Phenylalanine 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.

c) Phenylalanine reduced the clinical response to levodopa in a double-blind trial involving patients with idiopathic Parkinson's disease of 8 to 22 years' duration. Patients (n=9) were selected for the study because of unpredictable response to levodopa. Following a high-protein meal (65 to 104 grams protein), absorption of oral levodopa was minimally affected in 3 patients, delayed in 4 patients, and markedly reduced in 2 patients. Area under the curve for the 2 hours after drug absorption was reduced an average of 27% (range -18% to +65%, p less than 0.05). Peak plasma concentrations were reduced and average of 29% (range 5% to 69%, p less than 0.05). Peak plasma concentrations were delayed an average of 34 minutes (range -30 minutes to +90 minutes, p less than 0.05). During intravenous infusion of levodopa in 2 patients, a high-protein meal (65 to 104 grams protein) doubled the plasma concentration of large neutral amino acids, and reduced the clinical response to levodopa without altering the plasma levodopa concentration. Oral phenylalanine 100 milligrams/kilogram during levodopa infusion in 4 patients increased plasma concentrations of large neutral amino acids two- to three-fold, and slightly increased the plasma levodopa concentration. The clinical response to levodopa declined with the rise in large neutral amino acids. Patients' condition changed from a mobile and dyskinetic state to a bradykinetic, tremulous "off" state within a few minutes. Recovery was related to the reduction in plasma large neutral amino acids. Glycine, a small neutral amino acid, and lysine, a basic amino acid, had no effect on plasma levels of large neutral amino acids or levodopa levels and did not affect the clinical response to levodopa ³.