Abstract
Abstract: :
Purpose: The omega-3 long-chain polyunsaturated fatty acid, DHA is an integral component of membranes in photoreceptors and influences functional responses in the retina. To index tissue DHA status in patients, red blood cell (RBC) fatty acid levels are utilized. Since approximately 75% of patients with XLRP have 30-to-40% lower than normal RBC levels of DHA, we conducted an intervention trial with daily nutritional supplementation of DHA. The goals of this trial were to elevate RBC-DHA in patients and to determine whether variations in RBC-DHA are related to disease progression. Methods: Male patients diagnosed with early stage XLRP (mean age=16 year; range=4-38 year) were randomized to groups receiving gel capsules containing DHA-enriched oil (400 mg DHA/day; n=23) or a corn/soy oil placebo (n=21). Due to variations in age and bodyweight, the dosage of DHA in the supplemented group ranged between 4 and 23 mg/kg body weight/day (mean=9±5 mg/kg/day). RBC-DHA concentrations and functional assessments (ERG, visual acuity, peripheral fields) were determined every 6 months and 12 months, respectively, throughout the 4-year trial with full-field ERG response amplitudes to 31-Hz flicker serving as the primary trial outcome measure. Intent-to-treat protocol was utilized for all data analysis. Results:Mean concentrations of RBC-DHA were significantly (p<0.0005) elevated (2.5-fold) upon supplementation. In DHA-supplemented patients, the time to reach a significant (40%) cone loss was delayed by 2.1 years (p=0.025) compared to patients in the placebo group. A significant correlation was found such that patients with elevated RBC-DHA levels had reduced rates of cone ERG loss over the 4-year duration (p=0.011). No group differences or correlations with DHA were found for visual acuity or peripheral fields. Biological safety concerns and adverse events associated with DHA supplementation were negligible. Conclusions:The ERG measures of retinal function suggest a beneficial role for long-term nutritional supplementation with DHA in retarding disease progression of XLRP. Further research is needed to establish effective dosages and benefits for XLRP and other types of retinitis pigmentosa.
Keywords: clinical (human) or epidemiologic studies: tre • retinal degenerations: hereditary • lipids