BACKGROUND: Prescription omega-3-acid ethyl ester (P-OM3; Lovaza) therapy is indicated for treating very high triglyceride levels (>or= 500 mg/dL) at a dose of 4 g/day. The caloric content associated with each 1-g capsule of P-OM3 is approximately 11 Cal (Cal = kilocalories) - approximately 9 Cal from the oil in the capsule that contains omega-3 fat and approximately 2 Cal attributed to the components of the capsule shell. Thus, the 4-g/day dose contributes approximately 44 Cal/day, with approximately 36 Cal/day derived from the oil. METHODS: This analysis evaluated 167 dyslipidemic (triglycerides: >or= 500 mg/dL and < 1300 mg/dL), overweight/obese (body mass index [BMI] >or= 25 kg/m(2) and <or= 43 kg/m(2)) patients aged 18 to 79 years. Data were derived from an 8-week, randomized, double-blinded, placebo-controlled, parallel-group trial comparing P-OM3 4 g/day + fenofibrate 130 mg/day (n = 84) versus placebo (4 g/day of corn oil) + fenofibrate 130 mg/day (n = 83), and an 8-week open-label extension (n = 117), during which all subjects received P-OM3 + fenofibrate. Subjects who received P-OM3 + fenofibrate continued the same treatment in the extension phase (non-switchers; n = 59). Those who initially received corn oil placebo + fenofibrate received P-OM3 + fenofibrate in the extension phase (switchers; n = 58). RESULTS: During the 8-week double-blind phase in subjects receiving fenofibrate, the addition of P-OM3 (versus placebo) did not significantly change median (minimum, maximum) body weight (P-OM3 = 0 [-4.6, +4.2] kg, placebo = 0 [-3.6, +5.5] kg; P = 0.088) or waist circumference (P-OM3 = +0.1 [-12.1, +17.5] cm, placebo = +0.5 [-9.9, +12.2] cm; P = 0.162). In the 8-week extension phase, non-switchers and switchers did not differ in median change from the end of the double-blind phase in body weight (non-switchers = +0.2 [-3.2, +5.6] kg, switchers = +0.1 [-6.9, +7.9] kg; P = 0.982), or waist circumference (non-switchers = +0.1 [-9.8, +41.8] cm, switchers = +0.2 [-12.0, +7.0] cm; P = 0.685). CONCLUSION: When coadministered with fenofibrate for up to 16 weeks, the modest daily caloric contribution of P-OM3 (4 g/day) did not alter body weight or waist circumference compared with baseline or compared with fenofibrate plus placebo in patients with very high triglyceride levels.