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

----- Original Message -----
From: "Rich Murray" <rmforall@...>
To: <weekly@...>
Cc: <Robert_Swift_MD@...>; "joe.schwarcz" <joe.schwarcz@...>;
"Woodrow Monte" <woodymonte@...>; "Mark D. Gold"
<mgold@...>; <jonmargo@...>
Sent: Friday, January 16, 2004 10:21 PM
Subject: Avoiding Hangover Hell 12.31.3 Mark Sherman, AP writer: Robert
Swift, MD: [formaldehyde from methanol in aspartame]: Murray 1.16.4 rmforall

[ http://groups.yahoo.com/group/aspartameNM/message/1045
aspartame and formaldehyde toxicity discussion:
Schwarcz: Murray 12.13.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1049
let us examine an aspartame reactor: Schwarcz: Murray 1.18.4 rmforall ]

Jan 18 2004 Hey, Joe Schwarcz, It's easy to toss off a 'shoot the
messenger' crack like "anti-aspartame fanatics are nuts". Would you please
buttress your credibility as a scientist by citing specific faults in the
following mainstream scientific selections:

Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-986-9103

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

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

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

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

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

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

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

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours,
with little additional elimination, as carbon dioxide in exhaled air
and as water in the urine. They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body. They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol. This study did not monitor long-term use of aspartame.

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

Their followup report in 1976 included only three human subjects, who were
tested with aspartame made with C-14 phenylalanine and then C-14 aspartate--
but never the methanol component! Instead of mentioning the dreaded word
"formaldehyde" anywhere in the text and citations, they only showed, on
Figure 1, Metabolic pathways followed by aspartame, using arrows to show
reaction paths,

Asp-Phe-Me --> intestinal esterases ---> Asp-Phe + MeOH -->
one-carbon metabolic pool --> CO2 + formyl metabolites

J Toxicol Environ Health. 1976 Nov; 2(2): 441-51.
Comparative metabolism of aspartame in experimental animals and humans.
Ranney RE, Oppermann JA, Muldoon E, McMahon FG.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening
agent that organoleptically has about 180 times the sweetness of sugar.
The metabolism of aspartame has been studied in mice, rats, rabbits, dogs,
monkeys, and humans.
The compound was digested in all species in the same way as are natural
constituents of the diet.
Hydrolysis of the methyl group by intestinal esterases yielded methanol,
which was oxidized in the one-carbon metabolic pool to CO2.
The resultant dipeptide was split at the mucosal surface by dipeptidases and
the free amino acids were absorbed.
The aspartic acid moiety was transformed in large part to CO2 through its
entry into the tricarboxylic acid cycle.
Phenylalanine was primarily incorporated into body protein either unchanged
or as its major metabolite, tyrosine. PMID: 827618

[ At the end of this post are more lengthly details on industry bias in
aspartame, methanol, formaldehyde, formic acid research. ]

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

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

http://www.drthrasher.org/formaldehyde_1990.html full text Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223. "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation." PMID: 2400243

Med Hypotheses. 1984 Jan; 13(1): 63-75.
Chronic methanol poisoning with the clinical and pathologic-anatomical
features of multiple sclerosis.
Henzi H.

The details of two cases of chronic methanol poisoning are presented. Both
patients initially developed clinical symptoms of multiple sclerosis: visual
disturbances, intention tremor, reduced abdominal reflexes, impaired
coordination and difficulties with walking. After the exposure to methanol
had ceased the multiple sclerosis symptoms persisted in patient 1 but
disappeared gradually in patient 2 (patient 2 had a history of excessive
alcohol consumption, which is a critical fact in this discussion).
Ultimately autopsies confirmed this picture: histological examination of
patient 1 revealed plaques in the spinal cord, in the stem and in the
proximity of the lower horn of one lateral ventricle, whereas no localized
demyelination could be found in patient 2. The results are discussed in
connection with the theory ("Methanol Hypothesis") that under certain
circumstances multiple sclerosis itself is induced by formaldehyde stemming
from the metabolism of methanol. Publication Types: Case Reports PMID:
6708848

"This article outlines the case of a biology teacher whose chronic
formaldehyde exposure resulted in heightened sensitivity to formaldehyde,
three tonic-clonic seizures, and dramatic amnesia as well as other cognitive
dysfunction."
Robert B. Perna, Ernest J. Bordini, Maria Deinzer-Lifrak
A Case of Claimed Persistent Neuropsychological Sequelae of Chronic
Formaldehyde Exposure. Clinical, Psychometric, and Functional Findings
Archives of Clinical Neuropsychology 16 (1) (2001) pp. 33-44.
Arch Clin Neuropsychol. 2001 Jan; 16(1): 33-44. [27 citations]
A case of claimed persistent neuropsychological sequelae of chronic
formaldehyde exposure. Clinical, psychometric, and functional findings.
Perna RB, Bordini EJ, Deinzer-Lifrak M.
Comprehensive Neuropsychological Services of the Southern Tier, Vestal, NY

