunity, aspartame safety
      evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more,
      2007 Sept, Ajinomoto funded 98 pages html [ $ 32 pdf ]:
      Murray 2007.09.15
      http://rmforall.blogspot.com/2007_09_01_archive.htm
      Saturday, September 15, 2007 ]

      "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 120 members, 1,532 posts in a public archive

      http://groups.yahoo.com/group/aspartame/messages
      group with 1,085 members, 22,467 posts in a public archive

      Hawaii Senate Health Committee will consider resolution SCR191
      by Sen. Suzanne Chun Oakland, and 10 other of 25 Senators,
      to have FDA ban aspartame
      and for National Academy of Sciences to review research:
      Murray 2008.03.14
      http://rmforall.blogspot.com/2008_03_01_archive.htm
      Friday, March 14, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1527

      http://groups.yahoo.com/group/aspartameNM/message/1525
      House Concurrent Resolution #132 for Health Department panel
      to decide aspartame ban by early 2010,
      Hawaii Rep. Josh Green MD, Health Committee Chair:
      Murray 2008.03.12
      http://rmforall.blogspot.com/2008_03_01_archive.htm
      Wednesday, March 12, 2008
      ____________________________________________________


      Note: many recent aspartame bans.....

      http://groups.yahoo.com/group/aspartameNM/message/1426
      ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
      will join Tesco and also Sainsbury to ban and limit aspartame,
      MSG, artificial flavors dyes preservatives additives, trans fats, salt
      "nasties" to protect kids from ADHD: leading UK media:
      Murray 2007.05.15

      http://groups.yahoo.com/group/aspartameNMmessage/1451
      Artificial sweeteners (aspartame, sucralose) and coloring agents
      will be banned from use in newly-born and baby foods,
      the European Parliament decided: Latvia ban in schools 2006:
      Murray 2007.07.12

      http://groups.yahoo.com/group/aspartameNM/message/1341
      Connecticut bans artificial sweeteners in schools, Nancy Barnes,
      New Milford Times: Murray 2006.05.25

      http://groups.yahoo.com/group/aspartameNM/message/1369
      Bristol, Connecticut, schools join state program to limit artificial
      sweeteners, sugar, fats for 8800 students, Johnny J Burnham,
      The Bristol Press: Murray 2006.09.22


      bias, omissions, incuriosity = opportunity, aspartame safety
      evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more,
      2007 Sept, Ajinomoto funded 98 pages html [ $ 32 pdf ]:
      Murray 2007.09.15
      http://rmforall.blogspot.com/2007_09_01_archive.htm
      Saturday, September 15, 2007

      http://groups.yahoo.com/group/aspartameNM/message/1491
      industry scientists praise aspartame safety and benefits in Paris on
      2006.05.30, Herve Nordmann, Andrew G. Renwick,
      Carlo La Vecchia, Tommy Visscher, Jaap Seidell, France Bellisle,
      Adam Drewnowski, Margaret Ashwell, Anne de la Hunty,
      Sigrid A. Gibson, Alan R. Boobis: Murray 2007.11.18

      http://groups.yahoo.com/group/aspartameNM/message/1070
      critique of aspartame review, French Food Safety Agency AFSSA
      2002.05.07 aspartamgb.pdf (18 pages, in English), Martin Hirsch:
      Murray 2004.04.13

      http://groups.yahoo.com/group/aspartameNM/message/957
      safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
      Murray 2003.01.12 EU Scientific Committee on Food, a whitewash

      http://groups.yahoo.com/group/aspartameNM/message/1045
      http://www.holisticmed.com/aspartame/scf2002-response.htm
      Mark Gold exhaustively critiques European Commission Scientific
      Committee on Food re aspartame ( 2002.12.04 ):
      59 pages, 230 references

      http://www.eatright.org/Nutritive(1).pdf
      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.

