Effect of omega-3 supplements on plasma apolipoprotein C-III concentrations: a systematic review and meta-analysis of randomized controlled trials

Ann Med. 2018 Nov;50(7):565-575. doi: 10.1080/07853890.2018.1511919. Epub 2018 Sep 29.

Abstract

Background: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides metabolism. The aim of this meta-analysis was to assess the effect of fish omega-3 polyunsaturated fatty acids (PUFAs) on apo C-III levels.

Methods: Randomized placebo-controlled trials investigating the impact of omega-3 on apo C-III levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters.

Results: This meta-analysis comprising 2062 subjects showed a significant reduction of apo C-III concentrations following treatment with omega-3 (WMD: -22.18 mg/L, 95% confidence interval: -31.61, -12.75, p < .001; I2: 88.24%). Subgroup analysis showed a significant reduction of plasma apo C-III concentrations by eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as compared with supplements containing EPA and docosahexaenoic acid (DHA) or only DHA. A positive association between the apo C-III-lowering effect of omega-3 with baseline apo C-III concentrations and treatment duration was found.

Conclusions: This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo C-III. Key messages Omega-3 PUFA supplements significantly reduce apo C-III plasma levels, particularly in hypertriglyceridemic patients when applied in appropriate dose (more than 2 g/day) Triglyceride (TG)-lowering effect is achieved via peroxisome proliferator-activated receptors α Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA.

Keywords: Omega-3 fatty acids; PUFA; cardiovascular disease; coronary heart disease; docosahexaenoic acid; eicosapentaenoic acid.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Apolipoprotein C-III / antagonists & inhibitors
  • Apolipoprotein C-III / blood*
  • Apolipoprotein C-III / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Dietary Supplements*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / epidemiology
  • Hypertriglyceridemia / prevention & control*
  • Oligonucleotides / administration & dosage
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Apolipoprotein C-III
  • Fatty Acids, Omega-3
  • ISIS 304801
  • Oligonucleotides
  • Triglycerides