Many anecdotal cases and some clinical studies have demonstrated that
formaldehyde exposure can cause multiple health-related problems and
cerebral dysfunction.
The U.S. Consumer Product Safety Commission has documented multiple hazards
related to formaldehyde exposure.
Some of this research has suggested that low levels of exposure can be very
hazardous to one's health and can potentially result in heightened chemical
sensitivities, seizures, and cognitive decline.
Some research suggests that exposure results in long-term immunological
changes, cell neurofilament protein changes, and demyelination.
Symptomatically, exposure has been associated with respiratory problems,
excessive fatigue, headaches, mood changes, and impaired attention,
concentration, and memory functioning.
This article outlines the case of a biology teacher whose chronic
formaldehyde exposure resulted in heightened sensitivity to formaldehyde,
three tonic-clonic seizures, and dramatic amnesia as well as other cognitive
dysfunction. PMID: 14590191

http://www.cpancf.com/
Clinical Psychology Asssociates of North Central Florida
Gainesville Office 2121 NW 40th Terr. Ste B. Gainesville, FL 32605
Ph: (352) 336-2888 Fax: (352) 371-1730

Ocala Office 3002 SE 1st Ave., Bldg. 300 Ocala, FL 32 Ph: (352) 629-1100

http://www.cpancf.com/NRE00151.pdf
NeuroRehabilitation 17 (2002) 93-104 IOS Press
Advances and issues in the diagnostic differential of malingering versus
brain injury

Robert B Perna, Ph.D. Neuropsychologist Dr.Perna@...
Department: pain management
Facility: Southern Tier Pain Management Ctr.
Vestal, New York, 13850
Work Phone: 607-754-2313 Fax: 607-754-6926

http://www.usm.maine.edu/lac/ot/faculty%20&%20staff.htm
Robert B. Perna, Ph.D.; Part Time Instructor, OTH 610
Educational and Experiential Background
Robert is a part-time adjunct faculty who teaches Neuroscience in the
Occupational Therapy program. He is a clinical neuro-psychologist, the
director of a CARF accredited post-acute brain injury program, and is board
certified in psychopharmacology. He has completed many residencies at
University of Michigan Medical School and the Miami Heart Institute. He has
authored and co-authored more than fifty journal articles related to
neuro-psychology and rehabilitation.

http://www.forensicneuropsychology.com/_wsn/page2.html

http://www.psyfin.com/directory/detail.asp?ListingsID=7041

Ernest J. Bordini Ph.D. http://www.cpancf.com cpancf@...
2121 NW 40th Terrace Ste B Gainesville/Ocala, FL 32605
Phone: (352) 336-2888 Fax: (352) 371-1730
Licenses: Psychologist
Services: Clinical Psychology Associates of N. Central Florida, P.A.
provides services to children, adolescents, adultis, and seniors.
Psychological, Forensic and Neuropsychological Assessment. Employee
Assistance Programs.

Maria Deinzer-Lifrak, PhD deinlif@...
Comprehensive Neuropsychological Services
490 Western Avenue Albany, NY 12203 518-458-2314

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male) alemany@...

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

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

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

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA. neurotulsa@...
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]

Here is a detailed personal case report. The jumbled, run-together syntax
and multiple typos are also common in aspartame reactors who are just
starting to detox. Note that this all unfolded within the last year, and
that symptoms are triggered by aspartame chewing gum, 6-8 mg aspartame per
stick. Ms Linsley has exercised unusual initiative in searching out and
testing possible dietary triggers. There are hundreds of similar reports in
the archives of http://health.groups.yahoo.com/group/aspartame/messages ,
759 members and 16,419 posts in just over 5 years.

From: "Linda Linsley" <lindalinsley@...>
To: <aspartame@yahoogroups.com>
Subject: [Aspartame Support] Aspartame Poisoned
Date: Saturday, January 17, 2004 9:01 PM

Here's where I am at this point in time.

