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.