EYELID CONTACT DERMATITIS BY FORMALDEHYDE FROM ASPARTAME

Compiled By Rich Murray, MA
Room For All
1943 Otowi Road
Santa Fe, New Mexico 87505 USA
Telephone: 505-501-2298
E-Mail: rmforall@comcast.net
Web Site: http://health.groups.yahoo.com/group/aspartameNM



Posted: 26 July 2005


http://groups.yahoo.com/group/aspartameNM/message/1067
Eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, Nov 2003: Murray 2004.04.04

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 To increase the readability of the dense, specialized, condensed text of a brief scientific letter (usually not peer reviewed), I have added spacing without altering text, while correcting minor typos.

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

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

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

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

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

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

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

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

Contact Dermatitis. 2003 Nov; 49(5): 258-9. Systemic contact dermatitis of the eyelids caused by formaldehyde derived from aspartame? Hill AM, Belsito DV. DBelsito@kumc.edu

Division of Dermatology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. PMID: 14996049

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

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

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

Sensitization is reported in between 2.2 and 9.6% of patients patch tested (1,2).

[ (Appendix C, for abstracts on rates of formaldehyde sensitivity in control groups, as a possible first estimate of the impact of widespread exposure to aspartame since 1981.) ]

Case Report

A 60-year-old Caucasian woman presented with a 6-month history of eyelid dermatitis. A corticosteroid-containing opthalmologic ointment improved but did not clear the rash. She failed to improve when she discontinued the use of all eyelid cosmetics and nail polishes for 2 months.

She had had a facial dermatitis in 1995, for which she had been patch tested and found to be allergic to formaldehyde, quaternium-15 and fragrances. She had also had incidental, non-relevant reactions to neomycin and ethylenediamine. Her dermatitis had resolved with a change to formaldehyde-, quaternium-15 and fragrance-free facial and nail cosmetics.

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

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

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

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

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

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

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

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

Discussion

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

It has been reported to cause dry eyes and difficulty in wearing contact lenses (3) but never allergic contact dermatitis. [ Reference (3) is given in full here. (Appendix H) Roberts H J. Dry eyes from use of aspartame (Nutrasweet): Associated insights concerning the Sjogren syndrome. The Townsend Letter for Doctors, January 1994. Appendix H also quotes several cases of eyelid dermatitis from his review of 1200 cases in Aspartame Disease: An Ignored Epidemic (2001). ]

Aspartame, an L-aspartyl-L-phynylalanine methyl ester, is hydrolysed in the intestine to phenylalanine (50%), aspartic acid (40%) and aspartaic acid methyl ester (10%).

The methyl ester is then converted to methyl alcohol (methanol) and carried by the portal vein to the liver.

Methanol is there oxidized to formaldehyde that is converted into formic acid (formate) by alcohol dehydrogenase, aldehyde dehydrogenase and the microsomal oxidase pathway.

This occurs not only in the liver, but also in other organs containing high levels of these enzymes, including the eye (4,5).

Formaldehyde binds proteins and nucleic acids, forming adducts difficult to eliminate via metabolism.

Trocho et al. (6) demonstrated the formation of formaldehyde adducts with DNA and proteins after administration of 20 mg/kg 14C-labelled aspartame to rats, concluding that these adducts were responsible for functional alterations of proteins and for DNA mutations leading to autoimmunity, cell death or malignant transformation. [ (Appendix E) gives links, comments, and quotes for the debate on the key Trocho study. ]

In contrast to Trocho et al. (6), McMartin et al. (7) studied formaldehyde levels after large doses (3,000 mg/kg) of 14C-labelled methanol and 14C-labelled formaldehyde in monkeys, which unlike rats are sensitive to the toxicities of methanol.

No increased formaldehyde derived from methanol was found.

High levels of formic acid were found in all monkeys that were given methanol or formaldehyde.

[ (Appendix F) reviews the major studies. Oppermann et al (1973, 1976) found that 30% of the methanol from aspartame fed to monkeys remained in body tissues, indubitably as toxic products of formaldehyde and formic acid. They did not test methanol product retention in humans. McMartin et al (1979) reported significant formaldehyde retention in the midbrain of one monkey from oral aspartame, and substantial formic acid in liver, kidney, optic nerve, cerebrum, and midbrain in two other monkeys. It is clear that his formaldehyde assays were too insensitive to give valid measurements. There has been a dearth of relevant primate and human studies ever since. ]

Based on the work of McMartin and al. (7), Tephly (8) concluded that the radioactive carbon from methanol, which was found in DNA and protein by Trocho et al., was due to the normal physiologic flow of single-carbon units through the folate pathway.

Stegink et al. (9) have shown that doses of 100 mg/kg or greater of aspartame are required to increase methanol blood levels (and thus, presumable formaldehyde formic acid levels) above control.

This would be equivalent to consuming 35 cans of diet beverage at one sitting for a 70 kg person. [ This is a typical aspartame industry PR ploy, well designed to plant the impression that only absurdly huge amounts of diet soda might supply damaging amounts of methanol-derived formaldehyde and formic acid toxic residuals in body tissues, thus reducing methanol blood levels. So, it is a classic red herring tactic to focus on methanol blood levels.

http://groups.yahoo.com/group/aspartameNM/message/910
Formaldehyde & formic acid from methanol in aspartame: Murray: 12.9.2

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

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

Bear in mind that the EPA limit for formaldehyde in drinking water is 1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

[ http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999 5.30.2 ]

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

Leon et al. (10) studied doses of 75 mg/kg of aspartame daily for 24 weeks and found no change in blood or urine methanol levels and no symptoms of methanol toxicity.

The dose used in Leon's study is 25 times the 90th percentile daily consumption of aspartame (11). [ Appendix E gives an abstract by Davoli (1986), using a properly sensitive assay, that proved a temporary rise in blood methanol levels in humans from a single aspartame dose. Trocho pointed out that formaldehyde adducts are persistent and thus cumulative. It is reasonable to state that with long-term chronic formaldehyde exposure, it may take a long time to both accumulate adducts and develop markedly increased sensitivity and a series of complex symptoms . Adequate studies would have to test substantial exposures over a year or longer with large numbers of vulnerable types of people and record all symptoms. ]

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame daily, well below the levels previously studied. [ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet soda gives 200 mg aspartame. An aspartame reactor can have immediate strong symptoms from an under-the-tongue wafer with 4 mg aspartame. Appendix A, for comments, abstracts, and links.) ]

However, it is possible that the eye, with its high level of metabolic activity, could be affected by methanol (and subsequently formaldehyde) released from these low levels of aspartame and respond as a localized target organ to minute amounts of her known allergen, formaldehyde, or its metabolite, formate.

It is also possible that the amplifying effects of cell-mediated immunity might detect trace amounts of a chemical not identified by more standard assays, such as blood or urine levels. [ (Appendix D gives Thrasher's data about immune system reactions from long-term, low-level formaldehyde exposure, while Martin Pall gives a complex general theory, specifically discussing formaldehyde as a major trigger.)

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

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
Testable theory of MCS type diseases, vicious cycle of nitric oxide & peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall: Murray: 12.9.2

FASEB J 2002 Sep; 16(11): 1407-17.
NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity.
Pall ML. PMID: 12205032 [ 162 references, received 1.3.2 ] School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4660, USA. martin_pall@wsu.edu ]
Such a hypothesis might explain why her dermatitis was limited to the eyelids and give clinical support to Trocho's theory of formaldehyde adducts.
Unfortunately, without rechallenging her with aspartame, we cannot test this hypothesis.
Nonetheless, her long-lasting remission following discontinuation of aspartame intake suggests that its breakdown to formaldehyde may have been a possible mechanism for her prior blepharitis.
References

  1. Christophersen J, Menne' T, Tanghoj P, Andersen K E, Brandrup F.
    Clinical patch test data evaluated by multivariate analysis.
    Contact Dermatitis 1989: 21: 291-299.

  2. Fransway AF, Schmitz N A.
    The problem of preservation in the 1990s. II. Formaldehyde and formaldehyde-releasing biocides: incidences of cross-reactivity and the significance of the positive response to formaldehyde.
    Am J Contact Dermat. 1991: 2: 78-88.

  3. Roberts H J.
    Dry eyes from use of aspatame (Nutrasweet): Associated insights concerning the Sjogren syndrome.
    The Townsend Letter for Doctors, January 1994. [ full text in Appendix H ]

  4. Murray T G, Burton T C, Rajani C, Lewandowski M F, Burke J M, Eells J T.
    Methanol poisoning: A rodent model with structural and functional evidence for reinal involvement.
    Arch Opthalmol 1991: 109: 1012-1016.

  5. Eells J T.
    Methanol-induced visual toxicity in the rat.
    J. Pharmacol Exp Ther 1991: 257: 56-63.

  6. Trocho C., Pardo R, Fafecas I, Virgili J, Remesar X, Fernandez-Lopez, J A.
    Formaldehyde derived from dietary aspartame binds to tissue components in vivo.
    Life Sci 1998 1988: 63: 337-349. [ abstract and quotes in Appendix E )

  7. McMartin K E, Mrtin-Amat G, Noker P E, Tephly T R.
    Lack of a role for formaldehyde in methanol poisoning in the monkey.
    Biochem Pharmacol 1979: 28: 645-649. [ abstract, quotes, discussion, related studies in Appendix F ]

  8. Tephly T R.
    Comments on the purported generation of formaldehyde from the sweetener aspartame.
    Life Sci 1999: 65: 157-160. [ letter, usually not peer-reviewed, abstract in Appendix E ]

  9. Stegink L D, Brummel M C, McMartin-Amat G., Filer L J, Baker G L, Tephly T R.
    Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame.
    J Toxicol Environ Health 1981: 7: 281-290.

  10. Leon A S, Hunninghake D B, Bell C, Rassin D K, Tephly T R.
    Safety of long-term large doses of aspartame.
    Arch Intern Med 1989: 149: 2318-2324.

  11. Tschanz C., Butachko H, Stargel W, Kotsonis F N (eds).
    The Clinical Evaluation of a Food Additive: Assessment of Aspartame Boca Raton
    CRC Press, 1996.

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Appendix A:

http://groups.yahoo.com/group/aspartameNM/message/846
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: Murray 7.16.2

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@aol.com
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research RLipton@IMRInc.com

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance: aspartame chewing gum headaches Nov 1997 7.28.2

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@aol.com
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://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums: full text: aspartame, MSG, fibromyalgia 1.17.2

Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums Relief of Fibromyalgia Symptoms Following Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.

BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively.

CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome for two to 17 years are described. All had undergone multiple treatment modalities with limited success. All had complete, or nearly complete, resolution of their symptoms within months after eliminating monosodium glutamate (MSG) or MSG plus aspartame from their diet.

All patients were women with multiple comorbidities prior to elimination of MSG.

All have had recurrence of symptoms whenever MSG is ingested. PMID: 11408989

Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@shands.ufl.edu
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629 352-376-5071

http://www.perque.org/Fibromyalgia.pdf
A Novel Treatment for Fibromyalgia Imrpoves Clinical Outcomes in a Community-Based Study.
Patricia A. Deuster, Russell M. Jaffe. RJaffe@perque.com
Journal of Musculoskeletal Pain. 1998; Vol. 6(2): 133-149.
http://www.perque.com info@perque.com 800-525-7372

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

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

MSG 42.5 % (17 out of 40 patients)
Candida albicans 37.5 %
Caffeine 37%
Chocolate/cocoa 37%
Food colorings 37%
Cola beverages 37%
Cow Dairy Products 25%
Sulfite/metabisulfite 22.5%
Xylene 22.5%
Yogurt 22.5%
Aspartame 20%
BHA 20%
Cadmium 20%
Lead 20%
Tylenol 20%
Yeast 20%
Sodium benzoate 20%
Orange 20%

Several recent pro-aspartame reviews simply ignore these reports by eminent mainstream researchers, as well as the tidal surge of complaints by users.

http://groups.yahoo.com/group/aspartameNM/message/957
Safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF: Murray 1.12.3 rmforall EU Scientific Committee on Food, a whitewash

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 (12.4.2): 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. PMID: 14760578

http://groups.yahoo.com/group/aspartameNM/message/1068
Critique of aspartame review by American Dietetic Association Feb 2004: Murray 4.1.4

"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@aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

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Appendix B:

D. V. Belsito has 71 items in PubMed since 1982.

Donald (Don) V. Belsito, MD Professor, Division Director Dermatology
+1 913 588-3840 fax +1 913 588-4060 DBelsito@kumc.edu
Main Phone Number: (913) 588-6028 Fax Number: (913) 588-8300
Mailing Address: 4008 Wescoe Pavilion Mail Stop 2025
3901 Rainbow Boulevard, Kansas City, KS 66160-7319 USA

The University of Kansas Medical Center
3901 Rainbow Boulevard, Kansas City, KS 66160 913-588-5000, 913-588-7963 TDD
KU Medical Center is a campus of the University of Kansas and is affiliated with The University of Kansas Hospital. The School of Medicine has a campus in Wichita.

http://www.centerwatch.com/professional/pro503.html
University of Kansas Medical Center Research Institute 3901 Rainbow Boulevard, Kansas City, KS 66160-7702 USA
Phone: 913-588-1242 Fax: 913-588-5729 lkemble@kumc.edu

The University of Kansas Medical Center comprises the School of Medicine, School of Allied Health, School of Nursing, and an independently run hospital with 415 staffed beds. KUMC is a regional health center treating approximately 35,000 emergency room patients, 17,000 inpatients, and more than 180,000 outpatients per year. KUMC is a 35 building, 50-acre campus with a staff of nearly 5,000 employees.

