On-off effects in Parkinson's disease: a controlled investigation of ascorbic acid therapy

Patients with PD who experience on-off effects have higher erythrocyte catechol-O-methyltransferase (COMT) activities and plasma 3-O-methyldopa concentrations than do patients without these levodopa-related motor fluctuations. We therefore administered ascorbic acid, a weak competitive inhibitor of COMT, to six PD patients with on-off effects. In this double-blind crossover investigation, ascorbic acid produced a modest improvement in functional performance. However, no fundamental change was observed in the pattern of on-off effects, severity of parkinsonism/dyskinesia, or self-assessment ratings. Ascorbic acid therapy reduced plasma concentrations of levodopa and 3-O-methyldopa but did not alter erythrocyte COMT activity. These findings are discussed in the context of the pharmacokinetic and pharmacodynamic factors that contribute to the pathogenesis of levodopa-induced dyskinesias and on-off motor fluctuations.