For More Information GO TO Aspartame (NutraSweet) Toxicity Home Page: http://www.holisticmed.com/aspartame/ 4. Methanol From the article: "The presence of small amounts of methanol in aspartame has generated a lot of undue concern. Although large amounts of methanol are harmful, the very small amounts of aspartame-derived methanol are easily handled by the body. "Methanol is a common component of the diet, and is found in many fruits, vegetables, and wines. Furthermore, the amount of methanol from foods far exceeds any contribution from aspartame (Lund 1981). Aspartame-sweetened soft drinks, for example, provide 60 mg of methanol per liter as compared to fruit juices which contain 140 mg of methanol per liter." The excerpt above contains so much NutraSweet Company propoganda, its hard to know where to begin. First, I will discuss how ingesting methanol from aspartame differs from ingesting methanol from alcohol, fruits and vegetables, and fruits and vegetable juices. Alcohol ------- An exhaustive literature search by Monte (1984) showed that all natural products which contain tiny amounts of methanol also contain significant amounts of ethanol. Many alcoholic beverages contain over 200 times more ethanol than methanol. The large ethanol content of alcoholic beverages has served to protect humans from methanol poisoning throughout the ages. Despite the wishful thinking of NutraSweet Company spokespersons (Sturtevant 1985), researchers agree that ethanol serves as a protective factor (Leaf 1952, Liesivuori 1991, McMartin 1980, Posner 1975, Roe 1982). Ethanol protects from methanol poisoning by preventing the conversion of methanol to toxic formaldehyde and formic acid metabolites thus allowing methanol to be excreted through the lungs and urine (Roe 1982, Kruse 1992). Methanol poisoning is treated with ethanol (Kini 1961, Pamies 1993). Leaf (1952) showed that co-administration of methanol with ethanol immediately stopped the conversion of methanol to its toxic metabolites. Fruits and Vegetables --------------------- Fruits and vegetables do contain methyl ester as part of the pectin. However, human beings do not have digestive enzymes such as pectin esterase to release the methanol (Garrison 1990, page 16, Monte 1984). As Monte (1984) points out: "Fermentation in the gut may cause disappearance of pectin but the production of free methanol is not guaranteed by fermentation (Braverman 1957). In fact, bacteria in the colon probably reduce methanol directly to formic acid or carbon dioxide (Campbell 1978) (aspartame is completely absorbed before reaching the colon)." Microorganisms in the feces can contribute to the production of methanol from pectin, but methanol will not be released in significant amounts unless the pectin sits in the intestines for 72 hours (Siragusa 1988). A couple of grams of pectin (found in an apple, for example) will probably produce only a maximum of 20 mg of methanol provided it stays in the colon fermenting for at least 24 hours. Much of this small amount of methanol is probably used and converted to less harmful substances by intestinal bacteria (e.g., Wolin 1993). Extremely high doses of pectin (i.e., 120 grams over 2 days) by itself can lead to a significant increase in blood methanol (Gruner 1994), but it is not known whether protective factors are absorbed as well. Even if some of the methanol was absorbed and converted to formaldehyde, 120 grams of pectin would amount to eating over 50 small apples (Garrison 1990, page 16). Fruits and Vegetable Juices --------------------------- When certain fruits and vegetables juices are extracted, the pectinmethylesterase enzymes demethylates some of the pectin and liberates methanol. However, the methanol content of most commonly ingested fruit juices do not average 140 mg per liter. The NutraSweet Company has been pushing this fallicy for years even though it has been disproven. The 140 mg/liter figure was obtained from a very old conference paper presented by Francot and Geoffroy (Francot 1956). The authors of this paper state that they did not perform many of the tests and give no original sources for the work except for grape juice and black current juice. No methodology was given although it is certain that in 1956 they did not use the more accurate techniques currently used. The methanol content of fresh juices is probably dependent upon the method used to extract the juice, the type of fruit used (including species), and the time harvested. Lund (1981) showed that the methanol content of fresh orange juice had a mean of 34 mg/liter. Fresh grapefruit juice averaged 27 mg/liter in the Lund study. Sauri (1981) tested fresh orange juice and showed that it contained 33 mg/kg. Nisperos-Carriedo (1990) determined that their sample of fresh orange juice had a mean of 38 mg/liter. The methanol content of processed juices were much less than fresh juices. Lund (1981) showed that orange juice concentrates average about 6 mg/liter of methanol. Grapefruit concentrates average about 2 mg/liter. The reconstituted juices contained no detectible methanol. Nisperos-Carriedo (1990) showed that pasteurized orange juice contained 22 mg/liter and frozen-concentrated orange juice contained 3.4 mg/liter. White (1950) showed that 10.1 kg of apple essence contained 2000 mg of methanol. Since apple essence is a concentration of 150 times that of juice, 10.1 kg of juice contains 132 mg of methanol. However, the author points out that not all of the volatiles were extracted, but we can assume that the concentration in fresh juice is probably less than 200 mg/10.1 kg or 20mg/liter. The most popular freshly-made juices have about one-half (or less) of the concentration of methanol than aspartame. Processed juices contain many times less methanol than aspartame and reconstituted juices contain only trace amounts of methanol. The average juice product ingested in the U.S. probably contains much less than 10 mg/liter if all types of fruits and processing is included since fresh juice is consumed by only a small segment of the population and in relatively small quantities. Some juices have been shown to contain methanol at equal or greater levels than aspartame. Nelson (1969) showed that after extracting the tomato juice and heating it for 30 minutes at 212oF in when enclosed in tin or enamel that the methanol content varied from 127 to 560 mg/liter. However, heating can-sealed tomato juice to extremely high temperatures without inactivating the pectinmethylesterase enzyme would likely increase the creation of methanol tremendously. This is something that is unlikely to happen in commercial or home preparation. Kazeniac (1970) found that blended tomatoes had a methanol content of between 64 and 138 mg/liter depending upon the speed of the blendor and the time blended. The small amounts of methanol in fresh juices or the larger amounts in some fresh juices (such as tomato juice) are probably irrelevant since it is unlikely that the methanol from these natural substances is absorbed and metabolised the same way as methanol from aspartame. The following points lead me to conclude that methanol from natural foods is not absorbed and/or metabolised into formaldehyde and formic acid in significant amounts: a. Alcoholic beverages contain large amounts of ethanol which prevent the large amounts of methanol from being converted to formaldehyde and formic acid. This is a reference point. It proves that we cannot automatically assume that a methanol-containing item will end up producing formaldehyde and formate after ingestion. b. If we can indulge NutraSweet's fantasy for a moment and pretend we find an "average" juice with 140 mg/l of methanol. Suppose that a person drinks 3 liters of this healthy juice per day. For a 50 kg adult woman that would amount to 8.4 mg/kg of methanol per day. Baumann (1979) showed that workers in a printing shop were exposed to methanol concentration in the air between 85 and 134 parts per million (111-174 mg/m3) for an 8-hour day. The total methanol intake of these workers at 60% absorption (twice resting respiration rate) was approximately 8 mg/kg (Kavet 1990). The average blood formate levels nearly doubled (3.2 mg/l to 7.9 mg/l) at this exposure. The urinary formate levels rose from 13.1 mg/l to 20.2 mg/l. Heinrich (1982) showed a similar blood and urinary formate increase for a single work day at a chemical plant at an exposure level of 92 ppm (120 mg/m3). Three liters of fruit juice, leading to a theoretical ingestion of 8 mg/kg of methanol has never been shown to spike urinary and blood formate levels as the experiments discussed above. Such a plasma formate level spike would be highly unlikely to say the least. I would challenge NutraSweet to find any independent research would shows such a spike in formate levels from fruit juice ingestion. c. Under the manufacturer's theory, someone "unfortunate" enough to drink two liters of one of the higher methanol- containing juices such as black current juice (Monte 1984) would be getting about 1.3 grams of methanol (according to NutraSweet claims). The lowest recorded single lethal dose is 15 ml of 40% methanol. This equals 6 ml of methanol or 4.8 grams. (Bennett 1953). 1.3 grams (more than 25% of the minimum recorded lethal dose) of methanol would be an enormous quanity of methanol to ingest every day! God forbid this person would ingest tomatoes which NutraSweet claims is another source of large amounts of methanol (Butchko 1991). Methanol is also found in some cooked foods (Casey 1963). If NutraSweet actually believes its own theories about methanol absorption and metabolism from fruit, they should call for a ban on black currents, tomatoes, and juices with high amounts of methanol. A useful experiment would be to have an independent researcher test the equivalent methanol believed by NutraSweet to be found in 2 liters of black current juice plus a days worth of cooked foods and other methanol-containing foods -- say 1.8 grams per day. The test would be conducted on Monsanto and NutraSweet executives who would ingest 1.8 grams of methanol every day in a single dose with distilled water half way in between lunch and dinner. The experiment would be conducted for two years. Each day that alcohol is ingested would increase the experiment by a day for that subject. Regular blood and urine methanol and formate levels would be tested to make sure that the subjects were getting proper doses. In this way, the company excecutives can see first-hand how "safe" methanol from juices is when taken without the rest of the juice. d. A growing number of people are extremely sensitive to methanol or formaldehyde exposure, hardly being able to tolerate a short exposure in a print shop or chemical plant, but easily being able to drink fresh juice. It would have been relatively easy for NutraSweet researchers to test tomato juice to see if it raises the blood methanol and urinary excretion of formate as does aspartame in the experiments discussed later in this section. Two to three liters of tomato juice given to a 30 kg child could contain the same amount of methanol as was shown in NutraSweet experiments to significantly increase blood methanol levels. Similar equivalent amounts could have been determined to correspond to the NutraSweet experiments which showed a significant increase in urinary formate levels. It's been almost two decades since tests relating to aspartame and methanol have been published and this obviously important experiment has not been conducted or has, more likely, been avoided. At this point, however, the experiment would have to be conducted and funded by corporate-neutral parties to have any validity. The simple fact is that methanol from natural products such as juices is almost certainly not absorbed or metabolised to formaldehyde and formic acid in signficant amounts. Researchers have not taken the time and effort to discover all of the protective factors in juices (similar to ethanol in alcoholic beverages). Juices contain a significant number