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Comparing the efficacy of different antioxidants for improving sperm quality in men with subfertility

Of the 8 antioxidants included in this meta-analysis, carnitine and coenzyme Q10 were the best at improving sperm concentration and motility. While vitamin C was the most likely to improve sperm morphology, it was not more effective than placebo.

Background

Reactive oxygen species (ROS) are byproducts of normal cellular aerobic metabolism. They are essential for healthy sperm function when present in normal amounts. However, excessive ROS production can overwhelm the body’s antioxidant defenses and result in oxidative stress, which can negatively affect sperm quality. While some studies have reported that antioxidant supplementation in men with subfertility can improve sperm quality parameters (potentially by counteracting excess ROS in sperm), the comparative efficacy of different antioxidants has not been examined.

The study

This network meta-analysis of 18 randomized controlled trials compared the efficacy of 8 antioxidants for improving sperm concentration (13 trials), motility (16 trials) , and morphology (10 trials) in 1,790 men with abnormal sperm quality parameters.

The examined antioxidants were folic acid, zinc, vitamin E, carnitine, selenium, coenzyme Q10, N-acetylcysteine, and vitamin C. The participants were 26–36 years old, on average, and interventions had durations of 3–6 months.

In order to rank the antioxidants in terms of relative efficacy, the researchers used the Surface Under the Cumulative RAnking (SUCRA) curve. SUCRA values range from 0 to 100%. The higher the SUCRA value for a treatment, the more likely it’s in the top rank, or one of the top ranks.

The results

The results of the network meta-analysis were as follows:

  • Sperm concentration: Compared to placebo, only coenzyme Q10 improved sperm concentration. Among the different antioxidants, coenzyme Q10 had the highest SUCRA value (79%), followed by carnitine (65%), and folic acid (56%).

  • Sperm motility: Compared to placebo, carnitine and coenzyme Q10 improved sperm motility. Among the different antioxidants, carnitine had the highest SUCRA value (89%), followed by selenium (71%), and coenzyme Q10 (65%).

  • Sperm morphology: Compared to placebo, none of the antioxidants improved sperm morphology. Among the different antioxidants, vitamin C had the highest SUCRA value (94%), followed by coenzyme Q10 (76%), and N-acetylcysteine (53%).

The risk of bias was low in 10 trials, unclear or moderate in 5 trials, and high in 3 trials.

Network diagram showing antioxidants compared against placebo

The size of each node corresponds to the number of studies involving the specific intervention. The thickness of each line corresponds to the number of comparisons included in the analysis. Pink lines signify a statistically significant benefit from the treatment, compared to placebo. SUCRA values are displayed in parentheses.

The big picture

Previous research generally reports that antioxidant supplementation can have positive effects on sperm quality. For example, a 2018 meta-analysis found that sperm count was improved by coenzyme Q10; sperm motility was improved by coenzyme Q10, carnitine, selenium, and zinc; and sperm morphology was improved by coenzyme Q10, carnitine, and selenium.[1] Overall, these findings support the efficacy of coenzyme Q10 and carnitine for improving sperm quality parameters, and align with the findings of the meta-analysis summarized here.

Coenzyme Q10 is a lipid-soluble (i.e., fat-soluble) antioxidant that is both produced in the body and obtained from the diet, mainly from meat, fish, dairy, and eggs. It is a versatile molecule that plays important roles in energy metabolism, vitamin E recycling (another antioxidant), autophagy modulation, and the regulation of physicochemical properties of cell membranes. Since spermatogenesis is a complex molecular biochemical process, the observed improvements in sperm quality parameters may be related to coenzyme Q10’s involvement in these biological functions.[2]

Carnitine is a water-soluble antioxidant found in the epididymis (the tube that stores and transports sperm), where it can reach concentrations that are about 2,000-fold higher than concentrations found in circulating plasma.[3] Carnitine may improve sperm quality parameters, at least partly, through its antioxidant properties, but also because it plays an important role in cellular energy metabolism. Specifically, carnitine transports long-chain fatty acids to the mitochondria so that they can be broken down for energy, which is used by spermatozoa for respiration and motility.[4]

When interpreting these results, keep in mind that research examining the effects of coenzyme Q10, carnitine, and other antioxidants on pregnancy rate and live births is scarce and, so far, inconclusive.

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