METHANOL (FORMALDEHYDE, FORMIC ACID) DISPOSITION

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: 28 May 2005


http://groups.yahoo.com/group/aspartameNM/message/1143
Methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full plain text, 2001: substantial sources are degradation of fruit pectins, liquors, aspartame, smoke: Murray 2005.05.22

An earnest medical layman, I have been writing careful reviews of mostly mainstream medical research on aspartame toxicity for six years.

http://groups.yahoo.com/group/aspartameNM/message/1155
Continuing aspartame debate in British Medical Journal, John Biffra, Bob Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09

http://groups.yahoo.com/group/aspartameNM/message/1108
Faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland, abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde, lipid peroxidation, green tea, aging, Lyme disease: Murray 2004.08.08

In recent months I have become aware that evidence strongly shows that substantial methanol and thus formaldehyde and formic acid are released into humans from degradation of the pectins from fruits and vegetables by bacteria in the colon in many people. Whatever the source, the biochemical dispositions of methanol and its inevitable products, formaldehyde and formic acid, both potent, cumulative toxins, are actually largely unknown, according to the expert comprehensive review by Bouchard M et al, 2001

"Experimental studies on the detailed time profiles following controlled repeated exposures to methanol are lacking."

"Thus, in monkeys and plausibly humans, a much larger fraction of body formaldehyde is rapidly converted to unobserved forms rather than passed on to formate and eventually CO2."

"However, the volume of distribution of formate was larger than that of methanol, which strongly suggests that formate distributes in body constituents other than water, such as proteins."

Their comprehensive review shows that there is little information about the details of methanol (formaldehyde and formic acid) dispositions in humans for long-term, chronic exposures. Their full text is given later in this post.

Research on hangovers, largely caused by the conversion of methanol impurity in alcohol drinks into formaldehyde after about eight hours, after most of the ethanol has been eliminated, shows that a quarter to a half of those who get inebriated do not get hangovers. This shows very large individual variation in vulnerability to formaldehyde toxicity, so as a corollary, probably there will be many who are not markedly vulnerable to aspartame.

I suggest that natural selection has given humans complex biochemical systems to store the large amounts of formaldehyde generated from pectins and to use them to attack pathogens. So far, I have not found any strong research to support this hypothesis. I hope to write a useful summary in the next few weeks.

There are many substances, such as folic acid, that protect against formaldehyde toxicity.

This long, complex review presents mainstream evidence for several ubiquitous, substantial sources of methanol and its inevitable chain of products, formaldehyde and formic acid, which I will initialize as "MCC", for Methanol Chain Compounds.

Monte WC in his seminal summary review (1984) mentions that humans are uniquely vulnerable to the conversion of methanol into formaldehyde:

"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)."

"Humans, due perhaps to the loss of two enzymes during evolution, are more sensitive to methanol than any laboratory animal; even the monkey is not generally accepted as a suitable animal model (42)." "The methyl ester bond of phenyalanine is the first to cleave due to its susceptibility to pancreatic enzymes (40). This is highly unusual; the methyl esters associated with pectin for instance are completely impervious to all human digestive enzymes (6)."

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

"The importance of ethanol as an antidote to methanol toxicity in humans is very well established in the literature (46, 55). The timely administration of ethanol is still considered a vital part of methanol poisoning management (11, 12, 19, 20, 50). Ethanol slows the rate of methanol's conversion to formaldehyde and formate, allowing the body time to excrete methanol in the breath and urine. Inhibition is seen in vitro even when the concentration of ethyl alcohol was only 1/16th that of methanol (62). The inhibitory effect is a linear function of the log of the ethyl alcohol concentration, with a 72% inhibition rate at only a 0.01 molar concentration of ethanol (2, 46).

Oxidation of methanol, like that of ethanol, proceeds independently of the blood concentration, but at a rate only one seventh (20) to one fifth (12) that of ethanol.

Folacin may play an important role in the metabolism of methanol by catalyzing the elimination of formic acid (41). If this process proves to be as protective for humans as has been shown in other organisms (50, 38) it may account, in part, for the tremendous variability of human responses to acute methanol toxicity. Folacin is a nutrient often found lacking in the normal human diet, particularly during pregnancy and lactation (14)."

It is well known that our primate ancestors were highly adapted to a diet of fruits and vegetables, and thus had the enzyme systems to prevent toxicity from the inevitable methanol content and from methanol from the degradation of pectins by bacteria in the colon.

