Infertility in men is more prevalent in the last two decades. An increasing percentage of men are today sub-fertile or infertile compared to two decades back and oxidative stress is a major factor. Around 15% of all couples face some form of impaired fertility.
It is true that certain cases of infertility are due to anatomical abnormalities such as ductal obstructions, varicocele or ejaculatory disorders, but a large percentage of infertile cases are mainly due to deficient sperm production of unidentifiable origin. Many such men usually respond to antioxidant supplementation.
In this article we will examine how antioxidant vitamins and supplements can significantly improve fertility in men who are otherwise sub-fertile.
- 1 AntiOxidant Supplements Can Help
- 2 Antioxidant Therapy Improves Sperm Parameters in Men With Persistent Oligospermia
- 3 Lycopene therapy in Idiopathic Male Infertility
- 4 Effects of L-carnitine on Infertile Men’s Spermogram
- 5 Efficacy of Coenzyme Q10 on semen parameters
- 6 Effects of Folic Acid & Zinc on Male Fertility
- 7 How Zinc Therapy Results in Improved Sperm Parameters in Asthenozoospermic Men
- 8 How Selenium plus Vitamin E supplementation Affects Semen parameters & Pregnancy Rate
- 9 Treating Idiopathic Oligoasthenospermia with Lycopene
- 10 Effects of N-acetylcysteine on Semen Parameters and Oxidative/Antioxidant Status
- 11 Efficacy of Selenium and/or N-Acetyl-Cysteine in Improving Semen Parameters in Infertile Men
- 12 Reduction of Sperm DNA Fragmentation by Oral Supplementation of Vitamin C and E
- 13 Antioxidants reduces sperm DNA fragmentation but there maybe an unexpected adverse effect
- 14 Protective role of vitamin E on Sperm
- 15 Effects of oral antioxidant treatment on sperm with highly degraded DNA
- 16 Oral antioxidant treatment improves integrity of human sperm DNA in infertile grade I varicocele patients
- 17 Use of combined l-cause of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia
- 18 Effect of Menevit antioxidant on pregnancy outcome during IVF-ICSI treatment
- 19 Can oral antioxidant treatment with Vitamin C and Vitamin E improve ICSI pregnancy outcomes?
- 20 Can vitamin E supplementation improve zona binding ratios of sperm
- 21 Conclusion
AntiOxidant Supplements Can Help
Oxidative stress can cause deficiencies in sperm count, motility and also result in broken or fragmented DNA, which could change the DNA’s epigenetic profile making them less attractive to female eggs during meiosis.
Ofcourse there can be more fundamental causes for male infertility, but in a lot of clinical studies most sperm parameters show marked improvements with antioxidant supplementation. Studies across the world have thrown up some interesting fact.
- A majority of male infertility has been linked to “oxidative stress”.
- The best defense against oxidative stress are antioxidants.
- You can get adequate antioxidants from a well-balanced diet, paleo diet is a good option.
- A large % of men have antioxidant-deficient diet.
- Men can include more fruits and veggies to improve fertility.
- Antioxidant supplements can be treated as prenatal vitamins for men.
Some of the common antioxidants that can be used for combating oxidative stress and improving sperm motility include:
|wdt_ID||Antioxidant||Mechanism of action|
|1||Ascorbic acid (vitamin C)||Neutralises free radicals|
|2||Carnitines||Neutralises free radicals and acts as an energy source|
|3||CoQ10||Scavenges free radicals intermediate in mitochondrial electron transport system|
|4||Folate (vitamin B9)||Scavenges free radicals|
|5||Lycopene||Quenches free radicals|
|6||NAC||Enhances enzymatic antioxidant activity|
|7||Selenium||Enhancement of enzymatic antioxidant activity|
|8||Tocopherol (vitamin E)||Neutralises free radicals|
|9||Zinc||Inhibition of NADPH oxidase|
Antioxidant Therapy Improves Sperm Parameters in Men With Persistent Oligospermia
Antioxidant therapy based on a combination of NAC 600mg and micronutrient supplementation was found to be helpful in improving the sperm count in oligospermic males 6 months after retrograde embolization. However, this improvement in sperm count was not associated with a significant increase in spontaneous pregnancies after 12 months. [Research Study]
Lycopene therapy in Idiopathic Male Infertility
30 men with idiopathic non-obstructive oligo/astheno/teratozoospermia were enrolled for the trial and administered 2000 mcg of Lycopene, 2 times a day for 3 months at the Department of Urology in All India Institute of Medical Sciences.
