aspartame toxicity

methanol impurity in alcohol drinks [ and aspartame ] is turned into neurotoxic formic acid, prevented by folic acid

2008-03-14T17:46:00.000-07:00

methanol impurity in alcohol drinks [ and aspartame ] is turned into
neurotoxic formic acid, prevented by folic acid, re Fetal Alcohol Syndrome,
BM Kapur, DC Lehotay, PL Carlen at U. Toronto, Alc Clin Exp Res 2007 Dec.
plain text: detailed biochemistry, CL Nie et al. 2007.07.18: Rich Murray
2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524
____________________________________________________

[ Rich Murray comments: As a medical layman volunteer information
activist for aspartame and related toxicity issues since January 1999,
I note with appreciation the remarkable exponential progress on all
fronts, including a rapidly emerging consensus about the primary
importance of all toxicity challenges for our world.

This lengthy review features in detail two quite different, revolutionary
contributions, from Canada, and England and China.

It is indicative of our times that the CL Nie et al. study, 2007
appears in a free, open access journal-- indeed,
as all life and death information must.

Following rather vigorously, indeed blindly, the imperatives of
single-minded, profit-driven capitalist competition -- manipulating
adroitly research, education, media, citizens, governments -- many
great global corporations have inevitably created results that
oppose the common good. Alcohol and tobacco are well known.

Realistically, any further manipulations can only lead to inevitable
and even sudden corporate meltdowns, in the context of an
unfettered, cooperative, democratic global information forum,
the Internet.

Now, it is as easy and cheap to compose and instantly post a
30-page review as 3 pages a decade ago -- and such reviews
are archived forever in multiple collections, open via global search
engines to a billion Net citizens.

Perforce, and increasingly happily, all societal entities will have to
operate by high and shared voluntary universal standards
for the common good. ]

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2007.00541.x

Alcoholism: Clinical and Experimental Research
Volume 31 Issue 12 Page 2114-2120, December 2007

Bhushan M. Kapur, b.kapur@utoronto.ca;
Arthur C. Vandenbroucke, PhD, FCACB
Yana Adamchik,
Denis C. Lehotay, dlehotay@health.gov.sk.ca;
Peter L. Carlen carlen@uhnres.utoronto.ca;
(2007) Formic Acid, a Novel Metabolite of Chronic Ethanol
Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid
Alcoholism: Clinical and Experimental Research 31 (12), 2114-2120.
doi:10.1111/j.1530-0277.2007.00541.x

Abstract

Background:
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.

Objective:
To determine if FA levels are higher in the alcohol-drinking
population and to assess its neurotoxicity in organotypic
hippocampal rat brain slice cultures.

Methods:
Serum and CSF FA was measured in samples from both ethanol
abusing and control patients, who presented to a hospital emergency
department. [ CSF = Cerebral Spinal Fluid ]

FA's neurotoxicity and its reversibility by folic acid were assessed
using organotypic rat brain hippocampal slice cultures using clinically
relevant concentrations.

Results:
Serum FA levels in the alcoholics
(mean ± SE: 0.416 +- 0.093 mmol/l, n = 23)
were significantly higher than in controls
(mean ± SE: 0.154 +- 0.009 mmol/l, n = 82) (p < n =" 20),">0.15 mmol/l in CSF of 3 of the 4 alcoholic cases.

Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours
to the rat brain slice cultures caused neuronal death as measured by
propidium iodide staining.

When folic acid (1 umol/l) was added with the FA,
neuronal death was prevented. [ umol = micromole ]

Conclusions:
Formic acid may be a significant factor in the neurotoxicity of
ethanol abuse.

This neurotoxicity can be mitigated by folic acid administration
at a clinically relevant dose.

Key Words:
Formic Acid, Folic Acid, Methanol, Neurotoxicity, Alcoholism.

From the Department of Clinical Pathology (BMK),
Sunnybrook Health Science Centre,
Division of Clinical Pharmacology and Toxicology,
The Hospital for Sick Children, Toronto, Ontario, Canada;

St. Michael's Hospital (ACV), Toronto, Canada;

Department of Laboratory Medicine and Pathobiology
(BMK, ACV), Faculty of Medicine,
University of Toronto, Toronto, Ontario, Canada;

Departments of
Medicine (Neurology) and Physiology (YA, PLC),
Toronto Western Research Institute,
University of Toronto, Toronto, Ontario, Canada;

and University of Saskatchewan (DLC), Saskatchewan, Canada.

Received for publication May 1, 2007;
accepted September 24, 2007.

Reprint requests: Dr. Bhushan M. Kapur,
Department of Clinical Pathology,
Sunnybrook Health Science Centre,
2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada;
Fax: 416-813-7562; E-mail: b.kapur@utoronto.ca;

Copyright 2007 by the Research Society on Alcoholism.
DOI: 10.1111/j.1530-0277.2007.00541.x
Alcoholism: Clinical and Experimental Research 2007 Dec.
Alcohol Clin Exp Res, Vol. 31, No 12, 2007: pp 2114-2120

NEUROTOXICITY AND BRAIN damage are common
concomitants findings of chronic alcoholism
(Carlen and Wilkinson, 1987; Carlen et al., 1981; Harper,
2007).

The cause of ethanol-induced neurotoxicity is still unclear.

We present here a novel hypothesis for neurotoxicity:
increased formic acid (FA) levels produced from methanol
(MeOH), whose catabolism is blocked by ethanol.

Axelrod and Daly (1965) demonstrated the endogenous formation
of MeOH from S-adenosylmethionine (SAM) in the pituitary
glands of humans and various other mammalian species.

Presence of MeOH in the breath of human subjects was
reported by Ericksen and Kulkarni (1963).

Most alcoholic beverages also have a small amount of MeOH
as a congener (Sprung et al., 1988).

As ethanol (EtOH) has a higher affinity for
alcohol dehydrogenase (ADH) than MeOH,
EtOH is preferentially metabolized (Mani et al., 1970).

As a result, MeOH accumulation from endogenously produced
MeOH, and/or, that consumed as part of an alcoholic beverage,
has been reported in concentrations up to 2 mmol/l in heavy
drinkers (Majchrowicz and Mendelson, 1971).

Toxicity resulting from MeOH consumption is extensively
documented in both humans and animals and has been
attributed to its metabolite, FA (Benton and Calhoun, 1952;
Roe, 1946, 1955; Wood, 1912; Wood and Buller, 1904).

The rate of formate oxidation and elimination is dependent on
adequate levels of hepatic folic acid, particularly hepatic
tetrahydrofolate (THF)
(Johlin et al., 1987; Tephly and McMartin, 1974).

Significantly higher formate levels were obtained when
folate-deficient animals were exposed to MeOH as compared
with folate-sufficient animals (Lee et al., 1994;
McMartin et al., 1975; Noker et al., 1980).

To understand ethanol's toxicity, one must consider FA
produced from MeOH, and its elimination mediated by folic acid.

We postulate that in the chronically drinking patient,
we will find higher levels of FA than in the nondrinking population,
and that formate is neurotoxic.

We also hypothesize that treatment with folic acid, which is a
critical factor in the catabolism of FA, can prevent or
diminish FA neurotoxicity.

METHODS

Patient Samples

During our study period of 4 months, 23 patients whose serum
showed the presence of both ethanol and trace amounts
(<2 n =" 82)" n =" 20)" n =" 7" nm =" nanometer" p =" NS" nd =" not" control =" no" acid =" 1" p =" NS"> *OH + Fe,3+ + OH,-

HCO2,- + *OH --> *CO2,- + H2O

*CO2,- + O2 --> CO2 + *O2,-

Chance has shown that formate can be metabolized by the
catalase-peroxidative system (Chance, 1950).

When anti-oxidants are depleted, increased ROS are formed
(Treichel et al., 2004).

Formic acid-induced cell damage has been attributed
to the generation of the cytotoxic ROS species.

FA disrupts mitochondrial electron transport and energy production
by inhibiting cytochrome oxidase activity (Nicholls, 1975, 1976;
Sharpe et al., 1982)
and causes cell death by increased production of cytotoxic ROS
secondary to the blockade of the electron transport chain
(Reed and Savage, 1995).

Formyl group (CHO) is transferred to THF
resulting in the formation of carbon dioxide and water
Makar et al., 1990; Medinsky et al., 1997).

Our organotypic brain slice studies suggest that there is a
dose and time relationship between FA and neuronal cell death.

FA levels achieved in the blood of the alcohol drinking
population can cause neuronal cell death.

The FA concentrations we used in our studies are representative
and were achieved in 2 of the 4 patients in whom we had sequential
samples.

It is remarkable that neuronal cell death could be prevented
by folic acid, although the mechanism of this protection is unknown.

There is a large body of literature relating folic acid deficiency
to neural tube defect, but, there are no references
relating low levels of FA to neurotoxicity.

There are a few studies relating FA and mitochondrial inhibition,
with MeOH intoxication and retinal damage
(Seme et al., 1999, 2001).

Another study demonstrated toxic effects of high concentrations
of formate in dissociated primary mouse neural cell cultures
(Dorman et al., 1993).

The concentration of formate that resulted
in 50% lactate dehydrogenase leakage after an 8-hour incubation
was estimated to be 45 mmol/l.

The total intracellular ATP concentration was significantly
decreased following either 20 or 40 mmol/l FA
exposure for 8 hour.

This is consistent with the hypothesis that FA may inhibit
mitochondrial function resulting in decreased intracellular ATP
and formate-induced neurotoxicity.

Using organotypic hippocampal slices, which preserve neuronal
circuitry and are easily accessible for experimental manipulations
(Stoppini et al., 1991),
our group has previously shown that
free radical overproduction in hippocampal pyramidal neurons
during ischemia/reoxygenation
depended on the activation of glutamate receptors,
and was associated with elevations of intracellular calcium.

Mitochondria are thought to be the principal source of
glutamate-mediated, calcium-dependent free radical production
in cultured cortical neurons
(Dugan et al., 1995; Reynolds and Hastings, 1995).

Although we did not investigate FA levels below 1 mmol/l,
it is conceivable that a continuous exposure to low,
but, above normal levels (>0.15 mmol/l), may also be cytotoxic
and may be part of the pathology of alcohol-related
organ damage (Jiang et al., 2003)
including the fetal alcohol spectrum disorder.

CONCLUSION

Our studies, for the first time, have shown that MeOH from
endogenous sources and from congeners present in alcoholic
beverages can lead to FA concentrations that are neurotoxic.

Therapeutic intervention with folic acid could be a significant
treatment modality in preventing FA mediated cytotoxicity,
especially neurotoxicity, in alcoholics.

ACKNOWLEDGMENT

This study was supported by a grant from the CIHR.

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____________________________________________________

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.:
Murray 2007.11.27
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 27, 2007
http://groups.yahoo.com/group/aspartameNM/message/1495

http://www.faslink.org/Formic%20Acid%20Kapur.htm

Brief Summary:

Methanol in small amounts is present along with ethanol in beverage
alcohol.
[Murray: and about the same amounts from aspartame diet sodas]

The body's natural enzymes preferentially metabolize ethanol while
methanol breaks down into highly neurotoxic Formic Acid.

Use of high levels of Folic Acid was found to inhibit brain damage
caused by the methanol.

The use of Folic Acid during pregnancy has been recommended
for several years to prevent neural tube defects.

However, this study indicates that even higher levels of Folic Acid
can be very beneficial to the developing baby, particularly where
alcohol exposure is a factor.

Folic Acid is mandated as an additive to all flour sold in Canada.

The debate has begun on its required addition to all beverage
alcohol to help mitigate damage caused to both infants and adults.

Formic Acid in the Drinking patient and the expectant mother
Dr. Bhushan M. Kapur
Departments of Laboratory Medicine,
St. Michael's Hospital , Toronto, Ontario, Canada

Abstract

Methanol is produced endogenously in the pituitary glands of humans
and is present as a congener in almost all alcoholic beverages.

Ethanol and methanol are both bio-transformed by alcohol
dehydrogenase; however, ethanol has greater affinity for the enzyme.

Since ethanol is preferentially metabolized by the enzyme, it is not
surprising that trace amounts of methanol, most likely originating from
both sources, have been reported in the blood of people
who drink alcohol.

Toxicity resulting from methanol is very well documented
in both humans and animals and is attributed to its toxic metabolite
formic acid.

To understand ethanol toxicity
and Fetal Alcohol Spectrum Disorders, it is important to consider
methanol and its metabolite, formic acid, as
potential contributors to the toxic effects of alcohol.

Accumulation of methanol suggests that alcohol-drinking
population should have higher than baseline levels of formic acid.

Our preliminary studies do indeed show this.