The University of Kansas Medical Center Research Institute is a private, non-profit corporation established to promote and support medical research. The Division of Clinical Trials at the Research Institute serves as the central liaison between the pharmaceutical industry, faculty investigators at KUMC, and the Institutional Review Board. The Division of Clinical Trials also assists the sponsor with identifying suitable clinical investigators.

http://author.emedicine.com/DERM/topic549.htm
Dermatologic Manifestations of Neurologic Disease
Authored by Theresa Conologue, DO, Staff Physician, Department of Dermatology, National Capital Consortium/Walter Reed Army Medical Center Coauthored by Jeffrey Meffert, MD, Program Director, Dermatology Service, San Antonio Uniformed Services Health Education Consortium.
Theresa Conologue, DO, is a member of the following medical societies: Association of Military Surgeons of the US Edited by Donald Belsito, MD, Program Director, Professor, Department of Internal Medicine, Division of Dermatology, University of Kansas; Richard Vinson, MD, Chief, Department of Dermatology, William Beaumont Medical Center; Jeffrey P Callen, MD, Chief, Professor, Department of Internal Medicine, Division of Dermatology, University of Louisville School of Medicine; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; and Dirk M Elston, MD, Consulting Staff, Department of Dermatology, Geisinger Medical Center
Author's Email: Theresa Conologue, DO Editor's Email: Donald Belsito, MD
eMedicine Journal, March 19 2003, Volume 4, Number 3
INTRODUCTION Section 2 of 12

Many disorders have a combination of neurologic and dermatologic findings in patients. This chapter provides an overview of neurocutaneous disorders and organizes them into clinically relevant groupings of use to the practicing physician.

http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3564t1.pdf
Center for Drug Evaluation
Dermatologic and Opthalmic Drugs Advisory Commitee Thursday, November 4, 1999
Ballroom, Hilton Hotel, 620 Perry Parkway, Taithersburg Maryland
Guest Speaker: Donald Belsito, M.M. 6516 Aberdeen Road, Mission Hills, KS 66208

http://www.simplywhispers.com/htdocs/html/Press%20Releases/bodypiercing.html
Dr. Donald Belsito, professor of Dermatology at the University of Kansas in Lawrence and a member of the North American Contact Dermatitis Group, notes, "Nickel allergies are on the increase - from 10.5 % cited in studies done from 1985 to 1989 to 14.3 % in studies done in 1996. More men are showing up with nickel allergies; coincidentally more men are having their bodies pierced. This indicates a possible correlation between piercing and allergies to nickel." In addition to setting off allergic reactions, Dr. Belsito, notes, "Piercing cartilage around the top of the ear poses greater risks than piercing the lobe. Cartilage is an inert material with very little blood supply and takes a long time to heal from the puncture. Also, when cartilage becomes infected, it is difficult to treat because of its low blood supply.

"Also, the growth of overwhelming scars known as keloids can occur and the condition is particularly prevalent among African Americans," says Dr. Belsito, adding, "Keloids can grow to be as big as the ear itself. The cure requires administering medication that reduces the tendency to develop scars. If scars do develop, they need to be removed by a plastic surgeon. The risk, of course, is that people who tend to scar, may not fare well in surgery which can promote new scar tissue." When it comes to protecting the consumer, Dr. Belsito adds, "I think hypoallergenic is a bad term since it only tells you that the product is manufactured without an ingredient to which most people are allergic. But it doesn't tell you other possible allergy provoking ingredients. For example, some rubber gloves labeled hypoallergenic are made without certain chemicals. However, these gloves could be made of latex which is lethal to some people."

Drs. Bendetsen, Scheinman and Belsito favor legislation governing body piercing due to the risk of nickel allergies, loss of sensation and communicable diseases resulting from poor sterilization procedures. To date, Arizona, California, Georgia, Michigan and Washington have passed legislation requiring parental consent for body piercing if you are a minor. Several states including Delaware, Missouri, Texas and Hawaii have legislation pending.

D. V. Belsito has 9 additional items that include formaledhyde in PubMed:

  1. Ravis SM, Shaffer MP, Shaffer CL, Dehkhaghani S, Belsito DV.
    Glutaraldehyde-induced and formaldehyde-induced allergic contact dermatitis among dental hygienists and assistants.
    J Am Dent Assoc. 2003 Aug; 134(8): 1072-8. PMID: 12956347

  2. Thompson TR, Belsito DV.
    Regional variation in prevalence and etiology of allergic contact dermatitis.
    Am J Contact Dermat. 2002 Dec; 13(4): 177-82. PMID: 12478532

  3. Rietschel RL, Mathias CG, Fowler JF Jr, Pratt M, Taylor JS, Sherertz EF, Marks JG Jr, Belsito DV, Storrs FJ, Maibach HI, Fransway AF, Deleo VA; North American Contact Dermatitis Group.
    Relationship of occupation to contact dermatitis: evaluation in patients tested from 1998 to 2000.
    Am J Contact Dermat. 2002 Dec; 13(4): 170-6. PMID: 12478531

  4. Deleo VA, Taylor SC, Belsito DV, Fowler JF Jr, Fransway AF, Maibach HI, Marks JG Jr, Mathias CG, Nethercott JR, Pratt MD, Reitschel RR, Sherertz EF, Storrs FJ, Taylor JS.
    The effect of race and ethnicity on patch test results.
    J Am Acad Dermatol. 2002 Feb; 46(2 Suppl Understanding): S107-12. PMID: 11807472

  5. Suneja T, Belsito DV.
    Comparative study of Finn Chambers and T.R.U.E. test methodologies in detecting the relevant allergens inducing contact dermatitis.
    J Am Acad Dermatol. 2001 Dec; 45(6): 836-9. PMID: 11712026

  6. Suneja T, Belsito DV.
    Thimerosal in the detection of clinically relevant allergic contact reactions.
    J Am Acad Dermatol. 2001 Jul; 45(1): 23-7. PMID: 11423830

  7. Shaffer MP, Belsito DV.
    Allergic contact dermatitis from glutaraldehyde in health-care workers.
    Contact Dermatitis. 2000 Sep; 43(3): 150-6. Review. PMID: 10985631

  8. Marks JG, Belsito DV, DeLeo VA, Fowler JF Jr, Fransway AF, Maibach HI, Mathias CG, Nethercott JR, Rietschel RL, Sherertz EF, Storrs FJ, Taylor JS.
    North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens.
    J Am Acad Dermatol. 1998 Jun; 38(6 Pt 1): 911-8. PMID: 9631997

  9. 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 Dec; 27(6 Pt 1): 962-8. PMID: 1479102

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Appendix C:

"Sensitization is reported in between 2.2 and 9.6% of patients patch tested (1,2)."

Widespread use of aspartame since 1981 must cause some of the formaldehyde sensitization found in many studies of control groups, so I offer a relevant abstract, which is the only data I know of that starts to assess the prevalence of aspartame disease in otherwise healthy people:

"One (2 percent) control subject had a reaction to glutaraldehyde, and one other (2 percent) had a reaction to formaldehyde." "51 nondental professionals "

Aspartame use must sensitize some users. This study's control group hints that about 2% of a control group of 51 professionals showed a sensitivity to formaldehyde in a skin patch test. Are there any data for nonusers of aspartame?

Am Dent Assoc. 2003 Aug; 134(8): 1072-8.
Glutaraldehyde-induced and formaldehyde-induced allergic contact dermatitis among dental hygienists and assistants.
Ravis SM, Shaffer MP, Shaffer CL, Dehkhaghani S, Belsito DV.
University of Miami, USA.

BACKGROUND: Research has found that among health care workers, dental personnel are especially likely to have reactions to glutaraldehyde and formaldehyde.

METHODS: The authors conducted patch test evaluations with a voluntary cohort of randomly recruited, healthy dental hygienists, or DHs, and dental assistants, or DAs, and nondental professionals to determine the incidence of glutaraldehyde-induced and formaldehyde-induced allergic contact dermatitis, or ACD; the potential for coreactivity between glutaraldehyde and formaldehyde; and the correlation between training methods in safe handling of sterilizing solutions and the sensitivity to glutaraldehyde and formaldehyde among DHs and DAs.

RESULTS: The researchers enrolled 101 DHs and DAs and 51 nondental professionals in the study. All except one DH/DA subject were female. The dental subjects' mean age was 34.3 +/- standard deviation of 10.7 years; the nondental subjects', 33.8 +/- 11.0 years.

DHs and DAs had worked in their profession for a mean of 11.0 +/- 9.3 years. Among the dental professionals, 80 (79.2 percent) had had a known exposure to cold sterilizing solutions, while the remainder were unable to provide a known history of exposure.

Eleven (10.9 percent) dental professionals had clear reactions to glutaraldehyde, four (4.0 percent) were questionably allergic to glutaraldehyde, and two (2 percent) were definitively allergic to formaldehyde. One (2 percent) control subject had a reaction to glutaraldehyde, and one other (2 percent) had a reaction to formaldehyde.

CONCLUSIONS AND CLINICAL: IMPLICATIONS: The authors found a statistically significant disparity in the rates of glutaraldehyde sensitivity among healthy DHs and DAs versus healthy control subjects (10.9 percent versus 2 percent reactively; P = .02).

They found no evidence of cross-reactivity between glutaraldehyde and formaldehyde. The preponderance of reactions among the DHs and DAs suggests that their present safety practices are largely ineffective in protecting against sensitization to glutaraldehyde in sterilizing solutions. PMID: 12956347

************************************************************

Appendix D:

http://groups.yahoo.com/group/aspartameNM/message/915
Formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Murray: Wilson: CIIN: 12.12.2

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. Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html
Full text

Environ Health Perspect. 2003 Sep; 111(12): 1461-4.
Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity: central role of N-methyl-D-aspartate receptors in the sensitivity mechanism.
Pall ML. School of Molecular Biosciences, 301 Abelson Hall, Washington State University, Pullman, WA 99164, USA. martin_pall@wsu.edu

The elevated nitric oxide/peroxynitrite and the neural sensitization theories of multiple chemical sensitivity (MCS) are extended here to propose a central mechanism for the exquisite sensitivity to organic solvents apparently induced by previous chemical exposure in MCS. This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA) receptors by organic solvents producing elevated nitric oxide and peroxynitrite, leading in turn to increased stimulating of and hypersensitivity of NMDA receptors. In this way, organic solvent exposure may produce progressive sensitivity to organic solvents.

Pesticides such as organophosphates and carbamates may act via muscarinic stimulation to produce a similar biochemical and sensitivity response. Accessory mechanisms of sensitivity may involve both increased blood-brain barrier permeability, induced by peroxynitrite, and cytochrome P450 inhibition by nitric oxide. The NMDA hyperactivity/hypersensitivity and excessive nitric oxide/peroxynitrite view of MCS provides answers to many of the most puzzling aspects of MCS while building on previous studies and views of this condition. PMID: 12948884

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

"Inhalation exposure to formaldehyde (HCHO) is associated with symptoms of irritation to mucous membranes, (1,2) chronic health problems (e.g., asthma, (2) nasopharyngeal cancer, (3) and multiple subjective health complaints. (4,5) ) Recent observations have shown that both humoral-and cell-mediated immunologic mechanisms occur in humans with long-term HCHO exposure. Antibodies of all isotypes to HCHO conjugated human serum albumin (HCHO-HSA) are demonstrable in HCHO anaphylaxis, (6) hemodialysis patients, (7) mobile home residents, (4) persons with occupational exposures, (5,8) office workers, (9) and in persons in other environments. (4) In addition, changes in cell-mediated immunity include increases in eosinophils, basophils, and T-suppressor cells following acute exposure of patients with HCHO asthma. (10)

Moreover, individuals with multiple subjective health complaints associated with long-term HCHO inhalation have evidence of immune activation and the presence of autoantibodies. (4,5)

The patients in our study had symptoms and complaints related to several organs, as described previously, (4,5,9) which were similar to symptoms of workers with multiple chemical sensitivity,(11) cacosmia,(12) and other chemical exposures. (13-15) We report on the differences in humoral and cell-mediated immunity in humans with long-term inhalation exposure to HCHO vs. asymptomatic students (controls) who experienced short-term, periodic exposure to the chemical."
[ http://lassesen.com/cfids/cacosmia.htm
Cacosmia (a.k.a. Multiple Chemical Sensitivity) Details:

Symptoms. All patients in this study had sought continuous medical attention because of multiple organ symptoms involving the central nervous system (CNS) (headaches, memory loss, difficulty completing tasks, dizziness), upper- and lower-respiratory symptoms, skeletal-muscle complaints, and gastroenteritis. Three common symptoms were expressed:

[1.] and initial flu-like illness from which they had not fully recovered; [2.] chronic fatigue; and [3.] an olfactory sensitivity to ambient conditions containing low concentrations of chemicals. (4,9,11)"

"It is recognized that chemicals and therapeutic drugs are associated with a Lupus-like syndrome. (28,29) The observations made on the patients in this study support this concept."

"Five groups of subjects exposed to HCHO, who gave informed consent, were included in this study.

[1.] Controls consisted of students of chiropractic medicine (16 males, 12 females), mean age = 29 +- 9 y) exposed to HCHO for 13 h/wk for 28 wk while studying human anatomy. Immunologic tests were performed 12 mo following the last classroom exposure. No measurements of HCHO concentrations were made. It is assumed that classroom ambient concentrations were at least 0.43 ppm. (1) The students stated that during exposure they experienced eye, nose and throat irritation and that there was a pungent odor of HCHO. They did not have residual health complaints (symptoms), and they were asymptomatic at the time blood was taken.