Semen analysis revealed that 20 patients showed a mean improvement of 22 million/ml in sperm concentration, 16 patients exhibited an average of 25% improved motility and 14 patients showed an average 10% improvement in sperm morphology. Higher baseline concentrations were associated with significant improvement and resulted in 6 pregnancies in 26 patients (23%).
Oral Lycopene therapy seems to have a role in the management of idiopathic male infertility. Maximum improvement occurred in the sperm concentration (66% cases) compared to other metrics. Patients without severe oligospermia (sperm density > 5 million/ml) may be given a trial of therapy with lycopene. [Research Study]
Effects of L-carnitine on Infertile Men’s Spermogram
Intake of l-carnitine significantly improved progressive sperm motility and mean sperm count.[Research Study]
Efficacy of Coenzyme Q10 on semen parameters
Supplementation of Coenzyme Q10 caused a definite improvement in semen parameters like sperm count, sperm motility and sperm morphology. A significant decrease in luteinizing hormone and serum follicle-stimulating hormone was seen at the 26-week treatment phase.
There was also a significant increase in mean acrosome reaction from 14% to 31%. Acrosome reaction is the reaction that occurs in the acrosome of the sperm as it approaches the egg, and it is a process that helps the sperm penetrate the hard exterior shell of the egg. [Research Study]
Effects of Folic Acid & Zinc on Male Fertility
In a combined Dutch study involving two outpatient fertility clinics and nine midwifery practices, it was found that the total normal sperm count increased by 74% when 108 fertile and 103 subfertile men were given a combined daily dose of 66 mg zinc sulfate and 5mg folic acid.
There was also minor increase in abnormal spermatozoa in the subfertile men, but the increase in number of healthy spermatozoa was many folds higher.
The pre intervention and post intervention values were measured for men taking only Zinc, men taking only Folate abd men taking Zinc and Folate. The improvements in total sperm count concentration is shown in the chart above. There was also a surprisingly significant increase in sperm count of normal fertile men too. [Research Study]
How Zinc Therapy Results in Improved Sperm Parameters in Asthenozoospermic Men
In a study conducted by Omu A.E and Al-Azemi at the Obstetrics & Gynaecology, Kuwait University on 45 asthenozoospermia (≧40% immotile sperm), it was found that Zinc therapy was associated with significantly improved sperm parameters with much lesser oxidative stress, sperm DNA fragmentation index (DFI) and sperm apoptosis. Adding vitamin E or vitamin C did not enhance this effect further.
Additionally, when Zinc was added directly to the semen sample in a lab, it resulted in reduced DNA fragmentation(14% to 29%). Asthenozoospermia is significantly linked to oxidative stress and low total antioxidant capacity. [Research Study]
How Selenium plus Vitamin E supplementation Affects Semen parameters & Pregnancy Rate
In a study involving 690 infertile young men with mean age of 28.5 years were diagnosed with idiopathic asthenoteratospermia and received daily supplementation of Selenium 200 μg in combination with vitamin E (400 units for at least 100 days.
Overall 52.6% showed marked improvements in sperm motility, morpholigy or both. 36.6% of cases showed no significant improvements. 10.8% (75 cases) had spontaneous pregnancies.
Combination of oral supplementation of Selenium and vitamin E was seen to be an effective treatment for asthenospermia, asthenoteratospermia and induction of spontaneous pregnancy.
The organic form of Selenium is primarily found in fish, poultry, eggs, meat, grains and dairy products. In the US, the typical dietary intake of Seleniumis 80–120 μg/daily, and the recommended daily allowance is 70 μg in men. But subfertile men can benefit from higher Selenium intake.
Increased reactive oxygen species (ROS) hampers male fertility because ROS attacks and harms the membrane of the spermatozoa. Increasing Selenium intake decreases ROS leading to increased fertility.[Research Study]
Treating Idiopathic Oligoasthenospermia with Lycopene
There was a study conducted by NK Mohanty and Sujit Kumar at the Department of Urology, Safdarjang Hospital, New Delhi that aimed to establish the role of Lycopene in treating infertile men whose infertility was without any obvious cause and who had normal hormone profile and antibodies.
The men in the study had Idiopathic oligoasthenospermia without any anatomical explanation. Oligoasthenospermia is a condition where the man has unexplained deficiency in sperm count and motility.
