Tyrosine and Levodopa Oral Inhalation: Interaction Details

a) In three patients taking levodopa for Parkinson's disease who experienced "on-off" symptoms, a high protein diet increased the occurrence of "off" periods in a double-blind study. "Off" periods (severe symptoms) occurred when plasma levodopa levels were low; "on" periods (nearly symptom-free) were preceded by increased levodopa levels. With the high-protein diet, plasma levels of large neutral amino acids (LNAA) were 26% to 214% higher than with the low-protein diet. Plasma dopa peak and mean concentrations were also greater on the high-protein diet, yet "off" periods lasted longer, which may reflect competition with LNAA for tissue uptake. The authors suggested that the dose of levodopa may need to be increased when high protein meals are consumed. The 3 patients were 71 to 76 years old, had Parkinson's disease for 10 to 17 years, had taken levodopa for more than 10 years, and were all treated with a peripheral decarboxylase inhibitor ¹.

b) In 6 patients with idiopathic Parkinson's disease, a single oral administration of a high-protein formula reduced the therapeutic response to levodopa/carbidopa. Patients were 59 +/- 2.5 years of age, 5 men, 1 woman, with symptom duration ranging from 8 to 16 years, and severity ranging from stage III to V. In a study of 3 subjects, the usual oral levodopa/carbidopa dose was given at 8 AM, followed by a protein load of 0.4 grams/kilogram body weight at 8:30 AM. All 3 patients had mild dyskinesia at the time of protein ingestion; within 30 to 60 minutes they had an abrupt return of parkinsonian signs. Plasma large neutral amino acid levels were increased following the protein load. In a second study of all 6 subjects, patients received one of two diets in single-blind, crossover design and were evaluated while receiving oral levodopa/carbidopa and intravenous levodopa plus oral carbidopa 50 milligrams every 3 hours while awake. Both diets met the recommended daily allowance (RDA) of protein (0.8 grams/kilogram/day). Diet A was given as three solid meals at 8 AM, noon, and 5 PM and contained 12% protein, 42% carbohydrate, and 46% fat. Diet B was given as 6 equal liquid meals (Ensure, Ross Laboratories, Columbus, Ohio) every 2 hours from 8 AM to 6 PM and contained 14% protein, 54% carbohydrate, and 32% fat. Plasma levodopa and large neutral amino acid levels were unaffected by either diet, and antiparkinsonian response was not affected by either diet. The authors suggested that during initial treatment with levodopa, the response to therapy is generally insensitive to dietary factors, and that disease progression and/or levodopa toxicity reduces the ability of the central nervous system to buffer changes in levodopa levels, such that dietary factors like protein load may modify the response to levodopa therapy ².