Efficacy of phospholipid-bound omega-3 versus standard omega-3 in patients with hypertriglyceridemia: a randomized clinical trial.

BACKGROUND: Hypertriglyceridemia is a modifiable risk factor for cardiovascular disease, and while omega-3 fatty acids (omega-3 FAs) are known to lower triglyceride (TG) concentrations, their effectiveness is influenced by formulation and bioavailability. Phospholipid-bound (PL) omega-3 FAs—such as those found in krill oil—demonstrate superior intestinal absorption and membrane integration compared with TG- and ethyl ester omega-3 FAs based forms. Preclinical studies have shown that PL omega-3 FAs exhibit anti-inflammatory, antithrombotic, and TG-lowering properties; however, clinical data remain limited. This pilot randomized clinical trial compared the efficacy of PL omega-3 FAs with standard omega-3 FAs in patients with mild to moderate hypertriglyceridemia. METHODS: We performed a randomized, controlled, double-blind, parallel-group pilot trial involving patients aged 18–65 years with fasting TG between 150 and 499 mg/dL. Patients were randomized to receive PL omega-3 FAs (eicosapentaenoic acid [EPA) + docosahexaenoic acid [DHA), 825 mg/day) or standard omega-3 FAs (EPA + DHA, 903 mg/day). Primary outcomes were changes in fasting TG and omega-3 index (O3I) after 12 weeks. Secondary outcomes included changes in lipid profile, glycemic markers, inflammatory markers, anthropometric measures, hemodynamic variables, and safety parameters. RESULTS: Of the 47 randomized participants, 44 (22 per group) completed the study and were included in the analysis. Mean TG levels decreased slightly in the PL group (-9.1 mg/dL) and increased in the standard group (+ 15.2 mg/dL), with no statistically significant difference between-groups (p = 0.416). Although the O3I increased significantly in both groups, the between-group difference was not statistically significant, despite a greater rise in the PL group (+ 1.78% vs. +1.50%, p = 0.446). At week 12, 36.4% of participants in the PL group achieved TG ≤ 150 mg/dL, compared with 13.6% in the standard group (p = 0.041). No serious adverse events were reported, and treatment adherence exceeded 95%. CONCLUSIONS: In summary, this pilot randomized trial did not demonstrate statistically significant differences between the PL and TG formulations in triglyceride or Omega-3 Index reduction. However, the numerically higher responder rate and favorable biochemical trends observed with the PL formulation warrant further investigation in larger, adequately powered studies. TRIAL REGISTRATION: NCT06749028 (retrospectively registered on December 19, 2024, after enrollment of the first participant). Available at: https://clinicaltrials.gov/study/NCT06749028 . EUROPEAN FOOD SAFETY AUTHORITY (EFSA): EFSA-2024-00030369.