Chronic low-level exposure to methanol has been suggested to
impair human visual functions.

Formic acid is known to be toxic to the optic nerve.

Ophthalmological abnormalities are a common finding in children
whose mothers used alcohol during pregnancy.

Formic acid, a low molecular weight substance, either crosses the
placenta or may be formed in-situ from the water soluble methanol
that crosses the placenta.

Embryo toxicity from formic acid has been reported
in an animal model.

To assess neurotoxicity we applied low doses of formic acid
to rat brain hippocampal slice cultures.

We observed neuronal death with a time and dose response.

Formic acid requires folic acid as a cofactor for its elimination.

Animal studies have shown that when folate levels are low, the
elimination of formic acid is slower and formate levels are elevated.

When folic acid was added along with the formic acid
to the brain slice cultures, neuronal death was prevented.

Therefore, folate deficient chronic drinkers may be at higher risk of
organ damage.

Women who are folic acid deficient and consume alcohol may have
higher levels of formic acid and should they become pregnant,
their fetus may be at risk.

To our knowledge low level chronic exposure to formic acid and its
relationship to folic acid in men or women who drink alcohol has
never been studied.

Our hypothesis is that the continuous exposure to low levels of
formic acid is toxic to the fetus and may be part of the etiology of
Fetal Alcohol Spectrum Disorders.
____________________________________________________

http://www.come-over.to/FAS/

The incidence of Fetal Alcohol Syndrome in America
is 1.9 cases per 1,000 births (1/500).

Incidence of babies with disabilities
resulting from prenatal alcohol exposure: 1/100!
____________________________________________________

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame,
AM Hill & DV Belsito, Nov 2003: Murray 4.4.4 rmforall [150 KB]

[ Extracts ]

McMartin, KE et al 1979, put 3,000 mg/kg methanol in the
stomachs of small monkeys and, 18 hours later found accumulation
of formate in liver, kidney, optic nerve, cerebrum, and midbrain
in 2 of three monkeys.

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 kmcmar@lsuhsc.edu;
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 their detection limit.

They did report widespread accumulation of formic acid
in five tissues.

The use of inadequate tests is common in industry research that is
funded to claim the safety of profitable toxins.

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

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

Methanol was administered [ by nasogastric tube ] either to untreated
cynomolgus monkeys [ 2-3.5 kg ] or to a folate-deficient cynomolgus
monkey which exhibits exceptional sensitivity to the toxic effects of
methanol.

Marked formic acid accumulation in the blood and in body fluids and
tissues was observed.

No formaldehyde accumulation was observed in the blood and no
formaldehyde was detected in the urine, cerebrospinal fluid, vitreous
humor, liver, kidney, optic nerve, and brain in these monkeys at a
time when marked metabolic acidosis and other characteristics of
methanol poisoning were observed.

Following intravenous infusion into the monkey, formaldehyde was
rapidly eliminated from the blood with a half-life of about 1.5 min
and formic acid levels promptly increased in the blood.

Since formic acid accumulation accounted for the metabolic acidosis
and since ocular toxicity essentially identical to that produced in
methanol poisoning has been described after formate treatment,
the predominant role of formic acid as the major metabolic agent
for methanol toxicity is certified.

Also, results suggest that formaldehyde is not a major factor in the
toxic syndrome produced by methanol in the monkey."

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

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

Monkeys, like people, are susceptible to methanol toxicity.

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

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

For the methanol sensitive, folate-deficient monkey A, the assay
used was the chromatropic acid method,
with a detection limit of .025 mmol/L.

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

Meanwhile, in the methanol sensitive, folate-deficient monkey A,
the blood formate level rose by 18 hours from 0.18 to 10.02 mEq/L.
[ I assume that a mEq is equivalent to a mmol -- let me know
if I'm wrong. ]

The formate detection limits for the assays were not given
in this report.

The formate level in the vitreous humor of the eye of monkey A
was 7.90 mEq/L.

It is well known that formate is extremely damaging to the eye.

For unexplained reasons, formate levels in the five tissues and
cerebrospinal fluid were not measured in the methanol sensitive,
folate-deficient monkey A.,
in the cerebrospinal fluid of monkey B,
or in the optic nerve of monkey C.

Formaldehyde was not measured in the optic nerve of Monkey A.

The kidney formate level for monkey B was 6.33
and for C was only 0.44,
with no comment or explanation given.

The experiment seems arbitrary, capricious, and erratic.

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

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

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

Monkeys B and C were normal, not extra vulnerable to methanol,
and were given 3,000 mg/kg methanol, and samples taken at 18 hr.

Formaldehyde was detected only in the blood of Monkey B,
while formate was found in 8 and 10, respectively,
of the 10 fluid and tissue samples in Monkeys B and C.

For instance, the lowest value of formate, except for zero-time blood,
for each monkey was in the midbrain, 2.16 mmol/kg for Monkey B
(24 times the detection limit for the chromatropic acid method)
and 1.02 mmol/kg (1.3 times the detection for the dimedon method)
for Monkey C.

This shows accumulation of formate in liver, kidney, optic nerve,
cerebrum, and midbrain.

"Thus, whereas one can associate formate intimately with ocular
toxicity in the monkey, no association of formaldehyde with ocular
toxicity can be made at this time.

It is not possible to completely eliminate formaldehyde as a toxic
intermediate because formaldehyde could be formed slowly within
cells and interfere with normal cellular function without ever obtaining
levels that were detectable in body fluids..."

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

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

"Abstract:
Methanol toxicity in humans and monkeys is characterized by a latent
period of many hours followed by a metabolic acidosis
and ocular toxicity.

This is not observed in most lower animals.

The metabolic acidosis and blindness is apparently due to
formic acid accumulation in humans and monkeys,
a feature not seen in lower animals.

The accumulation of formate is due to a deficiency in formate
metabolism which is, in turn, related, in part,
to low hepatic tetrahydrofolate (H4 folate).

An excellent correlation between hepatic H4 folate and
formate oxidation rates has been shown within and across species.

Thus, humans and monkeys possess low hepatic H4 folate levels,
low rates of formate oxidation and accumulation of formate
after methanol.

Formate, itself, produces blindness in monkeys in the absence of
metabolic acidosis.

In addition to low hepatic H4 folate concentrations, monkeys and
humans also have low hepatic 10-formyl H4 folate dehydrogenase
levels, the enzyme which is the ultimate catalyst for conversion of
formate to carbon dioxide.

This review presents the basis for the role of folic acid-dependent
reactions in the regulation of methanol toxicity.
Publication Types: Review Review, Academic PMID: 1997785"

p. 1035 "In the past, formaldehyde has often been suggested as the
methanol metabolite which produces toxicity (34,35).

Today, a great deal of information is available concerning its lack of
such a role.

The presence of elevated formaldehyde levels in body fluids or
tissues following methanol administration has not been observed.

No formaldehyde has been detected in blood, urine or tissues
obtained from methanol-treated animals (36,37) and,
in methanol-poisoned humans, formaldehyde increases
have not been observed....

About 85% of a low dose of 14C-formaldehyde [radioactive label]
is excreted as pulmonary 14CO2 (49,50)....."

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

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

50. Xenobiotica 1982 Feb; 12(2): 119-24.
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.
1. The metabolism of [14C]formaldehyde has been investigated
in the male Sprague-Dawley rat.
It is extensively oxidized to CO2 and formate,
which is excreted in the urine.
2. Two radioactive compounds isolated from the urine of rats dosed
with [14C] formaldehyde have been identified as
N-(hydroxymethyl)urea and
N,N'-bis-(hydroxymethyl)urea, and shown to be urinary 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
____________________________________________________

new details on how formaldehyde and formic acid from methanol are
neurotoxic: Chun Lai Nie, Rong Giao He, et al, PLoS ONE 2(7):
e629 2007.07.18 Chinese Academy of Sciences, Beijing:
Murray 2007.09.01
http://groups.yahoo.com/group/aspartameNM/message/1470

" Recent studies have shown that neurodegeneration
is closely related to misfolding and aggregation of neuronal tau. "

" The significant protein tau aggregation induced by formaldehyde
and the severe toxicity of the aggregated tau to neural cells may
suggest that toxicity of methanol and formaldehyde ingestion
is related to tau misfolding and aggregation. "

" Neuronal tau is an important protein in promoting and stabilizing
the microtubule system involved in cellular transport and neuronal
morphogenesis. "

" Both formaldehyde and acetaldehyde can go through the
blood-brain barrier and cause some lesions to CNS,
especially our visual system [38].

Clinically, the lethal dose of formaldehyde for human beings is
about 0.08% in the circulation [39].

We have shown in the present study that formaldehyde can
significantly induce tau aggregation and polymerization at
concentrations even lower than 0.08%,
the clinical dose of toxicosis. "

" Formaldehyde exposure leads to formation of DNA/protein
crosslinks, a major mechanism of DNA damage.

The DNA/protein crosslinks have been used as a measure
of dose in drug delivery [20].

Formaldehyde, as a crosslinking agent, also reacts with
thiol and amino groups, leading to protein polymerization [21], [22].

Furthermore, methanol ingestion is an important public health
concern because of the selective actions of its toxic metabolites,
formaldehyde and formic acid, on the retina, the optic nerves
and the central nervous system (CNS) [23].

Illicit consumption of industrial methylated spirits can cause severe
and even fatal illness [24].

In the liver and retina, methanol is oxidized by alcohol
dehydrogenase, resulting in formaldehyde.

In semicarbazide-sensitive amine oxidase (SSAO)-mediated
pathogenesis of Alzheimer's disease, formaldehyde interacts
with B-amyloids and produces irreversibly cross-linked neurotoxic
amyloid-like complexes [21], [22], [25].

We have examined the role of formaldehyde in misfolding
of protein tau [26].

In particular, we investigated the toxicity of formaldehyde-induced
tau aggregates on human neuroblastoma cells (SH-SY5Y cell line)
and rat hippocampal cells [27].

The results showed that low concentrations (0.01 - 0.1%) of
formaldehyde are sufficient to induce formation of amyloid-like tau
aggregates, which can induce apoptosis of both SH-SY5Y
and hippocampal cells.

This may be significant to understand the mechanism of chronic
damage caused by methanol toxicity
and formaldehyde stress [18], [28].

However, we have still not known the mechanism of protein tau
aggregation in the presence of formaldehyde at low concentrations.

The present study concerns the characteristic of misfolding and
polymerization of extracellular and intracellular neuronal tau induced
by formaldehyde at low concentrations. "

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17637844
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000629
free full text

Formaldehyde at Low Concentration Induces Protein Tau
into Globular Amyloid-Like Aggregates In Vitro and In Vivo
PLoS ONE. 2007 Jul 18; 2(7): e629.
doi:10.1371/journal.pone.0000629
Chun Lai Nie 1,
Yan Wei 1,
Xinyong Chen 2,
Yan Ying Liu 1,
Wen Dui 1,
Ying Liu 1,
Martyn C. Davies 2, Martyn.Davies@nottingham.ac.uk;
Saul J.B. Tendler 2, Saul.Tendler@nottingham.ac.uk;
Rong Giao He 1* herq@sun5.ibp.ac.cn;

1 State Key Laboratory of Brain and Cognitive Science,
Institute of Biophysics, Graduate School,
Chinese Academy of Sciences, Chaoyang District, Beijing, China,

2 Laboratory of Biophysics and Surface Analysis,
School of Pharmacy, The University of Nottingham,
Nottingham, United Kingdom

Received: March 5, 2007; Accepted: June 13, 2007;
Published: July 18, 2007

Copyright: © 2007 Nie et al.
This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

* To whom correspondence should be addressed.
E-mail: herq@sun5.ibp.ac.cn;

Abstract

Recent studies have shown that neurodegeneration is closely
related to misfolding and aggregation of neuronal tau.

Our previous results show that neuronal tau aggregates in
formaldehyde solution and that aggregated tau induces apoptosis
of SH-SY5Y and hippocampal cells.

In the present study, based on atomic force microscopy (AFM)
observation, we have found that formaldehyde at low concentrations
induces tau polymerization whilst acetaldehyde does not.

Neuronal tau misfolds and aggregates into globular-like polymers
in 0.01 - 0.1% formaldehyde solutions.

Apart from globular-like aggregation, no fibril-like polymerization
was observed when the protein was incubated with formaldehyde
for 15 days.

SDS-PAGE results also exhibit tau polymerizing in the presence
of formaldehyde.

Under the same experimental conditions, polymerization of bovine
serum albumin (BSA) or a-synuclein was not markedly detected.

Kinetic study shows that tau significantly misfolds and polymerizes
in 60 minutes in 0.1% formaldehyde solution.