      http://groups.yahoo.com/group/aspartameNM/message/1068
      critique of aspartame review
      by American Dietetic Association Feb 2004,
      Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 2004.05.14



      http://www.dorway.com/upipart1.txt
      http://groups.yahoo.com/group/aspartameNM/message/262
      aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon,
      UPI reporter: Murray 2000.07.10

      http://www.dorway.com/enclosur.html
      http://groups.yahoo.com/group/aspartameNM/message/53
      aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06

      http://groups.yahoo.com/group/aspartameNM/message/927
      Donald Rumsfeld, 1977 head of Searle Corp.,
      got aspartame FDA approval: Turner: Murray 2002.12.23

      http://groups.yahoo.com/group/aspartameNM/message/1483
      Donald Rumsfeld CEO 1977-85 G.D. Searle & Co., got new
      President Reagan to prohibit FDA opposition to aspartame
      1981.01.25, history by lawyer James S. Turner:
      Murray 2007.10.29

      http://groups.yahoo.com/group/aspartameNM/message/928
      revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23

      http://groups.yahoo.com/group/aspartameNM/message/858
      Samuels: Strong: Roberts: Gold: flaws in double-blind studies re
      aspartame and MSG toxicity: Murray 2002.08.01

      "Survey of aspartame studies: correlation of outcome and funding
      sources," 1998, unpublished: http://www.dorway.com/peerrev.html
      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 rwalton193@...
      http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm


      http://groups.yahoo.com/group/aspartameNM/message/1395
      Aspartame Controversy, in Wikipedia democratic
      encyclopedia, 72 references (including AspartameNM # 864
      and 1173 by Murray, brief fair summary of much more research:
      Murray 2007.01.01


      http://groups.yahoo.com/group/aspartameNM/message/1513
      metabolic syndrome is tied to diet soda, PL Lutsey, LM Steffen,
      J Stevens, Circulation 2008.01.22: role of formaldehyde and
      formic acid from methanol in wines, liquors, or aspartame?:
      Murray 2008.02.21

      "But the one-third who ate the most fried food increased their risk
      by 25 percent, compared with the one-third who ate the least, and
      surprisingly, the risk of developing metabolic syndrome was 34
      percent higher among those who drank one can of diet soda a day
      compared with those who drank none.

      "This is interesting," said Lyn M. Steffen, an associate professor of
      epidemiology at the University of Minnesota and a co-author of the
      paper, which was posted online in the journal Circulation on Jan. 22.
      "Why is it happening? Is it some kind of chemical in the diet soda,
      or something about the behavior of diet soda drinkers?""

      "The diet soda association was not hypothesized
      and deserves further study."


      http://groups.yahoo.com/group/aspartameNM/message/1143
      methanol (formaldehyde, formic acid) disposition:
      Bouchard M et al, full plain text, 2001:
      substantial sources are degradation
      of fruit pectins, liquors, aspartame, smoke:
      Murray 2005.04.02


      http://groups.yahoo.com/group/aspartameNM/message/1511
      vinyl acetate, ethyl alcohol, or aspartame in womb increases later
      cancers in adults with lifetime exposure in many studies, M Soffritti
      et al, Ramazzini Foundation, Basic Clin. Pharm. Toxicol. 2008 Feb.:
      Rich Murray 2008.02.07

      http://groups.yahoo.com/group/aspartameNM/message/1016
      President Bush & formaldehyde (aspartame) toxicity:
      Ramazzini Foundation carcinogenicity results Dec 2002:
      Soffritti: Murray 2003.08.03 rmforall

      p. 88 "The sweetening agent aspartame hydrolyzes in the
      gastrointestinal tract to become free methyl alcohol,
      which is metabolized in the liver
      to formaldehyde, formic acid, and CO2. (11)"
      Medinsky MA & Dorman DC. 1994;
      Assessing risks of low-level methanol exposure.
      CIIT Act. 14: 1-7.

      http://groups.yahoo.com/group/aspartameNM/message/1453
      Souring on fake sugar (aspartame), Jennifer Couzin,
      Science 2007.07.06: 4 page letter to FDA from 12 eminent
      USA toxicologists re two Ramazzini Foundation cancer studies
      2007.06.25: Murray 2007.07.18

      30 female pet store rats drinking lifelong 13.5 mg aspartame,
      1/3 packet of Equal, had 33% with obvious tumors -- also bulging,
      sick, and missing eyes, paralysis, obesity, skin sores -- agrees with
      Ramazzini Foundation results, Victoria Inness-Brown:
      Murray 2008.02.15
      http://rmforall.blogspot.com/2008_02_01_archive.htm
      Friday, February 15, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1521


      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

      http://groups.yahoo.com/group/aspartameNM/message/1340
      aspartame groups and books:
      updated research review of 2004.07.16: Murray 2006.05.11


      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

      "Alcohol dehydrogenase ADH is required for the conversion of
      methanol to formaldehyde (112).

