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

http://groups.yahoo.com/group/aspartameNM/message/1336
Re: Aspartame: please post a detailed report of your family's problems
with aspartame (11% methanol), as scientists are actually uninformed re
these common symptoms: Robinson: Sonderman: Murray 2006.05.06

May 6, 2006

Dear Carola Sonderman and colleagues,

http://www.efsa.eu.int/press_room/press_release/1472_en.html
http://www.efsa.eu.int/science/afc/afc_opinions/1471_en.html
http://www.efsa.eu.int/science/afc/afc_opinions/1471/afc_op_ej356_aspartame_en1.\
pdf


[ Please, Mr. N Alex Robinson, post a detailed report of your family's
problems with aspartame (11% methanol), as scientists are actually
uninformed about these common symptoms. ]

As a volunteer medical layman who has created an archive of 1336
long, detailed posts in 7 years that sensibly and fairly review mostly
mainstream scientific research on aspartame (methanol, formaldehyde,
formic acid) toxicity, I feel discouraged and sad that EFSA has once
again shown that official agencies are unable to deal with the actual
breadth of mainstream research information available and also the
shocking poverty of sound, detailed, adequate scientific evidence
about chronic, low-level methanol toxicity in humans.

I urge aspartame reactors to post detailed case histories.

It is moot for professionals to attend open-mindedly to the vast
amount of information available in mainstream research,
as well as in citizen feedback.

In order to successfully carry out its mission, EFSA very much needs
help in evaluating the wide range of scattered mainstream findings, as
well as citizen feedback.

I would like to be connected with a specific EFSA professional so
that we can share, cooperatively and respectfully, valuable information,
already at hand, essential for grasping major opportunities in the
needlessly obscure, difficult, persistent, and intractable scientific and
social problem of chronic, low-level methanol toxicity.

In mutual service, Rich Murray


----- Original Message -----
From: Mr Robinson
To: carola.sonderman@...
Cc: rmforall@...
Sent: Saturday, May 06, 2006 1:56 AM
Subject: Aspartame

Dear Carola,

I have read the FAQ's and could not see any question like:

How come whenever I consume any aspartame I become irritable,
have headaches and my skin itches?

or:

How come when my wife has anything containing aspartame,
her sex drive vanishes?

or

How come when my children have anything with aspartame in
they turn into insolent little brats?

You are maybe unaware of the Aspartame Victims Support Group,
this is made up of people who have managed to quit the aspartame habit,
I would urge you to look in on them at:
http://groups.yahoo.com/group/aspartame/
After all, the voices of thousands of 'unpaid' sufferers carries more
weight than a single department of 'paid' scientists.

I feel your department did the wrong studies on this chemical and
if you and your department insist on it being safe to consume
then I can only concur that you are on the payroll of the manufacturers
and so any reports you produce are worthless.

Regards, N Alex Robinson
*******************************************************


http://groups.yahoo.com/group/aspartameNM/message/1328
migraine from sucralose, Bigal ME & Krymchantowski AV,
Headache 2006 March; formaldehyde from 11% methanol part of
aspartame or from red wine causes same toxicity (hangover) harm:
Murray 2006.05.04

http://groups.yahoo.com/group/aspartameNM/message/1329
aspartame or MSG affects circadian rhythms in rats, two studies,
P. Subramanian, T. Manivasagam et al 2004:
Murray 2006.04.27


"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act upon the facts
about healthy and safe food, drink, and environment."

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

http://groups.yahoo.com/group/aspartameNM/messages
group with 152 members, 1,336 posts in a public, searchable archive
http://RMForAll.blogspot.com http://AspartameNM.blogspot.com

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 120 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Within hours, methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid -- the major causes of the dreaded
symptoms of "next morning" hangover.

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). If 30% of the methanol is turned
into formaldehyde, the amount of formaldehyde, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

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

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

http://groups.yahoo.com/group/aspartameNM/message/1291
European Food Safety Authority to decide aspartame safety by May:
caffeine diet drinks cause female hypertension, WC Winkelmayer et al,
JAMA 2005.11.09: PubMed lists 50 items for "diet soft drinks" since
2004 Oct.: Murray 2006.01.24

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

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

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

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

http://groups.yahoo.com/group/aspartameNM/message/1250
aspartame causes cancer in rats at levels approved for humans,
Morando Soffritti et al, Ramazzini Foundation, Italy &
National Toxicology Program
of National Institute of Environmental Health Sciences
2005.11.17 Env. Health Pers. 35 pages: Murray

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW:
Murray 2004.08.05 rmforall

Since no adaquate 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.

