The effects of fatty acid–based dietary interventions on circulating bioactive lipid levels as intermediate biomarkers of health, cardiovascular disease, and cardiovascular disease risk factors: a systematic review and meta-analysis of randomized clinical trials

Abstract Context Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic precursor lipoprotein-associated phospholipase A2 (Lp-PLA2) mass; however, the magnitude of this effect remains unclear. Objective The aim of this systematic review and meta-analysis was to evaluate the effect of different dietary FAs on the bioactive lipid profile of healthy participants and those with cardiovascular disease (CVD) and CVD risk factors. Data sources PubMed, SCOPUS and the Cochrane Library databases were searched for relevant articles published between October 2010 and May 2022. Data extraction Data were screened for relevance and then retrieved in full and evaluated for eligibility by 2 reviewers independently. Data analysis The net difference in the bioactive lipid mean values between the endpoint and the baseline, and the corresponding SDs or SEs, were used for the qualitative synthesis. For the meta-analysis, a fixed-effects model was used. Results Twenty-seven randomized clinical trials (representing >2560 participants) were included. Over 78% of the enrolled participants had ≥1 associated CVD risk factor, whereas <22% were healthy. In the meta-analysis, marine n-3 supplements (dose range, 0.37–1.9 g/d) significantly increased pro-inflammatory lysophosphatidylcholines (lyso-PCs; for lyso-PC(16:0): mean, +0.52 [95% confidence interval (CI), 0.02–1.01] µM; for lyso-PC(18:0): mean, +0.58 [95%CI, 0.09–1.08] µM) in obese participants. Additionally, n-3 supplementation (1–5.56 g/d) decreased plasma Lp-PLA2 mass, a well-known inflammation marker, in healthy (–0.35 [95%CI, –0.59 to –0.10] ng/mL), dyslipidemic (–0.36 [95%CI, –0.47 to –0.25] ng/mL), and stable coronary artery disease participants (–0.52 [95%CI, –0.91 to –0.12] ng/mL). Conclusions Daily n-3 provided as EPA+DHA supplements and consumed from 1 to 6 months reduced plasma Lp-PLA2 mass in healthy participants and those with CVD and CVD risk factors, suggesting an anti-inflammatory effect. However, the saturated lyso-PC response to n-3 was impaired in obese participants. Systematic Review Registration PROSPERO registration no. CRD42021218335