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Subject: Aspartame: Methanol and the Public Interest 1984: Monte: Murray 9.23.2
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Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall
Rereading this prescient classic review from 1984, I find its findings
are supported in much recent research, so I am again making the full
text widely available.
[I have put my comments or corrections in square brackets, and spaced
the text to ease the reader's task]
For instance, I had forgotten this, which answers the industry PR
"science" that fruits and vegetables
supply much more methanol than does aspartame:
Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required
for its hydrolysis to methanol (26).
Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3). In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3). Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).
Entrapment of these volatiles probably accounts for the elevation in
methanol levels of certain fruit and vegetable products
during canning (31, 33).
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
poisioning (59)....
If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.
Formaldehyde is a known
carcinogen (57) producing squamous-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)....
http://www.dorway.com/wmonte.txt
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
Director of the Food Science and Nutrition Laboratory
Arizona State University, Tempe, Arizona 85287
6411 South River Drive #61 Tempe, Arizona 85283-3337
602-965-6938 woody.monte@...
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.) [Monte has retired to New Zealand.]
ASPARTAME: METHANOL AND THE PUBLIC HEALTH
Woodrow C. Monte, Ph.D., R.D.**
ABSTRACT
Aspartame (L-asparty-L-phenylalanine methyl ester), a new sweetener
marketed under the trade name NutraSweet*, releases into the human
bloodstream one molecule of methanol for each molecule of aspartame
consumed.
This new methanol source is being added to foods that have considerably
reduced caloric content and, thus, may be consumed in large amounts.
Generally, none of these foods could be considered dietary methanol
sources prior to addition of aspartame.
When diet sodas and soft drinks, sweetened with aspartame,
are used to replace fluid loss
during exercise and physical exertion in hot climates,
the intake of methanol can
exceed 250 mg/day or 32 times the Environmental Protection Agency's
recommended limit of consumption for this cumulative toxin (8).
[7.8 mg daily methanol from 2 L drinking water:
8. Cleland, J.G. and Kingsbury, G.L., Multimedia Environmental
Goals For Environmental Assessment. U.S. Environmental Protection
Agency: EPA-600/7-77-136b, E-28, November 1977.]
There is extreme variation in the human response to acute methanol
poisoning, the lowest recorded lethal oral dose being 100 mg/kg, with
one individual surviving a dose over ninety times this level (55).
Humans, due perhaps to the loss of two enzymes during evolution, are
more sensitive to methanol than any laboratory animal; even the monkey
is not generally accepted as a suitable animal model (42).
There are no human or mammalian studies to evaluate the possible
mutagenic, teratogenic, or carcinogenic effects of chronic
administration of methyl alcohol (55).
The average intake of methanol from natural sources varies, but limited
data suggests an average intake of considerably less than 10 mg/day (8).
Alcoholics may average much more, with a potential range of between 0
and 600 mg/day, depending on the source
and in some cases the quality of their beverages (15).
Ethanol, the classic antidote for methanol toxicity,
is found in natural food sources
of methanol at concentrations 5 to 500,000 times that of
the toxin (Table 1).
Ethanol inhibits metabolism of methanol and allows the body
time for clearance of the toxin through
the lungs and kidneys (40, 46).
The question asked is whether uncontrolled consumption of this new
sweetener might increase the methanol intake
of certain individuals to a point beyond which
our limited knowledge of acute and chronic human
methanol toxicity can be extrapolated to predict safety.
*NutraSweet is a trademark of G.D. Searle & Co.
**Director of the Food Science and Nutrition Laboratory
Arizona State University Tempe, Arizona 85287
ASPARTAME
Aspartame (L-aspartyl-L-phenylalanine methyl ester) has recently been
approved as a sweetener for liquid carbonated beverages. It has had
wide acceptance as an additive in many dry food applications after Food
and Drug Administration approval on July 24, 1981 (48).
The Food and Drug Administration, Dr. Richard Wurtman and myself have
received well over a thousand written complaints relative to aspartame
consumption. [H.J. Roberts, MD has also used many of these reports.]
By far, the most numerous of these include dizziness,
visual impairment, disorientation, ear buzzing, high SGOT, tunnel
vision, loss of equilibrium, severe muscle aches, numbing of
extremities, pancreatitis, episodes of high blood pressure, retinal
hemorrhaging, menstrual flow changes, and depression. The validity of
these complaints has yet to be scientifically evaluated. However, a
thorough knowledge of just what makes this new sweetener stand apart
from other nutritional substances might aid
physicians in making dietary recommendations for their patients.
Aspartame (NutraSweet)* is a small molecule made up of three
components:
Phenylalanine, aspartic acid, and methanol (wood alcohol) (47). When
digested, these components are released into the bloodstream (48).
Phenylalanine and aspartic acid are both amino acids which are found in
natural proteins (14), and under normal circumstances are beneficial,
if not essential, for health. Proteins are complex molecules which
contain many chemically bonded amino acids.
