Abstract
BACKGROUND: Obesity is a major public health challenge. Pharmacological treatments are effective but limited by high cost, side effects, and restricted accessibility, particularly in low- and middle-income countries. Nutraceuticals may provide complementary or alternative approaches. Saccharomyces cerevisiae-derived bioactive hydrolysates have shown promise in clinical trials, but their efficacy has not previously been synthesized in a meta-analysis. METHODS: We conducted a systematic review and meta-analysis following Cochrane and PRISMA 2020 guidelines (PROSPERO CRD420251024965). PubMed, SciELO, CENTRAL, ClinicalTrials.gov, Europe PMC, bioRxiv, medRxiv, and Preprints.org were searched (April-August 2025) for blinded, randomized, placebo-controlled trials in adults with overweight or obesity. Primary outcomes were changes in body weight, body mass index (BMI), fat mass, and waist circumference. Risk of bias was assessed using ROB-2, and certainty of evidence was graded with GRADE. RESULTS: Six randomized controlled trials (n = 262) were included. Compared with placebo, S. cerevisiae bioactive hydrolysates significantly reduced body weight (MD - 3.08 kg; 95% CI - 4.02 to - 2.13; p < 0.001; I² = 10%), BMI (MD - 0.87 kg/m²; 95% CI - 1.32 to - 0.41; p < 0.01; I² = 50%), and fat mass (MD - 1.93 kg; 95% CI - 3.36 to - 0.49; p < 0.05; I² = 64%). A non-significant trend was observed for waist circumference (MD - 2.47 cm; 95% CI - 5.09 to 0.16; p = 0.06; I² = 78%). All trials were assessed as low risk of bias, but heterogeneity downgraded the certainty of evidence to low. CONCLUSIONS: This systematic review and meta-analysis demonstrate that S. cerevisiae-derived bioactive hydrolysates lead to statistically and clinically meaningful reductions in fat mass, BMI, waist circumference, and body weight. Their favorable safety and over-the-counter availability support their use as an accessible short-term option for obesity management. Further studies are warranted to evaluate long-term effects, durability of outcomes, and applicability in real-world settings. TRIAL REGISTRATION: PROSPERO: CRD420251024965.