Systematic Review and Meta-analysis of the Differential Effects of DHA and EPA on Inflammation

According to the World Health Organization, cardiovascular diseases (CVDs) are the number 1 cause of death globally. Systemic and local tissue inflammation is now recognized as a key etiological process leading to CVD. Hence, elevated blood levels of inflammation markers are classified among the well-established risk factors for the development of CVD. Among nutritional strategies to prevent and/or reduce chronic inflammation, long-chain omega 3 PUFA (LCn-3PUFA), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have raised tremendous interest for their purported anti-inflammatory effects. Previous meta-analysis of randomized controlled trials (RCTs) substantiated the anti-inflammatory effect of LCn-3PUFA supplementation as evidenced by significant reductions in plasma concentrations of specific inflammation markers such as C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha). However, it is stressed that almost all of the reported RCTs have used a mix of EPA and DHA in various ratios, as EPA and DHA occur concomitantly and naturally in food (fish oils) and in most dietary supplements. Yet, several recent RCTs have recently been undertaken to test the hypothesis that not all LCn-3PUFAs are equal, at least when it comes to their anti-inflammatory effects. Accordingly, there is increasing interest and evidence for potential distinctive effects of DHA compared to EPA on systemic inflammation, raising the question: Is DHA a more potent anti-inflammatory nutrient than EPA? To formally answer this question, we will conduct a systematic review and meta-analysis of RCTs to assess and compare the individual anti-inflammatory effects of DHA and of EPA. The present work will be a pairwise and network meta-analysis focusing on RCTs comparing the effects of EPA and DHA on surrogate markers of systemic inflammation. The findings generated by these analyses will provide invaluable and timely comparative information on the specific efficacy of DHA and EPA as one of the key nutritional modalities for the treatment of chronic inflammation in high-risk men and women. This is important considering that LCn-3PUFA supplements are increasingly being used by the population and an ever growing market in the dietary supplements' industry.