However, presence of 10% methanol prevents protein tau from
polymerization.

This suggests that formaldehyde polymerization is involved in tau
aggregation.

Such aggregation process is probably linked to the tau's special
"worm-like" structure, which leaves the e-amino groups of Lys
and thiol groups of Cys exposed to the exterior.

Such a structure can easily bond to formaldehyde molecules
in vitro and in vivo.

Polymerizing of formaldehyde itself results in aggregation of
protein tau.

Immunocytochemistry and thioflavin S staining of both endogenous
and exogenous tau in the presence of formaldehyde at low
concentrations in the cell culture have shown that formaldehyde can
induce tau into amyloid-like aggregates in vivo during apoptosis.

The significant protein tau aggregation induced by formaldehyde
and the severe toxicity of the aggregated tau to neural cells may
suggest that toxicity of methanol and formaldehyde ingestion is
related to tau misfolding and aggregation.

Funding: This project was supported by NSFB (06J11),
the NSFC (Nos. 90206041, 30570536 and 30621004)
and 973-Project (2006CB500703 and 2006CB911003).

Competing interests: The authors have declared that no competing
interests exist.

Academic Editor: Christophe Herman, Baylor College of Medicine,
United States of America

Introduction

Neuronal tau is an important protein in promoting and stabilizing the
microtubule system involved in cellular transport
and neuronal morphogenesis.

The tau molecule can be subdivided into an amino-terminal domain
that projects from the microtubule surface and a carboxy-terminal
microtubule-binding domain.

The discovery that incubation of bacterially expressed human tau
with sulphated glycosaminoglycans leads to bulk assembly of tau
filaments [1], making it possible to obtain structural information [2].

By using circular dichroism measurement, Schweer et al. have found
that protein tau lacks secondary structures and is considered in a
"worm-like" conformation with a high flexibility [3].

Therefore, the side-chains of amino acids such as Lys, Cys, Thr
and Ser are mostly exposed and vulnerable to chemical modification.

Recently, many laboratories have found that misfolding and
aggregation of protein tau are involved in neurodegeneration
[2], [4] - [6].

Protein tau has been found as the major component of paired
helical filaments in neurofibrillary tangles in the brains of Alzheimer's
patients, where abnormal hyper-phosphorylation induces tau to
misfold and form the paired helical filaments,
depositing in the cytoplasm of neurons [7] - [10].

Recently, a great deal of evidence has demonstrated that oxidation
and glycation stresses are key causal factors of neuronal degenerative
diseases [11] - [13].

Both of them inevitably produce a variety of unsaturated carbonyls
as intermediates, like malondialdehyde and 4-hydroxynonenal,
which usually cause carbonyl-amino crosslinking and lead to
accumulation of irreversible changes (like lipofuscin) related to
various neurodegenerative diseases in particular [14] - [16].

Such carbonyl stress-related reactions (carbonylation) can form
unstable and reversible 1:1 amino-carbonyl (Shiff's base)
compounds at an early stage of protein modification [16], [17].

Carbonylation binds and blocks a-/e- amino groups,
and results in changes in charge and conformation of a protein.

In order to investigate the relationship between carbonylation and
protein tau misfolding, the basic and simplest carbonyl compound
formaldehyde [18] has come into our attention.

Formaldehyde is a common environmental agent found in paint, cloth,
exhaust gas and many other medicinal and industrial products [19].

Formaldehyde exposure leads to formation of DNA/protein
crosslinks, a major mechanism of DNA damage.

The DNA/protein crosslinks have been used as a measure of dose
in drug delivery [20].

Formaldehyde, as a crosslinking agent, also reacts with thiol and
amino groups, leading to protein polymerization [21], [22].

Furthermore, methanol ingestion is an important public health
concern because of the selective actions of its toxic metabolites,
formaldehyde and formic acid, on the retina, the optic nerves
and the central nervous system (CNS) [23].

Illicit consumption of industrial methylated spirits can cause severe
and even fatal illness [24].

In the liver and retina, methanol is oxidized by alcohol
dehydrogenase, resulting in formaldehyde.

In semicarbazide-sensitive amine oxidase (SSAO)-mediated
pathogenesis of Alzheimer's disease, formaldehyde interacts
with B-amyloids and produces irreversibly cross-linked neurotoxic
amyloid-like complexes [21], [22], [25].

We have examined the role of formaldehyde
in misfolding of protein tau [26].

In particular, we investigated the toxicity of formaldehyde-induced
tau aggregates on human neuroblastoma cells (SH-SY5Y cell line)
and rat hippocampal cells [27].

The results showed that low concentrations (0.01 - 0.1%) of
formaldehyde are sufficient to induce formation of amyloid-like tau
aggregates, which can induce apoptosis of both SH-SY5Y
and hippocampal cells.

This may be significant to understand the mechanism of chronic
damage caused by methanol toxicity
and formaldehyde stress [18], [28].

However, we have still not known the mechanism of protein tau
aggregation in the presence of formaldehyde at low concentrations.

The present study concerns the characteristic of misfolding and
polymerization of extracellular and intracellular neuronal tau induced
by formaldehyde at low concentrations.....

Discussion

Clinical lethal dose of formaldehyde

Why did we investigate tau misfolding in the presence of
formaldehyde at low concentrations (0.01 - 0.1%)?

Methanol and ethanol are metabolized to formaldehyde and
acetaldehyde respectively in our hepatocytes
and some neural cells [36], [37].

Both formaldehyde and acetaldehyde can go through the
blood-brain barrier and cause some lesions to CNS,
especially our visual system [38].

Clinically, the lethal dose of formaldehyde for human beings is
about 0.08% in the circulation [39].

We have shown in the present study that formaldehyde can
significantly induce tau aggregation and polymerization at
concentrations even lower than 0.08%,
the clinical dose of toxicosis.

The same low concentration of formaldehyde did not induce
polymerization of BSA though theoretically it will cause any
protein to polymerize if the concentration is high enough.

On the other hand, although it is known that acetaldehyde is
acutely toxic and would covalently bind to proteins and other
macromolecules [40], in our AFM and SDS-PAGE studies
we did not observe tau polymerization caused by acetaldehyde at
the concentration range that we studied (0.1 - 1%)......

Tau aggregation relating to methanol and formaldehyde toxicity

Methanol is an ocular toxicant, which causes visual dysfunction and
often leads to blindness after acute exposure.

However, physiological and biochemical changes responsible
for the toxicity have not yet been well understood [28].

According to a recent report, humans are uniquely sensitive to the
toxicity of methanol, as they have limited capacity to oxidize and
detoxify formic acid.

Thus, the toxicity of methanol in humans is characterized by formic
acidaemia, metabolic acidosis, blindness or serious visual impairment,
mild central nervous system depression
and even death [23], [27], [28].

However, methanol toxicosis induces progressive complications
to CNS.

It is hard to explain the progressively chronic damage by local
accumulation of formic acid alone.

Therefore, the potential effect of formaldehyde on protein
misfolding may be significant, although formaldehyde remains
in the human body for only a short time.

In semicarbazide-sensitive amine oxidase (SSAO)-mediate
pathogenesis of Alzheimer's disease, formaldehyde interacts with
B-amyloids and produces irreversibly cross-linked neurotoxic
amyloid-like complexes [21], [22], [25].

Our studies showed that formaldehyde induced neuronal tau
to aggregate.

The amyloid-like tau induces apoptosis of SY5Y
and hippocampal cells [27].

In fact, chemically, formaldehyde reacts with thiol and
amino groups instantly,
resulting in subsequent misfolding of neuronal tau (Figure 11).

This suggests that amyloid-like tau is involved in methanol toxicosis,
especially the damage of neurons and the resulted complications
after exposure to formaldehyde.

Although there have been many studies on methanol and
formaldehyde intoxication [23], [24], none of them has addressed
the contribution of protein misfolding to the pathological mechanism,
in particular the effect of formaldehyde on protein conformation
and polymerization.

Interestingly, neurofibrillary tangles have been found in brains of
chronic alcoholics possessing neuropathological signs
of thiamine-deficiency [40], [47].

This suggests that tau misfolding may be involved in the
alcohol-induced pathological pathway.

Khlistunova and his colleagues found that neuronal tau repeat domain
could aggregate in vivo and was toxic to neuronal cells.

The degree of tau aggregation and toxicity depends on the propensity
of the B-structure [2], [48].

In the present study, we have demonstrated that amyloid-like
intracellular tau aggregates could induce cell apoptosis, a similar result
as that obtained for extracellular amyloid or a-synuclein [49] -- [51].

This suggests that an enriched B-sheet structure is important to
amyloid-like protein aggregation and neurotoxicity.

In our experiments, a low concentration of formaldehyde induced
both extracellular and intracellular tau proteins to aggregate into
cell-toxic amyloid-like granular aggregates [27].

It appears to provide a new mechanism for triggers of tauopathies
in the formaldehyde toxicosis.....

Acknowledgments

We thank Ms. Ya-Qun Zhang for technical assistance
and Dr. Ya-Jie Xu for providing the clone of HA-tau40.

Author Contributions

Conceived and designed the experiments: RH.
Performed the experiments: CN YW YL WD.
Analyzed the data: CN.
Wrote the paper: CN RH YL XC MD ST.

References.....

#19 Quievryn G, Zhitkovich A. (2000)
Loss of DNA-protein crosslinks from formaldehyde-exposed cells
occurs through spontaneous hydrolysis and an active repair process
linked to proteosome function.
Carcinogenesis 21: 1573 - 1580.

#20 Heck H, Casanova M. (1999)
Pharmacodynamics of formaldehyde: applications of a model for the
arrest of DNA replication by DNA-protein cross-links.
Toxicol Appl Pharmacol 160: 86 - 100.

#21 Yu PH, Lu LX, Fan H, Kazachkov M, Jiang ZJ, et al. (2006)
Involvement of semicarbazide-sensitive amine oxidase-mediated
deamination in lipopolysaccharide-induced
pulmonary inflammation.
Am J Pathol 168: 718 - 726.

#22 Yu PH. (2001)
Involvement of cerebrovascular semicarbazide-sensitive amine
oxidase in the pathogenesis of Alzheimer's disease
and vascular dementia.
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#23 Eells JT, Henry MM, Lewandowski MF, Seme MT,
Murray TG. (2000)
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Neurotoxicology 21: 321 - 330.

#24 Dayan AD, Paine AJ. (2001)
Mechanisms of chromium toxicity, carcinogenicity
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#25 Gubisne-Haberle D, Hill W, Kazachkov M,
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#26 Nie CL, Zhang W, Zhang D, He RQ. (2005)
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#27 Nie CL, Wang XS, Liu Y, Perrett S, He RQ. (2007)
Amyloid-like aggregates of neuronal tau induced by formaldehyde
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BMC Neurosci 8: 9.

#28 Garner CD, Lee EW, Louis-Ferdinand RT. (1995)
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#32 Pomerantz M, Bittner S, Khader SB. (1982)
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#36 Barceloux DG, Bond GR, Krenzelok EP,
Cooper H, Vale JA. (2002)
American Academy of Clinical Toxicology practice guidelines
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#37 Valentine WM. (1990)
Toxicology of selected pesticides, drugs, and chemicals.
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#38 Shcherbakova LN, Tel'pukhov VI, Trenin SO,
Bashilov IA, Lapkina TI. (1986)
[Permeability of the blood-brain barrier
to intra-arterial formaldehyde].
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[ Biull Eksp Biol Med. 1986 Nov; 102(11): 573-5.
[Permeability of the blood-brain barrier to intra-arterial
formaldehyde]
[Article in Russian]
Shcherbakova LN, Tel'pukhov VI, Trenin SO,
Bashilov IA, Lapkina TI.

Formaldehyde concentration was assessed in the brain,
cerebrospinal liquor, arterial and venous blood of intact animals
and following its intraarterial injections.

It is concluded that formaldehyde is capable of penetrating
through the blood-brain barrier, with the degree of permeability
depending on blood formaldehyde concentration.

The distribution of formaldehyde in the blood-brain-cerebrospinal
liquor system suggests the presence of both protein-bound
and unbound formaldehyde forms in the organism.
PMID: 3779084 ]

#39 Erkrath KD, Adebahr G, Kloppel A. (1981)
[Lethal intoxication by formalin during dialysis (author's transl)].
Z Rechtsmed 87: 233 - 236.

#40 Niemela O. (1999)
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ethanol-induced oxidative stress.
Front Biosci 4: D506 - D513.

#45 Jiang W, Schwendeman SP. (2000)
Formaldehyde-mediated aggregation of protein antigens:
comparison of untreated and formalinized model antigens.
Biotechnol Bioeng 70: 507 - 517.

