methanol (11% of aspartame), made by body into formaldehyde in many vulnerable tissues, causes modern diseases of civilization, summary of a century of research, Woodrow C Monte PhD, Medical Hypotheses journal: Rich Murray 2009.11.15
- methanol (11% of aspartame), made by body into formaldehyde in many
vulnerable tissues, causes modern diseases of civilization, summary of a
century of research, Woodrow C Monte PhD, Medical Hypotheses journal: Rich
Sunday, November 15, 2009
Methanol: A Chemical Trojan Horse as the Root of the Inscrutable U
Prepublication Copy; Medical Hypotheses -- 06 November 2009
Woodrow C. Monte PhD
Professor of Food Science (retired)
Arizona State University
corresponding author : Woodrow C. Monte PhD
470 South Rainbow Drive
Page, Arizona 86040
food epidemiology; diseases of civilization; methanol; formaldehyde;
aspartame; autism; multiple sclerosis; Alzheimer's; U-shaped curve.
Until 200 years ago, methanol was an extremely rare component of
the human diet and is still rarely consumed in contemporary hunter
and gatherer cultures.
With the invention of canning in the 1800s, canned and bottled
fruits and vegetables, whose methanol content greatly exceeds that
of' their fresh counterparts, became far more prevalent.
The recent dietary introduction of aspartame, an artificial sweetener,
11% methanol by weight, has also greatly increased methanol
Moreover, methanol is a major component of cigarette smoke,
known to be a causative agent of many diseases of civilization
Conversion to formaldehyde in organs other than the liver is
the principal means by which methanol may cause disease.
The known sites of class I alcohol dehydrogenase (ADH I),
the only human enzyme capable of metabolizing methanol to
formaldehyde, correspond to the sites of origin for many DOC.
Variability in sensitivity to exogenous methanol consumption may be
accounted for in part by the presence of aldehyde dehydrogenase
sufficient to reduce the toxic effect of formaldehyde production
in tissue through its conversion to the much less toxic formic acid.
The consumption or endogenous production of small amounts of
ethanol, which acts as a competitive inhibitor of methanol's
conversion to formaldehyde by ADH I, may afford some individuals
protection from DOC.
[ ----- Original Message -----
From: Woodrow Monte
To: rmforall@... ; mgold@...
Sent: Saturday, November 14, 2009 9:22 AM
Subject: Hi Rich Murray and Mark Gold from Woodrow Monte
Richard and Mark:
I hope all is well with you both.
I finally had the chance to put exactly what I have been thinking
relative to methanol and its relationship to formaldehyde and
formate [formic acid] into an article. The paper was accepted by the
journal Medical Hypothesis and is now on Pub Med in prepublication
corrected proof form.
I have attached the pre-publication copy of the article.
The quote that follows is what the journal says that I can do with
"the right to post a pre-print version of the journal article on
Internet web sites including electronic pre-print servers, and
to retain indefinitely such version on such servers or sites."
Please email me with any questions.
As you will see I have no faith in Formate or Formic Acid as
being the toxic agent for methanol.
The devil is in the aldehyde. [ Formaldehyde ]
Thanks for all your support in the past.
The quest for a small molecule as an etiological cause of the diseases
of civilization has always ignored one of its smallest and most stealthy
agents: methanol -- a molecule capable of effortless perivascular
A rare component of unprocessed food, methanol has increased
incrementally in the human diet since the advent of commercialized
canning in the 1800s and most recently due to the popularity of
products sweetened with aspartame.
Although the extreme sensitivity of humans to methanol is well
established, its conversion to formaldehyde in situ within the vessels
of the brain and elsewhere is undetectable, making methanol placed
formaldehyde a paradigm of toxicity that is as compelling in theory
as it is difficult in practice to study.
The methanol toxicity literature of the last forty years has been
overwhelmingly in favor of a benign role for environmental dosages
Drawing on scant evidence from arguably inadequate animal models,
this research denies any significant link to formaldehyde, pointing
instead to a considerably less toxic and considerably more detectable
secondary metabolite -- formate. [formic acid]
Not insignificantly, much of the funding for such studies comes from
sources with a vested interest in maintaining public confidence in the
dietary safety of methanol.
The fact remains, however, that environmental methanol in humans
allows formaldehyde greater access to regions of the body prone to
disease, exposing vulnerable protein and DNA to methylation and
other modifications capable of inducing carcinogenicity,
mutagenicity, teratogenicity, and direct macrophage phagocytosis.
Given its many harmful effects, the potentially critical role of dietary
methanol in the increasing incidence of diseases of civilization needs
to be reexamined.
Formaldehyde produced from dietary and environmental methanol
metabolized in situ at the non-hepatic sites of class I alcohol
dehydrogenase (ADH I) may play a role in many diseases of
Ethanol may in turn act as a competitive inhibitor of methanol's
conversion to formaldehyde by ADH I, as reflected in the
U-shaped curve of alcohol consumption.
July 24, 1981, should be a significant date for scientists investigating
worldwide epidemics of Alzheimer's disease (AD),[#540],[#533]
multiple sclerosis (MS),[#77],[#214] atherosclerotic cardiovascular
disease (ACD),[#532] lupus,[#536] skin[#95] and breast cancer,
[#250],[#193] autism,[#525] and other diseases of civilization
On this date the U.S. Food and Drug Administration approved the
use of aspartame,[#472] a new artificial sweetener.[#473]
As aspartame eventually became a major source of methanol in the
civilized human diet,[#1] the incidence of DOC gradually began to
Rarely found in nature and an insignificant component of the diets of
Pleistocene man and present-day foragers, methanol has been
increasing incrementally in the diet of civilized humanity since 1806
when Nicolas Appert commercialized canning, a process that traps
methanol derived from the heating and storage of plant materials
In addition to aspartame, and canned vegetables, fruits, and their
juices,[#28],[#29] a major source of the methanol
entering the modern civilized human body is cigarette smoke,[#62]
causatively linked to atherosclerosis, multiple sclerosis,[#68]
lupus,[#73] Alzheimer's disease,[#535] rheumatoid arthritis,[#332]
and other DOC.[#345]
A poison to which humans are particularly sensitive,[#3] methanol
was responsible for the loss of hundreds of lives at the beginning of
the twentieth century[#17] when extensive animal testing determined
it was safer than ethanol, allowing its first use in foods and
Because the toxicity of methanol in the human system cannot be
properly tested in animals, the results of this research were specious.
Searching for the cause of the metabolic anomaly that makes the
human relationship to methanol distinct from all laboratory animal
models, including primates,[#116] has always been muddied by
industrial agendas[#39] with a vested interest in proving that the
formaldehyde produced from methanol in the human body does no
The prevalence of compromised literature and the lack of an
applicable animal model may explain why methanol, which fits many
of the criteria of availability and stealth that one would expect of a
usual suspect, has not yet caught the attention of scientists searching
for the elusive etiologic agent of DOC.
The single article that posits methanol as the possible direct cause of
multiple sclerosis[#8] is never cited in the MS literature.