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%,
one part in ten thousand).

http://groups.yahoo.com/group/aspartameNM/message/1100
research on aspartame (methanol, formaldehyde, formic acid) toxicity:
Murray 2004.07.19 rmforall
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http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid) are main cause of
alcohol hangover symptoms [same as from similar amounts of
methanol, the 11% part of aspartame]: YS Woo et al, 2005 Dec:
Murray 2006.01.20

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

[ Han-Kyu Lee ]

A hangover is characterized by the unpleasant physical and mental
symptoms that occur between 8 and 16 hours after drinking alcohol.
After inducing experimental hangover in normal individuals,
we measured the methanol concentration prior to
and after alcohol consumption
and we assessed the association between the hangover condition
and the blood methanol level.

A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric
or medical disorders.

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

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

[ So, the normal methanol level was 2.62 mg per liter,
and increasing that by 50% = 1.3 mg per liter to 3.88 mg per liter
caused hangover symptoms. The human body has about
5.6 liters blood, so adding 1.3 mg per liter gives an estimate
of 7.3 mg added methanol, as much as 4 oz diet soda.

Diet soda is about 200 mg aspartame per 12 oz can,
which is 22 mg (11% methanol), 1.83 mg methnol per ounce.

This suggests that alcohol drinkers are more sensitive to methanol
than the average diet soda drinker, some of whom find symptoms
from a third of a diet soda.]

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.]
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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 2005.05.30 2005.07.24 rmforall

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

"However, the severe toxic effects are usually associated with the
production and accumulation of formic acid, which causes metabolic
acidosis 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 postexposure.

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 postexposure].

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 full text

Toxicological Sciences 64, 169-184 [2001]
Copyright © 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 *, #, bouchmic@...

Robert C. Brunet, # brunet@...

Pierre-Olivier Droz, #

and Gaétan Carrier* gaetan.carrier@...

* Department of Environmental and Occupational Health, Faculty of Medicine,
Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec,
Canada, H3C 3J7 Fax: (514) 343-2200.

# 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
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http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 2002.12.31 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin
in mice: Sasaki YF & Tsuda S Aug 2002: Murray 2003.01.01 rmforall
[ Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame --
a very high dose. Methanol is the only component of aspartame that can
lead to DNA damage. ]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 2003.01.27 rmforall [A detailed look at the data] ]

J Toxicol Sci. 2002 Dec; 27 Suppl 1: 1-8.
[Genotoxicity studies of stevia extract and steviol by the comet assay]
[Article in Japanese]
Sekihashi K, Saitoh H, Sasaki Y. yfsasaki-c@...
Safety Research Institute for Chemical Compounds Co., Ltd.,
363-24 Shin-ei, Kiyota-ku, Sapporo 004-0839, Japan.

The genotoxicity of steviol, a metabolite of stevia extract, was evaluated
for its genotoxic potential using the comet assay.
In an in vitro study, steviol at 62.5, 125, 250, and 500 micrograms/ml
did not damage the nuclear DNA of TK6 and WTK1 cells in the
presence and absence of S9 mix.
In vivo studies of steviol were conducted by two independent organizations.
Mice were sacrificed 3 and 24 hr after one oral administration of steviol
at 250, 500, 1000, and 2000 mg/kg.
DNA damage in multiple mouse organs was measured by the comet
assay as modified by us.
After oral treatment, stomach, colon, liver, kidney and testis DNA were
not demaged.
The in vivo genotoxicity of stevia extract was also evaluated for its
genotoxic potential using the comet assay.
Mice were sacrificed 3 and 24 hr after oral administration of stevia
extract at 250, 500, 1000, and 2000 mg/kg.
Stomach, colon and liver DNA were not damaged.
As all studies showed negative responses, stevia extract and steviol are
concluded to not have DNA-damaging activity in cultured cells and
mouse organs. PMID: 12533916
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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 2003.08.03 rmforall

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

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@...
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

Ann N Y Acad Sci. 2002 Dec; 982: 46-69.

Results of long-term experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Soffritti M, Belpoggi F, Cevolani D,
Guarino M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology
and Environmental Sciences, Bologna, Italy. crcfr@...
Methyl alcohol was administered in drinking water
supplied ad libitum at doses of
20,000, 5,000, 500, or 0 ppm to groups of male and female
Sprague-Dawley rats 8 weeks old at the start of the experiment.
Animals were kept under observation until spontaneous death.
Ethyl alcohol was administered by ingestion in drinking water at a
concentration of 10% or 0% supplied ad libitum to groups of male and
female Sprague-Dawley rats; breeders and offspring were included in
the experiment.
Treatment started at 39 weeks of age (breeders), 7 days before mating,
or from embryo life (offspring) and lasted until their spontaneous death.
Under tested experimental conditions, methyl alcohol and ethyl alcohol
were demonstrated to be carcinogenic for various organs and tissues.
They must also be considered multipotential carcinogenic agents.
In addition to causing other tumors, ethyl alcohol induced malignant
tumors of the oral cavity, tongue, and lips.
These sites have been shown to be target organs in man by
epidemiologic studies.
Publication Types: Review Review, Tutorial PMID: 12562628
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