Review: No Link Between Omega-3s, Cognitive Health

LONDONA new meta analysis published in the Cochrane Database of Systematic Reviews 2012 suggests omega-3 PUFA supplementation has no benefit for cognitive function among healthy older adults. The authors concluded omega-3 supplements may have other health benefits, and recommended consumption of fish as part of a healthy diet.

Researchers from the London School of Hygiene & Tropical Medicine and the Tan Tock Seng Hospital in Singapore reviewed studies where healthy participants over age 60 years who were cognitively healthy at the start of the study were randomly assigned to receive extra omega-3 PUFA in their diet or a placebo (such as olive oil). The main outcomes of interest were new cases of dementia diagnosed during the study period, cognitive decline, side effects and adherence to the intervention.

The authors included three randomized controlled trials involving 3,536 participants. In two studies participants were randomly assigned to receive gel capsules containing omega-3 PUFA or olive or sunflower oil for six or 24 months. In the third study, participants were randomly assigned to receive tubs of margarine spread for 40 months (regular margarine versus margarine fortified with omega-3 PUFA).

None of the studies examined the effect of omega-3 PUFA on new dementia cases over the study period. In two studies involving 3,221 participants there was no difference between the omega-3 PUFA and placebo group in mini-mental state examination score at final follow-up. In two studies (1,043 participants), other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced little or no cognitive decline during the studies.

The main reported side effect of omega-3 PUFA supplementation was mild gastrointestinal problems, but overall minor symptoms were reported by fewer than 15% of participants, and people in the control group were just as likely to report symptoms as those receiving an omega-3 PUFA supplement. Adherence to the supplementation protocol was high in all trials with on average over 90% of supplements being apparently consumed by trial participants.

Harry B. Rice, Ph.D., vice president, regulatory and scientific affairs, Global Organization for EPA and DHA Omega-3s (GOED) questioned why the three studies included in the review did not appropriately assessed the effects of omega-3 supplementation for the prevention of dementia and cognitive decline in the population of interest, especially when studies that fit this criteria are available. Rice noted MIDAS5 (Memory Improvement With Docosahexaenoic Acid Study), published in 2010, demonstrated that 24-week supplementation with 900 mg/d docosahexaenoic acid (DHA) improved learning and memory function in age-related cognitive decline.

He said the small amount of data that exists for this particular population is not enough to warrant a review. Of the studies that were included in the review, GOED said they all had limitations:

Rice further said cognitive decline studies should screen for apolipoprotein E4 (Apo E4), a risk factor for cognitive decline. "Clinical trials not accounting for Apo E4 are destined for failure because they are likely to be grossly underpowered," he said, adding of the three trials included in the review, only MEMO looked at the Apo E4 status of the subjects. "In that study, there was an effect on cognitive attention of EPA and DHA supplementation in subjects carrying the APO E4 allele. While this was only a subgroup analysis, this is nothing short of amazing given that the study included so few subjects to begin with and only about one-third of the subjects were carriers. Imagine the results that might have been seen if the subject pool had been screened appropriately."