A recent series of comprehensive in-vitro studies has also
convincingly linked Alzheimer's disease to very low concentrations of
This research mentions methanol as a possible invivo source,[#234],
[#235] but significantly, it neglects to stress the fact that there is no
simpler way for formaldehyde to get past the blood brain barrier
than in the form of this smallest of alcohols.[#367]
Methanol is itself harmless but is a Trojan horse for formaldehyde,
a chemical that can pose a severe risk to humans,[#7] who appear
to be the only mammal exclusively endowed with a hepatic catalase
enzyme incapable of removing dietary methanol before it can enter
the general circulation.[#52]
Once methanol runs the gauntlet of first-pass metabolism, its
detoxification is no longer exclusive to the liver.
Formaldehyde, the first metabolite of methanol, can then be
produced within the arteries and veins,[#220] heart,[#503]
brain,[#218] lungs,[#221] breast,[#358] bone,[#503]
These major organs harbor extra hepatic sites of the only remaining
human enzyme capable of metabolizing methanol,
class I alcohol dehydrogenase (ADH I).[#112]
Methanol transports its potential to become formaldehyde past
normal biological barriers in the brain and elsewhere that
environmental formaldehyde itself cannot usually penetrate.[#122]
That formaldehyde produced in these organs from methanol has
not been detected directly in humans should not be surprising since
formaldehyde vanishes within minutes, binding to
macromolecules[#114] even when a solution of it is injected directly
into tissue[#122] or spiked into cell-free human serum.[#236]
Although methylation caused by this toxic process could be
functionally destructive to the macromolecule so modified, the
addition of methyl groups to large molecules renders the modification
and its source invisible to any clinical or histological testing
However, in a study by Trocho et al., a portion of the C14 labeled
methanol moiety of aspartame was shown to bind to such
macromolecules via formaldehyde and not pass directly into the
one-carbon cycle via formate as predicted by the generally accepted
model of methanol toxicity,[#40] a model developed from studying
the severe methanol poisoning of monkeys, not the chronic
environmental exposure of humans.
Formate derived from methanol metabolism is never measurable in
human blood when small environmentally reflective doses of methanol
During acute methanol poisoning, where the methanol concentration
of the portal vein far exceeds that of ethanol, liver ADH I would be
saturated with methanol.
The liver's ample supply of aldehyde dehydrogenase would assure
production of formic acid, which is metabolized very slowly,
causing leakage of formate into the general circulation.
Formate is not, however, a significant poison to humans and has,
in fact, been used therapeutically and as a food additive.[#365]
It certainly would be more convenient to have a stable, measurable
entity such as formate to predict the danger of exposure to methanol,
but an iron-clad case for the toxicological significance of this much
less toxic, secondary metabolite has not yet been made.[#55]
Moreover, the results of Trocho's elegant study should give one
pause before accepting the widely held premise that formate and
not formaldehyde is the toxic component of methanol poisoning.
Laboratories that publish the most cited works are often financially
supported by industries with much to lose were the safety of methanol
This research must be carefully reconsidered before we can dismiss
the potential threat posed by formaldehyde strategically placed by
Formaldehyde produced within the cell immediately reacts with water
to produce formal hydrate,[#27] a strong acid[#114] with twice the
number of available hydrogen ions as the next methanol metabolite,
Formal hydrate produced from methanol by the ADH I sites found in
the intima, media, and adventitia lining of the circulatory system of the
heart and brain[#220] would be expected to diffuse into the localized
tissue, quickly methylating basic molecules such as myelin basic
protein (MS)[#224] and tau protein (Alzheimer's).[#234]
Such changes have been shown in these disease states.
Formaldehyde, also known to uncouple oxidative phosphorylation
and inhibit phosphorylation within cells,[#113] could contribute to
these changes reported in MS[#224] and Alzheimer's.[#506]
The immune system reacts swiftly to methylation of protein by
formaldehyde -- a phenomenon put to good use by the vaccine
industry for the last hundred years.[#26]
Macrophages have activation sites specifically for formaldehyde
modified protein[#23] and are well known to have a ravenous
appetite for LDLs reacted with small aldehydes.[#507]
This induces the esterification of phagocytized LDL cholesterol and
the subsequent transformation of the macrophages to
foam cells,[#508] similar to the sequence of events leading to
atheroma production adjacent to the intima layer of the human aorta,
rich in ADH I.[#220]
The potential for antibody production against methylated self-protein
phagocytized by macrophages has never been investigated.
Ethanol in low concentrations acts as a powerful competitive
inhibitor[#439] with a 16:1 preference for ethanol to acetaldehyde
over the conversion of methanol of formaldehyde by ADH I.[#389]
For this reason, ethanol is used, without FDA approval, as the
preferred antidote for accidental methanol poisoning in emergency
rooms throughout the world.[#253]
Very low levels of ethanol in the bloodstream would substantively
prevent all formaldehyde production from dietary methanol
anywhere in the body.
Protection from formaldehyde production may account for the yet
unexplained dose region of apparent improvement in the
U-shaped curve of alcohol consumption.
Epidemiologic studies show moderate consumption of alcohol is
associated with a reduced risk of myocardial infarction,[#485]
dementia,[#534] lupus,[#73] and other DOC.
Low doses of ethanol appear to provide a preventative measure
against the causes of DOC.[#279]
Recent studies of individuals who consumed at least one alcoholic
drink per day show subjects had an additional 86 percent
reduction in risk of myocardial infarction if they were genetically
endowed with a genotype of ADH I that was 2.5 times slower to
metabolize ethanol than the control
These findings were "consistent with the hypothesis that a slower
rate of clearance of alcohol enhances the beneficial effect of
moderate alcohol consumption on the risk of cardiovascular
A compelling explanation of the dose region of adverse effects of
the U-shaped curve with high ethanol consumption, which shows
increased risk of these same diseases, could be the mechanism by
which humans habituate to high consumption of ethanol.
The induction of the P450 hepatic microsomal ethanol oxidizing
system[#175] results in a considerably higher clearance rate of
ethanol from the bloodstream for an extended period of time, thus
accounting for more consumption leading to statistically less time
Small amounts of supplemental alcohol not sufficient to induce
P450 might be expected to prolong the residence time and avoid
gaps in the protection afforded by ethanol in preventing methanol
It appears that the average person, whether or not an imbiber,
may typically have endogenous ethanol in the blood[#174]
produced by gut fermentation.[#363]
This ethanol must pass through the liver via the hepatic portal vein
coincidently with dietary methanol absorbed from the gut contents.
The liver has the highest concentration of ADH I in the body.
Even traces of ethanol in the blood, however, would seem to
indicate the absence of available sites remaining for the oxidation
of the much less competitive methanol, allowing most dietary
methanol to pass freely into the general circulation.
What follows is a biochemical game of musical chairs as methanol
travels round and round the circulation, waiting for the ethanol levels
to reach zero and the music to stop.