[2.] Mobile home residents consisted of 19 patients (6 males, 13 females), mean age 41+-20 y) who currently lived in mobile homes. The patients had lived in their environments for 2-7 y and reported multiple symptoms. (4,9) Measured HCHO concentrations ranged from 0.05 to 0.5 ppm at the time blood samples were taken.

[3.] Office workers included 21 patients (5 males, 16 females, mean age of 40 +-10 y) who worked in new office buildings where there was inadequate ventilation (closed buildings). The patients had multiple health complaints. (9) It was determined from medical histories that their symptoms commenced with employment, waned when away from work (i.e., weekends, holidays, vacations) and became worse upon return to work. No HCO measurements were done; however, closed buildings have ambient concentrations ranging from 0.01 to 0.77 ppm. (1,16)

[4.] This group included 21 patients (10 males, 11 females, mean age of 35 + -17 y) who had multiple symptoms and who had been removed from their original sources of HCHO exposure (mobile homes and/or particleboard subflooring) for at least 1 y. The HCHO concentrations measured during their exposures ranged from 0.14 to 0.81 ppm.

[5.] Occupationally exposed patients (6 males, 2 females, mean age of 45 + -11 y) had HCHO exposures from the following: biology and human anatomy classes, mortuary, pathology, physical therapy, formica furniture (particleboard), and carbonless copy paper. Information on six of these patients was previously published. (5)"

"In conclusion, measurements of changes in WBCs, T cells, and H/S ratios in individuals with apparent chemical sensitivities appear to be inadequate immune parameters to examine. If one assumes that these individuals respond immunogically to environmental chemicals, investigations into autoimmunity and immune activation and perturbations in the interleukins, luekotreines, prostglandins, and other immunologic mediators appear to be fruitful areas for further research. (29-32) Thus, it appears that HCHO sensitivity is a real phenomenon and requires further research. (4,27-32)"

************************************************************

Appendix E:

"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 6.26.98: Murray 12.22.2

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
LÝnies 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. MariÓ Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559 Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544, FAX: (93)4021559
alemany@porthos.bio.ub.es bioq@sun.bq.ub.es josefer@porthos.bio.ub.es rafecas@porthos.bio.ub.es remesar@porthos.bio.ub.es

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."

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde adducts in rats 9.8.2
Prof. Alemany vigorously affirms the validity of the Trocho study against criticism: Butchko, HH et al [24 authors], Aspartame: review of safety. Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review available for $35, [an industry paid organ]. Butchko: "When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol in fruits and vegetables is as as biochemically available as that in aspartame-- see the 1984 rebuttal by Monte in (Appendix G). ]
In the same report, Schiffman concludes on page S49, not citing any research after 1997, "Thus, the weight of the scientific evidence indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University sss@acpub.duke.edu 919-684-3303, 660-5657

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2

Subject: Re: Murray: Butchko: Tephly: critique of Trocho report Apr 2002 8.29.2
Date: Fri, 30 Aug 2002 09:49:56 +0200
From: MariÓ Alemany
To: "Rich Murray" rmforall@att.net
References: 1

Dear Rich,

Thank you for the opportunity to say something about the "paper" by Tephly that followed our study on the incorporation of aspartame-derived methanol label into DNA and protein of rats. I don't know if responding to that publication is worth the effort.

Surprisingly, a serious journal, such as Life Sciences published a rebuttal of our previous paper as a normal "research paper", but including no new information neither experimental work. This is only a sample of the "scientific" power of the advocates of aspartame.

Anybody can extract conclusions from this anomaly, but it seems to me that there was nothing new in that pamphlet that may add information to what we already explained in our paper. The responses to the questions raised by Tephly are already in our paper, which means that either that it was not read or, worst, it was misread.

The presence of aspartame-derived label in DNA and protein adducts is unquestionable and unquestioned, and agrees with previous studies. Then, what importance has the mechanism of incorporation? There were adducts, and they represent loss of function and mutation. That was our thesis.

The reference to previous studies showing very low levels of formaldehyde in blood do not refute our data. First of all, measuring formaldehyde is tricky, and in any case, the circulating levels would be below the current limit of detection for most of the methods used. That is the current explanation for the low levels of methanol in plasma after aspartame loading: they are zero, using most of the methods available for methanol, since the expected levels are currently below the limit of detection...

In addition, it is not logical to expect to find measurable levels of formaldehyde in a medium (blood) containing a huge amount of protein. Formaldehyde reacts immediately with proteins because it is highly reactive: that is the reason why we have found it in cell protein and DNA. It is absurd to expect it to forfeit binding with cell proteins and go all the way into the bloodstream! Remember that formaldehyde is used to preserve corpses precisely because it binds protein (including those of putrefactive bacteria) and prevents its degradation.

The "alternative" point expressed by Tephly, suggesting that aspartame methanol-label goes all the way into formic acid and the C1 pathway was thoroughly refuted by us, using experimental data. There was no labeled methionine nor thymine in protein and DNA respectively in the rat protein we recovered from rats treated with aspartame. This means--unequivocally-- that the label present in DNA and protein adducts was NOT incorporated into amino acids or nucleic acid bases. The only explanation for our data was that the label was in the form of formaldehyde adducts.

If this explanation does not satisfy other scientists, they are free to repeat the experiment and show where we went wrong, or to probe and prove experimentally their hypotheses. Otherwise, our results stand unchecked and, consequently, should be deemed true.

I hope that this information will help any attentive reader understand why we have left for good this field of study.

Best regards.

------------------------------
Prof.Dr. MariÓ Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutriciˇ i Bromatologia
Facultat de Biologia, Universitat de Barcelona Av. Diagonal, 645; 08028 Barcelona Espanya/Espa˝a/Spain
tel. +34 93 403 4606; fax: +34 93 403 7064
E-mail: alemany@bio.ub.es

Life Sci 1999; 65(13): PL157-60. [ letter, usually not peer reviewed ]
Comments on the purported generation of formaldehyde and adduct formation from the sweetener aspartame.
Tephly TR Thomas R. Tephly 319-335-7979
thomas-tephly@uiowa.edu ttephly@blue.weeg.uiowa.edu
Department of Pharmacology recent paper by Trocho et al. (1) describes experiments meant to show that formaldehyde adducts are formed when rats are administered the sweetener aspartame. These authors assume that the methanol carbon of aspartame generates formaldehyde which then forms adducts with protein, DNA, and RNA. Doses employed range widely. In this letter, studies which have been published previously and which were not cited by these authors are reviewed in order to put into perspective the disposition of methanol and formaldehyde in monkeys and humans, species relevant to the toxicity of methanol and its toxic metabolite, formic acid. PMID: 10503962, UI: 99431287

[ A number of pro-aspartame studies by Tephly and associates, invariably funded by the aspartame industry (Monsanto, NutraSweet) are criticized in detail at:

"Scientific Abuse in Aspartame Research"
http://www.holisticmed.com/aspartame/abuse/methanol.html
Aspartame Toxicity Information Center
Mark D. Gold
http://www.HolisticMed.com/aspartame
603-225-2100
mgold@tiac.net
12 East Side Drive #2-18 Concord, NH 03301

Gold points out that industry methanol assays were too insensitive to properly measure blood methanol levels.

http://groups.yahoo.com/group/aspartameNM/message/34
Davoli: aspartame causes rise in blood methanol 1986: Mario Negri Institute for Pharmacological Research: Murray 10.30.99

[selection]

Davoli, E., Cappellini L, Airoldi L, Fanelli R, 1986. "Serum Methanol Concentrations in Rats and in Men After a Single Dose of Aspartame," Food and Chemical Toxicology, Volume 24, No. 3, page 187-189.

Abstract:

Serum methanol concentrations were measured in rats and in humans given oral aspartame. The dose given to rats was the FDA's projected 99th percentile daily intake for humans, assuming aspartame were to replace all sucrose sweeteners in the diet (34 mg/kg). Four male adult volunteers each received 500 mg, equivalent to 6-8.7 mg/kg, which is approximately the FDA's estimate of mean daily human consumption.

Both treatments caused a rise in serum methanol.

In rats the mean peak value was 3.1 mg/litre 1 hr after administration; serum methanol returned to endogenous values 4 hr after treatment. In the men, the mean rise over endogenous values was 1.06 mg/litre after 45 min.

Two hours after treatment, serum methanol had returned to basal levels. The temporary serum methanol increase showed peak values within the range of individual basal levels. PMID: 3957170, UI: 86166135 Enrico Davoli has 22 citations in PubMed.

Regulatory Toxicology and Pharmacology 35, S1-S93 (2002)
doi:10.1006/rtph.2002.1542, available online at http://www.idealibrary.com $ 35.00
Aspartame: Review of Safety page S1 0273-2300/02 $35.00
C 2002 Elsevier Science (USA) All rights reserved.
Harriett H. Butchko
Medical and Scientific Affairs, The NutraSweet Company, Mt. Prospect, Illinois
To whom correspondence should be addressed at Medical and Scientific Affairs, The NutraSweet Company, 699 Wheeling Road, Mt. Prospect, IL 60056.
Fax: (847) 463-1755.
harriett.h.butchko@nutrasweet.com.
W. Wayne
Stargel Research and Development, The NutraSweet Company, Mt. Prospect, Illinois
C. Phil Comer
Graystone Associates, Inc., Macon, Georgia
Dale A. Mayhew
Regulatory Affairs, The NutraSweet Company, Mt. Prospect, Illinois
Christian Benninger (EEGs and Cognitive Function in PKU Heterozygotes)
Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
George L. Blackburn (Appetite, Food Intake, and Weight Control)
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Leo M. J. de Sonneville (Neuropsychological Function and Phenylalanine) Departments of Pediatrics and Neurology, Vrije Universiteit, Medical Center, Amsterdam, The Netherlands Raif S. Geha (Allergy)
Division of Immunology, The Children's Hospital, Harvard Medical School, Boston, Massachusetts
Zsolt Hertelendy (Liver Disease)
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio
Adalbert Koestner (Brain Tumors)
Department of Veterinary Biosciences, Ohio State University School of Veterinary Medicine, Columbus, Ohio
Arthur S. Leon (Long-Term Safety in Humans)
Division of Kinesiology, College of Education and Human Development and Department of Medicine, The Medical School, University of Minnesota, Minneapolis, Minnesota
George U. Liepa (Renal Disease)
Department of Human, Environmental, and Consumer Resources, Eastern Michigan University, Ypsilanti, Michigan
Kenneth E. McMartin (Methanol)
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, Louisiana
Charles L. Mendenhall (Liver Disease)
Digestive Diseases Section, Department of Veterans Affairs Medical Center, Cincinnati, Ohio
Ian C. Munro (Preface)
Cantox Health Sciences, Inc., Mississauga, Ontario, Canada
Edward J. Novotny (Seizures and EEGs)
Department of Pediatrics and Neurology, Yale University School of Medicine, New Haven, Connecticut
Andrew G. Renwick (Preface)
Department of Pharmacology, University of Southampton, Southampton, United Kingdom
Susan S. Schiffman (Headaches)
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina
Donald L. Schomer (Neurochemistry, Seizures and EEGs, Behavior, Cognitive Function, and Mood)
Department of Neurology, Division of Neurophysiology and Epilepsy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Bennett A. Shaywitz (Behavior, Cognitive Function, Mood in Children, Seizures, and EEGs)
Departments of Pediatrics, Neurology, and Child Study, Yale University School of Medicine, New Haven, Connecticut
Paul A. Spiers (Behavior, Cognition, and Mood)
Department of Psychiatry, Boston University School of Medicine, and Clinical Research Center, Massachusetts Institute of Technology, Boston, Massachusetts
Thomas R. Tephly (Methanol)
Department of Pharmacology, The University of Iowa, Iowa City, Iowa
John A. Thomas (Metabolism and Endocrine)
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas
Friedrich K. Trefz (Phenylketonuria)
Department of Pediatrics, Children's Hospital of Reutlingen, University of Tubingen, Reutlingen, Germany
Received January 8, 2002

DEDICATION

The authors dedicate this supplement to the memories of Lewis D. Stegink, Ph.D., and L. J. Filer, Jr., M.D., Ph.D., from the University of Iowa. Their early research on aspartame metabolism in humans formed the basis for much of the future research on aspartame that is discussed in this supplement. Their objectivity and long-standing dedication to science as well as their medical and scientific expertise are greatly missed.

pages S36 to S41 of S1 to S93
Safety of Methanol from Aspartame and the Diet

[Thomas R. Tephly (Methanol) thomas-tephly@uiowa.edu
Department of Pharmacology, The University of Iowa, Iowa City, Iowa

Kenneth E. McMartin (Methanol) kmcmar@lsumc.edu
Department of Pharmacology and Therapeutics, Louisiana State University]

page S39 [Extract]
Evaluation of Recent Issues Regarding Methanol Safety from Aspartame

Trocho et al. (1998) concluded from a study in rats that aspartame may be hazardous because formaldehyde adducts from aspartame may accumulate in tissue proteins and nucleic acids. However, according to Tephly (1999), the dose of aspartame used in the study (20 mg/kg body wt =2 mg of methanol/kg body wt) would not yield blood methanol concentrations outside control values.

Further, the administration of aspartame at 200 mg/kg body wt (equal to that in a single bolus of about 25 liters of beverage sweetened 100% with aspartame) to adult humans results in no detectable increase in blood formate concentrations (Stegink et al., 1981).

