The Truth About Aspartame
By Oliver Starr
What is Aspartame?
Aspartame is a low-calorie sweetener used in foods and beverages in more than 90 countries around the world. Aspartame was approved by the U.S. Food and Drug Administration (FDA) in 1981 for use in powdered mixes and as a tabletop sweetener. In 1996, it was approved for use in all foods and beverages, including products such as syrups, salad dressings and certain snack foods where prior approval had not yet been obtained. Aspartame is made by joining two protein components, aspartic acid and phenylalanine, and a small amount of methanol. Aspartic acid and phenylalanine are amino acids and are found naturally in all protein-containing foods, including meats, grains and dairy products. Methanol is found naturally in the body and in many foods such as fruit and vegetable juices. Our bodies break down aspartame into its basic components, which do not accumulate in the body over time.
Is Aspartame Safe?
Regulators consider aspartame as one of the most widely tested ingredients in the food supply. Aspartame has undergone one of the most thorough scientific reviews ever conducted. It was tested in more than 100 scientific studies prior to its approval by the FDA in 1981. These tests were conducted in animals and humans, including normal adults and children, lactating women and persons with diabetes, obesity and special genetic conditions. Aspartame was tested in amounts many times higher than individuals could consume in the diet. Today scientists continue to conduct new studies on this sweetener as they do many other ingredients used in the food supply. The FDA also monitors and evaluates all research on this and other food ingredients. The FDA and leading independent health groups such as the American Medical Association have affirmed the safety of aspartame. The use of aspartame in foods has become widespread. This has led to much publicity, including concerns and accusations regarding its safety. The FDA has concluded that aspartame is safe for the general public, including diabetics, pregnant and nursing women, and children. Persons with a rare hereditary disease known as phenylketonuria (PKU) must control their phenylalanine intake from all sources, including aspartame. This disease is diagnosed at birth by a blood test performed on all infants. Products sweetened with aspartame carry a statement on the label that they contain phenylalanine.
Overall, repeated studies in peer reviewed journals show no adverse effects of aspartame on seizures (rats, adults, and children), weight gain, body temperature, cognitive/behavioral/neuropsychiatric/ neurophysiologic function, brain/intestinal/liver hormones or enzymes, brain tumors, cancer, birth defects (rats and humans), Parkinson's disease, allergic responses, blood pressure, or carbohydrate and fat metabolism.
Can I Get Too Much Aspartame?
There have been anecdotal reports suggesting that aspartame leads to "methanol toxicity." Opponents of aspartame suggest that the phenylalanine and methanol released during digestion are dangerous. They also assert that methanol can be converted to formaldehyde and then to formic acid, causing acidosis and neurotoxicity. However, methanol exists naturally in many fruits and vegetables. A 330ml (about 11oz) can of aspartame-sweetened soda will yield about 20mg methanol, whereas the same volume of fruit juice produces 40mg methanol, and an alcoholic beverage about 60-100mg. The yield of phenylalanine is about 100mg for a can of diet soda, compared with 300mg for an egg, 500mg for a glass of milk, and 900mg for a hamburger . Therefore, the amount of methanol or phenylalanine is trivial, compared with other dietary sources . Clinical studies have shown no evidence of toxic effects and no increase in plasma concentrations of methanol, formic acid, or phenylalanine with daily consumption of 50mg/kg aspartame , . Numerous scientific studies have shown that the methanol derived from aspartame does not accumulate in the body and thus cannot reach harmful levels. The FDA uses the concept of an Acceptable Daily Intake (ADI) for many food additives, including aspartame. Maintaining the ADI level for every day of a person's life is considered to be safe. The ADI for aspartame has been set at 50 milligrams per kilogram (about 22.7mg/lb) of body weight. To put this into perspective, a 150-lb adult would have to drink twenty 12-oz cans of diet soda every day to reach the ADI, while a 50-lb child would have to drink 7 cans. According to FDA dietary surveys, Americans consume an average daily intake less than 2 percent of the FDA guideline. The most frequent consumers of aspartame are consuming only 4 percent to 7 percent of the ADI. Children consume larger amounts of all food ingredients than adults in relation to their body weight. Therefore, since children are smaller in size they consume slightly more per kilogram of weight. The average consumption of aspartame in children between the ages of 2 and 5 is 3 percent of the ADI. Children who consume aspartame most frequently have been found to consume from 4 percent to 16 percent of the ADI.
