Scientific Abuse in Methanol /
Formaldehyde Research Related to
Aspartame
Please print and read
completely through this document!
Back to Aspartame Scientific
Abuse Main Page Back to Aspartame Toxicity
Information Center
Table of Contents
* Summary
of Aspartame Methanol/Formaldehyde Toxicity
* Hiding
the Blood Plasma Methanol Increase From
Aspartame Ingestion
* Methanol
and Fruit/Tomatos: Convince the World
That a Poison is "Natural"
* Avoiding
the Discussion of Chronic Methanol
Toxicity
* Convince
Scientists & Physicians With
Irrelevant and Flawed Formate Measurements
* The "It
is Found in the Body, so a Proven Poison
Must be Safe" Excuse to Eat Poison
*
Formaldehyde & Formic Acid in Foods: A Final
Attempt to Prove a Poison is "Safe"
*
Formaldehyde Dose: Fabricating Numbers (Updated
Oct. 16 2000)
*
References
Summary of Aspartame
Methanol/Formaldehyde Toxicity
"These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible for chronic deleterious effects that has also
been considered carcinogenic.
....
"It
is concluded that aspartame consumption may constitute a hazard because
of its contribution to the formation of formaldehyde adducts." (Trocho
1998)
"It was a very interesting paper, that
demonstrates that formaldehyde formation from aspartame ingestion is
very common and does indeed accumulate within the cell, reacting with
cellular proteins (mostly enzymes) and DNA (both mitochondrial and
nuclear). The fact that it accumulates with each dose, indicates grave
consequences among those who consume diet drinks and foodstuffs on a
daily basis." (Blaylock 1998)
Methanol from aspartame is
released in the small intestine when the
methyl group of aspartame encounters the enzyme chymotrypsin (Stegink
1984, page 143). A relatively small amount of aspartame (e.g., one can
of soda ingested by a child) can significantly increase plasma methanol
levels (Davoli 1986a).
Clinically, chronic, low-level
exposure to methanol has been seen to
cause headaches, dizziness, nausea, ear buzzing, GI distiurbances,
weakness, vertigo, chills, memory lapses, numbness & shooting
pains, behavioral disturbances, neuritis, misty vision, vision
tunneling, blurring of vision, conjunctivitis, insomnia, vision loss,
depression, heart problems (including disease of the heart muscle), and
pancreatic inflammation (Kavet 1990, Monte 1984, Posner 1975).
The methanol from aspartame is
converted to formaldehyde and then
formic acid (DHHS 1993, Liesivuori 1991), although some of the
formaldehyde appears to accumulate in the body as discussed above.
Chronic formaldehyde exposure at very low doses has been shown to cause
immune system and nervous system changes and damage as well as
headaches, general poor health, irreversible genetic damage, and a
number of other serious health problems (Fujimaki 1992, He 1998, John
1994, Liu 1993, Main 1983, Molhave 1986, National Research Council
1981, Shaham 1996, Srivastava 1992, Vojdani 1992, Wantke 1996). One
experiment (Wantke 1996) showed that chronic exposure to formaldehyde
caused systemic health problems (i.e., poor health) in children at an
air concentration of only 0.043 - 0.070 parts per million!
Obviously, chronic exposure to
an extremely small amount of
formaldehyde is to be avoided. Even if formaldehyde adducts did not
build up in the body from aspartame use, the regular exposure to excess
levels of formaldehyde would still be a major concern to independent
scientists and physicians familiar with the aspartame toxicity issue.
In addition to chronic
formaldehyde poisoning, the excitotoxic amino
acid derived from aspartame will almost certainly worsen the damage
caused by the formladehyde. Synergistic effects from aspartame
metabolites are rarely, if ever, mentioned by the manufacturer.
Aspartame breaks down into a free-form (unbound to protein) excitotoxic
amino acid which is quickly-absorbed (as long as it is not given in
slow-dissolving capsules) and can raise the blood plasma levels of this
excitotoxin (Stegink 1987). It is well known that free-form
excitotoxins can cause irreversible damage to brain cells (in areas
such as the retina, hypothalamus, etc.) in rodents and primates (Olney
1972, Olney 1980, Blaylock 1994, Lipton 1994). In order to remove
excess, cell-destroying excitotoxic amino acids from extracellular
space, glial cells surround the neuron and supply them with energy
(Blaylock 1994, page 39, Lipton 1994). This takes large amounts of ATP.
However, formate, a formaldehyde metabolite, is an ATP inhibitor
(Liesivuori 1991). Eells (1996b) points out that excitatory amino acid
toxicity may be the "mediators of retinal damage secondary to formate
induced energy depletion in methanol-intoxication." The synergistic
effects from the combination of a chronic formaldehyde exposure from
aspartame along with a free-form excitotoxic amino acid is extremely
worrisome.
It appears that methanol is
converted to formate in the eye (Eells
1996a, Garner 1995, Kini 1961). Eells (1996a) showed that chronic,
low-level methanol exposure in rats led to formate accumulation in the
retina of the eye.
More details about chronic
Methanol / Formaldehyde poisoning from
aspartame can be found on the Internet at
http://www.holisticmed.com/aspartame/aspfaq.html.
How did the manufacturer
convince scientists and physicians that it is
"safe" to be exposed regularly to low levels of an exceptionally toxic
poison? Answer: Deceptive research and deceptive statements!
