Is aspartame safe?

Townsend Letter for Doctors and Patients,  May, 2005  by Alan R. Gaby

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There is a great deal of controversy regarding the safety of the artificial sweetener aspartame (NutraSweet[R]). On the one hand, according to the Council of Scientific Affairs of the American Medical Association, the available evidence suggests that consumption of aspartame by normal humans is safe and is not associated with serious adverse health effects. (1) On the other hand, there are numerous anecdotal reports of adverse reactions to the sweetener, including migraines, seizures, cardiac arrhythmias, ocular problems, mental changes (including depression, mania, and panic attacks), and allergic reactions.

Aspartame is a dipeptide consisting of the methyl ester of phenylalanine and aspartic acid. Aspartame has the same caloric content as regular sugar (4 kcal/g), but because it is 180 to 200 times sweeter than sugar, much smaller amounts are needed. The FDA approved aspartame in 1981 as a sugar substitute, and today it is used in a wide range of foods including soft drinks, chewing gum, desserts, and cereals, and as a table sweetener. It is popular among people who wish to reduce their intake of high-calorie sweeteners such as sucrose and corn syrup, while still enjoying the sweet taste of food.

Consumption of aspartame increases blood levels of phenylalanine, and in animal studies administration of aspartame in amounts that might be consumed by humans almost doubled brain phenylalanine levels. This increase was doubled again if carbohydrate was administered concurrently with aspartame. In addition, aspartame inhibited the increase in brain serotonin levels that normally follows a carbohydrate meal. (2) Thus, aspartame ingestion causes changes in brain chemistry and neurotransmitter metabolism. While the clinical implications of these changes are not clear, they have the potential to cause a wide range of physical and mental symptoms. Certainly, people with phenylketonuria (PKU), who are unable to metabolize phenylalanine normally, should not consume aspartame. (3) It has also been suggested that the 4 million or so Americans who are heterozygous for PKU may be especially sensitive to the effects of aspartame. In addition, it is possible that repeated episodes of hyperphenylalaninemia would adversely affect brain development in young children, as it does in people with PKU. Hyperphenylalaninemia might occur in a child who consumes aspartame. It may also occur in a fetus or infant, if a pregnant or lactating mother who is heterozygous for PKU consumes aspartame.

Approximately 10% by weight of aspartame is converted in the body to methanol (wood alcohol). An increase in the serum methanol concentration can be detected in humans after ingestion of 500 mg of aspartame, an amount present in about one liter of a soft drink. (4) While methanol is a known poison when administered in large doses, it is not known what effects, if any, the small amounts of methanol released from aspartame would have on the average person. It is possible, however, that a small increase in the serum methanol concentration could cause symptoms in people with subtle weaknesses in their detoxification mechanisms.

Published case reports have attributed grand mal seizures, (5) urticaria, (6) angioedema and other allergic reactions, (7) mania, (8) migraines (9) or other headaches, (10) orofacial granulomatosis, (11) and granulomatous panniculitis (12) to aspartame ingestion. A wide range of other adverse reactions has also been reported anecdotally. (13) In many of these reports, symptoms were relieved by avoidance of aspartame, but recurred rapidly after aspartame was reintroduced into the diet, either deliberately or inadvertently.

Some double-blind trials (mostly funded by the NutraSweet Company) have failed to confirm the anecdotal reports of adverse reactions. (14-16) Other double-blind trials, however, showed that aspartame significantly increased the frequency of migraines in patients with recurrent migraines, (17) and caused EEG abnormalities in people with newly diagnosed but untreated generalized absence seizures. (18) Another double-blind trial found evidence that people with a history of depression may be unusually sensitive to aspartame. Of the eight participants in that study, one developed retinal detachment and one experienced conjunctival hemorrhage for the first time in her life after ingesting 30 mg/kg/day of aspartame (equivalent to 10-12 cans of soda per day). (19) The latter patient and two others spontaneously reported that they felt like they had been "poisoned."

Critics of the industry-funded studies that found aspartame to be safe point out that administering the chemical in capsule form or in freshly prepared cool solutions does not mimic the way aspartame is consumed in the real world. While aspartame is stable in dry foods, it decomposes on prolonged exposure to high temperatures or in liquids. In carbonated beverages stored for 8 weeks at 20 degrees C (68 degrees F), 3-4% of the added aspartame was degraded to diketopiperazine. Storage at 30 degrees C (86 degrees F) for 8 weeks resulted in 12% being converted to diketopiperazine. (20) Although not much is known about the safety of diketopiperazine, it has been found to cause bladder tumors in mice. In addition, it has been suggested that this compound could promote the development of allergic reactions by acting as a hapten.