Fish oil might prevent asthma

The investigators randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n−3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children’s lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n−3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there were no statistically significant associations between supplementation and asthma exacerbations, eczema, or allergic sensitization.

The authors concluded that supplementation with n−3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third.

The authors must be congratulated. This trial is stunning in many ways: it was carefully designed and executed; its results are clear and important; its write-up is excellent. The research was supported by private and public research funds, all of which are listed at www.copsac.com. The Lundbeck Foundation, the Danish Ministry of Health, the Danish Council for Strategic Research, the Danish Council for Independent Research, and the Capital Region Research Foundation provided core support.

It is debatable whether the intake of fish oil falls under the umbrella of alternative medicine. In a way, it reminds me of the famous saying: what do we call alternative medicine that works? We call it medicine. It also holds an important reminder for all who make claims about the benefit of alternative therapies: extraordinary claims require extraordinary evidence.

Can these findings be translated into practical advice to consumers? The NEJM discussed this question in an accompanying article in which the case of a fictional pregnant woman (Ms. Franklin) was considered. Here is what they concluded: …there is benefit and little risk associated with n−3 LCPUFA supplementation. Even though we do not know Ms. Franklin’s EPA and DHA levels, there is likely to be a benefit for her child, at little risk, cost, or inconvenience. She should start taking n−3 LCPUFA supplements.

Despite my soft spot for fish oil, I might add that, while we give advice of this nature, we nevertheless need to insist on independent replications to have certainty.