#46 Rait VK, O'Leary TJ, Mason JT. (2004)
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#47 Cullen KM, Halliday GM. (1995)
Neurofibrillary tangles in chronic alcoholics.
Neuropathol Appl Neurobiol 21: 312 - 318.
____________________________________________________

Note: many recent aspartame bans.....

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit aspartame,
MSG, artificial flavors dyes preservatives additives, trans fats, salt
"nasties" to protect kids from ADHD: leading UK media:
Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring agents
will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham,
The Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1513
metabolic syndrome is tied to diet soda, PL Lutsey, LM Steffen,
J Stevens, Circulation 2008.01.22: role of formaldehyde and
formic acid from methanol in wines, liquors, or aspartame?:
Murray 2008.02.21

"But the one-third who ate the most fried food increased their risk
by 25 percent, compared with the one-third who ate the least, and
surprisingly, the risk of developing metabolic syndrome was 34
percent higher among those who drank one can of diet soda a day
compared with those who drank none.

"This is interesting," said Lyn M. Steffen, an associate professor of
epidemiology at the University of Minnesota and a co-author of the
paper, which was posted online in the journal Circulation on Jan. 22.
"Why is it happening? Is it some kind of chemical in the diet soda,
or something about the behavior of diet soda drinkers?""

"The diet soda association was not hypothesized
and deserves further study."

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

http://groups.yahoo.com/group/aspartameNM/message/1511
vinyl acetate, ethyl alcohol, or aspartame in womb increases later
cancers in adults with lifetime exposure in many studies, M Soffritti
et al, Ramazzini Foundation, Basic Clin. Pharm. Toxicol. 2008 Feb.:
Rich Murray 2008.02.07

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.

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation cancer studies
2007.06.25: Murray 2007.07.18

30 female pet store rats drinking lifelong 13.5 mg aspartame,
1/3 packet of Equal, had 33% with obvious tumors -- also bulging,
sick, and missing eyes, paralysis, obesity, skin sores -- agrees with
Ramazzini Foundation results, Victoria Inness-Brown:
Murray 2008.02.15
http://rmforall.blogspot.com/2008_02_01_archive.htm
Friday, February 15, 2008
http://groups.yahoo.com/group/aspartameNM/message/1521

http://groups.yahoo.com/group/aspartameNM/message/1490
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: Murray 2007.11.27

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books:
updated research review of 2004.07.16: Murray 2006.05.11

http://groups.yahoo.com/group/aspartameNM/message/1469
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:
Murray 2007.08.31

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
http://rmforall.blogspot.com/2008_02_01_archive.htm
Monday, February 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1517

"Alcohol dehydrogenase ADH is required for the conversion of
methanol to formaldehyde (112).

ADH is not a common enzyme in the human body -- not many cells
in the human body contain this enzyme.

The human breast is one of the few organs in the body with a high
concentration of ADH (190b), and it is found there exclusively in the
mammary epithelial cells, the very cells known to transform into
adenocarcinoma (190c) (breast cancer).

The most recent breast cancer scientific literature implicates ADH
as perhaps having a pivotal role in the formation of breast cancer,
indicating a greater incidence of the disease in those
with higher levels of ADH activity in their breasts (190a)."

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
http://rmforall.blogspot.com/2007_12_01_archive.htm
Wednesday, December 26 2007
http://groups.yahoo.com/group/aspartameNM/message/1498

bias, omissions, incuriosity = opportunity, aspartame safety
evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more,
2007 Sept, Ajinomoto funded 98 pages html [ $ 32 pdf ]:
Murray 2007.09.15
http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007

MSG and Aspartame -- A Personal Story, TV health reporter
Dick Allgire (vegetarian) healed of migraines and panic attacks:
Murray 2008.02.12
http://rmforall.blogspot.com/2008_02_01_archive.htm
Tuesday, February 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1520

"Of course, everyone chooses, as a natural priority, to enjoy
peace, joy, and love by helping to find, quickly share, and positively
act upon evidence about healthy and safe food, drink, and
environment."

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

http://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 120 members, 1,524 posts in a public archive

http://groups.yahoo.com/group/aspartame/messages
group with 1,077 members, 22,286 posts in public archive
____________________________________________________

Hawaii House Concurrent Resolution #132 for Health Department panel to decide asparetame ban by early 2010

2008-03-14T17:42:00.000-07:00

Hawaii House Concurrent Resolution #132 for Health Department panel to decide
aspartame ban by early 2010, Hawaii Rep. Josh Green MD, Health Committee
Chair: Murray 2008.03.12
http://rmforall.blogspot.com/2008_03_01_archive.htm
Wednesday, March 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1525
_____________________________________________________

www.capitol.hawaii.gov/session2008/bills/HCR132_.pdf

Hawaii House of Representatives H.C.R. No. 132,
Twenty-fourth Legislature,

State of Hawaii -- House Concurrent Resolution

Requesting the Director of Health to form a work group to explore
the need to ban or better label products containing the artificial
sweetener aspartame.

WHEREAS, discovered in 1965, aspartame was first approved in the
United States in 1981 and is one of the most widely used artificial
sweeteners; and

WHEREAS, when metabolized by the body, aspartame is broken
down into two common amino acids, aspartic acid and phenylalanine,
and a small amount of a third substance, methanol; and
[ Note: the aspartame molecule becomes equal numbers of aspartic
acid, phenylalanine, and methanol molecules (which although light weight,
are more chemically active by far, being turned quickly into nearly the
same number of molecules of formaldehyde and then formic acid,
enough to have toxic effects in every cell in the body by binding with
and impairing DNA, RNA, and protein molecules. ]

WHEREAS, these three substances occur in similar or greater amounts
in common foods; and
[ Note: methanol and formaldehyde are also supplied by dark wines
and liquors (the major cause of "morning after" hangovers), tobacco and
wood smoke, fumes from faulty furnaces, heaters and stoves, many fruits
and vegetables (when heated in canning, fermented, or degraded by
colonic bacteria), mobile homes and RVs, particleboard, new buildings
new cars, carpets, drapes, and furniture, mortuaries, medical training
and research, many cleaners and disinfectants, many personal care
products ranging from leather to hair dyes, and more, including many
Asian foods. ]

WHEREAS, aspartame continues to be the subject of strong public
controversy regarding its safety; and

WHEREAS, some studies have recommended further investigation into
the possible connection between aspartame and diseases such as brain
tumors, brain lesions, and lymphoma; and
[ Note: the range of symptoms also includes headache, fatigue, poor
memory, irritability, lassitude, mania, anxiety, depression, "brain fog",
insomnia, dizziness, many body pains and muscle cramps, restless legs,
interstitial cystitis, eye and vision problems, tinnitus, dry eyes and
mouth,
skin rashes, diarrhea or constipation, partial paralysis (often confused as
MS), ideopathic seizures, weight gain or loss, blood sugar swings,
craving and addiction, impaired fertility and pregnancy, "spontaneous"
abortion, premature birth, low birth weight, birth defects, sudden infant
death syndrome, autism, and early diabetes -- this dazzling litany of
outcomes is the natural result of chronic, long-term, low-level exposure
to formaldehyde and formic acid. Naturally, there are countless
interactions with other drugs and toxins, as well as major and complex
individual genetic variations.

Cheap, safe folic acid protects against formaldehyde toxicity in most
people. ]

WHEREAS, some human and animal studies have found adverse effects
and some have found no adverse effects; and [ Note: almost all industry
and vested interest funded research claims no evidence of problems,
while the opposite is found by independent teams. ]

WHEREAS, while there have been a number of studies on the effects
of aspartame on people, there is a great deal of argument by both
proponents and opponents on the methods used in the testing and
whether accurate representations of the consequences of average
consumption by people have been achieved by these studies; and
Note: a major need is to focus on the effects for long-term heavy users,
above 6 12-oz cans daily diet drink, from vulnerable groups like fetus,
infants, kids, teens, students, difficult critical jobs like police, pilots,
military, and nuclear plant operators, pregnant women, seniors, obese,
diabetic, depressed, violent criminal, cancer, and, especially,
over-worked PR agents lavishly funded to defend aspartame as,
"the most tested food additive in history".

WHEREAS, the Internet has become a tool for many to spread and
promote the opinion they adhere to as fact whether it is that aspartame
is a neurotoxin derived from toxic sludge or it is a harmless product
enabling a healthy lifestyle; and

WHEREAS, while many may find that the simple answer to the
problem is to not purchase or use any product containing aspartame
in it, there are those who maintain that some products do not
specifically list aspartame as an ingredient, rather it is hidden under
the label of "natural flavors"; now, therefore,

BE IT RESOLVED by the House of Representatives of the
Twenty-fourth Legislature of the State of Hawaii, Regular Session
of 2008, the Senate concurring, that the Director of Health is
requested to form a work group to explore the need to ban or
improve labeling for products containing the artificial sweetener
aspartame; and

BE IT FURTHER RESOLVED the members of the work group
should include:

(1) One member from the House of Representatives
appointed by the Speaker of the House of Representatives;

(2) One member of the Senate
appointed by the President of the Senate;

(3) The Director of Health or the director's designee;

(4) The President of the Calorie Control Council or the President's
designee; and [ the preminent aspartame lobby ]

(5) The President and Chief Executive Officer
of the American Beverage Association or a designee;
[ With their original name, The National Soft Drink Association, they
condemned aspartame on July 28, 1983 in a detailed critique:
http://dorway.com/dorwblog/?page_id=60 ]

(6) The President of the Hawaii Society of Naturopathic Physicians or a
designee;

(7) The Founder of Mission Possible International or a designee; and

(8) Two consumers appointed by the Director of Health; and

BE IT FURTHER RESOLVED the work group is requested to submit
a report of its findings, as well as any suggested legislation, to the
Legislature no later than 20 days prior to the convening of the
Regular Session of 2010; and

BE IT FURTHER RESOLVED that certified copies of this
Concurrent Resolution be transmitted to the Director of Health,
President of the Calorie Control Council,
webmaster@caloriecontrol.org;
President and Chief Executive Officer
of the American Beverage Association, info@ameribev.org;
President of the Hawaii Society of Naturopathic Physicians,
dr_nguyen@msn.com;
and Founder of Mission Possible International, Betty Martini,
bettm19@mindspring.com

Offered by Josh Green, MD March 4, 2008

Honorable Rep. Josh Green, M.D., Chair, Health Committee
repgreen@Capitol.hawaii.gov;
6th Representative District
Hawaii State Capitol, Room 327
415 South Beretania Street
Honolulu, HI 96813
phone 808-586-9605; fax 808-586-9608
From the Big Island, toll free 974-4000 + 69605

Hawaiian aspartame ban bills in House and Senate challenge
corporate clout, Sen. J. Kalani English & Suzanne Chun Oakland,
Rep. Calvin K.Y. Say & Mele Carroll: Murray 2008.01.25
http://rmforall.blogspot.com/2008_01_01_archive.htm
Friday, January 25, 2008
http://groups.yahoo.com/group/aspartameNM/message/1505
_____________________________________________________

www.hawaiind.org/index.htm
Hawaii Society of Naturopathic Physicians
750-D Kapahulu Ave
Honolulu, HI 96816 808-732-6996
Dr. Ye Nguyen - President dr_nguyen@msn.com;
Dr. Monique Yuen - Vice President: drmoniqueyuen@gmail.com;
Dr. Karen Tan - Treasurer
Dr. Madeleine Portuondo madeleine_portuondo@yahoo.com;
_____________________________________________________

methanol impurity in alcohol drinks [ and aspartame ] is turned into
neurotoxic formic acid, prevented by folic acid, re Fetal Alcohol
Syndrome, BM Kapur, DC Lehotay, PL Carlen at U. Toronto,
Alc Clin Exp Res 2007 Dec. plain text: detailed biochemistry,
CL Nie et al. 2007.07.18: Rich Murray 2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524

[ Rich Murray comments: As a medical layman volunteer information
activist for aspartame and related toxicity issues since January 1999,
I note with appreciation the remarkable exponential progress on all
fronts, including a rapidly emerging consensus about the primary
importance of all toxicity challenges for our world.

This lengthy review features in detail two quite different, revolutionary
contributions, from Canada, and England and China.

It is indicative of our times that the CL Nie et al. study, 2007
appears in a free, open access journal-- indeed,
as all life and death information must.

Following rather vigorously, indeed blindly, the imperatives of
single-minded, profit-driven capitalist competition -- manipulating
adroitly research, education, media, citizens, governments -- many
great global corporations have inevitably created results that
oppose the common good. Alcohol and tobacco are well known.

