Mark D. Gold 12 East Side Dr., Suite 2-18 Concord, NH 03301 (603) 225-2110 mgold@holisticmed.com http://www.holisticmed.com/ http://www.holisticmed.com/aspartame/ December 4, 1995 Mr. Alan Paul Editor-In-Chief Editorial Office Muscular Development - Fitness - Health 2120 Smithtown Ave., Ronkonkoma, NY 11779 Re: "Aspartame: Healthier than Sugar" by Brian Leibovitz, Ph.D. Dear Mr. Paul, I was shocked that aspartame was portrayed as an acceptable substitute to sugar in the April 1995 issue of Muscular Development - Fitness - Health. I have seen many serious acute and chronic illnesses contributed to by the short- and long-term use of aspartame. There are thousands of persons throughout the U.S., who, like myself have seen adverse reactions from aspartame, and are working to warn people to stay away from it. Therefore, I ask that you give equal time to an appropriate expert for presentation of the non-industry point of view. I have utmost respect for much of Dr. Leibovitz' work, but I believe that he totally misses the problem with aspartame. While I don't expect Dr. Leibovitz to agree with me on every item related to the aspartame situation, I would hope that he would at least investigate the situation thoroughly by speaking with people who collect adverse reactions, speaking with people who have experienced serious health problems from aspartame, and reading the scientific literature. I have enclosed a review of Dr. Leibovitz' article. It is currently in draft form as I intended to make it into a general review of the aspartame situation over the next few months. Many health professionals, including Nutritionists have known all along that aspartame was hazardous. Now, a growing number of those professionals are seeing the consequences of medium- and long-term aspartame use and have begun to warn their clients off of the junk. Dr. Atkins recently changed his books and warned his readers to stay away from aspartame. I hope that both Muscular Development - Fitness - Health and Dr. Leibovitz consider the growing evidence of danger from aspartame and take the appropriate steps as well. Sincerely, Mark D. Gold © 1995 Mark D. Gold All rights reserved. A. Overall Article Impression 1. Article Bias A person reading the article might believe that they obtained a balanced picture aspartame issue. This is far from the truth. What follows is a breakdown of the 11 scientific references cited by the author in the article: Category Reference # Research funded by NutraSweet Company 6 (Leon 1989) 8 (Schiffman 1987) Researchers/Consultants for the NutraSweet Industry 1 (Stegink 1984a) 8 (Schiffman 1987) 10 (Moser 1994) Funded by Organizations connected with or given money by NutraSweet Company 4 (Roak-Foltz 1984) 9 (Wolraich 1994)* 11 (Garriga 1991)* AMA Council on Scientific Affairs 5 (AMA 1985) Unrelated to Aspartame 2 (Balon 1994) Independant Research on Aspartame 7 (Walton 1993) *The International Life Science Institute (ILSI) partially funded these studies. ILSI's connection to the NutraSweet Company is described later in this document). The author of the article is well-aware of the importance of keeping conflict-of-interest out of the field of Nutritional Science as evidenced by his statements regarding "Vested Interests" in his article entitled, "Nutrition: At the Crossroads" (Liebovitz 1992). Yet, simply by looking at the references cited in this article and the complete lack of opposing viewpoints, one can conclude that the article unintentionally become little more than an advertisement for the NutraSweet Company. 2. Article Conclusion Dr. Leibovitz opened the article by stating his conclusion as to the "safety" of aspartame: "Aspartame is made from phenylalanine, aspartic acid, and methanol--three naturally- occurring compounds; it is virtually non- toxic, and a very potent sweetening agent, as detailed elsewhere1 [Stegink 1984a]" [Emphasis added.] The reference cited for this statement is an 11-year-old book compiled by researchers for the NutraSweet industry. The book is a biased look at the NutraSweet industry's viewpoint on the "safety" of aspartame. Much of the key information in the book is out-of-date and has been proven to be incorrect in subsequent research. The truth about aspartame's toxicity is far different than what the NutraSweet Company would have your readers believe. In February of 1994, the U.S. Department of Health and Human Services released the listing of adverse reactions reported to the FDA (DHHS 1994). Aspartame accounted for more than 75% of all adverse reactions reported to the FDA's Adverse Reaction Monitoring System (ARMS). Many reactions to aspartame were very serious including seizures and death. Other reactions reported included: Headaches/Migraines Dizziness Joint Pain Nausea Numbness Muscle spasms Weight gain Rashes Depression Fatigue Irritability Tachycardia Insomnia Vision Loss Hearing Loss Heart palpitations Breathing difficulties Anxiety attacks Slurred Speech Loss of taste Tinnitus Vertigo Memory loss In an epideimological study which appeared in the Journal of Applied Nutrition (Roberts 1988), 551 persons who have reported reactions to aspartame were surveyed. What follows is a listing of the adverse health effects which were found. # of people (%) Eye - Decreased vision and/or other eye problems 140 (25%) (blurring, "bright flashes," tunnel vision) - Pain (or or both eyes) 51 (9%) - Decreased tears, trouble with contact lens, 46 (8%) or both - Blindness (one or both eyes) 14 (3%) Ear - Tinnitus ("ringing," "buzzing") 73 (13%) - Severe intolerance for noise 47 (9%) - Marked impairment of hearing 25 (5%) Neurologic - Headaches 249 (45%) - Dizziness, unsteadiness, or both 217 (39%) - Confusion, memory loss, or both 157 (29%) - Severe drowsiness and sleepiness 93 (17%) - Paresthesias ("pins and needles," "tingling") 82 (15%) or numbness of the limbs - Convulsions (grand mal epileptic attacks) 80 (15%) - Petit mal attacks and "absences" 18 (3%) - Severe slurring of speech 64 (12%) - Severe tremors 51 (9%) - Severe "hyperactivity" and "restless legs" 43 (8%) - Atypical facial pain 38 (7%) Psychologic-Psychiatric - Severe depression 139 (25%) - "Extreme irritability" 125 (23%) - "Severe anixiety attacks" 105 (19%) - "Marked personality changes" 88 (16%) - Recent "severe insomnia" 76 (14%) - "Severe aggravation of phobias" 41 (7%) Chest - Palpitations, tachycardia (rapid heart action), 88 (16%) of both - "Shortness of breath" 54 (10%) - Atypical chest pain 44 (8%) - Recent hypertension (high blood pressure) 34 (6%) Gastrointestinal - Nausea 79 (14%) - Diarrhea 70 (13%) Associated gross blood in the stools (12) - Abdominal pain 70 (13%) - Pain on swallowing 28 (5%) Skin and Allergies - Severe itching without a rash 44 (8%) - Severe lip and mouth reactions 29 (5%) - Urticaria (hives) 25 (5%) - Other eruptions 48 (9%) - Aggravation of respiratory allergies 10 (2%) Endocrine and Metabolic - Problems with diabetes: loss of control; 60 (11%) precipitation of clinical diabetes; aggravation or simulation of diabetic complications - Menstrual changes 45 (6%) Severe reduction or cessation of periods (22) - Paradoxic weight gain 34 (5%) - Marked weight loss 26 (6%) - Marked thinning or loss of the hair 32 (6%) - Aggravated hypoglycemia (low blood sugar 25 (5%) attacks) Other - Frequency of voiding (day and night), burning 69 (13%) on urination (dysuria), or both - Excessive thirst 65 (12%) - Severe joint pains 58 (11%) - "Bloat" 57 (10%) - Fluid retention and leg swelling 20 (4%) - Increased susceptibility to infection 7 (1%) According to researchers and physicians studying the adverse effects of aspartame, the following list contains a selection of chronic illnesses which may be triggered or worsened by ingesting of aspartame (Mission Possible 1994)*: Brain tumors Multiple sclerosis Epilepsy Chronic faigue syndrome Parkinson's Disease Alzheimer's Mental retardation Lymphoma Birth defects Fibromyalgia Diabetes *Note: In some cases such as MS, the severe symptoms mimic the illness or exacerbate the illness, but do not cause the disease. Both the U.S. Air Force's magazine "Flying Safety" and the U.S. Navy's magazine, "Navy Physiology" published articles warning about the many dangers of aspartame including the cumlative deliterious effects of methanol and the greater likelihood of birth defects. The articles note that the ingestion of aspartame may make pilots more susceptible to seizures and vertigo (US Air Force 1992). Recently, a hotline was set up for pilots suffering from acute reactions to aspartame ingestion. Nearly 1,000 pilots have reported symptoms including some who have reported suffering grand mal seizures in the cockpit due to aspartame (Stoddard 1995b). The danger to pilots of tunnel vision, blurred vision, seizures, vertigo and other serious adverse reactions, who may ingest large amounts of aspartame products during flight, are so great that articles and letters warning about aspartame have appeared in many aviation-related journals including The Aviation Consumer (1988), Aviation Medical Bulliten (1988), Pacific Flyer (1988), CAA General Aviation (1989), Aviation Safety Digest (1989), General Aviation News (1989), Plane & Pilot (1990), Canadian General Aviation News (1990), National Business Aircraft Association Digest (NBAA Digest 1993), International Council of Air Shows (ICAS 1995), Pacific Flyer (1995) and a paper warning about aspartame was presented at the 57th Annual Meeting of the Aerospace Medical Association (Gaffney 1986). Well over 7,000 citizens have submitted adverse reaction reports to the FDA since 1982 (DHHS 1993b, DHHS 1995). These reports detail well over 10,000 complaints of 92 different symptoms, many of them very serious. Many more people may have called the FDA to report adverse reactions only to get turned away. James Turner, Esq. had this to say about the FDA not accepting adverse reaction reports in his testimony before the U.S. Senate (Turner 1987): Mr. Turner. We have numerous instances of people calling the FDA and sayings, "We feel there is a connection. What information do you have?" and the person who answered the phone that they are speaking to telling them there is no connection between NutraSweet and side effects and not taking any further information. We have reported this to the FDA and discussed it with them, and I believe it is very important to understand--my understanding when we finished that meeting was they were going to correct that process by having all NutraSweet calls referred to an appropriate official, so that any suggestion that the number of complaints received prior to August of 1987 when we met with the FDA indicates all the calls that were received by FDA is an inaccurate presentation. Senator Metzenbaum. Can you document that statement