Brown Macroalgal Polyphenols and Oxidative Stress: A Systematic Review and Meta-Analysis of In Vivo Evidence in Vertebrate Models

Brown macroalgal polyphenols, particularly phlorotannins, have demonstrated antioxidant and anti-inflammatory bioactivity, but in vivo evidence remains heterogeneous across organisms, stress models, and preparations. This systematic review and meta-analysis synthesized in vivo evidence on the effects of brown macroalgal polyphenols on oxidative stress-related biomarkers. PubMed, Cochrane, Scopus, and Web of Science were searched. Of 415 records identified, 22 in vivo studies involving zebrafish embryos, mice, and rats met the inclusion criteria. Interventions included extracts, fractions, and purified compounds. Random-effects meta-analyses were performed for prespecified outcomes, with subgroup analyses by compound, macroalgal species, and stressor/model. In zebrafish, brown macroalgal polyphenols reduced ROS generation, lipid peroxidation, and nitric oxide production. In rodents, they increased catalase activity and serum superoxide dismutase, and reduced hepatic malondialdehyde and TBARS, whereas glutathione peroxidase showed no consistent pooled effect. Risk-of-bias assessment using SYRCLE indicated predominantly unclear reporting for randomization, allocation concealment, and blinding, while attrition and reporting domains were mostly low-risk. Overall, brown macroalgal polyphenols show promising antioxidant effects in vivo, but substantial heterogeneity and incomplete methodological reporting limit certainty and preclude direct extrapolation to humans.