Realistically, any further manipulations can only lead to inevitable
and even sudden corporate meltdowns, in the context of an
unfettered, cooperative, democratic global information forum,
the Internet.

Now, it is as easy and cheap to compose and instantly post a
30-page review as 3 pages a decade ago -- and such reviews
are archived forever in multiple collections, open via global search
engines to a billion Net citizens.

Perforce, and increasingly happily, all societal entities will have to
operate by high and shared voluntary universal standards
for the common good. ]

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2007.00541.x

Alcoholism: Clinical and Experimental Research
Volume 31 Issue 12 Page 2114-2120, December 2007

Bhushan M. Kapur, b.kapur@utoronto.ca;
Arthur C. Vandenbroucke, PhD, FCACB
Yana Adamchik,
Denis C. Lehotay, dlehotay@health.gov.sk.ca;
Peter L. Carlen carlen@uhnres.utoronto.ca;
(2007) Formic Acid, a Novel Metabolite of Chronic Ethanol
Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid
Alcoholism: Clinical and Experimental Research 31 (12), 2114-2120.
doi:10.1111/j.1530-0277.2007.00541.x

Abstract

Background:
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.

Objective:
To determine if FA levels are higher in the alcohol-drinking
population and to assess its neurotoxicity in organotypic
hippocampal rat brain slice cultures.

Methods:
Serum and CSF FA was measured in samples from both ethanol
abusing and control patients, who presented to a hospital emergency
department. [ CSF = Cerebral Spinal Fluid ]

FA's neurotoxicity and its reversibility by folic acid were assessed
using organotypic rat brain hippocampal slice cultures using clinically
relevant concentrations.

Results:
Serum FA levels in the alcoholics
(mean ± SE: 0.416 +- 0.093 mmol/l, n = 23)
were significantly higher than in controls
(mean ± SE: 0.154 +- 0.009 mmol/l, n = 82) (p < n =" 20),">0.15 mmol/l in CSF of 3 of the 4 alcoholic cases.

Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours
to the rat brain slice cultures caused neuronal death as measured by
propidium iodide staining.

When folic acid (1 umol/l) was added with the FA,
neuronal death was prevented. [ umol = micromole ]

Conclusions:
Formic acid may be a significant factor in the neurotoxicity of
ethanol abuse.

This neurotoxicity can be mitigated by folic acid administration
at a clinically relevant dose.

Key Words:
Formic Acid, Folic Acid, Methanol, Neurotoxicity, Alcoholism.
____________________________________________________

Note: many recent aspartame bans.....

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit aspartame,
MSG, artificial flavors dyes preservatives additives, trans fats, salt
"nasties" to protect kids from ADHD: leading UK media:
Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring agents
will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham,
The Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1513
metabolic syndrome is tied to diet soda, PL Lutsey, LM Steffen,
J Stevens, Circulation 2008.01.22: role of formaldehyde and
formic acid from methanol in wines, liquors, or aspartame?:
Murray 2008.02.21

"But the one-third who ate the most fried food increased their risk
by 25 percent, compared with the one-third who ate the least, and
surprisingly, the risk of developing metabolic syndrome was 34
percent higher among those who drank one can of diet soda a day
compared with those who drank none.

"This is interesting," said Lyn M. Steffen, an associate professor of
epidemiology at the University of Minnesota and a co-author of the
paper, which was posted online in the journal Circulation on Jan. 22.
"Why is it happening? Is it some kind of chemical in the diet soda,
or something about the behavior of diet soda drinkers?""

"The diet soda association was not hypothesized
and deserves further study."

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

http://groups.yahoo.com/group/aspartameNM/message/1511
vinyl acetate, ethyl alcohol, or aspartame in womb increases later
cancers in adults with lifetime exposure in many studies, M Soffritti
et al, Ramazzini Foundation, Basic Clin. Pharm. Toxicol. 2008 Feb.:
Rich Murray 2008.02.07

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.

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation cancer studies
2007.06.25: Murray 2007.07.18

30 female pet store rats drinking lifelong 13.5 mg aspartame,
1/3 packet of Equal, had 33% with obvious tumors -- also bulging,
sick, and missing eyes, paralysis, obesity, skin sores -- agrees with
Ramazzini Foundation results, Victoria Inness-Brown:
Murray 2008.02.15
http://rmforall.blogspot.com/2008_02_01_archive.htm
Friday, February 15, 2008
http://groups.yahoo.com/group/aspartameNM/message/1521

http://groups.yahoo.com/group/aspartameNM/message/1490
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: Murray 2007.11.27

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books:
updated research review of 2004.07.16: Murray 2006.05.11

http://groups.yahoo.com/group/aspartameNM/message/1469
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:
Murray 2007.08.31

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
http://rmforall.blogspot.com/2008_02_01_archive.htm
Monday, February 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1517

"Alcohol dehydrogenase ADH is required for the conversion of
methanol to formaldehyde (112).

ADH is not a common enzyme in the human body -- not many cells
in the human body contain this enzyme.

The human breast is one of the few organs in the body with a high
concentration of ADH (190b), and it is found there exclusively in the
mammary epithelial cells, the very cells known to transform into
adenocarcinoma (190c) (breast cancer).

The most recent breast cancer scientific literature implicates ADH
as perhaps having a pivotal role in the formation of breast cancer,
indicating a greater incidence of the disease in those
with higher levels of ADH activity in their breasts (190a)."

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
http://rmforall.blogspot.com/2007_12_01_archive.htm
Wednesday, December 26 2007
http://groups.yahoo.com/group/aspartameNM/message/1498

bias, omissions, incuriosity = opportunity, aspartame safety
evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more,
2007 Sept, Ajinomoto funded 98 pages html [ $ 32 pdf ]:
Murray 2007.09.15
http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007

MSG and Aspartame -- A Personal Story, TV health reporter
Dick Allgire (vegetarian) healed of migraines and panic attacks:
Murray 2008.02.12
http://rmforall.blogspot.com/2008_02_01_archive.htm
Tuesday, February 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1520

"Of course, everyone chooses, as a natural priority, to enjoy
peace, joy, and love by helping to find, quickly share, and positively
act upon evidence about healthy and safe food, drink, and
environment."

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

http://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 120 members, 1,525 posts in a public archive

http://groups.yahoo.com/group/aspartame/messages
group with 1,080 members, 22,439 posts in public archive
_____________________________________________________

Hawaii Senate Health Committee will consider resolution SCR191 to ban aspartame 2008.03.14

2008-03-14T17:36:00.000-07:00

[ corrected title ] Hawaii Senate Health Committee will consider resolution SCR191 by Sen. Suzanne Chun Oakland, and 10 other of 25 Senators, to have FDA ban aspartame and for National Academy of Sciences to review research: Murray 2008.03.14

http://rmforall.blogspot.com/2008_03_01_archive.htm
Friday, March 14, 2008
http://groups.yahoo.com/group/aspartameNM/message/1527
_____________________________________________________

[ See also:

http://groups.yahoo.com/group/aspartameNM/message/1525
House Concurrent Resolution #132 for Health Department panel to
decide aspartame ban by early 2010, Hawaii Rep. Josh Green MD,
Health Committee Chair: Murray 2008.03.12
http://rmforall.blogspot.com/2008_03_01_archive.htm
Wednesday, March 12, 2008
www.opednews.com/articles/1/opedne_stephen__080311_testimony_re_3a_hawaii.htm

http://groups.yahoo.com/group/aspartameNM/message/1505
Hawaiian aspartame ban bills in House and Senate challenge
corporate clout, Sen. J. Kalani English & Suzanne Chun Oakland,
Rep. Calvin K.Y. Say & Mele Carroll: Murray 2008.01.25
http://rmforall.blogspot.com/2008_01_01_archive.htm
Friday, January 25, 2008 ]

http://www.hawaiireporter.com/story.aspx?8013b05c-d8ec-4d71-8ed7-389bc5add130

Hawaii Senate Committee Will Consider Resolution on Aspartame
By Stephen Fox, 3/13/2008 10:49:31 AM

There is now a Hawaii Senate Resolution,
authored by Sen. Suzanne Chun Oakland, which requests the
Department of Health and National Academy of Sciences
to review existing reports and studies related to aspartame,
by funding source.

It resolves that given the enormous amount of evidence
that has been compiled concerning the neurodegenerative harm
it can cause, that the U.S. Food and Drug Administration
is requested to rescind approval of aspartame immediately
on a phase-out basis over six months to one year.

We are very pleased to note that this is the strongest legislative
document concerning aspartame ever presented anywhere
in the world.

On March 12, another resolution, HCR132, introduced by Rep.
Josh Green, M.D., Chairman of the House Committee on Health,
was approved by its first committee (Health),
and moves on to the next (Consumer Protection and Commerce).

This would set up a work group to explore the need to ban
or improve labeling containing aspartame.

It was again opposed by Dr. Chiyome Fukino, M.D.,
Director of the Health Department,
an appointee of Republican Governor Linda Lingle,
who opposed the House Bill to ban aspartame on the flawed basis
of an Ajinomoto-funded review study;
Ajinomoto is the world's largest manufacturer of Aspartame,
and another proven neurotoxic food additive,
Monosodium Glutamate.

Betty Martini, D. Hum, sent Dr. Fukino a detailed rebuttal
to this study, showing the links to Ajinomoto
and flawed industry research.

Dr. Fukino's opposition today, March 12 was surprisingly opposed
by Rep. Green, M.D., the only physician in the entire Hawaii
Legislature, in view of him having 'deferred' a prior bill to ban
aspartame outright, by statute.

Here is the rebuttal to the Ajinomoto Study, written by Mark Gold,
Founder, Aspartame Toxicity Information Center, New Hampshire:

http://www.holisticmed.com/aspartame/burdock/
Aspartame and Manufacturer-Funded Scientific Reviews

This flawed Ajinomoto-funded report,
which has been touted far and wide by aspartame manufacturers
and corporate hacks and lobbyists, shows how far the world's
largest aspartame manufacturer will go to deceive the public.

However, today, there is no doubt that Ajinomoto's
Board of Directors as well as the Board of Directors of
Coca Cola, Pepsi, Wrigley's Gum, and Merisant
(manufacturer of Equal) are extremely worried about these
late-breaking developments in Hawaii, which should also
encourage consumer protection activists all over the world
to contact their legislators and parliamentarians, asking them
to introduce similar legislation and Resolutions.

We cordially thank Senator Chun Oakland and Representative
Josh Green, M.D., for advancing our consumer protection initiative
as far as they have.

Text of Senate Resolution:
http://www.capitol.hawaii.gov/session2008/bills/SCR191_.pdf

Requesting the Hawaii Department of Health and
the National Academy of Sciences to review existing reports
and studies related to Aspartame, and Requesting the United States
Food and Drug Administration to Rescind Approval for
United States Markets,
carried by Hawaii Senator Suzanne Chun Oakland

Whereas, aspartame was originally developed as a drug to treat
peptic ulcers; and

Whereas, manufacturers state that aspartame is made up of
forty per cent aspartic acid, fifty percent phenylalanine,
and ten per cent methanol; and

Whereas, aspartic acid is a nonessential amino acid
that is used by the body to initiate apoptosis or cell death
in aging cells,
and that excess aspartic acid from aspartame consumption causes
apoptosis in health cells that can destroy healthy tissue,
especially in the brain; and

Whereas, phenylalanine is an essential amino acid found naturally
in protein but when isolated becomes neurotoxic, lowers the seizure
threshold, depletes serotonin -- triggering psychiatric and behavioral
problems -- and interacts with depressants and other drugs; and

Whereas, methanol is a severe metabolic poison classified as a
narcotic that converts to formaldehyde and formic acid,
and can embalm living tissue and damage DNA; and

Whereas, aspartame metabolites include formaldehyde,
a 'class A' carcinogen, and diketopiperazine, a brain tumor agent,
and formic acid, and

Whereas, in 1974, the United States Food and Drug Administration
approved aspartame as an artificial sweetener,
but asked its manufacturer Searle to hold back from selling it on the
market until further tests could be made with regards to its safety;
and

Whereas, scientific data revealed that there was a problem with
aspartame safety date and the United States Food and Drug
Administration withdrew its approval; and

Whereas, in 1975, the United States Food and Drug
Administration initiated an investigation into Searle's laboratory
practices and discovered fraud in scientific experiments as well as
manipulated data giving favorable results proving aspartame
to be safe; and

Whereas, the results of this investigation are included in
what is called 'The Bressler Report' by Jerome Bressler; and
[ http://dorway.com/dorwblog/?page_id=56
(Note: This is the text of an FDA report on Searle)
EIR 4/25/77 to 8/4/77 Searle Laboratories
JSA/DME/JT/LF Div. G.D. Searle & Co.
4901 Searle Parkway
Skokie, Illinois 60076 ]