The Science Behind the Safety of Aspartame
Aspartame has been accused of provoking several diseases and causing a long list of adverse effects. The publications in medical literature of the world support the safety of aspartame in the general population. In these citations there is no information about deleterious effects of aspartame on multiple sclerosis, systemic lupus erythematosis (SLE or lupus), or fibromyalgia. Additionally, there is no evidence that aspartame causes, provokes, mimics, or worsens multiple sclerosis. There is no indication or proof of an "aspartame disease." Aspartame has not been shown to be dangerous to diabetics. There is one small study that did find some worsening of depression when depressed patients took large doses of aspartame, but these results have not been repeated . These subjects received aspartame (30 mg/kg-body weight daily) or placebo for 7 days. Despite the small number of patients, there was a difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. Therefore, patients with mood disorders may be sensitive to aspartame and its use in this population should be limited.
Aspartame and Brain Function
One example of this research related to brain function is a controlled study that tested the effects of aspartame on neuropsychologic and neurophysiologic function . These researchers sought to determine whether aspartame can disrupt cognitive (learning, thinking, and knowing), neurophysiologic (relationship between neurological function and behavior), or behavioral functioning in normal individuals. By testing these functions, brain dysfunction and central nervous system disorders can be evaluated. Mood, aggression and selected cognitive functions were tested during this study in which some of the subjects consumed doses of aspartame nearly 20 times the daily amount taken by the majority of the general population. During a four-month period, subjects received either aspartame, sugar or a placebo and underwent physical and psychological testing. For aspartame, the people were assigned to either a high or low dose. The high dose was equal to 45mg per kilogram of body weight--the equivalent of 17 to 24 12-ounce diet beverages for males and 14 to 19 12-ounce drinks for females. The "low" dose was equal to 15mg per kilogram of body weight. In the general population, most Americans who consume aspartame take in 3 milligrams per kilogram of body weight a day, the equivalent of one or less 12-ounce diet beverage. Despite the high consumption of aspartame, the 48 normal subjects in this study showed no changes in mood, memory, behavior, electroencephalograms (which record the electrical signals of the brain) or physiology that related to aspartame. Although some subjects reported headaches, fatigue, nausea and acne, the same number of incidences were reported by subjects taking placebo and sugar as those taking aspartame. Therefore, even large daily doses of aspartame had no adverse effect on the subjects' health and well-being. The researchers concluded, "aspartame is safe for the general population." These findings confirm the results of another recent study of aspartame on the activity level, behavior, and cognitive ability of preschool and elementary school children . This study found no effect on the children's moods, activity levels, behavior or thinking after they consumed high doses of aspartame. The amount of aspartame given to the children ranged from 23 to 53mg per kilogram of body weight. From these results, one can conclude that even when intake exceeds typical dietary levels, aspartame does not affect children's behavior or cognitive function.
Aspartame and ADD
Research has also been conducted on children with attention deficit disorder (ADD). In a controlled study, unmedicated children with ADD were given a daily dose of aspartame (34mg/kg-body weight) for 2 weeks . Using behavioral and cognitive tests, the effects of large doses of aspartame on behavior and cognition were measured. The results indicate that aspartame at greater than 10 times usual consumption has no effect on the cognitive and behavioral status of children with attention deficit disorder.
