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Dianna K. Hughbanks-Wheaton, David G. Birch, Gary E. Fish, Rand Spencer, N. Shirlene Pearson, Alison Takacs, Dennis R. Hoffman; Safety Assessment of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa: The 4-Year DHAX Trial. Invest. Ophthalmol. Vis. Sci. 2014;55(8):4958-4966. doi: 10.1167/iovs.14-14437.
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Docosahexaenoic acid (DHA) continues to be evaluated and recommended as treatment and prophylaxis for various diseases. We recently assessed efficacy of high-dose DHA supplementation to slow vision loss in patients with X-linked retinitis pigmentosa (XLRP) in a randomized clinical trial. Because DHA is a highly unsaturated fatty acid, it could serve as a target for free-radical induced oxidation, resulting in increased oxidative stress. Biosafety was monitored during the 4-year trial to determine whether DHA supplementation was associated with identifiable risks.
Males (n = 78; 7–31 years) meeting entry criteria were enrolled. The modified intent-to-treat cohort (DHA = 33; placebo = 27) adhered to the protocol ≥ 1 year. Participants were randomized to an oral dose of 30 mg/kg/d DHA or placebo plus a daily multivitamin. Comprehensive metabolic analyses were assessed for group differences. Treatment-emergent adverse events including blood chemistry metabolites were recorded.
By year 4, supplementation elevated plasma and red blood cell–DHA 4.4- and 3.6-fold, respectively, compared with the placebo group (P < 0.00001). Over the trial duration, no significant differences between DHA and placebo groups were found for vitamin A, vitamin E, platelet aggregation, antioxidant activity, lipoprotein cholesterol, or oxidized LDL levels (all P > 0.14). Adverse events were transient and not considered severe (e.g., gastrointestinal [GI] irritability, blood chemistry alterations). One participant was unable to tolerate persistent GI discomfort.
Long-term, high-dose DHA supplementation to patients with XLRP was associated with limited safety risks in this 4-year trial. Nevertheless, GI symptoms should be monitored in all patients taking high dose DHA especially those with personal or family history of GI disturbances. (ClinicalTrials.gov number, NCT00100230.)
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