      ADH is not a common enzyme in the human body -- not many cells
      in the human body contain this enzyme.

      The human breast is one of the few organs in the body with a high
      concentration of ADH (190b), and it is found there exclusively in the
      mammary epithelial cells, the very cells known to transform into
      adenocarcinoma (190c) (breast cancer).

      The most recent breast cancer scientific literature implicates ADH
      as perhaps having a pivotal role in the formation of breast cancer,
      indicating a greater incidence of the disease in those
      with higher levels of ADH activity in their breasts (190a)."

      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


      Since no adequate data has ever been published on the
      exact disposition of toxic metabolites in specific tissues in humans
      of the 11 % methanol component of aspartame,
      the many studies on morning-after hangover from the methanol
      impurity in alcohol drinks are the main available resource to date.

      http://groups.yahoo.com/group/aspartameNM/message/1469
      highly toxic formaldehyde, the cause of alcohol hangovers, is
      made by the body from 100 mg doses of methanol from
      dark wines and liquors, dimethyl dicarbonate, and aspartame:
      Murray 2007.08.31

      http://groups.yahoo.com/group/aspartameNM/message/1052
      DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
      ( becomes formaldehyde in body ): EU Scientific Committee on Foods
      2001.07.12: Murray 2004.01.22

      http://europa.eu.int/comm/food/fs/sc/scf/out96_en.pdf

      "...DMDC was evaluated by the SCF in 1990 and considered
      acceptable for the cold sterilization of soft drinks and fruit juices
      at levels of addition up to 250 mg/L (1)
      ...DMDC decomposes primarily to CO2 and methanol ...

      [ Note: Sterilization of bacteria and fungi is a toxic process,
      probably due to the inevitable conversion in the body of methanol
      into highly toxic formaldehyde and then formic acid. ]

      The use of 200 mg DMDC per liter would add 98 mg/L
      of methanol to wine which
      already contains an average of about 140 mg/L from natural sources.

      http://groups.yahoo.com/group/aspartameNM/message/1286
      methanol products (formaldehyde and formic acid) are main cause
      of alcohol hangover symptoms [same as from similar amounts of
      methanol, the 11% part of aspartame]: YS Woo et al, 2005 Dec:
      Murray 2006.01.20

      Addict Biol. 2005 Dec;10(4): 351-5.
      Concentration changes of methanol in blood samples during
      an experimentally induced alcohol hangover state.
      Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT, Kim DJ.
      Chuncheon National Hospital, Department of Psychiatry,
      The Catholic University of Korea, Seoul, Korea.
      http://www.cuk.ac.kr/eng/ sysop@...
      Songsin Campus: 02-740-9714 Songsim Campus: 02-2164-4116
      Songeui Campus: 02-2164-4114
      http://www.cuk.ac.kr/eng/sub055.htm eight hospitals

      [ Han-Kyu Lee ]

      A hangover is characterized by the unpleasant physical and mental
      symptoms that occur between 8 and 16 hours after drinking alcohol.

      After inducing experimental hangover in normal individuals,
      we measured the methanol concentration prior to
      and after alcohol consumption
      and we assessed the association between the hangover condition
      and the blood methanol level.

      A total of 18 normal adult males participated in this study.

      They did not have any previous histories of psychiatric
      or medical disorders.

      The blood ethanol concentration prior to the alcohol intake
      (2.26+/-2.08) was not significantly different from that
      13 hours after the alcohol consumption (3.12+/-2.38).

      However, the difference of methanol concentration
      between the day of experiment (prior to the alcohol intake)
      and the next day (13 hours after the alcohol intake)
      was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).

      A significant positive correlation was observed
      between the changes of blood methanol concentration
      and hangover subjective scale score increment when covarying
      for the changes of blood ethanol level (r=0.498, p<0.05).

      This result suggests the possible correlation of methanol
      as well as its toxic metabolite to hangover. PMID: 16318957

      [ The toxic metabolite of methanol is formaldehyde, which in turn
      partially becomes formic acid -- both potent cumulative toxins
      that are the actual cause of the toxicity of methanol.]

      This study by Jones AW (1987) found next-morning hangover
      from red wine with 100 to 150 mg methanol
      (9.5 % w/v ethanol, 100 mg/l methanol, 0.01 %).
      Fully 11% of aspartame is methanol --
      1,120 mg aspartame in 2 L diet soda,
      almost six 12-oz cans, gives 123 mg methanol (wood alcohol).

      Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
      Elimination half-life of methanol during hangover.
      Jones AW. wayne.jones@...
      Department of Forensic Toxicology,
      University Hospital, SE-581 85 Linkoping, Sweden.

      This paper reports the elimination half-life of methanol in human
      volunteers.
      Experiments were made during the morning after the subjects had
      consumed 1000-1500 ml red wine
      (9.5 % w/v ethanol, 100 mg/l methanol)
      the previous evening. [ 100 to 150 mg methanol ]
      The washout of methanol from the body
      coincided with the onset of hangover.
      The concentrations of ethanol and methanol in blood were
      determined indirectly by analysis of end-expired alveolar air.
      In the morning when blood-ethanol dropped
      below the Km of liver alcohol dehydrogenase (ADH)
      of about 100 mg/l (2.2 mM),
      the disappearance half-life of ethanol was 21, 22, 18 and 15 min.
      in 4 test subjects respectively.
      The corresponding elimination half-lives of methanol
      were 213, 110, 133 and 142 min. in these same individuals.
      The experimental design outlined in this paper can be used
      to obtain useful data on elimination kinetics of methanol
      in human volunteers without undue ethical limitations.
      Circumstantial evidence is presented to link methanol
      or its toxic metabolic products, formaldehyde and formic acid,
      with the pathogenesis of hangover. PMID: 3588516

      http://groups.yahoo.com/group/aspartameNM/message/1047
      Avoiding Hangover Hell 2003.12.31 Mark Sherman, AP writer:
      Robert Swift, MD [ formaldehyde from methanol in aspartame ]:
      Murray 2004.01.16

      http://groups.yahoo.com/group/aspartameNM/message/1048
      hangovers from formaldehyde from methanol (aspartame?):
      Schwarcz: Linsley: Murray 2004.01.18


      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. toxicology@...
      Sam-1 Trust, Alto, New Mexico, USA.
      www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

      http://www.drthrasher.org/formaldehyde_1990.html 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



      formaldehyde in FEMA trailers and other sources (aspartame,
      dark wines and liquors, tobacco smoke): Murray 2008.01.30
      http://rmforall.blogspot.com/2008_01_01_archive.htm
      Wednesday, January 30, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1508

      The FEMA trailers give about the same amount of formaldehyde
      daily as from a quart of dark wine or liquor, or two quarts
      (6 12-oz cans) of aspartame diet soda, from their over 1 tenth gram
      methanol impurity (one part in 10,000),
      which the body quickly makes into formaldehyde -- enough
      to be the major cause of "morning after" alcohol hangovers.

      Methanol and formaldehyde also result from many fruits and
      vegetables, tobacco and wood smoke, heater and vehicle exhaust,
      household chemicals and cleaners, cosmetics, and new cars, drapes,
      carpets, furniture, particleboard, mobile homes, buildings, leather ...
      so all these sources add up and interact
      with many other toxic chemicals.

      BN Ames and LS Gold, 1998, have presented detailed information
      that there is no increase in recent decades for most cancers,
      and that common carcinogens do not result in significant exposures
      to the average human population.

      However, individuals are not average -- each person has a unique
      genetic makeup, resulting in a huge range of variation of vulnerability
      to specific chemicals, as is well evidenced in the case of methanol,
      formaldehyde, and formic acid, especially with regard
      to behavioral effects.

      Each is subject to very wide ranges of exposure levels.

      Many are in especially vulnerable groups, depending on diet, obesity,
      sex, exercise, life stress, age from conception to very old, unusually
      severe toxic exposures, injuries, and diseases.

      It is clear that a variety of multiple chemical sensitivity syndromes do
      exist, often with remarkable hypersensitivity.

      Methanol, formaldehyde, and formic acid toxicity are unusual, in that
      humans are far more vulnerable than any other mammal, as much as
      ten to sixty-fold, which complicates the utility of animal data.