> I'm 50, a former athlete (my dad became an olympic
> coach), a self-learner and I always ask "why", "what
> happens if",etc. I learned a long time ago that just
> because someone "says so" isn't always enough. So
> when things began to go wrong a year ago I recovered
> quickly from the shock and set out to find out what
> else it could be. Long story abbreviated:
> symptoms;(each time I re-tell this I remember more
> clearly what happened. my notes are tucked away
> somewhere). White flashes in eyes, re-curring
> dejavu's, dizziness, confusion, disorientation,
> nausea, vomiting, undescribable/unidentifiable tase
> and smell, thrown off feet/chair, head-bobbing, one
> time only--loss of consciousness while driving, foot
> bouncing off ground for no reason, incredible
> sleepiness that I HAD to stop for and pass out
> for(always had warning), inability to
> focus/concentrate, memory loss, decline in grammar
> and math skills, decline in reading and figuring out
> written/oral directions, disproportionate loss of
> muscle tone, stiffness, joint pain, asthma-like
> symptoms, hearing loss, vision changes, pains in
> chest and liver, poor coordination and balance, mood
> swings, depression, fatigue, when under physical
> stress/exertion my body would swell like arthritis(I
> could have sworn it was attacking itself!),
> reactions of doctors over the years; many tests, all normal.
> The first list of symptoms that involved the head were
> the ones I went for help with in 2002. Prior to that I
> was actually kicked out of my physicians office because
> I complained about all the tests and the money I spent
> on them. With a new doctor that I'd hardly been to,
> I was a bit hesitant. I didn't want to scare him, too,
> and get the reputation of being a hypochondriac, so
> I was real pleasant with him. He said I needed a
> psychiatrist. Second opinion, and third doctor, did
> mri, saw spots, referred me to neurologist, said to
> call him if I needed any help, tossed out phrase
> "m.s." POSSIBILITY, said needed more tests. When I
> had another episode while waiting for neurologist
> appointment that was 4 months away, he was merely
> polite. no help. Then I thought I'd mention a few
> more symptoms to him and he replied "You'd be surprised
> what we can imagine when we think there's something
> wrong with us". Finally saw neurologist, had second
> mri, spots the same. She said "Yes, you have the
> symptoms of m.s., but until you lose the use of an
> arm or leg for three days due to numbness and tingling,
> I won't even consider the possibility of it! Check the
> internet (but be careful--there's a lot of
> mis-information out there). Check with the M.S.
> Society!" I did. They said "Get a different doctor!" !
> I had noticed, on my own, that these "dejavu
> incidents" seemed connected to foods. I got a
> different doctor after a while. After the run I'd
> had with doctors, I was tired of the whole thing and was
> planning on only using the E.R. from then on. While
> in limbo between the old/new doctor, I practiced the
> diet a proffessor had told me about. His wife was
> diagnosed with m.s. and had recovered quite a bit on it.
> Things were going quite well as I was able to stick to it
> better (with new motivation). One day I had another
> "dejavu episode" and was worried that I didn't have
> a doctor I could rely on, as well as confused at what
> caused it. If my theory about food was right, then
> what happened? I was driving down the road at the
> time ( I'm a good compensator for the dizziness), and it
> was passed, so I popped a piece of gum in my mouth
> and THAT WAS IT! I had just bought another pack of
> Extra. I hadn't had any for a month now...same time when I
> was doing well! O.K.! If my theory was correct, then
> I could eat anything (within reason--I still wasn't
> sure yet) that I'd been avoiding and IF IT WAS the gum, I
> should have no other symptoms. (they would go in
> clusters for a period of 12-42 hours)..So I dropped
> the gum, pigged out on forbidden items and HAD NO
> TROUBLE AT ALL! The doctors refused to respond to
> and acknowledge that. When I got my new doctor, I said
> not much about it. I began to search the Internet. Found
> Dr. Betty Martini on the aspartame group, then
> Connie at the Kicksugar group, while also changing my
> experiments on myself which lead to discovering a
> variety of additives that were responsible for the
> symptoms. As I found out more additives I would
> check it out on the sites forconfirmation.
> foods I avoid now are aspartame, msg, hydrolyzed
> animal protien, aspartic acid, natural flavorings
> sucrose, dextrose, maltodextrin, corn syrup, high
> fructose corn syrup, disodium guanylate, monosodium
> glutamate, disodium phosphate( and any other "ate"),
> diglycerides and artificial flavorings.
> For now, that's the way things are. Have I totally
> ruled out m.s. or something else? Not really because
> of the mri that showed spots on the brain. Only
> time and consistency will prove anything. There seems to
> be a period of de-toxification when tolerance levels
> are better (saturation point?) during which I can
> indulge in damaging substances for a while with no
> reactions. However, saturation point is reached again and I
> notice tiny occurances of some of the earlier
> symptoms. Sticking with the "pure diet" is
> difficult, especially when there are those around who don't
> follow it....and that's just about everyone I come
> in contact with!
> BUT THE RESPONSIBILITY LIES WITH ME
> to do what is best for me regardless of what is considered "normal".
********************************************************************

Sent: Jan 17 2003 3:35 PM joe.schwarcz@...

Ohhhhh ...how a little learning is a dangerous thing...
The stuff about hangover is all correct, in fact I have written on it
myself (attached) but it has nothing to do with aspartame toxicity. In
fact if you take the trouble to check with Dr. Swift you will learn that
he thinks the anti-aspartame fanatics are nuts.

