Levodopa, homocysteine and Parkinson's disease: What's the problem?

Elevated circulating homocysteine levels have been associated with cognitive impairment and cardio-cerebro-vascular events. Levodopa treatment of Parkinson's disease tends to further elevate circulating homocysteine levels due to the metabolism of levodopa via catechol-O-methyltransferase (COMT). COMT co-factors are vitamins B12, B6 and folic acid. Accumulating deficiencies of these vitamins are presumed to be the substrate for the homocysteine elevation. B-vitamin therapy reduces homocysteine levels. This begs the question of whether Parkinson's disease patients on levodopa should be concurrently treated with ongoing B-vitamin therapy (versus long-term monitoring of B-vitamins/homocysteine). There is a substantial literature on this topic that has accumulated over the last quarter-century, and this topic is still debated. This review summarizes the relevant literature with the aim of approximating closure on this issue. Also, noteworthy is that Parkinson's disease patients with renal insufficiency may not tolerate cyanocobalamin, the standard oral B12 supplement due to facilitation of renal decline; alternatives are discussed.