This review was written for and published in our local Parkinson support group paper. I thought it might be relevant to the topic discussed here recently namely PD and diabetes. Although I have been retired for sveral years, I feel I still qualify as a research chemist. ------------------------------------------------------------------------------ ------------------- ASPARTAME A question arose through Internet as to whether the ingestion of aspartame, the generic name for NUTRASWEET, has any effect on the therapeutic efficacy of Sinemet in Parkinson patients. One contributor to Internet denounced aspartame for a multidude of ills and sins of the world except for the Viet Nam, Korean, and World War II. Chemically, aspartame is the methyl ester of a dipeptide and has a nutritive value of 4 calories per gram, but is about 160 times as sweet as sucrose (table sugar). It was first approved by the FDA in 1974 as a sugar substitute for table use, and as a sweeetener in various products, and later in carbonated beverages. Formal objections based on safety issues were evaluated thoroughly and at length, but the government concluded that the proposed food additive use is safe under the proposed usage. It has become a major ingredient in diet sodas and many other dietetic drinks and food preparations. The quantities of the substance that can be consumed can be quite significant when compared to the dosage amounts of Sinemet: for instance, one glass of soda contains about 160mg of aspartame. However, 3 Oz or 100Gm (1Gm=1,000mg) of beef or other protein food is enormous in comparison. Aspartame is easily hydrolyzed (broken down) into two different amino acids, aspartic acid and phenylalanine. This hydrolysis occurs in vivo (in the body) as the substance is metabolized but can also be achieved in vitro by boiling it in a liquid, which is why it is not to be used in cooking, and likewise occurs in the early stage of metabolism. Aspartic acid and phenylalanine obtained from aspartame are identical to those derived from any protein and likewise should compete with Sinemet for the active receptor sites in the brain, if taken within at least one half hour, the recommended interval, from dosing time. However, a brief note in the Winter '93-'94 APDA Bulletin reported no adverse effect in a double blind study with aspartame and L-dopa by Dr. P.J. Karsteadt and J.H. Pincus of the Georgetown University Hospital (Neurology, 43:611-613, 1993). It would be good to know there is no adverse effect from aspartame on Sinemet, even at a high dietary level, no matter what the age of the patient nor the elapsed time since the onset of Parkinson's disease. However, this study does not give enough information to provide this assurance. The premise that ingestion of large neutral amino acids within a specific time frame of dosing with Sinemet may affect the response to the drug, and consequently, motor performance, is an important one to examine. This study consisted of administering 600mg or 1200mg of aspartame, intended to bracket a high, but larger amount than ordinarily consumed to a group of 18 patients from 45 to 75 years, a range of 30 years. These patients had been ill from 4 to 30 years. Various physico-chemical tests were used to measure disability, dyskinesia, walking, and blood levels at various times after administration. There is no way to know from this paper whether the patients were assigned in a balanced way to the two groups, but the particular measures of motor performance and disability could be expected to vary by age and extent of illness. Thus, if one group consisted of the younger and also the less able patients, it could be that the group would not show changes across the course of the study. That would not, however, account for differences or lack thereof in plasma phenylalanine. It should be noted that the higher exposed group did show differences in this measure. The authors' concluded that the aspartame has no adverse effects on Parkinson patients even at high levels of consumption. Yet, the study does not include enough people, nor even enough in subgroups like the aged or more disabled, to conclude that there is no effect at the lower amount tested. Further repeated intake (e.g., several diet sodas a day) might produce a different motor performance profile and level of plasma phenylalanine. Therefore, it is suggested that it would be prudent to treat aspartame like any protein and avoid it at least within half an hour before and after a dose of Sinemet. Michel Margosis