It takes several enzymes to break these bonds and liberate the amino
acids. This is a slow process and the amino acids
are released gradually into the blood stream (40).
The quaternary structure of protein also slows
the digestion of these amino acids; the amino acids in the center of
the protein molecule aren't released until the outer layers of amino
acids on the surface have been swept away. This natural time release
process saves the body from large numbers of any one of these 21 amino
acids being released into the bloodstream at any one time.
Aspartame requires the breaking of only two bonds for absorption (47).
This happens very quickly with the potential to raise component blood
levels rapidly (52).
The methyl ester bond of phenyalanine is the first
to cleave due to its susceptibility to pancreatic enzymes (40).
This is highly unusual; the methyl esters
associated with pectin for instance
are completely impervious to all human digestive enzymes (6).
AMINO ACID COMPONENTS
Phenylalanine
Phenylalanine is an essential amino acid,
the daily consumption of which is required to maintain life.
However, Dr. Richard J. Wurtman,
Professor of Neuroendocrine Regulation at
the Massachusetts Institute of Technology,
presented data to the FDA demonstrating that in humans the
feeding of a carbohydrate with aspartame significantly enhances
aspartame's positive effect on plasma and brain phenylalanine and
tyrosine levels (48 Federal Register at 31379). There are sound
scientific reasons to believe that increasing the brain levels of these
large neutral amino acids could affect the synthesis of
neurotransmitters and in turn affect bodily functions controlled by the
autonomic nervous system (61) (e.g., blood pressure).
The proven ability of aspartame to inhibit the glucose-induced release
of serotonin within the brain may also affect behaviors,
such as satiety and sleep (61).
Aspartic Acid
Aspartic acid, is not an essential amino acid but is normally easily
utilized for human metabolism. However, under conditions of excess
absorption it has caused endocrine disorders in mammals with markedly
elevated plasma levels of luteinizing hormone and testosterone in the
rat (52) and release of pituitary gonadotropins and prolactin in the
rhesus monkey (58). The amount of luteinizing hormone in the blood is a
major determinant of menstrual cycling in the human female (39).
METHANOL
Methanol (methyl alcohol, wood alcohol), a poisonous substance (60), is
added as a component during the manufacture of aspartame (47). This
methanol is subsequently released within hours of consumption (51)
after hydrolysis of the methyl group of the dipeptide
by chymotrypsin in the small intestine (40).
Absorption in primates is hastened considerably if
the methanol is ingested as free methanol (40) as it occurs in soft
drinks after decomposition of aspartame
during storage or in other foods after being heated (48).
Regardless of whether the aspartame-derived
methanol exists in food in its free form or still esterified to
phenylalanine, 10% of the weight of aspartame intake of an individual
will be absorbed by the blood stream as methanol within hours after
consumption (51). [The precise value is 11%.]
Methanol has no therapeutic properties and is considered only as a
toxicant (20). The ingestion of two teaspoons is considered lethal in
humans (19). [~9.4 cc = ~ 30 gm]
Methyl alcohol produces the Methyl alcohol syndrome,
consistently , only in humans and no other test animal,
including monkeys (42, 54).
There is a clear difference between "toxicity",
which can be produced in every living thing,
and the "toxic syndrome" (54).
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, and 8 g/kg, respectively (43);
ethyl alcohol is more toxic than methanol to these test animals (43).
No human or experimental mammalian studies have been
found to evaluate the possible mutagenic, teratogenic or carcinogenic
effects of methyl alcohol (55), though a 3.5% chromosomal aberration
rate in testicular tissues of grasshoppers was induced by an injection
of methanol (51).
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)
Role of Formaldehyde
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
poisioning (59).
The localized retinal production of formaldehyde from
methanol is still thought to be principally responsible for the optic
papillitis and retinal edema always associated with the toxic syndrome
in humans (20). This is an intriguing issue since formaldehyde
poisoning alone does not produce retinal damage (20).
If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.
Formaldehyde is a known
carcinogen (57) producing squamous-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). Glycerol formal, a condensation product of glycerol
and formaldehyde (which may be formed in vivo), is a potent teratogen
causing an extremely high incidence of birth defects in laboratory
animals (52).
Even the staunchest critic of formaldehyde involvement
in methanol toxicity admits:
"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 are detectable in body fluids or tissues." (34)
[34. McMartin, K.E., Martin-Amat, G., Noker, P.E. and Tephly, T.R.,
Lack of a Role for Formaldehyde in Methanol Poisoning in the Monkey.
Biochem. Pharm., 28: 645-649 (1978).]
Acute Toxicity in Man "Toxic Syndrome"
A striking feature of methyl alcohol syndrome is the asymptomatic
interval (latent period) which usually lasts 12 to 18 hours after
consumption. [This can account for the failure of many laboratory and
clinical tests to finds symptoms hours after exposure to aspartame.]