Aspartame and Seizures
There have been numerous animal and human studies done to evaluate the possibility that aspartame causes seizures or enhances the susceptibility to seizures. In these clinical studies done in adults and children with preexisting seizures, there was no evidence of contributing to the frequency of occurrence or severity of seizures in seizure-prone individuals. There were additional studies done on seizure-prone experimental animal models to assess the possible influence of aspartame on their seizure activity. Again, the result was the same and aspartame demonstrated no influence on the frequency or severity of seizures. Another study has shown no relation between consumption of aspartame and the frequency of seizures in children with well-documented seizures . These children received a single morning dose of aspartame (34 mg/kg) for 2 weeks. These results suggest that, in this group of vulnerable children, aspartame does not provoke seizures.
In adults, there have been anecdotal implications that aspartame provokes seizures. Over several years and after surveying more than 8,000 neurologists, 18 patients who had seizures allegedly related to aspartame consumption were identified . These 18 people (16 adults and 2 children) received aspartame (50 mg/kg body weight) or placebo on the second and forth days of a 5-day trial. On these treatment days, the participants ate the same diet. No clinical seizures or other adverse experiences were observed after aspartame ingestion. Therefore aspartame, in acute dosage of approximately 50 mg/kg, is no more likely than placebo to cause seizures in individuals who reported that their seizures were provoked by aspartame consumption.
Aspartame and Headache
Aspartame has also been targeted as causing headaches. A placebo-controlled trial published in the New England Journal of Medicine examined 40 "aspartame sensitive" people . These people had previously reported having headaches after consuming products containing aspartame. Aspartame in a dose of 30mg per kilogram of body weight resulted in an incidence rate of headache not statistically different from that after placebo. Other factors besides aspartame may have been contributing to headaches in these people. One woman, who often ate peanuts with her diet soda, was allergic to peanuts. Another subject consumed excessive amounts of caffeine. These researchers concluded that in these people, aspartame is no more likely to produce headache than placebo.
Aspartame and Allergies
Anecdotes have also suggested that aspartame may be associated with allergic/hypersensitivity-type reactions. Researchers have evaluated people who had experienced allergic conditions allegedly associated with ingestion of an aspartame-containing product . These individuals had experienced urticaria (an allergic skin condition characterized by patching, hitching and hives) and/or angioedema (a vascular reaction involving the deep dermis or subcutaneous tissues). Despite extensive recruiting efforts for over 4 years, only 21 people who had these allergic reactions allegedly in response to aspartame could be studied. With doses of 50, 300, and 600mg of aspartame, the results were that aspartame and its conversion products are no more likely than placebo to cause urticaria and/or angioedema reactions in people with a history consistent with hypersensitivity to aspartame. Carefully controlled clinical studies show that aspartame is not an allergen. However, certain people with the genetic disease phenylketonuria (PKU), those with advanced liver disease, and pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) have a problem with aspartame because they do not effectively metabolize the amino acid phenylalanine, one of aspartame's components. High levels of this amino acid in body fluids can cause brain damage. Therefore, FDA has ruled that all products containing aspartame must include a warning to those with phenylketonuria that the sweetener contains phenylalanine. Also, the FDA warns that persons with certain medical conditions, including pregnant women with hyperphenylalanine, should avoid aspartame.
Aspartame and Weight Loss
There have also been claims that artificial sweeteners such as aspartame hamper weight loss efforts. A University of Toronto study on the effects of Aspartame sweetened diet soda on randomly assigned subjects found no effect on food selection at a meal 60 minutes afterwards . The people who drank 2 cans of a diet soda experienced reduced hunger for about 45 minutes. The researchers concluded from these results that drinking soft drinks containing aspartame does not increase short-term hunger or food intake. A more recent study conducted at Harvard Medical School indicated that aspartame facilitated long term weight maintenance in a multidisciplinary weight loss program . Among individuals consuming aspartame during a 19-week weight loss program, consuming more aspartame was associated with a greater weight loss. The women consuming aspartame-sweetened foods lost more weight overall and regained less weight during maintenance and follow-up than those abstaining from aspartame. Thus, aspartame was associated with better long-term weight control.