of volatiles including ethanol, some of which may prevent absorption or metabolism of the methanol. Fructose has been shown to significantly slow methanol oxidation in some species when given in significant quantities (Bradford 1993). Whether this has an effect on humans ingesting small amounts of methanol with fruit juices is unknown. Certain intestinal bacteria have been shown to convert methanol or formaldehyde to acetate (Wolin 1993). It is possible that tiny amounts of methanol from fruit juices may be converted by bacteria in the human digestive tract before it can be absorbed. Some bacteria which convert methanol to acetate are known to do so many times faster in the presence of sodium (Na+) ions (Blaut 1992, Heise 1989). Sodium ions may be found more readily in natural juices than in junky diet sodas. Since methanol toxicity is blocked by ethanol in alcoholic beverages and since inhaled methanol has been shown to spike plasma formate (formic acid) levels, yet similar quantities of methanol from juices has not been shown to spike plasma formate levels, it seems rather ridiculous to automatically assume that methanol from juices would be absorbed and metabolized in the same way as methanol from an artificial sweetener. The high caloric content of fruit and vegetable juices as well as their osmolarity places limits on the quanity of these products ingested on a regular basis (Monte 1984). Monte (1984) shows, using U.S. Department of Agriculture survey figures that the regular juice drinker probably ingests between 1 and 7 mg of methanol per day from these sources. Aspartame, on the other hand, has a low calorie content, leading to the possibility of ingesting large quantities. In fact, in hot whether, it is not uncommon for a person to drink anywhere from 1 to 3 liters of aspartame- containg beverages every day (Monte 1995). Wurtman describes a case of a person who ingested 3.5 liters of diet Coke and a nearly equal amount of diet lemonade every day (Wurtman 1985a). This person was ingesting approximately 350 mg of methanol every day! I know several people who drink well over a liter (i.e., three 12-ounce cans) of diet beverage every day. A person ingesting two to three liters of diet orange soda on a daily basis, for example is ingesting 180 to 270 mg of methanol every day. Fresh juices contain vitamins and minerals which can help protect cells from damage caused by methanol. Folic acid, for example, is an important nutrient which helps break down and eliminate methanol metabolites. It is common that many chemicals in foods protect us from toxic substances in those foods. Remington (1987, page 88) gives a couple of examples of toxic substances causing more damage when not co-ingested with nutrients. In one example, rats which were fasted for six days died at 1/25th the dosage of a toxic substance as compared to rats which ate a normal diet. In the other example, it was shown that giving cabbage and brussels sprouts to rats increased the hydroxylase activity by 100 fold, protecting them from aflatoxin. Diet drinks and other aspartame-containing foods rarely contain significant amounts of nutrients that can protect against methanol damage and often contain other unnecessary and unhealthy chemical additives. In summary, juices usually contain much less methanol than aspartame. Due to the calorie content and osmolarity of juices, much less is ingested on a regular basis. Nutrients such as folic acid serve as protective factors against ingestion of methanol. And most important, it is very unlikely that methanol from juices is absorbed and metabolised in a similar way as methanol from aspartame. Most likely none or only trace amounts from natural juices are converted to formaldehyde. Therefore, NutraSweet's comparison of methanol from aspartame to methanol from natural products is flawed. Methanol Metabolism ------------------- Methanol from aspartame is released in the small intestine when the methyl group of aspartame encounters the enzyme chymotrypsin (Stegink 1984, page 143). Free methanol rapidly forms in liquid aspartame-containing products at temperatures over 145oF (62oC) (Mullarkey 1992, page 9). Free methanol is absorbed and metabolised somewhat differently than methanol from freshly-prepared aspartame as pointed out by researchers for the NutraSweet industry (Stegink 1983a). Methanol is absorbed in the stomach and more quickly when it is in its free form (Ranney 1976, Monte 1984, Stegink 1981a). There may be a greater toxicity for the quickly absorbed free methanol as discussed by Monte (Mullarkey 1992, page 9). Monte goes on to point out that when people are dieting or have not eaten for a while there is little gut fermentation producing the protective factor, ethanol. Whether absorbed quickly as free methanol or somewhat slower in the small intestine from fresh aspartame, the total amount of methanol absorbed will be approximately 10% of aspartame ingested. The absorbed methanol is then slowly converted to formaldehyde by alcohol dehydrogenase in the liver (DHHS 1993a, Liesivuori 1991). If methanol is co-ingested with a significant amount of ethanol, the methanol conversion is temporarily blocked since ethanol has nine times the affinity for alcohol dehydrogenase as does methanol (DHHS 1993a). This allows the body time to eliminate methanol via the lungs and urine before it gets converted to formaldehyde. The formaldehyde is then converted to formic acid by aldehyde dehydrogenase in the liver, by formaldehyde dehydrogenase in the blood, or through the tetrahydrofolic acid-dependent one-carbon pool (Liesivuori 1991). Methanol Dangers ---------------- Methanol, also known as wood alcohol, is a deadly poison in small amounts. The toxic effects of methanol vary widely from person to person (Posner 1975, Roe 1982, Tephly 1984). As little as 6 ml (0.2 ounces) of methanol has killed a person (Bennett 1953) although it usually takes as much as 80 ml to 150 ml (2.8 oz. to 5.3 oz.) to cause fatalities in the average adult (EPA 1994). In extremely small amounts and taken without a protective factor (e.g., ethanol), methanol is a cumulative poison, despite the wishful thinking of the NutraSweet Company spokespersons (Sturtevant 1985). The U.S. Environmental Protection Agency published the following about methanol (Cleland 1977): "[Methanol] is considered a cumulative poison due to the low rate of excretion once it is absorbed." After studying workers exposed to formic acid, a toxic methanol metabolite, Liesivuori addressed the issue of it being a cumulative poison (Liesivuori 1986): "The data indicated that formic acid may have a long biological half-life possibly causing an accumulation of the acid in the body. This might constitute a hitherto unappreciated toxicological hazard, as the acid is an inhibitor of oxygen metabolism." Liesivuori later points out that formic acid can accumulate in the brain, kidneys, spinal fluid, and other organs because of the slow excretion from the body (Liesivuori 1991). He also described formic acid's effects at the cellular level: "Exposure to either methanol or formic acid leads to accumulation of acid in the body. Formic acid inhibits cytochrome oxidase, causing decreased synthesis of ATP. This is followed by anaerobic glycolysis and lactic acidosis. At the same time, and also because of acidosis, the generation of superoxide anions and hydroxyl radicals is enhanced leading to membrane damage, lipid peroxidation and mitochondrial damage. This, and the decreased pH in acidosis, allows the influx of calcium into the cells. Although the mitochondrial dysfunction may be secondary to calcium overload in the mitochondria, the final consequence is cell death." While severe acidosis would obviously not likely by a consequence of small amounts of formic acid, the other damaging aspects of formic acid such as the inhibition of cytochrome oxidase and decreased production of ATP are still possible problems. Side Effects ------------ The most well-known effect caused by acute or chronic poisoning of methyl alcohol is damage to the optic nerve fibers. However, there are many other symptoms and optic nerve damage is not always one of the symptoms which appear as pointed out by Monte (1984): "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. The most characteristic signs and symptoms of methyl alcohol poisoning in humans are the various visual disturbances which can occur without acidosis although they unfortunately do not always appear. Some of these symptoms are the following: misty vision, progressive contraction of visual fields (vision tunneling), mist before the eyes, blurring of vision and obscuration of vision." "Chronic occupational exposure to methanol often produces human complaints of neuritis with paresthesia, numbing, prickling and shooting pains in the extremeties." "Methanol is one of the few etiologic factors associated with acute pancreatic inflammation." Many of these symptoms are common in persons ingesting aspartame for long periods of time (FDA 1993). Since the susceptibility of humans to methanol varies greatly and since aspartame provides no protective factors such as ethanol, it is not surprising that many people have experienced methanol poisoning-like symptoms after chronic, long-term aspartame ingestion. The damage is often slow and silent. The following is a letter presented before the U.S. Senate hearings on NutraSweet. It was written by Dr. Margan B. Raiford, M.D., Ps, Msc Med. Ophthalmology (Raiford 1987): "I had the opportunity, in Atlanta, Ga., to see the effects of methyl alcohol toxicity in 1952- 1953 which resulted in visual damage to the optic nerves and retina in over 300 cases and the deaths of over 30 persons. "I examined Shannon Roth on July 7, 1986, along with several other patients [65 cases as of July 10, 1986 (Roberts 1990a, page 136)]. I observed evidence of effects in her eye and the eyes of the other patients that were comparable to the effects observed in the patients who suffered methyl alcohol toxicity in 1952-1953. "There was damage in the central fibers, 225,000 of the total 137,000,000 optic nerve fibers (resulting in optic nerve atrophy) in her case, which would be comparable to that observed from patients suffering methyl alcohol toxicity. The extent of damage to these fibers would explain partial to total blindness. . . . . "But in the kind of chronic low dose exposure to methyl alcohol experienced by Shannon Roth (in NutraSweet consumption) and other NutraSweet consumers, it is likely that they would experience the impact on the optic nerve differently in each eye. "The important point is that the damage observed in Shannon Roth's eye was identical to the damage I observed repeatedly in the eyes of individuals whose eyes have been damaged by methyl alcohol toxicity." The large number of eye disturbances including cases of blindness that are being caused by aspartame led Dr. H.J. Roberts to dedicate an entire chapter to these problem and detail quite a few case histories (Roberts 1990a, page 128). Dr. Roberts surveyed 551 aspartame-reactors (Roberts 1988) and had this to say about eye problems (Roberts 1990a): "Decreased vision was a major complaint in 140 (25.4%), severe pain (one or both eyes) in 51 (9.3%), 'dry eyes' or trouble wearing contact lens in 46 (8.3%), and blindness (one or both eyes) in 14 (2.5%). . . . . "in most of these patients, there was no convincing evidence for underlying glaucoma, occlusion of a retinal vessel, toxic amblyopia (related to excessive alcohol or smoking), or optic neuritis due to multiple sclerosis and other causes that might account for the symptoms. CT scans and MRI studies of the brain or optic nerves generally proved normal in these patients. "Furthermore, that patients had known cataracts, astigmatism, macular degeneration or diabetic retinopathy did not necessarily disprove the role of aspartame . . . especially when vision promptly improved after stopping aspartame products. . . . . "Ophthalmologists and other professionals have told