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Aspartame: Methanol and the Public Interest 1984: Monte: Murray 9.23.2 rmforall

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  • Rich Murray
    http://groups.yahoo.com/group/aspartameNM/message/870 Aspartame: Methanol and the Public Interest 1984: Monte: Murray 9.23.2 rmforall Rereading this prescient
    Message 1 of 1 , Sep 24, 2002
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      http://groups.yahoo.com/group/aspartameNM/message/870
      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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      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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