In the 20-week MoKaRi randomized trial, adults with elevated LDL-C (≥3.0 mmol/L) not on lipid-lowering therapy who received 3 g/day of EPA+DHA alongside a personalized cardioprotective diet achieved significantly greater reductions in the CERT2 score compared to diet alone — by 2.44 points at week 10 and 2.18 points at week 20. The ceramide-to-phosphatidylcholine ratios, the mechanistic core of CERT2, shifted favorably only in the fish oil group. The effect persisted, though attenuated, at 40 weeks.
CERT2 matters because ceramide-based risk scores predict cardiovascular events independently of LDL-C, capturing lipotoxic pathways — particularly ceramide-induced endothelial dysfunction and apoptosis — that statins do not fully address. Most dietary interventions target LDL-C; this trial demonstrates that omega-3 fatty acids remodel the sphingolipid landscape in a clinically meaningful direction, a finding with real preventive relevance.
Limitations are worth noting: CERT2 reduction was an exploratory, not primary, endpoint; the trial was relatively small and short; and it is unclear whether CERT2 score reductions translate directly into fewer cardiovascular events. Still, this is confirmatory evidence that high-dose omega-3 supplementation operates through mechanisms orthogonal to conventional lipid-lowering, suggesting clinicians managing borderline-risk patients might consider fish oil as a complement to dietary counselling — particularly in those with unfavorable ceramide profiles.