me about dramatic improvement of vision in their patients after the cessation of aspartame products." Susceptibility -------------- Folic acid is believed by most researchers to play a large role in protecting from methanol poisoning by increasing the conversion of formic acid to carbon dioxide and water (Roe 1982, Tephly 1984, DHHS 1993a). Persons who have a folic acid deficiency are likely to be much more susceptible to damage from chronic methanol ingestion. Other nutrients may play an important part in protecting from formic acid damage. As Tephly points out (Stegink 1984a, page 114): "Nutritional differences among individuals, such as folic acid deficiency, may play an iportant part in the ability of an individual to metabolize formate. Different degrees of nutritional deficiency may be observed in debilitated and inebriated persons who have not had an adequate diet. In monkeys we observed variability in the metabolism of methanol to formate and carbon dioxide when the animals were studied at different times. Some laboratories have been unable to duplicate results obtained by others. This failure may not be due to differences in experimental design or differences in the procedures of those individual laboratories. Instead, it is possible that animals maintained on the best nutritional regimens may be less susceptible to methanol poisoning, owing to a better hepatic capacity to metabolize methanol and formate to carbon dioxide." In addition to the protective factors of ethanol, folic acid, and possibly other nutrients, Posner (1975) pointed out that the presence of food in the stomach seems to lower the toxicity of methanol. The reason food slightly lowers the toxicity is probably because the food offers protective factors (as does alcohol and juices) and/or the food delays absorption (as does the administration of aspartame in capsules). This does not mean that aspartame in food is safe in long-term use, but probably slightly less toxic. Methanol ingestion may be even more dangerous for persons taking certain pharmaceuticals. The enzyme aldehyde dehydrogenase is believed to play a major role in methanol oxidation and elimination (DHHS 1993a, Liesivuori 1991). The drug disulfiram (trade name Antabuse) inhibits the activity of aldehyde dehydrogenase (Merck 1992, page 2638). Animal experiments have shown a significant increase in toxicity of methanol and a slowing down of methanol elimination when disulfiram was given (Posner 1975). The results are likely to be similar in humans for this particular adverse effect. Antabuse is currently being taken by 400,000 persons in the U.S. and many more are taking generic brands of disulfiram (Roberts 1990a, page 43). Posner (1975) lists research on several pharmaceuticals which shows that ingesting aspartame while on these drugs may present an additional health hazard. Some of these include sulfonylureas (for diabetics), metronidazole (anti- bacterial), and allopurinol (reduces uric acid). There may be other pharmaceuticals which cause adverse reactions when taken with the methanol in aspartame, but few studies have been done. Pilots are another group which may be more susceptible to acute reactions from methanol ingestion. Dr. Phil Moskal, Professor of Microbiology, Biochemistry, and Pathology, Chairman of the Department of Pathology, Director of Public Health Laboratories, discussed one possibility of why pilots may be suffering from dangerous adverse reactions to methanol from aspartame in a letter to George Leighton (Moskal 1990): A. Military studies indicate that a smoking person at sea level is physiologically at 8,000 ft. MSL. Ref. Col. Mauriel Udol. C.O. Ellington AFB, Top Gun - William Tell 1980 B. One (1) ounce of (C2H5OH ) (Ethanol) at sea level doubles in its effects at 10,000 ft. MSL. Ref. AOPA C. (Methanol) (CH3OH) displaces binding sites on the Hemoglobin molecule the same way that Carbon Monoxide (CO) does, reducing O2 (Oxygen) binding sites as CH3OH is acting as a blocking agent to the Oxygen-O2. D. Methanol is metabolized to an aldehyde OHOO - Methal - dehyde which is neuro-toxic (including respiratory, olfactory and ocular nerves. E. Physiology of the human body indicates that an average 170# person's liver metabolizes 1.0 oz. of alcohol/hours. F. Density altitude affects lung performance the same as it affects engine performance. We previously discussed and both know this through personal experience. The FAR's say that the pilot must use supplemental oxygen above 12,500 MSL beyond 30 minutes. As we painfully know, the lung (engine) does not decipher MSL or pressure altitute, only density altitude. AOPA recommends supplemental O2 (oxygen) above 10,000 MSL. That makes sense. However, the FAA doesn't use that rule. Conclusion ---------- A through F are additive and if you are 29,000 fee things begin to happen. Low Dosages ----------- It is very important to understand that serious health problems can start on a microscopic scale. For example, cancer, atherosclerosis, multiple sclerosis, excitotoxic neural cell damage, and many other diseases can start on a very small scale and build very slowly over the years. Excitotoxic neural cell damage can happen gradually over a lifetime and symtpoms often do not appear until after a large percentage of neural cells in a particular area has died (Blaylock 1994, page 92). The damage caused by these diseases cannot usually be detected until they are much more widespread. By the same token, damage from formic acid and formadehyde, toxic methanol metabolites, may occur very slowly over a long period of time. Even the skeptics agree that laboratory-detectable changes in measurements do not preclude toxic damage. "It is not possible to completely elminate 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" (McMartin 1978). It is also very important to keep in mind that short, low- level exposure to methanol or its toxic metaboites (e.g., formaldehyde) does not cause laboratory-detectible changes even though longer exposures at those levels do lead to changes and can cause health problems over time. As an example, Schmid showed that persons exposed to a single dose of significant amounts of formaldehyde did not show a statistically significant increase in the excretion of formic acid through the urine (Schmid 1994). Triebig (1989) concurs that formic acid excretion is a "unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure." 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." A number of investigators have found that a very short, low- level methanol exposure at 200 parts per million (260 mg/m3), the current occupational exposure limit, does not significantly increase the urinary and plasma formic acid measures (average for all subjects) (d'Alessandro 1994, Franzblau 1992, Lee 1992). d'Alessandro found that one subject had a large jump in blood formate levels after exposure to methanol, but this large increase was lost when the average increases were presented (similar to the way the data is usually presented by NutraSweet industry researchers). Kingsley (1954-55) found that workers exposed to a methanol concentrations of 200 to 375 ppm (260-487 mg/m3) when using spirit duplicators experienced adverse reactions such as headaches. Frederick (1984) showed that spirit duplicator exposure caused adverse reactions such as headaches, dizziness, nausea, blurred vision, and behavior disturbances at levels from 365 to 3080 ppm (474-3704 mg/m3). What is important to understand is that most of these workers did not spend most of their day at the spirit duplicator and therefore were breathing in air with a much lower concentration of methanol most of the time. Many of these workers who experienced adverse reactions to intermittant exposures to methanol concentrations as low as 200 ppm (260 mg/m3) probably had been working at the job for a reletively short period of time as compared to a lifetime of methanol exposure from aspartame use. Cook (1991), in a double-blind study, found that after only a 75 minute exposure to 192 ppm (250 mg/m3) of methanol (below the exposure time and level that would lead to a significant change in urinary or plasma formate measurements), the overall results show no changes in some categories, but did show statistically significant changes in other, important measurements. The subjects showed: - slightly greater fatigue from workload - a slight impairment of concentration and memory - a slight change in brain wave patterns in response to light and sound. The amount of methanol absorbed was less than 2 liters of (non-orange) diet soda for a 60 kg adult or less than 1 liter for a 30 kg child. (This assumes 1.3 times resting respiration rate such that 250 mg/m3 * 60% absorption * .6m3/75 minutes = 90 mg of methanol.) One wonders what the results would be had the subjects had this exposure every day for one year, or five years or more, especially if the subjects are more susceptible to the toxic effects of methanol. Unfortunately, it is unlikely that this experiment will be repeated with more participants or for a longer period (e.g., 3 months of regular exposures) to confirm the findings as there is no longer an interest in methanol as a fuel (Cook 1995). Two Russian studies published eight years apart showed that very low levels of methanol exposure affect visual and peripheral olfactory receptors and produced changes in EEG measurements (Kavet 1990). While the experimental protocols were not ideal, these studies seem to agree with Cook (1991) in that minor neurological changes were found for small, short exposures. While it is likely that formic acid is being eliminated when exposed to low levels for a short period of time (although some may accumulate in various organs as discussed earlier), the changes in laboratory measurements may not be statistically significant. However, that does not mean that low levels of formaldehye and formic acid are not causing damage. Getting back to our printing shop analogy, a child who ingests the highest daily amount of aspartame in the study conducted by Frey (1976) will be ingesting nearly 8 mg/kg per day of methanol. In other words, this developing child will be working full-time, 7-days per week in a methanol- laden printing shop (or chemical plant) breathing in methanol fumes (at twice resting respiration rate). A 30 kg child who ingests a two-liter diet cola will be working more than half-days at the printing shop (unless, of course, the child ingests diet orange soda). Please remember that many people will ingest a variety of aspartame-containing "foods" that would be equivalent to 2 liters (or more) of diet soda. Equivalent Weekly Hours Worked at Printing Shop With 140 mg/m3 of Methanol in Air Compared to Aspartame Ingestion Weekly Intake ------------------------------------------------ 2 liters 2 liters six cans soda, cereal diet cola diet orange six Equal packets FDA ADI 30 kg child 26.1 43.4 37.3 33.0 50 kg adult 15.7 26.0 22.4 33.0 70 kg adult 11.2 18.6 16.0 33.0 The formula used to calculate methanol inhaled in the Baumann (1979) study was discussed by Kavet (1990): (140 mg/m3 * 6.67 m3/workday * 5 workdays * 60 absorption rate) / 70 kg = 40 mg/kg/week of methanol. The equivalent weekly hours is calculated with the following formula: ( (mg methanol * 7 days) / kg ) * (40 hours/workweek / 40.0 mg/kg/week) Now NutraSweet may try to make the following claims: a. That only 75% of the methanol gets absorbed from aspartame as discussed by Kavek (1990). This is not certain, but based on industry estimates. If it does turn out to be true then multiply the weekly hours at the methanol-laden printing shop by 0.75. b. That 108 ppm (140 mg/m3) is within environmental exposure limits and therefore "safe." There are several problems with this claim. i. As we can see from the Baumann (1979) and Heinrich (1982) experiments detailed earlier, one would expect quite a significant change in blood chemistry (e.g., plasma methanol levels) in the course of regular, long-term aspartame ingestion. A single dose of aspartame