Plasma levels of amino acids correlate with motor fluctuations in parkinsonism.

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.

[1]  J. Langston,et al.  Permanent human parkinsonism due to 1‐methy 1–4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) , 1985, Neurology.

[2]  Modification of Parkinson's disease by long-term levodopa treatment. , 1986, Archives of neurology.

[3]  Richard S. J. Frackowiak,et al.  Inhibition of L‐{18F}fluorodopa uptake into human brain by amino acids demonstrated by positron emission tomography , 1986, Annals of neurology.

[4]  F. Mcdowell,et al.  Plasma dopa concentrations and the “on‐off” effect after chronic treatment of Parkinson's disease , 1974, Neurology.

[5]  J. Pincus,et al.  Influence of dietary protein on motor fluctuations in Parkinson's disease. , 1987, Archives of neurology.

[6]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.

[7]  W. Pardridge KINETICS OF COMPETITIVE INHIBITION OF NEUTRAL AMINO ACID TRANSPORT ACROSS THE BLOOD‐BRAIN BARRIER , 1977, Journal of neurochemistry.

[8]  J. Sturman,et al.  TAURINE IN THE BRAIN AND LIVER OF THE DEVELOPING HUMAN AND MONKEY , 1975, Journal of neurochemistry.

[9]  G. C. Cotzias,et al.  Protein intake and treatment of Parkinson's disease with levodopa. , 1975, The New England journal of medicine.

[10]  R. Katzman.,et al.  SYNTHETIC AMINO ACIDS AND THE NATURE OF l‐DOPA TRANSPORT AT THE BLOOD‐BRAIN BARRIER , 1975, Journal of neurochemistry.

[11]  A. Lieberman,et al.  Parkinson's disease: a clinical review. , 1974, The American journal of the medical sciences.

[12]  J. Fields,et al.  Neurotransmitter receptor alterations in Parkinson's disease. , 1977, Life sciences.

[13]  C. Markham,et al.  Long‐term follow‐up of early dopa treatment in Parkinson's disease , 1986, Annals of neurology.

[14]  Pincus Jh,et al.  Dietary method for reducing fluctuations in Parkinson's disease. , 1987 .

[15]  H. Pakkenberg,et al.  The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1985, The New England journal of medicine.

[16]  O. Hornykiewicz The mechanisms of action of L-dopa in Parkinson's disease. , 1974, Life sciences.

[17]  C. Marsden,et al.  SUCCESS AND PROBLEMS OF LONG-TERM LEVODOPA THERAPY IN PARKINSON'S DISEASE , 1977, The Lancet.

[18]  U. Rinne,et al.  Problems associated with long‐term levodopa treatment of Parkinson's disease , 1983, Acta neurologica Scandinavica. Supplementum.

[19]  D. Faller,et al.  NEUTRAL AMINO ACIDS IN THE BRAIN: CHANGES IN RESPONSE TO FOOD INGESTION 1 , 1978, Journal of neurochemistry.

[20]  W R Woodward,et al.  The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport. , 1984, The New England journal of medicine.