The closest ADH I free to service the methanol will convert it to
formaldehyde. If this happens in the liver, where there are ample
supplies of aldehyde dehydrogenase, metabolism to carbon dioxide
will proceed safely.
In mammary epithelium, however,
where human class I alcohol dehydrogenase is highly expressed[#358]
but active aldehyde dehydrogenase[#216] is scarce, methanol placed
formaldehyde could become a problem.
Formaldehyde is a class I carcinogen[#11] and mutagen[#449]
with methanol providing its only easy avenue into this tissue.
In the vasculature of the brain[#218] and other ADH I positive
organs, the consequences may be similarly troublesome.
The obvious way to prevent formaldehyde from damaging this
sensitive tissue is to keep the music playing, a solution dependent
on our ability to answer the following questions:
Just how much ethanol is essential in this seemingly inscrutable
What measures should we take to combat this chemical Trojan horse,
thereby reducing the methanol contamination in the diet of civilization
and making it more like the diet of our ancient ancestors?
Both research areas present intriguing inquiries, but as a food
scientist, I would stress the relative ease and greater benefits of
investigating the latter.
Proposed test of the hypothesis:
Under strict medical supervision this hypothesis would best be tested
on experimental subjects suffering from relapsing multiple sclerosis.
Without here getting into great detail, the preferred mode of
administration of small amounts of ethanol would be via gaseous
administration at sufficient, carefully controlled, atmospheric
concentration to maintain a constant 1-2 parts per million ethanol
concentrations in the test subjects bloodstream.
At such low levels, well below the ambient concentrations of ethanol
in the average pub environment, ethanol is quite safe and not
detectable in the air via the olfactory system of most people.
A water vaporization control would work well and be conducive to
a double blind study.
Vaporous administration of ethanol is well covered in the literature,
and is used frequently to induce alcohol intoxication of test animals
for toxicity testing purposes.
1. Monte WC.
Aspartame; Methanol and the Public Health.
Journal of Applied Nutrition 1984;36(1):42-58.
3. Roe O.
Methanol Poisoning Its clinical course pathogenesis and treatment.
Acta Medica Scandinavica 1946;126:1-252.
7. Trocho C, Pardo R, Fafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, et al.
Formaldehyde derived from dietary aspartame
binds to tissue components in vivo.
Life Sci 1988;63(5):337-49.
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22 ]
8. Henzi H.
Chronic Methanol Poisoning with the Clinical and
Pathologic-Anatomical Features of Multiple Sclerosis
Med Hypothesis 1984;13:63-75.
11. Rousseau M, Straif K, Siemiatycki J.
IARC Carcinogen Update (Formaldehyde now Class 1
Environmental Health Perspectives 2005;113(9):A580.
17. Wimer W, Russell J, Kaplan H.
Southwest Research Institute
San Antonio TX: Noyes Data Corporation.; 1983.
18. Gaul H, Wallace C, Auer R.
MR findings in methanol intoxication.
Am J Neuroradiol 1995;16:1783-6.
26. Metz B, Jiskoot W, Hennink W, Crommelin D, Kersten G.
Physicochemical and immunochemical techniques predict the
quality of diphtheria toxoid vaccines.
27. Means G, Feeney R.
Chemical Modification of Proteins.
Francisco, CA.: Holden-Day, Inc; 1971.
28. Kirchner J, Miller J.
Volatile Water-Soluble and Oil Constituents of Valencia
Agricultural and Food Chemistry 1957;5(4):283.
29. Lund E, Kirkland C, Shaw P.
Methanol. Ethanol. and Acetaldehyde Contents of Citrus Products.
Agricultural and Food Chemistry 1981;29:361.
39. Gordon G.
NutraSweet Questions Swirl
(How Sweet It Isn't -- a UPI Investigative Report ).
Seattle Times. Seattle, Wash. Oct 13, 1987. p. F1:
United Press International; 1987.
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon,
UPI reporter: Murray 2000.07.10 ]
40. Tephly T.
Comments on the purported generation of formaldehyde from
the sweetener aspartame [letter: not peer-reviewed].
Life Sci 1999;65:157-60.
42. Heinzow B.
Formic acid in urine -- a significant parameter in environmental
Zentralbl Hyg Umweltmed 1992;192(5):455-61.
52. Roe O.
Species Differences in Methanol Poisoning.
I. Minimal Lethal Doses. Symptoms. and
Toxic Sequelae of Methanol Poisoning in Humans
and Experimental Animals.
CRC Critical Reviews in Toxicology 1982;18:376-90.
55. Smith E, Taylor R.
Acute Toxicity of Methanol in the Folate-Deficient Acatalasemic
62. Neuberg C, Kobel M.
Uber die encymatische Abspaltung von Methylalkohol aus Pektin
durch ein Ferment dis Tabaks.
Zeitschrift Für Lebensmitteluntersuchung Und -Forschung A
68. Hernan M, Jick S, Logroscino G, Olek M, Ascherio A,
Cigarette smoking and the progression of multiple sclerosis.
73. Hardy C, Palmer B, Muir K, Sutton A, Powell R.
Smoking history. alcohol consumption. and systemic lupus
erythematosus: a case-control study.
Ann Rheum Dis 1998;57:451-5.
77. Hirtz D, Thurman D, Gwinn-Hardy K, Mohamed M,
Chaudhuri A, Zalutsky R.
How common are the "common" neurologic disorders?
95. Christenson L, Borrowman T, Vachon C, Tollefson M,
Otley C, Weaver A, et al.
Incidence of Basal Cell and Squamous Cell Carcinomas
in a Population Younger Than 40 Years.
112. Kini M, Cooper J.
Biochemistry of Methanol Poisoning-III;
The Enzymic Pathway for the Conversion of Methanol to
Biochemical Pharmacology 1961;8:207.
113. Kini M, Cooper J.
Biochemistry of Methanol Poisoning;
The Effect of Methanol and its Metabolites on Retinal Metabolism.
Biochemical Journal 1962;82:164.
114. French D, Edsall J.
The Reactions of Formaldehyde with Amino Acids and Proteins.
Adv.Protein Chem 1945;2:277.
116. Cooper J, Kini M.
Biochemical Aspects of methanol Poisoning.
Biochemical Pharmacology 1962;11:405
121. Tephly T, McMartin K.
Methanol metabolism and toxicity.
In: Stegink L, Filer L, editors.
Aspartame: Physiology and Biochemistry.
New York: Marcel Dekker Inc.; 1984. p. 111-40.
122. von Oettingen W.
The Aliphatic Alcohols Their Toxicity and Potential Dangers in
Relation to Their Chemical Constitution and Their Fate in
Public Health Bulletin 1943;281:8.
165. Wood C.
Death and Blindness as a Result of Poisoning by Methyl Alcohol
or Wood Alcohol and Its Various Preparations.
International Clinics; A Quarterly of Clinical Lectures 1906;16:68.
174. Lester D.
The Concentration of Apparent Endogenous Ethanol.
Q J StudAlcohol 1962;23:17.