This is followed by a rapid and severe acidosis caused
partially by the production of formic acid (19). Insufficient formic
acid is generated to account for the severity of metabolic acidosis
produced and, therefore, other organic acids may also be involved (32).
Patients may complain of lethargy, confusion, and impairment of
articulation, all frequently encountered signs in moderate central
nervous system (CNS) intoxications resulting from other toxic
compounds (20).
Patients may also suffer leg cramps, back pain, severe headache,
abdominal pain, labored breathing, vertigo and visual loss, the latter
being a very important clue to making a diagnosis of methanol
poisoning (20). Other striking clinical features associated only with
the oral administration of methanol are elevated serum amylase and the
finding of pancreatitis or pancreatic necrosis on autopsy (20, 55).
In fatal cases liver, kidneys and heart may show parenchymatous
degeneration. The lungs show desquamation of epithelium, emphysema,
edema, congestion and bronchial pneumonia (12).
Chronic Human Exposure
This is the most important aspect of methanol toxicity to those who are
interested in observing the effect of increased methanol consumption on
a population.
The data presented here were compiled by the Public Health Service. The
individuals studied were working in methanol contaminated environments.
It is interesting to note that the visual signs always associated with
acute toxicity often do not surface under chronic conditions (20).
Many of the signs and symptoms
of intoxication due to methanol ingestion
are not specific to methyl alcohol.
For example, headaches, ear buzzing, dizziness,
nausea and unsteady gait (inebriation), gastrointestinal
disturbances, weakness, vertigo, chills, memory lapses, numbness and
shooting pains in the lower extremities hands and forearms, behavioral
disturbances, and neuritis (55).
The most characteristic signs and
symptoms of methyl alcohol poisoning in humans are the various visual
disturbances which can occur without acidosis (55) although they
unfortunately do not always appear (20). Some of these symptoms are
the following: misty vision, progressive contraction of visual fields
(vision tunneling), mist before eyes, blurring of vision, and
obscuration of vision (20, 55).
ALCOHOLICS: CHRONIC METHANOL CONSUMPTION
Alcoholics in general, but particularly those who consume large
quantities of wine or fruit liqueur, would seem, from the available
evidence, to be the only population thus far exposed to consistently
high levels of methanol ingestion (Table 1).
The high ethanol/methanol
ration of alcoholic beverages must have a very significant protective
effect, though enzyme kinetics mandate some constant but low level of
methanol metabolism.
One could speculate that the delicate balance which
maintains this defense might be jeopardized by the general nutrition
neglect and specifically the folic acid deficiency (21) associated with
the meager food intake of some alcoholics.
Alcoholics have a much higher incidence of cancer and other
degenerative diseases, none of which
can be attributed to ethanol alone (56).
The fascinating similarities linking unusual clinical features
of methanol toxicity and alcoholism are worth noting.
Neuritis:
Chronic occupational exposure to methanol often produces human
complaints of neuritis with paresthesia, numbing, pricking and shooting
pains in the extremities (4, 55).
Alcoholic polyneuropathy (36) or multiple peripheral neuritis (21)
differs symptomatically from the methanol induced syndrome only in its
first and often exclusive affinity for legs. The unpleasant sensations
of intolerable pain associated with slight tactile stimulation (36) is
not an uncommon anecdotal consumer complaint following long term
consumption of aspartame.
In one such case reported to me, my
interpretation of an electromyogram indicated the signs of denervation
indicative of alcoholic polyneuropathy (36). The individual's ischemic
lactate pyruvate curve, before and after fasting, was flat. Less than
six weeks after aspartame consumption ceased the major symptoms
subsided and repetition of these tests produced normal responses,
although the individual still experienced intermittent pain.
Pancreatitis:
Methanol is one of the few etiologic factors associated with acute
pancreatic inflammation (16, 20). Microscopic findings of pancreatic
necrosis on autopsy have been reported after acute oral methanol
poisoning (55) which marks the end of the latent period.
There is a generally accepted association between alcoholism and
pancreatitis. Most patients, however,
give a history of 5 to 10 years of heavy drinking
before the onset of the first attack (16).
The fact that 40% of all cases of acute
pancreatitis complaints are attributable to
alcoholics (21), however, must be taken into consideration to avoid
artifactual association. Pancreatitis has been a complaint associated
with aspartame consumption.
Methanol and the Heart:
A 21-year-old non-drinking male who had been exposed daily to the fine
dust of aspartame at the packaging plant he had worked for over a year,
was complaining of blurred vision, headaches, dizziness, and severe
depression before his sudden death.