for the Committee? Mr. Turner. We have individual statements that we can provide for the record, that is correct. Senator Metzenbaum. And has the FDA followed up? Mr. Turner. We are unclear. The Commissioner said this morning that he had undertaken steps to improve that system. However, since the August meeting there have been instances of individuals calling the FDA and then being referred to the AIDS hotline. Senator Metzenbaum. To the what? Mr. Turner. The AIDS hotline. When the AIDS hotline was answered, the individual said, "We are taking the NutraSweet calls because we don't get enough of them now to have an independent hotline for NutraSweet." Senator Metzenbaum. You have got to be kidding. Mr. Turner. I am not kidding. That is an event that occurred. We are still having communications with the FDA to straighten out the collection. The important point is that the collection system is getting a small number of the cases that occur. They are getting a small number of the cases that actually know enough to call the FDA at all. There are many other people who do not call the FDA. For example, these individuals here have not called the FDA and launched complaints. FDA officials believe that as little as 1% of the serious adverse drug reactions are reported to the FDA (Kessler 1993). Most physicians are aware of the Adverse Reaction Monitoring System (ARMS) and are required by law to report adverse drug reactions. The lay public is generally unaware of ARMS and much less likely to report adverse reactions to the FDA. In addition, most people would not know enough to link their acute reactions and chronic health problems to aspartame. In the unlikely event that they report the adverse reaction to their physician, there is no guarantee that it will be forwarded to the FDA. The reporting rate may be lower than 1% for the following reasons. a. There is no requirement that adverse reactions to food additives be reported. b. The reporting rate cited above applies to serious adverse reactions. The FDA has stated that, "What should be reported are those cases in which the physician suspects that an FDA-regulated product was associated with a serious outcome -- death, a life-threatening condition, initial or prolonged hospitalization, disability, or congenital anomaly, or when intervention was required to prevent permenent impairment or damage." (Kessler 1993) Therefore, the reporting rate for all adverse reactions to aspartame is much likely lower than 1%. c. Many physicians do not take such reports seriously having been told that aspartame is "safe" by the FDA and AMA. d. It is often very difficult for a comsumer to link advese reactions to aspartame because many of the adverse effects are either delayed and/or gradual damage from prolonged use. Immediate reactions such as headaches and asthma are more easily linked to the culprit. Using the FDA's own calculations on actual as opposed to reported reactions, well over 700,000 persons are likely to have experienced adverse reactions from aspartame since 1982. Of course, some unknown percentage of these adverse reactions may have been actually caused by something other than aspartame. However, anyone who has taken the time to read the countless chilling first- and second-hand accounts of severe acute and chronic health problems caused by aspartame poisoning will be hard-pressed to dismiss these reactions, "out-of-hand" as is done by the FDA. I have personally received several first-hand accounts via electronic mail of aspartame poisoning. The FDA and NutraSweet claim that the number of reported adverse reactions have declined substantially since the mid- 1980s (Pauli 1995, Butchko 1994). Adverse reaction figures provided by the FDA are suspect as you will see in the "FDA Response" chapter. The Aspartame Consumer Safety Network (ACSN) has received over 7,000 adverse reaction reports since July 1987 (Stoddard 1995b). The ACSN does not place advertisements asking people to report adverse reactions. People hear about the ACSN by word-of-mouth or from news reports. According to the ACSN, adverse reaction reports to their organization have been increasing every year since 1987. The president of the ASCN, Mary Nash Stoddard states that, increasingly, the callers reporting health problems due to aspartame ingestion say that they know that the FDA does not care about the health problems caused by aspartame and would therefore not bother calling them to report their adverse reactions. The ACSN and other persons taking adverse reaction reports generally do not encourage people to waste their time by calling the FDA, but instead, encourage others to warn their friends and family about the dangers of aspartame. Over the years, the public has, to a large extent, lost faith in the FDA and that is why adverse reaction reports to them have decreased. Many of these accounts are accessable to the public in various books, articles available from the Aspartame Consumer Safety Network, P.O. Box 780634, Dallas, Texas 75378, (214/352-4268). A few selections follows: a. One of the many accounts from "Aspartame (NutraSweet): Is It Safe?" by H.J. Roberts, M.D. (Roberts 1990a). "A 59-Year-old forester had his initial seizure during March 1984. He was consuming three packets of an aspartame tabletop sweetener and up to eight glasses of an aspartame soft drink daily. He then suffered two convulsions in July 1984 after unknowingly ingesting aspartame. Severe convulsions recurred in March 1985-- again after taking aspartame in an unrecognized form. His wife described their ordeal when he went on a business trip during July 1985 to evaluate timber. 'It was a hot day and a tiring trip, so he bought two cans of a soft drink which he did not realize had changed to aspartame from saccharin that week. He drank them, and later on the way home stopped and drank two glasses of punch which we later found out was made from aspartame. When he got home at 7 p.m., he wouldn't eat any dinner and was cranky and tired, and went right to bed. At about 5:30 a.m., I was awakened by this roaring sound. He was having another violent convulsion . . . he dislocated his shoulder and was in lots of physical pain. I asked the doctor if this didn't prove that it was the aspartame causing his convulsions. He said "Maybe," I said, "Shouldn't someone write the aspartame company and tell them what had happened?" All he said was, "Yeah, you do it." We asked to see a neurologist. He was even less interested in aspartame . . . A week later, we went out to dinner at a local restaurant with friends. While we had a cocktail from the bar, he ordered a regular soft drink. They evidently used the nozzle with the brand's aspartame drink . . . We came home and went to bed. About 2:30 a.m., he went into the first of seven consecutive convulsions.'" [Note: There have been hundreds of reported cases of seizure linked to aspartame and probably many times more unreported and undiagnosed cases.] b. One account of a case of extremely high phenylalanine levels caused by aspartame was recently published the the "Wednesday Journal" in an article entitled "An Aspartame Nightmare." John Cook began drinking 6 to 8 diet drinks every day. His symptoms started out as memory loss and frequent headaches. He began to crave more aspartame-sweetened drinks. His condition deteriorated so much that he experienced wide mood swings and violent rages. Even though he did not suffer from PKU, a blood test revealed a phenylalanine level of 80 mg/dl. (Normal fasting phenylalanine levels are usually below 3 mg/dl.) He also showed abnormal brain function and brain damage. After he kicked his aspartame habit, his symptoms improved dramatically (Mullarkey 1994b). c. From Letters to the Editor in local Atlanta publication (EHSA 1994): "My 3 year old daughter had a seizure while drinking soda sweetened with NutraSweet. Now we find out NutraSweet has a reputation of causing seizures and brain tumors. "In the "Journal of Advancement in Medicine, Vol. 4 #4, 1991, Dr. H.J. Roberts reports high incidence of brain tumors in rats after the experimental administration of aspartame. He warns there is an unacceptably large number of aspartame-related seizures reported to the FDA and to him, this warrents an 'imminent public health hazard.' "Where is the FDA warnings of fatal diseases caused by consuming NutraSweet? Searle and Monsanto who market and make the venom are selling an unlabeled poison that can kill our babies." . . . . --------------- "Aspartame killed my wife. No words can express the agony and horror sweet Joyce endured. This poison destroyed her brain, ravaged all her organs and blinded her. She died at age 46 in 1991. "When we filed suit we were harassed and threatened. Our gung-ho attorneys with a medically documented case suddenly seemed scared away. The case had to be dropped. Joyce deteriorated so quickly she would not have been able to participate in the legal proceedings anyway. "Don't listen to the paid Judas-goats and TV celebrities who say its safe. Save your life and those you love, and avoid the grief I endured. The makers of this poison considered her death an acceptable cost of business. I'm a man without a wife because the NutraSweet Company is a business without a conscience. April is Anti-Aspartame month. Take dead serious the warnings you will hear. The life you save may be your own." d. In a statement concerning the use of products containing aspartame by persons with diabetes and hypoglycemia, Dr. Roberts states (Roberts 1994): "Unfortunately, many patients in my practice, and others seen in consultation, developed serious metabolic, neurologic and other complications that could be specifically attributed to using aspartame products. This was evidenced by: "The loss of diabetic control, the intensification of hypoglycemia, the occurrence of presumed 'insulin reactions' (including convulsions) that proved to be aspartame reactions, and the precipitation, aggravation or simulation of diabetic complications (especially impaired vision and neuropathy) while using these products." "Dramatic improvement of such features after avoiding aspartame, and the prompt predictable recurrence of these problems when the patient resumed aspartame products, knowingly or inadvertently." "I regret the failure of other physicians and the American Diabetes Association (ADA) to sound appropriate warnings to patients and consumers based on these repeated findings which have been described in my corporate-neutral studies and publications." There are countless other accounts of both minor and serious health effects from aspartame available for persons who are seriously interested in investigating the issue. Many of these people rechallenged themselves as many as ten times before finally