Docosahexaenoic Acid Supplementation and Alzheimer Disease—Reply

In Reply: We agree with Dr Umhau's contention that our trial of DHA for the treatment of AD does not exclude the possibility that non-DHA components of fish, consumed over long periods of time, may have beneficial effects on the aging brain that were not detected in our trial. We elected to use DHA rather than fish oil or mixed omega-3 fatty acids because animal studies showed that DHA alone is sufficient to modify Alzheimer-like brain pathology in transgenic mouse models,^1- 2 brain levels of EPA are exceedingly low, EPA has antiplatelet properties that might increase the risk of complications, and this strategy also avoided the risk of other ocean-borne contaminants in fish oil. However, we recognize that this strategy may have excluded potentially beneficial components of fish oil, including selenium and vitamin D, as well as EPA. With respect to EPA in particular, however, we have as-yet-unpublished data from this trial relevant to Umhau's hypothesis that DHA supplementation might actually “decrease the abundance of EPA”: plasma levels of EPA increased from mean (SD) 0.86 (0.53) weight percent (wt%) at baseline to 1.83 (0.82) wt% at 18 months in participants who took DHA supplements, with no significant change in placebo-treated participants (0.78 [0.4] wt% at baseline and 0.67 [0.26] wt% at 18 months; P < .001). This is presumably due to retroconversion of DHA to EPA.^3- 4