175. Lieber C, DeCarli L.
Hepatic Microsomal Ethanol-Oxidizing System. In vitro
characteristics and adaptive properties in vivo.
The Journal of Biological Chemistry 1970;245(10):2505-12.
193. Kingsbury K.
The Changing Face Of Breast Cancer.
TIME Magazine 2007;107(16):36.
214. Redelings M, McCoy L, Sorvillo V.
Multiple Sclerosis Mortality and Patterns of Comorbidity in the
United States from 1990 to 2000.
216. Crabb D, Matsumoto M, Chang D, You M.
Overview of the role of alcohol dehydrogenase and aldehyde
dehydrogenase and their variants in the genesis of
Proceedings of the Nutrition Society 2004;63:49-63.
218. Mori O, Haseba T, Kameyama K, Shimizu H.
Histological distribution of class III alcohol dehydrogenase in
Brain Research 2000;852:186-90.
220. Allili-Hassani A, Martinez S, Peralba J.
Alcohol dehydrogenase of human and rat blood vessels.
FEBS Letters 1997;405:26-30.
221. Buehler R, Hess M, Wartburg J.
Immunohistochemical Localization of Human Liver Alcohol
Dehydrogenase in Liver Tissue. Cultured Fibroblasts and
American Association of Pathologists 1982;108(1):89-99.
224. Kim J, Mastronardi F, Wood D, Lubman D, Zand R,
Multiple Sclerosis: An important role for post-translational
modifications of myelin basic protein in pathogenesis.
Molecular & Cellular Proteomics 2003;2(7):453-62.
234. Nie C, Wei Y, Chen X, Liu Y, Dui W, Liu Y, et al.
Formaldehyde at Low Concentration Induces Protein Tau
into Globular Amyloid-Like Aggregates In Vitro and In Vivo.
PLoS ONE 2007;2(7:e629):1-13.
235. Nie C, Wang X, Liu Y, Perrett S, He R.
Amyloid-like aggregates of neuronal tau induced by formaldehyde
promote apoptosis of neuronal cells.
BMC Neuroscience 2007;8(9):1-16.
236. Köppel C, Baudisch H, Schneider V, Ibe K.
Suicidal ingestion of formalin with fatal complications.
Intensive Care Med 1990;16(3):212-4.
250. Krieger N.
Is breast cancer a disease of affluence. poverty. or both?
The case of African American women.
Am J Public Health 2002;92(4):611-13.
253. McCoy H, Cipolle R, Ehlers S, Sawchuk R, Zaske D.
Severe Methanol Poisoning: Application of a Pharmacokinetic
Model for Ethanol Therapy and Hemodialysis.
Amer J Med 1979;67:604-7.
279. Kloner R, Rezkalla S. Kloner RA. Rezkalla SH.
To drink or not to drink? That is the question.
332. Costenbader K, Karlson E.
Cigarette smoking and autoimmune disease: what can we learn
345. Wald N, Hackshaw A.
Cigarette smoking: an epidemiological overview.
Brit. Med. Bull 1996;52(1):3-11.
358. Triano E, Slusher L, Atkins T, Beneski J, Gestl S.
Class I Alcohol Dehydrogenase Is Highly Expressed in Normal
Human Mammary Epithelium but not in Invasive Breast Cancer:
Implications for Breast Carcinogenesis.
Cancer Research Arch 2003;63:3092-100.
363. Turner C, Spanel P, Smith D.
A longitudinal study of ethanol and acetaldehyde in the exhaled
breath of healthy volunteers using selected-ion flow-tube mass
Rapid Commun Mass Spectrom 2006;20:61-8.
365. Irving GW.
Evaluation of the Health Aspects of Formic Acid, Sodium Formate,
and Ethyl Formate as Food Ingredients.
Bethesda Md: Federation of American Societies for Experimental
Biology; 1974 No.: NTIS Doc PB-266 282, 1976.
(NTIS Doc PB-266 282, 1976).
367. Yant W, Schrenk H.
Distribution of methanol in dogs after inhalation and administration
by stomach tube and subcutaneously.
J Ind Hyg Toxicol 1937;19:337-45.
389. Jones A.
Elimination Half-life of Methanol During Hangover.
Pharmacology & Toxicology 1987;60:217-20.
439. Zatman L.
The Effect of Ethanol on the Metabolism of Methanol in Man.
Biochem J 1946;40:67.
449. Grafstrom R, Fornace A, Autrup H, Lechner J, Harris C.
Formaldehyde Damage to DNA and Inhibition of DNA Repair
in Human Bronchial Cells.
472. Smith R.
Aspartame Approved Despite Risks.
473. Dickson D.
Aspartame sugar substitute. New court overruled.
Nature 292:283 1981;292(July 23):283.
483. Hines LM., Meir S, Stampfer J, Jingma H, Gaziano M.
Genetic Variation in Alcohol Dehydrogenase and the Beneficial
Effect of Moderate Alcohol Consumption on Myocardial
N Engl J Med 2001;344(8):549-55.
485. Klatsky A.
Alcohol, wine, and vascular diseases -- an abundance of paradoxes.
Am J Physiol Heart Circ Physiol 2008;294:582-83.
503. Estonius M, Svensson S, Höög J.
Alcohol dehydrogenase in human tissues: localisation of transcripts
coding for five classes of the enzyme.
FEBS Lett. 1996;397:338-42.
506. Luo Y, Ingram V.
Uncoupling of mitochondria activates protein phosphatases and
inactivates MBP protein kinases.
J Alzheimers Dis 2001;3(6):593-98.
507. Kawamura M, Heinecke J, Chait A.
Increased uptake of alpha-hydroxy aldehyde-modified
low density lipoprotein by macrophage scavenger receptors.
J Lipid Res. 41(7):1054 2000;41(7):1054-59.
508. Fogelman A, Shechter I, Seager J, Hokom M, Child J,
Malondialdehyde alteration of low density lipoproteins leads to
cholesteryl ester accumulation in human monocyte-macrophages.
Proc Natl Acad Sci. 1980;77(4):2214-8.
525. Blaxill M.
What's going on? The question of time trends in autism.
Public Health 2004;119(6):536-51.
532. Yusuf S, Ounpuu S, Anand S.
The global epidemic of atherosclerotic cardiovascular disease.
Med Princ Pract 2002;11(Suppl 2):3-8.
533. Waldman M.
Are We Experiencing an Alzheimer's Epidemic?
Presentation (Abstract 90)
[AD/PD 2009: 9th International Conference on Alzheimer's
and Parkinson's Diseases:] ; 2009.
534. Sink K.
Moderate Alcohol Consumption May Lower Dementia Risk in
Cognitively Normal Elderly.
Presentation. Alzheimer's Association
2009 International Conference on Alzheimer's Disease (ICAD),
535. Mehlig K, Skoog I, Guo X, Schütze M, Gustafson D,
Waern M, et al.
Alcoholic Beverages and Incidence of Dementia: 34-Year Follow-up
of the Prospective Population Study of Women in Göteborg.
