Abstract
Previous randomized controlled trials (RCTs) made direct comparisons between EPA/DHA versus ALA on improving cardiovascular risk factors and have reached inconsistent findings. The aim of this meta-analysis was to compare the effects of EPA/DHA vs. ALA supplementation on cardiometabolic disturbances. Databases including MEDLINE, Embase, PubMed and Cochrane Trials were searched until December 2019. The pooled effects (weighted mean difference, WMD) of outcomes with moderate and high heterogeneity were calculated with a random-effects model, while low heterogeneity was calculated with a fixed-effect model. Fourteen RCTs with 1137 participants who met the eligibility criteria were pooled. Compared with participants supplemented with ALA, those who received EPA/DHA supplementation experienced a greater reduction in triglycerides (TG) (WMD -0.191 mmol l-1; 95% CI -0.249, -0.133) but a greater increase in high-density lipoprotein (HDL) (WMD 0.033 mmol l-1; 95% CI 0.004, 0.062), low-density lipoprotein (LDL) (WMD 0.130 mmol l-1; 95% CI 0.006, 0.253) and total cholesterol (TC) (WMD 0.179 mmol l-1; 95% CI 0.006, 0.352). In subgroup analyses, the WMD for TG was much lower in trials with participants >40 years old (-0.246 mmol l-1; 95% CI -0.325, -0.167). When DHA and EPA were separately administered, modest increases in HDL were observed in trials that used DHA as a supplement (0.161 mmol l-1; 95% CI 0.017, 0.304), but not in trials using EPA (0.040 mmol l-1; 95% CI -0.132, 0.212). In conclusion, dietary EPA/DHA supplementation improved the TG and HDL status but increased LDL levels in comparison with ALA.
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Key Points
Evidence from epidemiological studies suggests that the mean daily dietary intakes of ALA are much higher than those of EPA and DHA. An increasing number of randomized controlled trials (RCTs) have been performed to directly compare the influence of ALA and its long-chain fatty acid derivatives on a wide range of cardiovascular risk markers. Two previous meta-analyses including RCT trials have been performed to evaluate the influences of EPA/DHA or ALA on cardiometabolic disturbances but no meta-analysis has been conducted to make a direct comparison between EPA/DHA and ALA. The main objective of the present study was to systematically carry out a meta-analysis of randomized controlled trials to assess the effects of ALA with those of EPA/DHA on cardiometabolic risk factors. The findings suggested that compared with subjects supplemented with ALA, subjects supplemented with EPA/DHA experienced a greater TG reduction but greater increases in TC, HDL and LDL after 2 weeks to six months of intervention. No differences on the impacts of the EPA/DHA versus ALA supplementation on VLDL, glucose and TC: HDL were found. In the present meta-analysis, subjects in the EPA/DHA groups showed greater TG reduction and greater increases in TC, HDL and LDL in comparison with those of the ALA group.
It is well established that intakes of EPA and DHA in excess of ∼1 g d−1 lower plasma TG concentrations in a dose-dependent manner, but ALA lacks this effect even at high intakes. But the reduction in serum triglyceride concentration is also accompanied by altered cholesterol ester transfer protein activity, resulting in increases in the less-dense fractions of LDL and HDL. EPA was not superior to ALA in improving HDL status. In comparison with ALA, supplementing with EPA/DHA could elicit more favourable changes in HDL and TG levels and less favourable changes in LDL and TC levels. This differential effect may be affected by the subtypes and dosage of marine n-3 PUFAs, age and BMI of participants, which suggested inter-individual variations for requirements in n-3 PUFA.