50 men received high dose Lycopene (8mg) daily till one of the following two end points were reached: pregnancy or optimal sperm parameters.
In the followup that was maintained for 1 year; an excellent 36% pregnancy rate was achieved, total sperm count improved in 70% of men, sperm concentration improved in 60% of men, sperm motility improved in 54% of men and sperm morphology improved in 38% of men.
Patient compliance was excellent and there were no side effects. Lycopene supplementation is an effective treatment option for idiopathic oligoasthenospermia. [Research Study]
Effects of N-acetylcysteine on Semen Parameters and Oxidative/Antioxidant Status
N-acetylcysteine significantly improved the effects on the motility, volume and viscosity of semen. After receiving NAC treatment(600 mg/d orally for 3 months), the men exhibited higher serum total antioxidant capacity and lower total peroxide and oxidative stress index compared with the control group.
However there were no significant differences in sperm count and morphology of the sperm. [Research Study]
Efficacy of Selenium and/or N-Acetyl-Cysteine in Improving Semen Parameters in Infertile Men
A large study involving 468 infertile men with idiopathic oligo-asthenoteratospermia was conducted at the Urology and Nephrology Research Center, Shahid Beheshti University (MC), Iran. This was a randomized placebo controlled study.
Men were divided into 4 groups and given 200 μg selenium (or) 600 mg N-acetyl-cysteine orally (or) 200 μg selenium plus 600 mg N-acetyl-cysteine (or) similar regimen of placebo.
A statistically significant positive correlation existed between selenium and N-acetyl-cysteine plasma concentrations and semen parameters (sperm conc, motility and morphology). The improved effects seemed more permanent in nature as the final measurements were made after a period of 30 weeks during which the oral supplementation was ceased.[Research Study]
Reduction of Sperm DNA Fragmentation by Oral Supplementation of Vitamin C and E
64 men with elevated (≥15%) percentage of DNA‐fragmented spermatozoa in the ejaculate and unexplained infertility were randomized between an antioxidant treatment (1 g vitamin C and 1 g vitamin E daily for 2 months) group and a placebo group.
There was a significant reduction in the percent of DNA‐fragmented spermatozoa(−58.4% ± 27.8 P < .001) in the antioxidant treatment group after the treatment and there was no meaningful difference in the placebo group.
20 out of the 32 patients in the antioxidant treatment group also showed a definite increase in sperm concentration, but there were wild variances in this metric and so this aspect was not considered statistically significant. [Research Study]
Antioxidants reduces sperm DNA fragmentation but there maybe an unexpected adverse effect
In this study, the DNA fragmentation index and the degree of sperm decondensation were measured before and after 90 days treatment with antioxidant vitamins associated with zinc and selenium.
Antioxidant treatment led to a 19.1% decrease in sperm DNA fragmentation, but also led to a rather unexpected increase in sperm decondensation with the same order of magnitude 22.8%. It is to be noted that pregnancies rarely occur when the decondensation factor is over 28%. [Research Study]
Antioxidants can be beneficial, but should be prescribed with care.
Protective role of vitamin E on Sperm
Research conducted by S A Suleiman and M E Ali at the Department of Clinical Biochemistry, College of Medicine, King Saud University, Saudi Arabia revealed that when asthenospermic patients were treated with oral supplementation of Vitamin E, it caused significant decrease of the MDA concentration in spermatozoa and also enhanced sperm motility.
MDA is a major factor that reduces fertility due to lipid peroxidation.The decrease in MDA concentration in sperm pellet is a positive development as the suspensions of asthenospermic and oligoasthenospermic patients had MDA concentration that was almost double the normal males.
21% of the treated patients were able to impregnate their spouses; and most of the impregnated women ended with normal term deliveries. The placebo group reported no pregnancies. [Research Study]
Effects of oral antioxidant treatment on sperm with highly degraded DNA
In this clinical study 20 men were given oral antioxidant treatment containing L‐Carnitine (1500 mg), Coenzyme Q10(20 mg), Vitamin C(60 mg), Selenium(50 μg), Vitamin E(10 mg), Zinc(10 mg), Vitamin B9(200 μg), ,Vitamin B12(1 μg) for 3 months.
Sperm DNA fragmentation was then studied at different periods of sperm storage (0 h, 2 h, 6 h, 8 h and 24 h) at 37 °C.