Administration of [14 C] methanol itself at 3000 mg/kg body wt to monkeys produces no detectable [14 C] formaldehyde in body fluids and tissues (McMartin et al., 1979), while there is ample accumulation of formate. An alternative explanation for tissue incorporation of label from [14 C] aspartame as described by Trocho et al. (1998) would be incorporation into amino acids and nucleotides via one-carbon moieties from the folate-dependent metabolism of formate. The lack of formaldehyde accumulation at very high doses of methanol questions considerably the conclusion that formaldehyde adducts are forming from low doses of methanol (derived from high doses aspartame). Thus, Tephly (1999) concluded, "the normal flux of one-carbon moieties whether derived from pectin, aspartame, or fruit juices is a physiologic phenomenon and not a toxic event." (Next, Appendix F critiques the McMartin study.) ]

MariÓ Alemany alemany@bio.ub.es
Thomas R. Tephly thomas-tephly@uiowa.edu
Kenneth E. McMartin kmcmar@lsumc.edu
Harriett H. Butchko harriett.h.butchko@nutrasweet.com
Susan S. Schiffman sss@acpub.duke.edu
Arthur S. Leon leonx002@tc.umn.edu
Christian Benninger Christian_Benninger@med.uni-heidelberg.de
George L. Blackburn gblackbu@caregroup.harvard.edu
Leo M.J. de Sonneville lmj.sonneville@vumc.nl
Raif S. Geha raif.geha@tch.harvard.edu
Edward J. Novotny, Jr. edward.novotny@yale.edu
Andrew G. Renwick agr@soton.ac.uk
Donald L. Schomer dschomer@caregroup.harvard.edu
Bennett A. Shaywitz bennett.shaywitz@yale.edu

************************************************************

Appendix F:

The exponential fragmentation of science into a fractile structure of ever more atomized specialties ensures that every expert is a layman outside his own specialty.

Capable laymen play an essential role by summarizing and integrating scattered lines of inquiry that certain vested interests have long-term campaigns for obscuring, since outright opposition would tend to attract discussion and scrutiny that would soon vitiate billion dollar products. Most professionals simply do not have the free time to investigate such arcane, but possibly crucial, details. Capable laymen now join together on the Net to establish credibility by common sense, polite mobilization of specialized research, backed by support from informed specialists. For instance, I started investigating aspartame in early January 1999 and within two months was being given papers by Woodrow C. Monte and Ralph G.Walton.

The route of aspartame to methanol to formaldehyde to formic acid is a classic example. Were this line of inquiry already suspected to be sure to establish the harmlessness of aspartame, then the industry would have every motive to spend a few paltry millions to both complete the research in humans and widely publicize the results.

The fact that on the contrary, there is no industry funded research in humans at all in the public domain on the specific biochemical and tissue outcomes of formaldehyde and formic acid from aspartame leads to a reasonable surmise that the industry has reason to fear, obscure, and derail this inquiry. Following the crooked but unmistakable trail of missing research, i.e., avoided, ignored, misstated, discounted, obscured, explained away, or simply never mentioned, is an excellent strategy for uncovering the lurking secret.

In spring 1999, an eminent pro-aspartame scientist Christian Tschanz had NutraSweet Co. give me their $130 review text of their research, "The Clinical Evaluation of a Food Additive: Assessment of Aspartame" (1996), by Christian Tschanz, Harriett H. Butchko, W. Wayne Stargel, and Frank N. Kotsonis, all aspartame stalwarts.

Chapter 5: "Metabolism and Pharmacokinetics of Radiolabeled Aspartame in Normal Subjects", by Aziz Karim and Thomas Burns, has 10 pages and 10 citations. Page 63, Figure 4, Metabolic products derived from aspartame, beta-aspartame, and DKP, does not list formaldehyde or formic acid.

The tangle of black arrows includes two paths from Aspartame to Methanol to "CO2 + Body Constituents". Now, that's pretty good public relations spin, eh? "Body Constituents", indeed? This is systematic and persistent deceit, as pernicious as it is profitable. Aziz Karim, PhD is a "Distinguished Research Fellow and Sr. Director, Clinical Research, G.D. Searle and Company, Skokie, Illinois", where Thomas Burns, M.S. is a "Clinical Research Manager".

They state that "in monkeys" with methanol or aspartame labeled in the methyl ester, both with 14C, "...excretion of 14CO2 in the expired air occurred to the same extent (about 70% of the 14C dose) with both compounds, indicating complete hydrolysis of the methyl ester moiety of aspartame (Figure 6)." They said nothing about resulting levels in blood plasma, urine, feces, or any body tissues. This is the typical commission by omission strategy of industry research on aspartame.

Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories, Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680

They found that about 70% of the radioactive methanol in aspartame put into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little additional elimination afterwards, as carbon dioxide in exhaled air and in the urine. They did not mention that this meant that about 30% of the methanol must transform into formaldehyde and then into formic acid, both of which must remain as toxic products in all parts of the body. They did not report any studies on the distribution of radioactivity in body tissues, nor give the absolute levels for declining blood plasma proteins. This study did not monitor long-term use of aspartame, which might reveal cumulative effects.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg, about 1 part per million [ppm] of the acute toxicity level of 2,000 mg/kg, 67,000 mmol/kg, used by McMartin (1979). Two L daily use of diet soda provides 123 mg methanol, 2 mg/kg for a 60 kg person, a dose of 67 mmole/kg, a thousand times more than the dose in this study.

By eight hours excretion of the dose in air and urine had leveled off at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine, so 68.7 % was excreted, and 31.3% was retained. [This data is the average of 4 monkeys.]

"...the 14C in the feces was negligible."

"That fraction not so excreted (about 31%) was converted to body constituents through the one-carbon metabolic pool."

"All radioactivity measurements were counted to +-1% accuracy..."

This indicates that the results could not be claimed to have a precision of a tenth of a percent. OK, so this is a nit-pick-- but I believe espousing spurious accuracy is a sign of scientific insecurity.

The abstract ends, "It was concluded that aspartame was digested to its three constituents that were then absorbed as natural constituents of the diet." Thus, the concept is very subtly insinuated that methanol, as a constituent of aspartame, is absorbed as a natural constituent of the diet. "Dietary methanol is derived in large part from fresh fruits and vegetables." Nowhere in this report, or in the book chapter are mentioned the dread words, "formaldehyde" and "formic acid".

Woodrow C. Monte, a Professor of Food Science at Arizona State University in Tempe, drew completely opposite conclusions in his seminal review in 1984. (Appendix G)

The same three researchers, plus F.G. McMahon of Tulane University Medical School, published a follow-up study, "Comparative metabolism of aspartame in experimental animals and humans", J. Toxicology and Environmental Health 2: 441-451, 1976.

The abstract says, "Hydrolysis of the methyl group by intestinal esterases yielded methanol, which was oxidized in the one-carbon metabolic pool to CO2."

"The hypothetical pathways of metabolism, which aspartame was expected to follow, are diagrammed in Fig. 1....The principle used to test the validity of this hypothetical description of the metabolism of aspartame..."

Figure 1. shows in an nice orderly sequence that:
(a) MeOH ---> one-carbon metabolic pool ---> CO2 + formyl metabolites.

Meanwhile, this sentence jumps from p. 441 to 442 under Figure 1., "The absorbed methanol would be incorporated into the one-carbon pool and would be converted [ page jump in sentence ] primarily to CO2 (Makar et.al., 1968; Tephly et al, 1964), although a small fraction might be incorporated into body constituents."

The graphs present the same methanol in monkey data as in 1973, but the nowhere is the specific percentage of exhaled CO2 mentioned. Methanol and aspartame were also given to a few [ unspecified ] number of rats: "The major fraction of the 14C was excreted in the expired air (Fig. 2)...Plasma levels of 14C reached a peak [ absolute data not given ] at about 3 hr..."

In this follow-up report, for methanol and the methyl group in aspartame, excretion in urine and feces were not mentioned in either the former monkey or the new rat studies, the absolute plasma levels were not given, and, of course, no measures were taken of 14C in body tissues. The only hint of the possible role of formaldehyde and formic acid was the rather diffident term "formyl metabolites" in Figure 1. Overall, we see consistent patterns of avoiding any focus on the actual disposition of extremely toxic formaldehyde and formic acid, both persistent and cumulative, products in body tissues. Subtle equivocation and qualification was expressed by such words as "hypothetical", "was expected to follow", "would be", "primarily", "although a small fraction might be incorporated into body constituents", "major fraction".

Methanol from aspartame was not studied in the other species: rabbits, dogs, and humans.

It pays to investigate early studies, because then the cover-up was less well organized, more patchy. The loosely organized world-wide exponential growth of science ensures that the line of inquiry of methanol to formaldehyde and formic acid will pop up here and there, but no one is encouraged to make the connection with aspartame, widely proclaimed as "the most thoroughly tested food additive in history"-- until the momentous, unheralded Trocho study established explosive results in June 1998. (Appendix E)

http://groups.yahoo.com/group/aspartameNM/message/1025
Aspartame & formaldehyde toxicity: Murray 9.9.3

http://groups.yahoo.com/group/aspartameNM/message/910
Formaldehyde & formic acid from 11% methanol in aspartame: Murray: 12.9.2

http://groups.yahoo.com/group/aspartameNM/message/872
Immune system reactions due to formaldehyde from the 11% methanol in aspartame: Thrasher: Tephly: Monte: Murray 9.27.2

Life Sci 1991; 48(11): 1031-41. The toxicity of methanol. Tephly TR. Department of Pharmacology, University of Iowa, Iowa City 52242.

"Abstract:

Methanol toxicity in humans and monkeys is characterized by a latent period of many hours followed by a metabolic acidosis and ocular toxicity. This is not observed in most lower animals. The metabolic acidosis and blindness is apparently due to formic acid accumulation in humans and monkeys, a feature not seen in lower animals. The accumulation of formate is due to a deficiency in formate metabolism which is, in turn, related, in part, to low hepatic tetrahydrofolate (H4 folate).

An excellent correlation between hepatic H4 folate and formate oxidation rates has been shown within and across species. Thus, humans and monkeys possess low hepatic H4 folate levels, low rates of formate oxidation and accumulation of formate after methanol. Formate, itself, produces blindness in monkeys in the absence of metabolic acidosis.

In addition to low hepatic H4 folate concentrations, monkeys and humans also have low hepatic 10-formyl H4 folate dehydrogenase levels, the enzyme which is the ultimate catalyst for conversion of formate to carbon dioxide. This review presents the basis for the role of folic acid-dependent reactions in the regulation of methanol toxicity. Publication Types: Review Review, Academic PMID: 1997785"

p. 1035 "In the past, formaldehyde has often been suggested as the methanol metabolite which produces toxicity (34,35). Today, a great deal of information is available concerning its lack of such a role. The presence of elevated formaldehyde levels in body fluids or tissues following methanol administration has not been observed. No formaldehyde has been detected in blood, urine or tissues obtained from methanol-treated animals (36,37) and, in methanol-poisoned humans, formaldehyde increases have not been observed.... About 85% of a low dose of 14C-formaldehyde [radioactive label] is excreted as pulmonary 14CO2 (49,50)....."

[ This suggests that 15% of the formaldehyde is indeed retained in the body, a very significant result, considering its extreme and complex toxicity. ]

49. W.B. Neely, Biochem. Pharmacol.
13: 1137-1142 (1964).

50. Xenobiotica 1982 Feb; 12(2): 119-24.
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.

  1. The metabolism of [14C]formaldehyde has been investigated in the male Sprague-Dawley rat. It is extensively oxidized to CO2 and formate, which is excreted in the urine.

  2. Two radioactive compounds isolated from the urine of rats dosed with [14C]formaldehyde have been identified as N-(hydroxymethyl)urea and N,N'-bis-(hydroxymethyl)urea, and shown to be urinary artifacts.

  3. Previous studies of the metabolism of formaldehyde by rats have been re-appraised. Differences in the rate of oxidation of formaldehyde in various strains of rats result in the excretion of different urinary metabolites and, in some cases, formaldehyde. Excretion of formaldehyde leads to the formation of several artefacts depending on the components present in the urine. PMID: 6806997

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

K.E. McMartin and T.R. Tephly, authors of many pro-aspartame studies, in Biochemical Pharmacology (1979) remarked, "It is now generally accepted that the toxicity of methanol is due to the formation of toxic metabolites, either formaldehyde or formic acid." They put damage doses of methanol into the stomachs of three monkeys, and, using insensitive tests, found no formaldehyde in many tissues-- except for a single datum in the midbrain, 1.5 times the detection limit. They did report widespread accumulation of formic acid in five tissues. The use of inadequate tests is common in industry research that is funded to claim the safety of profitable toxins.

Since then, industry scientists have been very wary of doing studies on primates, which all too easily show the dangers to humans.

"Abstract [ not given in PubMed ]: [ My briefer comments are in square brackets. ] 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."

"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."

So, this is an acute toxicity study, with little relevance for chronic long-term, low-level exposure. Monkeys, like people, are susceptible to methanol toxicity.

This team cites their six previous methanol in monkey studies, from 1975 to 1977.

The report is difficult to understand, since the three monkeys were treated differently, and different assays were used.