      The unusally long human life span also increases the role of long-term
      chronic low-level exposure.

      http://groups.yahoo.com/group/aspartameNM/message/1455
      FEMA slow to safety test Katrina toxic trailers, Charles Babington,
      Associated Press -- 1 ppm formaldehyde in air is about half the daily
      dose from 3 cans aspartame diet soda and ten times the 1999 EPA
      alarm level for drinking water: Murray 2007.07.23



      http://groups.yahoo.com/group/aspartameNM/message/1277
      50% UK baby food is now organic - aspartame or MSG
      with food dyes harm nerve cells, CV Howard 3 year study
      funded by Lizzy Vann, CEO, Organix Brands,
      Children's Food Advisory Service: Murray 2006.01.13

      http://groups.yahoo.com/group/aspartameNM/message/1271
      combining aspartame and quinoline yellow, or MSG and
      brilliant blue, harms nerve cells, eminent
      C. Vyvyan Howard et al, 2005 education.guardian.co.uk,
      Felicity Lawrence: Murray 2005.12.21


      http://groups.yahoo.com/group/aspartameNM/message/1373
      aspartame rat brain toxicity re cytochrome P450 enzymes,
      especially CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al,
      2006 Aug, Hum Exp Toxicol: relevant abstracts re formaldehyde
      from methanol in alcohol drinks: Murray 2006.09.29


      http://groups.yahoo.com/group/aspartameNM/message/1463
      Direct and indirect cellular effects of aspartame on the brain,
      Humphries P, Pretorius E, Naude H, U. Pretoria, South Africa,
      Eur J Clin Nutr. 2007 Aug 8: Murray 2007.08.12

      http://groups.yahoo.com/group/aspartameNMmessage/1452
      phenylalanine and aspartic acid from low dose aspartame
      in rabbits interfere with blood coagulation,
      Pretorius E and Humphries P, U. of Pretoria,
      Ultrastruct Pathol 2007 March: Murray 2007.07.14



      http://groups.yahoo.com/group/aspartameNM/message/1459
      third study by expert Greek team of neurotoxicity in infant rats by
      aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH
      Schulpis et al, Food Chem Toxicol 2007.06.16: Murray 2007.08.05

      http://groups.yahoo.com/group/aspartameNMmessage/1447
      second study by expert Greek team of neurotoxicity in infant rats by
      aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH
      Schulpis et al, Toxicology 2007.05.18: Murray 2007.07.04

      http://groups.yahoo.com/group/aspartameNMmessage/1444
      expert Greek group finds aspartame (or its parts, methanol,
      phenylalanine, aspartic acid) harm infant rat brain enzyme activity,
      KH Schulpis et al, Pharmacol. Res. 2007.05.13: Murray 2007.06.23

      http://groups.yahoo.com/group/aspartameNM/message/939
      aspartame (aspartic acid, phenylalanine) binding to DNA:
      Karikas July 1998: Murray 2003.01.05 rmforall
      Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
      Measurement of molecular interaction of aspartame and
      its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
      Dept. of Chemistry, University of Athens, Greece
      http://www.chem.uoa.gr gkokotos@...
      K.H. Schulpis inchildh@... ; G.J. Reclos reklos@...

      5 recent aspartame reports by S Tsakiris, KH Schulpis, I Simintzi,
      with responses to critiques by AG Renwick and
      by EB Abegaz, RG Bursey, 2005-2008 2008.03.05

      Pharmacological Research 57 (2008) 89-90
      Letter to the Editor
      Answer to Letter sent to the Editor by
      Drs. E. Abegaz and R. Bursey
      (Ajinomoto Corporate Services LLC, Washington, USA)
      related to Simintzi et al. report published in
      Pharmacol Res 2007; 56: 155-9
      Letter to the Editor / Pharmacological Research 57 (2008) 89-90

      Stylianos Tsakiris a,? stsakir@...;
      Kleopatra H. Schulpis b inchildh@...;
      a Department of Experimental Physiology, Medical School,
      Athens University, P.O. Box 65257, GR-15401 Athens, Greece

      b Inborn Errors of Metabolism Department, Institute of Child
      Health, Research Center, Greece
      ? Corresponding author.
      E-mail addresses:
      S. Tsakiris stsakir@...;
      K.H. Schulpis inchildh@...;

      Pharmacological Research 57 (2008) 87-88
      Response to "The effect of aspartame on the acetylcholinesterase
      activity in hippocampal homogenates of suckling rats"
      by Simintzi et al.