Am J Epidemiol 2008;167(6):684-91.
536. Uramoto K, Michet C, Thumboo J, Sunku J, O'Fallon W,
Trends in the incidence and mortality of systemic lupus
Arthritis Rheum 1999;42(1):46-50.
540. Casserly I, Topol E.
Convergence of atherosclerosis and Alzheimer's disease:
inflammation, cholesterol, and misfolded proteins.
old tiger roars -- Woodrow C Monte, PhD -- aspartame causes
many breast cancers, as ADH enzyme in breasts makes methanol
from diet soda into carcinogenic formaldehyde -- same in dark
wines and liquors, Fitness Life 2008 Jan.: Murray 2008.02.11
Monday, February 11, 2008
role of formaldehyde, made by body from methanol from foods
and aspartame, in steep increases in fetal alcohol syndrome,
autism, multiple sclerosis, lupus, teen suicide, breast cancer,
Nutrition Prof. Woodrow C. Monte, retired, Arizona State U.,
two reviews, 190 references supplied, Fitness Life,
New Zealand 2007 Nov, Dec: Murray 2007.12.26
Wednesday, December 26 2007
Monte WC., Is your Diet Sweetener killing you?
Fitness Life. 2007 Nov; 33: 31-33.
Monte WC., A Deadly Experiment.
Fitness Life. 2007 Dec; 34: 38-42.
Monte WC., Bittersweet: Aspartame Breast Cancer Link.
Fitness Life. 2008 Feb; 34: 21-22.
Article 1 http://www.thetruthaboutstuff.com/review1.shtml
Article 2 http://www.thetruthaboutstuff.com/review2.shtml
Article 3 http://www.thetruthaboutstuff.com/review3.shtml
223 references with abstracts or full and partial texts
Aspartame: Methanol and the Public Interest 1984: Monte:
Murray 2002.09.23 rmforall
Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science [retired 1992]
Arizona State University, Tempe, Arizona 85287
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame.
The EPA limit for water is 7.8 mg daily for methanol (wood alcohol),
a deadly cumulative poison.
Many users drink 1-2 L daily.
The reported symptoms are entirely consistent with chronic methanol
toxicity. (Fresh orange juice has 34 mg/L, but, like all juices, has 16
times more ethanol, which strongly protects against methanol.)
"The greater toxicity of methanol to man is deeply rooted in the
limited biochemical pathways available to humans for detoxification.
The loss of uricase (EC 220.127.116.11.),
formyl-tetrahydrofolate synthetase (EC 18.104.22.168.) (42)
and other enzymes (18) during evolution sets man apart from all
laboratory animals including the monkey (42).
There is no generally accepted animal model
for methanol toxicity (42, 59).
Humans suffer "toxic syndrome" (54) at a minimum lethal dose
of <1 gm/kg, much less than that of monkeys, 3-6 g/kg (42, 59).
The minimum lethal dose of methanol
in the rat, rabbit, and dog is 9.5, 7.0 , and 8.0 g/kg, respectively (43);
ethyl alcohol is more toxic than methanol to these test animals (43)."
Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:
"The United States Environmental Protection Agency in their
Multimedia Environmental Goals for Environmental Assessment
recommends a minimum acute toxicity concentration
of methanol in drinking water at 3.9 parts per million,
with a recommended limit of consumption below 7.8 mg/day (8).
This report clearly indicates that methanol:
"...is considered a cumulative poison due to the low rate of excretion
once it is absorbed. In the body, methanol is oxidized to
formaldehyde and formic acid; both of these metabolites are
Recently the toxic role of formaldehyde (in methanol toxicity) has
been questioned (34).
No skeptic can overlook the fact that, metabolically, formaldehyde
must be formed as an intermediate to formic acid production (54).
Formaldehyde has a high reactivity which may be why it has not been
found in humans or other primates during methanol poisoning (59)....
If formaldehyde is produced from methanol and does have a
reasonable half life within certain cells in the poisoned organism
he chronic toxicological ramifications could be grave.
Formaldehyde is a known carcinogen (57) producing squanous-cell
carcinomas by inhalation exposure in experimental animals (22).
The available epidemiological studies do not provide adequate data
for assessing the carcinogenicity of formaldehyde in man (22, 24, 57).
However, reaction of formaldehyde with deoxyribonucleic acid
(DNA) has resulted in irreversible denaturation that could interfere
with DNA replication and result in mutation (37)..."
It is certain that high levels of aspartame use,
above 2 liters daily for months and years,
must lead to chronic formaldehyde-formic acid toxicity.
Fully 11 % of aspartame is methanol -- 1,120 mg aspartame
in 2 L diet soda, almost six 12-oz cans, gives 123 mg methanol
(wood alcohol). The methanol is immediately released
into the body after drinking .
Within hours, the liver turns much of the methanol into formaldehyde,
and then much of that into formic acid, both of which in time
are partially eliminated as carbon dioxide and water.
However, about 30 % of the methanol remains in the body
as cumulative durable toxic metabolites of formaldehyde
and formic acid -- 37 mg daily,
a gram every month, accumulating in and affecting every tissue.
If only 10 % of the methanol is retained daily as formaldehyde,
that would give 12 mg daily formaldehyde accumulation -- about
60 times more than the 0.2 mg from 10 % retention
of the 2 mg EPA daily limit for formaldehyde in drinking water.
Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms,
starting with headache, fatigue, joint pain, irritability, memory loss,
rashes, and leading to vision and eye problems, and even seizures.
In many cases there is addiction. Probably there are immune system
disorders, with a hypersensitivity to these toxins and other chemicals.
J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70 % of the radioactive methanol in aspartame
put into the stomachs of 3 to 7 kg monkeys
was eliminated within 8 hours, with little additional elimination,
as carbon dioxide in exhaled air and as water in the urine.
They did not mention that this meant that about 30 % of the methanol
must transform into formaldehyde and then into formic acid,
both of which must remain as toxic products in all parts of the body.
They did not report any studies on the distribution of radioactivity
in body tissues, except that blood plasma proteins after 4 days
held 4 % of the initial methanol.
This study did not monitor long-term use of aspartame.
aspartame rat brain toxicity re cytochrome P450 enzymes,
especially CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al,
2006 Aug, Hum Exp Toxicol: relevant abstracts re formaldehyde
from methanol in alcohol drinks: Murray 2006.09.29
Direct and indirect cellular effects of aspartame on the brain,
Humphries P, Pretorius E, Naude H, U. Pretoria, South Africa,
Eur J Clin Nutr. 2007 Aug 8: Murray 2007.08.12
aspartame groups and books: updated research review
of 2004.07.16: Murray 2006.05.11
details on 6 epidemiological studies since 2004 on diet soda
(mainly aspartame) correlations, as well as 14 other mainstream
studies on aspartame toxicity since summer 2005:
Wednesday, November 14, 2007
older women drinking over 2 aspartame beverages daily had 30%
decline kidney function in 11 years, Nurses Health Study, Julie Lin,
Gary C Curhan, Brigham and Women's Hospital, Boston:
Rich Murray 2009.11.02
Monday, November 2, 2009
consider co-factors (methanol, formaldehyde, and protective folic
acid), re UK FSA test of aspartame in candy bars on 50 reactors,
Stephen L Atkin, Hull York Medical School:
Rich Murray 2009.09.29
Tuesday, September 29, 2009
Included herein is substantial mainstream evidence that the natural
conversion in humans of orally ingested methanol into formaldehyde
and then formic acid results in substantial, durable, cumulative
retention of toxic reaction products.
