Why the change of heart?
There are two things going on here. First, the reason studies are yielding neutral results in areas where there is strong evidence that EPA and DHA have beneficial effects appears to lie in the experimental design. Second, many of these studies are demonstrating positive effects, but they are understated in the conclusions and media reporting of the studies. It’s not clear why this is happening, but it is.
While there is no perfect experimental design, scientists need to weigh the pros and cons when designing any experiment. The following are issues with experimental design that don’t receive enough attention and could be responsible for the recent run of neutral results in omega-3 studies.
- Drug Cocktails: Today’s standard of care for cardiac patients is to maintain them on an aggressive therapy of multiple drugs. It’s difficult for omega-3s to demonstrate a benefit when patients are already taking drugs that have similar benefits. Imagine if you added another cardiac drug to an already heavy drug regime. The likelihood of demonstrating any additional benefit is on par with adding omega-3s to the mix.
- Sample Size: Too few subjects yields an underpowered study and the conclusion from such a study should not be described as a failure to have an effect, rather a failure to detect an effect. This is particularly problematic in omega-3 studies that mix healthy subjects with cardiac patients.
- Background Omega-3 Intake: While people in most countries continue to fall short of ingesting a sufficient amount of EPA+DHA, average intakes have crept up in many countries. As a result, people are no longer as “deficient,” making it more difficult to demonstrate a benefit. This does not mean that omega-3s do not provide protective effects; in fact, it may mean that the subjects in the study are already protected.
- Treatment Duration: Many of the neutral studies have been too short in duration. For cardioprotection, many scientists believe that most omega-3 studies need to follow patients for at least five years to see statistically significant benefits, but many have only lasted 2-3 years.
- Control/Placebo: There’s some thought that olive oil, which is a popular placebo, may not be appropriate, given that oleic acid, the primary fatty acid in olive oil, has been demonstrated to have heart health benefits. Is there a better choice?
- Omega-3 Dosage: In general, 250-500 mg/day of EPA+DHA is recommended for primary prevention (prevention of disease before it develops), while 1 g+/day is recommended for secondary prevention (detection and treatment of disease before it is symptomatic). It’s worth noting that many secondary prevention studies are inappropriately characterized by the media as being primary prevention, implying the results would be applicable to the general, healthy population. Obviously, this is not true.
- Endpoints: In many of the more recent omega-3 studies, a combination of endpoints has been studied as a single variable, including endpoints that omega-3s have not previously been shown to effect. The cleanest experimental design would be to study cardiovascular disease endpoints in isolation, rather than creating artificial noise by adding unreasonable endpoints.
- O-3 Assessment Method: These methods include, but are not inclusive of, subjective measurements like validated food frequency questionnaires and objective measurements like plasma or RBC omega-3s. While subjective measurements are prone to more noise, they have been used successfully for many decades. The more recent issues have been that these successful methods have limitations that are often ignored to the point of overstating the significance of the findings.
This blog is excerpted from an article written by Harry B. Rice, GOED V.P., Regulatory & Scientific Affairs, in the April issue of Nutraceutical Business Review.