Dr. Joe Schwarcz, Director McGill Office for Science and Society
514-398-6238 joe.schwarcz@...
McGill University, 801 Sherbrooke St., West Montreal, QC. Canada H3A 2K6

"... But in all likelihood, the greatest contributor to the hangover is
methanol. This alcohol is found in small concentrations in many beverages,
a byproduct of fermentation. It is metabolized by the same enzymes as
ethanol, but the products this time are formaldehyde and formic acid which
produce the hangover symptoms. Why does this happen only the morning after?
Because the enzymes prefer to work on ethanol instead of methanol. Only
when all the ethanol has been metabolized, do they switch to methanol.... "

The Scoop On Booze
The police officers could hardly believe their eyes. The eighteen year-old
driver they had just pulled over sat there speechless, a wad of white fabric
sticking out of his mouth. He had ripped the crotch out of his underwear
and stuffed it into his mouth in an apparent attempt to fool the
breathalyzer. Some scientific memory about the absorbency of cotton must
have stirred in his confused mind to prompt the bizarre act. But the
breathalyzer was not fooled. Neither was it fooled by the teenager who was
caught ferociously sucking on pennies after being stopped. He must have
remembered a bit of the chemistry he had learned about alcohol. The bit
about alcohol being oxidized to acetaldehyde by the action of copper. He
figured he'd be in the clear since the breathalyzer tests for alcohol in the
breath, and not acetaldehyde. Unfortunately the genius didn't remember the
reaction quite right. Ethanol, the alcohol of beverages, can indeed be
converted to acetaldehyde by copper, but only when the copper is red hot!

Then there are those whose alibi is that they had just rinsed their mouth
with mouthwash. But this doesn't wash either. Sure, mouthwashes contain
alcohol, and a false breathalyzer reading is possible, but only if the
mouthwash was used immediately before giving a breath sample. Alcohol from
a mouthwash dissipates within a couple of minutes and guidelines state that
a suspect has to be observed for several minutes before a breathalyzer test
is undertaken.

Is it surprising that people resort to such curious acts when they've
overindulged? Not really. After all, alcohol certainly affects the brain.
And the rest of the body as well. The chemistry involved is absolutely
fascinating. Of course, before alcohol can affect the brain, it has to get
there. Most of the alcohol we consume is absorbed into the bloodstream from
the stomach and the small intestine. But not all of the alcohol makes it
through. Some is metabolized in the mucosa that lines the stomach and
intestine. Here, enzymes convert ethanol first to acetaldehyde and then to
acetic acid, neither of which is inebriating. In men, about 30% of a dose
of alcohol meets its metabolic end in this fashion, but there is a definite
gender bias here. The female stomach and intestinal lining is only about
half as efficient at breaking down ethanol, so more makes it into the
circulation. This explains why women may become tipsy more easily.

Once the alcohol is in the bloodstream, it passes through the liver. The
liver is the body's main detoxicating organ and it detects alcohol as a
potential troublemaker. First, an enzyme called alcohol dehydrogenase snips
a couple of hydrogen atoms out of the ethanol molecule, converting it to
acetaldehyde. Then aldehyde dehydrogenase transforms this intermediate into
acetic acid which is either excreted or used by the body as a source of
energy as it is broken down into carbon dioxide and water. A gram of
ethanol can provide about seven calories in this fashion. If the intake of
alcohol is sufficiently high, the liver's detoxicating system becomes
overburdened and some of the alcohol slips through unmetabolized. It can
then wreak havoc in the brain.

Ethanol does this by interfering with "neurotransmitters," the chemicals
brain cells use to communicate among themselves. At low alcohol levels,
receptors for glutamate are activated leading to stimulation and a loss of
inhibition. This is the "social lubricant" effect of alcohol. But as the
concentration of alcohol rises, glutamate receptors actually become less
responsive and words begin to slur and "cocktail party amnesia" begins.
Other neurotransmitter systems are also affected. Gamma aminobutanoic acid
(GABA) is known as an inhibitory neurotransmitter because it prevents nerve
cells from firing excessively. Alcohol stimulates GABA activity which
eventually causes sedation and relaxation. And that is only part of a very
complex picture.

Eventually the effects wear off as the alcohol is excreted or is metabolized
as it passes through the liver again. But as this is happening, there is
often a matter of nausea, headaches and a flushed face to deal with. The
culprit here is acetaldehyde, some of which escapes from the liver before
being converted to acetic acid. As we well know, not everyone suffers these
symptoms to the same degree. Many people of Asiatic origin are severely
affected by facial flushing because nature has dealt them a very slow acting
version of aldehyde dehydrogenase, the enzyme that normally degrades
acetaldehyde. Indeed, the same concept lies behind a prescription drug
known as disulfiram (Antabuse) which is given to alcoholics. The idea is
that the drug inactivates aldehyde dehydrogenase, forcing acetaldehyde into
the circulation. This should make the drinker so sick that he gives up the
booze. Unfortunately, he usually gives up the drug instead.