      Eyassu G. Abegaz ?
      Robert G. Bursey
      Ajinomoto Corporate Services LLC,
      Scientific & Regulatory Affairs,
      1120 Connecticut Ave., N.W., Suite 1010, Washington, DC 20036,
      United States

      ? Corresponding author. Tel.: +1 202 457 0284;
      fax: +1 202 457 0107.
      E-mail addresses: abegazee@...; (E.G. Abegaz),
      burseyb@...; (R.G. Bursey)

      Keywords:
      Aspartame; Aspartate; Phenylalanine; Methanol; AChE activity

      Tsakiris S, Schulpis KH.
      Answer to letter sent by Professor A.G. Renwick
      (University of Southampton, UK)
      related to Simintzi et al. report published in Food and Chemical
      Toxicology 2007; 45(12): 2397-401.
      Food Chem Toxicol. 2008 Mar; 46(3): 1208-9.
      Epub 2007 Oct 25. No abstract available. PMID: 18054419
      doi:10.1016/j.fct.2007.10.016
      Copyright © 2007 Elsevier Ltd All rights reserved.

      Renwick AG.
      The effect of aspartame metabolites on the suckling rat frontal cortex
      acetylcholinesterase. An in vitro study. By I. Simintzi, K.H. Schulpis,
      P. Angelogianni, C. Liapi and S. Tsakiris.
      Food Chem Toxicol. 2008 Mar; 46(3): 1206-7.
      Epub 2007 Oct 26. No abstract available. PMID: 18061330

      1: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
      The effect of aspartame metabolites on the suckling rat frontal cortex
      acetylcholinesterase. An in vitro study.
      Food Chem Toxicol. 2007 Dec;45(12):2397-401.
      Epub 2007 Jun 16. PMID: 17673349

      2: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
      L-Cysteine and glutathione restore the reduction of rat
      hippocampal Na+, K+-ATPase activity
      induced by aspartame metabolites.
      Toxicology. 2007 Jul 31;237(1-3):177-83.
      Epub 2007 May 18. PMID: 17602817

      3: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
      The effect of aspartame on acetylcholinesterase activity in
      hippocampal homogenates of suckling rats.
      Pharmacol Res. 2007 Aug;56(2):155-9.
      Epub 2007 May 13. PMID: 17580119

      4: Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S.
      The effect of L-cysteine and glutathione
      on inhibition of Na+, K+-ATPase activity by aspartame metabolites
      in human erythrocyte membrane.
      Eur J Clin Nutr. 2006 May;60(5):593-7. PMID: 16391576

      5: Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH.
      The effect of aspartame metabolites on human erythrocyte membrane
      acetylcholinesterase activity.
      Pharmacol Res. 2006 Jan;53(1):1-5.
      Epub 2005 Aug 29. PMID: 16129618



      C. Trocho (1998):
      "In all, the rats retained, 6 hours after administration, about 5 % of the
      label, half of it in the liver."

      They used a very low level of aspartame ingestion, 10 mg/kg, for rats,
      which have a much greater tolerance for aspartame than humans.
      So, the corresponding level for humans would be
      about 1 or 2 mg/kg.
      Many headache studies in humans used doses of
      about 30 mg/kg daily.

      http://groups.yahoo.com/group/aspartameNM/message/925
      aspartame puts formaldehyde adducts into tissues, Part 1/2
      full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22

      http://ww.presidiotex.com/barcelona/index.html full text
      Formaldehyde derived from dietary aspartame
      binds to tissue components in vivo.
      Life Sci June 26 1998; 63(5): 337-49.
      Departament de Bioquimica i Biologia Molecular,
      Facultat de Biologia, Universitat de Barcelona, Spain.
      http://www.bq.ub.es/cindex.html Línies de Recerca: Toxicitat de
      l'aspartame http://www.bq.ub.es/grupno/grup-no.html
      Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
      Sr. Jordi Virgili, Dr. Xavier Remesar, Dr. Jose Antonio
      Fernandez-Lopez, Dr. Marià Alemany [male]
      Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
      Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544,
      FAX: (93)4021559 alemany@...;
      bioq@...

      Abstract:
      Adult male rats were given an oral dose of 10 mg/kg aspartame,
      14C-labeled in the methanol carbon.
      At timed intervals of up to 6 hours, the radioactivity in plasma
      and several organs was investigated.
      Most of the radioactivity found (>98 % in plasma, >75 % in liver)
      was bound to protein.
      Label present in liver, plasma and kidney was in the range
      of 1-2 % of total radioactivity administered per g or mL,
      changing little with time.
      Other organs (brown and white adipose tissues, muscle, brain,
      cornea and retina) contained levels of label
      in the range of 1/12th to 1/10th of that of liver.
      In all, the rats retained, 6 hours after administration,
      about 5 % of the label, half of it in the liver.