Aspartame and Cancer
Concerns have also been raised about possible carcinogenic effects of aspartame. In 1996, one study claimed that data collected by the National Cancer Institute demonstrated an increase in the incidence of brain tumors in human patients since aspartame was approved for use in the U.S. food supply (1981). However, the Mayo Clinic Health Letter (March 1997) notes that the incidence of brain tumors has been rising since the 1970's, long before aspartame was approved. A causal relationship has not been established. The FDA has recently reported that several scientists that have evaluated these claims and disagree with the validity. The increase in the number of reported brain tumors might be attributed to the technological advances that have been made in diagnosis. A case-control study examined aspartame consumption in relation to childhood brain tumor risk . In this study published in 1997, case patients had been diagnosed with a primary brain tumor between 1984 and 1991. There were 56 case patients and 94 control subjects, all born in 1981 or later (corresponding with the FDA approval of aspartame) who were evaluated for aspartame exposure. The investigators also examined brain tumor risk in relation to mother's consumption of aspartame during pregnancy and breast-feeding for 49 case patients and 90 control subjects who were in utero in 1981 or later. The results were that "case children were no more likely than control children to consume foods containing aspartame, either from all sources of aspartame combined or from diet drinks" . In addition, the researchers did not observe an elevated brain tumor risk to the child from maternal consumption of aspartame during pregnancy or breast-feeding.
Scientific Review of Aspartame by the FDA
In January of this year, the FDA's Center for Food Safety and Applied Nutrition responded to claims that ingestion of aspartame results in the occurrence of a number of toxicities. This review of the safety of aspartame provides a more accurate and complete assessment of the data/findings, both from animal and clinical studies that are currently available on aspartame. The scientists that have worked on questions relating to the safety of aspartame repeatedly since 1978 compiled this review. These scientists are familiar with the scientific studies that have been conducted to support the safety of this food additive. There were well over 100 separate toxicological and clinical studies conducted to establish the safety of aspartame before it was approved for regulatory acceptance. Since its approval in 1981 by the FDA, there have been many additional studies performed to follow up on some of the more credible reports of aspartame-mediated adverse effects. In response to reports of aspartame by patients who later have suffered multiple sclerosis or systemic lupus, this review states that "there is obviously not scientifically sustainable evidence that aspartame is responsible for the occurrence of either disease." Also, since both of these disorders are subject to spontaneous remissions and worsening of symptoms, it is possible that when patients stopped using aspartame they might have also coincidentally have had remission of their symptoms. Alternatively, the worsening of disease symptoms could be only chronologically correlated with the start of aspartame use. According to this review, the most important consideration is that there is no credible evidence suggesting that aspartame induces multiple sclerosis or systemic lupus. This FDA review also includes a rebuttal to the claim that aspartame ingestion results in the production of methanol, formaldehyde and formate. The reviewers support the fact that aspartame is hydrolyzed to one of its component materials, methanol, as well as the two amino acids, phenylalanine and aspartic acid in the gastrointestinal tract. This methanol is taken up by the cells of the body and metabolized first to formaldehyde and then to formate. However, the review adds that there is key information missing from the allegations of aspartame's toxicity. This critical fact is that the levels of ingestion are very modest. As mentioned previously, there are other foods that we ingest that supply as much and sometimes even more methanol (e.g., citrus fruits and juices, and tomatoes or tomato juice). There are even higher quantities of methanol ingested when ethanol is consumed. Thus, in the final analysis this methanol produced from aspartame is the same as from other sources of food. In addition, in the quantities consumed from aspartame, methanol is readily and naturally metabolized to entirely harmless and natural body components. There is also a claim that the two amino acids, phenylalanine and aspartic acid have neurotoxic effects. The FDA review ensures that although this is true in certain individuals and in high enough doses, the only group of individuals potentially susceptible to adverse effects from phenylalanine is homozygous phenylketonurics. In these people, food itself with much higher levels of phenylalanine from protein contributes a much higher toxicity. The scientists add that phenylketonurics who want to carefully control their intake levels of phenylalanine can simply take into consideration the amount of phenylalanine supplied by the aspartame product or, even more likely, simply refrain from use of these products. The FDA requires that the aspartame product be labeled specially for phenylketonuric patients so that they will be aware of its presence in these products. As for the other amino acid in aspartame (aspartic acid), the levels ingested with aspartame use are many fold less than those levels responsible for causing adverse effects on the brain of animals and/or humans. In fact, it is not clear that the results from studies with animals are relevant to humans. In any case, the levels of aspartic acid (a normal component of dietary protein) intake from aspartame are several times lower than those needed to initiate neurotoxic effects.