Humans have been living in groups in lifelong close proximity with fire and smoke, a potent source of formaldehyde, for about 2 million years. Fire has ever since been essential for survival, as has been intimate enclosed group living, especially as homo erectus, Neanderthals, and moderns successively adapted to very cold habitats.

Yet formaldehyde is among the most potent of toxins, and cumulative to boot. Yet intimate enclosed group living in a variety of environments promotes extreme exposure to a variety of contagious, infectious diseases. And yet, humans lack two enzymes that protect against Methanol Chain Compounds toxicities. What is an obvious evolutionary explanation for this?

MCC toxicities must serve to prevent and treat contagious infections from bacteria, fungi, parasites, and possibly viruses. This would generate a potent positive selection pressure to cause humans to evolve the ability to have increased MCC exposures, and to be multiply adapted to tolerate MC toxicities.

Wine and beer serve throughout history to protect against water bourne pathogens. For centuries formaldehyde has been used to protect medical scientists from highly infected cadaver tissues. What is the scientific literature about MCC and the various groups of contagious infectious agents? It is a testable hypothesis as to whether MCC in many types of people, with the inevitable complex variations of genetics and diet, impede many simple infectious agents more than they harm critical body processes in complex human cells.

It may be that MCC are important unexamined co-factors that strongly affect research and treatment of many infectious diseases.

We might find, for instance, that in many humans some infections cause reduction of folic acid or folate levels, and thus increased MCC levels.

Many traditional societies treat diseases with exposure to smoke, whether in a hut with a wood fire, or in a temple with incense. Likewise, alcohol drinks have been widely used as remedies. Did the daily ration of grog in the British Navy serve to reduce infections in the close and dirty confines of life on wooden ships? In the trenches of World War I, the British also had a daily ration -- were their rates of infection lower than for troops that had little liquor?

These questions throw an entirely new light, expansive, tantalizing, and unifying, on the often contentious and poorly researched issues of MCC toxicity, especially the aspartame controversy. It would also be ironic, but typical of the actual complex evolution of science, for tobacco and wood smoke to be shown to have some benefits for infectious diseases.

http://groups.yahoo.com/group/aspartameNM/message/1140
EPA Preliminary Remedial Goals, PRGs, 2003 Oct, air and tap water -- methanol, formaldehyde, formic acid -- not mentioned is methanol from aspartame, dark wines and liquors: Murray 2004.11.20

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame (methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

The Nurses Health Study is a bonanza of information about the health of probably hundreds of nurses who use 6 or more cans daily of diet soft drinks -- they have also stored blood and tissue samples from their immense pool of subjects.

Dark wines and liquors, as well as aspartame, provide similar levels of methanol, above 100 mg daily, for long-term heavy users. Methanol is inevitably largely turned into formaldehyde, and thence largely into formic acid.

Both products are toxic, and at this level of use, about 2 L daily, almost six 12-oz cans of diet drink, are above recent lifetime EPA safety limits in tap water for methanol and formaldehyde of respectively, for a 60 kg person, 30 mg and 9 mg daily.

The immediate health effects for dark wines and liquors are the infamous "morning after" hangover, for which many informed experts cite as the major cause the conversion of the methanol impurity, over one part in ten thousand (red wine has 128 mg/L methanol), into formaldehyde and formic acid. Everyone knows the complex progression of symptoms at this level of long-term, chronic toxicity.

Aspartame reactors have a very similar progression.

If 1% of all people exposed to alcohol and/or aspartame are heavy users with symptoms, then there would easily be about 2 million cases in the USA alone.

This is a public health emergency.

At the very least, professionals and the public should be alerted to investigate their own exposure, and be given a chance to try a very safe, simple, inexpensive treatment for complex, intractable, progressive symptoms -- reducing or eliminating their intake.

There are as well, many safe substances that prevent or treat the toxicities -- for example, high folic acid levels expedite the elimination of formaldehyde.

These toxicities are largely uncontrolled co-factors that affect every disease and must confuse and impede many health research programs on all levels.

People in high-pressure, critical occupations, such as pilots, nuclear plant operators, and national leaders, should certainly be alerted.

Also, two careful studies show substantial methanol release from degradation of pectins by bacteria in the colon from fruits and vegetables -- a topic that deserves careful, thorough research.

