Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease

Abstract

Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) micromol/L increased to 10.1 (3.1) micromol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L-dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 micromol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined.

Effect of MTHFR Polymorphisms on Hyperhomocysteinemia in Levodopa-treated Parkinsonian Patients

“…It is noteworthy that Hcy values ‡17.7 lmol/l have been associated to an elevated risk of coronary artery disease (Rogers et al 2003). L-DOPA treatment and homozygosity for the T mutated allele of MTHFR genotype, separately or in combination, have long been recognized as potential risk factors for hyperhomocysteinemia development in PD patients (Yasui et al 2000;Brattstrom 2001;Kuhn et al 2001;Rogers et al 2003;O'Suilleabhain et al 2004;Woitalla et al 2004;Religa et al 2006;Todorovic et al 2006). However, a number of aspects still need to be elucidated in detail.…”

“…from 9.5 up to 18 lmol/l or more, in PD (Yasui et al 2000;Kuhn et al 2001;O'Suilleabhain et al 2004). It is noteworthy that Hcy values ‡17.7 lmol/l have been associated to an elevated risk of coronary artery disease (Rogers et al 2003).…”

“…Recent evidence show a crucial role of levodopa (L-DOPA) therapy in Hcy increase (Yasui et al 2003;O'Suilleabhain et al 2004;Zoccolella et al 2005;Religa et al 2006). L-DOPA, in fact, is metabolised via Omethylation by catechol-O-methyl-transferase (COMT) using S-adenosyl-L-methionine (SAM), the main methyl group donor in the brain, as substrate.…”

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

“…28 The resulting elevation of HC is modest. 32,33 These elevations are blunted when COMT inhibitors are used as adjunctive therapy. 34,35 Studies of the risk of stroke in PD have not consistently demonstrated increased risk.…”

Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

“…Serum hcy has various neuronal and endothelial cellular toxicities, and hyperhomocysteinemia is associated with cardiovascular, ocular, cerebrovascular, and neurodegenerative disease [1,3]. Elevated hcy levels have also been reported to correlate with depression, mild cognitive impairment, and dementia in the elderly population, and hcy levels have been found to predict rates of cognitive decline in healthy elderly individuals [4,5]. Therefore, elevated serum hcy levels have been implicated in the pathogenesis of cognitive impairment such as vascular dementia and Alzheimer' s disease [5,6].…”