For the methanol sensitive, folate-deficient monkey A, the assay used was the chromatropic acid method, with a detection limit of .025 mmol/L. None of the five tissues showed any formaldehyde with this assay, 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).
[ Since 1 kg of water is 1 L, 1 mmol/kg is equivalent to 1 mmol/L. ]

Meanwhile, in the methanol sensitive, folate-deficient monkey A, the blood formate level rose by 18 hours from 0.18 to 10.02 mEq/L. [ I assume that a mEq is equivalent to a mmol-- let me know if I'm wrong. ] The formate detection limits for the assays were not given in this report. The formate level in the vitreous humor of the eye of monkey A was 7.90 mEq/L. It is well known that formate is extremely damaging to the eye. For unexplained reasons, formate levels in the five tissues and cerebrospinal fluid were not measured in the methanol sensitive, folate-deficient monkey A., in the cerebrospinal fluid of monkey B, or in the optic nerve of monkey C. Formaldehyde was not measured in the optic nerve of Monkey A. The kidney formate level for monkey B was 6.33 and for C was only 0.44, with no comment or explanation given.

The experiment seems arbitrary, capricious, and erratic.

For monkey A, after 18 hours, the urine formaldehyde level was below detection level, while urine formate was 115.80 mEq/L-- so much of the formaldehyde had been converted into formic acid, another cumulative, potent toxin.

"In the presence of high formate values and definitive evidence of toxicity in methanol-poisoned monkeys, no measurable formaldehyde was found in the body tissues that were tested."

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-- just as the 1998 Trocho study confirmed. (Appendix E)

Monkeys B and C were normal, not extra vulnerable to methanol, and were given 3,000 mg/kg methanol, and samples taken at 18 hr. Formaldehyde was detected only in the blood of Monkey B, while formate was found in 8 and 10, respectively, of the 10 fluid and tissue samples in Monkeys B and C. For instance, the lowest value of formate, except for zero-time blood, for each monkey was in the midbrain, 2.16 mmol/kg for Monkey B (24 times the detection limit for the chromatropic acid method) and 1.02 mmol/kg (1.3 times the detection for the dimedon method) for Monkey C. This shows accumulation of formate in liver, kidney, optic nerve, cerebrum, and midbrain.

"Thus, whereas one can associate formate intimately with ocular toxicity in the monkey, no association of formaldehyde with ocular toxicity can be made at this time. It is not possible to completely eliminate formaldehyde as a toxic intermediate because formaldehyde could be formed slowly within cells and interfere with normal cellular function without ever obtaining levels that were detectable in body fluids..."

Acknowledgements-- This research was supported by NIH grant GM 19420 and GM 12675." [not funded by the industry]

Often, pro-aspartame studies have titles and summaries that are not supported by a close study of the details:
http://groups.yahoo.com/group/aspartameNM/message/891
Flawed test for aspartame DNA damage: Jeffrey & Williams 2000: Murray: 11.20.2

************************************************************

Appendix G:

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984: Monte: Murray 9.23.2

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@xtra.co.nz
[ Summary: 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.) ]

"Fruit and vegetables contain pectin with variable methyl ester content. However, the human has no digestive enzymes for pectin (6, 25) particularly the pectin esterase required for its hydrolysis to methanol (26).

Fermentation in the gut may cause disappearance of pectin (6) but the production of free methanol is not guaranteed by fermentation (3). In fact, bacteria in the colon probably reduce methanol directly to formic acid or carbon dioxide (6) (aspartame is completely absorbed before reaching the colon). Heating of pectins has been shown to cause virtually no demethoxylation; even temperatures of 120 deg C produced only traces of methanol (3). Methanol evolved during cooking of high pectin foods (7) has been accounted for in the volatile fraction during boiling and is quickly lost to the atmosphere (49). Entrapment of these volatiles probably accounts for the elevation in methanol levels of certain fruits and vegetable products during canning (31, 33)."

"The scientific literature indicates that a fair estimate of methanol content of commonly consumed fruit juices is on the order of 40 parts per million (Table 1). Stegink, et al. points out that some neutral spirits contain as much as 1.5 grams/liter of methanol (51); what is not mentioned is the fact that if these spirits are at least 60 proof (30% ethanol) this still represents the presence of over 200 molecules of ethanol for every molecule of methanol that is digested.

An exhaustive search of the present literature indicates that no testing of natural substances has ever shown methanol appearing alone; in every case ethanol is also present, usually, in much higher concentrations (15, 27, 28, 30, 31, 35, 44, 45).

Fresh orange juices can have very little methanol (0.8 mg/liter), and have a concomitant ethyl alcohol content of 380 mg/liter (28)."

"-- Data obtained in a Department of Agriculture survey of the food intake of a statistically sampled group of over 17,000 consumers nationwide (1), indicate that the 17.6% of the population that consume orange juice daily take in an average of 185.5 gm of that juice. These statistics indicate that 1.1% of the population consume an average of 173.9 gm of grapefruit juice while only 1.8% drink approximately 201 gm of tomato juice daily. Table 1 shows that under normal conditions these individuals would only be expected to consume between 1 and 7 mg of methanol a day from these sources. Even if an individual consumed two juices in the same day or a more exotic juice such as black currant, there would still be some protection afforded by the ethanol present in these natural juices.

Consumption of aspartame sweetened drinks at levels commonly used to replace lost fluid during exercise yields methanol intake between 15 and 100 times these normal intakes (Table 1).

This is comparable to that of "winos" but without the metabolic reprieve afforded by ethanol. An alcoholic consuming 1500 calories a day from alcoholic sources alone may consume between 0 and 600 mg of methanol each day depending on his choice of beverages (Table 1).

The consumption of aspartame sweetened soft drinks or other beverages is not limited by either calories or osmolarity, and can equal the daily water loss of an individual (which for active people in a state like Arizona can exceed 5 liters). The resultant daily methanol intake might then rise to unprecedented levels.

Methanol is a cumulative toxin (8) and for some clinical manifestations it may be a human-specific toxin."

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 the 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)..."

************************************************************

Appendix H:

http://www.dorway.com/tldaddic.html
5-page review full text Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan; HJRobertsMD@aol.com
http://www.sunsentpress.com sunsentpress@aol.com
Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416 800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text "Aspartame Disease: An Ignored Epidemic" published May 30 2001
$ 60.00 postpaid data from 1200 cases available at http://www.amazon.com
Over 600 references from standard medical research

http://groups.yahoo.com/group/aspartameNM/message/790
RTM: Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2

http://groups.yahoo.com/group/aspartameNM/message/883
Three texts by H.J. Roberts, 1958, 1971, 1979: Murray 11.6.2

http://groups.yahoo.com/group/aspartameNM/message/880
Roberts 45 clinical research reports in mainstream journals: Murray 10.20.2

[ I found two cases reported that specifically described eyelid dermatitis. ] Aspartame Disease (2001), pages 330 to 370, Chapter VIII, Allergies and Skin reactions: Immunologic Perspectives:

p. 337 "B. Itching and Hives: In this series of 1,200 aspartame reactors, 87 (7 %) developed severe itching without a rash, 47 (4 %) hives, and 108 (9 %) other eruptions....As with other foods and additives, hives due to ingesting aspartame products generally occurred within 6-12 hours....The high incidence of such reactions among females (see above) is also noteworthy."

p. 346 "Reports by Others: In its initial monitoring of adverse reactions to aspartame, the FDA received reports of 111 rashes and 80 cases of hives among 3,326 aspartame complainants.

Tollefson, L., Barnard, R. J., Glinsmann, W. H.: Monitoring of adverse reactions to aspartame reported to the U.S. Food and Drug Administration. In, Proceedings of the First International Meeting on Dietary Phenylalanine and Brain Function, edited by R. J. Wurtman and E. Ritter-Walker, Wash., D.C., May 8-10, 1987, 347-372.

Kulczycki (1986) initially described two patients with aspartame-induced hives and angioedema.

[...Hives of the eyelids,...]

"Hives of the eyelids, lips, hands, face and trunk, along with shortness of breath and joint swelling, were precipitated by diet colas and an aspartame table sweetener in a 23-year-old female. The causative role of aspartame was confirmed by open challenge and by two double-blind challenges using opaque capsules of aspartame or a placebo. Itching and hives occurred within one and a half to two hours after swallowing the aspartame. Their severity tended to correlate with the challenge dose (25 or 50 mg). [A 12-0z can of diet soda gives 200 mg.] *A 42-year-old woman developed hives and angioedema within one hour after swallowing aspartame drinks. They reoccurred within 90 minutes after challenge with 75 mg aspartame in a double-blind study. Kulczycki A, Jr.: Aspartame-induced urticaria. Annals of Internal Medicine 1986 Feb; 104(2): 207-208. PMID: 3946947

Kulczycki (1987) subsequently reported an additional 224 patients who contacted him for possible aspartame sensitivity; 154 had chronic hives, angioedema or both. Fifty of the first 75 refrained from ingesting aspartame for two weeks, and noted complete resolution of their hives. Of these 50 patients, 22 reacted positively when rechallenged with aspartame. Kulczycki, A., Jr.: Aspartame allergy. Allergy Observer 1987; June: 6.

Kulczycki, A., Jr.: Aspartame induced hives (Letter) J. of Allergy and Clinical Immunolology 1995 Feb; 95(2): 639-640. PMID: 7852678 Comment on: J Allergy Clin Immunol. 1993 Oct; 92(4): 513-20.

Downham (1992) reported 23 patients with hypersensitivity skin reactions attributable to drinking 12-72 ounces of aspartame sodas daily. Twenty were women. Their reactions included urticaria (19), angioedema (2), macular purpura (2), panniculitis (2), and eczematous dermatitis (1). In each instance, the reaction recurred after rechallenge with a diet soda, or coffee/tea sweetened with an aspartame product. Downham, T. F. II: Possible hypersensitivity reactions to aspartame. Clinical Cases in Dermatology 1992; 4 (Number 4): 12-15."
[ Department of Dermatology, Henry Ford Hospital, Detroit, Mich, USA.

Thomas F. Downham, M.D. (1-800-436-7936)
Specialties: Dermatology
Locations: Taylor
Board Certifications: American Board of Dermatology
American Board of Dermatology: Dermatopath
Medical School Education: University of Michigan Medical School Post Graduate Training:
Henry Ford Hospital - Internal Medicine Wayne State University - Dermatology
Clinical and Special Medical Interests: General dermatology, drug eruptions, bullous dermatoses, lupus erythematosus
The physician-patient relationship is sacred and is the key to quality medical care.
Downham Dermatology, Henry Ford Medical Center-Taylor
24555 Haig Street Taylor, MI 48180 313-375-2101 Fax: 313-375-2140
info@downhamdermatology.dermdex.net
Thomas F. Downham II, MD Chairman, Internet Committee
Michigan Dermatological Society June 15, 2001 thomasd@ic.net. ]

[ ... a painful violaceous rash of the eyelids... ]

p. 352 "Case VIII-E-2: A 57-year-old medical secretary suffered aspartame disease. Many of her manifestations were previously diagnosed as systemic lupus erythematosus. She had been seen in consultation by an allergist, two hematologists, two opthalmologists, a neurologist, an internist, an endocrinologist and three dermatologists! Repeat ANA titers were elevated to 1:2,560 or higher.

She experienced pain in both eyes, marked photosensitivity (interfering with her ability to drive or travel), dry eyes, loss of hearing in both ears, unexplained facial pain, palpitations, pain of the tongue and lips, intense thirst, a painful violaceous rash of the eyelids, other eruptions, and thinning of the hair. Various diagnostic procedures had been negative-- including skin biopsies of the lids and arms, a salivary gland biopsy, and various antibody studies.

The patient was told about aspartame disease by her pharmacist-son. Her daily consumption included up to 12 packets of an aspartame tabletop sweetener, one or two cans of diet cola, eight ounces or more of an aspartame yogurt, and other aspartame products (cereal, gelatins, gum, mints, juice cocktails). Her eyes began to improve within several days after avoiding aspartame products."

[ "Dry eyes, ocular irritation from contact lens, or both, occurred in 46 (8.3%) aspartame reactors, In addition to the sensation of local discomfort and "sand" in the eyes, the eyelids of such patients tend to become swollen and infected, at times with loss of eyelashes.

The causative or contributory role of aspartame was indicated by these clear-cut clinical correlates: (1) prompt and gratifying improvement of ocular and other symptoms following the cessation of aspartame, generally within several days; and (2) their recurrence shortly after resuming such products. This sequence predictably recurred after rechallenge with aspartame, known or inadvertent." ]

"DRY EYES" FROM USE OF ASPARTAME (NUTRASWEET): [ full text ] Associated Insights Concerning the Sjogren Syndrome The Townsend Letter for Doctors, Jan. 1994, by H. J. Roberts, M.D., FCCP, FACA.

"It is of use from time to time to take stock, so to speak of our knowledge of a particular disease, to see exactly where we stand in regard to it, to inquire what conclusions the accumulated facts seem to point to, and to ascertain in what direction we may look for fruitful investigations in the future." Sir William Osler

Abstract

"Dry eyes" and associated difficulty in wearing contact lenses were prominent complaints offered by 56 (8.3%) of 551 aspartame reactors. Xerostomia (dry mouth) was a frequent concomitant. The symptoms promptly improved after they stopped aspartame-containing products, and predictably recurred on aspartame rechallenge. The concomitant joint pains, severe confusion, memory loss and depression also have clinical significance, with special reference to the Sjogren syndrome.

The cause and management of "dry eyes" challenge ophthalmologists and primary care physicians. This symptom was unexpectedly and repeatedly encountered among patients manifesting other reactions to products containing aspartame, a sweetener currently being consumed by 54% of adults in the United States. This complaint was encountered in both the routine questioning of apparent aspartame reactors and a computerized, 9-page survey of such individuals. Many also volunteered difficulty in wearing contact lenses due to decreased tears, dry mouth (xerostomia), joint pains, confusion and memory loss - all specifically attributed to the use of aspartame products.