believing that aspartame was causing their problem (Roberts 1990a, page 73).The fortunate individuals are those who react badly to aspartame and then avoid all products that contain it. The unfortunate individuals are those who either a) have health problems which they do not realize are caused or contributed to by aspartame, or b) do not have immediate reactions to aspartame and then continue ingesting it -- not realizing the silent long-term damage that it may be causing. I suggest starting by reading the selection of accounts in the book, "Aspartame (NutraSweet): Is It Safe?" by H.J. Roberts, M.D. Dr. Roberts does an excellent job presenting an overview of the science of aspartame and case histories from his epidemiological study. One critic (Rolla 1990) tries to attack the book by comparing it to a journal article, which it is not. It is a book for a general audience and scientists alike. Rolla also suggests that the data be presented to a scientific journal first. Roberts (1988) did publish the epidemiological study two years before the book was published. The information collected by Dr. Roberts from persons who have had health problems from aspartame is similiar to the FDA or any researcher collecting data on case histories. This should be encouraged. Presenting this data to the general public was a great service as the FDA did not release this type of data, so the general public was being kept in the dark about the health problems linked to aspartame. Now that the FDA is no longer interested in recording adverse effects from aspartame (Food 1995), information such as that kept by Dr. Roberts becomes even more important. Two legitamate questions are often brought up about adverse reactions to aspartame: a. "Aspartame doesn't cause problems for me/my friends even after several years of ingestion. Therefore it is not dangerous for me. Right?" Wrong! Reactions to aspartame or to the individual breakdown products of aspartame have been shown to vary considerably from person to person. I have seen many people tolerate cigarettes for many years, or many years of a poor diet (i.e., high fat, junk food, etc.) or a poor lifestyle even though they are silently doing damage to the body. But the negative effects will catch up with most of these people. The same is true for aspartame. Some people experienced severe reactions soon after they began ingesting it. For many others, serious reactions began with a few years of use, still more people are experiencing serious health problems from 5 to 10 years of use. Not unlike the cigarette and lung cancer connection, once the damage is done from years or decades of ingesting aspartame, there may be little that can be done to reverse the damage. The damage is often slow and silent. For example, regular use of aspartame use has changed the brain chemistry in some people. This can be a causitive or contribuatory factor in many serious chronic illnesses. It is my understanding that coal miners used to use canaries in the mines to check the air quality before deciding whether to go in. If the canary died, it was an early warning signal that the air quality was dangerous. The people who are experiencing serious health problems from aspartame after only a relatively short period of use (i.e., 5 to 10 years of use compared to a lifetime of use) are our canaries giving us a warning that something is seriously amiss. Since aspartame has only been used for a very short period of time in significant quantities (i.e., since ~1987), I strongly suggest that those who would consider a lifetime of use of this neurotoxin to please carefully weigh these early warning signals. b. "I use aspartame and don't have disease xyz, therefore aspartame doesn't cause disease xyz." A corollary is, "I had disease xyz before I began using aspartame, therefore it doesn't cause disease xyz." Diseases and especially syndromes can often have multiple causes or contribuatory factors. Persons with diabetes, for example, can suffer eye damage from retinopathy. They can also suffer eye damage from long-term aspartame use or from some combination of these two (or more) contribuatory factors. (Examples will be given later.) Due to the complex nature of what causes many diseases and due to the fact that patients and physicians are nearly force-fed innaccurate NutraSweet PR, the overwhelming majority of people will not connect their illness to the medium- to long-term damage from aspartame unless they permanently get it out of their diet. They may incorrectly assume that their illness is "fate" or that their worsening symptoms are part of the "normal" progression of their illness. Even in the cases where aspartame is not one of the major causitive factors of an illness, it is absolutely crucial to remove it from the diet -- at least for those people who have any concern for their health now and in the future. B. Science Throughout the article there are citations of hopelessly flawed studies funded by the NutraSweet Company (owned by Monsanto Company) or organizations with financial ties to the NutraSweet Company. In addition, there are points made and values quoted which do not match what is listed in the references. I will take each area one-by-one to point out some of the more obvious mistakes. 1. By-Products and Breakdown constituents From the article: "Let's begin the safety question by examining aspartame's components: aspartic acid, phenylalanine, and methanol. This is an inaccurate picture of the chemical composition of aspartame-containing products at the time of consumption. Aspartame is created from aspartic acid, phenylalanine, and methanol to form the chemical, L-aspartyl-L-phenylalanine methyl ester. However, what is consumed is much different than what was created in the laboratory. Aspartame in Solution --------------------- As soon as aspartame is dissolved in liquid is becomes unstable and begins to break down into its individual components as opposed to keeping a single stable chemical structure. In addition, aspartylphenylalanine diketopiperazine begins to form. (Note: There are different forms of diketopiperazines (DKPs), but to simplify terminology, we will, from now on, refer to aspartylphenylalanine didetopiperazine simply as "DKP.") The rate of breakdown is dependant upon several factors, mainly temperature and pH (Stamp 1989a). G.D. Searle, the company which originated aspartame, conducted their own stability research and forwarded their results to the FDA as part of the effort to get aspartame approved in carbonated beverages (Federal Register 1983). According to the information provided by G.D. Searle, when carbonated beverages are stored for eight weeks at 68oF (20oC), 11-16% of the aspartame will break down into various chemicals such as aspartic acid, phenylalanine, and significant amounts of DKP. (The breakdown into free methanol -- wood alcohol -- occurs at higher temperatures, and otherwise, always occurs in the small intestine after ingestion.) At 86oF (30oC) for eight weeks of storage, 38% of the aspartame will break down into its components. At 104oF (40oC), over 50% of the aspartame stored for nine weeks will break down forming large amounts of DKP, methanol and free amino acids. In 1983, the National Soft Drink Association (NSDA) drafted a document objecting to the use of aspartame in soft drinks (NSDA 1983). In that document they described in detail the many mistakes that were made by G.D. Searle when testing for aspartame's by-products and breakdown constituents. A selection of problems found by the NSDA follows: a. "Only in the cases of APM [aspartame] and DKP did Searle use high pressure liquid chromotography (HPLC). For the other four known principal breakdown products, Searle used thin-layer chromotography (TLC). HPLC is a far superior analytical method relative to TLC and numerous HPLC methods exist for the detection and quantification of amino acids. . . . The unfortunate and inexplicable choice of an inferior analytical technique, when superior and recognized methods are available, has resulted in inadequate characterization of [aspartame's] decomposition products." b. "Aside from its choice of TLC over HPLC, the anaylses conducted by the petitioner [Searle] to identify and quantify the breakdown products of [aspartame] in soft drinks are plagued by numerous significant deficiences which result in clear and unmistakeable inadequacies in the detection and quantification of the major decomposition products of [aspartame] in soft drinks." [The NSDA goes on to list six major deficiencies in Searle's HPLC testing procedure and analysis.] c. "Likewise, the TLC analyses are deficient (these deficiencies are in addition to the inherent limitations of the TLC method). [The NSDA goes on to list three major deficiencies in Searle's TLC testing procedure and analysis.] d. "The inability to account for as much as thirty-nine (39) percent of [aspartame's] decomposition porducts is significant. With such a high unknown factor, judgments about the safety of [aspartame] in soft drinks cannot be made confidently." e. "Searle has not characterized the decomposition products of [aspartame] in soft drinks under temperature conditions to which the beverages are likely to be exposed in the United States." More recent independent tests by Tsang have shown how quickly aspartame can break down in carbonated beverages stored near room temperature (Tsang 1985). One of his tests was conducted on a diet cola with aspartame stored at 71.6oF (30oC). The following are relevant figures for a one liter (1.057 quarts) bottle of diet cola. Sampe 1 Sample 2 Date of 6 Months 36 Months Bottling After Bottling After Bottling Aspartame 550.0 mg* 155.34 mg 19.70 mg L-phenylalanine methyl 0.0 mg** 28.62 mg 13.01 mg DKP 0.0 mg** 135.66 mg 173.28 mg L-aspartylphenylalanine 0.0 mg** 158.31 mg 189.05 mg L-phenylalanine 0.0 mg** 42.22 mg 101.27 mg Total aspartame account for (%) 108.38 % 111.74 % *Amount of aspartame claimed on label of diet cola from Canada. **Trace amounts may be present at time of bottling. Other breakdown chemicals such as free methanol which were not included in the list above, appear in much larger amounts at temperatures over 145oF. It is not difficult to imagine that carbonated beverages being shipped in unairconditioned trucks or trains can be exposed to very high temperatures for significant periods of time. It is obvious that wharehouse and grocery store storage conditions can lead to significant temperatures or long storage times. Many stores have diet sodas stacked outside of the cooler in direct sunlight. Finally, a person, family, or group sometimes purchases large quanities of diet soda for indenfinate storage. The time from when the beverage was created to when it was ingested can be a significant