has already been shown to increase urinary formate levels despite numerous experimental errors which would tend to negate the increase (Stegink 1981a). ii. It is quite common for long-term exposure to environmental toxins below the industry limits to cause adverse effects. (Ziem 1989) Occupational exposure limits were set long before chronic methanol testing was done and it had never been done until aspartame came on the market. iii. The toxic load of chemicals including methanol and formaldehyde (toxic methanol metabolite) has increased tremendously over the last 15 years. Methanol is used as a fuel on a small scale (EPA 1994). It is also used in paint strippers, duplicator fluid, model airplane fuel and dry gas. Formaldehyde can be found in carpeting, clothing, glues, adhesives, cements, paste, resins, urea-foam insulation, particle board, plywood, cellulose esters, paint, primer, paint stripping agents, paper, polishes, waxes, disinfectants, cleansers, fumigators, cosmetics, preservatives, medication, mouthwash, inks, sealers, and many other products (Remington 1987, page 89). With aspartame ingestion, we are adding tremendously to this toxic load. iv. As discussed earlier, short term exposures to methanol (i.e., 75 minutes) at levels which would not cause a statistically significant increase in average formate levels has been shown to cause subtle changes memory and concentration, slightly greater fatigue, and a slight change in brain wave patterns in response to light and sound (Cook 1991). v. In occupational exposure to methanol, we are only exposing the relatively healthy (to a large extent). With aspartame, we are exposing the healthy and the sick, the developing child and fetus, persons who may be susceptible to methanol such as persons with nutritional deficiencies and persons taking certain drugs which may increase the toxicity of methanol. A large part of the population has become NutraSweet lab rats for life-long exposure to methanol and its toxic metabolites. Some people, such as those with certain chronic immune system disorders, are more susceptible, of course. Some people may not experience the symptoms from the slow, silent damage caused by regular exposure to methanol for 2 years, 5 years, 20 years, etc. vi. Aspartame's other breakdown products also effect some of the same areas of the brain that can be damaged by methanol exposure and may have a synergistic negative effect by potentiating the toxicity of the formaldehyde or formic acid. Formaldehyde ------------ Repeated exposure to low doses of formaldehyde, a formic acid precursor and a methanol metabolite has been shown to cause a wide range of health problems (John 1994, Liu 1991, Molhave 1986, National Research Council 1981 page 175-220, Srivastava 1992). Srivastava (1992) stated the following at such low level exposure: "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, the high rates of sickness emphasise the need for detailed studies on formaldehye-exposed subjects...." While some of the damage from methanol and formaldehyde may be due to formic acid (since some of the formaldehyde appears to be converted to formic acid), it is not inconceivable for formadehyde itself to cause significant damage from repeated exposures over time. Formaldehyde appears to be much more toxic to the body in small amounts than formic acid. The National Research Council (1981, page 179) stated the following about formaldehyde: "Some adverse effects of formaldehyde may be related to its high reactivity with amines and formation of methylol adducts with nucleic acids, histones, proteins, and amino acids. The methylol adducts can react further to form methylene linkages among these reactants. "It appears that before formaldehyde reacts with amino groups in RNA, the hydrogen bonds forming the coiled RNA are broken. Formaldehyde reacts with DNA less frequently than with RNA, because the hydrogen bonds holding DNA in its double helix are more stable. "Reaction of formaldehyde with DNA has been observed, by spectrophotometry and electron microscopy, to result in irreversible denaturation. In reactions with transfer RNA, formaldehyde interferes with amino acid acceptance. The equilibrium reaction of formaldehyde with DNA involves thermally activated opening and closing of hydrogen bonds between matching base pairs in the helix. If permanent cross links are formed between DNA reactive sites and formaldehyde, these links could interfere with the replication of DNA and may result in mutations." It is now thought by some researchers that persons with certain illnesses may be suffering from formaldehyde toxicity when excess methylamine and semicarbazide-sensitive amine oxidase (SSAO) react to form formaldehye (Yu 1993, Boor 1992). Yu states the following: "The cytoxicity seems, therefore, to be a consequence of the deamination of methylamine. Our findings suggest that formaldehyde, the deaminated product of methylamine, may be responsible for these toxic effects. Human serum, which also contains SSAO, was also capable of deaminating methylamine and cause cytotoxicity to cultured endothelial cells. Both methylamine and SSAO circulate in human blood, and their concentrations in the blood of normal healthy subjects are quite close to those required to induce cytotoxicity in tissue-cultured cells. Both SSAO activity and methylamine levels have been reported to be increased in the blood of diabetic individuals. ... It is possible, therefore, that an abnormal metabolism of methylamine may be involved in endothelial injury, and that it may subsequently induce atherosclerotic plaque formation and thus be involved in the cardiovascular disorders seen in diabetes." Therefore, regular ingestion of aspartame may be adding "formaldehyde fuel to the fire" so to speak. It would be especially worrisome to give aspartame to persons with abnormally high SSAO and methylamine levels such as some diabetics. Persons with chronic immune system disorders are often very sensitive to low level chemical exposure including formaldehye. As stated by the National Resource Council (1981, page 177): "In some persons not previously sensitized, repeated exposure to formaldehyde may result in the development of hypersensitivity." Fujimaki (1992) and Vojdani (1992) have shown immune system alteration from exposure to formaldehye. Dr. Sherry Rogers, an expert in environmental exposure and chemical sensitivity discusses how aldehydes, especially formadehyde can cause significant damage in the body (Rogers 1990). She lists the following symptoms found for persons exposed to urea foam formaldehyde insulation (UFFI) at levels of formaldehyde as low as 0.12 ppm: Depression fatigue poor memory inability to concentrate can't think straight "like thinking in a fog" feel unreal headache dizzy or spacey flushing of face burning eyes or throat laryngitis chronic cough, asthma arthritis rashes heart palpitations and much more...... Dr. Rogers cites Main (1983) where adverse health effects to formaldehyde exposure were found at levels between 0.12-1.6 ppm. "One path the chemical may pass through in order for the body to get rid of it is called the ALDEHYDE PATHWAY. When the adehyde pathway, for example, becomes over burdened through inhaling many other chemicals, or through an undiscovered vitamin or mineral deficiency that is cruicial in that pathway, the body then shunts the chemistry to produce chloral hydrate, the old 'Mickey Finn' or 'knockout drops.' So, indeed, these people have a very good reason for the spacey, dizzy, inability to think and concentrate symptoms that they complain of." .... "But it's fairly easy for the aldehyde path to become overloaded. Breathing plastic fumes, formaldehyde-coated paper, carpet and fabric fumes, trichloroethylene from newly shampooed carpets or dry cleaned clothes, aldehydes from auto exhaust can all raise the blood level of aldehydes. So can being highly stressed, since most brain hormones or neurotransmitters also metabolize to aldehydes. Unfortunately, to make matters worse, sometimes the aldehyde pathway does not function well because of undiagnosed deficiencies." [Rogers 1990] Dr. Rogers goes on to discuss the important of zinc, molybdenum dependent enzymes, glutathion (GSH) and other nutrients which are crucial for the conversion of aldehydes (e.g., formaldehyde) to acids (e.g., formic acid). Many of these nutrients are often found lacking in typical American diet. Dr. Rogers' books should be required reading by medical practitioners. It may very well be that it is the formaldehyde metabolite of the methanol in aspartame that causes the most slow and silent damage, especially in combination with other breakdown products of aspartame. If this is the case the formic acid measurements may not tell us what we need to know about the damage being done by the formaldehyde. Summary ------- Given the following points, I believe it is definately premature for researchers to discount the role of methanol in aspartame side effects: 1. The amount of methanol ingested from aspartame is unprecidented in human history. Methanol from fruit juice ingestion does not even approach the quantity of methanol ingested from aspartame, especially in persons who ingest one to three liters (or more) of diet beverages every day. Unlike methanol from aspartame, methanol from natural products is probably not absorbed or converted to its toxic metabolites in significant amounts as discussed earlier. 2. Lack of laboratory-detectable changes in plasma formic acid and formaldehyde levels do not preclude damage being caused by these toxic metabolites. Laboratory- detectable changes in formate levels are often not found in short exposures to methanol. 3. Aspartame-containing products often provide little or no nutrients which may protect against chronic methanol poisoning and are often consumed in between meals. Persons who ingest aspartame-containing products are often dieting and more likely to have nutritional deficiencies than persons who take the time to make fresh juices. 4. Persons with certain health conditions or on certain drugs may be much more susceptible to chronic methanol poisoning. 5. Chronic diseases and side effects from slow poisons often build silently over a long period of time. Many chronic diseases which seem to appear suddenly have actually been building in the body over many years. 6. An increasing body of research is showing that many people are highly sensitive to low doses of formaldehyde in the environment. Environmental exposure to formaldehyde and ingestion of methanol (which converts to formaldehyde) from aspartame likely has a cumulative deleterious effect. 7. Formic acid has been shown to slowly accumulate in various parts of the body. Formic acid has been shown to inhibit oxygen metabolism. 