Due to my bias, based on detailed reviews by Monte WC (1984) and by Mark D Gold (2003), for months I have been discounting the startlingly high methanol levels reported in the abstract for Lindinger W (1997). I had been reducing the values in their abstract from g to mg, an unwarrented "correction" by a factor of a thousand, only to find that the full text study and their many related studies supply expert, robust results:

Alcohol Clin Exp Res. 1997 Aug; 21(5): 939-43.
Endogenous production of methanol after the consumption of fruit.
Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W.
Institut fur Ionenphysik, Leopold Franzens Universitat Innsbruck, Austria.

After the consumption of fruit, the concentration of methanol in the human body increases by as much as an order of magnitude. This is due to the degradation of natural pectin (which is esterified with methyl alcohol) in the human colon.

In vivo tests performed by means of proton-transfer-reaction mass spectrometry show that consumed pectin in either a pure form (10 to 15 g) or a natural form (in 1 kg of apples) induces a significant increase of methanol in the breath (and by inference in the blood) of humans. The amount generated from pectin (0.4 to 1.4 g) [ 400 to 1400 mg ] is approximately equivalent to the total daily endogenous production (measured to be 0.3 to 0.6 g/day) [ 300 to 600 mg ] or that obtained from 0.3 liters of 80-proof brandy (calculated to be 0.5 g). [ 500 mg ] This dietary pectin may contribute to the development of nonalcoholic cirrhosis of the liver. PMID: 9267548

Alcohol Clin Exp Res. 1995 Oct; 19(5): 1147-50.
Methanol in human breath.
Taucher J, Lagg A, Hansel A, Vogel W, Lindinger W.
Institut fur Ionenphysik, Universitat Innsbruck, Austria.

Using proton transfer reaction-mass spectrometry for trace gas analysis of the human breath, the concentrations of methanol and ethanol have been measured for various test persons consuming alcoholic beverages and various amounts of fruits, respectively.

The methanol concentrations increased from a natural (physiological) level of approximately 0.4 ppm up to approximately 2 ppm a few hours after eating about 1/2 kg of fruits, and about the same concentration was reached after drinking of 100 ml brandy containing 24% volume of ethanol and 0.19% volume of methanol. PMID: 8561283

I urge Channing Laboratory and its participating universities to rapidly mount an in-house study to study the Nurses Health Study database for the hundreds of nurses who are long-term users, above 6 cans diet drinks daily, for correlations with every disease, as well as ubiquitous co-factors like wine and liquor, cigarette smoke, and fruits and vegetables. It could vastly serve the world public health to make the initial findings widely available immediately. The disparaged issue of aspartame toxicity could be swiftly made legitimate, and the resulting progress on all levels remarkably accelerated.

A single scientist could do this.

Comments pro and con are welcome. A convenient venue would be the moderated newsgroup: bionet.toxicology.

http://groups.yahoo.com/group/aspartameNM/message/1162
Santa Fe area physicians who oppose aspartame: Citizens Nutrition Council, Santa Fe: Murray 2005.03.29

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

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

"C. Public Relations, Aspartame, Methanol, and Formaldehyde

Before we discuss what little the Committee did say related to aspartame and formaldehyde, it is important to answer all of the typical public relations statements from the manufacturer and their consultants who claim there is no problem with aspartame and formaldehyde. The answers provided below will be brief. Much more detailed and referenced answers can be found at ATIC (2001) on the Internet at:

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

Chart of Aspartame Manufacturer Public Relations Statements Related to Methanol and Formaldehyde

Manufacturer Claim --- Independent Response

Methanol is found in fruits and alcoholic beverages at higher levels than in aspartame products. --- Alcoholic beverages contain large amounts of ethanol (a protective factor) which allows methanol to be excreted before much of it is converted into formaldehyde (Leaf 1952, Liesivuori 1991, Roe 1982).

Fruit juices have protective factors as well that prevent formaldehyde poisoning. Fruit juices produce enough methanol to "qualify as significantly methanol-contaminated liquor" (Lindinger 1997) -- more methanol than what causes chronic health problems in occupational exposure (Kazeniac 1970, Kavet 1990, Frederick 1984, Kingsley 1954-55). Since we do not see chronic poisoning from fruit juices, they must contain protective factors as well. Fruit juices have ethanol as well as other possible protective factors."

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

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
Arizona State University, Tempe, Arizona 85287 woodymonte@xtra.co.nz

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

"That substantial amounts of methanol metabolites or by-products are retained for a long time is verified by Horton et al. (1992) who estimated that 18 h following an iv injection of 100 mg/kg of 14C-methanol in male Fischer-344 rats, only 57% of the dose was eliminated from the body.