An autopsy revealed (aside from the organ involvement
one might expect from methanol toxicity) myocardial
hypertrophy and dilatation with the myocardiopathy and left ventricle
involvement reminiscent of alcoholic cardiomyopathy. Alcoholic
cardiomyopathy, however, typically occurs
in 30-55 year old men who have a history
of alcohol intake in quantities comprising 30-50 percent of
their daily caloric requirement over a 10 to 15 year period (56).
It has been suggested that alcohol is the etiologic factor in at least
50 percent of the cases of congestive cardiomyopathy (56). The
significantly lower hospitalization incidence
for coronary disease among moderate drinkers
than among nondrinkers and the protection to coronary
risk afforded the moderate drinker
(less than two drinks a day) over the
nondrinker (56) seems contradictory.
However, if we implicate methanol
as the etiologic factor, then clearly the nondrinker is at a
disadvantage with a much lower ethanol to methanol ratio (Table 1) when
consuming naturally occurring methanol
in a diet otherwise equivalent to the drinkers.
The chronic alcoholic for reasons already proposed might
sacrifice this protection.
As mentioned below, high temperature canning as developed late in the
19th century should increase significantly the methanol content of
fruits and vegetables. The increased availability and consumption of
these food products in various countries over the years may parallel
better than most other dietary factors the increase in incidence of
coronary disease in their populations.
Cigarette smoke, a known coronary risk factor, contains four times as
much methanol as formaldehyde and only traces of ethanol.
ETHANOL AND FOLIC ACID
The importance of ethanol as an antidote to methanol toxicity in humans
is very well established in the literature (46, 55). The timely
administration of ethanol is still considered a vital part of methanol
poisoning management (11, 12, 19, 20, 50). Ethanol slows the rate of
methanol's conversion to formaldehyde and formate, allowing the body
time to excrete methanol in the breath and urine. Inhibition is seen in
vitro even when the concentration of ethyl alcohol was only 1/16th that
of methanol (62). The inhibitory effect
is a linear function of the log of the
ethyl alcohol concentration, with a 72% inhibition rate at only
a 0.01 molar concentration of ethanol (2, 46).
Oxidation of methanol, like that of ethanol, proceeds independently of
the blood concentration, but at a rate only one seventh (20) to one
fifth (12) that of ethanol.
Folacin may play an important role in the metabolism of methanol by
catalyzing the elimination of formic acid (41). If this process proves
to be as protective for humans as has been shown in other organisms
(50, 38) it may account, in part, for the tremendous variability of
human responses to acute methanol toxicity. Folacin is a nutrient
often found lacking in the normal human diet, particularly during
pregnancy and lactation (14).
METHANOL CONTENT OF ASPARTAME SWEETENED BEVERAGES
An average aspartame-sweetened beverage would have a conservative
aspartame content of about 555 mg/liter (48, 51) and therefore, a
methanol equivalent of 56 mg/liter (56 ppm).
For example, if a 25 kg child consumed on a warm day,
after exercising, two-thirds of a two-liter bottle
of soft drink sweetened with aspartame, that child
would be consuming over 732 mg of aspartame (29 mg/kg). This alone
exceeds what the Food and Drug Administration considers the 99+
percentile daily consumption level of aspartame (48). The child would
also absorb over 70 mg of methanol from that soft drink.
This is almost ten times the Environmental Protection Agency's
recommended daily limit of consumption for methanol [in water].
To look at the issue from another perspective, the literature reveals
death from consumption of the equivalent of 6 gm of methanol (55, 59).
It would take 200 12 oz. cans of soda to yield the lethal equivalent of
6 gm of methanol.
According to FDA regulations,
compounds added to foods that are found to cause
some adverse health effect at a particular usage level are
actually permitted in foods only at much lower levels. The FDA has
established these requirements so that an adequate margin of safety
exists to protect particularly sensitive people and heavy consumers of
the chemical.
Section 170.22 of Title 21 of the Code of Federal Regulations
mandates that this margin of safety by 100-fold below the
"highest no-effect" level.
If death has been caused by the methanol equivalent of 200 12 oz. cans
of aspartame sweetened soda, one hundredth of that level
would be two cans of soda.
The relationship of the lethal dose
to the "highest no effect" level has tragically
not been determined for methanol (9, 11) but assuming very
conservatively that the level is one tenth of the lethal dose, the FDA
regulations should have limited consumption to approximately 2.4 ounces
of aspartame sweetened soft drink per day. [Published case reports show
severe reactions to tiny doses of aspartame in some reactors:
1.5, 4, or 6-8 mg aspartame, while a 12 oz can of diet soda provides
about 200 mg aspartame.]
The FDA allows a lower safety margin only when "evidence is submitted
which justifies use of a different safety factor." (21.C.F.R.170.22)
No such evidence has been submitted to the FDA for methanol.
Thus, not only have the FDA's requirements for acute toxicity not been
met, but also, no demonstration of chronic safety has been made. The
fact that methyl alcohol appears in other natural food products
increases greatly the danger of chronic toxicity developing by adding
another unnatural source of this dangerous cumulative toxin to the food
system.