8. The are a very large and growing number of persons are experiencing chronic health problems similar to the side effects of chronic methanol poisoning when ingesting aspartame-containing products for a significant length of time. This includes many cases of eye damage similar to the type of eye damage seen in methanol poisoning cases. Research -------- From the article: "This small amount [of methanol] is readily metabolized by the body. This fact is illustrated by clinical studies in which aspartame failed to increase the levels of methanol (or formate, a metabolite) in blood or urine." [Stegink 1984a, Roak-Foltz 1984] First of all, the author cites a whole 650-page compilation of 33 articles for his first reference (Stegink 1984a). It would have been helpful if he had just cited one or two articles rather than the whole book. The second reference cited by the author to back up the above-quoted statement (Roak-Foltz 1984) is nothing more than a NutraSweet estimate of projected aspartame intake and has nothing to do with methanol or formic acid in the blood or urine. Rather than belaboring the point, I will address the clinical studies in the cited reference (Stegink 1984a) which does measure methanol and formic acid after aspartame ingestion. I will also address the recent chronic dosing study (Leon 1989) which the author cited earlier in the article. a. Frey (1976), page 496 of book. This G.D. Searle (NutraSweet)-funded study tested aspartame on 61 healthy children and sucrose on 65 healthy children (ages 2 - 21) for 13 weeks. Methanol blood and urine measurements were obtained after an overnight fast on 22 aspartame-ingesting subjects at the end of week 7 and week 13. No changes in blood or urine methanol were noted. Flaws ----- i. After an overnight fast, all of the ingested methanol would have either been eliminated or converted to formaldehyde and formic acid (DHHS 1993a, Liesivuori 1986, Stegink 1981a). It is ridiculous to test for methanol in the blood after an overnight fast. ii. Plasma phenylalanine measurements were also taken after the overnight fast. The fast allowed the plasma phenylalanine levels to return to normal or near normal levels. Another worthless test. iii. The subjects were all healthy. It is important to test healthy subjects, but the detrimental effects of methanol would likely be much greater in in subjects with particular health problems such as multiple chemical sensitivities, folic acid deficiency, or persons on pharmaceuticals that may increase the toxicity of methanol. iv. Test product was freshly prepared and not real-world aspartame products which would have a higher percentage of DKP, beta-aspartame, and possibly other breakdown products such as free methanol. v. Test product was given with food more often than normal. This would significantly delay the absorbtion of methanol and cut down on its toxicity. (Posner 1975). Conclusion ---------- A worthless methanol test and other major flaws in this industry-funded research project only proves that the researcher was completely unaware of how to properly test aspartame and its breakdown products. It is interesting to note that the eye complaints were limited to people ingesting aspartame as opposed to sucrose. b. Stegink (1981a), page 542 of book. While one may be able to imagine that the researcher in the Frey (1976) experiment didn't know how to properly take plasma methanol and amino acid measurements, this "experiment" contains so many ridiculous flaws that it seems to me to approach blatent dishonesty as opposed to a legitimate research project. This G.D. Searle (NutraSweet)-funded one-day experiment was performed with 30 healthy adults. Twelve subjects received a dose of 34 mg/kg of aspartame mixed in cold orange juice. The remaining 18 subjects were divided into three groups of six and received either 100, 150, or 200 mg/kg of aspartame. The blood methanol was measured for eight hours after ingestion. No significant blood methanol concentration increase was found at the 34 mg/kg dose. Significant increases in blood methanol concentrations were found in the 100, 150, and 200 mg/kg dose. The increases returned to near fasting levels eight hours after aspartame ingestion. Blood and urine formate concentrations were measured for the six subjects receiving 200 mg/kg of aspartame. The mean of the blood formate concentrations was listed for the first eight hours after aspartame ingestion. There were no statistically significant changes in the blood formate concentrations noted. There was a large, significant increase in urinary formate excretion during the first eight hours after aspartame ingestion. This increase was especially large (three times fasting levels) during the first four hours after aspartame ingestion. The authors claimed that "the rate of formate synthesis did not exceed the rate of format excretion, since blood formate levels were not elevated." Flaws ----- i. The aspartame was given with orange juice. This major flaw, by itself, renders the entire experiment worthless. The researchers claim that the "methanol content of fruit juices may range from 12 to 640 mg/l, with an average of 140 mg/l." Since the intent of the experiment was to measure methanol and formate levels, why in the world would they add what they claim to be a large amount of methanol in the form of fruit juice! By their own standards, this totally screws up their methanol and formate measurements. The important point to remember, though, is that the fruit juice almost certainly protects against methanol poisoning by keeping much of the methanol from being absorbed or converted to toxic metabolites such as formaldehyde and formic acid. Extremely high doses of aspartame such as 200 mg/kg will, of course, overwhelm the protective factors in orange juice. I believe that the researchers deliberately used fruit juice to lower the toxicity and skew methanol and formate measurements by changing its metabolism. They certainly didn't use it to add accuracy to their methanol and formate measurements. ii. The limit for methanol detection was 4 mg/l (or 0.4 mg/dl)! This very serious flaw renders their methanol tests completely worthless. Researchers who are actually interested in measuring methanol levels (as opposed to hiding negative results) from low- level exposure to methanol do not use tests that are incapable of measuring all but the largest spikes in plasma methanol levels. Cook (1991) used a test that was developed in 1981 that was capable of measuring plasma methanol levels lower than 0.26 mg/l. Cook showed that after exposure to methanol, the plasma levels rose in the subjects from a low of 0.26 mg/l to a high of 3.2 mg/l. (Averages increased from 0.57 mg/l to 1.88 mg/l.) Even the highest methanol spike in Cook's experiment would not show up using the worthless methanol test from this NutraSweet- sponsored experiment! d'Alessandro (1994) measured methanol levels below 1 mg/l in test subjects exposed to methanol. Davoli (1986) showed that only 8 mg/kg of aspartame caused a statistically significant rise in plasma methanol levels. It is obvious that a 34 mg/kg dose of aspartame will increase plasma methanol levels substantially. It appears that these researchers deliberately used an outdated, worthless methanol testing procedure so that they could claim that "no increase in blood methanol concentration was detected...." While they were clear in the publication what the limits of the methanol detection was, most people would not know that they used a bad test. iii. It may take as much as 12 to 16 hours after exposure to methanol for plasma formate to reach its maximum levels (McMartin 1975, Liesivuori 1987). The researchers in this project tested formate at intervals up to only 8 hours after exposure and then at the 24-hour mark. Therefore, it seems that they may have missed the period of time when plasma formate levels would be expected to spike to their highest level. iv. The average base blood formate concentration was 19.1 mg/l. This is an unusually high base blood formate level. This is more than twice as high as found by d'Alessandro (1994), Baumann (1979), and Heinrich (1982). Buttery (1988) measureed the plasma formate levels of 30 subjects and found that they ranged from approximately 4.8 to 11.2 mg/l. Osterloh (1986) noted an average value of 4 mg/l and an upper limit of 12 mg/l. While it is possible to find some people with that high a base formate level, for that to be an average seems a little bit ridiculous -- unless the subjects were breathing formaldehyde fumes before the test. As Kavet (1990) points out, the extremely high base formate levels and the variability in the formate measurements during this experiment would keep what might otherwise be a significant change in plasma formate levels from being noticed. It is also quite possible that there were errors in the plasma formate measurements or the assay itself may be faulty. Liesivuori (1986) mentions that analytical methods for measuring formic acid (including the method used in this industry experiment) are "notoriously inaccurate." v. The charts and numbers listed were averages for all the subjects for each time period. As discussed earlier, this technique tends to hide significant changes since following the administration of aspartame or methanol, each person's peak methanol and formate levels would likely occur at a different time. If Subject A's methanol level is sky-high at 2 hours, yet Subject B's level at two hours is still low and doesn't reach it's maximum until 4 hours, this would significantly bring down the average. In addition, any unusual increases in a small proportion of the subjects' measurements tend to not be seen in presentations of average values. vi. Each experimental group ingesting the higher doses of aspartame had a ridiculously small number of subjects, making statistical significance much more difficult to obtain. There were only 6 subjects in the group that had formate measurements taken. Given the wide variability in formate levels from one time period to the next and the tiny number of subjects in this group, obtaining statistical significance was highly unlikely. vii. This experiment was simply a one time ingestion of aspartame. As discussed earlier, short, single exposures to methanol or formaldehyde in the air often does not significantly raise formate levels. However, regular or longer-term exposure does show an increase in formate levels. While it can be helpful to conduct a few quality acute dosing studies, such experiments prove very little as far as the "safety" of aspartame or methanol when ingested regularly or even when ingested from time-to-time. It is important to keep in mind that conducting hundreds of these acute dosing studies shows us very little about the affect of aspartame as it is used in the real world-- regular, long-term ingestion. The very poor quality of these acute-dosing studies simply means that instead of showing us very little, they show us only that research on aspartame must be conducted independently in order to study the adverse health effects of aspartame. viii. The subjects were all healthy. It is important to test healthy subjects, but the detrimental effects of methanol would likely be much greater in subjects with particular health problems such as multiple chemical sensitivities, folic acid deficiency, or persons on pharmaceuticals that may increase the toxicity of methanol. ix. There were numerous useless tests for an experiment of this length. There was an ophthalmological examination before and after the aspartame ingestion. Eye damage occurs gradually after chronic methanol exposure, e.g., months or years after aspartame ingestion begins. There were blood tests for total protein, albumin, Ca, inorganic P, lactate dehydrogenase, total bilirubin, glutamic-oxaloacetic transaminase, Na, K, Cl, and CO2. All of these tests are worthless for such a short experiment which had so many experimental errors. Once again, the researchers measured the plasma amino acids levels after the subjects had fasted overnight. The plasma amino acid levels would return to normal or near normal after that length of time. Unfortunately, the large number of tests allow the researchers to claim that this proves the "safety" of aspartame. x. The aspartame given to the subjects was fresh aspartame and not nearly the same product that many unfortunate people are taking on a regular basis. The product sold at the stores have often degraded due to the length of time they have sat on the shelves and/or due to the exposure to high temperatures. Conclusion ---------- This experiment appears to be quite deceptive. Giving aspartame with a product that you know will screw up your measurements it quite a mistake! Using an outdated methanol test that can only measure very high levels of methanol is another particular serious mistake. Add to that, all of the other flaws: ridiculously high base formate levels, possible inappropriate times at which formate measurements were taken, use of average values for each time period, small numbers of subjects in each group, only a single ingestion of aspartame, healthy subjects, numerous useless tests, and fresh aspartame used. This experiment is a perfect example of just how bad "research" can get when G.D. Searle or the NutraSweet Company is connected in any way with the project. One wonders what good, if any, is the "peer review" process if a study like this can get published. The fact that a number of editors of this publication worked for G.D. Searle (the company that developed aspartame), may have something to do with how this study got published. It also may help explain why so many flawed industy- connected aspartame studies were published in this journal (Journal of Toxicology and Environmental Health). Even with all of its major flaws, this study contradicts the author's statement that "aspartame failed to increase the levels of methanol (or formate, a metabolite) in blood or urine." c. (Stegink 1983a), page of book. This General Foods Corporation-funded study was similar to the previous study, except that it was conducted on infants (8-14 months of age). Ten infants were given a single 34 mg/kg dose of aspartame mixed in a freshly-prepared, cherry-flavored beverage. Eight infants were given a dose of 50 mg/kg, and 6 received a dose of 100 mg/kg. Only the blood methanol concentrations were measured from the 1 ml of blood withdrawn at 4 different intervals within 3 hours following aspartame ingestion. Important measurements of blood formate and urinary excretion of formate were not done because, according to the researchers, there was too small an amount of blood available in the samples. The results of the blood methanol test were similar to that in the experiment discussed immediately above. Blood methanol concentrations showed no significant increase for infants ingesting the 34 mg/kg dose. Significant increases were seen in doses of 50 and 100 mg/kg. Flaws ----- i. It is two years later and these researchers are still using the same outdated, worthless methanol testing procedure that was used in the experiment discussed above. Therefore, any claim by the researchers that "no increase in blood methanol concentration was detected after administration of aspartame [34 mg/kg]..." is blatently deceptive. ii. Stegink's comparison of methanol from juices and methanol from aspartame seems particularly ridiculous. Stegink shows that a dose of 100 mg/kg of aspartame raises an infant's plasma methanol levels approximately 10 times above its base level. Stegink assumes that an infant weighs 10 kg. This means that they gave the infants approximately 1000 mg of aspartame. This is equivalent to 100 mg of methanol. The researchers cite the Francot (1956) study which claims that black current juice contains over 600 mg/l of methanol. One hundred milligrams (100 mg) of methanol (the equivalent amount to what the infants were given with aspartame) would be found in approximately six ounces of black current juice according to Francot's study. Stegink uses an example of an infant drinking six ounces of liquid and thus he must believe that this is a reasonable volume that an infant can ingest. Therefore, according to Stegink's reasoning, 6 ounces of black current juice given to an infant should raise that infant's blood methanol level by nearly 10-fold. I would love to see them try to show a 10-fold increase in blood methanol levels and a corresponding increase in blood formate levels after 6 ounces of black current juice were given to a 10kg infant. iii. This experiment did not test blood and urinary formate levels. Therefore, we do not know much about what happened to the methanol after it was absorbed into the bloodstream. iv. This experiment was simply a one time ingestion of aspartame. While it can be helpful to conduct a few quality acute dosing studies, such experiments prove very little as far as the "safety" of aspartame or methanol when ingested regularly or even when ingested from time-to-time. It is important to keep in mind that conducting hundreds of these acute dosing studies shows us very little about the affect of aspartame as it is used in the real world-- regular, long-term ingestion. v. The aspartame given to the subjects was fresh aspartame and not nearly the same product that many unfortunate people are taking on a regular basis. The product sold at the stores have often degraded due to the length of time they have sat on the shelves and/or due to the exposure to high temperatures. vi. The charts and numbers listed were averages for each time period. As discussed earlier, this technique tends to hide significant changes since following the administration of aspartame or methanol, each person's peak methanol and formate levels would likely occur at a different time. If Subject A's methanol level is sky-high at 2 hours, yet Subject B's level at two hours is still low and doesn't reach it's maximum until 4 hours, this would significantly bring down the average. In addition, any unusual increases in a small proportion of the subjects tend to not be seen in presentations of average values. Conclusion ---------- These researchers are still using a worthless methanol testing procedure. One wonders how many years this same "test" will be used to "prove" that aspartame does not increase plasma methanol levels. We will find out later in this document. They also repeated many of the same mistakes they made in the previous experiment. Finally, this experiment was of less use since formate levels were not measured at all. Even with all of its major flaws, this study contradicts the author's statement that "aspartame failed to increase the levels of methanol (or formate, a metabolite) in blood or urine." d. Leon (1989). From the article: "Results of this study showed no significant differences between [experimental and placebo] groups with regard to urinary excretion of formate (a metabolite of methanol)." In this G.D. Searle (NutraSweet)-funded study, 108 subjects were divided into two groups. Fifty-three (53) subjects ingested capsules containing 75 mg/kg per day of aspartame in three equal doses along with meals. The 55 subjects in the placebo group ingested cellulose capsules along with meals. Each group took their doses for 6 months. A large number of laboratory tests were performed throughout the study. In addition, plasma amino acid tests were performed to test for phenylalanine and LNAA levels. (These tests will be discussed in later sections.) Blood methanol and blood formate measurements were taken at the start of the experiment and after weeks 6, 12, 18, and 24. Urinary formate measurements were taken at the start of the experiment and after weeks 6, 12, and 24. Most of the blood methanol readings were below the detectable levels. Only at the week 18 test was there a much greater proportion of persons in the aspartame group with a detectable blood methanol level. No data was given, but the investigators stated that there was no significant difference in the measured blood formate, urinary formate excretion (or formate to creatinine excretion ratio) between the aspartame and the placebo group. Flaws ----- i. The aspartame used was fresh, dry aspartame administered in capsules. Sixteen years after the FDA pointed out the lack of information on the difference in bioavailability between real-world aspartame and capsule administration (Freeman 1973), six years after the National Soft Drink Association pointed out the enormous chemical differences in real-world aspartame as compared to fresh aspartame (NSDA 1983), four years after Tsang published detailed data proving an enormous difference in the chemical composition between aspartame freshly prepared in capsules and real- world products, and two years after Stegink proved that aspartame dissolved in liquid has a much more extreme effect than capsule-enclosed aspartame (Stegink 1987a), these researchers had no legitimate excuse for using capsule administration of aspartame. One of the investigators on this project was from the University of Iowa and should have been intimately familiar with the work of Stegink (who is also from the University of Iowa), especially Stegink's (1987a) study showing the difference in bioavailability between liquid and encapsulated aspartame. This obvious mistake of using encapsulated aspartame completely invalidates much of this experiment. The plasma amino acid measurements are worthless. Capsule administration reduces the toxicity of aspartame significantly for the following reasons: - Fresh aspartame is used instead of the more toxic soup that is found in real-world products. - The plasma amino acid (i.e., phenylalanine and aspartate) spikes are considerably lessened with capsule administration of aspartame. - Methanol absorption is delayed. This may reduce the methanol toxicity as pointed out earlier. The researchers may claim that they needed to use capsules for a double-blind study. The answer to such a claim is as follows: 1) Even if it were a good excuse to use capsule administration, the lack of bioequivalence between capsule and real-world aspartame administration still invalidates much of this experiment; 2) Most of the experiment was simply performing blood tests which do not need a double-blind protocol; 3) It may be possible to create a double-blind experiment using real-world, liquid aspartame-containing products as long as the taste is disguised. This has been done with MSG experiments in the past. ii. The aspartame capsules were ingested with full meals. This is one of many mistakes which combine to invalidate this experiment. The effects from the free amino acids would not be nearly pronounced when aspartame is taken with full meals. (I will go into more detail about this in a later section.) As Posner (1975) points out, taking methanol with meals slows its absorption and may affect its toxicity. The combination of this flaw plus the use of capsules would render formate and other measurements nearly useless. The chance of finding an adverse reactions to fresh, encapsulated aspartame, taken with full meals is tremendously reduced. One wonders if these researchers deliberately designed this experiment to produce negative results. iii. The blood methanol tests were taken after a 12-hour fast. Anyone who has done any reading on the subject of methanol would know that a blood test for methanol would be worthless after a 12-hour fast (as discussed earlier in this section). Had the investigator who conducted the blood methanol test in this experiment, Thomas Tephly, Ph.D., taken the time to read another paper that he co- authored (Stegink 1981a), he would have known that methanol gets converted to formic acid in the body causing the methanol concentration in the blood to return to normal levels within twelve hours after aspartame ingestion. On top of the worthlessness of taking the methanol test at the wrong time, these researchers used the same worthless blood methanol test that was used in the experiments discussed previously. This time, however, these researchers claimed that the blood methanol test had a limit of detection of 0.31 mmol/liter or, using the conversion factor presented in DHHS (1993a), approximately 1.0 mg/dl (10 mg/l). This is three times less sensitivity claimed than the previous experiments dicussed and as much as 45 times less sensitive than the methanol test used by Cook (1991)! One wonders how these researchers could possibly have found any of the methanol measurements over the limits of detection let alone 10 to 20 percent of the limits of detection. iv. The blood methanol and formate tests were taken on weeks 0, 6, 12, 18, and 24. The urine formate and creatinine tests were taken on weeks 0, 6, 12, and 24. What happened to week 18? Is it typical to skip an important test for no particular reason? Is it possible that the test was done, but the data did not meet the researchers' expectations? This seems rather strange to say the least especially since this happens to be the week that blood methanol tests somehow showed the aspartame group well above the placebo group. v. The exclusion criteria stated, in part, that "All women included in the study were required at entry to be postmenopausal, to have been surgically sterilized, to