Hiding the Blood Plasma
Methanol Increase From Aspartame Ingestion
On February 22, 1984, the
acting FDA Commissioner, Mark Novitch stated
(Federal Register 1984):
"... aspartame showed no detectable
levels of methanol in the blood of human subjects following the
ingestion of aspartame at 34 mg/kg ...."
The American Medical
Association repeated this statement one year later
(AMA 1985). This statement was repeated in American Family Physician in
1989 (Yost 1989). Shaywitz (1994) stated that there was no detectable
levels of methanol in the blood after aspartame administration.
Puthrasingam (1996) stated that methanol from aspartame is
"undetectable in peripheral blood or even in portal blood."
All of these statements were
very convincing ... and very wrong! The
statements were based on aspartame industry research which used an
outdated plasma methanol measuring test (Baker 1969). The test they
used had a limit of methanol detection of 4 mg/l. However, Cook (1991)
measured an average baseline (unexposed) methanol level of ~0.6 mg/l.
Others (Davoli 1986, d'Alessandro 1994, Osterloh 1996) have measured an
average baseline methanol level of close to 1 mg/l. This means that a
person's methanol levels would have to rise 350% to 600% before an
increase would have been noticed by the industry researchers using this
outdated test! An increase of less than 350% to 600% appeared as no
increase at all!
Probably only a handful of
people in the world would have noticed that
by using a plasma methanol measuring test with limits of 4 mg/l, they
avoided seeing an methanol level increase -- even though there was a
large increase. Below are some of the experiments which used the
inappropriate methanol measuring technique.
Research
Aspartame Dosage
Claimed to Not
Raise Methanol Levels
Lowest Possilbe
Methanol Measurement
Other Methanol Issues
Frey 1976
77 mg/kg
Not stated
Test
conducted after 12-hour fast. All methanol
would have been converted to formaldehyde.
Stegink 1981
34 mg/kg
4 mg/l
Orange
juice given despite discussion of high level
of methanol in fruit.
Stegink 1983
34 mg/kg
4 mg/l
...
Leon 1989
75 mg/kg
4 mg/l
Test
conducted after 12-hour fast. All methanol
would have been converted to formaldehyde.
Stegink 1989
8 hourly doses of 10 mg/kg
4 mg/l
...
Stegink 1990
8 hourly doses of 10 mg/kg
4 mg/l
Fig. 4:
Graph of blood methanol concentrations shown
with all points well below 4 mg/l -- the lower limit of their methanol
test.
Hertelendy 1993
15 mg/kg
4 mg/l
...
Shaywitz 1993
34 mg/kg
4 mg/l
...
Shaywitz 1994
34 mg/kg
4 mg/l
...
Note: 10 mg/kg is approximately a one
liter bottle of diet soda for a 60 kg adult and 1.5 cans of diet soda
for a 30 kg child. Children with aspartame freely-available can ingest
between 27 mg/kg - 77 mg/kg (Frey 1976) and adults dieters have been
shown to ingest between 8 mg/kg and 36 mg/kg (Porikos 1984).
In 1986, Davoli (1986a)
published a study which showed that 6 mg/kg to
8.7 mg/kg of aspartame could significantly raise the plasma methanol
levels. The methanol levels nearly doubled in some cases. While there
were some logical errors in Davoli's conclusion (discussed below), the
study proved that by using a reasonable methanol testing method, plasma
methanol levels will increase from a relatively low dose of aspartame
ingestion. The methanol measuring technique used by Davoli was
published in 1985 (Davoli 1986b) and was sensitive to 0.012 mg/l.
Other researchers have used
sensitive plasma methanol measurement
techniques. d'Alessandro (1994) measured plasma methanol levels in
humans well below 1 mg/l. Cook (1991) used a methanol test developed in
1981 to measure methanol plasma methanol levels in humans below 0.5
mg/l.
What did industry scientists
know or should have known?
1. They knew and
admited that their methanol testing
procedure developed in 1969 was not sensitive enough to detect the
large increases of plasma methanol levels when aspartame was given at
doses of 34 mg/kg (Stegink 1984b).
2. They must have
been aware that Davoli found methanol
levels increase significantly when aspartame was given at doses of 6
mg/kg to 8.7 mg/kg. To believe that they were not aware of this, one
has to believe that none of the researchers choose to or knew how to
conduct a simple Medline database search.
3. They should
have known that there were several
legitimate plasma methanol measurement techniques developed since 1969.
Given that they admited their technique was not appropriate for
aspartame doses of less than 34 mg/kg (Stegink 1984b), they should have
at least looked to find an appropriate test.
4. Given that
Leon (1989) was aware enough to test for
formate levels, he must have been aware that all of the methanol from
aspartame would have already converted to formaldehyde after a 12-hour
fast.
I believe that
Monsanto/NutraSweet and the aspartame industry are
clearly taking advantage physicians and scientists who lack the time to
carefully investigate each number in a study to see if there is
deception. While these actions may not amount to "scientific fraud," it
does amount to an abuse of the scientific method in my opinion.
Methanol and Fruit/Tomatos:
Convince the World That a Poison is
"Natural"
Monsanto/NutraSweet's all time
favorite aspartame fairy tale is:
"In addition, exposure to methanol from
many fruits, vegetables, and juices in the normal diet is several times
greater than that from beverages sweetened with APM [aspartame]."