"From the data of Dorman et al. (1994) and Medinsky et al. (1997), it can further be calculated that 48 h following the start of a 2-h inhalation exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys, only 23% of the absorbed 14C-methanol was eliminated from the body.

"These findings are corroborated by the data of Heck et al. (1983) showing that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h postexposure."

"Exposure to methanol also results from the consumption of certain foodstuffs (fruits, fruit juices, certain vegetables, aspartame sweetener, roasted coffee, honey) and alcoholic beverages (Health Effects Institute, 1987; Jacobsen et al., 1988)."

"However, the severe toxic effects are usually associated with the production and accumulation of formic acid, which causes metabolic acidosis and visual impairment that can lead to blindness and death at blood concentrations of methanol above 31 mmol/l (Røe, 1982; Tephly and McMartin, 1984; U.S. DHHS, 1993).

Although the acute toxic effects of methanol in humans are well documented, little is known about the chronic effects of low exposure doses, which are of interest in view of the potential use of methanol as an engine fuel and current use as a solvent and chemical intermediate.

Gestational exposure studies in pregnant rodents (mice and rats) have also shown that high methanol inhalation exposures (5000 or 10,000 ppm and more, 7 h/day during days 6 or 7 to 15 of gestation) can induce birth defects (Bolon et al., 1993; IPCS, 1997; Nelson et al., 1985)."

"The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h."

"Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules..."

"Animal studies have reported that systemic methanol is eliminated mainly by metabolism (70 to 97% of absorbed dose) and only a small fraction is eliminated as unchanged methanol in urine and in the expired air (< 3-4%) (Dorman et al., 1994; Horton et al., 1992).

Systemic methanol is extensively metabolized by liver alcohol dehydrogenase and catalase-peroxidase enzymes to formaldehyde, which is in turn rapidly oxidized to formic acid by formaldehyde dehydrogenase enzymes (Goodman and Tephly, 1968; Heck et al., 1983; Røe, 1982; Tephly and McMartin, 1984).

Under physiological conditions, formic acid dissociates to formate and hydrogen ions.

Current evidence indicates that, in rodents, methanol is converted mainly by the catalase-peroxidase system whereas monkeys and humans metabolize methanol mainly through the alcohol dehydrogenase system (Goodman and Tephly, 1968; Tephly and McMartin, 1984).

Formaldehyde, as it is highly reactive, forms relatively stable adducts with cellular constituents (Heck et al., 1983; Røe, 1982)."

"The whole body loads of methanol, formaldehyde, formate, and unobserved by-products of formaldehyde metabolism were followed.

"Since methanol distributes quite evenly in the total body water, detailed compartmental representation of body tissue loads was not deemed necessary."

"According to model predictions, congruent with the data in the literature (Dorman et al., 1994; Horton et al., 1992), a certain fraction of formaldehyde is readily oxidized to formate, a major fraction of which is rapidly converted to CO2 and exhaled, whereas a small fraction is excreted as formic acid in urine.

However, fits to the available data in rats and monkeys of Horton et al. (1992) and Dorman et al. (1994) show that, once formed, a substantial fraction of formaldehyde is converted to unobserved forms.

This pathway contributes to a long-term unobserved compartment.

The latter, most plausibly, represents either the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules (Heck et al., 1983; Røe, 1982) or is incorporated in the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of a number of synthetic pathways (Røe, 1982; Tephly and McMartin, 1984).

That substantial amounts of methanol metabolites or by-products are retained for a long time is verified by Horton et al. (1992) who estimated that 18 h following an iv injection of 100 mg/kg of 14C-methanol in male Fischer-344 rats, only 57% of the dose was eliminated from the body.

From the data of Dorman et al. (1994) and Medinsky et al. (1997), it can further be calculated that 48 h following the start of a 2-h inhalation exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys, only 23% of the absorbed 14C-methanol was eliminated from the body.

These findings are corroborated by the data of Heck et al. (1983) showing that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h post-exposure.

In the present study, the model proposed rests on acute exposure data, where the time profiles of methanol and its metabolites were determined only over short time periods (a maximum of 6 h of exposure and a maximum of 48 h post-exposure).

This does not allow observation of the slow release from the long-term components.