Adequate folic acid levels expedite the safe metabolism of methanol
in most people.
Ethyl alcohol and folic acid in vegetables and fruits are sufficient
to protect most people from conversion of their methanol into
Many common agents interfere with folic acid (folic acid antagonists).
Additionally, genetic variations are potent.
About 3/4 of reactors are female.
Those who rarely have alcohol hangovers may be substantially immune
to methanol and formaldehyde.
Recent exposure to alcohol beverages, tobacco and wood smoke,
and a large variety of formaldehyde sources may compromise the
clarity of aspartame reaction tests.
Aspartame reactors often report allergies to many agents, with similar
symptoms: mercury (amalgams and fish), MSG and free glutamate in
foods (for instance, hydrolyzed vegetable or yeast protein), carbon
monoxide, molds, many foods, etc. -- up to Multiple Chemical
Aspartame reactors often take many steps to exercise, reduce stress,
lower salt, emphasize organic plant foods, reduce drug and chemical
exposures, limit protein and fat intake, use vitamin and mineral
supplements, limit processed foods -- thus complicating attempts to
create a matching control group, and introducing uncertainty about
whether the reactors are as vulnerable now as in the past, when they
may have had more negative factors for years.
So, genetic background, age, sex, obesity, existing illnesses, diet,
exercise, environmental toxins, medicines and drugs, parental
exposure to all these factors, and more may corrode the "gold
standard" of a single exposure double-blind experimental test,
especially for a rather modest test group of 50.
Perhaps, a more productive research strategy would be to test 10
reactors, one at a time, for 24 hours each, using a wide range of
tests, recording the enormous individual variations that are usually
swamped by taking group data averages.
Computerized tests facilitate fast, affordable measures of cognitive
and memory effects.
Full audio and video recording is now available.
Dimethyl dicarbonate, an approved additive for reducing fungi in
wines, perhaps with a neutral taste, quickly releases about the same
level of methanol upon ingestion as aspartame drinks, making
possible studies free of any possible "excitotoxic" effects of
aspartic acid and phenylalanine, while allowing a third beverage
to be a control substance.
This approach would also contribute to the meager research literature
about the role of methanol in alcohol hangovers.
aspartame reactors may send detailed feedback to Andrew Wadge,
UK Food Standards Agency to guide new pilot study re bad
reactions: Rich Murray 2009.06.22
Monday, June 22, 2009
unexamined cofactors re folic acid antagonist research include
methanol (quickly turns into formaldehyde and then formic acid in
humans) from tobacco and wood smoke, alcohol beverages,
aspartame, demethylation of caffeine: Rich Murray
Monday, December 1, 2008
[ rearranged, 11% methanol added ]
From the Nutrasweet Web Site: (amounts in various "foods")
Product Category -- Serving Size -- aspartame -- 11% methanol
Gelatin Dessert ----------- 8 ounces -----190 mg ---- 21 mg
Carbonated Beverage --- 12 ounces ----- 180 ------- 20
" ------------------------ 48 ounces ----- 720 ------- 79
Powdered Drink -------- 12 ounces ----- 180 -------- 20
Fruit Drink (10% juice) -- 12 ounces ----- 140 -------15.4
Hot Chocolate ----------- 12 ounces ----- 100 -------11
Yogurt ------------------- 8 ounces ----- 124 --------13.6
Ice Cream ---------------- 8 ounces ----- 100 ------- 11
Pudding Dessert ---------- 8 ounces ------ 50 --------- 5.5
Frozen Novelty ----------- 2-3 ounces ---- 50 --------- 5.5
Gum ----------------------- 1 stick -------- 6-8 -------- 0.7-0.9
Vitamins ------------------ 1 vitamin ------ 4 ---------- 0.44
Breath mint ---------------- 1 mint --------- 1.5 -------- 0.17
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 2002.07.16
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center,
New York, NY
Department of Neurology newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research RLipton@...
Blumenthall & Vance: aspartame chewing gum headaches
Nov 1997: Murray 2002.07.28
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of
Medicine, Tulsa, USA. neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in
some susceptible individuals. Herein, we describe three cases of
young women with migraine who reported their headaches could be
provoked by chewing gum sweetened with aspartame.
[ 6-8 mg aspartame per stick chewing gum ]
antiseptic? antifungal? antiviral? methanol (formaldehyde, formic
acid) disposition: Bouchard M et al, full plain text, 2001:
sources are degradation of fruit pectins, liquors, aspartame, smoke:
Murray 2005.01.05 rmforall
free full text
A Biologically Based Dynamic Model for Predicting the Disposition
of Methanol and Its Metabolites in Animals and Humans.
Robert C. Brunet,
and Gaétan Carrier.
Toxicological Sciences 64, 169-184 (2001)
Copyright © 2001 by the Society of Toxicology
[ extracts ]
"Exposure to methanol also results from the consumption of certain
foodstuffs (fruits, fruit juices, certain vegetables, aspartame
sweetener, roasted coffee, honey) and alcoholic beverages (Health
Effects Institute, 1987; Jacobsen et al., 1988).
[ It's unusual for a mainstream journal article to mention "fruits,
fruit juices, certain vegetables, aspartame sweetener" and "alcoholic
beverages" to be methanol sources.]
... little is known about the chronic effects of low exposure doses...
Systemic methanol is extensively metabolized by liver alcohol
dehydrogenase [ ADH ] and catalase-peroxidase enzymes to
formaldehyde, which is in turn rapidly oxidized to formic acid by
formaldehyde dehydrogenase enzymes...
Formaldehyde, as it is highly reactive, forms relatively stable
adducts with cellular constituents...
Primates and humans appear to be more susceptible to the acute
toxicity of methanol than rodents...
Although methanol has been reported to be metabolized mainly in
the liver, pulmonary metabolism is also likely to occur. Indeed,
the catalase-peroxidase system responsible for a major fraction of
methanol metabolism in rats is widely distributed in mammalian
The model included a constant background whole body methanol
burden of 2.133 mmol, which corresponds to the mean blood
concentration of 0.5 mg/L of methanol measured by Osterloh et al.
(1996) in control subjects at the end of an 8-h frequent blood
... 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
binds to various endogenous molecules (Heck et al., 1983; Roe,
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
Experimental studies on the detailed time profiles following
controlled repeated exposures to methanol are lacking...
Thus, in monkeys and plausibly humans, a much larger fraction of
body formaldehyde is rapidly converted to unobserved forms
rather than passed on to formate and eventually CO2."