      The specific radioactivity of tissue protein, RNA and DNA
      was quite uniform.
      The protein label was concentrated in amino acids,
      different from methionine, and largely coincident
      with the result of protein exposure to labeled formaldehyde.
      DNA radioactivity was essentially in a single different adduct base,
      different from the normal bases present in DNA.
      The nature of the tissue label accumulated was, thus,
      a direct consequence of formaldehyde binding to tissue structures.

      The administration of labeled aspartame to a group of cirrhotic rats
      resulted in comparable label retention by tissue components,
      which suggests that liver function (or its defect) has little effect
      on formaldehyde formation from aspartame
      and binding to biological components.

      The chronic treatment of a series of rats with 200 mg/kg of
      non-labeled aspartame during 10 days results in the accumulation
      of even more label when given the radioactive bolus,
      suggesting that the amount of formaldehyde adducts
      coming from aspartame in tissue proteins and nucleic acids
      may be cumulative.

      It is concluded that aspartame consumption may constitute
      a hazard because of its contribution
      to the formation of formaldehyde adducts. PMID: 9714421

      [ Extracts ]
      "The high label presence in plasma and liver is in agreement with the
      carriage of the label from the intestine to the liver via the portal vein.
      The high label levels in kidney and, to a minor extent, in brown
      adipose tissue and brain are probably a consequence
      of their high blood flows (45).
      Even in white adipose tissue, the levels of radioactivity found 6 hours
      after oral administration were 1/25th those of liver.
      Cornea and retina, both tissues known to metabolize actively
      methanol (21,28) showed low levels of retained label.
      In any case, the binding of methanol-derived carbon to tissue proteins
      was widespread, affecting all systems,
      fully reaching even sensitive targets such as the brain and retina....

      The amount of label recovered in tissue components was quite high
      in all the groups, but especially in the NA rats.
      In them, the liver alone retained, for a long time, more than 2 % of
      the methanol carbon given in a single oral dose of aspartame,
      and the rest of the body stored an additional 2 % or more.
      These are indeed extremely high levels for adducts of formaldehyde,
      a substance responsible of chronic deleterious effects (33),
      that has also been considered carcinogenic (34,47).
      The repeated occurrence of claims that aspartame
      produces headache and other neurological and psychological
      secondary effects --
      more often than not challenged by careful analysis --
      (5, 9, 10, 15, 48)
      may eventually find at least a partial explanation in the permanence
      of the formaldehyde label,
      since formaldehyde intoxication can induce similar effects (49).

      The cumulative effects derived from the incorporation of label in the
      chronic administration model suggests that regular intake of
      aspartame may result in the progressive accumulation
      of formaldehyde adducts.
      It may be further speculated that the formation of adducts can help to
      explain the chronic effects aspartame consumption may induce on
      sensitive tissues such as brain (6, 9, 19, 50).
      In any case, the possible negative effects that the accumulation of
      formaldehyde adducts can induce is, obviously, long-term.
      The alteration of protein integrity and function may needs some time
      to induce substantial effects.
      The damage to nucleic acids, mainly to DNA,
      may eventually induce cell death and/or mutations.
      The results presented suggest that the conversion of aspartame
      methanol into formaldehyde adducts in significant amounts in vivo
      should to be taken into account because of the widespread utilization
      of this sweetener.
      Further epidemiological and long-term studies are needed to
      determine the extent of the hazard that aspartame consumption
      poses for humans."



      Many scientific studies and case histories report: * headaches
      * many body and joint pains (or burning, tingling, tremors, twitching,
      spasms, cramps, stiffness, numbness, difficulty swallowing)
      * fever, fatigue, swollen glands * "mind fog", "feel unreal",
      poor memory, confusion, anxiety, irritability, depression, mania,
      insomnia, dizziness, slurred speech, sexual problems,
      poor vision, hearing (deafness, tinnitus), or taste
      * red face, itching, rashes, allergic dermatitis, hair loss,
      burning eyes or throat, dry eyes or mouth, mouth sores,
      burning tongue * obesity, bloating, edema, anorexia,
      poor appetite or excessive hunger or thirst
      * breathing problems, shortness of breath
      * nausea, diarrhea or constipation * coldness * sweating
      * racing heart, low or high blood pressure, erratic blood sugar levels
      * hypothryroidism or hyperthyroidism * seizures * birth defects
      * brain cancers * addiction * aggrivates diabetes, autism, allergies,
      lupus, ADHD, fibromyalgia, chronic fatigue syndrome,
      multiple chemical sensitivity, multiple sclerosis, pseudotumor cerebri
      and interstitial cystitis (bladder pain).