Methods

Data were obtained from 551 persons who appeared to have systemic reactions to aspartame. They consisted of 160 private patients or aspartame reactors who were personally interviewed, and 391 individuals who described their adverse side effects in the survey questionnaire...including observations after rechallenge. The names of the latter group were supplied by Aspartame Victims and Their Friends (courtesy of Mrs. Shannon Roth), the Community Nutrition Institute (courtesy of Mr. Rod Leonard), and Dr. Woodrow Monte of Arizona State University.

The completed questionnaires were analyzed with the assistance of the Management Information System staff at the Good Samaritan Hospital, West Palm Beach, Florida.

Results

Dry eyes, ocular irritation from contact lens, or both, occurred in 46 (8.3%) aspartame reactors, In addition to the sensation of local discomfort and "sand" in the eyes, the eyelids of such patients tend to become swollen and infected, at times with loss of eyelashes.

The causative or contributory role of aspartame was indicated by these clear-cut clinical correlates: (1) prompt and gratifying improvement of ocular and other symptoms following the cessation of aspartame, generally within several days; and (2) their recurrence shortly after resuming such products. This sequence predictably recurred after rechallenge with aspartame, known or inadvertent.

These observations have been duplicated by more than a score of patients complaining of dry eyes in subsequent aspartame reactors. There were related problems. For example, a physician who consumed considerable diet sodas developed a type of corneal dystrophy generally associated with the chronic use of certain drugs (e.g., indomethacin).

Computerized correlations between aspartame-associated dry eyes, and "marked memory loss," "severe depression" and "severe mental confusion" were done on the first 362 aspartame reactors who completed the questionnaire. (There was a 30.8% response to the initial mailing of 1,177 forms.) The correlates were as follows:

Other complaints offered by the larger cohort had considerable significance, with particular reference to the Sjogren syndrome. They included excessive thirst due to dry mouth (xerostomia) in 65 (12%), and severe joint pains in 58 (11%). It is noteworthy that three-fourths of patients in this and the large series of aspartame reactors were women averaging 50 years, a phenomenon also encountered in the Sjogren syndrome.

Representative Case Reports

Case 1 - A 47 year-old woman complained of severe dryness of the eyes that required one bottle of artificial tears a week. Her consumption of aspartame included 10-12 glasses or cups of aspartame-sweetened beverages, the addition of a tabletop sweetener to 3 cups of coffee in the morning, and considerable aspartame pudding. She also suffered confusion, significant memory loss, intense headaches (never previously a problem), impaired hearing, lightheadedness, severe "nervousness," muscle cramps, and depressions with suicidal thoughts. These symptoms markedly improved after stopping aspartame, and disappeared within several weeks. She no longer required artificial tears. Such dramatic improvement enabled her to travel abroad several weeks later with her church group for relief work.

Case 2 - A 36 year-old businesswoman complained of recent difficulty wearing contact lenses. She had been consuming considerable amounts of soft drinks and gum containing aspartame. These and other symptoms - including lightheadedness, headache and leg cramps - abated within two weeks after all aspartame products were avoided.

Case 3 - a 61 year-old female court reporter developed dry eyes and bilateral blurring of vision. Other recent complaints included marked memory loss, severe headache, dizziness, extreme irritability, and atypical facial and joint pains. As a result, she had been making many errors at work. The patient improved "immediately" when she ran out of aspartame-containing beverages, and resumed regular sodas. She therefore deduced that aspartame products had been causing her problems. Her previous daily consumption included 4 cans of aspartame soft drinks, 2 glasses of aspartame hot chocolate, and 6 packets of an aspartame tabletop sweetener.

Comment

The unexpected associated of aspartame use and dry eyes offers clues concerning this symptom and the Sjogren syndrome. Other problems encountered in aspartame reactors, especially dry mouth and joint pains provide related insights. Two reactors who complained of "thick saliva" developed enlargement and tenderness of the parotid glands. The secretory structures of the salivary glands presumably had been affected by aspartame, as well as the lacrimal glands. The affinity of aspartame for salivary glands were demonstrated experimentally by the prompt uptake of isotopically-labelled aspartame.

The Sjogren or sicca syndrome affects an estimated 2% of the adult population. The reduction or absence of lacrimal and salivary secretions results in dry eyes and dryness of the mouth. (The diagnostic lipstick-on-teeth sign consists of lipstick adhering to the upper front teeth). This disorder is presently regarding as a chronic autoimmune disorder resulting from lymphocyte-mediated destruction of these glands and changes in the points.

A vicious cycle is likely to ensue if considerable aspartame-containing beverages are consumed because of the intense thirst created by severe dryness of the mouth. Weiffenbach et al. demonstrated that taste impairment is not a necessary consequence of salivary gland dysfunction among patients with "dry mouth" caused by the chronic absence of saliva. Accordingly, such individuals may come to prefer the taste of aspartame in satisfying their chronic thirst, with perpetuation of the sicca syndrome.

The systemic and central nervous system sequelae of the Sjogren syndrome underscore the potential importance of these findings. Cognitive impairment and lamenting features have been reported by one-fourth of Sjogren patients. Severe confusion and memory loss also were noted in 157 (28.5%) aspartame reactors in the present series. Indeed, many reactors in their third and fourth decades asked, "Could I be developing early Alzheimer's disease?" The prompt and impressive regression of their confusion and memory impairment after abstinence from aspartame proved reassuring.

Several phenomenon may explain cerebral dysfunction associated with aspartame use. They include flooding of the brain with large amounts of phenylalanine (50% of the aspartame molecule), disturbances of neurotransmitters (especially dopamine), other effects of its three chemical components (phenylalanine, aspartic acid, methanol), methanol-induced cerebral edema, and glucopenia due to increased insulin release and concomitant decreased food intake in an attempt to lose weight.

************************************************************

Appendix I:

[ I have not corrected text, typos, or spelling, except to assemble longer lines. Each of these cases describes major improvements within weeks of giving up aspartame. The varied symptoms are consistent with chronic long-term low-dose formaldehyde toxicity ]

"...I had unexplained rashes, my hair started to fall out..."

TO: Rhonda and Randy Rhockinrho@*****
FROM: bettym19@mindspring.com
DATE: Sat, 14 Dec 2002 23:47:22 -0500
SUBJECT: Re: I'm a new person Aspartame Disease /Markle/World Environmental Conference post

-0500, Rhockinrho@***** wrote:

Dear Ms. Betty,

Thank you for all your (and your friends) wonderful work. I firmly believe it saved my life.

I was always a very active person, worked long hours, raised a family and continued to follow my love of art. I started drinking Diet Coke in the early 80's when it came on the market, but in very small quantities. Over the years I started to have mood swings and unexplained physical problems. Doctors wrote it off as having had a hysterectomy at an early age or the stress of being a single parent.

In Aug. of 2000 I was injured at work and due to the nature of my injury, chronic pain in both wrists, I began to see a round of Doctors trying to get a diagnosis. In the mean time depression and anxiety attacks started to take over my life. I had also started drinking 6, 8 and sometimes more 12 oz. cans of Diet Coke. I gained 30 pounds, on my thin frame I looked bloated all the time. I had unexplained rashes, my hair started to fall out, memory loss, loss of focus ( I could no longer read a book and remember what I had just read - I've always been an avid reader and this was devastating). My friends and family started thinking that I was a chronic alcoholic due to my mood swings and unpredictable behavior. At first they tried to help but then began to avoid me. My social life became going to doctors and whoever happened to be on TV. (Sometimes I would change the channel and forget what I had just watched on the other channel)

Doctors tested me for everything from Lupus and MS to having several MRI and other types of scans. The only thing they didn't test me for was leprosy and I was beginning to think that was next.

I've only been married for 3 years (2nd time around) and I thank God he is man he is . He stuck by me and encouraged me to find an answer when most men would have bailed out . I was sick for 2 years of our 3 year marriage, unable to perform even the most simple of tasks. He would work and then come home to cook dinner and do most of the household chores. I continued to go to doctors, both for my hands and therapy for the depression. I was diagnosed with everything from Carpal Tunnel to faking it, one Dr. at Vanderbuilt went so far as to call me a liar. About 3 months ago I was told by a neurologist that I had Acute Fibralmyalgia, the great dumping ground for "We don't know what the heck it is".

I prayed so hard for something that would head me in the right direction. I was taking meds for the depression and panic attacks then washing it down with Diet Coke. Then one day out of the blue my brother sent me the Markle letter. That letter started me on the path to finding you and the information I needed. Then on to finding my health, I'm still recovering and still have plenty of problems but now I have hope, something I didn't have 3 months ago. My entire family has given up anything that says Sugar Free or Artificial Sweeteners.

I have lost 20 of the 30 pounds I gained, 17 of them in the first 2 weeks! My depression is under control for the most part but I'm still fighting the panic attacks. After 20 years of partaking of something I thought safe I'm sure it's going to be a long road back but at least now I have a road map. I still have good days and bad days but now the good is way ahead! My hands I'm afraid will probably never recover fully as I have Peripheral Neuropathy, the outer coating of the nerves in my wrists are worn off, due to the type of work I have done. But at least I know I'm not going crazy and my quality of life has improved dramatically.

I don't know how to thank you and everyone else enough except to spread the word. And I'm doing that the old fashioned way, by talking to everyone I possibly can.

My husband made the comment to me when I finally discovered the truth about this poison, He said " I tried it once and it smelled like embalming fluid, and I just couldn't drink it" When Diet Coke first came on the market worked for a funeral home and was quite familiar with the smell. We never put the two together until I found the dorway site. He too is thankful for your information and giving him his wife back.

Keep up the good work and I will try to do the same on my end.

Thank you for giving us our life back.

With all Love and Respect, Rhonda and Randy

P.S. I just talked with my Aunt who's daughter is living with MS. I have given her the web address but I'm also having lunch with her tomorrow and will continue the discussion. I'm praying that my cousin is at least open to the idea. If my talking, which I love to do, can help one person, then I've accomplished something and all my pain was worth it.

May the Angels be with you.
*********************

[ Wanda had a variety of eye, skin, and hair problems: "I went from doctor to doctor...dermatologist to dermatologist...and back giving medication and all sorts of things that didn't work....I even order proactive and it didn't work either.....I had growths on my face that resembled moles but wasn't moles some kind of acne I uess...skinned started to get wrinkled and around my eyes was turning "dark" above and below and wrinkly... ]

To: wlw 74218bjw@*****
FROM: bettym19@mindspring.com
DATE: Sun, 15 Dec 2002 04:38:50 -0500
SUBJECT: Aspartame Disease: Joint pain, surgery effect, vertigo, etc. (plus info on prolotherapy)

From: "wlw" 74218bjw@*****
To: bettym19@mindspring.com
Subject: Aspartame Poisoning (You are a God Send)
Date: Tue, 26 Nov 2002 19:56:18 -0600 X-Mailer: Microsoft Outlook Express 5.00.2615.200

Hello

First I would like to thank you for all the information on the web about aspartame poisoning. This is my story:

I have been sick for approximately the past six or seven years. I have gone to the doctor so many times that I have lost count. Betty Martini I can't thank you enough for the information on the web about Aspartame Poisoning. If not for this site I truly believe that in a year I would have been crippled and I would have finally died. I had lost my spirit...my soul was leaving and I was beginning not to care. I had lost most of my faith in the medical system and in doctors. I truly had lost all faith in medication!!!!!!!! I truly have my own pharmacy here at home!!!

About two months ago my health went spiraling down hill fast. When I truly think back I was progressively getting sick even before that. These were my symptoms:

Headache...Blurred Vision...Dizziness....Constant Sinus problems to the point where the doctor had given me an inhaler...(it had progressed to wheezing)...eyes burring at times...coughing at times uncontrollably...tired all the time...bouts with diarrhea...nauseated all the time...stomach bloated...forgetfulness...rash...chills...fever...chills where I would be shaking...weight gain....Heart Palpitations....Chest Pain...Menstrual Cramps from HELL had started to plaque me that lasted the whole time with terrible headaches...Itching...Hunger...numbness in my legs sometimes and my hands...fingers...my skin started to get dry and cracked...acne was bad...started getting bad spots on my face and really dry skin....my skin started turning dark in areas.....my finger nails changed colors...started splitting and grew out with ridges in them from the nail beds...toe nails to same thing....heart beating fast...ringing in my ears...numbness in my face and my ear... my gums changing colors....from a brown (I'm African American) to a light dull red or pink...rash on my back and chest...had to hold on to the banister and the wall to walk down the stairs...when I got up in the mornings I couldn't stand straight up for about an hour...had to work my way up to it....

I went from doctor to doctor...dermatologist to dermatologist...and back giving medication and all sorts of things that didn't work...I even order proactive and it didn't work either...I had growths on my face that resembled moles but wasn't moles some kind of acne I uess...skinned started to get wrinkled and around my eyes was turning "dark" above and below and wrinkly... I was scared and didn't know what the hell was going on with my body and the doctors couldn't tell me. I was having hormonal symptoms to.

