Until now, there has been very little guidance about what dose of EPA and DHA should be tested in a study. And with the wide differences in study results in recent years, it is likely that it does play a role in the relative success or failure of omega-3 studies. In other words, if the dose of EPA and DHA in a study isn't high enough to make an impact on blood levels (i.e., the Omega-3 Index), there may be no effect on the desired endpoint, leading to a neutral result.
When it comes to cardiovascular disease (CVD) in particular, the literature supporting the benefits of omega-3s EPA and DHA has been mixed. On the one hand, a 2018 meta-analysis concluded that current evidence does not support a role for omega-3s in CVD risk reduction.
On the other hand, three major randomized trials reported in late 2018 showed that omega-3s significantly reduced the risk for vascular death, myocardial infarction, and major adverse cardiovascular events. The latter study was particularly compelling because it used 4 grams of EPA (as opposed to the usual 0.84 grams of EPA and DHA) in statin-treated patients and found a 25% risk reduction in CVD events.
According to Kristina Harris Jackson, Ph.D., RD, who was the co-lead author on this latest paper, "A low dose could make a study show no effect of EPA and DHA, which makes the literature more indecisive and the medical community more skeptical of omega-3 benefits," she said. "Hopefully, ensuring the dose of EPA and DHA is high enough to reach a target Omega-3 Index level will clarify whether or not EPA and DHA are effective."
How to Use the Calculator
The model equation developed in this paper can be used to estimate the final Omega-3 Index (and 95% CI) of a population given the omega-3 EPA and DHA dose and baseline Omega-3 Index. As an example, a population with a baseline Omega-3 Index of 4.9% that is given 840 mg EPA and DHA per day (as a 1-gram ethyl ester capsule) would achieve a mean Omega-3 Index of 6.5% (95% CI: 6.3%, 6.7%).
Rearranging the equation, one can calculate the approximate EPA/DHA doses (of triglyceride forms) needed to achieve a mean Omega-3 Index of 8% in 13 weeks. This would require about 2200 mg of EPA and DHA for a baseline Omega-3 Index of 2%, approximately 1500 mg for a baseline Omega-3 Index of 4%, and roughly 750 mg of EPA and DHA for a baseline Omega-3 Index of 6%.
Using this example, Jackson and her colleagues predicted that the minimum dose of EPA and DHA necessary to be 95% certain that the mean baseline Omega-3 Index of 4% will increase to 8% (in 13 weeks) is ?1750 grams per day of a triglyceride formulation or 2500 grams per day of an ethyl ester formulation. Both of these forms are common in fish oil preparations.
So in order for 95% of subjects (not just 50%) to achieve a desirable Omega-3 Index from a baseline of? 4%, roughly 2000 grams per day of EPA and DHA (depending on the chemical form) would likely be required.
Do Researchers Still Need the Omega-3 Index if They Have a Calculator?
The calculator presented in this paper does not eliminate the need for Omega-3 Index testing. In fact, establishing a baseline Omega-3 Index is essential to use the calculator.
"The recommended doses are simply average responses, but individual responses to EPA and DHA are still very difficult to predict," said Dr. Jackson. "In a recent consumer cohort, we found individuals spanned the full range of Omega-3 Index despite reporting the same amount of fish intake and supplement use."
This paper showed that if people want to reach 8% in a relatively short amount of time, such as three to four months, they would need 1-2 grams EPA and DHA per day, depending on their starting Omega-3 Index.
"As noted, the equation developed [in this paper] can aid in predicting population Omega-3 Index changes, but because of the large interindividual variability in the Omega-3 Index response to EPA and DHA supplementation, it will likely be less useful in the clinical setting where direct testing of the Omega-3 Index would be the preferred approach to assessing EPA and DHA status," the study authors explained.