(Butchko 1991)
This statement from NutraSweet
scientists has been repeated countless
times (AMA 1985, FDA 1984, Hertelendy 1993, Lajtha 1994, Monsanto 1999,
Nelson 1996, Stegink 1981, Stegink 1983, Yost 1989, etc.). This is very
convincing ... but deceptive and irrelevant!
It is well known that
alcoholic beverages such a wine contain a large
amount of ethanol, a protective factor which prevents methanol
poisoning by preventing the conversion of methanol to the highly toxic
formaldehyde (Leaf 1952, Liesivuori 1991, Roe 1982). Because alcoholic
beverages contain protective factors which prevent chronic poisoning
from methanol metabolites (formaldehyde, formate), comparisons between
the methanol derived from aspartame and the methanol derived from
alcoholic beverages are inappropriate.
Clinical reports and a small
number of epidemiological studies appear
to demonstrate that prolonged exposure to methanol air concentrations
(in the workplace) of > 260 mg/m3 (200 ppm) can cause chronic
methanol toxicity (Kavet 1990, Frederick 1984, Kingsley 1954-55). The
weekly amount of methanol absorbed from a 260 mg/m3 workday exposure is
(formula in Kavet 1990):
(260 mg/m3 * 6.67 m3/workday *
5 workdays * 60% absorption rate) / 70
kg adult
= 75 mg/kg weekly methanol
Note: While this seems like a high
weekly methanol dose, please keep in mind that 1) much lower levels may
cause toxicity in some individuals; and 2) that aspartame breaks down
into an excitotoxin which will likely enhance the toxicity of methanol
metabolites as described above.
However, the ingestion of a
moderate amount of apples or oranges (or
juice equivalent) per week leads to a similar exposure to methanol
(Lindinger 1997):
(750 mg methanol (1.5 kg
fruit) * 7 days) / 70 kg adult
= 74 mg/kg weekly methanol
Keep in mind that tomatoes may
have more than five times the amount of
methanol as that found in oranges (Kazeniac 1970, Nisperos-Carriedo
1990), so exposure to regular ingestion of tomatoes and tomato juice
may produce very large amounts of methanol.
Lindinger (1997) points out
that the amount of methanol released in the
human body from a few apples or oranges is equivalent to:
"...0.3 liters of brandy (40% ethanol)
containing 0.5% of methanol (compared with ethanol), which would
qualify as significantly methanol-contaminated liquor."
Because of the high amounts of
methanol in fruits/tomatoes, enough that
would clearly cause chronic methanol poisoning, these foods must
contain protective factors (as does alcoholic beverages). If they did
not contain protective factors, we would be seeing widespread methanol
poisoning for persons who ingestion fruits and tomatoes regularly.
The manufacturer showed that
the protective factor in fruits cannot be
ethanol by itself (Sturtevant 1985), but there are a myriad of
chemicals in fruits which might serve as protective factors.
What did industry scientists
know or should have known?
1. They knew that
alcoholic beverages contain protective
factors which prevent chronic methanol poisoning (Sturtevant 1985).
2. Because
industry scientists regularly announced that
certain fruits contain extremely high levels of methanol, they should
have taken the time to find out that fruits have protective factors
which help prevent chronic poisoning from methanol metabolites.
Avoiding the Discussion of
Chronic Methanol Toxicity
A number of
Monsanto/NutraSweet public relations statements as well as
statements from government officials imply that the amount of methanol
obtained from aspartame is not toxic:
"From estimates based on blood levels in
methanol poisonings, it appears that the ingestion of methanol on the
order of 200 to 500 mg/kg body weight is required to produce a
significant accumulation of formate in the blood which may produce
visual and central nervous system toxicity" (Federal Register 1984)
Lajtha (1994) claimed that
"blood methanol concentrations greater than
200 to 100 mg/L are required for clinical neurotoxicity or for
measurable formate formation." Non-scientists on the Internet often
make similar claims. Shahangian (1984) claimed that the amount of
formate (methanol and formaldehyde metabolite) is not enough to cause
toxicity.
This sounds very convincing
until one realizes that the doses they are
refering to are the single doses required for death or near death in
humans! Monsanto/NutraSweet and persons promoting aspartame will
avoiding discussing chronic, low-level methanol or formaldehyde
poisoning because once this issue is raised it becomes apparent that
the manufacturer did not conduct or even cite any legitimate studies on
chronic, low-level methanol exposure in humans!
Only on very rare occassion
will the manufacturer mention chronic
methanol toxicity (Nelson 1996, Sturtevant 1985). When they do this,
they always cite a study of infant monkeys (a species closely related
to rhesus monkeys) (Reynolds 1984). A dose of 3,000 mg/kg of aspartame
was given to the monkeys for nine months. This amounts to a daily
methanol dose of 300 mg/kg -- a huge dose.
What Monsanto/NutraSweet fails
to mention is 300 mg/kg of methanol has
been estimated as the minimum single dose which can cause death in
humans (Kavet 1991). If such a study were conducted on humans, nine
months of daily ingestion of the minimum lethal single dose of methanol
would clearly kill everyone in the study!. As pointed out by Roe
(1982), methanol is significantly more toxic in humans than in monkeys
or rodents. It is important to note that the free-form excitotoxin
derived from aspartame and which will likely increase the
formaldehyde/formate damage from aspartame, appears to be approximately
twenty times more toxic in humans than in monkeys due to differences in
excitotoxin metabolism (Olney 1988, Stegink 1979, page 90).
