Objective: The purpose of this study was to determine if Docosohexanoic acid (DHA) affects the speed and severity of development of levodopa induced dyskinesia (LID) in subjects starting levodopa (LD). Using objective LID quantification, we compared the median time to onset of LID in subjects taking concomitant DHA or placebo.

Background: Administration of DHA, the most abundant omega-3 fatty acid in the brain, delays onset  and progression of LID (de novo strategy) in parkinsonian macaques treated with levodopa¹.  Given these preclinical findings, we investigated the possibility of delaying LID in a RCT design of DHA versus placebo.   We also wanted to determine DHA’s tolerability and safety in PD subjects.

The time to onset of LID is unclear in the literature.  Studies using more objective means to measure LID tend to demonstrate the highest incidence rates however. In a prospective four year evolution of response to LD study with careful observation, 67% developed LID by 1 year²                                                                                                        

Methods: A randomized, double-blind, placebo controlled trail of DHA supplementation in individuals with levodopa-naïve PD between December 2010 and June 2016.

LD naïve participants were randomized to DHA 2g/day or placebo 2 weeks prior to clinical initiation of LD, to be continued for the duration of the study.  Participants completed dyskinesia, tremor, and Parkinson’s ratings during an inpatient intravenous LD infusion at weeks 0, 6, 24, 52, and 76.  Safety and tolerability of DHA was assessed each month and during each visit.

Results: 34 subjects were screened based on the prior 67% incidence rate of LID in the first year of LD exposure.  33 were randomized to treatment or placebo, 30 subjects completed at least 12 months of study participation.  No differences in age, food DHA intake, baseline MoCA, Hoehn & Yahr, LD dose, symptom duration, or years from diagnosis were detected between groups. 

DHA was well tolerated.  In the placebo group 7/15 subjects developed LID within 12 months versus 3/15 subjects taking DHA.  There was no difference in peak severity between the two groups. 

Full analysis will be completed in time for the meeting.

Conclusions: In this preliminary study of PD patients beginning Levodopa, concomitant use of DHA may delay onset of LID.  This finding warrants a larger study and suggests the possibility of LID prevention. 

References: 1. Samadi P, Gregoire L, Rouillard  C, Bedard PJ, DiPaolo T, Levesque D  Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1.2.3.6-tetramydropyridine monkeys.  Ann Neurol 2006 Feb; 59 (2):  282-8

2.  Nutt JG, Carter JH, Lea ES, Sexton GJ Evolution of the response to levodopa during the first 4 years of therapy.  Ann Neurol  2002 Jun; 51 (6):686-93.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/preventing-levodopa-induced-dyskinesia-with-docosohexanoid-acid-in-parkinson-disease/