l-carnitine and l-acetylcarnitine supplementation for idiopathic male infertility

Summary Fifteen percent of couples are globally estimated to be infertile, with up to half of these cases attributed to male infertility. Reactive oxidative species (ROS) are known to damage sperm leading to impaired quantity and quality. Although not routinely assessed, oxidative stress is a common underlying pathology in infertile men. Antioxidants have been shown to improve semen analysis parameters by reducing ROS and facilitating repair of damage caused by oxidative stress, but it remains unclear whether they improve fertility. Carnitines are naturally occurring antioxidants in mammals and are normally abundant in the epididymal luminal fluid of men. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of carnitine supplementation for idiopathic male infertility. We searched ClinicalKey, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, PubMed and ScienceDirect for relevant studies published from 1 January 2000 to 30 April 2020. Of the articles retrieved, only eight randomised controlled trials were identified and included. Analysis showed that carnitines significantly improve total sperm motility, progressive sperm motility and sperm morphology, but without effect on sperm concentration. There was no demonstrable effect on clinical pregnancy rate in the five studies that included that outcome, although patient numbers were limited. Therefore, the use of carnitines in male infertility appears to improve some sperm parameters but without evidence of an increase in the chance of natural conception. Lay summary Although male infertility affects 1:15 men, there is no obvious reason in the vast majority of cases. Reactive oxidative species (ROS) are highly active molecules containing oxygen and are natural byproducts of normal metabolism. However, high concentrations of ROS have been shown to damage sperm, which negatively impacts a couple’s ability to conceive. Carnitines are natural antioxidants found in the body that counterbalance the damaging effects of ROS. We conducted a comprehensive review of published studies to assess whether carnitine supplements are safe and effective in improving sperm quality and pregnancy rates. Our analysis shows that carnitines improve sperm swimming and production of normal-shaped sperm cells but do not affect sperm count or pregnancy rates, although there are only a few studies and scientific evidence is limited. Whilst it is possible that carnitines may benefit male infertility, more evidence is required regarding chances of pregnancy after carnitine therapy.