NATURAL SOURCES OF METHANOL
Methanol does appear in nature.
To determine what impact the addition of a toxin will have on an
environment it is very helpful to accurately determine the background
levels of consumption.
Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase
required for its hydrolysis to methanol (26).
Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3). In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120? C produced
only traces of methanol (3). Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).
Entrapment of these volatiles
probably accounts for the elevation in methanol levels of
certain fruit and vegetable products during canning (31, 33).
In the recent denial by the Food and Drug Administration of my request
for a public hearing on this issue (13), the claim is made by them that
methanol occurs in fruit juices at an average of 140 parts per million
(a range of between 15-640 parts per million). This often used average
originates from an informative table in a conference paper presented by
Francot and Geoffroy (15). The authors explain that the data presented
in the table "may not" represent their work but "other authors" (15).
There is no methodology given nor is the original source cited and only
the identity of the lowest methanol source, grape juice (12 ppm), and
the highest, black currant (680 ppm), are revealed.
The other 22 samples used to generate this disarmingly high average are
left completely to the imagination.
The authors conclude their paper by insisting that "the
content of methanol in fermented or non-fermented beverages should not
be of concern to the fields of human physiology and public health."
They imply that wines "do not present any toxicity" due to the presence
of certain natural protective substances (15).
When they present their original data
relating to the methanol content of French wines (range 14-265 ppm)
or when the methanol content of any alcoholic beverage is given,
the ration of methanol to ethanol is also presented. Of the wines
they tested, the ratio associated with the highest methanol content
(265 ppm) indicates over 262 times as much ethanol present as methanol.
The scientific literature indicates that a fair estimate of methanol
content of commonly consumed fruit juices is on the order of 40 parts
per million (Table 1). Stegink, et al. Points out that some neutral
spirits contain as much as 1.5 grams/liter of methanol (51);
what is not mentioned is the fact that if these spirits are at least 60
proof (30% ethanol) this still represents the presence of over 200
molecules of ethanol for every molecule of methanol that is digested.
An exhaustive search of the present
literature indicates that no testing of
natural substances has ever shown methanol appearing alone; in
every case ethanol is also present, usually, in much higher
concentrations (15, 27, 28, 30, 31, 35, 44, 45).
Fresh orange juices can have very little methanol (0.8 mg/liter), and
have a concomitant ethyl alcohol content of 380 mg/liter (28).
Long term storage in cans has a tendency to cause an increase in these
levels, but even after three years of storage,
testing has revealed only 62 mg/liter
of methanol, with an ethanol content of 484 mg/liter. This
is a ratio of almost eight times ethanol/methanol (28).
Testing done recently in Spain showed orange juice with
33 mg/liter methanol and 651 mg/liter ethanol (20/1 ratio) (45).
The range for grapefruit juices are similar, ranging
from 0.2 mg methanol/liter (27) to 43 mg methanol/liter (27).
The lowest ratio of any food item was found in canned grapefruit
sections with 50-70 mg/liter methanol
and 200-400 mg/liter ethanol (27), thus
averaging six molecules ethanol for every molecule of methanol.
This high ethanol to methanol ratio, even at these low ethanol
concentrations, may have some protective effect. As stated previously,
ethanol slows the rate of methanol's conversion to formaldehyde and
formate allowing the body time to excrete methanol in the breath and
urine. Inhibition is seen in vitro even when the concentration of ethyl
alcohol was only 1/16th that of methanol (62). The inhibitory effect is
a linear function of the log of the ethyl alcohol concentration, with a
72% inhibition rate at only a 0.01 molar concentration of ethanol (2).
Therefore if a liter of a high methanol content orange juice is
consumed, with 33 mg/liter of methanol and a 20/1 ration of
ethanol/methanol, only one molecule of methanol in 180 will be
metabolized into dangerous metabolites
until the majority of the ethanol has
been cleared from the bloodstream.
If a similar amount of methanol equivalent from aspartame were
consumed, there would be no competition (46).
Another factor reducing the potential danger associated with methanol
from natural juices is that they have an average caloric density of 500
Kcal/liter and high osmolarity which places very definite limits to
their consumption level and rate.
Data obtained in a Department of Agriculture survey of the food intake
of a statistically sampled group of over 17,000 consumers nationwide
(1), indicate that the 17.6% of the
population that consume orange juice daily
take in an average of 185.5 gm of that juice. These statistics
indicate that 1.1% of the population consume an average of 173.9 gm of
grapefruit juice while only 1.8% drink approximately 201 gm of tomato
juice daily. Table 1 shows that under normal conditions these
individuals would only be expected to consume between 1 and 7 mg of
methanol a day from these sources. Even if an individual consumed two
juices in the same day or a more exotic juice such as black currant,
there would still be some protection afforded by the ethanol present in
these natural juices.
