A new study in the journal Antioxidants discusses the benefits of antioxidant supplementation (AS) in several semen parameters such as motility, morphology, DNA damage, sperm concentration, and fertility rate.
Study: Antioxidant Supplementation on Male Fertility—A Systematic Review. Image Credit: SciePro / Shutterstock.com
Oxidative stress and infertility
Infertility is defined as the inability to conceive after one year of unprotected sex. Over 80 million couples worldwide are affected by infertility, with infertility among men accounting for 30-50% of these cases.
Factors contributing to male infertility include varicocele, which is defined as the enlargement of veins within the scrotum, smoking, radiation exposure, urinary tract infections, nutritional deficiencies, alcohol abuse, psychological stress, strenuous exercise, spinal cord injury, and environmental factors.
Oxidative stress arises due to an imbalance between the production and accumulation of reactive oxygen species (ROS) in cells and tissues and the ability of the body to detoxify these reactive products. As ROS produce more energy than the body's ability to protect against them, oxidative stress becomes more prominent.
A rise in ROS can be due to high temperatures, air pollution, electromagnetic waves, alcohol consumption, poor nutrition, insecticides, and obesity. Recent research indicates that the Mediterranean diet helps improve male infertility and cancer risk induced by environmental pollutants. One recent study reported severe abnormalities and molecular alterations in the spermatozoa of men who lived in polluted areas.
ROS and male infertility
Spermatozoa consist of a unique plasma membrane structure comprising polyunsaturated fatty acids (PUFAs) that improve membrane flexibility for the penetration of oocytes. Following exposure to ROS, lipid peroxidation appears to directly alter the integrity of spermatozoa, which subsequently reduces sperm motility and, as a result, fertility capabilities.
In addition to the impact of ROS on spermatozoa, these highly reactive molecules also directly damage sperm DNA. Spermatozoa lack downstream DNA repair proteins that can mitigate oxidative damage caused by ROS, subsequently leading to DNA fragmentation. Spermatozoa with fragmented DNA cannot mature and fertilize an oocyte; however, if sperm carrying damaged DNA enters the zygote during fertilization without being repaired, genetic mutations can arise that subsequently affect the development of the fetus.
About the study
Several natural antioxidants, such as vitamins C and E, thioredoxin, superoxide dismutase, and glutathione, are naturally produced in the human body. These antioxidants can protect spermatozoa and neutralize free radical activity from ROS. Notably, few studies have reported oral AS to improve semen quality, whereas other studies have reported negative results.
The current study involved searching Cochrane, Medline, and PubMed electronic bibliographies for finding studies concerning the benefits of antioxidants for male infertility. Keywords such as 'antioxidants,' 'sperm function,' 'semen parameters,' 'male infertility,' and others were used for the search, along with several Medical Subject Heading (MeSH) phrases.
The title and abstract of the articles were evaluated, followed by data extraction, cross-checking, and verification. The mechanism of action, AS type, and dosage, as well as their impact on semen parameters, sperm function tests, and live birth rates, were also evaluated.
A total of 50 articles were reviewed and demonstrated that considerable improvement in male fertility could be attributed to AS therapy. The most commonly studied AS and their doses included 500-1,000 mg of vitamin C, 400 mg of vitamin E, 25-400 mg of zinc, 100-300 mg of co-enzyme Q10, 500-1,000 mg of carnitines, 6-8 mg of lycopene, 0.5 mg of folic acid, 200 mg of selenium, and 600 mg of N-acetyl cysteine.
The combination of vitamins C and E have been shown to contribute to collagen synthesis and the maintenance of proteoglycans and the intercellular matrix. In one study, one gram of vitamins C and E improved ICSI rates in patients with impaired sperm DNA damage, as well as reduced their rate of DNA damage.
L-carnitine, which is otherwise known as 3-aminobutyric acid, can be found at high concentrations within the epididymis at levels that are up to 2,000 times greater than those found within the serum. Notably, increased LC levels in the epididymis and L-acetyl carnitine (LAC) in semen have been correlated with improved sperm movement. Although LC supplementation and its impact on male fertility have not been well studied, one study on 60 infertile men receiving 2 g LC/day and 1 g LAC/day indicated that this supplementation regimen significantly improved sperm motility as compared to baseline levels.
Zinc supplementation has similarly been shown to protect spermatozoa against oxidative stress and, as a result, improve semen function. For example, when daily zinc supplementation was evaluated in 60 infertile men for a three-month period, oxidized thiol levels within semen returned to normal.
Despite the reported benefits of AS on male fertility parameters, the highly complex nature of infertility has prevented researchers from determining the ideal AS treatment approach for this condition. The heterogeneity of available studies, combined with the unknown baseline levels of antioxidants, also makes it challenging to determine ideal treatment options.
Thus, further research is needed to determine the optimal AS combination treatment for treating male infertility. These studies should also consider how different extrinsic and environmental factors may also contribute to the efficacy of these therapies.