length of time. I beleive that Pepsi is the only brand that stamps their date of expiration on their aspartame-containing products. On April 2, 1995 I saw a bottle of diet Pepsi which had a stamped date of May 23, 1994, 09:45am. Even in bottles where the expiration date has not passed, enough time has often elapsed for a significant amount of breakdown to occur. In their objection to approval of aspartame in carbonated beverages, the National Soft Drink Association addressed the issue of temperature exposure (NSDA 1983): "The range of temperature conditions to which soft drinks are exposed during the summer months in the southern United States is illustrated by a study conducted by the Coca-Cola Company's Corporate Packaging Department in 1976 and submitted to the Consumer Product Safety Commission. (High summer temperatures are by no means limited to the southern states. During the period July 10 to July 24, 1983, for example, St. Louis, Missouri experienced 14 consecutive days of temperatures over 90oF, and 10 days of temperatures of 95oF or greater.) That study shows that during the summer months, soft drinks are often exposed to relatively high temperatures for certain time periods in the course of distribution from the bottling plant to the consummer. High temperatures do, of course, routinely occur in much of the United States, including the southern regions; conditions of storage and distribution for soft drinks can elevate these temperatures significantly. "In summary, the study assessed: (1) warehouse temperatures in Marietta, Georgia and Wichita Falls, Texas; (2) route truck temperatures in Wichita Falls; (3) full sun and outside ambient temperatures in Wichita Falls; and (4) parked car temperatures in Atlanta, Georgia and Wichita Falls. Each of these test environments is known to occur in practice and the tests were performed under actual, as opposed to laboratory, conditions. "Several significant conclusions can be drawn from this study. First, in those situations where the bottled beverage is heated only by conduction from the surrounding air (shaded location in a warehouse or in an automobile trunk parked indoors) the raio of product temperature to the termperature of the surrounding air would be 0.92 to 0.94. In enclosed environments exposed to sunlight, however, ratios much greater than one would be expected. For example, a ratio of product temperature to air temperature of 1.45 was found for a test car parked in full sunlight. In other situations where sunlight was a direct heating factor (e.g., open air service station promotions or open bay delivery trucks) typical ratios were 1.10 to 1.15. "The effects of these ratios on product temperature are domonstrated by using summer temperatures for Phoenix, Arizona, where the average daily high in July is 40oC (104oF). During July in Phoenix, a soft drink in full sunlight could reach a temperature of 49oC (120oF) (104oF x 1.15). The same product in a car parked in full sunlight could reach 66oC (151oF) (104oF x 1.45); soft drinks in a warehouse with an ambient temperature of 110oF could reach temperatures of 38oC (101oF) to 39oC (103oF) (0.92-0.94 x 110oF). "Overall, the study, considered together with representative historical temperature data show that soft drinks will frequently be exposed to temperatures of 32oC (90oF) to 49oC (120oF). In some cases product temperatures as high as 66oC (151oF) (especially in the southwestern United States) can be reached. "The effects of these high product temperatures on [aspartame] degradation and the formation of degradation products, and the effects of temperature variation (for example, soft drinks displayed at a service station may reach temperatures of 49oC (120oF) for most of the afternoon, drop in temperature overnight, and heat up again during the following day) cannot be determined from the data submitted by Searle to the FDA." When aspartame in liquid is subjected to high temperatures, the breakdown of aspartame and the formation of large amounts of DKP happens very quickly as shown by Prudel (1986). In addition, Boehm and Bada showed that high tempatures can cause racemization of the free amino acids leading to significant amounts of unnatural D-type amino acids--much more than is produced through cooking normal, healthy foods (Boehm 1984). Gaines (1987) also showed that racemization can occur in the breakdown products of aspartame. The health affects of large amounts of these D- type amino acids are not well known. In a statement submitted to the U.S. Senate hearings on aspartame, Dr. Jeffrey Bada had this to say about aspartame decomposition (Bada 1987): "Aspartame, a dipeptide containing the amino acids phenylalanine and aspartic acid, is prone to a number of decomposition/alteration reactions. Dominant are cyclization to the cyclic dipeptide or diketopiperazine [DKP] and stereochemical (racemization) inversion producing the unnatural D- stereoisomers of the amino acids. . . In some instances, however, these reactions are very significant, and the reaction products which are produced are not well-studied as far as their nutritional/toxicological properties are concerned. Some examples where these reactions could be significant are in soft drinks exposed to warm temperatures for prolonged periods and in consumer misuse of aspartame such as in cooking or baking." In an article for the Wednesday Journal, Jeffrey Bada, Ph.D. discusses some of his concerns relating to the chemical rearrangement of aspartame (Mullarkey 1992, page 10): "The chemistry of aspartame is changed when Boiled," says Bada. "There is internal rearrangement of its structure. The L-isomers of phenylalanine and aspartic acid change to unnatural D-isomers which are metabolized differently. How it is metabolized is anybody's guess. "Searle people," Bada Continues, "tend to dismiss stereo chemical inversion as unimportant. Chris Tschanz, director of aspartame clinical research, and Louis D. Stegnik, M.D. of the University of Iowa College of Medicine, visited me and admitted that nobody thought of looking at aspartame the way we did." In 1993, the FDA approved aspartame for use in tea beverages, baked goods and mixes, frostings and toppings (Mullarkey 1994a, page 51). There are many products on the market which contain aspartame and are heated to high temperatures. Therefore, Dr. Bada's comment of aspartame's "misuse" in cooking or baking no longer applies--it is now a condoned use of aspartame. Beta-aspartame is another breakdown product which has been found in aspartame-containing products which may contribute to health problems in some individuals (Lawrence 1987, Stamp 1989b). The fact that it occurs in small amounts does not necessarily mean that it is harmless. It has been shown that aspartame can react with other food additives to form chemicals of unknown health consequences. Hussein showed that aspartame reacts with aldehydes which are commonly found flavor compounds in sodas and chewing gum (Hussein 1984). Cha has shown that aspartame can react with vanillin used in foods (Cha 1988). These reactions are very important considerations. As an example of how additive reactions can cause the formation of toxic substances, researchers tested three different food additives individually on mice. None of the mice reacted negatively. When the three food additives were tested in pairs, the mice became ill. When all three food additives were tested at once, the mice died (Ershoff 1976). Aspartame In Solid Food Products -------------------------------- Graves showed that in a dried and acidified state, aspartame that is heated to 230oF breaks down into its components as described above (Graves 1987). It was also shown that other, previously unknown degredation products are formed when the dried product is heated to high temperatures. This type of aspartame breakdown would occur in baking goods that contain aspartame. Conclusion ---------- Aspartame-containing products which are ingested in the real- world are chemically very different than 98-100% aspartame which is given in laboratory experiments. The large amount of breakdown products such as DKP, free phenylalanine, methanol, and others may play an important role in aspartame's negative health affects. Aspartame's strong tendancy to react with other food ingredients to form unique chemical compounds and the tendancy of the free amino acids to racemize at high temperatures are also very important considerations regarding its toxicity. Please keep this in mind while you read the rest of this review. What people are ingesting in the real world IS NOT the same aspartame as it was originally put into the food, but a very different and possibly much more dangerous toxic chemical soup. 2. Average Daily Intake of Aspartame The article states: "The replacement of all sweeteners with aspartame has been estimated to yield an intake of 867 mg of aspartame/day, which translates to only 87 mg of methanol." Before we can discuss aspartame toxicity, it is crucial to set the record straight regarding aspartame intake. The statement in the article has three problems: a. The increasing use of aspartame has not lead to a decreased use in caloric sweeteners. According to the U.S. Department of Agriculture, the per capita consumption of aspartame quadrupled between the years 1983 and 1988 (USDA 1988). Since that time, the use of aspartame has continued to increase. Dr. H.J. Roberts reported on Wall Street Journal articles which stated that "the diet beverage market was increasing at a rate of 20-25% annually" and that "consumers began drinking up to six times as many diet drinks as those using sugared sodas." (WSJ 1988, WSJ 1989) Gregory Gordon wrote in a UPI Investigation that "Roy Burry, an analyst with Kidder-Peabody, Inc., said the exploding diet market now accounts for 24 percent of soft drink sales, compared with 10 percent in the late 1970s, and is growing at 20 to 25 percent a year (Gordon 1987, page 484 of US Senate 1987). From 1982 to 1988, the per capita consumption of caloric sweeteners jumped from 123.2 pounds to 133.5 pounds per year. Therefore the increased use of aspartame has not decreased the use of caloric sweetener products in the United States (USDA 1988). b. Studies have shown that when their diet is not closely monitored, many people use artificial sweeteners in addition to sugar products and not instead of sugar products (Chen 1991, Stellman 1986). Therefore, an increased use of aspartame will not necessarily alter the sugar-craving feeding behavior of the majority of persons. If they consume a non-sugar, aspartame- containing beverage at one point in the day, they will simply make up for the lack of sugar at some other point in the day. Some studies have shown an increased consumption of sugar