Consumption of aspartame sweetened drinks at
levels commonly used to replace lost fluid during exercise yields
methanol intake between 15 and 100 times these normal intakes (Table 1).
This is comparable to that of "winos"
but without the metabolic reprieve afforded
by ethanol. An alcoholic consuming 1500 calories a day from
alcoholic sources alone may consume between 0 and 600 mg of methanol
each day depending on his choice of beverages (Table 1).
The consumption of aspartame sweetened soft drinks or other beverages
is not limited by either calories or osmolarity,
and can equal the daily water loss
of an individual (which for active people in a state like
Arizona can exceed 5 liters). The resultant daily methanol intake might
then rise to unprecedented levels.
Methanol is a cumulative toxin (8)
and for some clinical manifestations it may be a human-specific toxin.
CONCLUSION
Simply because methanol is found "naturally" in foods, we can not
dismiss the need for carefully documented safety testing in appropriate
animal models before allowing a dramatic increase in its consumption.
We know nothing of the mutagenic, teratogenic or carcinogenic effect of
methyl alcohol on man or mammal (55, 59). Yet, if predictions are
correct (5), it won't be long before an additional 2,000,000 pounds of
it will be added to the food supply yearly (53).
Must this, then, constitute our test of its safety?
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Portion sizes and days intakes of selected foods, ARS-NE-67 (1975).
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the Rat.Am. J. Physiol., 163: 619-621 (1950).
3. Braverman, J.B.S. and Lifshitz, A., Pectin Hydrolysis in
Certain Fruits During Alcoholic Fermentation. Food Tech., 356-358,
July, (1957).
4. Browning, E., Toxicity and Metabolism of Industrial Solvents,
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5. Bylinsky, G., The Battle for America's Sweet Tooth. Fortune,
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Dimethyl Sulphide from Cooked Foods. Nature, 200: 885 (1963).
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Goals For Environmental Assessment. U.S. Environmental Protection
Agency: EPA-600/7-77-136b, E-28, November 1977.
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Poisoning. Biochem. Pharmacol., 11: 405-416 (1962).
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Ed., Washington DC, National Research Council, National Academy of
Science, (1980).
15. Francot, P. and Geoffroy, P., LeMethanol dans les jus de
fruits, les boissons, fermentees, les alcools et spiritueux. Rev.
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Am., 68(1): 57-75 (1984).
17. Gilman, A., Goodman & Gilman's The Pharmacological Basis of
Therapeutics. 6th ed. Alfred Gilman, et al., eds., New York:
Macmillian Publishing Co. Inc. (1980).
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Methanol in Human Liver: The Role of Hepatic Microbody and Soluble
Oxidases. Res. Commun. Chem. Pathol. Pharm., 1(4): 441-450 (1970).
19. Gosselin, R.E., Clinical Toxicology of Commercial Products.
4th ed. Gosselin, R.E., et al., eds., Baltimore, Maryland: Williams
& Wilkins (1981).
20. Hadden, L., et al., Clinical Management of Poisoning.
Philadelphia, Pennsylvania: W. B. Saunders Company (1983).
21. Holvey, D.N., the Merck Manual. 12th ed Rahway, New Jersey:
Merck and Company (1972).
22. International Agency for Research on Cancer., IARC Monographs
on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.
Supplement 4. Lyon, France: IARC, 1982.
23. International Agency for Research on Cancer., IARC Monographs
on the Evaluation of the Carcinogenic Risk of Chemical to Man.
Vol. 7 Lyon, France: IARC, 1974, pp. 45-52.
24. International Agency for research on Cancer., IARC Monographs
on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.
Vol. 29 Lyon, France: IARC, 1982, pp. 345-89.
25. Kertesz, Z.I., The Pectic Substances. Interscience Publishers,
Inc., New York, (1951).
26. Kertesz, Z.I., The Pectic Enzymes,
J. Nutr., 20: 289-296 (1940).
27. Kirchner, J.G., Miller, J.M., Rice, R.G., Keller, G.J., and
Fox, M.M., Volatile Water-Soluble Constituents of Grapefruit Juic. J.
Agric. Food Chem., 1(7): 510-518 (1953).
28. Kirchner, J.G. and Miller, J.M., Volatile Water-Soluble and
Oil Constituents of Valecia Orange Juice.
Agric. Food Chem., 5(4): 283-291 (1957).
29. Leaf, G. and Zatman, L.J., A Study of the Conditions Under
Which Methanol May Exert a Toxic Hazard in Industry.
Brit. J. Ind. Med., 9: 1931 (1952).
30. Lee, C.Y., Acree, T.E. and Butts, R.M., Determination of
Methyl Alcohol in Wine by Gas Chromatography.
Anal. Chem., 47(4): 747-748 (1975).