What did industry scientists
know or should have known?
1. They knew that
there was never a controlled, long-term
study of methanol exposure in humans. Given that the manufacturer was
expecting to dose the human population with aspartame for a lifetime
and even generations, some might consider it criminal to sell a poison
under these circumstances.
2. They should
have known that an excitotoxin will likely
increase the toxicity of the formaldehyde/formate based upon the way
these chemicals produce cell damage and cell death. At the very least,
the manufacturer should have exhausted all reasonable possibilities of
synergistic reactions as opposed to using flawed research and flawed
logic to explain away the countless cases of aspartame poisoning.
Convince Scientists &
Physicians With Irrelevant and Flawed Formate
Measurements
The FDA Commissioner has
claimed (Federal Register 1984):
"In the Searle [manufacturer] clinical
study using abuse doses of aspartame equivalent to 20 mg/kg body weight
of methanol, no significant increases were observed in plasma
concentrations of formate, suggesting that the rate of formate
production does not exceed its rate of urinary excretion."
The AMA (1985) claimed that
abuse doses of aspartame have not been
shown to increase blood formate levels. Stegink (1989, 1990) claimed
that large doses of aspartame did not raise blood and urine formate
levels significantly. Leon (1989) claimed to show no increase in
urinary formate from a daily dose of 75 mg/kg of aspartame. Hertelendy
(1993) claimed that there was not increase in urine or plasma formate
levels from 15 mg/kg aspartame ingestion.
Since methanol metabolizes
into formaldehyde and formaldehyde
metabolizes into formate, all of these statements appear to point to
safety ... at first glance. But what the manufacturer does not tell you
is that these tests are now known to be irrelevant and flawed!
Formate (formic acid)
measurement of the urine is not an appropriate
test for low-level formaldehyde poisoning. (Keep in mind that extremely
low doses of formaldehyde have been shown to cause chronic poisoning
symptoms as discussed above.) Triebig (1989) states that formic acid
excretion in the urine is a "unspecific and insensitive biological
indicator for monitoring low-dose formaldehyde exposure." Schmid (1994)
found that neither a single significant exposure to formaldehyde nor a
week-long exposure to formaldehyde correlated with urine formic acid
measurements. After testing subjects exposed to formaldehyde, Heinzow
(1992) stated:
"Excretion [of formic acid] in the
general population is determined by endogenous metabolism of amino
acids, purine- and pyrimidine-bases rather than the uptake and
metabolism of precursors like formaldehyde. Hence in contrast to recent
recommendations in environmental medicine, formic acid in urine is not
an appropriate parameter for biological-monitoring of low level
exposure to formaldehyde."
Therefore, all of the
aspartame industry's urine formate measurements
are useless for chronic methanol/formaldehyde poisoning from aspartame.
Blood formate measurements
also appear to be inadequate for chronic,
low-level methanol or formaldehyde poisoning. d'Alessandro (1994)
stated:
"While exposure to several different
levels of methanol above the threshold limit [200 ppm] might
demonstrate slight increases in formate concentrations, it seems
doubtful that this measure would be useful for monitoring individual
low-level exposure."
And after further study,
Osterloh (1996) stated:
"Previously, we reviewed exposure
studies (both occupational and experimental) in which formate
concentrations were measures, along with these data, as a basis for the
conclusion that methanol, not formate, in serum can be used as a
biological marker of exposures."
Three other reasons why
aspartame industry formate measurements can be
considered useless include:
1. Trocho (1998)
showed a significant amount of
formaldehyde from aspartame binding with proteins and accumulating in
tissues rather than metabolizing into formate.
2. The average
baseline (pre-exposure) measurements of
formate in the aspartame industry research (e.g., Stegink 1981, 1989,
1990) is unexplicabally 1.5 to 3 times higher than any other
independent researcher (d'Alessandro 1994, Baumann 1979, Buttery 1988,
Heinrich 1982, Osterloh 1986, Osterloh 1996). As pointed out by Kavet
(1990), high pre-exposure blood formate levels "may have masked any
subtle increases that the aspartame may have caused."
3. A respected
formaldehyde and formic acid exposure
researcher has pointed out that several formate measurement techniques
including the one used by aspartame industry researchers (Makar 1982)
are "notoriously inaccurate." (Liesivuori 1986).
Unfortunately, there are still
researchers who cite old tests of
formate levels related to aspartame ingestion even though these tests
have proven to be meaningless and flawed.
What did industry scientists
know or should have known?
1. The industry
researchers should have keep up-to-date on
formate measurment research. Had they done that, they would have known
that such measurements are inappropriate for chronic, low-level
methanol and formaldehyde exposure.
The "It is Found in the Body,
so a Proven Poison Must be Safe" Excuse
to Eat Poison
From time to time, it will be
implied that because methanol and
formaldehyde are in the body, it is perfectly safe to add more. Acting
FDA Commissioner Mark Novitch stated the following (Federal Register
1984):
"Normal metabolic processes such as
purine and pyrimidine biosynthesis and amino acid metabolism require
methyl groups from compounds like methanol. It also appears that either
methanol or formaldehyde may serve as precursors for the methyl groups
in choline synthesis."
