Abstract
Oxidative stress is a key contributor to impaired semen quality in male infertility. Ceratonia siliqua L. (carob), a polyphenol-rich plant traditionally used to improve male fertility, has been investigated as a potential intervention for improving semen parameters and reproductive hormonal profiles. This systematic review and meta-analysis evaluated the effects of carob supplementation on semen parameters and reproductive hormones in randomized controlled trials (RCTs) and in vitro studies. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform were searched up to December 2024. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool for RCTs and QUIN for in vitro studies. Random-effects meta-analyses with Knapp–Hartung adjustment were performed. Ten studies were included, comprising five RCTs and five in vitro studies. Four RCTs involving 206 participants were eligible for meta-analysis; one RCT was excluded because data were reported as percentages without extractable means. Carob supplementation significantly increased sperm count (3 RCTs; n=166; WMD: 11.58 × 10?/ml; 95% CI:9.79–13.38; I²=38%) and total sperm motility (4RCTs; n=206; WMD: 10.93%; 95% CI:2.97–18.89; I²=69.9%), but had no significant effect on sperm morphology. Testosterone levels increased significantly (3 RCTs; n=157; WMD: 1.30; 95% CI: 0.93–1.67; I²=37.6%), whereas FSH and LH remained unchanged. In vitro studies showed improvements in progressive motility (5 studies; n=180; SMD=4.37; 95% CI:1.46–7.28; I²=98.6%) and viability (4studies; n=140; SMD=3.97; 95% CI:1.30–6.64; I²=98.0%), although the effect on viability lost statistical significance after Knapp–Hartung correction. The most favorable in vitro effects were observed at concentrations of 10–20µg/ml. Overall, carob supplementation may improve sperm count and motility, which are relevant parameters in male fertility and assisted reproductive settings, and in vitro findings suggest a potential role as a cryoprotectant additive. However, because of moderate-to-high heterogeneity and variable study quality, larger, well-designed randomized controlled trials are required to confirm these effects.