Docosahexaenoic Acid Supplementation and Alzheimer Disease

To the Editor: The recent clinical trial by Dr Quinn and colleagues shows that docosahexaenoic acid (DHA) had no effect on the progression of Alzheimer disease (AD).¹ Multiple epidemiological studies examining fish consumption and tissue DHA levels are cited to support the proposition that increased DHA intake might protect the brain from the devastating effects of dementia. However, epidemiological studies cannot tease apart an isolated contribution of DHA as the determining beneficial factor in fish and seafood.² Fish are an important source of trace minerals, such as iodine and selenium, and increased selenium associated with fish consumption may also contribute to the health benefits ascribed to DHA.² Fish are a major source of vitamin D, which through neurotrophic, anti-inflammatory, and neuroprotective effects may work synergistically with DHA to protect the brain.³ Other omega-3 fatty acids in addition to DHA are also found in fish. These essential fats, including eicosapentaenoic acid (EPA), can themselves have important vascular and anti-inflammatory effects. DHA might interfere with the metabolism of other essential fatty acids from shorter precursors. For example, DHA-only supplements may decrease the abundance of EPA by inhibiting enzymatic conversion from alpha-linolenic acid.⁴ It would be interesting to know if the DHA given in this clinical trial induced changes in other essential fatty acids.