On the Internet, this is a
popular technique used to try to convince
people that methanol and formaldehyde exposure is safe. What the FDA
Commissioner and other persons unfamiliar with this issue did not point
out is that chronic poisoning from low-level methanol and formaldehyde
exposure is already accepted in the medical community. In fact,
children who were chronically-exposed to formaldehyde in the air at
concetrations of 0.05 parts per million (ppm) developed systemic health
problems after several months (Wantke 1996). This is equivalent to a
daily exposure of only 0.75 mg of formaldehyde (or less if 100% of the
formaldehyde is not absorbed):
0.05 ppm formaldehyde ~= 0.075 mg/m3
0.075 mg/m3 * 10 m3/workday = 0.75
mg/day (for a workday/schoolday)
Other researchers have noted
formaldehyde toxicity symptoms appearing
at chronic, low-level exposure (Srivastava 1992):
"Complaints pertaining to
gastrointestinal, musculoskeletal and carbiovascular systems were also
more frequent in exposed subjects. In spite of formaldehyde
concentrations being well within the prescribed ACGIH [American
Conference of Governmental Industrial Hygienists] limits of 1 ppm...."
This proves that formaldehyde
levels in the body must be very
tightly-controlled since a very low daily exposure leads to health
problems. Even a very small, regular increase can lead to chronic,
low-level poisoning.
Davoli (1986) showed that
aspartame significantly increases plasma
methanol levels. However, he mistakenly concluded that because the
post-aspartame administration methanol levels did not rise above the
baseline methanol levels of every other human being, those levels might
not be toxic. What Davoli failed to consider, however, is that 1) we
know that methanol and formaldehyde levels in the body must be tightly
controlled because exposure to very low levels of these chemicals have
been shown to lead to chronic toxicity; and 2) that people have their
own individual metabolism so that a slight addition of formaldehyde to
the current tightly-controlled level in one individual could cause
toxicity even though it might not rise above the baseline level of
another individual's formaldehyde level. As one can see from the Davoli
(1986) study, the administration of aspartame lead to a fairly sudden
and significant increase in plasma methanol levels and would be
expected to cause a significant formaldehyde exposure.
Formaldehyde & Formic Acid
in Foods: A Final Attempt to Prove a
Poison is "Safe"
"... formaldehyde [exposure from
aspartame is] comparable to a serving of fresh broccoli." (Weber 1999)
Every once in a while there
will be a statement pointing out that some
foods have relatively high levels of formaldehyde and formic acid. What
is not pointed out is that formaldehyde in food is much less toxic than
formaldehyde from air exposure or formaldehyde from aspartame exposure
due to the way the body metabolizes it.
Restani (1991) points out that
formaldehyde can be found in seafood,
honey, fruits, vegetables, etc. Restani (1991) points to a human study
showing where 200 mg of formaldehyde per day was ingested for 13 weeks
without showing adverse effects. This would be equivalent to an daily
air exposure of:
200 mg/day / 10 m3/workday = 20.0 mg/m3
= 13.3 ppm
13.3 ppm daily air exposure is
many times over the 0.05 levels which
caused chronic toxicity in Wantke (1996) and many times over the
American Conference of Governmental Industrial Hygienists limit of 1
ppm which was shown to cause chronic toxicity in Srivastava (1992).
This proves that formaldehyde
found in foods is either not absorbed
well:
"Ingestion represents a minor route of
[formaldehyde] exposure because the dilution factor and the binding to
the macromolecules present in food reduce substantially the
[formaldehyde] concentration that enters into contact with the
gastrointestinal mucosa" (Restani 1991)
Or formaldehyde may be broken
down by the digestive system. With
aspartame, however, the methanol has been proven to be absorbed and
then after it is already in the bloodstream, it is converted to
formaldehyde (or directly to formate in certain tissues such as the
retina).
Formaldehyde Dose: Fabricating
Numbers
One way to convince at least a
few people that it is 'safe' to be
poisoned with aspartame is to simply make up numbers that appear to
show that formaldehyde exposure from aspartame is low. One author
claimed that formaldehyde exposure was only 30 micrograms -- a figure
off by a factor of over 400,000 for the aspartame dose that was used!
The following web page calculates and discusses the dose of
formaldehyde exposure and accumulation due to aspartame ingestion:
http://www.holisticmed.com/aspartame/fm.html
References
AMA 1985. "Aspartame: Review
of Safety Issues," Journal of the American
Medical Association, Volume 254, No. 3, page 400-402.
Baker, R.N., A.L. Alenty, J.F.
Zack, 1969. "Simultaneous Determination
of Lower Alcohols, Acetone and Acetaldehyde in Blood by Gass
Chromatography," Journal of Chromatographic Science, Volum 7, pages
312-314, 1969.
Baumann, K., J. Angerer, 1979.
"Occupational Chronic Exposure to
Organic Solvents. VI. Formic Acid Concentration in Blood and Urine as
an Indicator of Methanol Exposure," International Archives of
Occupational and Environmental Health, Volume 42, page 241.
Blaylock, Russell L., 1994.
"Excitotoxins: The Taste That Kills,"
Health Press, Santa Fe, New Mexico, c1994.
Blaylock, Russell L.,
Neurosurgeon, 1998. Personal communication on
December 30, 1998.
Butchko, Harriett H., Frank N.
