The Effect of Ceratonia siliqua (Carob) on Male Infertility: A Systematic Review and Meta-analysis of invitro and randomized controlled trials.

Abstract

Oxidative stress is a key contributor to impaired se-men quality in male infertility. Ceratonia siliqua L. (car-ob), a polyphenol-rich plant traditionally used to improve male fertility, has been investigated as a potential in-tervention for improving semen parameters and repro-ductive hormonal profiles. This systematic review and meta-analysis evaluated the effects of carob supplemen-tation 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-ef-fects 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 sig-nificantly increased sperm count (3 RCTs; n=166; WMD: 11.58 × 106/ml; 95% CI: 9.79-13.38; I2=38%) and total sperm motility (4 RCTs; 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 signifi-cantly (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 mo-tility (5 studies; n=180; SMD=4.37; 95% CI: 1.46-7.28; I2=98.6%) and viability (4 studies; 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 ob-served at concentrations of 10-20µg/ml. Overall, carob supplementation may improve sperm count and motility, which are relevant parameters in male fertility and as-sisted 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.