Whereas, in 1980, Dr. John Olney submitted scientific data to a
United States Food and Drug Administration Public Board of Inquiry
showing that aspartic acid, the excitotoxic ingredient in aspartame,
caused holes in the brains of mice; and

Whereas, Dr. John Olney stated that it warranted special emphasis
that excitotoxins act by an acute but silent mechanism, requiring
only a single exposure for CVO neurons to be quietly destroyed,
that clearly Searle failed to establish the safety of their product,
aspartame, for use in children's food, and that all age comparative
data support the following conclusions:
(1) orally administered excitotoxins destroy CVO neurons
at any age;
(2) immature animals are most vulnerable; and
(3) the toxic threshold increases only gradually between birth and
adulthood; and

Whereas, in 1980, the Public Board of Inquiry unanimously
voted against aspartame approval, but was overruled by a new
United States Food and Drug Administration Commissioner,
Dr. Arthur Hull Hayes, against the advice of Food and Drug
Administration scientific personnel and advisers; and

Whereas, the United States Food and Drug Administration
approved aspartame use in sodas, despite the fact that the
National Soft Drink Association argued vehemently against
aspartame in these quotes from their protest:
[ With their original name, The National Soft Drink Association, they
condemned aspartame on July 28, 1983 in a detailed critique:
http://dorway.com/dorwblog/?page_id=60 ]

* (1) "The present record does not contain data which
demonstrate that the use of APM in soft drinks will not result in the
adulteration of the beverages under Section 402(a)(3) of the
FDC Act 21 U.S.S. 342 (a)(3),
which provides that a food is adulterated if it contains, in whole
or in part, 'a decomposed substance
or it is otherwise unfit for food'�)";

(2) "An important decomposition product of aspartame,
aspartic acid, cannot be detected at all using TLC"�;

(3) "�G.D. Searle and Company has not demonstrated to a reasonable
certainty that the use of aspartame in soft drinks, without quantitative limitations, will not adversely affect human health as a result of the changes such use is likely to cause in brain chemistry and under certain reasonably anticipated conditions of use"; and

(4) "Specifically, Searle has not met its burdens under section
409 'to demonstrate that aspartame is safe and functional for use
in soft drinks.' Collectively, the extensive deficiencies in the stability studies conducted by Searle to demonstrate that aspartame and its degradation products are safe in soft drinks intended to be sold in the United States, render those studies inadequate and unreliable."�
Senate Congressional Record, May 7, 1985, S5507-5511: and

Whereas, the United States Food and Drug Administration
has compiled a list of ninety-two symptoms attributed to aspartame
consumption including four types of seizures, coma, and death; and

Whereas, the Ramazzini Studies by the European Foundation for Oncology in Italy conducted exhaustive studies over three years with thousands of rats, and proved aspartame to be a multipotential carcinogen, thus confirming the United States Food and Drug Administration's original findings;
and

Whereas, the United States Food and Drug Administration
admitted that aspartame caused cancer over two decades ago,
when the Administration's toxicologist, Dr. Adrian Gross, told
Congress at least one of Searle's studies:

"has established beyond any reasonable doubt that aspartame is
capable of inducing brain tumors in experimental animals and that
this predisposition of it is of extremely high significance". In view
of these indications that the cancer causing potential of aspartame
is a matter that had been established way beyond any reasonable
doubt, one can ask: What is the reason for the apparent refusal
by the FDA to invoke for this food additive the so-called Delaney
amendment to the Food, Drug, and Cosmetic act?
Given the cancer causing potential of aspartame, how would the
FDA justify its position that it views a certain amount of aspartame
as constituting an allowable daily intake or 'safe' level of it?
Is that position in effect not equivalent to setting a 'tolerance'
for this food additive and thus a violation of that law?
And if the FDA itself elects to violate the law,
who is left to protect the health of the public?"�
Congressional Record, August 1, 1985, SID835: 131: and

Whereas, aspartame is linked to sudden death, multiple sclerosis,
lupus, and many neurodegenerative diseases, as cited in may medical
texts, most notably: Aspartame Disease: An Ignored Epidemic,
by H.J. Roberts, M.D., and
Excitotoxins: the Taste that Kills, By Russell Blaylock, M.D., and

Whereas, on November 3, 1987, Dr. Louis Elsas told Congress:

"I am a pediatrician, a Professor of Pediatrics at Emory
and have spent twenty-five years in the biomedical sciences,
trying to prevent mental retardation and birth defect caused by excess
phenylalanine, and therein lies my basic concern, that aspartame is
in fact a well known neurotoxin and teratogen which, in some as yet
undefined dose, will irreversibly in the developing child or fetal brain, produce adverse effects." and

Whereas, there are tens of thousands of case histories and anecdotal
accounts from victims of aspartame poisoning who have come forward to make their case histories known; now, therefore,

BE IT RESOLVED by the Senate of the Twenty-Fourth Legislature
of the State of Hawaii, Regular Session of 2008,
the House of Representatives concurring,
that the Department of Health is requested to create,
within their existing budget,
an evidentiary repository accessible to the public for patients and
physicians to submit of the next year their cases involving victims
of aspartame poisoning; and

BE IT FURTHER RESOLVED that the Director of Health
is requested to report to the Legislature on the status of the
evidentiary repository during periodic interim meetings
with the Chairs of the Hawaii State Senate Committees
n Health and Human Services and Public Housing,
the House of Representatives Committees on Health and
Human Services and Housing, and the state Attorney General; and

BE IT FURTHER RESOLVED that the Department of Health
is requested to review all existing reports, studies, experiments,
and related literature on aspartame, including clinical studies,
differentiating each study by its funding source,
and submit a report to the Legislature no later than twenty days
prior to the convening of the 2008 Regular Session; and

BE IT FURTHER RESOLVED that the
Nation Academy of Sciences is requested to review all existing
reports, studies, experiments, and related literature on aspartame,
including clinical studies, differentiating each study by its funding
source, and that, if funding is required to undertake this extended
evaluation, that the appropriate funding be sought from various
foundations and from Congress; and

BE IT FURTHER RESOLVED that given the enormous amount of
evidence that has been compiled concerning the neurodegenerative
harm it can cause,
that the United States Food and Drug Administration is requested
to rescind approval of aspartame immediately
on a phase-out basis over six months to one year; and

BE IT FURTHER RESOLVED that certified copies of this Resolution
be transmitted to the members of Hawaii's Congressional Delegation,
the Commissioner of the
United States Food and Drug Administration,
the Executive Director of the National Academy of Sciences,
the Director of Health,
the Director of Human Services,
the Attorney General,
and the Director of Commerce and Consumer Affairs.

The resolution was signed by 40 percent of the Senate
11 of 25 Senators,
including: Senator Suzanne Chun Oakland, Chair,
Human Services Committee, primary sponsor:

http://www.capitol.hawaii.gov/site1/senate/senate.asp Senate

senchunoakland@Capitol.hawaii.gov;
senbunda@Capitol.hawaii.gov; senenglish@Capitol.hawaii.gov;
senespero@Capitol.hawaii.gov; senfukunaga@Capitol.hawaii.gov;
sendige@Capitol.hawaii.gov; senihara@Capitol.hawaii.gov;
senkim@Capitol.hawaii.gov; senmenor@Capitol.hawaii.gov;
sennishihara@Capitol.hawaii.gov; sentokuda@Capitol.hawaii.gov;

Senator Robert Bunda, President Emeritus, Hawaii Senate
senbunda@Capitol.hawaii.gov;
Senator Kalani English, Chairman, Transportation
and International Affairs senenglish@Capitol.hawaii.gov;
Senator Will Espero, Chairman, Public Safety Committee
senespero@Capitol.hawaii.gov;
Senator Carol Fukunaga, Vice Chair, Health Committee
senfukunaga@Capitol.hawaii.gov;
Senator David Ige, Chairman, Health Committee
sendige@Capitol.hawaii.gov;
Senator Les Ihara, Majority Policy Leader
senihara@Capitol.hawaii.gov;
Senator Donna Mercado Kim, Vice President of Hawaii Senate
senkim@Capitol.hawaii.gov;
Senator Ron Menor, Chairman, Energy and Environment
senmenor@Capitol.hawaii.gov;
Senator Clarence Nishihara, Chairman, Tourism and
Government Operations sennishihara@Capitol.hawaii.gov;
Senator Jill N. Tokuda, Agriculture and Hawaiian Affairs,
Chair and Education, Vice-Chair sentokuda@Capitol.hawaii.gov;

For more information, please contact Sen. Suzanne Chun Oakland
at 808-586-6130; fax 808-586-6131
email mailto: senchunoakland@Capitol.hawaii.gov;
or Rep. Josh Green, M.D. 808-586-9605; fax 808-586-9608
From the Big Island, toll free 974-4000 + 69605
E-mail or at mailto: repgreen@Capitol.hawaii.gov;

Stephen Fox is the Managing Editor, Santa Fe Sun News
and Founder, New Millennium Fine Art.
More at mailto: stephen@santafefineart.com;

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http://www.honoluluadvertiser.com/apps/pbcs.dll/section?Category=LEGISLATURE08

http://www.capitol.hawaii.gov/session2008/lists/getstatus2.asp?billno=SCR191
Introducer(s):
Introducer(s): CHUN OAKLAND, ENGLISH, Bunda, Espero,
Fukunaga, Ige, Ihara, Kim, Menor, Nishihara, Tokuda

http://www.capitol.hawaii.gov/site1/docs/status/searchstatus.asp?query=aspartame&currpage=1

1. SCR191 SCR191 Status
Context: NATIONAL ACADEMY OF SCIENCES
TO REVIEW EXISTING REPORTS AND STUDIES RELATED
TO ASPARTAME, AND REQUESTING THE UNITED STATES
FOOD AND DRUG ADMINISTRATION TO ... RESCIND
APPROVAL OF ASPARTAME
FOR UNITED STATES MARKETS.
WHEREAS, aspartame was originally developed as a drug
to treat peptic ulcers; or cell death in aging cells,
and that excess aspartic acid from aspartame consumption
causes apoptosis in healthy cells that can destroy healthy tissue,
Filesize: 20797
Electronic File Date: 3/12/2008 6:14:24 PM
http://www.capitol.hawaii.gov/session2008/bills/SCR191_.pdf
_____________________________________________________

[ Note: folic acid protects against aspartame (methanol, formaldehyde,
formic acid) toxicity in as much as 90% of users -- many will also still
have problems from aspartic acid, phenylalanine, and DKP. ]

methanol impurity in alcohol drinks [ and aspartame ] is turned into
neurotoxic formic acid, prevented by folic acid, re Fetal Alcohol
Syndrome, BM Kapur, DC Lehotay, PL Carlen at U. Toronto,
Alc Clin Exp Res 2007 Dec. plain text: detailed biochemistry,
CL Nie et al. 2007.07.18: Rich Murray 2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524

[ Rich Murray comments: As a medical layman volunteer information
activist for aspartame and related toxicity issues since January 1999,
I note with appreciation the remarkable exponential progress on all
fronts, including a rapidly emerging consensus about the primary
importance of all toxicity challenges for our world.

This lengthy review features in detail two quite different, revolutionary
contributions, from Canada, and England and China.

It is indicative of our times that the CL Nie et al. study, 2007
appears in a free, open access journal -- indeed, as all life and
death information must.

Following rather vigorously, indeed blindly, the imperatives of
single-minded, profit-driven capitalist competition -- manipulating
adroitly research, education, media, citizens, governments -- many
great global corporations have inevitably created results that
oppose the common good. Alcohol and tobacco are well known.

Realistically, any further manipulations can only lead to inevitable
and even sudden corporate meltdowns, in the context of an
unfettered, cooperative, democratic global information forum,
the Internet.

Now, it is as easy and cheap to compose and instantly post a
30-page review as 3 pages a decade ago -- and such reviews
are archived forever in multiple collections, open via global search
engines to a billion Net citizens.

Perforce, and increasingly happily, all societal entities will have to
operate by high and shared voluntary universal standards
for the common good. ]

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2007.00541.x

Alcoholism: Clinical and Experimental Research
Volume 31 Issue 12 Page 2114-2120, December 2007

Bhushan M. Kapur, b.kapur@utoronto.ca;
Arthur C. Vandenbroucke, PhD, FCACB
Yana Adamchik,
Denis C. Lehotay, dlehotay@health.gov.sk.ca;
Peter L. Carlen carlen@uhnres.utoronto.ca;
(2007) Formic Acid, a Novel Metabolite of Chronic Ethanol
Abuse, Causes Neurotoxicity, Which Is Prevented by Folic Acid
Alcoholism: Clinical and Experimental Research 31 (12), 2114-2120.
doi:10.1111/j.1530-0277.2007.00541.x

Abstract

Background:
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.

