This project will provide the explanation for the deleterious effect of alimentary large neutral amino acids (INAA)l on l-dopa treated Parkinsonians who suffer with unpredictable motor fluctuations or drug resistant """"""""off"""""""" periods. The sample size will be expanded. The biochemical mechanism that allows the protein redistribution diet to work; and the longitudinal outcome of this dietary intervention will be determined. On admission, Parkinson patients with fluctuations will be placed on a diet with 70 gm protein to be consumed almost entirely during the evening meal. L-dopa dose will e adjusted to obtain optimum function. On one of two study days patients will receive a 70 gm protein diet with the protein given at breakfast and lunch. On the other study day patients will eat all protein at supper. On these two days of study, between 8 a.m. and 5 p.m., hourly plasma samples will be obtained for the determinations of l-dopa and INAA with concomitant video documentation of clinical performance. The Beck Depression inventory will be completed on each of the two days. If indicated for clinical reasons, lumbar puncture will be performed and CSF samples will be assayed for 5-HIAA; MPHG; and HVA. Upon discharge patients will receive instructions for hat regimen of drug aNd diet that seemed best to provide functional relief. Monthly telephone follow-up and biannual return for reevaluation to determine patient outcomes will be conducted for up to five years. A samples size of 100 patients (20 patients/year) is anticipated. Analysis of the clinical and laboratory correlative data will establish whether and how LNAA interferes with the effect of l-dopa and if clinical beneifit and sensitivity to l-dopa therapy can be sustained with the protein redistribution diet. Analysis of the depression inventories and CSF samples will determine if depression in Parkinsonism correlates with alterations in CSF levels of 5-HIAA and if either of both of these caN be manipulated by diet.
Karstaedt, P J; Kerasidis, H; Pincus, J H et al. (1994) Unilateral destruction of dopamine pathways increases ipsilateral striatal serotonin turnover in rats. Exp Neurol 126:25-30 |
Karstaedt, P J; Pincus, J H (1992) Protein redistribution diet remains effective in patients with fluctuating parkinsonism. Arch Neurol 49:149-51 |
Karstaedt, P J; Pincus, J H; Coughlin, S S (1991) Standard and controlled-release levodopa/carbidopa in patients with fluctuating Parkinson's disease on a protein redistribution diet. A preliminary report. Arch Neurol 48:402-5 |