Some of the effects of acetaldehyde can linger till the morning after and
contribute to hangover. Interestingly, the hangover business hasn't been as
extensively researched as one would think. That's because solving the
problem would come with quite a bit of social baggage. The concern is that
elimination of the hangover could cause people to drink more. Still, we do
know that there is more to the hangover than just the remnants of
acetaldehyde. The metabolism of alcohol in the liver produces some free
radical debris which is usually taken care of by glutathione, one of the
body's most important antioxidants. When the system is overwhelmed, these
free radicals can contribute to the hangover. That is why there has been
some success in treating hangovers with supplements of N-acetylcysteine
(NAC) which serves as a source of cysteine, the critical compound the body
needs to generate more glutathione. Eggs also contain cysteine which may
explain their folkloric use to treat hangovers.

The hangover is actually multifactorial. Dehydration plays an important
role as does hypoglycemia caused by the alcohol mediated loss of sugar in
the urine. But in all likelihood, the greatest contributor to the hangover
is methanol. This alcohol is found in small concentrations in many
beverages, a byproduct of fermentation. It is metabolized by the same
enzymes as ethanol, but the products this time are formaldehyde and formic
acid which produce the hangover symptoms. Why does this happen only the
morning after? Because the enzymes prefer to work on ethanol instead of
methanol. Only when all the ethanol has been metabolized, do they switch to
methanol. This then explains the "hair of the dog" remedy for hangovers. A
drink in the morning supplies ethanol for the enzymes to act on so they'll
leave methanol alone. As the enzymes busily metabolize the ethanol,
methanol is excreted in the urine without being converted to formic acid. A
Bloody Mary may be the best choice here, because vodka contains very little
methanol. Confirmation about the critical role of methanol in hangovers
comes from a study showing that treatment with 4-methylpyrazole, a drug that
blocks the breakdown of methanol, can eliminate the symptoms.

I must admit to feeling a little queasy talking about hangover cures.
Alcohol can be an extremely destructive beverage. It is probably more
damaging to society than all illicit drugs combined. Cirrhosis of the
liver, strokes, breast cancer, oral cancers, domestic violence and sexual
assault have all been linked to alcohol abuse. In North America there is an
alcohol related car accident every 30 seconds. And if that isn't
frightening enough, excessive alcohol can shrink the genitals and have
feminizing effects on men. Less testosterone is produced, so the sex drive
suffers. But for those who want to look on the bright side, less
testosterone means less likelihood of baldness.

Henny Youngman, whom some would call a comedian, once remarked that when he
read about the evils of drinking he gave up reading. I hope you won't do
the same. There is nothing funny about being drunk. Drunks destroy their
own lives and kill others. What can we do? Well, University of Georgia
researchers have found that blood alcohol can be reduced significantly by
inserting a tube into the rectum and piping in alcohol dehydrogenase and
oxygen. Sounds good to me.
*******************************************************************

[more details on industry bias in aspartame, methanol, formaldehyde, formic
acid research]

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

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

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

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

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 afterwards, as carbon dioxide in exhaled
air and in the urine. They did not mention
that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, both of which must remain
as toxic products in all parts of the body. They did not report any
studies on the distribution of radioactivity in body tissues, nor give the
absolute levels for declining blood plasma proteins. This study did not
monitor long-term use of aspartame, which might reveal cumulative effects.

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

By eight hours excretion of the dose in air and urine had leveled off
at 67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine,
so 68.7 % was excreted, and 31.3% was retained. [This data is the
average of 4 monkeys.] "...the 14C in the feces was negligible."
"That fraction not so excreted (about 31%) was converted to body
constituents through the one-carbon metabolic pool."

"All radioactivity measurements were counted to +-1% accuracy..."
This indicates that the results could not be claimed to have a precision of
a tenth of a percent. OK, so this is a nit-pick-- but I believe espousing
spurious accuracy is a sign of scientific insecurity.

The abstract ends, "It was concluded that aspartame was digested to its
three constituents that were then absorbed as natural constituents of the
diet."
Thus, the concept is very subtly insinuated that methanol, as a constituent
of aspartame, is absorbed as a natural constituent of the diet. "Dietary
methanol is derived in large part from fresh fruits and vetetables."

Nowhere in this report, or in the book chapter are mentioned the dread
words, "formaldehyde" and "formic acid".

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

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

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

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

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

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

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

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

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

http://groups.yahoo.com/group/aspartameNM/message/872
immune system reactions due to formaldehyde from the 11% methanol in
aspartame: Trasher: Tephly: Monte: Murray 9.27.2 rmforall
[selections]
Life Sci 1991; 48(11): 1031-41. The toxicity of methanol. Tephly TR.
Department of Pharmacology, University of Iowa, Iowa City 52242.

Methanol toxicity in humans and monkeys is characterized by a latent
period of many hours followed by a metabolic acidosis and
ocular toxicity. This is not observed in most lower animals. The
metabolic acidosis and blindness is apparently due to formic acid
accumulation in humans and monkeys, a feature not seen in lower animals.