      http://groups.yahoo.com/group/aspartameNM/message/870
      Aspartame: Methanol and the Public Interest 1984: Monte:
      Murray 2002.09.23 rmforall

      Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
      Journal of Applied Nutrition 1984; 36 (1): 42-54.
      (62 references) Professsor of Food Science [retired 1992]
      Arizona State University, Tempe, Arizona 85287
      woodymonte@...; woodymonte@...;
      The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
      112 mg, 10% of the aspartame.
      The EPA limit for water is 7.8 mg daily for methanol (wood alcohol),
      a deadly cumulative poison.
      Many users drink 1-2 L daily.
      The reported symptoms are entirely consistent with chronic methanol
      toxicity. (Fresh orange juice has 34 mg/L, but, like all juices, has 16
      times more ethanol, which strongly protects against methanol.)

      "The greater toxicity of methanol to man is deeply rooted in the
      limited biochemical pathways available to humans for detoxification.
      The loss of uricase (EC 1.7.3.3.),
      formyl-tetrahydrofolate synthetase (EC 6.3.4.3.) (42)
      and other enzymes (18) during evolution sets man apart from all
      laboratory animals including the monkey (42).

      There is no generally accepted animal model
      for methanol toxicity (42, 59).

      Humans suffer "toxic syndrome" (54) at a minimum lethal dose
      of <1 gm/kg, much less than that of monkeys, 3-6 g/kg (42, 59).

      The minimum lethal dose of methanol
      in the rat, rabbit, and dog is 9.5, 7.0 , and 8.0 g/kg, respectively (43);
      ethyl alcohol is more toxic than methanol to these test animals (43)."

      Recent research [see links at end of post] supports his focus on the
      methanol to formaldehyde toxic process:

      "The United States Environmental Protection Agency in their
      Multimedia Environmental Goals for Environmental Assessment
      recommends a minimum acute toxicity concentration
      of methanol in drinking water at 3.9 parts per million,
      with a recommended limit of consumption below 7.8 mg/day (8).

      This report clearly indicates that methanol:

      "...is considered a cumulative poison due to the low rate of excretion
      once it is absorbed. In the body, methanol is oxidized to formaldehyde
      and formic acid; both of these metabolites are toxic." (8)...

      Recently the toxic role of formaldehyde (in methanol toxicity) has been
      questioned (34).
      No skeptic can overlook the fact that, metabolically, formaldehyde
      must be formed as an intermediate to formic acid production (54).

      Formaldehyde has a high reactivity which may be why it has not been
      found in humans or other primates during methanol poisoning (59)....

      If formaldehyde is produced from methanol and does have a
      reasonable half life within certain cells in the poisoned organism
      he chronic toxicological ramifications could be grave.

      Formaldehyde is a known carcinogen (57) producing squanous-cell
      carcinomas by inhalation exposure in experimental animals (22).
      The available epidemiological studies do not provide adequate data
      for assessing the carcinogenicity of formaldehyde in man (22, 24, 57).

      However, reaction of formaldehyde with deoxyribonucleic acid
      (DNA) has resulted in irreversible denaturation that could interfere
      with DNA replication and result in mutation (37)..."



      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.

      Fully 11 % of aspartame is methanol -- 1,120 mg aspartame
      in 2 L diet soda, almost six 12-oz cans, gives 123 mg methanol
      (wood alcohol). The methanol is immediately released
      into the body after drinking .
      Within hours, the liver turns much of the methanol into formaldehyde,
      and then much of that into 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, accumulating in and affecting every tissue.

      If only 10 % of the methanol is retained daily 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 drinking 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.

      http://groups.yahoo.com/group/aspartameNM/message/835
      ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
      Murray 2002.05.30

      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,
      rashes, and leading to vision and eye problems, and even seizures.
      In many cases there is addiction. Probably there are immune sys<br/><br/>(Message over 64 KB, truncated)
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