If we assume 30% retention of durable cumulative toxic products of
formaldehyde and formic acid, then a 12-oz can diet drink gives 200
mg aspartame, 22 mg methanol, and 7 mg formaldehyde and formic
acid at 30% cumulative retention. We may add that well known
sources of formaldehyde include both wood and tobacco smoke,
and, notoriously, mobile homes. Two teams give evidence that
formaldehyde and formic acid from methanol in ethanol drinks
(often far above the 100 mg/L methanol in red wines, two times the
level in aspartame drinks) are the main cause of the many symptoms
of "morning after" hangovers.
folic acid prevents neurotoxicity from formic acid, made by body
from methanol impurity in alcohol drinks [ also 11 % of aspartame ],
BM Kapur, PL Carlen, DC Lehotay, AC Vandenbroucke,
Y Adamchik, U. of Toronto, 2007 Dec., Alcoholism Cl. Exp. Res.:
Furthermore, BM Kapur et al, 2007 give evidence that formic acid
from methanol in ethanol drinks is a major cause of Fetal Alcohol
Syndrome, readily preventable by adequate levels of folic acid,
which expedites the safe metabolism of formaldehyde, in most
"Methanol is endogenously formed in the brain and is present as a
congener in most alcoholic beverages.
Because ethanol is preferentially metabolized over methanol
(MeOH) by alcohol dehydrogenase, it is not surprising that
MeOH accumulates in the alcohol-abusing population.
This suggests that the alcohol-drinking population will have higher
levels of MeOH's neurotoxic metabolite, formic acid (FA).
FA elimination is mediated by folic acid.
Neurotoxicity is a common result of chronic alcoholism.
This study shows for the first time that FA, found in chronic
alcoholics, is neurotoxic and this toxicity can be .mitigated by
folic acid administration." ...
"MeOH concentrations between 4 and 4500 mg/l can be present
in various alcoholic beverages (Sprung et al., 1988)."
A variety of mutations, as well as aspirin and many painkillers,
impede folic acid. However, fruits and vegetables give enough folic
acid to mitigate harm from their methanol. Then again, formaldehyde
may in many people treat infections by fungi, bacteria, and virusus.
All these unexamined co-factors have confused attempts to study
aspartame toxicity for three decades.
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, over 100,000 for decades.
details on 6 epidemiological studies since 2004 on diet soda
(mainly aspartame) correlations, as well as 14 other mainstream
studies on aspartame toxicity since summer 2005:
A widely proclaimed NIH-AARP mass survey by U Lim et al. 2006,
while failing to show specific cancers with feeble diet drink
consumption data for a year for seniors, did find that 4% of a
half-million seniors drank 3 and more cans daily diet soda
[ 12-oz can gives 200 mg aspartame, 22 mg methanol,
7 mg formaldehyde and formic acid at 30% cumulative retention ]
0 ---- under 100 - 100-200 - 200-400 - 400-600 - 600-1200 -
46 ------- 25 ------ 13 ------- 7 --------- 5 ------ about 3 ----
over 1200 mg/d
This is the first good data about the percentage of aspartame users
who use over 3 cans daily, averaging 5 cans daily at 200 mg per 12
oz can diet soda.
About 4% of 473,984 is 19,000 people, with a peak intake of 17
cans daily, and average 5 cans daily.
It would be worthwhile to investigate a wide variety of symptoms for
the 0.1 % of highest level users, about 500 people.
For about 200 million USA aspartame users, this would be 200,000
The highest level 3400 mg aspartame [ 17 12-oz cans ] gives
11% = 374 mg methanol, 48 times the recommended daily limit of
consumption of 7.8 mg as recommended by the
Environmental Protection Agency (EPA).3
At 30% retention of cumulative toxic products of formaldehyde and
formic acid, these would be 125 mg, 60 times higher than the 1999
EPA alarm level for formaldehyde in daily drinking water of
1 ppm = 2 mg for average daily drinking water of 2 L daily.
Since no adequate data has ever been published on the
exact disposition of toxic metabolites in specific tissues in humans
of the 11 % methanol component of aspartame,
the many studies on morning-after hangover from the methanol
impurity in alcohol drinks are the main available resource to date.
highly toxic formaldehyde, the cause of alcohol hangovers, is
made by the body from 100 mg doses of methanol from
dark wines and liquors, dimethyl dicarbonate, and aspartame:
DMDC: Dimethyl dicarbonate 200mg/L in drinks
adds methanol 98 mg/L ( becomes formaldehyde in body ):
EU Scientific Committee on Foods 2001.07.12:
"...DMDC was evaluated by the SCF in 1990
and considered acceptable for the cold sterilization of soft drinks
and fruit juices at levels of addition up to 250 mg/L (1)
...DMDC decomposes primarily to CO2 and methanol ...
[ Note: Sterilization of bacteria and fungi is a toxic process,
probably due to the inevitable conversion in the body of methanol
into highly toxic formaldehyde and then formic acid. ]
The use of 200 mg DMDC per liter would add 98 mg/L of
methanol to wine which already contains an average of about
40 mg/L from natural sources.
methanol products (formaldehyde and formic acid) are main
cause of alcohol hangover symptoms [same as from similar
amounts of methanol, the 11% part of aspartame]:
YS Woo et al, 2005 Dec: Murray 2006.01.20
Addict Biol. 2005 Dec;10(4): 351-5.
Concentration changes of methanol in blood samples during
an experimentally induced alcohol hangover state.
Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT,
Chuncheon National Hospital, Department of Psychiatry,
The Catholic University of Korea, Seoul, Korea.
Songsin Campus: 02-740-9714
Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm eight hospitals
[ Han-Kyu Lee ]
A hangover is characterized by the unpleasant physical and
mental symptoms that occur between 8 and 16 hours after
After inducing experimental hangover in normal individuals,
we measured the methanol concentration prior to
and after alcohol consumption
and we assessed the association between the hangover
condition and the blood methanol level.
A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric
or medical disorders.
The blood ethanol concentration prior to the alcohol intake
(2.26+/-2.08) was not significantly different from that
13 hours after the alcohol consumption (3.12+/-2.38).
However, the difference of methanol concentration
between the day of experiment (prior to the alcohol intake)
and the next day (13 hours after the alcohol intake)
was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).
A significant positive correlation was observed
between the changes of blood methanol concentration
and hangover subjective scale score increment when covarying
for the changes of blood ethanol level (r=0.498, p<0.05).
This result suggests the possible correlation of methanol
as well as its toxic metabolite to hangover. PMID: 16318957
[ The toxic metabolite of methanol is formaldehyde, which in turn
partially becomes formic acid -- both potent cumulative toxins
that are the actual cause of the toxicity of methanol.]
This study by Jones AW (1987) found next-morning hangover
from red wine with 100 to 150 mg methanol
(9.5 % w/v ethanol, 100 mg/l methanol, 0.01 %).
Fully 11% of aspartame is methanol --
1,120 mg aspartame in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol).
