Fish oil supplementation reduces the CERT2 risk score in adults with increased cardiometabolic risk: Findings from the MoKaRi trial.

BACKGROUND: Ceramides and phosphatidylcholines, key components of the Coronary Event Risk Test 2 (CERT2), are strong predictors of cardiovascular events beyond low-density lipoprotein cholesterol (LDL-C). Whether dietary strategies targeting lipidomic risk profiles can modify these biomarkers remains insufficiently explored. OBJECTIVE: To investigate whether long-chain n-3 polyunsaturated fatty acid supplementation, within a structured cardioprotective dietary program, modifies ceramide- and phosphatidylcholine-associated cardiovascular risk in adults at increased cardiometabolic risk in a primary prevention setting. METHODS: The MoKaRi trial was a 20-week, randomized, parallel-group dietary intervention followed by a 20-week follow-up. Adults aged 20-80 years with LDL-C ≥3.0 mmol/L, not receiving lipid-lowering medication, were included. Participants received either personalized cardioprotective menu plans (MP) or identical MP supplemented with 3 g/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (MP-fish oil [FO]). The exploratory endpoint was the change in the CERT2 risk score following the dietary intervention. RESULTS: The MP-FO group demonstrated significantly greater reductions in the CERT2 score throughout the 20-week intervention when compared to the MP group (Week 10: -2.44, 95% CI -3.42--1.47; Week 20: -2.18, 95% CI -3.15--1.21). Although the effect attenuated after 40 weeks, it remained significant (-1.63, 95% CI -2.61--0.65). Only the FO-supplemented group displayed favorable changes in ceramide-phosphatidylcholine ratios. CONCLUSIONS: High-dose EPA + DHA supplementation embedded in a structured heart-healthy diet reduces CERT2 in adults with increased cardiometabolic risk, indicating that this lipidomic risk score is modifiable by nutritional intervention. CERT2 may therefore serve as a responsive biomarker for monitoring improvements in cardiovascular risk beyond LDL-C in preventive cardiology.