Kotsonis 1991. "Acceptable Daily Intake
vs Actual Intake: The Aspartame Example," Journal of the American
College of Nutrition, Volume 10, No. 3, page 258-266.
Buttery, J.E., B.R.
Chamberlain, 1988. "A Simple Enzymatic Method for
the Measurement of Abnormal Levels of Formate in Plasma," Journal of
Analytical Toxicology, Volume 12, page 292-294.
Cook, M.R., F.J. Bergman, et
al., 1991. "Effects of Methanol Vapor on
Human Neurobehavioral Measures," Research Report No. 42 (Peer
Reviewed), Health Effects Institute, 141 Portland Street, Suite 7300,
Cambridge, MA 02139, (617) 621-0266, August 1991.
d'Alessandro, Alessandra, et
al., 1994, "Formate in Serum and Urine
after Controlled Methanol Exposure at the Threshold Limit Value,"
Environmental Health Perspectives, Volume 102, No. 2, February, 1994,
page 178-181.
Davoli, E., et al., 1986a.
"Serum Methanol Concentrations in Rats and
in Men After a Single Dose of Aspartame," Food and Chemical Toxicology,
Volume 24, No. 3, page 187-189.
Davoli, E., et al., 1986b.
"Trace Analysis of Methanol in Rat Serum by
Headspace High Resolution Gass Chromatography/Selected Ion Monitoring,"
Journal of Chromatographic Science, Volume 24, pages 113-116, 1986.
DHHS 1993. "Methanol
Toxicity," American Family Physician, Volume
71(1):163-171, January 1993. Adapted from Case Studies in Environmental
Medicine published by the Agency For Toxic Substances and Disease
Registry, U.S. Department of Helath and Human Services.
Eells, Janis T., et al.,
1996a. "Formate-Induced Alterations in Retinal
Function in Methanol-Intoxicated Rats," Toxicology and Applied
Pharmacology, Volume 140, page 58-69.
Eells, Janis T., 1996b.
"Mechanism of Methanol-Induced Retinal
Alterations," NIH Grant Application, Project No. 5 R01 ES06648-03,
FY96, NIH CRISP Database: gopher://gopher.nih.gov:70/11/res/crisp
Federal Register 1984. "Food
Additives Permitted for Direct Addition to
Food for Human Consumption; Aspartame," Volume 49, No. 36, February 22,
1984, page 6672-6682.
Frederick, Linda J., et al.,
1984. "Investigation and Control of
Occupational Hazards Associated with the Use of Spirit Duplicators,"
American Industrial Hygiene Association Journal, Volume 45, No. 1, page
51-55.
Frey, Gunther H., 1976. "Use
of Aspartame By Apparently Healthy
Children and Adolescents," Journal of Toxicology and Environmental
Health, Volume 2, page 401-415.
Fujimaki, H., et al., 1992.
"Mast Cell Response to Formadehyde,"
International Archives of Allergy & Immunology, Volume 98, No. 4,
page 324-331.
Garner, C.D., et al. 1995.
"Role of Retinal Metabolism in
Methanol-Induced Retinal Toxicity," Journal of Toxicology and
Environmental Health, Volume 44, No. 1, pages 43-56.
He, J.L., L.F. Jin, H.Y. Jin,
1998. "Detection of Cytogenetic Effects
in Peripheral Lymphocytes of Students Exposed to Formaldehyde With
Cytokinesis-Blocked Micronucleus Assay," Biomedical Environmental
Science, Volume 11, No. 1, pages 87-92.
Heinrich, R., J. Angerer,
1982. "Occupational Chronic Exposure to
Organic Solvents. X. Biological Monitoring Parameters for Methanol
Exposure," International Archives of Occupational and Environmental
Health, Volume 50, page 341.
Heinzow, B., T. Ellrott 1992.
"Formic Acid in Urine -- A Significant
Parameter in Environmental Diagnosis?" Zentralbl Hyg Umweltmed, Volume
192, No. 5, page 455-461.
Hertelendy, Zsolt, et al.,
1993. "Biochemical and Clinical Effects of
Aspartame in Patients with Chronic, Stable Alcoholic Liver Disease,"
The American Journal of Gastroenterology, Volume 88, No. 5, 1993.
John, E.M., et al., 1994.
"Spontaneous Abortion Among Cosmetologists,"
Epidemiology, Volume 5, No. 2, page 147-155.
Kavet, Robert, Kathleen M.
Nauss, 1990. "The Toxicity of Inhaled
Methanol Vapors," Critical Reviews in Toxicology, Volume 21, Issue 1,
page 21-50.
Kazeniac, S.J., R.M. Hall,
1970. "Flavor Chemistry of Tomato
Volatiles," Journal of Food Science, Volume 35, page 519-530.
Kingsley, W.H., F.G. Hirsch,
1954-1955. "Toxicological Considerations
in Direct Process Spirit Duplication Machines," Compen. Medicine,
Volume 40, page 7-8.
Kini, M.M., J.R. Copper, 1961.
"Biochemistry of Methanol
Poisoning--III: The Enzymic Pathway For the Conversion of Methanol to
Formaldehyde," Biochemical Pharmacology, Volume 8, pages 207-215, 1961.
Lajtha, Abel, Margaret Reilly,
David Dunlop, 1994. "Aspartame
Consumption: Lack of Effects on Neural Function," Journal of
Nutritional Biochemistry, Volume 5, page 266-283.
