Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial.

Randomized, placebo-controlled trial in adults with probable mild to moderate Alzheimer disease recruited from 51 US centers. In the DHA arm, 238 participants were randomized, 238 were included in the ITT analysis, 152 in the per-protocol analysis, and 171 completed 18 months; stable cholinesterase inhibitor or memantine use was allowed, and baseline DHA or omega-3 supplement use was excluded.

Oral algal-derived docosahexaenoic acid (DHA) was given as 1 g per capsule twice daily for a total dose of 2 g/day for 18 months, compared with placebo. The product contained approximately 45% to 55% DHA by weight and did not contain EPA.

DHA supplementation did not slow cognitive or functional decline in mild to moderate Alzheimer disease. The primary outcomes were not significant: ADAS-cog P=.41 and CDR sum of boxes P=.68; ADCS-ADL P=.38 and NPI P=.11 were also null. An APOE ε4-negative subgroup showed less ADAS-cog decline with DHA than placebo (6.23 points [95% CI, 4.08 to 8.38] vs 10.11 points [95% CI, 7.12 to 13.10]; P=.03), but this did not alter the overall conclusion that DHA provided no clinical benefit.

The trial was limited to 18 months and the overall result was null despite a favorable subgroup signal in APOE ε4-negative participants. Subgroup findings should be interpreted cautiously, and the provided extract does not report detailed adherence or adverse-event comparisons. Generalizability is limited to medically stable adults with mild to moderate Alzheimer disease who were not using omega-3 supplements at baseline.