Complementary Mechanisms of Action and Potential Synergies Between Nutrition, Physical Activity, and Phytotherapy in Cardiometabolic Prevention : A Narrative Review and Theoretical Framework for the African Context

This record contains the full research protocol of a randomized controlled factorial trial entitled “Integrated Lifestyle Intervention Combining Nutrition, Physical Activity, and Phytotherapy for Cardiometabolic Disease Prevention in Sub-Saharan Africa (INPACT-Africa)”. The protocol describes a community-based, multicenter 2×2×2 factorial randomized controlled trial designed to evaluate the individual and synergistic effects of nutritional intervention, structured physical activity, and African phytotherapy on cardiometabolic risk factors in adults. The scientific rationale is grounded in shared pathophysiological mechanisms underlying cardiometabolic diseases, including insulin resistance, chronic low-grade inflammation, oxidative stress, and endothelial dysfunction. The protocol integrates a theoretical mechanistic framework highlighting convergent biological pathways such as AMP-activated protein kinase (AMPK) signaling, inflammatory modulation, and vascular function improvement. Primary and secondary outcomes include changes in insulin resistance (HOMA-IR), blood pressure, glycemic control, lipid profile, anthropometric measures, and inflammatory and oxidative stress biomarkers. The protocol follows international standards (SPIRIT, CONSORT) and is intended for registration in public clinical trial registries and submission to peer-reviewed international journals. This work aims to contribute high-quality, context-specific evidence to support integrative, culturally adapted, and sustainable cardiometabolic prevention strategies in Africa, and to inform future clinical trials, public health interventions, and policy development.