Does coenzyme Q10 improve semen quality and circulating testosterone level? a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Seminal oxidative stress has been shown to be a key factor in the development of male infertility. However, the benefits of infertility treatments with antioxidants such as coenzyme Q10 (CoQ10) remains controversial.

Objectives: The aim of the present study was to assess the effects of CoQ10 supplementation on semen quality, i.e., semen volume, total sperm number, sperm concentration, total sperm motility, percentage of progressive sperm motility and sperm morphology. In addition, the effects of CoQ10 supplementation on circulating testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B levels were evaluated.

Design: A systematic review and a meta-analysis of randomized controlled trials (RCTs) were performed to assess the effects of CoQ10 supplementation on semen quality and serum levels of male reproductive hormones.

Methods: We conducted a strategic literature search in the Cochrane, EMBASE, PubMed/MEDLINE, Scopus, and Web of Science databases and collected only RCTs. The data in the collected RCTs were then meta-analyzed according to PRISMA guidelines.

Results: Out of 2,144 collected studies, only eight were classified eligible. The studies included a total of 877 male subjects; 462 CoQ10-treated and 415 untreated/placebo-treated. We found significantly higher total sperm counts (SMD -13.38 [95% CI: -16.33, -10.43] P< 0.0001), total (SMD -7.26 [95% CI: -10.15, -4.36] P< 0.00001) and progressive motility (SMD -6.386 [95% CI: -10.04, -2.73] P= 0.0006), and normally formed sperm (SMD -1.96 [95% CI: -3.29, -0.62] P= 0.004) in CoQ10-treated male subjects compared with untreated/placebo-treated male subjects. Nonetheless, there was a significant inter-study heterogeneity in these studies. Moreover, significantly higher serum testosterone (SMD -0.59 [95% CI: -0.79, -0.40] P< 0.00001) and inhibin B levels (SMD -0.92 [95% CI: -1.47, -0.37] P= 0.001) were recorded in CoQ10-treated subjects compared to untreated/placebo-treated subjects. In addition, CoQ10 supplementation significantly lowered serum LH (SMD 1.77 [95% CI: 1.26, 2.28] P< 0.00001) and FSH concentrations (SMD 1.60 [95% CI: 1.38, 1.81] P< 0.00001). Interestingly, there was no significant inter-study heterogeneity in the hormonal studies. However, CoQ10 supplementation had no significant effect on semen volume (SMD 0.12 [95% CI: -0.13, 0.37] P= 0.34) and sperm concentration (SMD -6.69 [95% CI: -16.28, 2.90] P= 0.17).

Conclusion: Our study shows that CoQ10 supplementation increases total sperm count, total and progressive sperm motility, and the proportion of normally formed sperm in association with higher serum testosterone and inhibin B levels. Our study therefore supports the view in the literature of a beneficial use of CoQ10 in male infertility treatment. However, further well-designed RCTs with sufficiently large numbers of subjects are required to reach a final conclusion.

Keywords: antioxidant; infertility treatment; male infertility; male reproduction; spermatogenesis; testes.

FIGURE 1

PRISMA flowchart for the identification, screening, and inclusion of eligible studies.

FIGURE 2

Risk of bias analysis of the included studies. The risk of bias summary showing each risk of bias item for each included study (A) and each risk of bias item presented as percentages across all included studies (B). Green indicates the percentage probability that there is a low risk of bias.

FIGURE 3

CoQ10 supplementation does not change ejaculate volume (mL). In the unrestricted, sugbroup and sensitivity analyses, there were no changes in ejaculate volume after CoQ10 supplementation and this was consistent across studies. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the right show that the variable is higher in the control.

FIGURE 4

CoQ10 supplementation had consistent effects on total sperm count (million). The unrestricted analysis of all studies resulted in significantly higher total sperm count in CoQ10-treated individuals. Also, the subgroup analyses for different durations and combinations of treatment, and the sensitivity analysis revealed that CoQ10 treatment significantly increased sperm count. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups, while the boxes on the right show that the variable is higher in the control.

FIGURE 5

CoQ10 supplementation had no effect sperm concentration (million/mL). Sperm concentration did not change in the unrestricted, and subgroup and sensitivity analyses. There were significant differences between studies, indicated by the significant heterogenity of both analysis. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups, while the boxes on the right show that the variable is higher in the control.

FIGURE 6

CoQ10 supplementation had a consistent effect on total sperm motility (%). The unrestricted analysis of all studies showed a significant increase in total sperm motility in CoQ10-treated group compared to the control. This significant difference psersisted with the various subgroup analyses and sensitivity analysis. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups.

FIGURE 7

CoQ10 supplementation significantly increased sperm progressive motility (%). The unrestricted analysis, subgroup analyses for ≤3 months of treatment and combined therapy, and sensitivity analysis demonstrated a significant increase in sperm progressive motility in CoQ10-treated subjects when comapred to the control. However, subgroup analysis for >3 months of treatment and single therapy revealed an insignificant increase in the percentage of sperm progressive motility after CoQ10 supplementation. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups, while the boxes on the right show that the variable is higher in the control.

FIGURE 8

CoQ10 supplementation significantly increased normal sperm morphology. In the unresssicted analysis, there was a significant increase in sperm morphology after CoQ10 supplementation, however these findings were inconsistent between studies. Subgroup analyses of treatments >3 months and single therapy also showed significant increase of normal sperm morphology in CoQ10-treated group compared with the control, but subgroup analyses of treatments ≤3 months and combined therapy demonstrated that CoQ10 did not alter normal sperm morphology. Nonetheless, the sensitivity analysis showed a significant increase in sperm morphology in CoQ10-treated group compared with the control. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups, while the boxes on the right show that the variable is higher in the control.

FIGURE 9

CoQ10 supplementation significantly increased serum testosterone. Two studies measured circulating testosterone levels in men after 26 weeks of treatment with CoQ10 or placebo. CoQ10 treatment resulted in significantly increased testosterone levels. These findings were consistent across studies and this data cooberates the decreased levels of serum LH and FSH from the same studies. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups.

FIGURE 10

CoQ10 supplementation significantly lowered serum LH. Two studies measured circulating LH levels in men after 26 weeks of treatment with CoQ10 or placebo. CoQ10 treatment resulted in significantly lowered LH levels. These findings were consistent across studies and this data cooberates the increased levels of serum testosterone from the same studies. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The on the right show that the variable is higher in the control.

FIGURE 11

CoQ10 supplementation significantly lowered serum FSH. Two studies measured circulating FSH level in men after 26 weeks of treatment with CoQ10 or placebo. CoQ10 treatment resulted in significantly lowered FSH levels. These findings were consistent across studies and this data cooberates the increased levels of serum testosterone from the same studies. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the right show that the variable is higher in the control.

FIGURE 12

CoQ10 supplementation significantly increased serum Inhibin B. Two studies measured circulating Inhibin B levels in men after 26 weeks of treatment with CoQ10 or placebo. CoQ10 treatmetn resulted in significantly higher Inhibin B levels. These findings were consistent across studies and this data cooberates the increased levels of serum testosterone from the same studies. The green boxes represent the mean effects of the included studies, while the diamond-shaped black boxes are the global mean effects of all studies. The boxes on the left side show that the variable is higher in CoQ10-treated groups.

FIGURE 13

The strengths, weaknesses, opportunities, and threats (SWOT) analysis of the present meta-analysis.