Leaf, G., L.J. Zatman 1952, "A
Study of the conditions Under Which
Methanol May Exert a Toxic Hazard in Industry," British Journal of
Industrial Medicine, Volume 9, page 19- 31.
Leon, Arthur S., et al., 1989.
"Safety of Long-Term Large Doses of
Aspartame," Archives of Internal Medicine, Volume 149, page 2318-2324.
Liesivuori, Jyrik, 1986. "Slow
Urinary Elimination of Formic Acid in
Occupationally Exposed Farmers," Annals of Occupational Hygiene, Volume
30, No. 3, page 329-333.
Liesivuori, Jyrki, Heikki
Savolainen, 1991. "Methanol and Formic Acid
Toxicity: Biochemical Mechanisms," Pharmacology & Toxicology,
Volume 69, page 157-163.
Lindinger, W., J. Taucher, A.
Jordan, A. Hansel, W. Vogel, 1997.
"Endogenous Production of Methanol after the Consumption of Fruit,"
Alcoholism: Clinical and Experimental Research, Volume 21, No. 5, pages
939-943.
Lipton, Stuart A., Paul A.
Rosenberg, 1994. "Excitatory Amino Acids as
a Final Common Pathway for Neurologic Disorders," New England Journal
of Medicine, Volume 300, No. 9, page 613-622.
Liu, Kai-Shen, et al., 1993.
"Irritant Effects of Formaldehyde Exposure
in Mobile Homes," Environmental Health Perspectives, Volume 94, page
91-94.
Main, D.M., T.J. Hogan, 1983.
"Health Effect of Low-Level Exposure to
Formaldehyde," Journal of Occupational Medicine, Volume 25, page
896-900.
Makar, A.B., T.R. Tephly,
1982. "Improved Estimation of Formate in Body
Fluids and Tissues," Clinical Chemistry, Volume 28, page 385, 1982.
Molhave, L., et al., 1986.
"Dose-Response Relation of Volitile Organic
Compounds in the Sick Building Syndrome," Clinical Ecology, Volume 4,
No. 2, page 52-56.
Monsanto (NutraSweet) 1999.
"Frequently Asked Questions," NutraSweet
Web Page, http://www.nutrasweet.com/
Monte, Woodrow C., 1984.
"Aspartame: Methanol and the Public Health,"
Journal of Applied Nutrition, Volume 36, No. 1, page 42-54.
National Research Council
1981. "Formaldehyde and Other Aldehydes,"
National Research Council, National Academy Press, Washington, D.C.,
c1981.
Nelson, Richard (VP Public
Affairs, NutraSweet Company), Internet post
to several USENET newsgroups, October 24, 1996. View at web address:
http://x8.dejanews.com/getdoc.xp?AN=191830590&CONTEXT=916551634.1925513337&hitnum=29
Nisperos-Carriedo, Myrna O.,
Philip E. Shaw, 1990. "Comparison of
Volatile Flavor Components in Fresh and Processed Orange
Juices,"Journal of Agriculture & Food Chemistry, Volume 38, page
1048-1052.
Olney, John W., et al., 1972.
"Glutamate-Induced Brain Damage of Infant
Primates," Journal of Neuropathology and Experimental Neurology, Volume
31, page 464-488.
Olney, John W., et al., 1980.
"Brain Damage in Mice From Voluntary
Ingestion of Glutamate and Aspartate," Neurobehavioral Toxicology and
Teratology, Volume 2, page 125-129.
Olney, John W., 1988.
"Excitotoxic Food Additives: Functional
Teratological Aspects," In Progress in Brain Research, Volume 73 --
Biochemical Basis of Functional Neuroteratology: Permanent Effects of
Chemicals on the Developing Brain, Edited by Boer, G.J., et al.,
Elsevier, New York, c1988.
Osterloh, J., 1986. "The
Utility of Tetrabromophenophthalein Methyl
Ester (TBPME) Spot Test for the Identification of Drug Positive
Urines," Journal of Analytical Toxicology, Volume 10, page 255.
Osterloh, John D., A.
d'Alessandro, P. Chuwers, H. Mogadeddi, T. Kelly,
1996. "Serum Concentrations of Methanol After Inhalation of 200 ppm,"
Journal of Occupational and Environmental Medicine, Volume 38, Issue 6,
pages 571-576.
Porikos, Katherine P.,
Theodore B. Van Italie, 1984. "Efficacy of
Low-Calorie Sweeteners in Reducing Food Intake: Studies with Aspartame"
IN Stegink, L., Filer L., 1984. "Aspartame: Physiology and
Biochemistry," Marcel Dekker, Inc., N.Y., page 273-286.
Posner, Herbert S., 1975.
"Biohazards of Methanol in Proposed New
Uses," Journal of Toxicology and Environmental Helath, Volume 1, page
153-171.
Puthrasingam S., et al., 1996.
"Aspartame Pharmacokinetics - The Effect
of Ageing," Age and Ageing, Volume 25, Number 3, pages 217-220.
Restani, Patrizia, Corrado
Galli, 1991. "Oral Toxicity of Formaldehyde
and Its Derivatives," Critical Reviews in Toxicology, Volume 21, Issue
5, pages 315-328.
Reynolds, W. Ann, A.F. Bauman,
Lewis Stegink, L.J. Filer, Jr., S. Naidu
1984. "Developmental Assessment of Infant Macaques Receiving Dietary
Aspartame or Phenylalanine," IN Stegink, L., Filer L., 1984.
