A systematic review of 21 randomised control trials reported that
n-3 PUFA supplementation had no effect on TC [20]. In line with this,
we found no significant association between O3I and TC. However, a
converse trend in the relationship between O3I and risk of hypercholesterolaemia
was noted in males and females. The systematic review
by Balk et al. did not report separate gender analyses. It is therefore
possible that the heterogeneity introduced by including both males
and females in the analyses may have masked or ameliorated the
effect of n-3 PUFA supplementation on circulating levels of TC. A recent
large multinational double-blinded randomised control trial reported
a significant reduction in serum TC following n-3 PUFA supplementation
for 12 weeks [42]. Since 77% of the participants in this study
were males, it is possible that any positive trend between O3I and
hypercholesterolaemia risk in the females remained undetected.