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
Elimination half-life of methanol during hangover.
Jones AW. wayne.jones@...;
Department of Forensic Toxicology,
University Hospital, SE-581 85 Linkoping, Sweden.
This paper reports the elimination half-life of methanol in human
Experiments were made during the morning after the subjects had
consumed 1000-1500 ml red wine
(9.5 % w/v ethanol, 100 mg/l methanol)
the previous evening. [ 100 to 150 mg methanol ]
The washout of methanol from the body
coincided with the onset of hangover.
The concentrations of ethanol and methanol in blood were
determined indirectly by analysis of end-expired alveolar air.
In the morning when blood-ethanol dropped
below the Km of liver alcohol dehydrogenase (ADH)
of about 100 mg/l (2.2 mM),
the disappearance half-life of ethanol was 21, 22, 18 and 15 min.
in 4 test subjects respectively.
The corresponding elimination half-lives of methanol
were 213, 110, 133 and 142 min. in these same individuals.
The experimental design outlined in this paper can be used
to obtain useful data on elimination kinetics of methanol
in human volunteers without undue ethical limitations.
Circumstantial evidence is presented to link methanol
or its toxic metabolic products, formaldehyde and formic acid,
with the pathogenesis of hangover. PMID: 3588516
four Murray AspartameNM reviews in SE Jacob & SA
Stechschulte debate with EG Abegaz & RG Bursey of
Ajinomoto re migraines from formaldehyde from aspartame,
Dermatitis 2009 May: TE Hugli -- folic acid with V-C
protects: Rich Murray 2009.08.12
Wednesday, August 12, 2009
[ extracts ]
Formaldehyde, aspartame, migraines: a possible connection.
Abegaz EG, Bursey RG.
Dermatitis. 2009 May-Jun;20(3):176-7; author reply 177-9.
No abstract available. PMID: 19470307
Eyassu G. Abegaz *
Robert G. Bursey
Ajinomoto Corporate Services LLC, Scientific & Regulatory
Affairs, 1120 Connecticut Ave., N.W., Suite 1010,
Washington, DC 20036
* Corresponding author. Tel.: +1 202 457 0284;
fax: +1 202 457 0107.
abegazee@... (E.G. Abegaz),
burseyb@... (R.G. Bursey)
"For example, fruit juices, coffee, and alcoholic beverages produce
significantly greater quantities of formaldehyde than aspartame-
containing products. "
" Magnuson BA, Burdock GA, Doull J, et al. Aspartame: a
safety evaluation based on current use levels, regulations, and
toxicological and epidemiological studies.
Crit Rev Toxicol 2007;37:629-727"
[ two detailed critiques of industry affiliations and biased science
in 99 page review with 415 references by BA Magnuson,
GA Burdock and 8 more, Critical Reviews in Toxicology,
2007 Sept.: Mark D Gold 13 page:
also Rich Murray 2007.09.15: 2008.03.24
Monday, March 24, 2008
"Nearly every section of the Magnuson (2007) review has
research that is misrepresented
and/or crucial pieces of information are left out.
In addition to the misrepresentation of the research,
readers (including medical professionals) are often not told that
this review was funded by the aspartame manufacturer, Ajinomoto,
and the reviewers had enormous conflicts of interest." ]
Dermatitis. 2008; 19(3): E10-E11.
© 2008 American Contact Dermatitis Society
Formaldehyde, Aspartame, and Migraines: A Possible Connection
Sharon E. Jacob; Sarah Stechschulte
[ Extract ]
Aspartame is a widely used artificial sweetener that has been linked
to pediatric and adolescent migraines.
Upon ingestion, aspartame is broken, converted, and oxidized into
formaldehyde in various tissues.
We present the first case series of aspartame-associated migraines
related to clinically relevant positive reactions to formaldehyde
on patch testing.
Six patients (ages 16 to 75 years) were referred for evaluation of
recalcitrant dermatitis. By history, five of the patients were noted
to have developed migraines following aspartame consumption; the
sixth reported dermatitis flares associated with diet cola
consumption of >2 liters/day.
All six patients had current environmental exposures to formaldehyde
or formaldehyde-releasing preservatives in their personal hygiene
products and/or regular consumption of "sugar-free food" artificially
sweetened with aspartame.
Based on their histories and clinical presentations, these patients
were patch-tested with the North American Contact Dermatitis
Group 65-allergen Standard Screening Series and selected
chemicals from the University of Miami vehicle, fragrance, bakery,
and textile trays.
All six patients had positive reactions to formaldehyde, and four had
additional positive reactions to formaldehyde-releasing preservatives
(FRPs). Expert counseling on allergen avoidance (including
avoidance of formaldehyde, FRPs, and aspartame) and alternative
product recommendations were provided to the patients.
At their follow-up appointments (between 8 and 12 weeks), all the
patients showed clearance of their dermatitis. Four patients (two
inadvertently) resumed their consumption of aspartame and
subsequently returned for an additional follow-up visit. Three of the
first five patients had recurrences of both their migraines and their
dermatitis; the sixth patient (who had no migraines) had a positive
rechallenge dermatitis. These four patients were again counseled on
formaldehyde, aspartame, and migraines, the first case series,
Sharon E Jacob-Soo, Sarah A Stechschulte, UCSD, Dermatitis
2008 May: Rich Murray 2008.07.18
Friday, July 18, 2008
formaldehyde from many sources, including aspartame, is major
cause of Allergic Contact Dermatitis, SE Jacob, T Steele, G
Rodriguez, Skin and Aging 2005 Dec.: Murray 2008.03.27
Thursday, March 27, 2008
"For example, diet soda and yogurt containing aspartame
(Nutrasweet), release formaldehyde in their natural biological
One of aspartame's metabolites, aspartic acid methyl ester, is
converted to methanol in the body, which is oxidized to
formaldehyde in all organs, including the liver and eyes. 22
Patients with a contact dermatitis to formaldehyde have been seen
to improve once aspartame is avoided. 22
Notably, the case that Hill and Belsito reported had a 6-month
history of eyelid dermatitis that subsided after 1 week of avoiding
diet soda. 22"
Avoiding formaldehyde allergic reactions in children, aspartame,
vitamins, shampoo, conditioners, hair gel, baby wipes, Sharon E
Jacob, MD, Tace Steele, U. Miami, Pediatric Annals 2007 Jan.:
eyelid contact dermatitis, AM Hill, DV Belsito, 2003 Nov.:
Thursday, March 27, 2008
Sharon E. Jacob, MD, Assistant Professor of Medicine
University of California, San Diego 200 W. Arbor Drive #8420,
San Diego, CA 92103-8420 Tel: 858-552-8585 ×3504
Fax: 305-675-8317 sjacob@...;
Sarah A. Stechschulte, BA sstechschulte@...
Rich Murray, MA
Boston University Graduate School 1967 psychology,
BS MIT 1964, history and physics,
1943 Otowi Road, Santa Fe, New Mexico 87505
http://RMForAll.blogspot.com new primary archive
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