"Aspartame: Physiology and Biochemistry," Marcel Dekker, Inc., N.Y.,
page 405-423.
Roe, O., 1982. "Species
Differences in Mehtanol Poisoning," CRC
Critical Reviews In Toxicology, October 1982, page 275-286.
Schmid, K., et al., 1994. "The
Importance of Formic Acid Excretion in
the Urine for Environmental and Occupational Medicine Questions,"
Zentralbl Hyg Umweltmed, Volume 196, No. 2, page 139-152.
Shaham, J., Y. Bomstein, A.
Meltzer, Z. Kaufman, E. Palma, J. Ribak,
1996. "DNA--protein Crosslinks, a Biomarker of Exposure to
Formaldehyde--in vitro and in vivo Studies," Carcinogenesis, Volume 17,
No. 1, page 121-125.
Shahangian, Shahram, K. Owen
Ash, 1984. "Aspartame Not a Source of
Formate Toxicity," Clinical Chemistry, Volume 30, No. 7, pages
1264-1265, 1984.
Shaywitz, B.A., et al., 1993.
"Evaluation of Aspartame on Behavior and
Cognitive Function in Children With Attention Deficit Disorder (ADD),"
Journal of Clinical and Experimental Neuropsychology, Volume 15, page
407
Shaywitz, Bennett A., et al.,
1994b. "Aspartame, Behavior, and
Cognitive Function in Children With Attention Deficit Disorder,"
Pediatrics, Volume 93, page 70-75.
Srivastava, A.K., et al.,
1992. "Clinical studies of employees in a
sheet-forming process at a paper mill," Veterinary and Human
Toxicology, Volume 34, No. 6, page 525-527.
Stegink, Lewis D., W.A.
Reynolds, L.J. Filer, et al. 1979. "Comparative
Metabolism of Glutamate in the Mouse and Man," In Filer L.J. Jr.,
Garattini, S., Dare MR, Reynolds WA, Wurtman RJ (eds): "Glutamic Acid:
Advances in Biochemistry and Physiology," Raven Press, New York 1979,
pages 85-102.
Stegink, Lewis D., et al.,
1981. "Blood Methanol Concentrations in
Normal Adult Subject Administered Abuse Doses of Aspartame," Journal of
Toxicology and Environmental Health, Volume 7, page 281-290.
Stegink, Lewis D., L. Filer,
G.L. Baker, 1983. "Blood Methanol
Concentrations in One-Year-Old Infants Administered Graded Doses of
Aspartame," Journal of Nutrition, Volume 113, page 1600-1606.
Stegink, Lewis D., Filer L.,
1984a. "Aspartame: Physiology and
Biochemistry," Marcel Dekker, Inc., N.Y.
Stegink, Lewis D., 1984b.
"Aspartame Metabolism in Humans: Acute Dosing
Studies" IN Stegink, L., Filer L., 1984. "Aspartame: Physiology and
Biochemistry," Marcel Dekker, Inc., N.Y., page 509-553.
Stegink, Lewis D., et al.
1987a. "Plasma Amino Acid Concentrations in
Normal Adults Administered Aspartame in Capsules or Solution: Lack of
Bioequivalence," Metabolism, Volume 36, No. 5, page 507-512.
Stegink, Lewis D., et al.,
1989. "Effect of Repeated Ingestion of
Aspartame-Sweetened Beverage on Plasma Amino Acid, Blood Methanol, and
Blood Formate Concentrations in Normal Adults," Metabolism, Volume 38,
No. 4, page 357-363.
Stegink, Lews D., et al.,
1990. "Repeated Ingestion of
Aspartame-Sweetended Beverages: Further Observations in Individuals
Heterozygous for Phenylketonuria," Metabolism, Volume 39, No. 10, page
1076-1081.
Sturtevant, F., 1985. "Does
Aspartame Cause Methanol Toxicity" (Letter
To The Editor), Food and Chemical Toxicology, Volume 23, No. 10, page
961, 1985.
Triebig, G., et al., 1989.
"Formaldehyde exposure at various
workplaces," Science of the Total Envirnment, Volume 79, No. 2, page
191-195.
Trocho, C., et al., 1998.
"Formaldehyde Derived From Dietary Aspartame
Vinds to Tissue Components in vivo," Life Sciences, Vol. 63, No. 5, pp.
337+, 1998
Vojdani, A., 1992. "Immune
Alteration Associated With Exposure to Toxic
Chemicals," Toxicol Ind Health, Volume 8, No. 5, page 239-254.
Wantke, F., C.M. Demmer, P.
Tappler, M. Gotz, R. Jarisch, 1996.
"Exposure to Gaseous Formaldehyde Induces IgE-Mediated Sensitization To
Formaldehyde in School-Children," Clinical and Experimental Allergy,
Volume 26, pages 276-280.
Weber, James Matthew, 1999.
Internet post to USENET newsgroup on
January 5, 1999 by former G.D. Searle (owner by Monsanto) employee.
Reference post on the web at:
http://x8.dejanews.com/getdoc.xp?AN=428867791&CONTEXT=916601874.949026972&hitnum=0
Yost, David A., 1989.
"Clinical Safety of Aspartame," American Family
Physician, Volume 39, Number 2, pages 201-206, 1989.