Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients

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Abstract
Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O‐methylation of levodopa catalyzed by catechol‐O‐methyltransferase (COMT) that produces S‐adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT‐I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT‐I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT‐I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa‐treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT‐I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT‐I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT‐I effectively reduces HHcy. © 2004 Movement Disorder Society