To our knowledge, the present study is the first to report a significant increase in blood EPA and DHA levels, as Omega-3 Index, in a group of healthy individuals who were regular consumers of fish oil supplements at baseline. Maximizing the response to omega-3 supplementation may be a prudent clinical target for the reduction of certain risk factors, and Omega-3 Index may be an appropriate biomarker for assessing and monitoring the effectiveness of omega-3 supplementation.
An increase in the Omega-3 Index has been correlated with reductions in cardiovascular risk factors, and low Omeg-3 Index has been reported as a predictor of sudden cardiac death [24–27]. Importantly, it has also been suggested that an Omega-3 Index of greater than 8% was associated with a lower risk for acute coronary syndromes and decreased morbidity and mortality in those with cardiovascular disease . Conversely, an Omega-3 Index less than 4% was associated with a ten-fold increase in risk of cardiac death compared to subjects with an Omega-3 Index greater than 8% . Inflammatory markers were also shown to be inversely related to Omega-3 Index , and an Omega-3 Index of 8% or higher was associated with slowed cellular aging as measured by the five-year rate of telomere shortening .
In the current study, we demonstrated a significant increase in Omega-3 Index in 120 days of regular supplementation with a high potency fish oil. Assuming a clinical target of >8%, the percentage of subjects meeting this target increased from 5.6% at baseline to 24.8% of subjects following supplementation. Such an increase may be expected to yield clinically relevant outcomes among responders, although this would require further study. It is unknown whether continued supplementation would further raise Omega-3 Index scores beyond what was observed at 120 days or increase the number of subjects achieving a score of >8%, although this seems a reasonable extrapolation of the current data.
The SF-12 health survey provides a quick assessment of an individual’s physical and mental health. The average baseline mental health and physical health scores from this study are similar to those previously reported . In this study, we also detected a small but significant increase in mental health scores based on the SF-12 mental health composite compared to baseline. However, the study design did not include a placebo control, and there are insufficient corroborative data to conclude that omega-3 supplementation and a corresponding increase in Omega-3 Index can improve cognitive function in a healthy population.
The current study had certain limitations in design and execution. First, information was not obtained about the composition of omega-3 fatty acid products being consumed prior to the study, and only a basic analysis of omega-3 intake from food sources was performed (not reported). Subjects were instructed to maintain normal dietary habits, and fish consumption was not restricted. Further, it is possible that the subjects could have self-reported inaccurate information regarding their supplement use; however, over-reporting of supplement use is not likely as their omega-3 status was higher than what has been reported in the typical population. Next, the use of an open-label design creates the potential for bias by both investigator and subject. The virtual CRO is designed to track and monitor the subject compliance with minimal human interaction and influence. While this is a positive, the tradeoff may be in overall compliance. While the absence of a placebo does not allow for the determination of normal changes in blood EPA and DHA levels associated with daily nutritional practices, because the subjects had already been taking a fish oil supplement, the baseline value served as the surrogate placebo or comparator value. Further, it was impractical and perhaps unethical, given the known health benefits of omega-3 consumption, to restrict omega-3 supplementation in a currently supplementing healthy population for a prolonged period of 4 months. Therefore, it was determined that a placebo was not required. Clearly, the lack of a placebo arm does not allow for the assessment of causality in the subjective assessment of mental health scores.