be taking oral contraceptives, or to have had an intrauterine device in place for at least 6 months to prevent the possibility of pregnancy." The problem with this exclusion criteria is that women make of the majority of reported adverse reactions to aspartame (Mullarkey 1992, page 70, CDC 1984). It is not inconceivable that women who have certain hormonal fluctuations may be more susceptible to acute adverse effects from aspartame. Therefore, the researchers may have excluded a large percentage of the population who would have actually experienced adverse reactions (had the experiment not been so badly flawed). There appears to be no good reason for excluding this population of women. If these researchers insist on not studying anything but a perfectly healthy population, the least they could do is use a reasonable representation of a healthy population rather than further limiting it to whatever their whimsical desires call for. If, in the very unlikely occurrance, one of the women had become pregnant and experienced an adverse reaction, they could have simply noted that in their discussion. Instead, they chose to take an unrepresentative sample of subjects (healthy persons) and make it less representative by excluding women who may be more susceptible to acute adverse reactions.. vi. One subject with a history of bronchial asthma was dropped from the study due to symptoms of headaches, nausea, and malaise after aspartame capsule ingestion. The subject was rechallenged for a much shorter period of time (9 days as compared to 6 months), with a much smaller dosage (9 - 25 mg/kg capsules over a nine day period as compared to 75 mg/kg per day) with customized meals (which may have included foods to further offset the effects of methanol and amino acids). The subject experienced fewer reactions to aspartame under these conditions. The subject was rechallenged at least one more time (the paper does not mention under what conditions) and no aspartame reactions were found. This is an abuse of double-blind studies. The researchers cannot simply take results that they don't like such as a serious adverse reaction and then keep challenging the subject and changing the protocol until the desired results are achieved. Why didn't the researchers change the protocol and rechallenge persons who did not experience reactions? vii. The subject that was dropped from the study had a history of bronchial asthma. The exclusion criteria stated that subjects should be excluded from the experiment if they had "any chronic disease detected by history, physical examination, or routine laboratory tests." What was this person doing in the experiment in the first place? He should have been excluded according to the protocol. If these researchers cannot even follow their own exclusion criteria, and change the protocol for rechallenges of this subject as described above, one wonders how many other times they deviated from the protocol and did not mention it in the publication. viii. Plasma phenylalanine and phenylalanine/LNAA measurements were taken after the overnight fast. The fast allowed the plasma phenylalanine levels to return to normal or near normal levels. Another worthless test. While fasting plasma phenylalanine levels in some persons may change over time and cause serious health problems after regular ingestion of aspartame (as per the example given near the start of this review), that would not have been seen here because the use of fresh, encapsulated aspartame taken with meals skewed the results so badly. ix. The formate test had only an 80% chance of detecting an average change of 0.13 mmol/L (5.2 mg/l) in blood levels. (Blood formate levels average approximately 0.1 mmol/l or 4 mg/l as discussed earlier.) Therefore, a significant increase could occur using this test without it being noticed. The blood formate measurements were not even presented. These values would have been much more relevant than the hematology values had the experiment not otherwise had so many major flaws. Even if the values had been presented, Liesivuori (1986) mentions that analytical methods for measuring formic acid (including the method used in this industry experiment are "notoriously inaccurate." x. Once again, the charts and numbers listed were averages for all subjects at each time period. As discussed earlier, this technique tends to hide significant changes since following the administration of aspartame or methanol, each person's peak methanol and formate levels would likely occur at a different time. If Subject A's methanol level is sky-high at 2 hours, yet Subject B's level at two hours is still low and doesn't reach it's maximum until 4 hours, this would significantly bring down the average. In addition, any unusual increases in a small proportion of the subjects tend to not be seen in presentations of average values. xi. The quality of the study was monitored by an employee of the NutraSweet Company. This, in itself, I believe is a flaw due to the extreme corporate bias. Conclusion ---------- Even with all of these major flaws, the aspartame group experienced approximately 50% more adverse reactions than the placebo group. This significant increase was played down in the text by breaking up the adverse reactions into categories such as "headaches." One wonders if the results would have even been more striking had the researchers used real-world aspartame products at a similar dose and not built so many other serious flaws into this experiment. A research project like this can make a person lose all faith in the scientific process. Only industry (e.g., NutraSweet) would fund and monitor a study this poorly designed. The study was presented at the 1988 Annual Meeting of the Federation of American Societies for Experimental Biology (FASEB). Such a presentation should have caused the audience to begin crying over the death of the scientific process. It boggles the mind that a peer-reviewed journal would accept this study for publication without addressing some of the serious questions raised above. It simply proves that the peer- review process does not prevent worthless, industry- sponsored studies. I would prefer to say that the experiments discussed above are the worst research I have ever seen. Unfortunately, these are quite typical of industry-sponsored studies. Many of the pre-approval studies for aspartame which will be discussed later were much worse -- so bad that rolling dice would have been a more accurate method for determining the "safety" of aspartame. Yet, somehow, even the pre-approval studies met the FDA's "standards" for acceptable research upon which a safety determination could be made. NutraSweet/FDA Arguments ------------------------ Animal Studies -------------- Studies of methanol on rats and Rheusus monkeys cannot be extrapolated to humans. The differences between how these species handle methanol is described in detail by Roe (1982). Sturtevant (1985) of G.D. Searle & Co. claims that Martin- Amat (1978) created an animal model using Rhesus monkeys. However, Roe (1982) points out that, as other investigators have found, it is "very unlikely that in rhesus monkeys (blood pH about 7.2 (av.) and blood formate about 7.5 mmol/l) amaurosis and atrophy of the optic nerve can be caused by methanol." Roe also details the significant differences between methanol metabolism in rhesus monkeys and humans as well as the many times greater toxicity of methanol in humans. Finally, even if an animal model for acute methanol poisoning is created in the future, it is unlikely that the model will apply to low-level, chronic methanol poisoning since the mechanism is probably somewhat different (i.e., no severe acidosis) The NutraSweet Company's attempts to use the Rheusus monkey as a test animal for aspartame/methanol poisoning only proves that they do not understand or care about the researched differences of the effects of methanol between humans and that particular species of monkeys. Human Studies ------------- Sometimes, as "proof" that low levels of methanol does not cause damage, the NutraSweet Company or the FDA cite several references. One study that is sometimes cited is a 1952 study published in the British Journal of Industrial Medicine (Leaf 1952). The FDA states (Federal Register 1984, page 6677): "In fact, studies in human subjects given oral dosages of methanol of 71 to 84 mg/kg body weight showed no toxic effects with blood levels of methanol reaching 47 to 76 mg per liter 2 to 3 hours afterwards." The reality is: 1. The study was performed on only five men given a dose of 2.5 to 7.0 ml (29-84 mg/kg) not 71 to 84 mg/kg. 2. It was a one-day, single-dose study of methanol and did not test chronic ingestion over months or years as happens with aspartame ingrestion. 3. There was no detailed discussion of reactions that may have been caused by the single dose of methanol in this experiment. 4. The first part of the study where methanol was given by itself showed that a large percentage of methanol was converted to formic acid. In the second part of the study where ethanol was taken concurrently with methanol, the ethanol blocked the conversion of methanol to formaldehyde and formic acid. (Remember, aspartame contains no protective ethanol.) 5. The investigators summarize as follows: "Owing to the slow rate of elimination of methanol from the body, repeated exposure to the vapour or liquid may result in accumulation and under such conditions the use of methanol would constitute a toxic hazard. . . . The elimination of methanol after doses of 2.5 to 7.0 ml has been studied in five human subjects. At any time the rate of elimination was found to be proportional to the concentration of methanol in the body. The significance of this finding is discussed. Only a very small fraction of the ingested methanol (about 2%) was eliminated via the respiratory and urinary routes." 6. A significant portion of this publication addressed the important part ethanol plays in protecting against methanol poisoning. As was mentioned earlier, aspartame contains no ethanol or other protective factors. The FDA attempts to give further examples of the alleged lack of toxicity of methanol at low levels (Federal Register 1984, page 6677): "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 (Rowe 1982, Friedman 1980)." The references cited by the FDA are only discussing severe, acute toxicity (i.e., poisoning) and not long-term, chronic toxicity (i.e., slow poisoning). Unfortunately, this is the type of obfuscation that one can expect from the FDA and the NutraSweet Company -- keeping people busy chasing down references which are irrelevant, but which allow them to convince the uninformed scientist that aspartame is "safe." NutraSweet researchers will sometimes cite two more recent studies which they claim to show that methanol poisoning cannot occur from aspartame (Stegink 1989, Stegink 1990). Many of the same serious problems, bordering on outright deception, that were found in Stegink (1981a) are also found in these studies. Stegink (1989) tested six normal adult subjects ingesting eight 8-ounce servings of Kool-Aid each sweetened with 600 mg of aspartame. The servings were taken at one hour intervals. On another day, the subjects followed the same procedure, but the Kool-Aid was unsweetened (i.e., no aspartame). Stegink (1990) was nearly the same experiment, but the subjects were individuals heterozygous for Phenylketonuria (PKU). (PKU is a genetic disorder where the person lacks an enzyme necessary to metabolize the amino acid, phenylalanine. A PKU Heterozygote has a slightly impaired phenylalanine metabolism.) Both experiments showed a significant increase in plasma phenylalanine levels as well as plasma phenylalanine/LNAA ratios. (This will be discussed in more detail in the Phenylalanine section.) No statistically significant difference was seen in the blood methanol levels, blood formate levels, or urinary formate levels on the day where aspartame was ingested compared to the day it was not