due to aspartame (Blundell 1986). In fact, Stellman showed that outside the confines of the highly structured, supervised environment, the subjects he surveyed who choose to use artificial sweeteners actually gained weight. Roberts (1988) showed in his survey of people outside of the laboratory that 5% of the people reported adverse reactions had extreme weight loss when using aspartame and tended towards anorexia. He also noted that 6% of the respondants had a unexplained weight gain which averaged 19 pounds! c. Since diet products with aspartame have few calories and since many people have been conned into believing that they are safe, a significant percentage of people would likely "throw caution to the wind," by drinking large quantities of diet soft drinks and eating large quantities of other products with aspartame. This is something that they would not be as likely to do with high-calorie, sugar-containing products. The NutraSweet Company has been trying to convince people that persons who ingesting aspartame regularly ingest only 1-3 mg/kg (of body weight)/day of aspartame (Butchko 1991, Abrams 1992). This is based on surveys and diaries of consumers. What these surveys do not mention is that aspartame-containing products are often ingested as part of snacks and that people often forget what snacks they've eaten. This was aptly described by Dr. Richard Wurtman of MIT in a meeting with FDA officials on April 21, 1986 (Lisa 1994, page 201): "[NutraSweet's estimates of current use] show, among other things, that people consume less aspartame in the summer than in other months, a finding which violates good sense and reason. (This probably reflects the fact -- affirmed in our laboratories at MIT -- that people have much more difficulty accurately remembering snack than meal intakes . . . and most of the aspartame in the American diet comes via cold beverages and other snack foods.)" Another set of similar surveys shows that persons living in Canada (7-day survey) have more than 2.5 times the daily intake of aspartame than persons living in the U.S. (at the 90th percentile level of consumption). This is ridiculous because aspartame ingestion (the bulk of which comes from cold diet beverages) in warm climates would almost certainly be much larger than in cold climates. In addition, it appears that it is mathematically impossible for Canada to have an equal per capita aspartame consumption let alone a much greater per capita consumption. Aspartame net sales outside the U.S. amounts to only 10% of all net sales (Monsanto 1994) Canada's population is 10.8% of the U.S. population (CIA 1994). Therefore, Canada's per capita intake of aspartame cannot possibly be even equal to that in the U.S., even in the extremely unlikely scenerio where all aspartame sold outside the U.S. is sold only to Canada. (According to figures provided by the NutraSweet Company, the percentage of regular aspartame users in the United States and Canada are approximately the same (Farber 1989, page 56, Butchko 1991). Another preposturous claim can be seen in a paper by Butchko (1991). In this paper aspartame consumption for 6-12 year old children was shown to decrease significantly from 1984 (the year after aspartame was approved for use in carbonated beverages) to 1989 despite nearly tripling the sales of aspartame from the middle of 1984 to 1989. (USDA 1988, Monsanto 1990). By the time this survey began the percentage of regular aspartame eaters in this age category was approximately 25% (Abrams 1991) according to NutraSweet Company figures. The NutraSweet Company admits that the use of aspartame had not risen to over 50% of the U.S. population at that time (Farber 1989, page 56). Therefore, an increase in the percentage of regular aspartame users could not have possibly accounted for the bulk of the increase in sales. Who are they kidding!? It shows that these surveys cannot be trusted to show anything close to accurate figures. Perhaps another reason the average daily intake of aspartame from these surveys is so low is due to the way that the amount of aspartame ingested is calculated. For example, Abrams (1991) points out that what is recorded on these surveys is not the amount of aspartame ingested, but only "the number of times an APM [aspartame] containing item of food was eaten on that day by that person." This value is then multiplied by the "average number of grams per eating occasion of that food for a person of that age and sex group" to give the total number of milligrams of aspartame ingested. However, the "average number of grams per eating occasion of that food for a person of that age and sex group" is drawn from a 1977-1978 USDA National Food Consumption Survey. Therefore, the calculations for the total milligrams of aspartame ingested is based on an old survey which is probably equally inaccurate as far as snack food ingestion goes and is most likely out of date. For example, these calculations assume that the average person would ingest the exact same amount of soft drink or diet food per item 1977 as they would in 1994. With the skyrocketing popularity of one- and two-liter bottles of soft drinks and the marketing push for diet foods, this is a ridiculous assumption. By making this assumption, NutraSweet are skewing the per capita intake figures and are using this "information" to justify studies on very small amounts of aspartame. What the NutraSweet tries to show with flawed studies and surveys is often contradicted by other studies which they fund or by statements made by their representatives. In 1976, Frey showed that children who are 7 to 12 years old can have an aspartame intake anywhere from 35 mg/kg to 76 mg/kg per day when aspartame-containing snack food is notrestricted (Frey 1976) (Note: No aspartame capsules were administered to the 7-12 year-old children. Only the 13-21 year-old children received capsules.). Three studies on obese individuals showed that their aspartame intake averaged 20 mg/kg per day (ranging from 8 to 36 mg/kg per day) (Porikos 1984). The Frey study and the three studies by Porikos monitored aspartame intake much more closely than the surveys often quoted by NutraSweet researchers. Those surveys relied on the ability of people to remember their snacks. In an article from Science Times, Jane E. Brody states the following (Brody 1985): "The drug agency has set an allowable daily intake of 50 milligrams of aspartame per kilogram of body weight, and the agency predicted that actual average use would run around eight to ten milligrams. According to Dr. Gaull of Searle, levels of use found in a national survey last spring showed that the average was then already twice that--19 milligrams--and the maximum level consumed by 'aspartame abusers' was 28 milligrams. A United States attorney representing the F.D.A. said in court last month that average consumption is now 30 milligrams and that many consumers are above the 50 milligrams maxiumum suggested." Farber gave an example of what a typical aspartame consumption may be for a child (Farber 1989, page 146): "An 8-year-old of 20 kg, might eat the following: Cereal 250.0 mg Soda 200.0 mg Milkshake 350.0 mg Ice Pop 250.0 mg Total 1,050.0 mg of aspartame "This would equal 52.5 mg/kg of aspartame consumption....' [Note that even for a 60 kg adult, the above-listed example would amount to over 17 mg/kg per day.] On a hot Summer day, the child may ingest the aspartame listed above and several more carbonated beverages. There may be many children who are ingesting a full 2-liter bottle of pop during an active Summer day (1100 mgs. of aspartame). On top of that ingestion, there may be Jello, cereal, gum, and many other aspartame-containing foods. It is important to note that all aspartame-containing products of the same type do not contain the same amount of aspartame. For example, a one liter bottle of diet cola averages aproximately 560 mg of aspartame. However, orange soda contains as much as 930 mg of aspartame per liter (Federal Register 1984). In addition, the Tsang (1985) study showed that there may be an addition 10% or more amount of aspartame in the product than what is claimed by the manufacturer. Neuroscience researcher and Professor of Medicine at the University of California, Dr. William Partridge testified about the intake of aspartame before the U.S. Senate (Pardrige 1987): "The first question is the dosage problem. We are led to believe by the FDA this morning that the typical consumer will have 2 to 4 milligrams per kilogram of aspartame per day; that the 99th percentile intake is 34 milligrams per kilograms per day; and that the advisable daily intake or ADI is 50 milligrams per kilogram per day. "Now, the layperson sitting in the audience is really in no position to analyze these esoteric numbers. But if we put it in a different context and recognize that 50 milligrams per kilogram per day is equal to 5 servings of NutraSweet per 50- pound body weight, we can see that children, owing to their reduced body weight, are at a great risk for overconsumption of NutraSweet. "All one has to do in t his room is look up at that chart and ask yourself if a 50-pound or 60- pound 7 year-old is going to consume 5 or 6 servings of that per day. If they are, then they have consumed 50 milligrams per kilogram per day, or the advisable daily intake. "Now, an 11-year[-old] study in the literature has already shown this, that the average 7-to-12-year- old, when made freely available to products like that, consumes 5 servings per 50-pound body weight per day, and up to 77 milligrams per kilogram per day." In the National Soft Drink Association's draft objection to use of aspartame in carbonated beverages it was stated (NSDA 1983): "FDA relied upon an intake value of 34 mg/kg/day in assessing the possible risks of aspartame, describing that level as the '. . . highest obtained from any estimate of potential consumption and exceed[ing] the 99th percentile consumption (25 mg/kg) for all age groups . . .' 