Biological Safety Assessment of Docosahexaenoic Acid Supplementation in a Randomized Clinical Trial for X-Linked Retinitis Pigmentosa

Abstract

Background: In a 4-year placebo-controlled trial to elevate blood docosahexaenoic acid levels in patients with X-linked retinitis pigmentosa (XLRP), the goal was to assess the potential benefit of docosahexaenoic acid supplementation in altering disease progression. However, docosahexaenoic acid (22:63) is a highly unsaturated fatty acid and considered a target molecule for free-radical oxidative damage. Thus, nutritional provision of docosahexaenoic acid might lead to an increase in antioxidant stress. Additional concerns, such as decreased platelet aggregation, increased bleeding time, and alterations in lipoprotein cholesterol levels, have been reported in supplementation studies with long-chain polyunsaturates.Objective: To assess the biological safety of long-term docosahexaenoic acid supplementation.Design: Forty-four male patients (mean age, 16 years) enrolled in a randomized, double-masked, clinical trial and received docosahexaenoic acid, 400 mg/d, or placebo. Blood samples were collected every 6 months. Biological safety analysis included fatty acids, vitamin A and E concentrations, antioxidant capacity, platelet aggregation, alanine aminotransferase activity, and lipoprotein cholesterol and triglyceride profiles.Results: Mean plasma docosahexaenoic acid levels were elevated 2.5-fold by supplementation compared with baseline. Patients receiving placebo capsules exhibited no change (P = .35) in plasma docosahexaenoic acid content. All adverse events reported were minor and equivalently distributed between groups. Plasma vitamin A concentrations remained unchanged during the trial. Mean plasma vitamin E concentrations were correlated with age (P = .005), such that as patients with XLRP matured, plasma vitamin E concentrations increased to approach normal values. There was a trend (P =.10) toward lower mean vitamin E concentrations in the docosahexaenoic acidsupplemented group after 4 years. Docosahexaenoic acid supplementation did not compromise plasma antioxidant capacity, platelet aggregation, liver function enzyme activity, or plasma lipoprotein lipid content in patients with XLRP. Conclusion:Long-term docosahexaenoic acid supplementation to patients with XLRP was associated with no identifiable safety risks in this 4-year clinical trial.

Vitamin A and fish oils for retinitis pigmentosa

“…Of the eleven articles with a full text review, we excluded seven studies (Bergsma 1977;Berson 2010;Dagnelie 2000;Fex 1996;Sibulesky 1999;Tcherkes 1950;Wheaton 2003). We present the reasons for their exclusion in the 'Characteristics of excluded studies' table.…”

Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review

“…Finally, 8 studies informed in 13 articles were included in the present review. [9][10][11][12][13][14][15][16][17][18][19][20][21] Characteristics of studies…”

“…12 Except Lee et al which studied Best disease, 18 all included studies are on RP. [9][10][11][12][13][14][15][16][17][19][20][21] They assessed supplements based on vitamin A and vitamin E, 12 docosahexaenoic acid (DHA), 9,10,14,16,18 and the carotenoids lutein, 11,13 and β-carotene. 19 We did not identify eligible studies about other HRDs.…”

“…Some of these events were consistent with normal events of adolescence (acne, headaches or weight gain) while others were related to the consumption of DHA capsules (nausea, flatulence and eructation, among others). 21 Through quarterly diaries and in the annual follow-up visits, Hoffman et al gathered self-reported treatmentemergent adverse events. No severe adverse effects were reported.…”

Nonpatentable drugs and the cost of our ignorance

“…9,10 In an epidemiologic study, 11 patients with a diet high in DHA (a median of 0.10 g/d) were at lower risk of Alzheimer's disease than those who consumed less DHA (median 0.03 g/d; relative risk 0.3, 95% confidence interval 0.1-0.9) after adjustments for sex, race, education, total energy intake and the presence of the ε4 polymorphism of the apolipoprotein E gene, the ApoE ε4 allele. Furthermore, various studies [12][13][14][15] (though not all of them) 16 have indicated that blood concentrations of DHA and other n-3 fatty acids are lower in patients with Alzheimer's-related dementia. Because n-3 fatty acids are readily incorporated in cellular membranes, adverse effects from high consumption are rare.…”