It is to be noted that most of the published studies on the detailed disposition kinetics of methanol regard controlled short-term (iv injection or continuous inhalation exposure over a few hours) methanol exposures in rats, primates, and humans (Batterman et al., 1998; Damian and Raabe, 1996; Dorman et al., 1994; Ferry et al., 1980; Fisher et al., 2000; Franzblau et al., 1995; Horton et al., 1992; Jacobsen et al., 1988; Osterloh et al., 1996; Pollack et al., 1993; Sedivec et al., 1981; Ward et al., 1995; Ward and Pollack, 1996).

Experimental studies on the detailed time profiles following controlled repeated exposures to methanol are lacking."

"Thus, in monkeys and plausibly humans, a much larger fraction of body formaldehyde is rapidly converted to unobserved forms rather than passed on to formate and eventually CO2."

"However, the volume of distribution of formate was larger than that of methanol, which strongly suggests that formate distributes in body constituents other than water, such as proteins.

The closeness of our simulations to the available experimental data on the time course of formate blood concentrations is consistent with the volume of distribution concept (i.e., rapid exchanges between the nonblood pool of formate and blood formate)."

"Also, background concentrations of formate are subject to wide interindividual variations (Baumann and Angerer, 1979; D'Alessandro et al., 1994; Franzblau et al., 1995; Heinrich and Angerer, 1982; Lee et al., 1992; Osterloh et al., 1996; Sedivec et al., 1981)."

http://www.toxsci.oupjournals.org/cgi/content/full/64/2/169

Toxicological Sciences 64, 169-184 (2001)
Copyright (c) 2001 by the Society of Toxicology

BIOTRANSFORMATION AND TOXICOKINETIC

A Biologically Based Dynamic Model for Predicting the Disposition of Methanol and Its Metabolites in Animals and Humans

Michèle Bouchard *, #,1, bouchmic@magellan.umontreal.ca

Robert C. Brunet, # brunet@dms.umontreal.ca

Pierre-Olivier Droz, #

and Gaétan Carrier* gaetan.carrier@umontreal.ca

* Department of Environmental and Occupational Health, Faculty of Medicine, Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec, Canada, H3C 3J7

# Institut Universitaire romand de Santé au Travail, rue du Bugnon 19, CH-1005, Lausanne, Switzerland, and

# Département de Mathématiques et de Statistique and Centre de Recherches Mathématiques, Faculté des arts et des sciences, Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec, Canada, H3C 3J7

NOTES

  1. To whom correspondence should be addressed at Département de santé environnementale et santé au travail, Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec, H3C 3J7, Canada. Fax: (514) 343-2200.
    E-mail: bouchmic@magellan.umontreal.ca

Received May 10, 2001; accepted August 28, 2001

ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHOD AND MODEL PRESENTATION
RESULTS
DISCUSSION
APPENDIX
REFERENCES

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http://groups.yahoo.com/group/aspartameNM/message/1145
EPA Preliminary Remedial Goals (PRG) 2003 Oct, air and tap water -- methanol, formaldehyde, formic acid -- sources omitted are methanol from aspartame, dark wines and liquors, fruit pectins: Murray 2005.01.18

[Introductory summary by Rich Murray: They gave the same data on 2004.10.27. I have put the data for methanol, formaldehyde, and formic acid together in this plain text version, since oral ingestion of methanol, whether from the 11% methanol component of aspartame, or the similar level of methanol impurity in dark wines and liquors, about one part in ten thousand, inevitably leads to full absorption in the human GI tract. Some is excreted, but most is largely converted into formaldehyde, and thence largely converted into formic acid -- both potent, cumulative toxins that affect all cells and tissues.

Very large amounts of methanol are released by bacterial degradation of pectins from fruits and vegetables in the human colon:

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

So, the key fact here is the RfDo, a lifetime safe level for daily ingested oral exposure, which for these three chemicals are:

0.5 mg, 0.15 mg, and 2 mg per kg per day, which for a smallish adult of 60 kg, is 30 mg, 9 mg, and 120 mg daily for methanol, formaldehyde, formic acid.

