Elevated Plasma Homocysteine Levels in Patients Treated With Levodopa

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Abstract
ELEVATIONS IN plasma levels of homocysteine, a sulfur-containing amino acid, is an emerging risk factor for vascular disease, including coronary artery disease (CAD), stroke, peripheral vascular disease, and venous thrombosis.1-6 More recently, hyperhomocysteinemia has been implicated as a risk factor in Alzheimer disease7-11 and has been associated with mild cognitive deficits in nondemented elderly subjects12,13 and with affective disorders.14,15 Elevations in plasma homocysteine levels result from a complex interaction of acquired and genetic factors, but quantitatively the most important are deficiencies of folate, vitamin B12, and vitamin B6.1 Recently, several reports16-19 have indicated that patients with Parkinson disease (PD) have significant elevations of plasma homocysteine levels. In PD, elevated homocysteine levels may result from treatment with levodopa, rather than vitamin deficiency. An important pathway for metabolism of levodopa is methylation by catechol O-methyltransferase (COMT), an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine (SAH). Since SAH is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels.