ATLANTIS Trial: Phospholipid Omega-3 Versus Conventional Omega-3

Mixed dyslipidemia is a metabolic condition characterized by elevated triglyceride levels and other lipid abnormalities and is associated with increased residual cardiovascular risk despite standard lipid-lowering therapy. Addressing lipid abnormalities beyond low-density lipoprotein cholesterol may help reduce this residual risk.

The Omega-3 Index is defined as the percentage of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes and reflects long-term omega-3 fatty acid exposure and tissue incorporation. Higher Omega-3 Index values have been associated with more favorable cardiovascular risk profiles.

The chemical form of omega-3 fatty acids influences their absorption and bioavailability. Phospholipid-bound omega-3 formulations have demonstrated more efficient intestinal absorption and cellular membrane incorporation compared with conventional triglyceride-based formulations. This study was designed to evaluate whether different dose levels of a phospholipid-based omega-3 supplement result in greater changes in the Omega-3 Index compared with a conventional triglyceride-based omega-3 supplement.

This is a randomized, double-blind, parallel-group clinical trial with three study arms. Eligible participants are adults with mixed dyslipidemia receiving stable statin therapy. Participants are randomly assigned to receive either a phospholipid-based omega-3 supplement at a moderate dose, the same supplement at a higher dose, or a conventional omega-3 supplement in triglyceride form. All study products are administered orally once daily with food for a total duration of 24 weeks.

The primary objective of the study is to compare the Omega-3 Index at week 24 among treatment groups, adjusted for baseline values. Secondary objectives include evaluation of changes in lipid parameters, inflammatory biomarkers, glucose metabolism, anthropometric measures, blood pressure, treatment adherence, and safety outcomes.

The study is conducted in accordance with ethical principles for research involving human participants and has been approved by an institutional ethics committee. Participation is voluntary, and all participants provide written informed consent prior to any study-related procedures.

Inclusion criteria

• Inclusion Criteria:
• Adults aged 18 years or older.
• Diagnosis of mixed dyslipidemia.
• Fasting triglyceride levels between 135 and 499 mg/dL.
• Body mass index (BMI) ≥27 kg/m².
• High-sensitivity C-reactive protein (hs-CRP) >2 mg/L.
• Stable statin therapy for at least 8 weeks prior to enrollment.
• Ability and willingness to provide written informed consent.

Exclusion criteria

• Fasting triglyceride levels ≥500 mg/dL.
• History of a recent cardiovascular event.
• Significant hepatic or renal disease.
• Pregnancy or breastfeeding.
• Known allergy or hypersensitivity to fish or seafood.
• Use of omega-3 supplements within 8 weeks prior to randomization.
• Participation in another interventional clinical trial within 8 weeks prior to enrollment.