Toxicity of Antioxidant Supplements in Patients with Male Factor Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Massimiliano Creta,
Davide Arcaniolo,
Giuseppe Celentano,
Luigi Napolitano,
Roberto La Rocca,
Marco Capece,
Gianluigi Califano,
Francesco Mangiapia,
Lorenzo Spirito,
Felice Crocetto,
Ciro Imbimbo,
Nicola Longo,
Marco De Sio,
Ferdinando Fusco
Affiliations
Massimiliano Creta
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Davide Arcaniolo
Department of Woman, Child and General and Specialized Surgery, Urology Unit, University of Campania ‘Luigi Vanvitelli’, 80131 Naples, Italy
Giuseppe Celentano
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Luigi Napolitano
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Roberto La Rocca
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Marco Capece
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Gianluigi Califano
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Francesco Mangiapia
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Lorenzo Spirito
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Felice Crocetto
Department of General and Specialized Surgeries, Renal Transplantation, Nephrology, Care and Pain Management, University of Federico II, 80100 Naples, Italy
Ciro Imbimbo
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Nicola Longo
Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy
Marco De Sio
Department of Woman, Child and General and Specialized Surgery, Urology Unit, University of Campania ‘Luigi Vanvitelli’, 80131 Naples, Italy
Ferdinando Fusco
Department of Woman, Child and General and Specialized Surgery, Urology Unit, University of Campania ‘Luigi Vanvitelli’, 80131 Naples, Italy
Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of antioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted.
