Benefit of folic acid supplementation in parkinsonian patients treated with levodopa.

CORRESPONDENCE Benefit of folic acid supplementation in parkinsonian patients treated with levodopa We read with interest the recent excellent review by Reynolds on the role of folic acid and the risks and benefits of its supplementa-tion in the nervous system. 1 It emphasises the beneficial importance of folate on the numerous methylation processes in combination with S-adenosylmethionine (SAM), which donates its methyl group to prevent hyperhomocysteinaemia. 1 However SAM deficiency , which is associated with, for example, cognitive decline and/or mood disturbances, and increased total homocysteine levels, which support onset of vascular disease, may also caused by drugs, for example, levodopa. 2 3 Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by the ubiquitious enzyme catechol-O-methyltransferase (COMT) in blood, peripheral tissues and in nigrostriatal neurons. 2 3 COMT requires Mg 2+ as cofactor and SAM as methyl donor. Thus O-methylation of levo-dopa to 3-OMD is associated with conversion of SAM to S-adenosylhomocysteine and subsequently homocysteine. 2 3 We already demonstrated this association between homo-cysteine, SAM and 3-OMD in treated Parkinson's disease (PD) patients, 2 3 who often suffer from depression and bradyphre-nia in the course of the disease and show an increased mortality risk of vascular disease. 4 The objective of our follow up study 2 3 was to determine total plasma homocysteine in 212 levodopa treated and 29 previously untreated PD patients and 110 controls. Standardised measurement of total homocysteine plasma concentrations with high performance liquid chromatography was only performed in subjects with no metabolic disturbances, like diabetes mellitus, hypertension, reduced levels of vitamin B6, cobalamine and/or folic acid or neurological diseases other than PD. Each PD patient fasted and was withdrawn from drug treatment for at least 12 hours before taking of blood samples in the morning. All participants gave informed consent, the local ethical committee approved this study. Homo-cysteine levels were significantly (analysis of covariance F (dF 2, dF 346) =17.5, p=5.9E-08; post hoc analysis (Tukey's HSD test): levodopa treated PD patients compared with controls: p=2.2E-05, previously untreated compared with levodopa treated PD patients: p=0.005; previously untreated PD patients compared with controls: p=0.92) increased in levodopa/ DDI treated PD patients (17.3 (8.2) µmol/l (mean (SD)) compared with previously untreated PD patients (11.4 (5.8) µmol/l) and controls (12.2 (5.5) µmol/l). There was no significant impact of covariates age, sex, daily levodopa dose, and Hoehn and …