48 Fed. Reg. at 31377. For a 30 kg child, however, it would not be unualual for that level to be achieved or, in terms of the effect on plasma PHE (phenylalanine) levels, even exceeded. For example, if a 30 kg child consumed on a warm day after exercise approximately two-thirds of a two- liter bottle of soft drink sweetened soley with aspartame, that child would be consuming 700 mg of aspartame, or approximately 23 mg/kg. This alone roughly equals what FDA considered, the 99th percentile consumption level. If during the day this child consumed other aspartame-sweetened products, the exposure level could quickly [reach] FDA's so called 'loading dose' of 34 mg/kg. 48 Fed. Reg. at 31377." Had the child in the above example consumed two-thirds of a two-liter bottle of aspartame-sweetened orange soda, the values could be as high as 1240 mg of aspartame or 41.3 mg/kg/day for a 30 kg child. Another way to look at intakes is to look at what a child may ingest in a single sitting. At the popular convenience store chain, 7-11, the drinks, "Big Gulp" and "Super Big Gulp" are popular items for both children and adults. A 30kg child purchasing a Big Gulp (32 ounces) of diet soda would ingest 510 mg to 846 mg of aspartame depending upon whether it was diet cola or diet orange. This works out to between 17 mg/kg or 28.2 mg/kg of aspartame in a single sitting! The same child purchasing a Super Big Gulp of diet soda would ingest 700 mg to 1162 mg of aspartame. This works out to 23.3 mg/kg or 38.7 mg/kg of aspartame in one sitting! As an adult who plays basketball outside in the warm whether, I know many people, including myself who can easily drink twice the amount of liquids as found in a Super Big Gulp in one sitting in order to prevent dehydration. What is generally agreed upon when discussing the intake amounts of aspartame is the following: The majority of aspartame users ingest much less than the FDA's Acceptible Daily Intake (ADI). When plotting milligrams per day of aspartame ingested against the percentage of U.S. population, a smaller percentage of the population will ingest the largest amounts. However, a regular, smaller dose of a neurotoxin such as aspartame is not necessarily safe and certainly not health- building. Dr. Roberts found many serious adverse effects from ingestion of aspartame at levels many times lower than the FDA's ADI (Roberts 1990a, page 71-72). The use of aspartame for a lifetime at even very small levels is foolish in my opinion. Looking a studies I have seen in the literature as well as USDA figures for artificial sweetener usage, I would estimate that the average person in the U.S. who ingests aspartame regularly ingests approximately 8 mg/kg per day. This is based on the following estimates: - Approximately 35% of the U.S. population (81 million people -- CIA 1994) are regular aspartame "eaters." Heybach (1988) showed that in adult women (a population likely to have a higher percentage of regular aspartame users than the general population), only 25% ingested aspartame in the survey. Since the survey was only a single day, I will give the NutraSweet Company the benefit of the doubt and assume 35% regular usage for the general population. The FDA submitted an aspartame intake survey to the U.S. Senate which admited that approximately 35% of the survey participants were regular consumers of aspartame (FDA PMS 1987). I do not believe the contrived NutraSweet Company estimates that more than 50% of the U.S. population uses aspartame regularly. - The average weight of regular aspartame users I estimate to be 50kg. This includes many thin women, adolescents, children, and infants who would tend to bring the average way down. - The amount of aspartame used in the U.S. in 1995 I estimate is 28 million pounds. McNamara (1995) stated that 20 million pounds will be sold in the U.S. in 1995. The author probably got that figure from the NutraSweet Company and does not realize that every "fact" spewed out by this company is suspect at best. Figures from the USDA (1988) showed that 7 million pounds were consumed in 1984 and approximately 17.1 million pounds were consumed in 1987 Given that aspartame is now in over 5,000 junk food products worldwide (Geha 1993, Trefz 1994) and was only in hundres of products in 1987, and given that diet beverage sales have increased tremendously in the last 8 years, an estimate of 28 million pounds is quite reasonable (This estimate is probably too low. The actual figure may be as high as 35 million pounds). It is possible to determine the average usage of aspartame in regular eaters using the following formula: (lbs * 1,000,000 mg/kg) / (2.2 kg/lbs. * days/year * # of eaters * kg/person) = 8.6 mg/kg/day for regular eaters. I realize that this is an estimate, but given how ridiculous the "results" of NutraSweet-connected surveys are, an estimate is better than nothing. I believe that at least 10 percent of regular aspartame users ingest at least 20 mg/kg per day. This may amount to over 8 million people in the U.S. I would estimate that nearly 1 percent of aspartame users ingest at least 50 mg/kg per day. This may amount to over 800,000 people. This group would most likely be mostly made up of children and young, adolescent girls due to their low body weight and high intake of junk foods. For many of these people, the warm and hot weather intake will far exceed their Winter intake, such that a person ingesting 20 mg/kg per day in the Winter may ingest 40 mg/kg per day in the hot Summer months. According to Dr. Woodrow Monte, Director of the Arizona State University Food Science and Nutrition Laboratory, a significant number of people in Arizona drink as much as two or three liters of diet soda every day during the Summer (Monte 1995). Even if we accept the FDA's projection that only 1% of the regular aspartame users will consume more than 34 mg/kg/day of aspartame, that still may amount to over 800,000 people. While the national average may be lower than 34 mg/kg/day of aspartame, there are undoubtedly several hundreds of thousands of people who are consuming well over 34 mg/kg/day of aspartame, especially on hot Summer days. NutraSweet researchers sometimes use the following ploy to try and convince gullible listeners that people cannot ingest over 20 mg/kg/day or approach a level of 50 mg/kg/day (despite their own studies which prove them wrong). They compare the amount of one single product that would need to be ingested by an adult male in order to reach these high levels (e.g., Rowen 1995). For exampe, they might say that it takes 100 packets of Equal or 19 cans of diet soda for a 70kg man to reach a dose of 50 mg/kg. First of all, not everyone is a 70kg man. Many people are 50kg women or 20-30kg children where the amount of aspartame required to reach a dose of 50 kg/mg is much less. Secondly, many people who put themselves at risk by ingesting aspartame do so using a wide variety of aspartame-containing "food" products such as soda, puddings, cereal, hot chocolate, coffee, tabletop sweeteners, gum toppings, supplements and pharmaceuticals, fruit drinks, etc. People abusing themselves with aspartame in this way can easily ingest hugh doses. Finally, even doses of only a few mg/kg/day is not safe in the long run. Some researchers try to argue that they can use much less than the current FDA Acceptable Daily Intake (ADI) in their experiments as long as they use a test dosage well above the average intake of aspartame as deterimined by these (flawed) surveys. Stegink states the following (Stegink 1989): "Initial consideration of these projected intakes might lead one to question their validity since 12 oz of aspartame-sweetened beverage ingested by a 27-kg 8-year-old child would account for 7.4 mg aspartame/kg body weight. However, when beverage intake data are examined, the projected aspartame intake values are consistent with these data. For example, Morgan et al reported that 7- to 8-year- old children ingest, on average 6.0 ± 4.2 oz soft drink daily (mean ± SD; value includes both regular and diet beverage) (Morgan 1985). Thus, an average 27-kg 8-year-old child would ingest 3.7 mg aspartame/kg body weight daily if all 6 oz of beverage were sweetened with aspartame. A 27-kg child ingesting beverage at 2 SD above the mean (approximately 97% of expected values) would ingest 14.4 oz of beverage. This would provide 8.9 mg aspartame/kg body weight if all beverage consumed was sweetened with aspartame. Therefore, young children would have to drink unusually large quantities of beverage to ingest much larger quantities of aspartame." What Stegink neglects to mention is the following: 1. The study cited by Stegink (Morgan 1985), does not take into account that, as Dr. Wurtman stated, snacks are commonly forgotten in daily food surveys so that the average ingestion of soft drinks would likely be much greater. 2. The study cited by Stegink uses data from a three-day survey instead of the more accurate seven-day survey. 3. The study cited by Stegink was published in 1985. This study was an evaluation of data from the 1977-78 Nationalwide Food Consumption Survey. Thus, the data was over ten years old when Stegink cited it and is now over 16 years old! Anyone adult in the U.S. who was not in a coma for the last 16 years knows that soft drink consumption has increased tremendously since the late 1970s. 4. Stegink neglects to mention that there are thousands of products with aspartame and that 7- to 8-year-old children can be ingesting significant amounts from foods and beverages other than soft drinks. 5. While the average intake may be relatively low, although much higher than reported by Stegink and not necessary safe, there are undoubtedly a significant number of 7- to 8-year old children who are ingesting large quantities of aspartame by their own choice or by the choice of their parents to avoid sugar. It is ridiculous to use the "average" (even if it was accurately determined) to judge test amounts of aspartame. Conclusion ---------- NutraSweet-written survey summaries show a negligable increase in daily aspartame consumption since 1983. Aspartame sales has skyrocketed since 1983. Therefore, the numbers from these surveys which are flawed as described by Dr. Richard Wurtman above, do not make any sense and should be ignored until large, well-designed surveys are conducted separate from the influence of the NutraSweet Company. Until that time, estimates of average consumption for regular eaters at 8 mg/kg/day, 20 mg/kg/day at the 90% level, and over 50 mg/kg/day at the 99% level seem quite reasonable. The NutraSweet Company researchers have begun a concerted effort to convince scientists and laypersons that they are testing high doses of aspartame. This is based on consumer surveys. The reality is that a) the surveys are flawed; b) their own studies show subjects ingesting much higher intakes of aspartame than they use in tests; and c) they are often testing using doses significantly below the FDA's Allowable Daily Intake (ADI). Their efforts to test small doses is a big con job. Don't buy into it. What should be used in experiments is double the ADI of real world aspartame. Any argument for using less should be taken as an admission that the ADI is not a safe amount of aspartame. 