The accumulation of formate is due to a deficiency in
formate metabolism which is, in turn, related, in part, to low hepatic
tetrahydrofolate (H4 folate). An excellent correlation between
hepatic H4 folate and formate oxidation rates has been shown within and
across species. Thus, humans and monkeys possess low
hepatic H4 folate levels, low rates of formate oxidation and
accumulation of formate after methanol. Formate, itself, produces
blindness in monkeys in the absence of metabolic acidosis. In addition
to low hepatic H4 folate concentrations, monkeys and humans
also have low hepatic 10-formyl H4 folate dehydrogenase levels, the
enzyme which is the ultimate catalyst for conversion of formate
to carbon dioxide. This review presents the basis for the role of folic
acid-dependent reactions in the regulation of methanol toxicity.
Publication Types: Review Review, Academic PMID: 1997785

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

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

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

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

1. The metabolism of [14C]formaldehyde
has been investigated in the male Sprague-Dawley rat.
It is extensively oxidized to CO2
and formate, which is excreted in the urine. 2. Two radioactive
compounds isolated from the urine of rats dosed with
[14C]formaldehyde have been identified as N-hydroxymethylurea and
N,N'-bis-(hydroxymethyl)urea, and shown to be urinary
artefacts. 3. Previous studies of the metabolism
of formaldehyde by rats have been re-appraised.
Differences in the rate of oxidation
of formaldehyde in various strains of rats result in the excretion of
different urinary metabolites and, in some cases, formaldehyde.
Excretion of formaldehyde leads to the formation of several artefacts
depending on the components present in the urine. PMID: 6806997

http://groups.yahoo.com/group/aspartameNM/message/1025
aspartame & formaldehyde toxicity: Murray 9.9.3 rmforall
[selection]
Biochemical Pharmcacology 1979: 28; 645-649.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
and Thomas R. Tephly
The Toxicology Center, Dept. of Pharmacology,
University of Iowa, Iowa City, Iowa 52242
K.E. McMartin and T.R. Tephly, authors of many pro-aspartame studies, in
Biochemical Pharmacology (1979) remarked, "It is now generally accepted
that the toxicity of methanol is due to the formation of toxic metabolites,
either formaldehyde or formic acid." They put damage doses of methanol
into the stomachs of three monkeys, and, using insensitive tests, found no
formaldehyde in many tissues-- except for a single datum in the midbrain,
1.5 times the detection limit. The use of inadequate tests is common in
industry research that is funded to claim the safety of profitable toxins.
Since then, industry scientists have been very wary of doing studies on
primates, which all too easily show the dangers to humans.
[end of selection]

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from 11% methanol in aspartame:
Murray: 12.9.2 rmforall
[selections]
This study admitted one datum that showed accumulation of formaldehye
in the midbrain from an acute toxicity dose of methanol, and widespread
accumulation of formic acid in five tissues.

Biochemical Pharmcacology 1979: 28; 645-649.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
and Thomas R. Tephly
The Toxicology Center, Dept. of Pharmacology,
University of Iowa, Iowa City, Iowa 52242

Abstract [not given in PubMed]: [My comments are in square braclets.]
Methanol was administered [by nasogastric tube] either to untreated
cynomolgus monkeys [2-3.5 kg] or to a folate-deficient cynomolgus
monkey which exhibits exceptional sensitivity to the toxic effects of
methanol.
Marked formic acid accumulation in the blood and in body fluids and
tissues was observed.
No formaldehyde accumulation was observed in the blood and no
formaldehyde was detected in the urine, cerebrospinal fluid, vitreous
humor, liver, kidney, optic nerve, and brain in these monkeys at a time
when marked metabolic acidosis and other characteristics of methanol
poisoning were observed.
Following intravenous infusion into the monkey, formaldehyde was
rapidly eliminated from the blood with a half-life of about 1.5 min and
formic acid levels promptly increased in the blood.
Since formic acid accumulation accounted for the metabolic acidosis and
since ocular toxicity essentially identical to that produced in
methanol poisoning has been described after formate treatment, the
predominant role of formic acid as the major metabolic agent for
methanol toxicity is certified.
Also, results suggest that formaldehyde is not a major factor in the
toxic syndrome produced by methanol in the monkey.

[ So, this is an acute toxicity study, with little relevance for chronic
long-term, low-level exposure.

"It is now generally accepted that the toxicity of methanol is due to
the formation of toxic metabolites (1,2), either formaldehyde or formic
acid."

Monkeys, like people, are susceptible to methanol toxicity.

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

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

The assay used was the chromatropic acid method, with a detection limit
of .025 mmol/L. None of the five tissues showed any formaldehyde with
this assay, except the midbrain, 0.14 mmol/kg wet weight tissue [units
converted from their 0.14 micromole/gm]-- just 1.5 times the detection
limit of .09 mmol/kg wet tissue weight (given on p. 648).
[Since 1 kg of water is 1 L, 1 mmol/kg is equivalent to 1 mmol/L.]

