Docosapentaenoic acid (DPA, C22:5n-3) is a long-chain omega-3 fatty acid that is the intermediary between EPA and DHA in the metabolic pathway. Recent studies have demonstrated a relationship between blood levels of DPA and brain, heart, and metabolic health. This begs the question, why is DPA not included in the Omega-3 Index?
In 2002-2003 when Drs. Harris and Von Schacky were “inventing” the concept of the Omega-3 Index, they focused primarily on two studies available at the time: Siscovick DS et al. JAMA, 1995 and Albert CM et al. NEJM, 2002. Both of these studies showed that red blood cell or whole blood omega-3s strongly predicted risk for sudden cardiac death. Siscovick only reported red blood cell EPA+DHA. Albert showed case-control values for EPA, DHA, and DPA, but only EPA and DHA were associated with future events and DPA was not different between cases and controls. Combine that with the very limited knowledge about DPA in those days, it made the most sense to them to focus on EPA+DHA alone. Fast forward 10 years and we are beginning to see some signs that DPA is also predictive certain events. So, should we add it to the Index?
One question is, “How well correlated is the original with the modified Index?” Below are the data from the Framingham Offspring. The modified Index is extremely highly correlated (r=0.98) with the original Index, so adding DPA adds no more information to the original Index. The modified Index is about 2.7% points higher than the original (since that’s what red blood cell DPA typically is).
The other major question is, “Does a modified Omega-3 Index (with DPA) predict events significantly better than the original Index?” This question is harder to answer, but if the two Indexes are that highly correlated, the chances of one metric being significantly better at predicting outcomes (any outcome) than the other are vanishingly small.
With this background, the question becomes, “Is it worth ‘upsetting the apple cart’ to change the numerical cut points for the Omega-3 Index just because some studies are showing DPA to be a predictor on its own?” The upside of adding DPA is that it’s more “intellectually satisfying” to accommodate all the evolving science in biostatus metrics. The downside is that the new cut points would confuse the nascent literature in this field (i.e. “Is that the OLD Index or the NEW one?”), and it would confuse the growing number of practitioners who are managing patients’ Omega-3 Index values in clinical care. We believe the DPA is important scientifically, but that it is not necessary to add to the Omega-3 Index at this time.