Aspartame and Flying
This review also adds that aspartame was comprehensively evaluated for its potential to mediate adverse reactions on the ability of pilots to fly planes. There were a number of individual complaints registered with the FDA claiming that ingestion of aspartame resulted in an interference with individuals' ability to fly planes. For example, dizziness, impairment of vision and mental acuity were reported. The FDA assures that it took these reports seriously and instituted a contract to perform a study to see if these effects could, indeed, be reproduced. The FDA contracted with the Federal Aviation Agency who subcontracted studies with psycho-physiological testing laboratories to determine whether aspartame could affect mental functioning, and manual dexterity. The overall outcome of the studies was that there was "no difference between placebo (control) treatment and exposure to aspartame although a positive control group receiving ethanol did show impairment of manual dexterity and ability to deal with complex information." In other words, the only group that showed any impairment was the group that had consumed an alcoholic beverage! In 1996, Dr. John Olney of Washington University in St. Louis, Missouri claimed that data collected by the National Cancer Institute demonstrated an increase in the incidence of brain tumors in human patients since aspartame was approved for use in the US food supply . The FDA report adds that "a number of scientists both in government and in academic settings have carefully evaluated Dr. Olney's claim and have refuted it." While there has been an increase in the number of brain tumors reported during recent years, these reviewers attest that the explanation for this increase is most likely to be the technological enhancements of tumor diagnosis (e.g., computerized tomography and magnetic resonance imaging) introduced during this same time. These advances have therefore allowed greater sensitivity and certainty in the diagnosis of tumors. In the more recent data on tumor occurrence in the US, there is a plateauing or even a slight decrease of brain tumor incidence while the presence and use of aspartame in many food products has continued. Lastly, aspartame was subjected to several specially designed animal tests to determine its potential to adversely influence reproduction and to mediate birth defects. All of the well-designed and conducted tests demonstrated that aspartame was safe and did not produce birth defects or adverse responses on reproductive function. This FDA review also adds that aspartame is one of the most thoroughly tested food additives ever submitted to the FDA. In conclusion, "all of the early testing in animals and human subjects conducted to support the safety of aspartame as well as the well-designed and conducted studies subsequently performed to assess whether aspartame might mediate a number of anecdotally reported symptoms have reinforced the appropriateness of the FDA's approval and regulation of aspartame as a safe food additive."