31. Lund, E.D., Kirkland, C.L. and Shaw, P.E., Methanol, Ethanol,
and Acetaldehyde Contents of Citrus Products.
J. Agric. Food Chem., 29: 361-366 (1981).
32. McMartin, K.E., Makar, A.B., Martin-Amat, G., Palese, M. and
Tephly, T.R., Methanol Poisoning. I. The Role of Formic Acid in the
Development of Metabolic Acidosis in theMonkey and the Reversal by
4-Methylpyrazole. Biochem. Med., 13: 310-333 (1975).
33. McMartin, K.E., Martin-Amat, G., Makar, A.B. and Tephly, T.R.,
Methanol Poisoning. V. Role of Formate Metabolism in the Monkey. J.
Pharmacol. Exp. Ther., 201(3): 564-572 (1977).
34. McMartin, K.E., Martin-Amat, G., Noker, P.E. and Tephly, T.R.,
Lack of a Role for Formaldehyde in Methanol Poisoning in the Monkey.
Biochem. Pharm., 28: 645-649 (1978).
35. Moshonas, M.G. and Lund, E.D., A Gas Chromatographic Procedure
for Analysis of Aqueous Orange Essence.
J. Food Sci., 36: 105-106 (1971).
36. Nakada, T., and Knight, R.T., Alcohol and the Central Nervous
System. Med. Clin. N. Am., 68(1): 121-131 (1984).
37. Newell, G.W., Overview of Formaldehyde. Formaldehyde Toxicity.
J.E. Gibson Ed., Hemisphere Publishing Corporation, pp. 3-12 (1983).
38. Noker, P.E. and Tephly, T.R., the Role of Folates in Methanol
Toxicity. Adv. Exp. Med. Biol., 132: 305 (1980).
39. Olney, J.W., Cicero, T.J., Mayer, E.R., and deGubareft, T.,
Acute glutamate-induced elevations in serum testosterone and
lenteinizing hormone. Brain Res., 112: 420-424 (1976).
40. Oppermann, J.A., Muldoon, E. and Ranney, R.E., Metabolism of
Aspartame in Monkey. J. Nutr., 103: 1454-1459 (1973).
41. Rietbrock, N., Herken, W. and Abshagen, V., Folate Catalyzed
Elimination of Formic Acid from Methanol Poisoning.
Biochem. Pharmacol, 20: 2613 (1971).
42. Roe, O., Species Differences in Methanol Poisoning. CRC
Critical Rev. in Tox., pp. 275-286, October, (1982).
43. Roe, O., The Metabolism and Toxicity of Methanol.
Pharmacol. Rev., 7: 399 (1955).
44. Roe, B. and Bruemmer, J.H., Enzyme-Mediated Aldeyhde Change in
Orange Juice. J. Agr. Food Chem., 22: 285-288 (1974).
45. Sauri, E., Nadal, I., Alberola, J., Sendra, J.M., Izquierdo, L.
(Inst. Agroquim. Tecnol. Alimentos, CSIC, Valencia, Spain 10).
Rev. Agroquim Tecnol. Aliment. 1981, 21 (2): 276-80 (Span).
46. Searle Aspartame Petition. Document No.: MRC-751-0022 (E-92).
Methanol Metabolism in the Monkey, Mol. Pharmacol., 4: 471-483, (1963).
47. Searle Food Resources, Inc., Sources and Metabolism of
Aspartame and Representative Sweeteners. (1981).
48. Searle Research and Development., Aspartame for use as a
Sweetener in Carbonated Beverages. Petition submitted to the United
States Food and Drug Administration - FAP 2A3661.
49. Self, R., Casey, J.C., Swain, T., The Low-Boiling Volatiles of
Cooked Foods. Chem. And Indust., 863-864 (1963).
50. Smith, E.N. and Taylor, R.T., Acute Toxicity of Methanol in
the Folate-Deficient Acatalasemic Mouse.
Toxicology, 25: 271-287 (1982).
51. Staples, R.E., Teratogenicity of Formaldehyde. Formaldehyde
Toxicity. J.E. Gibson, Ed., Hemisphere Publishing Company pp 51-60
(1983).
52. Stegink, L.D., Brummel, M.C., McMartin, K., Martin-Amat, G.,
Filer, L.J., Jr., Baker, G.L. and Tephly, T.R., Blood Methanol
Concentrations in Normal Adult Subjects Administered Abuse Doses of
Aspartame. J. Toxicol. Environ. Health, 7: 281-290 (1981).
53. Strittmatter, P. and Ball, E.G., Formaldehyde Dehydrogenase, A
Glutathione-Dependent Enzyme System.
J. Biol. Chem., 213: 445-461 (1955).
54. Tephly, T.R., Watkins, W.D. and Goodman, J.I., The Biochemical
Toxicology of Methanol. Essays Toxicol., 5: 149-177 (1974).