ingested. Flaws ----- i. These "researchers" are still using the same outdated (1969), non-sensitive, worthless methanol test that they were using in 1981! With all the money being poured into this lab from the NutraSweet Company, one would think that they could afford equipment for accurate and useful tests. Stegink (1990) took it one step beyond a mere deceptive, worthless methanol test. A graph was shown of blood methanol levels over 24 hours. The "apparent" aspartame day methanol levels were shown as the exact same as the Kool-Aid (alone) day. This is extremely deceptive for two reasons. The levels shown were more than three times below the detection limit of the methanol test used and therefore the figures on the graph were a wild guess (at best). Davoli (1986) had already shown a significant increase in blood methanol levels after a single dose of 500 mg of aspartame and therefore Stegink, et al. must have known that the methanol levels rose significantly and that the graph was complete nonsense. ii. It may take as much as 12 to 16 hours after exposure to methanol for plasma formate to reach its maximum levels (McMartin 1975, Liesivuori 1987). The researchers in this project tested formate at intervals up to only 8 hours after exposure and then at the 24-hour mark. Therefore, it seems that they may have missed the period of time when plasma formate levels would be expected to spike to their highest level. iii. The average base blood formate concentration was again ridiculously high -- 21.0 mg/l in Stegink (1990). This is two or three times higher than in almost any independent experiment (d'Alessandro 1994, Baumann 1979, Heinrich 1982, Buttery 1988, Osterloh 1986). While it is possible to find some people with that high a formate level, for that to be an average seems ridiculous -- unless the subjects were breathing formaldehyde fumes before the test. As Kavet (1990) points out, the extremely high base formate levels and the variability in the formate measurements during this experiment would keep what might otherwise be a significant change in plasma formate levels from being noticed. It is also quite possible that there were errors in the plasma formate measurements or the assay itself may be faulty. Liesivuori (1986) mentions that analytical methods for measuring formic acid (including the method used in this industry experiment are "notoriously inaccurate." iv. The charts and numbers listed were averages for all the subjects for each time period. As discussed earlier, this technique tends to hide significant changes since following the administration of aspartame or methanol, each person's peak methanol and formate levels would likely occur at a different time. If Subject A's methanol level is sky-high at 2 hours, yet Subject B's level at two hours is still low and doesn't reach it's maximum until 4 hours, this would significantly bring down the average. In addition, any unusual increases in a small proportion of the subjects' measurements tend to not be seen in presentations of average values. v. Each experimental group ingesting the higher doses of aspartame had a ridiculously small number of subjects, making statistical significance much more difficult to obtain. There were only 6 subjects in the test groups. Given the wide variability in formate levels from one time period to the next and the tiny number of subjects in this group, obtaining statistical significance was highly unlikely. vii. This experiment was simply a one day ingestion of aspartame. As discussed earlier, short, single exposures to methanol or formaldehyde in the air often does not significantly raise formate levels. However, regular or longer-term exposure does show an increase in formate levels. While it can be helpful to conduct a few quality acute dosing studies, such experiments prove very little as far as the "safety" of aspartame or methanol when ingested regularly or even when ingested from time-to- time. It is important to keep in mind that conducting hundreds of these acute dosing studies shows us very little about the affect of aspartame as it is used in the real world--regular, long-term ingestion. The very poor quality of these acute-dosing studies simply means that instead of showing us very little, they show us only that research on aspartame must be conducted independently in order to study the adverse health effects of aspartame. viii The aspartame given to the subjects was fresh aspartame and not nearly the same product that many unfortunate people are taking on a regular basis. The product sold at the stores have often degraded due to the length of time they have sat on the shelves and/or due to the exposure to high temperatures. Conclusion ---------- These two studies, while slightly better than the single dose experiments, were still only one day long. Numerous other flaws as well as deceptively faulty testing procedures make it impossible to draw any useful conclusion from the experiment. Sometimes NutraSweet researchers will try to argue that aspartame cannot possibly increase formate levels more than 9 mg/l (for 3 liters of diet cola) and is therefore within "normal" blood formate range -- meaning that it could not possibly be harmful. This argument was put forth by Shahangian (1984). The problem with this argument is that people have their own unique blood chemistry. To arbitrarily add a significant amount of formate to the blood and say that it is okay simply because they can find someone else in the world with that level of formate (meaning that the level is still "normal") does not make sense. An increase in formate of 9 mg/l would be considered by many health professionals to be a dangerous jump in formate levels if it occurred regularly. Chronic methanol poisoning does not necessarily mean that there are large jumps in the blood and urine methanol and formic acid levels. Small increases occurring regularly, over many months or years may be enough to cause damage a little bit at a time, especially in persons who 1) do not take the ethanol protective factor with aspartame ingestion, 2) have a folic acid or other nutrient deficiencies, 3) have a sensitivity to methanol or its toxic metabolites such as the growing number of persons with Multiple Chemical Sensititives (MCS), and 4) are taking pharmaceuticals which may react negatively with methanol ingestion. Finally, we have to keep in mind that the mechanism(s) for acute methanol toxicity and chronic methanol toxicity may be different in some ways and similar in others. Any highly technical argument by NutraSweet trying to convince readers that low levels of methanol is safe will have to address the following issues: a. Low levels of chronic methanol exposure in industry has caused adverse reactions after a relatively short period of time. The technical argument will have to show how and why low levels in industry cause adverse reactions, but levels not much lower than that from aspartame would somehow miraculously not cause any reactions even though it is proposed for a lifetime of use in even the most chemically sensitive individuals. b. Given that environmental researchers agree that there is a lack of data on long-term exposure to low-levels of methanol, how can NutraSweet, with any conscience, conduct a clinical trial of low levels of an extremely dangerous, human-specific poison on much of the population. This is especially true since prelimary experiments of short-term exposure to low levels of methanol show minor changes in brain function. Recent Case History Samples --------------------------- 1. I'm a 29 year old atheletic female victim of deadly NutraSweet poisoning. I began to use it in the spring of 1990, and soon afterwards my condition began to deteriorate. I never imagined my strange symtoms were from this chemical, after all its approved by the FDA and on restaurant tables. My eyesight began to fade until I was almost blind in one eye. Next my hearing became dull and my legs, feet and torso lost sensation and became numb. I was dizzy most of the time, irritable and depressed and had constant terrible headaches. I became very clumsy, dropped and bumped into things. I used to skate but having lost my balance I had to give it up. My mind was affected and I thought I had a brain tumor. Reading comprehension and memory drastically decreased. I though I was dying. Two different doctors made the diagnosis of Multiple Sclerosis. One was an eye specialist I saw about my vision loss. This spring a friend explained to me that all my symptoms were coming from aspartame (NutraSweet) and that I had methanol toxicity which mimics Multiple Sclerosis. I was only drinking three Diet Cokes a day. I could hardly believe the horrible nightmare I was living was sold in 6 packs at the grocery store, but I would try anything so I stopped. Right away I began to feel better and today most of my symptoms have completely disappeared. My friend, Betty, was right, I was suffering from methanol toxicity. My hearing and vision have returned and so has my memory. I'm no longer clumsy and have regained my balance, and feeling has returned to my lower extremities. 2. I became a big drinker of Diet Coke, drinking more and more because I liked the taste. When I had vision disturbances my physician said it was optic migraines. There were silvery lines in my eyes and I would get dizzy. Sometimes I would have these optic migraines twice a day, and up to 6 times a week. One day I baked cookies with NutraSweet and really got worse. Never did I associate my problems with this substance. About six months ago I was given some information on aspartame (NutraSweet) and immediately stopped using it in any form. Within a week I realized I wasn't having any optic migraines or dizziness. In six months I've only had two small episodes, and feel they are related to having accidently consumed something with aspartame in it like the ice cream I had recently. I was not aware aspartame was in it until after I had eaten it. .... P.S. Since we've been notifying others of the dangers of aspartame they, too, have abstained, many with the disappearance of symptoms, including my husband, Bob. It turns out this is a very serious problems and the average person does not consider the association of this toxin with their medical problems. It is easily established this is the culprit when symptomatology does not return after elimination. Conclusion ---------- Methanol ingestion by aspartame users is much greater than what they would naturally ingest with fruit juices. The lack of natural ethanol protective factor makes methanol from aspartame even more dangerous. It is likely that toxic methanol metabolites are not produced in significant amounts after ingestion of food products as they are after ingestion of aspartame. Persons with certain health conditions or who are taking certain pharmaceuticals may be even more susceptible to chronic methanol poisoning. Clinical experience has shown that many persons who have ingested aspartame regularly for an extended period have suffered from symptoms which are common in methanol poisoning. NutraSweet-funded studies usually do not test chronic ingestion of aspartame, are usually hopelessly flawed, at best, and, in my opinion, represent a deliberate attempt to deceive. The question we have to ask ourselves is whether it is fair to sell a product which essentially provides the equivalent of part-time employment for much of the population, from the healthiest to the sickest, from children to pregnant women, at methanol-laden printing shops and chemical plants. Given that more and more people are becoming sensitive to chemical exposure and that an increasing number of people are developing chronic immunological and neurological problems, is it fair to significantly add to the toxic load without warning the consumers? Not only is it not fair to experiment with low levels of poison on the population, but contributing to the destruction of so many people's health simply to make money borders on criminality in my opinion.