After awhile I stopped going to the doctor because all I got was medicine that didn't work and I stop taking because it wasn't working and I was losing faith in the medical system. I had to go to the emergency room because I was having the following symptoms some of which I had had all along but got worse. I packed my bags and called two of my friends to let them know because I truly thought I was going to have a heart attack or a stroke. Now these symptoms got progressively worse because I went the second day to the emergency room. These were my symptoms:

Headache...dizziness...pain in my body and joints...muscle spasms (painful) ...the right side of my face was numb...my right ear...down my neck right side and behind right side...heart beating fast...ringing in my ears...speed up for a while then slow down the speed up out of the blue...I could feel it. When I got in the examining room I ask for a bottle to urinate in because I made sure I drank enough so I would have to urinate. The intern said she didn't think I would have to but I insisted saying if the doctor doesn't need it then we can just throw it away. She agreed. After talking to an intern and the doctor (Dr Sellers) and the doctor doing a bunch of manual test on me the emergency room doctor diagnosed me with Vertigo and sent me home. He gave me something for nausea and dizziness (TIGAN and MECLIZINE).I asked a lot of questions but it just did not satisfy me because it didn't all fit. I got home and looked up Vertigo on the internet and all the symptoms did not fit. I knew something else was wrong or I needed to know what was causing the vertigo. I got so sick on the way home I had to pull over to the side of the road for a little while before proceeding home. Needless to say the medication did not work for I was still dizzy and still nauseated.

Approximately three weeks later my health was spiraling down hill again fast. I was scared but did not believe in the medical system anymore so I didn't go to the hospital. Instead I just started to finally give up. I had bad bad cramps in my stomach and stomach pain. I was dizzy...blurred vision...slurred speech...body pain and just sick all over. I just prayed about it and gave it to god literally. I told him that I wasn't scared to die because my grandmother was up there and my little dog.. my aunt and two uncles and a little cousin. I just wanted to know why. Not why is this happening to me just why am I sick ....what's the cause. Ms Martini I was really tired. I had already withdrawn from ALL my friends never answered my door if I heard it...didn't answer the phone to much. I guess I was depressed. I had mood swings and just a overall attitude of why am I even here to keep suffering like this and to make it worse "with no explanation". Then I just laid down just to feel my heart beating sooooo fast and my head hurting nauseated and running to the bathroom...chest pains...numbness in my face again dizziness...so I got on the computer again and looked up heart failure...diabetes...stroke...etc.

Then for some reason I just got mad and went in the bathroom and got everything I use on my face...everything I bath with (all cosmetics) everything that I eat and drink and brought it up here and put the ingredients in this computer to look it all up. It took me awhile but when I got to my CRYSTAL LIGHT and got to aspartame it hit me like a ton of breaks. There it was POISON. I was slowly poisoning myself to death. I drank Crystal Light All The Time for Years. I could not believe it. All this time being sick. I had even made a comment to a friend that if I didn't live by myself and cook my own food I would swear that someone was poisoning me. Little did I know I was poisoning myself with the APPROVAL OF THE FDA. Just sickening. Then I cried and I cried and I cried because I was mad I was sooo very angry and when I thought about all the older people I see putting those little packets of poison in their coffee and tea it just made me more angry. I thought about the kids who can't explain their symptoms and wonder do they even care. Children are so precious and should not be hurt in anyway and the elderly is just as precious. The should get old and die from old age not from poison. Then the elderly would think they were just getting old and getting sick like that was part of it. Then I thought about all the people who don't know and I made a promise that I would tell EVERYONE I know. I started making phone calls to Kraft Foods who were on a different time zone from me but of course they didn't call me back but I got a confirmation number. I went to their site and saw where people asked about the phenylalaine and their answer was full of it. I went to slim fast and their answer was even WORSE.

I called NatraTaste which I forgot to tell you. I went and bought some Green Tea after the time that I went to the emergency room. I was sweetening it with sugar. I thought that sweetened it with sugar was just defeating the purpose of why I'm drinking the green tea in the first place. I wanted to get some honey. When I went to get the honey the store was out so I went to Wal-Mart and found NatraTaste instead. I taste like sugar and even had almost the texture of sugar. I made my green tea and put about two of those in it because it was a oversized tea cup. Well I got a headache when I drank it but at the time I didn't know that was the cause. I didn't put it together until after I read your site. NatraTaste contains 100% aspartame. I sometimes got sugar free jello and a few other sugar free or light things. Sometimes chewed sugar free gum or gum sweetened with aspartame.

About March I had to go to the dentist because I had a growth on my gums and they were getting sore. Now I truly believe it was caused by aspartame usage. I drank Crystal Light all the time. I even took it to work with me to keep me from going to the drink machine. I would even buy diet sprite or diet 7up and sometimes added it to the Crystal Light unknowingly to me making myself a poison cocktail. I like Wine Coolers but I don't drink that often but I do remember that they sometimes made my body ache after I drank one ( something that I can't explain the feeling throughout my whole body ). I remembered when my nephew came to stay with me for the summer I let him drink crystal light to and not coolaid because it had so much sugar. I remember him telling me that he had a headache and I just told him to go lay down and I would come and lay down with him. I thought it was because it was so hot so I just made him drink water...(THANK GOD FOR THAT) he was just 6 years old then.

The night I saw your website I was drinking Crystal Light. I threw it out went and got some water and that's what I've been drinking every since. After about 3 days my headaches decreased. My body didn't ache so much and my VISION CLEARED. I wasn't so dizzy after about five days. Not one more stomach cramps since I stopped. It has been about 3 weeks now. I feel much better. I tell you what Ms Martini I feel better but I think I have done some long time damage to myself.

My face on the right side still gets a little numb though not like before. My ear on the right side gets numb. My ears still ring but not like before. The pain in my neck is still here and behind my ear. When I go back to the doctor I'm going to ask for a brain scan and a CT scan to make sure I don't have a brain tumor because when I look up my symptoms that's what comes up. I have some of them. My all over headache is gone but I do have a headache sometimes on the right side of my head above my ear and behind my ear in my neck somewhere close to the base of my scull. I'm scared but I'm going. I know if I do that the ASPARTAME did it.

There so many things that I can remember now and the common denominator for all is ASPARTAME. I can remember a female stationed with me at Fort Hood Texas. She use to have terrible migraine headaches to the point where she had to be put on bed rest or quarters for days at a time and I remember she use to drink Diet Coke and Diet Pepsi. Some people thought she was faking but I could see the pain in her face. If they only knew. I'm making a book and I want to take it to the head of the hospital at Fort Leonard to let him know about this. I have called the First Sergeants that I know and told them. I just retired last April and the last years in the Army were filled with pain and sickness from this poison. The doctor had even given me medicine for Arthritis and that didn't help either. Nothing could help because I was still drinking the poison. As I get better I realize different symptoms that I had that are leaving and I know it was the Crystal Light ...Wylers Lite ( same as crystal light just add something to make it dissolve better in water) sugar free jello...sugar free gum....

Ms Martini you and the others are helping so many people and I CANNOT THANK YOU ENOUGH. To think that I even drank that poison in Saudi and even then I had to go to the doctor for pain. When I came back I was still going to the doctor. I just cannot believe that the FDA or congress will allow this to continue. Don't they care about the CHILDREN.

I searched and searched for a case about crystal light making someone sick and I found them. Well I will email you again after holidays. I'm going to the doctor Wednesday to get those test.

THANK YOU AGAIN

WANDA

"Early on I started with a condition under both arms and in the groin that I considered to be "Jock itch". I started using Cortisone 10 cremes and if I used that at least every other day the condition could be controlled and if not the sores were very raw and bloody and boy did it burn. I continued to use the cortisone up until recently. Also about that time I developed a thick scaling in the scalp and around the ears that I thought might just be eczema or worse and I used head and shoulders shampoo but it didn't control it."

http://groups.yahoo.com/group/aspartameNM/message/1068
Classic aspartame case, Fred Keville, 62, diabetic 3 years, quit aspartame about 3 months ago: Murray 2.10.4

At 02:10 PM 3/9/2004, Fred Keville wrote [to Betty Martini]:

Hello, My name is Fred Keville. I am a 62 year old caucasian male who retired as a deputy sheriff in 1997 and who became a metal artist. Every thing in my life was going very well health wise until about three years ago when my personal physician diagnosed me with Diabetes. From day one he advised me to use diet foods and drinks such as "diet cokes and others" as I would have to stay away from the consumption of regular sugar. I didn't much like the taste of diet drinks or diet foods but he scared me enough about my diabetes condition that I switched to only diet foods. I began my diabetes life with oral medications of Glucaphage and Avandia. A couple of years later I had continued to gain weight and I was falling apart. I had occasional headaches that I couldn't explain as I never had them before. All of my joints ached constantly especially my knees and hands. I thought I had arthritis and the diabetes was taking hold of my health in a very negative way.

Early on I started with a condition under both arms and in the groin that I considered to be "Jock itch". I started using Cortisone 10 cremes and if I used that at least every other day the condition could be controlled and if not the sores were very raw and bloody and boy did it burn. I continued to use the cortisone up until recently. Also about that time I developed a thick scaling in the scalp and around the ears that I thought might just be eczema or worse and I used head and shoulders shampoo but it didn't control it. My lower legs and feet were swelling and I could no longer wear my favorite cowboy boots and most of the time I had to wear soft slippers.

Traveling became almost impossible. Besides all of these problems I had frequent urination problems and rarely got more than two hours of sleep at a time. I was becoming more and more irritable around my wife. My Doctor during this period of time was totally exasperated with me as I couldn't control my blood sugar levels and I continued to gain weight and by this time I was up to 320 pounds.

About a year ago my Doctor put my on insulin in an effort to control the blood sugar levels. He started me out on low doses at first but with 3 months I was up to using 65 units of 70/30 humilin in the AM and 60 units in the PM. Sometimes I would test in the morning and I would be 105 and sometimes I would be 205. I was not eating very much at all but I could never convince him of that. By this time I was developing so many physical problems that I couldn't keep track of them all. In the morning for the first few minutes my vision was blurry as if I had a film coating over my eyes but then it would gradually disappear. I started having ringing or hissing in my ears that wouldn't go away. Every morning I would run hot water over my hands so that I could close them. My knuckles were swollen and again I blamed it on arthritis. I blamed every thing on my age and diabetes. If I got down on my hands and knees to do something I was unable to get back up without crawling over to the wall or some furniture.

One day as I was driving my 84 year old mother to her dialysis appointment I began questioning her about any illnesses I might of had while growing up. "I never took you boys to the Doctor while you were growing up other than for broken bones." My brothers and I were very active living in the country. Our diet in those days was meat, potatoes, fresh vegetables, fruit and home made bread and fresh milk.

My Mother then said, "you worse off than me" to which I replied "He doesn't know what all is wrong with me as all my blood tests are O.K. and everything, I'm at my wits end. I was getting real depressed and even contemplated ending it all. My whole life I had been very healthy and real strong and now I was as weak as could be. I then started reading books and surfing the internet. After a few weeks I found "Dorway". Long story short, I cleaned out my pantry and kitchen of all the sugar free Jello, pudding, No sugar added Ice Cream, sugar free cookies and Diet Drinks that contained aspartame. Within 3 days I noticed some improvement. Within 2 weeks I felt like a thirty year old again. I could drop down and do about 5 push ups and wanted to go walking around the farm. My knees completely cleared up and the head aches went away. With the help of using Aloe Vera Gel in my scalp and in my shower soap my skin condition cleared up 90 percent. I have not had one bit of under arm and groin rash since I quit using aspartame products. Did I mention that I also had been writhing a book on my computer but I was unable to concentrate on spelling even the most simple of words until I got off that darn poison. I'm back to writing again. I'm now starting up in my metal shop which I stopped doing nine months ago.

Now here's the good part. I went in to see my Doctor about six weeks ago about a cyst on my inner thigh that may or may not be related to Aspartame use. Anyway he had already given up on me regarding my Diabetes condition and scheduled me to see a Diabetic Specialist for the 17th of this month. I had gain 18 pounds on the last visit with him and my blood sugar levels were still out of control.

He asked me in general conversation, "well how you been doing". I said "Great, never been better"

By the way Doctor do you still use sugar free food and drinks? Sure, I drink diet pepsi, to which I replied, Well Doc you might consider giving them up. You see Doc, I've had Aspartame toxins in me since you first advised me to use them three years ago. Besides feeling great now, my blood sugar levels have come down to about 95 in the morning and about 110 in the PM and besides did you notice what my weight is today compared to three weeks ago. He checked his Nurses notes and said your down considerably. About 20 pounds. I replied, Yeah Doctor and I don't even crave any thing sweet any more. Hmm, very interesting, let me know how your improving. He didn't have a clue about aspartame. I then took the new prescription and went to my trusted Pharmacist who didn't have a clue about the effects of Aspartame either.

Then it hit me, the medical profession doesn't have a clue about food additives not even Aspartame. By the way I also told my Doctor that probably a third of his patients probably has Aspartame poisoning and he never knew it. To that he didn't have a response.

I'm now reading every thing I can get my hands on regarding Aspartame. I've gotten three Diabetic friends off any thing sugar free or diet.

If you don't remember the sixties very well there was a saying back then. "Power to the People".

If I had my way there wouldn't be a congressman or Senator serving one more term unless he got on the bandwagon and helped all of us victims of this terrible injustice. We need to get literature out just before election time so any one would know how to vote responsibly. This is the only way we can get enough people educated. "I'M WONDERING, WHAT MORE CAN I DO". Should I mail all my sugar free drinks back to where they came from? No body and I mean nobody is so big and powerful that they can't be crippled legally. Forget your scientists and their truth full results as that hasn't worked and never will. Hit em where it hurts. You have to ask your self one more question. If the movement to educated people like me is having any success then how come this ol' cowboy had to go through three years of living hell before I accidentally "stumbled" across all the good word that you are putting out.

I'm not going to apologize for the length of this e-mail because it all had to be said. I'm just an average guy who fought for his country and did everything asked of me only to be poisoned by my own country the good ol' U.S. of A.

God Bless and Guide you now and always, Your Friend, Fred Keville, Lodi, Calif.

P.S. May I hear back from you, your thoughts.

