Systems biology modelling based evaluation of omega-3 formulation in managing cardiovascular and cerebrovascular risk.
Sanjaay Balakrishnan, Abha Saxena, Madhusmita Mahapatra, Aparna Damle, Shyam Ramakrishnan, Palaniyamma Durairaj, Venkatesh Kareenhalli
Abstract
Open AccessNatural therapies for cardiovascular and cerebrovascular disease management often use nutraceuticals and herbal supplements to improve lipid profiles. This in-silico study examined the effects of Omega-3 fatty acids, specifically Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA), on lipid metabolism using systems biology-based models. The pharmacokinetics and pharmacodynamics of EPA (1 g) and DHA (1 g) were analysed to understand their lipid-lowering mechanisms. The study also assessed the impact of omega-3 fatty acid-based formulation, (EPA 180 mg and DHA 120 mg), on lipid biomarkers in a simulated disease population. Over six months, the model predicted a 14.7% reduction in triglycerides, 1.7% reduction in total cholesterol, 3.7% increase in LDL, and a 22.38% increase in HDL. Non-traditional markers improved markedly, with triglyceride-to-HDL ratio reduced by 31%, total cholesterol-to-HDL by 21%, and LDL-to-HDL by 16%. A population-level subgroup analysis showed that individuals with high baseline lipid ratios (triglyceride-to-HDL > 8, total cholesterol-to-HDL > 12, LDL-to-HDL > 8) could achieve > 35% reductions within six months. These in-silico findings highlight subgroups with better predicted efficacy, guiding inclusion-exclusion criteria for future trials. Further, the study highlights the therapeutic potential of EPA and DHA in improving lipid profiles and managing cardiovascular and cerebrovascular diseases.