3. Serious NutraSweet Research Flaws Before we discuss individual studies, it is important to list common and very serious flaws in all of the research funded by NutraSweet. This is by no means meant to be a comprehensive list of flaws -- simply the most common serious flaws. The flaws I will discuss in this section related to studies after aspartame was approved (post- approval). The pre-approval studies bordered on criminally fraudulent activity in my opinion and will be discussed in a later section. a. Test Material In most of the NutraSweet-funded studies, the test material used was fresh, encapsulated aspartame. This is a major flaw for the following reasons: 1. The chemical makeup of the fresh aspartame used is almost 100% pure aspartame and differs significantly from what is being ingested by the general public. This is discussed thoroughly in the "By-Products and Breakdown constituents" section above. This means that DKP, beta-aspartame, free methanol, and other possible breakdown products are not being tested in these experiments. 2. In 1987, Stegink tested the effect of aspartame taken in liquid as opposed to capsules on plasma phenylalanine, phenylalanine/LNAA, tyrosine, and aspartate (Stegink 1987a). The difference was striking. The plasma phenylalanine and aspartate levels rose very quickly to extremely high levels when ingesting the liquid aspartame mixtures, but the plasma amino acid levels only rose moderately when ingesting encapsulated aspartame. While this experiment compared the effect of aspartame in liquid vs. capsules, it did not test real world liquid aspartame-containing products which would contain significant amounts of DKP, methanol, free amino acids, and other possibly dangerous chemicals. The rise in plasma amino acid levels may be even more striking and sudden with such products due to even faster absorbtion. 3. The experiment conducted by Stegink (1987a) showed that capsule administration of aspartame significantly delayed absorption of aspartic acid and phenylalanine. In fact, with liquid administration, the peak amino acid levels were reached within 32 minutes (average), yet capsule administration led to a gradual rise in amino acid levels and took approximately 2.5 times longer to reach much lower peak levels. Not only is the enormous difference in the plasma amino acid spikes important as discussed above, but the sudden spike that occurs in liquid administration that may also be very important. When a substance is gradually absorbed in a way that causes it to be slightly toxic, the body has a chance to adjust and mount a defense. Sudden absorption of single, potentially neurotoxic amino acids does not give the body a chance to mount a defense. It is also very important to note that delaying the absorption of methanol as would happen when ingesting encapsulated aspartame may reduce the methanol toxicity somewhat since food in the stomach, which also delays methanol absorption, seems to reduce methanol toxicity (Posner 1975). It is interesting to note that as early as 1973, the FDA told the manufacturer of aspartame that there is "No pharmacokinetic data . . . on absorption, excretion, metabolism, half-life; nor bioavailability of capsule vs. food additive administration" (Freeman 1973). It wasn't until 1987, 14 years later, that NutraSweet finally got around to testing capsule administration as compared to liquid administration! There was a striking difference as described above. To this day, there has been no tests comparing the administration of various real-world, aspartame-containing products to capsule administration. The large difference in biochemical reactions produced when ingesting real world aspartame-containing products as opposed to capsules given in the laboratory totally negates the results from experiments which used such capsules and found no adverse effects. When using aspartame-containing capsules, 1) much less aspartame gets absorbed (Stegink 1987a), 2) the absorption is much slower causing the increase in blood levels of aspartame by-products to be much more gradual (Stegink 1987a), and 3) other by-products and breakdown constituents do not get absorbed as they do in real-world products (Tsang 1985). Had real-world, liquid products been used, the number and severity of negative reactions due to aspartame would likely have been much greater. b. Test Product Administration In order to test the effects of aspartame on health it is important to simulate the way the product is taken by the general public. Sometimes aspartame is ingested with full meals. More frequently, however, aspartame is ingested by itself (e.g., diet colas) or with a sugary snack. It is important to test both methods of administration. It is obvious that the biochemical effect of the three original components of aspartame, aspartic acid, phenylalanine, and methanol will be much greater when it is ingested separate from a full meal. (This will be discussed in more detail in later sections.) When taking aspartame with meals the following things occur: i) The aspartame will not be absorbed as quickly leading to less of a rise in plasma aspartate and phenylalanine levels; ii) The other amino acids absorbed from the food will keep the plasma aspartate and phenylalanine levels from rising as high as they would normally; iii) The plasma phenylalanine to large neutral amino acid (LNAA) ratio will not be as large due to the LNAA's in the food. (This will be discussed in detail in a later section.); iv) The food may serve as a protective factor reducing the methanol toxicity as will be discussed in the Methanol section. It is obvious that the acute and chronic effects of aspartame ingestion will be slightly less when it is ingested with full meals. All previous experiments that tested aspartame ingestion with full meals, tested the best-case scenerio and not what is most common in the real world. Therefore, all such research of aspartame with full meals should be regarded as interesting, but not very useful. On the other hand, Yokogoshi (1984) has shown that aspartame ingestion with caloric sweeteners significantly raises to phenylalanine/LNAA ratio to even greater heights than by simply ingesting aspartame alone. Even a NutraSweet-funded, short study on healthy persons using a relatively small amount of aspartame showed a significant further increase in plasma phenylalanine/LNAA ratio when aspartame was ingested with a caloric sweetener (Wolf-Novak 1990). However, it is unclear whether the ingestion of carbohydrates along with aspartame renders the phenylalanine part of aspartame more dangerous. Carbohydrate ingestion lowers the levels of Large Neutral Amino Acids (LNAAs) and therefore the neutral amino acid trasport cites may become unsaturated causing a smaller change in brain chemistry than would otherwise happen with the phenylalanine alone. We will discuss this in more detail in a later section. Therefore, not only should more experiments be done using real-world aspartame products on persons not eating full meals, but experiments should be done on the combination of real-world liquid aspartame (at FDA ADI levels or greater) and caloric sweeteners. Only then will we begin to approach what happens in real-world aspartame ingestion. It is important to note, however, that the ingestion of aspartame with sugar reduces the possible negative effects from the aspartic acid part of aspartame (as will be discussed in the Aspartic Acid section). Such experiments (with caloric sweeteners plus aspartame are very useful, but lack of negative effects does not rule out possible negative effects from the aspartic acid or the aspartic acid plus another breakdown product (i.e., synergy). c. Short Experiments The majority of NutraSweet-funded experiments on humans tested aspartame for one day or less. Although there is a wide variation in when adverse reactions begin, it is usually several weeks or months after use begins before adverse reactions are noticed (Roberts 1990a, page 70). After the adverse reactions begin, regular aspartame use usually causes more frequent adverse reactions. Studies which are not funded by NutraSweet are usually much longer because the researchers are actually interested in testing aspartame. A quality study would be at least six months long, and preferably as long as one year or more. This way, the researchers will be testing adverse reactions that occur due to ongoing use of aspartame -- real world use. One to two year experiments would be ideal. James Scala, the former director of Health Sciences for General Foods Corporation said that most of the early NutraSweet research consisted of short-term studies that ignored possible subtle, long-term effects. Pediatrician and Geneticist Dr. Reubon Matalon stated "Let us say cigarettes were invented today, and you give 20 people two packs a day and after six weeks, no one has cancer, would you say that it is safe? That's what they did with NutraSweet." (Gordon 1987, page 486 of US Senate 1987) All single day or single challenge tests, usually conducted by NutraSweet-connected researchers, should be disregarded. No one is claiming that a single ingestion of even real-world aspartame-containing products represents an imminent health hazard. A single dose of aspartic acid, phenylalanine, methanol, DKP, etc., from aspartame is not acutely toxic in the majority of cases. It is the regular use that represents a extreme hazard. These concerns are not addressed in one-day studies. No reputable researcher would try to extrapolate a lack of negative effects from aspartame in a one-day experiment to a declaration of safety for onging use throughout a lifetime. Unfortunately, this is commonly done by some NutraSweet-supported researchers. It should be noted that some very subtle adverse reactions may be noticed in a single day experiment, especially in vulnerable populations. While a much longer test is necessary, any significant adverse reactions after only a single day test should be a cause for extreme concern. On the other hand, lack of adverse reations after only a single day test does not prove anything. d. Small Test Population The smaller the test population, the more difficult it is to get a statistically significant difference in amino acid and methanol/formate levels in the blood and urine. NutraSweet-funded research usually has such a ridiculously small test population that it is virtually impossible to have a statistically significant difference in measurements. This is especially true when this flaw is combined with other flaws such as capsule administration of aspartame. Another way a small test population can be a problem is if a particular symptom (e.g., seizures) appears in a small percentage of aspartame users -- let's say one out of every 100 regular users, then experiments with small numbers of people would usually not have a seizure victim. This problem is called "lack of statistical power" of the studies and will be dealt with in more detail when the cancer issue is discussed. The technique of using ridiculously small test populations helps to guarantee that reactions that are occurring in the general population do not occur in the test population. e. Irrelevant or Faulty Tests There are numerous NutraSweet-funded research projects which used irrelevant and faulty tests to draw their conclusions. An irrelevant or faulty test is useful only for press releases and convincing scientists who are not intimately familiar with the scientific issues surrounding aspartame ingestion. Performing many such irrelevant or faulty tests allows the researcher to proclaim, "Look! We tested aspartame, performed a whole battery of tests, and found no adverse effects!" When the protocol is examined closely, however, it becomes clear that many of these tests were meaningless or conducted improperly. Many of the improper testing methods appear to be deliberately created and used to avoid negative results. There are many cases of such irrelevant and faulty tests. I will discuss some of those when I get into the details of the research cited in the article. f. Dosage Tested In a number of NutraSweet-funded studies, the aspartame dosage used was much less than it should have been. As discussed in the previous section, NutraSweet's estimates of aspartame intake are obviously flawed. Frey (1976) showed that children can ingest as much as 76 mg/kg/day. In three studies on obese adults, Porikos (1984) showed that the average daily intake of aspartame varied from 8 to 36 mg/kg/day. The FDA's current Acceptable Daily Intake (ADI) is 50 mg/kg/day. NutraSweet researchers have made a significant effort to convince other researchers and the general population that it is okay to test small doses of aspartame. Much of their argument is based on average intake values presented in their ridiculous intake surveys. The fact is that hundreds of thousands of people are consuming amounts of aspartame approaching the FDA's Acceptable Daily Intake level. If the NutraSweet Company actually believes that the FDA's ADI is a safe amount of aspartame, then that is the minimum that should be tested. Either "put up, or shut up" so to speak. In order to have a safety margin, it is preferable to test at least double the ADI using read-world aspartame- containing products in long-term experiments. If they do not want to test at levels at or above the FDA's ADI (using real-world aspartame of course), then we should 1) lower the ADI back to 20 mg/kg/day, 2) label the amount of aspartame on each "food" product that it is in, 3) put a warning on the label stating that no more than 20 mg/kg/day (9 mg/lbs./day) should be consumed, and 4) start proper safety testing in humans at 20 mg/kg/day (or more) using real-world aspartame- containing products. g. Reaction Time Some research ignored certain adverse reactions if they did not occur soon after aspartame ingestion. This is one common way that food industry scientists significantly reduce the number of adverse reactions recorded during the experiment. They simply imply that the suspected reactions are "allergic" (i.e., IgE- mediated) and therefore must occur quickly after ingestion. The fact of the matter is that many food intolerance or toxicity reactions can occur as much as 48 hours after ingestion (Carroll 1992). This use of this flaw has occurred in several NutraSweet-funded experiments. The studies of MSG funded by the International Glutamate Association use this flaw quite often. Independent researchers usually design the experimental protocols to take into account the fact that people often experience delayed reactions. h. Average Values Shown In the publication of many NutraSweet-funded research projects only average values were shown in tables and plotted on graphs. This is fine in studies where there are a large number of participants and the substance being studied has similar biochemical effects on all people. However, most of these studies have very few subjects and it is well-known that there is a wide variation in the biochemical changes caused by methanol, phenylalanine, and aspartic acid. This may also be true with DKP and other breakdown products. If an experiment has six subjects, for example, and two of the subjects show biochemical changes that would be of concern, the significance of those changes would get lost in a listing of averages. Human studies of aspartame conducted by independent researchers often show measurements on an individual basis (not averages) so as not to obscure the possibility of individual susceptibilities (Koehler 1988, Matalon 1988, Van Den Eeden 1994, Walton 1993). Another related technique used by NutraSweet to help hide negative test results is to combine all of the subjects' measurements when they should not be combined. Suppose for a moment that we measure a blood plasma level of aspartate for the first 60 minutes after ingesting aspartame. Below are example values for five different subjects followed by the average values . 0 min 15 min 30 min 45 min 60 min Subject 1 6.0 38.0 32.0 16.0 9.0 Subject 2 5.0 14.0 28.0 51.0 50.0 Subject 3 7.0 8.0 12.0 41.0 12.0 Subject 4 5.0 23.0 41.0 21.0 19.0 Subject 5 6.0 9.0 24.0 37.0 53.0 Mean Values 5.8 18.4 27.4 33.2 28.6 In almost all NutraSweet funded experiments, all that would be shown in publication are the "Mean Values." Notice how the mean values only rise from 5.8 at 0 minutes to a maximum of 33.2 at 45 minutes. When going back to the actual data all of the rises in the subjects were much more extreme than what is apparent by looking only at the mean values. For example, the plasma aspartate level of Subject 2 rose from 5.0 to 51.0 at 45 minutes. Showing only the means values in a chart or a graph will obscure the true rise in blood plasma levels of the substance being measured. This is because some of the subjects reach their peak values at different times, so that when Subject 1 has a peak value of 38.0 at 15 minutes, Subject 3 has a value of only 8.0 at that time -- which brings the mean value at the 15 minutes time period down considerably. The appropriate thing to do would be to list all of measurements for each subject and list the mean starting values and mean peak values: Mean Starting Values = (6.0 + 5.0 + 7.0 + 5.0 + 6.0) / 5 = 5.8 Mean Peak Values = (38.0 + 51.0 + 41.0 + 41.0 + 53.0) / 5 = 44.8 If increases in certain measurements are only moderate, the NutraSweet Company researcher's use of mean values for each time period can sometimes enable the researcher to "prove" that the changes were not statistically significant. Therefore, NutraSweet-sponsored studies which show only mean values for each time period may be hiding some of the negative effects with their statistical games. i. Types of Volunteers Since serious health problems from aspartame seem to develop gradually in many people, it makes sense to conduct very long tests. The NutraSweet Company wants people to swallow this junk for their entire life. Experiments which last a lifetime are obviously impractical. Therefore, it is prudent to conduct relatively long experiments on susceptible populations first so as to get clues as to what will happen to healthy populations after years of use. Most of the studies funded by NutraSweet appears to have been conducted on healthy volunteers (for a very short test period). These experiments had numerous flaws. It seems that the experiments in which unhealthy volunteer were used, the number and seriousness of the experimental flaws increased significantly. The NutraSweet Company wants you to believe that out of the population that is currently allowed to consume aspartame, PKU Heterozygotes (persons who do not have phenylketonuria -- PKU, but have a single gene of PKU) would be the most susceptible to any possible negative effects from aspartame. While this population may be more susceptible than a healthy population, I submit that persons with the following illnesses will be much more susceptible: - Fibromyalgia - Chronic Fatigue Syndrome (CFS) - Chronic Depression - Multiple Chemical Sensitivities - Multiple Sclerosis There are other possibilities, but this is a good start for legitimate tests on susceptible populations. Please note, however, that healthy persons are very susceptible to the damage that can be caused by aspartame, just not quite as susceptible, on average, as persons with the above-mentioned illnesses. j. Animal Tests All three main ingredients in aspartame, methanol, aspartic acid, and phenylalanine have been shown to have much greater toxic effects in humans than in rodents. Methanol and aspartic acid is much more toxic in humans than in monkeys. Methanol tests in rodents are worthless. Methanol tests in rheusus monkeys are also worthless or guesswork at best as discussed in the Methanol section below. Methanol is much more toxic in humans than any other species. Aspartic acid is 5 times more toxic in humans than in rodents and at least 20 times more toxic in humans than in monkeys as discussed in the Aspartic Acid section. Phenylalanine tests in rodents are guesswork at best and probably worthless as discussed in the Phenylalanine section below. Phenylalanine is much more dangerous in humans than in rodents. It is unknown whether DKP, beta-aspartame, or racemized amino acids have different effects in humans as opposed to laboratory animals. Therefore, aspartame tests in animals, especially those which tested for the effects of methanol and phenylalanine in rodents, or methanol and aspartic acid effects in monkeys should be ignored -- as the negative effect in humans would likely have been much greater. It is important to point out that these flaws are not news to the NutraSweet Company. Many people have been pointing out these flaws for years and pushing for legitimate experiments instead of press releases disguised as research. It is also important to note that NutraSweet can make the following claims about their research: "We have studied aspartame in healthy individuals." "We have studied aspartame in diabetics." "We have studied aspartame in persons with liver disease." "We have studied aspartame in adults." "We have studied aspartame in children." "We have conducted acute-dosing tests." "We have conducted chronic use tests [a few weeks only]." etc., etc. However, each one of their experiments had multiple serious flaws, making it virtually useless for anything but a press release. For example, long-term studies often use capsules which were taken with meals and contained numerous irrelevant or poorly conducted tests. Given aspartame's history of what some people consider pre-approval fraud, it does not surprise me that the NutraSweet Company continues to flood the scientific community and the news services with results from badly flawed studies. 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 t