Review: Integrative Effects of Berberine with Lifestyle and Nutraceutical Interventions on Metabolic Health

Abstract

Berberine, a bioactive isoquinoline alkaloid derived from several medicinal plants, has garnered significant attention for its pleiotropic effects on metabolic health, inflammation, and gut microbiota regulation. While numerous clinical and preclinical studies have demonstrated its efficacy in conditions such as type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and obesity, the therapeutic impact of berberine may be further enhanced when combined with lifestyle or nutraceutical interventions. Emerging evidence suggests synergistic benefits of berberine with dietary modifications, exercise, probiotics, polyphenols, and omega-3 fatty acids, mediated through complementary mechanisms including AMPK activation, modulation of gut microbiota composition, reduction of systemic inflammation, and improved insulin sensitivity. These combined approaches hold promise not only for greater clinical efficacy but also for lowering required dosages and minimizing adverse effects. However, robust randomized controlled trials and mechanistic studies remain limited. This review will synthesize current findings on these synergistic strategies, highlight mechanistic pathways, and identify research gaps critical for translating berberine-based combinatorial therapies into evidence-based clinical practice.