Scientific Review from the U.K. C.O.T
As in the United States, the safety of aspartame use has been extensively examined in Great Britain. An evaluation from the U.K. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) concluded that aspartame is safe. This committee last fully reviewed aspartame in 1982, when it was classified as acceptable for use in food. Since 1982, the COT has reviewed issues related to the safety of aspartame in the scientific literature. The U.K. COT has stated that the reviews of literature has not caused them to change their advice that aspartame is safe. The animal studies evaluated by this committee have mainly investigated the potential effects of high doses of aspartame on brain neurotransmitters and behavior. The reviewers concluded that adverse neurochemical or neurobehavioral effects have only been seen in animal studies using exposures to aspartame, which far exceed extreme intake figures for the U.K. They attest that "at current intake levels no neurotoxic effects have been observed or would be expected." Overall, according to this evaluation, the results of animal studies conducted give no cause for concern. In addition, the COT adds that metabolism studies on aspartame in four species of animals and in humans indicate that aspartame is metabolized to methanol, aspartic acid and phenylalanine, with metabolism taking place largely in the gastrointestinal tract. As mentioned by several other sources, the amino acids aspartic acid and phenylalanine are normal components of dietary protein and methanol is a low-level constituent of common foods. The reviewers also add that the amount of methanol contributed to the diet by aspartame is very low compared with that from other foods (e.g. one pint of orange juice would provide more methanol to a three-year-old child than a 40mg/kg-bodyweight dose of aspartame). They also verify that unchanged aspartame is not likely to be present in the body's circulation even at high levels of human dietary intake. The COT reviewed the results of the extensive tolerance and pharmacokinetic (the action of drugs in the body over a long period of time) studies on aspartame in humans. The data indicates no adverse effects in various human subpopulations following exposure to aspartame at doses up to 75mg/kg body weight each day for 24 weeks or up to 135mg/kg body weight a day for a shorter period. Pharmacokinetic studies have established that both large doses and repeated doses of aspartame result in plasma levels of its components, which are considered safe. In response to anecdotal reports linking aspartame with a variety of adverse effects such as headache, seizures and behavioral difficulties in children, the COT has reviewed reports collected by the U.S. FDA along with consumer complaints received by Nutrasweet in the U.K. They report that most of the frequently reported symptoms were mild, and, were common background symptoms typically found in the general population. The most common adverse symptom reported was headache, which accounted for approximately 20% of all complaints in the U.S. The results of two studies that have investigated the relationship between aspartame and headache differed markedly from each other. The conclusions from one were that the incidence of headache from aspartame and placebo was equivalent. In the second study only 11 of 25 subjects, all who reportedly suffered from migraine, and all of whom presupposed that they were adversely affected by aspartame, finished the study. Because of the high dropout rate, the conclusions of this study are tentative. However, it was considered that the ingestion of aspartame by migraine sufferers may cause a statistical increase in the frequency of migraines in some subjects. Thus, it may be advisable for migraine sufferers to avoid aspartame. However, the COT reviewers note that more studies are needed to confirm these results. The COT evaluation also adds in response to claims that aspartame causes other adverse effects, such as behavioral effects or seizures, that these allegations have not been substantiated in controlled studies in humans. From the animal and human data, the COT then recommended an acceptable daily intake (ADI) of 0-40 mg/kg body weight for aspartame.
Aspartame has been approved for use by more than 90 nations worldwide. It is used widely in major industrialized countries such as the United Kingdom, Germany and Japan. Aspartame has been reviewed and found safe by the Joint Expert Committee on Food Additives (JECFA) of the United Nations Food and Agricultural Organization and World Health Organization. It also has been reviewed and approved for use by the Scientific Committee for Food of the European Community. In the United States, several organizations in addition to the FDA have recently attested to the safety of aspartame. The American Medical Association's Council on Scientific Affairs reviewed research on aspartame and found the sweetener to be safe. The American Dietetic Association also has concluded that moderate use of aspartame is acceptable as part of a healthful diet. The Epilepsy Institute, an organization devoted to people suffering from seizure-related problems, has concluded that aspartame is not related to seizures among epileptic patients. And, the Multiple Sclerosis Foundation has stated that there is no danger associated with aspartame ingestion. The American Diabetes Association issued a statement in February of this year stating that, along with the FDA, it recognizes that there is no credible scientific evidence linking aspartame to any health-related problems for people with diabetes. The American Diabetes Association considers aspartame an acceptable sugar substitute and a safe part of a diabetic meal plan. With FDA-approval, reputable and extensive scientific data, worldwide food committee approval and acceptance from numerous medical associations, clearly aspartame is a safe ingredient for the general population. The claims attacking the safety of aspartame are extremely inaccurate and lacking scientific foundation.
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