************************************************************

Appendix J:

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval: Turner: Murray 12.23.2

http://groups.yahoo.com/group/aspartameNM/message/1039
Three-page review: aspartame (methanol, formaldehyde) toxicity: Murray 11.22.3

http://groups.yahoo.com/group/aspartameNM/message/1026
Brief aspartame review: formaldehyde toxicity: Murray 9.11.3

http://groups.yahoo.com/group/aspartameNM/message/989
On 4.10.2003 the European Union Parliament voted 440 to 20 to approve sucralose, limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3

http://groups.yahoo.com/group/aspartameNM/message/1065
Politicians and celebrities hooked on diet sodas (aspartame): Murray 3.24.4

http://www.google.com Gives 221,000 websites for "aspartame", with the top 9 of 10 listings being anti-aspartame, while

http://groups.google.com Finds on 700 MB of posts from 20 years of Usenet groups, 83,800 posts, the top 10 being anti-aspartame.

http://news.google.com 28 recent aspartame items from 4500 sources.

http://www.AllTheWeb.com Gives 291,700, the top 7 of 10 being leading and very well informed volunteer anti-aspartame sites.

http://teoma.com/index.asp Gives 85,700 websites, top 8 of 10 anti.

http://www.ncbi.nlm.nih.gov/PubMed Lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
Aspartame & formaldehyde toxicity: Murray 9.9.3

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD: [formaldehyde from methanol in aspartame]: Murray 1.16.4

http://groups.yahoo.com/group/aspartameNM/message/1048
Hangovers from formaldehyde from methanol (aspartame?): Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200 mg/L in drinks adds methanol 98 mg/L (becomes formaldehyde in body): EU Scientific Committee on Foods 7.12.1: Murray 1.22.4

http://groups.yahoo.com/group/aspartameNM/message/1065
Politicians and celebrities hooked on diet sodas (aspartame): Murray 3.24.4

http://www.google.com Gives 221,000 websites for "aspartame", with the top 9 of 10 listings being anti-aspartame, while

http://groups.google.com Finds on 700 MB of posts from 20 years of Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com 28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com Gives 291,700, the top 7 of 10 being leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp Gives 85,700 websites, top 8 of 10 anti.
http://www.ncbi.nlm.nih.gov/PubMed Lists 751 aspartame items.

http://groups.yahoo.com/group/aspartameNM/message/1025
Aspartame & formaldehyde toxicity: Murray 9.9.3

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert Swift, MD: [formaldehyde from methanol in aspartame]: Murray 1.16.4

http://groups.yahoo.com/group/aspartameNM/message/1048
Hangovers from formaldehyde from methanol (aspartame?): Schwarcz: Linsley: Murray 1.18.4

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200 mg/L in drinks adds methanol 98 mg/L (becomes formaldehyde in body): EU Scientific Committee on Foods 7.12.1: Murray 1.22.4

http://groups.yahoo.com/group/aspartameNM/message/1024
Aspartame review: methanol, formaldehyde, formic acid toxicity: Murray 9.5.3

http://groups.yahoo.com/group/aspartameNM/message/910
Formaldehyde & formic acid from methanol in aspartame: Murray: 12.9.2

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

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

Bear in mind that the EPA limit for formaldehyde in drinking water is 1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999 5.30.2

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

http://groups.yahoo.com/group/aspartameNM/message/872
Immune system reactions due to formaldehyde from the 11% methanol in aspartame: Thrasher: Tephly: Monte: Murray 9.27.2

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories, Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680

They found that about 70% of the radioactive methanol in aspartame put into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little additional elimination, as carbon dioxide in exhaled air and as water in the urine. They did not mention that this meant that about 30% of the methanol must transform into formaldehyde and then into formic acid, both of which must remain as toxic products in all parts of the body. They did not report any studies on the distribution of radioactivity in body tissues, except that blood plasma proteins after 4 days held 4% of the initial methanol. This study did not monitor long-term use of aspartame.

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

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
Testable theory of MCS type diseases, vicious cycle of nitric oxide & peroxynitrite: MSG: formaldehyde-methanol-aspartame: Martin L. Pall: Murray: 12.9.2

Environ Health Perspect. 2003 Sep; 111(12): 1461-4.
Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity:
Central role of N-methyl-D-aspartate receptors in the sensitivity mechanism.
Pall ML.
School of Molecular Biosciences, 301 Abelson Hall, Washington State University, Pullman, WA 99164, USA. martin_pall@wsu.edu

The elevated nitric oxide/peroxynitrite and the neural sensitization theories of multiple chemical sensitivity (MCS) are extended here to propose a central mechanism for the exquisite sensitivity to organic solvents apparently induced by previous chemical exposure in MCS. This mechanism is centered on the activation of N-methyl-D-aspartate NMDA) receptors by organic solvents producing elevated nitric oxide and peroxynitrite, leading in turn to increased stimulating of and hypersensitivity of NMDA receptors. In this way, organic solvent exposure may produce progressive sensitivity to organic solvents.

Pesticides such as organophosphates and carbamates may act via muscarinic stimulation to produce a similar biochemical and sensitivity response. Accessory mechanisms of sensitivity may involve both increased blood-brain barrier permeability, induced by peroxynitrite, and cytochrome P450 inhibition by nitric oxide. The NMDA hyperactivity/hypersensitivity and excessive nitric oxide/peroxynitrite view of MCS provides answers to many of the most puzzling aspects of MCS while building on previous studies and views of this condition. PMID: 12948884

Prof. Pall describes processes by which an initial trigger exposure, such as carbon monoxide or formaldehyde, can generate hypersensitivity to many substances. He himself had recovered from a sudden, debilitating attack of multiple chemical sensitivity in June/July 1997.

http://groups.yahoo.com/group/aspartameNM/message/1055
Hormesis: possible benefits of low-level aspartame (methanol, formaldehyde) use: Calabrese: Soffritti: Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
Disorders of NMDA glutamate receptors in brain range from high activity (MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol, aspartame)-- Pall) to low activity (schizophrenia-- Coyle, Goff, Javitts): Murray 3.13.4

http://groups.yahoo.com/group/aspartameNM/message/946
Functional Therapeutics in Neurodegenerative Disease Part 1/2: Perlmutter 7.15.99: Murray 1.10.3

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 7.29.99: Excitotoxins 1999 Part 1/3 Blaylock: Murray 1.14.0
The Medical Sentinel Journal 1999 Fall; (95 references)

http://www.dorway.com/blayenn.html
Aspartame (methanol, formaldehyde) toxicity: Murray 1.1.4

http://groups.yahoo.com/group/aspartameNM/message/1034
Brain cell damage from amino acid isolates (aspartame releases phenylalanine, aspartate, methanol [formaldehyde, formic acid] Bowen & Evangelista May 6 2002: Murray 11.10.3

http://www.aspartame.ca/Brain%20Cell%20Damage.pdf
Brain cell damage from amino acid isolates 5.6.2 41 references detailed 22 page review by James D. Bowen, MD and Arthur M. Evangelista, former FDA Investigator orwilly@msn.com

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer: EPA: CPSC: formaldehyde toxicity 6.10.1

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1 Four double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity 6.4.1 Two double-blind studies

http://groups.yahoo.com/group/aspartameNM/message/1018
Aspartame toxicity cover-up increases danger of corporate meltdown: Michael C. Carakostas of Coca-Cola: Murray 8.11.3

http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory Affairs The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234 F. 404/676-7166
E-mail: mcarakostas@na.ko.com
http://www2.coca-cola.com/ourcompany/columns_aspartame.html [photo]
Aspartame: The world agrees it's safe By Michael Carakostas, DVM, PhD Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit disparagingly: "During digestion, aspartame yields a very small amount of methanol-- as do many other food substances. The body converts this methanol to formaldehyde, which is instantly converted to formate. Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973 shows that as much as 30% of the formaldehyde is retained in the body as toxic, cumulative adducts to the DNA, RNA, and proteins in all cells and tissues, leading to pointed reports by informed doctors and experts. Clearly, there are no safe levels for chronic, low-level formaldehyde exposure. If just 10% of the methanol from six cans of diet soda is retained in the body as toxic products of formaldehyde and formic acid, that is sixty times the EPA limit for allowable formaldehyde from daily drinking water.

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3

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.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and Environmental Sciences, Bologna, Italy. crcfr@tin.it

Formaldehyde was administered for 104 weeks in drinking water supplied ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L to groups of 50 male and 50 female Sprague-Dawley rats beginning at seven weeks of age. Control animals (100 males and 100 females) received tap water only. Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley rats beginning at six weeks of age at concentrations of 2,500, 1,500, 500, 250, 50, or 0 mg/L. Animals were kept under observation until spontaneous death. Formaldehyde and acetaldehyde were found to produce an increase in total malignant tumors in the treated groups and showed specific carcinogenic effects on various organs and tissues. PMID: 12562630

Surely the authors deliberately emphasized that aspartame is well-known to be a source of formaldehyde, which is an extremely potent, cumulative toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No. No. of Bioassays Species No. Route of Exposure
108. "Coca-Cola" 4 Rat 1,999 Ingestion, Transplantal Route
109. "Pepsi-Cola" 1 Rat 400 Ingestion
110. Sucrose 1 Rat 400 Ingestion
111. Caffeine 1 Rat 800 Ingestion
112. Aspartame 1 Rat 1,800 Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports: Murray 12.31.2

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3
[Also borderline evidence, in this pilot study of 39 food additives, using test groups of 4 mice, for DNA damage from for stomach, colon, liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame-- a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
Genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor; sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002: Murray 1.27.3
[A detailed look at the data]

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: http://www.dorway.com: original documents and long reviews of flaws in aspartame toxicity research 7.31.2

http://groups.yahoo.com/group/aspartameNM/message/858 RTM: Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity 8.1.2 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 7.10.0

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
Aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9

http://groups.yahoo.com/group/aspartameNM/message/928
Revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co., JW Childs Assc.: aspartame-neotame toxicity 7.10.2

http://groups.yahoo.com/group/aspartameNM/message/876
Hyperthyroidism (Graves disease) in George and Barbara Bush, 1991-- aspartame toxicity? Roberts 1997: Murray 10.9.2

http://groups.yahoo.com/group/aspartameNM/message/874
Re "dry drunk": Bisbort: danger to President Bush from aspartame toxicity: Murray: 2.24.2 9.29.2

http://groups.yahoo.com/group/aspartameNM/message/939
Aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 1.5.3
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@atlas.uoa.gr
"K.H. Schulpis" inchildh@otenet.gr "G.J. Reclos" reklos@otenet.gr

http://groups.yahoo.com/group/aspartameNM/message/960
Aspartame & MSG: possible role in autoimmune hepatitis: Prandota Jan 2003: Murray 1.15.3

http://groups.yahoo.com/group/aspartameNM/message/938
Aspartame harms mice brain cells: Hetle & Eltervaag: 2001 thesis abstract: Sonnewald 1995 study, full text: Murray 1.5.3

http://groups.yahoo.com/group/aspartameNM/message/346
WebMD: Barclay: Barth: survey shows aspartame hurts memory in students 11.9.00

http://www.psy.tcu.edu/psy/barth.htm
Timothy M. Barth Department of Psychology t.barth@tcu.edu
Texas Christian University TCU Box 298920 Fort Worth, TX 76129
Chairman, Physiological Psychology 817-921-7410

http://groups.yahoo.com/group/aspartameNM/message/760
Kovatsi L, Tsouggas M
The effect of oral aspartame administration on the balance of magnesium in the rat.
Magnes Res 2001 Sep;14(3): 189-94.
Laboratory of Forensic Medicine & Toxicology, Faculty of Medicine
Aristotle University of Thessaloniki, Greece kovatsi@med.auth.gr

http://groups.yahoo.com/group/aspartameNM/message/943
Aspartame, cell phones, brain cancer July 1999 Hardell: Murray 1.9.3

http://www.medscape.com/MedGenMed/braintumors
Lennart Hardell, M.D., PhD, in 1999 reported in Sweden that both cell phone use and heavy aspartame use correlate with increased brain cancers lennart.hardell@orebroll.se +46 19 602 15 46

http://groups.yahoo.com/group/aspartameNM/message/31
Murray: Wurtman: aspartame & seizures 11.9.85 10.30.99
Wurtman RJ Aspartame: possible effect on seizure susceptibility.
Lancet 1985 Nov 9; 2(8463): 1060.
Richard J. Wurtman, Ph.D. dick@mit.edu 617-253-3091
Professor of Neuroscience
Prof. of Health Sciences and Technology
Massachusetts Institute of Technlogy Cambridge, Mass. 02139

http://groups.yahoo.com/group/aspartameNM/message/32
Murray: Drake: aspartame & panic attacks 9.13.86 10.30.99
Miles E. Drake, MD
Panic attacks and excessive aspartame ingestion.
Lancet 1986 Sep 13; 2(8507): 631.
Department of Neurology and Psychiatry, Ohio State University Medical Center, Columbus, Ohio 43210, USA

http://www.truthinlabeling.org
Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD
The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999; 6: 259-310. 52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333 adandjack@aol.com

http://www.dorway.com Over 12,000 print pages
Mission-Possible-USA Betty Martini 770-242-2599 Bettym19@mindspring.com
http://www.dorway.com/asprlink.html many links http://www.dorway.com/nslawsuit.txt Jeff Martin, Attorney
http://www.dorway.com/doctors.txt

What many informed doctors are saying/have said about aspartame

http://www.HolisticMed.com/aspartame
603-225-2100
Aspartame Toxicity Information Center
Mark D. Gold mgold@holisticmed.com
12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

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, 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, and interstitial cystitis (bladder pain).