Objective:
To determine if FA levels are higher in the alcohol-drinking
population and to assess its neurotoxicity in organotypic
hippocampal rat brain slice cultures.

Methods:
Serum and CSF FA was measured in samples from both ethanol
abusing and control patients, who presented to a hospital emergency
department. [ CSF = Cerebral Spinal Fluid ]

FA's neurotoxicity and its reversibility by folic acid were assessed
using organotypic rat brain hippocampal slice cultures using clinically
relevant concentrations.

Results:
Serum FA levels in the alcoholics
(mean ± SE: 0.416 +- 0.093 mmol/l, n = 23)
were significantly higher than in controls
(mean ± SE: 0.154 +- 0.009 mmol/l, n = 82) (p < 0.0002).

FA was not detected in the controls' CSF (n = 20),
whereas it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases.

Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours
to the rat brain slice cultures caused neuronal death as measured by
propidium iodide staining.

When folic acid (1 umol/l) was added with the FA,
neuronal death was prevented. [ umol = micromole ]

Conclusions:
Formic acid may be a significant factor in the neurotoxicity of
ethanol abuse.

This neurotoxicity can be mitigated by folic acid administration
at a clinically relevant dose.

Key Words:
Formic Acid, Folic Acid, Methanol, Neurotoxicity, Alcoholism.

Note: many recent aspartame bans.....

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit aspartame,
MSG, artificial flavors dyes preservatives additives, trans fats, salt
"nasties" to protect kids from ADHD: leading UK media:
Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring agents
will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham,
The Bristol Press: Murray 2006.09.22

bias, omissions, incuriosity = opportunity, aspartame safety
evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more,
2007 Sept, Ajinomoto funded 98 pages html [ $ 32 pdf ]:
Murray 2007.09.15
http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007

http://groups.yahoo.com/group/aspartameNM/message/1491
industry scientists praise aspartame safety and benefits in Paris on
2006.05.30, Herve Nordmann, Andrew G. Renwick,
Carlo La Vecchia, Tommy Visscher, Jaap Seidell, France Bellisle,
Adam Drewnowski, Margaret Ashwell, Anne de la Hunty,
Sigrid A. Gibson, Alan R. Boobis: Murray 2007.11.18

http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA
2002.05.07 aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13

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

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

http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review
by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 2004.05.14

http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon,
UPI reporter: Murray 2000.07.10

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06

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

http://groups.yahoo.com/group/aspartameNM/message/1483
Donald Rumsfeld CEO 1977-85 G.D. Searle & Co., got new
President Reagan to prohibit FDA opposition to aspartame
1981.01.25, history by lawyer James S. Turner:
Murray 2007.10.29

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23

http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re
aspartame and MSG toxicity: Murray 2002.08.01

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished: http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100 %) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91 %)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern
Ohio Universities, College of Medicine, Dept. of Psychiatry,
Youngstown, OH 44501,
Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240
Youngstown, OH 44501 330-740-3621 rwalton193@aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray, brief fair summary of much more research:
Murray 2007.01.01

http://groups.yahoo.com/group/aspartameNM/message/1513
metabolic syndrome is tied to diet soda, PL Lutsey, LM Steffen,
J Stevens, Circulation 2008.01.22: role of formaldehyde and
formic acid from methanol in wines, liquors, or aspartame?:
Murray 2008.02.21

"But the one-third who ate the most fried food increased their risk
by 25 percent, compared with the one-third who ate the least, and
surprisingly, the risk of developing metabolic syndrome was 34
percent higher among those who drank one can of diet soda a day
compared with those who drank none.

"This is interesting," said Lyn M. Steffen, an associate professor of
epidemiology at the University of Minnesota and a co-author of the
paper, which was posted online in the journal Circulation on Jan. 22.
"Why is it happening? Is it some kind of chemical in the diet soda,
or something about the behavior of diet soda drinkers?""

"The diet soda association was not hypothesized
and deserves further study."

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

http://groups.yahoo.com/group/aspartameNM/message/1511
vinyl acetate, ethyl alcohol, or aspartame in womb increases later
cancers in adults with lifetime exposure in many studies, M Soffritti
et al, Ramazzini Foundation, Basic Clin. Pharm. Toxicol. 2008 Feb.:
Rich Murray 2008.02.07

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.

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation cancer studies
2007.06.25: Murray 2007.07.18

30 female pet store rats drinking lifelong 13.5 mg aspartame,
1/3 packet of Equal, had 33% with obvious tumors -- also bulging,
sick, and missing eyes, paralysis, obesity, skin sores -- agrees with
Ramazzini Foundation results, Victoria Inness-Brown:
Murray 2008.02.15
http://rmforall.blogspot.com/2008_02_01_archive.htm
Friday, February 15, 2008
http://groups.yahoo.com/group/aspartameNM/message/1521

http://groups.yahoo.com/group/aspartameNM/message/1490
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: Murray 2007.11.27

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books:
updated research review of 2004.07.16: Murray 2006.05.11

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
http://rmforall.blogspot.com/2008_02_01_archive.htm
Monday, February 11, 2008
http://groups.yahoo.com/group/aspartameNM/message/1517

"Alcohol dehydrogenase ADH is required for the conversion of
methanol to formaldehyde (112).

ADH is not a common enzyme in the human body -- not many cells
in the human body contain this enzyme.

The human breast is one of the few organs in the body with a high
concentration of ADH (190b), and it is found there exclusively in the
mammary epithelial cells, the very cells known to transform into
adenocarcinoma (190c) (breast cancer).

The most recent breast cancer scientific literature implicates ADH
as perhaps having a pivotal role in the formation of breast cancer,
indicating a greater incidence of the disease in those
with higher levels of ADH activity in their breasts (190a)."

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
http://rmforall.blogspot.com/2007_12_01_archive.htm
Wednesday, December 26 2007
http://groups.yahoo.com/group/aspartameNM/message/1498

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.

http://groups.yahoo.com/group/aspartameNM/message/1469
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:
Murray 2007.08.31

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ): EU Scientific Committee on Foods
2001.07.12: Murray 2004.01.22

http://europa.eu.int/comm/food/fs/sc/scf/out96_en.pdf

"...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 140 mg/L from natural sources.

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@catholic.ac.kr
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).

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@RMV.se
Department of Forensic Toxicology,
University Hospital, SE-581 85 Linkoping, Sweden.

This paper reports the elimination half-life of methanol in human
volunteers.
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

http://groups.yahoo.com/group/aspartameNM/message/1047
Avoiding Hangover Hell 2003.12.31 Mark Sherman, AP writer:
Robert Swift, MD [ formaldehyde from methanol in aspartame ]:
Murray 2004.01.16

http://groups.yahoo.com/group/aspartameNM/message/1048
hangovers from formaldehyde from methanol (aspartame?):
Schwarcz: Linsley: Murray 2004.01.18

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. toxicology@drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
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

formaldehyde in FEMA trailers and other sources (aspartame,
dark wines and liquors, tobacco smoke): Murray 2008.01.30
http://rmforall.blogspot.com/2008_01_01_archive.htm
Wednesday, January 30, 2008
http://groups.yahoo.com/group/aspartameNM/message/1508

The FEMA trailers give about the same amount of formaldehyde
daily as from a quart of dark wine or liquor, or two quarts
(6 12-oz cans) of aspartame diet soda, from their over 1 tenth gram
methanol impurity (one part in 10,000),
which the body quickly makes into formaldehyde -- enough
to be the major cause of "morning after" alcohol hangovers.

Methanol and formaldehyde also result from many fruits and
vegetables, tobacco and wood smoke, heater and vehicle exhaust,
household chemicals and cleaners, cosmetics, and new cars, drapes,
carpets, furniture, particleboard, mobile homes, buildings, leather ...
so all these sources add up and interact
with many other toxic chemicals.

BN Ames and LS Gold, 1998, have presented detailed information
that there is no increase in recent decades for most cancers,
and that common carcinogens do not result in significant exposures
to the average human population.

However, individuals are not average -- each person has a unique genetic
makeup, resulting in a huge range of variation of vulnerability to
specific chemicals, as is well evidenced in the case of methanol,
formaldehyde, and formic acid, especially with regard
to behavioral effects.

Each is subject to very wide ranges of exposure levels.

Many are in especially vulnerable groups, depending on diet, obesity,
sex, exercise, life stress, age from conception to very old, unusually
severe toxic exposures, injuries, and diseases.

It is clear that a variety of multiple chemical sensitivity syndromes do
exist, often with remarkable hypersensitivity.

Methanol, formaldehyde, and formic acid toxicity are unusual, in that
humans are far more vulnerable than any other mammal, as much as ten
to sixty-fold, which complicates the utility of animal data.

The unusally long human life span also increases the role of long-term
chronic low-level exposure.

http://groups.yahoo.com/group/aspartameNM/message/1455
FEMA slow to safety test Katrina toxic trailers, Charles Babington,
Associated Press -- 1 ppm formaldehyde in air is about half the daily
dose from 3 cans aspartame diet soda and ten times the 1999 EPA
alarm level for drinking water: Murray 2007.07.23

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic - aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

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/1373
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

http://groups.yahoo.com/group/aspartameNM/message/1463
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

http://groups.yahoo.com/group/aspartameNMmessage/1452
phenylalanine and aspartic acid from low dose aspartame
in rabbits interfere with blood coagulation,
Pretorius E and Humphries P, U. of Pretoria,
Ultrastruct Pathol 2007 March: Murray 2007.07.14

http://groups.yahoo.com/group/aspartameNM/message/1459
third study by expert Greek team of neurotoxicity in infant rats by
aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH
Schulpis et al, Food Chem Toxicol 2007.06.16: Murray 2007.08.05

http://groups.yahoo.com/group/aspartameNMmessage/1447
second study by expert Greek team of neurotoxicity in infant rats by
aspartame (or its parts, methanol, phenylalanine, aspartic acid), KH
Schulpis et al, Toxicology 2007.05.18: Murray 2007.07.04

http://groups.yahoo.com/group/aspartameNMmessage/1444
expert Greek group finds aspartame (or its parts, methanol,
phenylalanine, aspartic acid) harm infant rat brain enzyme activity,
KH Schulpis et al, Pharmacol. Res. 2007.05.13: Murray 2007.06.23

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@atlas.uoa.gr
K.H. Schulpis inchildh@otenet.gr ; G.J. Reclos reklos@otenet.gr

5 recent aspartame reports by S Tsakiris, KH Schulpis, I Simintzi,
with responses to critiques by AG Renwick and
by EB Abegaz, RG Bursey, 2005-2008 2008.03.05

Pharmacological Research 57 (2008) 89–90
Letter to the Editor
Answer to Letter sent to the Editor by
Drs. E. Abegaz and R. Bursey
(Ajinomoto Corporate Services LLC, Washington, USA)
related to Simintzi et al. report published in
Pharmacol Res 2007; 56: 155–9
Letter to the Editor / Pharmacological Research 57 (2008) 89–90

Stylianos Tsakiris a,∗ stsakir@cc.uoa.gr;
Kleopatra H. Schulpis b inchildh@otenet.gr;
a Department of Experimental Physiology, Medical School,
Athens University, P.O. Box 65257, GR-15401 Athens, Greece

b Inborn Errors of Metabolism Department, Institute of Child
Health, Research Center, Greece
∗ Corresponding author.
E-mail addresses:
S. Tsakiris stsakir@cc.uoa.gr;
K.H. Schulpis inchildh@otenet.gr;

Pharmacological Research 57 (2008) 87–88
Response to “The effect of aspartame on the acetylcholinesterase
activity in hippocampal homogenates of suckling rats”
by Simintzi et al.

Eyassu G. Abegaz ∗
Robert G. Bursey
Ajinomoto Corporate Services LLC,
Scientific & Regulatory Affairs,
1120 Connecticut Ave., N.W., Suite 1010, Washington, DC 20036,
United States

∗ Corresponding author. Tel.: +1 202 457 0284;
fax: +1 202 457 0107.
E-mail addresses: abegazee@ajiusa.com; (E.G. Abegaz),
burseyb@ajiusa.com; (R.G. Bursey)

Keywords:
Aspartame; Aspartate; Phenylalanine; Methanol; AChE activity

Tsakiris S, Schulpis KH.
Answer to letter sent by Professor A.G. Renwick
(University of Southampton, UK)
related to Simintzi et al. report published in Food and Chemical
Toxicology 2007; 45(12): 2397-401.
Food Chem Toxicol. 2008 Mar; 46(3): 1208-9.
Epub 2007 Oct 25. No abstract available. PMID: 18054419
doi:10.1016/j.fct.2007.10.016
Copyright © 2007 Elsevier Ltd All rights reserved.

