Aspartame is a nutritive sweetener approved by the Food and Drug Administration (FDA) in 1982. Its brand names include NutraSweet^®, Crystal Light^®, and Equal^®. This compound consists of two amino acids (L-phenylalanine and L-aspartic acid) and methyl alcohol. It is currently being consumed by an estimated 100 million persons in the United States.

The public and the medical profession have been assured by the Council on Scientific Affairs of the American Medical Association, the Centers for Disease Control (CDC), and a host of other organizations and regulatory bodies that aspartame is "completely safe." The CDC regards most consumer complaints as an "unusual sensitivity to the product." The manufacturer offers a bibliography of more than 100 published studies as evidence of safety.

Evolving doubts - I challenged the alleged safety of aspartame on the basis of my personal observations, a nationwide study of detailed data on 496 aspartame reactors, and considerable ongoing research by others and myself. Furthermore, I raised the possibility that this substance may constitute an imminent public health hazard during a recent address to the annual meeting of the Southern Medical Association.

More than 10,000 complaints have been directed by consumers to myself, the FDA, CDC, manufacturer, other interested investigators, and consumer organizations.

The causative role of aspartame has been shown by (a) the improvement or disappearance of symptoms and signs within days or weeks after stopping aspartame, and (b) their prompt recurrence (within hours or days) after resuming such products. The latter included self-testing on numerous occasions, inadvertent ingestion, or formal rechallenge. These sequences were impressive in patients experiencing grand mal convulsions, headaches, itching, rashes and severe gastrointestinal reactions.

Other physicians have documented similar reactions…. either as case reports or in personal communications to me.

Clinical date on 496 reactors - The general data on 496 aspartame reactors are summarized in Table 1. They included 115 patients and aspartame reactors who were personally interviewed, and 381 persons who detailed their adverse effects in a nine-page questionnaire survey. The names of the latter were proveded by Aspartame Victims and their friends courtesy of Mrs. Shannon Roth), the Community Nutrition Institute (courtesy of Mr. Rod Leonard), and Dr. Woodrow Monte of Arizona State University.

The most frequent and severe reactions to aspartame are listed in Table 2. The majority of reactors experienced multiple features.

Review of the general data - gender - there was a 3:1 preponderance of female aspartame reactors. Many influences may be operative - including their increased risk for severe depression, allergies and diabetes, the phenylalinemia noted in women with iron deficiency, and the greater insulin responses to oral or intravenous phenylalanine and other amino acids in healthy non-obese females.

Latent period - Latent periods of from several weeks to several months between the initial consumption or increased intake of aspartame and the onset of several symptoms were most common. Others reacted almost immediately.

Aspartame intake - Many consumed prodigious amounts of aspartame, especially during hot weather. On the other hand, some experienced convulsions, headache or other severe symptoms after chewing an aspartame-sweetened gum, analgesic or vitamin, or while breast-feeding as the mother drank an aspartame beverage.

Pathophysiology - Aspartame reactions may be caused by the compound itself, any of its three components (phenylalanine, aspartic acid, methyl alcohol), toxic breakdown products (10 identified to date) or combinations thereof. They often occurre in association with severe caloric restriction and excessive exercise to lose weight.

Damage to the retina or optic nerves is probably due to high methyl alcohol concentrations. Aspartame yields about 10% methanol by weight. Humans, unlike most animals, cannot efficiently metabolize it.

Many other metabolic and physiologic disturbances seem to explain the cited complications. Only a few will be listed.

• High concentrations of phenylalanine and aspartame occur in the brain, unlike the modest levels following protein intake.

• Aspartame alters the function of major amino acid-derived neurotransmitters - especially in obese persons and after increased carbohydrate intake.

• Phenylalanine stimulates increased release of insulin and growth hormone.

• The ambiguous signals to the satiety center following aspartame intake may result either in increased food consumption or severe anorexia.

Clinical implications - Physicians must question patients who present with the disorders listed in Table 2 about aspartame use. If it is being consumed, a brief trial of abstinence should be recommended before reflexively requesting consultations and expensive tests. Failure to appreciate the underlying role of aspartame has resulted in unnecessary medical costs…. especially CT scans and NMR studies of the brain, electroencephalograms, and multiple hospitalizations.

The following caveats reflect my clinical experience:

• Inquiry about aspartame use is necessary in every patient with an unresolved allergic, dermatologic, gastrointestinal or metabolic problem.

• The physician must not attribute visual, neurologic or bowel problems in diabetics, until responses to aspartame cessation are evaluated.

• Cataract surgery ought to be deferred at least one month in heavy aspartame users for symptomatic evaluation.

• Patients presenting with seizures, headache, facial or eye pain, the Meniere syndrome, depression and a host of neuropsychiatric problems of undetermined cause, or who fail to respond to conventional therapy, must be asked about aspartame use - especially before recommending invasive studies such as cerebral arteriography.

• Younger patients that express concern about having "early Alzheimer's disease" because of recent confusion and memory loss ought to be observed at least one month after stopping aspartame before such a definitive diagnosis is considered.

• A D&C or hysterectomy should be deferred for comparable observation in women consuming considerable aspartame who have heavier or more frequent periods.

The urgent need for research and education - Physicians and the public must be made aware of such concern. High-risk groups deserve special emphasis. They include pregnant and lactating women, young children, older persons, patients having iron deficiency anemia, liver disease, kidney impairment, migraine, hypoglycemia, diabetes mellitus and hypothyroidism, individuals with prior alcoholism or drug abuse, those at risk for phenlketonuria, and patients taking drugs that might interact with phenylalanine (e.g., L-dopa, monoamine oxidase inhibitors, alpha-methyldopa).

Aspartame was licensed for general use in spite of objections by three FDA scientists…especially brain tumors and birth defects. They still must be addressed. It is appropriate to recall that a longer period transpired before thalidomide was proven to be a cause of birth defects.

On the basis on mounting clinical and investigational observations, I also am concerned that aspartame might cause, accelerate or aggravate Alzheimer's disease, Parkinsonism, depression, intellectual deterioration, and other neuropsychiatric disorders.