55. U.S. Department of Health, Education, and Welfare.,
Occupational Exposure to Methyl Alcohol,
HEW Pub. No. (NIOSH) 76-148, March (1976).
56. U.S. Department of Health and Human Services. Alcohol and
Health., Fourth Special Report to the U.S. Congress. DeLuca, J.R., ed.
January 1981.
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Report on Carcinogens. PB: 33-135855, September, 1983.
58. Wilson, R.C., and Knobil, E., Acute effects of
N-methyl-DL-aspartate on the release of pituitary gonadotropins and
polactin in the adult female rhesus monkey.
Brain Res., 248: 177-179 (1982).
59. Wimer, W.W., Russell, J.A. and Kappplan, H.L., Alcohols
Toxicology. Park Ridge New Jersey, Noyes Data Corporation (1983).
60. Windholz, M., Merck Index. 9th Ed., Rahway, New Jersey: Merck &
Company Inc. (1976).
61. Wurtman, R.J., Neurochemical Changes Following High-Dose
Aspartame with Dietary Carbohydrates.
New Eng. J. Med., 309(7): 429-30 (1983).
62. Zatmann, L.J., The Effect of Ethanol on the Metabolism of
Methanol in Man. Biochem. J., 40: 67-68 (1946).
TABLE I
AVAILABLE METHANOL IN VARIOUS BEVERAGES
Methanol mg/liter
Caloric Density Calories/Liter
Methanol (mg.) Consumed per 1000 Calories
Ratio Ethanol (wt.)/Ethanol (wt.)
Methanol (mg.) Consumption
per day
Juices
*Orange, fresh (28)
1 470 2 475 1
*Orange, fresh (45)
33 470 70 20 6
*Orange, fresh (31)
34 470 72 16 6
*Orange, Canned (28)
31 470 66 15 6
*Grapefruit, fresh (27)
1 400 1 2000 1
*Grapefruit (31)
43 400 108 5 7
*Grapefruit, Canned (31)
27 400 68 9 5
Grape (15)
12 660 18 - -
Alcoholic Beverages
Beer (4.5%)
0 400 - - -
Grain Alcohol (55)
1 2950 1 500000 -
Bourbon, 100 proof (55)
55 2950 19 9090 -
Rum, 80 proof (15)
73 2300 32 5000 -
Wines (French) (15)
White
32 800 44 2500 -
Rose
78 800 98 1000 -
Red
128 800 160 667 -
Pear
188 1370 137 250 -
Wines (American) (30)
Low
50 800 62 2500 -
High
325 800 406 385 -
Aspartame sweetened Beverages (48) 2 Liters 5 Liters
Uncarbonated Drinks (48)
55 8 6875 0 110 mg 275 mg
Cola (Carbonated) (48)
56 8 7000 0 112 mg 280 mg
Orange (Carbonated) (48)
91 8 11375 0 182 mg 455 mg
Aspartame, pure
25000
*17.6% of U.S. Population consume an average of 185.5 gm. of
Orange Juice a day (1)
* 1.1% of U.S. Population consume an average of 173.9 gm. of
Grapefruit Juice a day (1)
**************************************************************
http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male) alemany@...
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
http://groups.yahoo.com/group/aspartameNM/message/867
Murray: Thatcher:
simple tests for immune system reactions due to formaldehyde from the
11% methanol in aspartame: Tholen 9.17.2 rmforall
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html
Arch Environ Health 2001 Jul-Aug; 56(4): 300-11
Embryo toxicity and teratogenicity of formaldehyde.
Thrasher JD, Kilburn KH.
http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer: EPA: CPSC:
formaldehyde toxicity 6.10.1 rmforall
http://groups.yahoo.com/group/aspartameNM/message/863
Murray: Wilson: CIIN: EPA: Gold: Thrasher & Kilburn: Shaham:
formaldehyde toxicity 8.22.2 rmforall
http://groups.yahoo.com/group/aspartameNM/message/645
Rich Murray: 18 recent formaldehyde toxicity [Comet assay] abstracts
6.25.1 rmforall
http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall
http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall
**********************************************************
Serious symptom syndrome summary:
Aspartame (NutraSweet, Equal, Canderel, Benevia) is reported by
scientific studies and case histories to be toxic: * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, or numbness) * fever, fatigue
* "mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech,
ringing in ears, sexual problems, poor vision, hearing, or taste
* red face, itching, rashes, burning eyes or throat,
dry mouth or eyes, mouth sores * hair loss
* obesity, bloating, edema, anorexia,
poor or excessive hunger or thirst * breathing problems
* nausea, diarrhea or constipation * coldness * sweating
* racing heart, high blood pressure, erratic blood sugar levels
* seizures * birth defects * brain cancers * addiction
* aggrivates diabetes, autism, ADHD, allergies,
and interstitial cystitis (bladder pain)
**********************************************************
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