Meanwhile, the blood formate level rose by 12 hours from .180 to
10.02 mEq/L. [I assume that a mEq is equivalent to a mmol-- let
me know if I'm wrong.] The formate detection limits for the assays
were not given in this report. The formate level in the vitreous humor
of the eye was 7.90 mEq/L. It is well known that formate is
extremely damaging to the eye. For unexplained reasons, formate levels
in the five tissues were not measured.

After 12 hours, the urine formaldehyde level was below detection level,
while urine formate was 115.80 mEq/L-- so much of the
formaldehyde had been converted into formic acid, another cumulative,
potent toxin.

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

It is reasonable to surmise that more sensitive assays would have
found formaldehyde and formate bound to and reacted with a variety of
cellular substances in all tissues-- just as the 1998 Trocho study
confirmed.

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

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

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

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

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
[selection]
"These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects (33), that has also
been considered carcinogenic (34,47). The repeated occurrence of claims
that aspartame produces headache and other neurological and
psychological secondary effects-- more often than not challenged by
careful analysis-- (5,9,10,15,48) may eventually find at least a partial
explanation in the permanence of the formaldehyde label, since
formaldehyde intoxication can induce similar effects (49).

The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame
may result in the progressive accumulation of formaldehyde adducts.

It may be further speculated that the formation of adducts can help to
explain the chronic effects aspartame consumption may induce on
sensitive tissues such as brain (6,9,19,50). In any case, the possible
negative effects that the accumulation of formaldehyde adducts can
induce is, obviously, long-term. The alteration of protein integrity
and function may needs some time to induce substantial effects.

The damage to nucleic acids, mainly to DNA, may eventually induce cell
death and/or mutations.

The results presented suggest that the conversion of aspartame methanol
into formaldehyde adducts in significant amounts in vivo should be
taken into account because of the widespread utilization of this
sweetener. Further epidemiological and long-term studies are needed to
determine the extent of the hazard that aspartame consumption poses for
humans."

http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male) alemany@...

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

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

Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science [retired 1992]
Arizona State University, Tempe, Arizona 85287 woodymonte@...
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.)

ETHANOL AND FOLIC ACID

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).

METHANOL CONTENT OF ASPARTAME SWEETENED BEVERAGES

An average aspartame-sweetened beverage would have a conservative
aspartame content of about 555 mg/liter (48, 51) and therefore, a
methanol equivalent of 56 mg/liter (56 ppm).

For example, if a 25 kg child consumed on a warm day,
after exercising, two-thirds of a two-liter bottle
of soft drink sweetened with aspartame, that child
would be consuming over 732 mg of aspartame (29 mg/kg). This alone
exceeds what the Food and Drug Administration considers the 99+
percentile daily consumption level of aspartame (48). The child would
also absorb over 70 mg of methanol from that soft drink.
This is almost ten times the Environmental Protection Agency's
recommended daily limit of consumption for methanol [in water].

To look at the issue from another perspective, the literature reveals
death from consumption of the equivalent of 6 gm of methanol (55, 59).
It would take 200 12 oz. cans of soda to yield the lethal equivalent of
6 gm of methanol.

According to FDA regulations,
compounds added to foods that are found to cause
some adverse health effect at a particular usage level are
actually permitted in foods only at much lower levels. The FDA has
established these requirements so that an adequate margin of safety
exists to protect particularly sensitive people and heavy consumers of
the chemical.
Section 170.22 of Title 21 of the Code of Federal Regulations
mandates that this margin of safety by 100-fold below the
"highest no-effect" level.

If death has been caused by the methanol equivalent of 200 12 oz. cans
of aspartame sweetened soda, one hundredth of that level
would be two cans of soda.

The relationship of the lethal dose
to the "highest no effect" level has tragically
not been determined for methanol (9, 11) but assuming very
conservatively that the level is one tenth of the lethal dose, the FDA
regulations should have limited consumption to approximately 2.4 ounces
of aspartame sweetened soft drink per day. [Published case reports show
severe reactions to tiny doses of aspartame in some reactors:
1.5, 4, or 6-8 mg aspartame, while a 12 oz can of diet soda provides
about 200 mg aspartame.]

The FDA allows a lower safety margin only when "evidence is submitted
which justifies use of a different safety factor." (21.C.F.R.170.22)
No such evidence has been submitted to the FDA for methanol.

Thus, not only have the FDA's requirements for acute toxicity not been
met, but also, no demonstration of chronic safety has been made. The
fact that methyl alcohol appears in other natural food products
increases greatly the danger of chronic toxicity developing by adding
another unnatural source of this dangerous cumulative toxin to the food
system.

NATURAL SOURCES OF METHANOL

Methanol does appear in nature.

To determine what impact the addition of a toxin will have on an
environment it is very helpful to accurately determine the background
levels of consumption.