Significant improvement in DNA integrity was noticed at all periods. There was marked decrease in the number of DNA degraded sperm (DDS). Semen analysis data showed a definite increase in motility, concentration, morphology and vitality parameters.
The study then went on to state that antioxidant treatment clearly improves sperm quality wrt to basal DNA damage and key seminal parameters and also helps maintain DNA integrity. Better outcomes with assisted reproductive techniques could be expected following antioxidant treatment. [Research Study]
Oral antioxidant treatment improves integrity of human sperm DNA in infertile grade I varicocele patients
An enlargement of veins within the loose bag of skin that holds your testicles (scrotum) is called a varicocele and it is not dissimilar to a varicose vein in the leg. It can cause low sperm count and also lower quality of sperm, both of which are common causes of infertility.
In this study, potential benefits of antioxidant supplementation in grade I varicocele males were investogated. 20 infertile men with grade 1 varicocele were given multivitamins containing 1500 mg L-Carnitine, 20 mg coenzyme Q10, 60 mg vitamin C, 50 μg selenium, 10 mg vitamin E, 200 μg vitamin B9, 1 μg vitamin B12, 10 mg zinc daily for 3 months.
After treatment, there was a mean relative reduction of 22.1% in sperm DNA fragmentation. Total sperm cells were higher (p = 0.04), but other semen parameters were overall unaffected.
The data indicated that oral antioxidant treatment may enhance sperm DNA integrity in grade I varicocele patients. [Research Study]
Use of combined l-cause of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia
When 60 infertile young patients between the age 20-40 were orally given a combination treatment of l-acetyl-carnitine (1 g/d) and l-carnitine (2 g/d) or placebo; improvements were seen in all sperm parameters. The most significant improvements were in men who had lower baseline values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate).
Combined treatment with l-acetyl-carnitine and l-carnitine was effective in improving sperm motility, especially in men with low baseline levels. [Research Study]
Effect of Menevit antioxidant on pregnancy outcome during IVF-ICSI treatment
ROS can cause DNA damage in sperm which can lead to conception failure, miscarriage and even childhood cancer. A study conducted by Kelton Tremellen and George Miari in Australia investigated the role of antioxidant supplementation in infertile men on pregnancy outcome and embryo quality in women undergoing invitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) treatment.
The men who were on Menevit antioxidant recorded a significant improvement in viable pregnancy rate with 38.5% of the transferred embryos resulting in a viable fetus at 13 weeks gestation. The group that were given placebo had a 16% viable pregnancy. No meaningful changes were noticed in embryo quality or oocyte fertilisation rate. [Research Study]
Can oral antioxidant treatment with Vitamin C and Vitamin E improve ICSI pregnancy outcomes?
Many of the studies that examine the use of ICSI for cases with increased sperm DNA fragmentation report poor pregnancy and implantation rates. A study conducted by Ermanno Greco and Stefania Romano (Centre for Reproductive Medicine, European Hospital, Rome, Italy) investigated the role of Vitamin C and Vitamin E supplementation prior to ICSI.
38 men with DNA fragmented spermatozoa of greater than 15% and whose partners had one failed ICSI were orally supplemented with 1 g vitamin C and 1 g vitamin E daily for 2 months. 76% of the cases showed a marked decrease in the % of DNA fragmentation. The treatment group had a 48.2% clinical pregnancy rate compared to just 6.9% in the placebo group. [Research Study]
Can vitamin E supplementation improve zona binding ratios of sperm
Binding ratio test is a useful predictor for sperm fertilizing ability invitro, particularly in men with poor sperm morphology.
In this study men were given either 600 mg/d of vitamin E or placebo for 3 months and after a washout period of 1 month, sperm tests were conducted.
The rise in the Vitamin E levels in the blood after treatment was found to be accompanied by improvement in the sperm function test: the zona binding assay.
The zona binding ratio for order A increased from 0.2 (range 0 to 0.5) pre treatment to 0.5 (range 0.1 to 1.0) after treatment, the The zona binding ratio for order B were 0.2 (range 0 to 1.0) pre-treatment and 0.3 (range 0.1 to 0.7) after treatment.
Oral administration of vitamin E caused a marked improvement in the function of human spermatozoa as revealed by the zona binding test. [Research Study]
Antioxidants have proven to have an overall favorable effect on male fertility. So, is it necessary for every male to take prenatal vitamins? Probably not, but then having an antioxidant-rich diet does help a person to live a healthier life.