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame (methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

http://groups.yahoo.com/group/aspartameNM/message/1108
Faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland, abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde, lipid peroxidation, green tea, aging, Lyme disease: Murray 2004.08.08

The moderated newsgroup, bionet.toxicology , has accepted 31 of my long reviews since March 24 2004:

Dr. Charles "Chuck" A. Miller III rellim@tulane.edu
Associate Professor of Environmental Health Sciences
374 Johnston Building, SL29
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Avenue
New Orleans, LA 70112
(504)585-6942
Bionet.toxicology news group http://www.bio.net/hypermail/toxicol/current

[NutraSweet, Equal, Canderel, Benevia, E951]

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

A very detailed, highly credible account of the dubious approval process for aspartame in July, 1981 is part of the just released two-hour documentary "Sweet Misery, A Poisoned World: An Industry Case Study of a Food Supply In Crisis" by Cori Brackett:
cori@soundandfuryproductions.com
http://www.soundandfuryproductions.com
520-624-9710
2301 East Broadway, Suite 111
Tucson, AZ 85719

http://www.HolisticMed.com/aspartame mgold@holisticmed.com
Aspartame Toxicity Information Center Mark D. Gold also Co-Moderator
12 East Side Drive #2-18 Concord, NH 03301 603-225-2110

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

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

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

http://www.sweetpoison.com
Janet Starr Hull, PhD, CN
jshull@sweetpoison.com

http://groups.yahoo.com/group/aspartameNM/message/1092
Janet Starr Hull, who also had Graves disease in 1991, told Justin Dumais to quit aspartame: Murray 2004.06.12

http://groups.yahoo.com/group/aspartameNM/message/1131
Genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text, Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray 2004.11.06

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http://groups.yahoo.com/group/aspartameNM/message/1123
Genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor; sucralose, cyclamate, saccharin bad: Sasaki YF, Aug, Dec 2002: Rencuzogullari E et al, Aug 2004: Murray 2003.01.27, 2004.10.17

"However, it must be taken into account that ASP induced the CA and micronuclei formation in a dose-dependent manner.

It is not possible to conclude that ASP is safe according to these results.

Therefore, it is necessary to be careful when using it in food and beverages as a sweetener."

Drug Chem Toxicol. 2004 Aug; 27(3): 257-68.
Genotoxicity of aspartame. reyyup@mail.cu.edu.tr
Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler SB. Biology Department, Faculty of Arts and Sciences, Natural and Applied Sciences Institute, Cukurova University, Adana, Turkey.

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http://groups.yahoo.com/group/aspartameNM/message/1088
Murray, full plain text & critique:
Chronic aspartame in rats affects memory, brain cholinergic receptors, and brain chemistry, Christian B, McConnaughey M et al, 2004 May: 2004.06.05
Pharmacol Biochem Behav. 2004 May; 78(1): 121-7.
Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na(+),K(+)-ATPase in rats.
Christian B, McConnaughey K, Bethea E, Brantley S, Coffey A, Hammond L, Harrell S, Metcalf K, Muehlenbein D, Spruill W, Brinson L, McConnaughey M.
Department of Pharmacology, Brody School of Medicine
East Carolina University
Greenville, NC 27858, USA
North Carolina School of Science and Mathematics, Durham, NC 27811.
http://www.ecu.edu/pharmacology/faculty/mcconnaughey.html
Mona M. McConnaughey, Ph.D. Research Assistant Professor
Department: PHARMACOLOGY & TOXICOLOGY
Office: Brody Medical Science 6E-120A 252-744-2756
MCCONNAUGHEYM@mail.ecu.edu

This study demonstrated that chronic aspartame consumption in rats can lead to altered T-maze performance and increased muscarinic cholinergic receptor densities in certain brain regions.

Control and treated rats were trained in a T-maze to a particular side and then periodically tested to see how well they retained the learned response.

Rats that had received aspartame (250 mg/kg/day) in the drinking water for 3 or 4 months showed a significant increase in time to reach the reward in the T-maze, suggesting a possible effect on memory due to the artificial sweetener.

Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label muscarinic cholinergic receptors and atropine (10(-6) M) to determine nonspecific binding in whole-brain preparations, aspartame-treated rats showed a 31% increase in receptor numbers when compared to controls.

In aspartame-treated rats, there was a significant increase in muscarinic receptor densities in the frontal cortex, midcortex, posterior cortex, hippocampus, hypothalamus and cerebellum of 80%, 60%, 61%, 65%, 66% and 60%, respectively.

The midbrain was the only area where preparations from aspartame-treated rats showed a significant increase in Na(+),K(+)-ATPase activity.

It can be concluded from these data that long-term consumption of aspartame can affect T-maze performance in rats and alter receptor densities or enzymes in brain. PMID: 15159141

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http://groups.yahoo.com/group/aspartameNM/message/1067
Eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV Belsito, Nov 2003: Murray 3.30.4 [150 KB]

[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, degradation by bacteria in the colon of pectins from fruits and vegetables]

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.)]

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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 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.