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

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

In the recent denial by the Food and Drug Administration of my request
for a public hearing on this issue (13), the claim is made by them that
methanol occurs in fruit juices at an average of 140 parts per million
(a range of between 15-640 parts per million). This often used average
originates from an informative table in a conference paper presented by
Francot and Geoffroy (15). The authors explain that the data presented
in the table "may not" represent their work but "other authors" (15).

There is no methodology given nor is the original source cited and only
the identity of the lowest methanol source, grape juice (12 ppm), and
the highest, black currant (680 ppm), are revealed.
The other 22 samples used to generate this disarmingly high average are
left completely to the imagination.

The authors conclude their paper by insisting that "the
content of methanol in fermented or non-fermented beverages should not
be of concern to the fields of human physiology and public health."
They imply that wines "do not present any toxicity" due to the presence
of certain natural protective substances (15).

When they present their original data
relating to the methanol content of French wines (range 14-265 ppm)
or when the methanol content of any alcoholic beverage is given,
the ration of methanol to ethanol is also presented. Of the wines
they tested, the ratio associated with the highest methanol content
(265 ppm) indicates over 262 times as much ethanol present as methanol.

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

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

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

Long term storage in cans has a tendency to cause an increase in these
levels, but even after three years of storage,
testing has revealed only 62 mg/liter
of methanol, with an ethanol content of 484 mg/liter. This
is a ratio of almost eight times ethanol/methanol (28).

Testing done recently in Spain showed orange juice with
33 mg/liter methanol and 651 mg/liter ethanol (20/1 ratio) (45).

The range for grapefruit juices are similar, ranging
from 0.2 mg methanol/liter (27) to 43 mg methanol/liter (27).

The lowest ratio of any food item was found in canned grapefruit
sections with 50-70 mg/liter methanol
and 200-400 mg/liter ethanol (27), thus
averaging six molecules ethanol for every molecule of methanol.

This high ethanol to methanol ratio, even at these low ethanol
concentrations, may have some protective effect. As stated previously,
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).

Therefore if a liter of a high methanol content orange juice is
consumed, with 33 mg/liter of methanol and a 20/1 ration of
ethanol/methanol, only one molecule of methanol in 180 will be
metabolized into dangerous metabolites
until the majority of the ethanol has
been cleared from the bloodstream.

If a similar amount of methanol equivalent from aspartame were
consumed, there would be no competition (46).

Another factor reducing the potential danger associated with methanol
from natural juices is that they have an average caloric density of 500
Kcal/liter and high osmolarity which places very definite limits to
their consumption level and rate.

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

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

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

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

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

CONCLUSION

Simply because methanol is found "naturally" in foods, we can not
dismiss the need for carefully documented safety testing in appropriate
animal models before allowing a dramatic increase in its consumption.

We know nothing of the mutagenic, teratogenic or carcinogenic effect of
methyl alcohol on man or mammal (55, 59). Yet, if predictions are
correct (5), it won't be long before an additional 2,000,000 pounds of
it will be added to the food supply yearly (53).

Must this, then, constitute our test of its safety?

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TABLE I
AVAILABLE METHANOL IN VARIOUS BEVERAGES

Methanol mg/liter
Caloric Density Calories/Liter
Methanol (mg.) Consumed per 1000 Calories
Ratio Ethanol (wt.)/Ethanol (wt.)
Methanol (mg.) Consumption
per day
Juices

*Orange, fresh (28)
1 470 2 475 1
*Orange, fresh (45)
33 470 70 20 6

*Orange, fresh (31)
34 470 72 16 6

*Orange, Canned (28)
31 470 66 15 6

*Grapefruit, fresh (27)
1 400 1 2000 1

*Grapefruit (31)
43 400 108 5 7

*Grapefruit, Canned (31)
27 400 68 9 5
Grape (15)
12 660 18 - -

Alcoholic Beverages

Beer (4.5%)
0 400 - - -

Grain Alcohol (55)
1 2950 1 500000 -

Bourbon, 100 proof (55)
55 2950 19 9090 -

Rum, 80 proof (15)
73 2300 32 5000 -

Wines (French) (15)
White
32 800 44 2500 -

Rose
78 800 98 1000 -
Red
128 800 160 667 -

Pear
188 1370 137 250 -

Wines (American) (30)
Low
50 800 62 2500 -

High
325 800 406 385 -

Aspartame sweetened Beverages (48) 2 Liters 5 Liters

Uncarbonated Drinks (48)
55 8 6875 0 110 mg 275 mg

Cola (Carbonated) (48)
56 8 7000 0 112 mg 280 mg

Orange (Carbonated) (48)
91 8 11375 0 182 mg 455 mg
Aspartame, pure
25000

*17.6% of U.S. Population consume an average of 185.5 gm. of
Orange Juice a day (1)
* 1.1% of U.S. Population consume an average of 173.9 gm. of
Grapefruit Juice a day (1)
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