Abstract
BACKGROUND: Obesity, defined as excess body fat that impairs health, is a major public health challenge associated with metabolic and inflammation-related complications across the lifespan. Conventional treatments often show limited long-term efficacy, leading to growing interest in complementary strategies. Nutraceuticals have been studied for their potential in weight management and metabolic improvement. This systematic review and network meta-analysis evaluates the role of nutraceuticals in obesity management, with attention also given to pediatric populations. METHODS: We performed a systematic review and network meta-analysis (NMA) following Cochrane and PRISMA-NMA 2020 guidelines. Eligible randomized and non-randomized trials enrolled children or adults with overweight/obesity, testing nutraceuticals (inulin, butyrate, long-chain omega-3 fatty acids, vitamin B, carnitine) versus placebo or standard care. Primary outcomes included anthropometric, metabolic, and inflammatory markers. The protocol was registered in PROSPERO (ID: CRD420251151333). RESULTS: L-carnitine emerged as the most effective and consistent intervention, producing significant reductions in body weight, body mass index (BMI), waist circumference, fasting blood glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and LDL-Cholesterol (LDL-C), along with a significant increase in HDL-Cholesterol (HDL-C). Inulin and long-chain omega-3 fatty acids (LC n3-PUFA) exhibited modest or non-significant effects on most outcomes, although LC n3-PUFA significantly reduced triglyceride levels. Butyrate demonstrated beneficial effects on BMI and waist circumference in children, whereas vitamin B showed limited impact. Dose-response analyses confirmed the efficacy of L-carnitine at relatively low dosages, while other supplements required higher intakes without achieving the predefined clinical targets. CONCLUSION: This NMA shows heterogeneous effects of nutraceuticals on obesity-related outcomes. L-carnitine emerged as the most consistent intervention, while LC n3-PUFA, inulin, butyrate, and vitamin B provided more limited benefits. Preliminary evidence suggests potential age-related differences, highlighting the need for further studies to define age-specific and tailored strategies for obesity management.