Renwick AG.
The effect of aspartame metabolites on the suckling rat frontal cortex
acetylcholinesterase. An in vitro study. By I. Simintzi, K.H. Schulpis,
P. Angelogianni, C. Liapi and S. Tsakiris.
Food Chem Toxicol. 2008 Mar; 46(3): 1206-7.
Epub 2007 Oct 26. No abstract available. PMID: 18061330

1: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
The effect of aspartame metabolites on the suckling rat frontal cortex
acetylcholinesterase. An in vitro study.
Food Chem Toxicol. 2007 Dec;45(12):2397-401.
Epub 2007 Jun 16. PMID: 17673349

2: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
L-Cysteine and glutathione restore the reduction of rat
hippocampal Na+, K+-ATPase activity
induced by aspartame metabolites.
Toxicology. 2007 Jul 31;237(1-3):177-83.
Epub 2007 May 18. PMID: 17602817

3: Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
The effect of aspartame on acetylcholinesterase activity in
hippocampal homogenates of suckling rats.
Pharmacol Res. 2007 Aug;56(2):155-9.
Epub 2007 May 13. PMID: 17580119

4: Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S.
The effect of L-cysteine and glutathione
on inhibition of Na+, K+-ATPase activity by aspartame metabolites
in human erythrocyte membrane.
Eur J Clin Nutr. 2006 May;60(5):593-7. PMID: 16391576

5: Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH.
The effect of aspartame metabolites on human erythrocyte membrane
acetylcholinesterase activity.
Pharmacol Res. 2006 Jan;53(1):1-5.
Epub 2005 Aug 29. PMID: 16129618

C. Trocho (1998):
"In all, the rats retained, 6 hours after administration, about 5 % of the
label, half of it in the liver."

They used a very low level of aspartame ingestion, 10 mg/kg, for rats,
which have a much greater tolerance for aspartame than humans.
So, the corresponding level for humans would be about 1 or 2 mg/kg.
Many headache studies in humans used doses of about 30 mg/kg daily.

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

http://ww.presidiotex.com/barcelona/index.html full text
Formaldehyde derived from dietary aspartame
binds to tissue components in vivo.
Life Sci June 26 1998; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html Línies de Recerca: Toxicitat de
l'aspartame http://www.bq.ub.es/grupno/grup-no.html
Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, Dr. Xavier Remesar, Dr. Jose Antonio
Fernandez-Lopez, Dr. Mari� Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544,
FAX: (93)4021559 alemany@porthos.bio.ub.es;
bioq@sun.bq.ub.es

Abstract:
Adult male rats were given an oral dose of 10 mg/kg aspartame,
14C-labeled in the methanol carbon.
At timed intervals of up to 6 hours, the radioactivity in plasma
and several organs was investigated.
Most of the radioactivity found (>98 % in plasma, >75 % in liver)
was bound to protein.
Label present in liver, plasma and kidney was in the range
of 1-2 % of total radioactivity administered per g or mL,
changing little with time.
Other organs (brown and white adipose tissues, muscle, brain,
cornea and retina) contained levels of label
in the range of 1/12th to 1/10th of that of liver.
In all, the rats retained, 6 hours after administration,
about 5 % of the label, half of it in the liver.

The specific radioactivity of tissue protein, RNA and DNA
was quite uniform.
The protein label was concentrated in amino acids,
different from methionine, and largely coincident
with the result of protein exposure to labeled formaldehyde.
DNA radioactivity was essentially in a single different adduct base,
different from the normal bases present in DNA.
The nature of the tissue label accumulated was, thus,
a direct consequence of formaldehyde binding to tissue structures.

The administration of labeled aspartame to a group of cirrhotic rats
resulted in comparable label retention by tissue components,
which suggests that liver function (or its defect) has little effect
on formaldehyde formation from aspartame
and binding to biological components.

The chronic treatment of a series of rats with 200 mg/kg of
non-labeled aspartame during 10 days results in the accumulation
of even more label when given the radioactive bolus,
suggesting that the amount of formaldehyde adducts
coming from aspartame in tissue proteins and nucleic acids
may be cumulative.

It is concluded that aspartame consumption may constitute
a hazard because of its contribution
to the formation of formaldehyde adducts. PMID: 9714421

[ Extracts ]
"The high label presence in plasma and liver is in agreement with the
carriage of the label from the intestine to the liver via the portal vein.
The high label levels in kidney and, to a minor extent, in brown
adipose tissue and brain are probably a consequence
of their high blood flows (45).
Even in white adipose tissue, the levels of radioactivity found 6 hours
after oral administration were 1/25th those of liver.
Cornea and retina, both tissues known to metabolize actively
methanol (21,28) showed low levels of retained label.
In any case, the binding of methanol-derived carbon to tissue proteins
was widespread, affecting all systems,
fully reaching even sensitive targets such as the brain and retina....

The amount of label recovered in tissue components was quite high
in all the groups, but especially in the NA rats.
In them, the liver alone retained, for a long time, more than 2 % of the
methanol carbon given in a single oral dose of aspartame,
and the rest of the body stored an additional 2 % or more.
These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects (33), that has also
been considered carcinogenic (34,47).
The repeated occurrence of claims that aspartame
produces headache and other neurological and psychological
secondary effects --
more often than not challenged by careful analysis --
(5, 9, 10, 15, 48)
may eventually find at least a partial explanation in the permanence
of the formaldehyde label,
since formaldehyde intoxication can induce similar effects (49).

The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame
may result in the progressive accumulation of formaldehyde adducts.
It may be further speculated that the formation of adducts can help to
explain the chronic effects aspartame consumption may induce on
sensitive tissues such as brain (6, 9, 19, 50).
In any case, the possible negative effects that the accumulation of
formaldehyde adducts can induce is, obviously, long-term.
The alteration of protein integrity and function may needs some time
to induce substantial effects.
The damage to nucleic acids, mainly to DNA,
may eventually induce cell death and/or mutations.
The results presented suggest that the conversion of aspartame
methanol into formaldehyde adducts in significant amounts in vivo
should to be taken into account because of the widespread utilization
of this sweetener.
Further epidemiological and long-term studies are needed to
determine the extent of the hazard that aspartame consumption
poses for humans."

Many scientific studies and case histories report: * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, stiffness, numbness, difficulty swallowing)
* fever, fatigue, swollen glands * "mind fog", "feel unreal",
poor memory, confusion, anxiety, irritability, depression, mania,
insomnia, dizziness, slurred speech, sexual problems,
poor vision, hearing (deafness, tinnitus), or taste
* red face, itching, rashes, allergic dermatitis, hair loss,
burning eyes or throat, dry eyes or mouth, mouth sores,
burning tongue * obesity, bloating, edema, anorexia,
poor appetite or excessive hunger or thirst
* breathing problems, shortness of breath
* nausea, diarrhea or constipation * coldness * sweating
* racing heart, low or high blood pressure, erratic blood sugar levels
* hypothryroidism or hyperthyroidism * seizures * birth defects
* brain cancers * addiction * aggrivates diabetes, autism, allergies,
lupus, ADHD, fibromyalgia, chronic fatigue syndrome,
multiple chemical sensitivity, multiple sclerosis, pseudotumor cerebri
and interstitial cystitis (bladder pain).

http://groups.yahoo.com/group/aspartameNM/message/870
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
woodymonte@xtra.co.nz; woodymonte@canyoncountry.net;
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 1.7.3.3.),
formyl-tetrahydrofolate synthetase (EC 6.3.4.3.) (42)
and other enzymes (18) during evolution sets man apart from all
laboratory animals including the monkey (42).

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 toxic." (8)...

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).
No skeptic can overlook the fact that, metabolically, formaldehyde
must be formed as an intermediate to formic acid production (54).

Formaldehyde has a high reactivity which may be why it has not been
found in humans or other primates during methanol poisoning (59)....

If formaldehyde is produced from methanol and does have a
reasonable half life within certain cells in the poisoned organism
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.

http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30

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.

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

Of course, methanol and formaldehyde toxicity studies are highly
relevant to the issue of aspartame toxicity.
[ Aspartame has to be turned into its toxic products,
formaldehyde and formic acid, in the body, before it is toxic,
so some pro-aspartame reseach studies test aspartame outside the
body, and then proclaim that they have proved that it is not toxic. ]

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

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

http://groups.yahoo.com/group/aspartameNM/message/790
Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic":
Murray 2002.02.07 rmforall

Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
aspartame disease, pages 627-685, 778-780

http://groups.yahoo.com/group/aspartameNM/message/859
Roberts: the life work of a brilliant clinician: aspartame toxicity:
Murray 2002.08.02 rmforall

Russell L. Blaylock, MD 601-982-1175 Madison, Mississippi
"Excitotoxins: The Taste that Kills", 1977, 298 p., 493 references.
"Health and Nutrition Secrets that can save your life", 2002, 459 p.,
558 + 30 references, $ 30 http://www.russellblaylockmd.com/

http://groups.yahoo.com/group/aspartameNM/message/1090
aspartame, MSG, excitotoxins, NMDA glutamate receptors,
multiple sclerosis: Blaylock: Murray 2004.06.09

http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 1999.07.29:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 2000.01.14
The Medical Sentinel Journal 1999 Fall; (95 references)
http://www.dorway.com/blayenn.html

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
[ 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 [A detailed look at the data] ]

MSG and Aspartame -- A Personal Story, TV health reporter
Dick Allgire (vegetarian) healed of migraines and panic attacks:
Murray 2008.02.12
http://rmforall.blogspot.com/2008_02_01_archive.htm
Tuesday, February 12, 2008
http://groups.yahoo.com/group/aspartameNM/message/1520

http://groups.yahoo.com/group/aspartame/messages
group with 1,080 members, 22,439 posts in a public archive
E. Bryant Holman bryanth@presidiotex.com
Carol Guilford CarolGuilford@sbcglobal.net
http://www.presidiotex.com/aspartame/ aspartame@presidiotex.com
http://www.presidiotex.com/aspartame/Links/links.html

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

http://health.groups.yahoo.com/group/GFCFKids/ an excellent group
Gluten Free Casein Free Kids
This list is unmoderated and unrestricted. The principle aim of this list is
to provide a discussion forum for parents of children on the autism
spectrum who are avoiding gluten and casein and other substances
in their children's diets.
9,108 members, 234,968 posts in public archive since Dec. 1998
http://health.groups.yahoo.com/group/GFCFKids/links

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

Mary Nash Stoddard
Toxicology Sourcebook: "Deadly Deception Story of Aspartame"
Aspartame Consumer Safety Network and Pilot Hotline [since 1987]
P.O. Box 2001 Frisco, Texas 75034 U.S. [ North of Dallas ]
Phone/FAX: 214.387.4001
marystod@airmail.net http://www.aspartamesafety.com
http://www.aspartamesafety.com/en_espanol.htm

http://www.sweetpoison.com/ http://www.issplendasafe.com/
http://www.sweetpoison.com/food-additives-to-avoid.html
Dr. Janet Starr Hull, PhD, CN jshull@sweetpoison.com
Splenda®: Is It Safe Or Not?

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

http://www.fedupwithfoodadditives.info/ an excellent group
These web pages provide:
independent information about the effects of food on behaviour,
health and learning ability in both children and adults.
support for families using a low-chemical elimination diet free of
additives, low in salicylates, amines and flavour enhancers (FAILSAFE)
for health, behaviour and learning problems.
Food Intolerance Network, Sue Dengate sdengate@ozemail.com.au;
http://www.fedupwithfoodadditives.info/biodata.htm
_____________________________________________________

www.capitol.hawaii.gov/site1/senate/members/sen13.asp

Suzanne Chun Oakland
13th Senatorial District
Hawaii State Capitol, Room 226
415 South Beretania Street
Honolulu, HI 96813
phone 808-586-6130; fax 808-586-6131
e-mail senchunoakland@Capitol.hawaii.gov;
_____________________________________________________

"Of course, everyone chooses, as a natural priority, to enjoy
peace, joy, and love by helping to find, quickly share, and positively
act upon evidence about healthy and safe food, drink, and
environment."

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

http://RMForAll.blogspot.com new primary archive

http://groups.yahoo.com/group/aspartameNM/messages
group with 121 members, 1,527 posts in a public archive
_____________________________________________________