Posted under Fertility Treatment by Dr. Dorothy

Role of Anti-Oxidants in Male Infertility Treatment

Oxidative stress may be one of the reasons behind “idiopathic” or unexplained male infertility. Studies [1]. Indicate 30% to 40% of infertile men have elevated levels of Reactive oxygen species in their seminal plasma. 

What is Oxidative stress?

Reactive oxygen species (ROS) are oxygen-derived free radicals that are generated in the body during the natural metabolic processes. Produced in small quantities, ROS is required for normal metabolic activity and gets readily detoxified by the body’s national antioxidant defense system. In large quantity, they cause a lot of unwanted Oxidative damage to the cell. 
During certain conditions where the ROS is produced in large amounts, the body doesn’t have sufficient Anti-oxidants to detoxify the ROS. This state of imbalance that results in increased cellular damage by the excess ROS is called Oxidative stress.

How does Oxidative stress contribute to male infertility?

Small amounts of ROS is required for normal sperm function. ROS play a crucial role in sperm function. They help in various physiological roles of sperm like capitation, acrosome reactions, hyperactivation, sperm-oocyte binding. 
However induced by certain conditions if the concentrations of ROS inside the sperms exceeds the acceptable levels, it has a negative impact on the quality of the spermatozoa and undermines their overall fertilizing capacity by causing significant damage to biomolecules such as lipids, proteins, nucleic acids, and sugars [2]. What makes make spermatozoa unique in their susceptibility to oxidative insult is that spermatozoa are unable to restore the damage induced by OS because they lack the necessary cytoplasmic-enzyme repair systems.

Define the kind of oxidative damage caused by ROS to Spermatozoa?

  • ROS metabolites can attack DNA and cause Sperm DNA fragmentation, which prevents them from fertilizing the egg. Also, if DNA damaged sperm is used to fertilize the egg in IVF the embryo will be of poor quality and may fail to implant. However, there is a way to sort this out: How to sort sperms based on DNA damage for use in IVF? Read more here.
  • Alter lipids, and proteins and alter enzymatic systems inside the sperm affecting the metabolic pathways that are necessary for giving energy and vitality to the sperms [3] .
  • ROS is known to contribute to defective sperm production by causing lipid peroxidation of sperm membranes
  • Produce irreparable alterations within sperm, causing morphological damage. 
  • ROS cause cell death that has a negative impact on sperm concentration, motility, and function –adversely affecting fusion events required for fertilization.
  • By and large, the Oxidative damage in sperms triggered by disproportionate levels of ROS is extensive and leads to a decline in the semen parameters associated with male infertility.

What conditions can cause a spike in ROS and contribute to Male Infertility?

In normal conditions, there is a balance between the levels of ROS and antioxidants. However, following conditions can cause a disproportionate rise of ROS the body that affects Male Reproduction:

  • Aging 
  • Recent infections
  • Varicocoel
  • Endogenous sources like leukocytes, immature spermatozoa
  • Exposure to pollutants, radiation, toxins and chemicals
  • Psychological stress
  • Alcohol and tobacco use
  • Certain Pharmaceutical medications
  • Poor diet and physical inactivity
Role of Oxidative stress on Male infertility: Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1–17. doi:10.5534/wjmh.2014.32.1.1
 

How does Anti-oxidant Therapy help in Male infertility?

If Oxidative damage is caused due to an imbalance in the ration of ROS to anti-oxidants, antioxidant therapy involves taking anti-oxidant supplements to restore balance by removing the ROS. This results in improvements in the sperm count, motility and shape (morphology) and prevents DNA damage to sperms. Anti-Oxidant supplements are prescribed for 3-4 months to help reduce the ROS giving the reproductive machinery time to heal and bounce back. In most cases where the Poor semen analysis report was due to ROS damage, there is an improvement in sperm parameters after taking anti-oxidant therapy.

Improvement in semen parameters by anti-oxidants

Showell et al. (2014) :  The probability of a couple having a live birth where the male is subfertile increases to between 10-31% after treatment with oral antioxidants.
 

Antioxidant treatment

Live birth

Pregnancy

DNA Damage

Sperm Motility

Sperm concentration

Vitamin E

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Vitamin C

 

 

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Magnesium

 

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Zinc

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N-acetyle Cysteine

 

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Folic Acid

 

 

 

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Carnitine

 

 

 

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Selenium

 

 

 

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DHA

 

 

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Coenzyme Q10

 

 

 

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Which antioxidants supplements are safe to take?

Antioxidants are essentially, vitamins, and there is a huge industry supplying such supplements to men. So the difficulty is to fins which anti-oxidant is safe to take and will give you good results. The best way to select is to see which brand offers most of the ingredients at the lowest cost. Your doctor will be able to best guide you on the best local brands available based on the costs. Most antioxidants supplements will contain the following ingredients:

  • Coenzyme Q10 (Ubidecarenone)
  • Lycopene(Carotenoids)
  • Omega-3 fatty acids
  • Carnitine (amino acid the body needs for producing energy)
  • Vitamin E and C
  • Vitamin B12
  • Selenium and Zinc
  • Glutathione
  • N-acetyl cysteine

Other ingredients you may see in these supplements include vitamin B6, vitamin D, vitamin K, copper, manganese, fructose, arginine, quercetin, L-glutathione, niacin, thiamine, riboflavin, iodine, and chromium. 

Natural Antioxidants are available in many types of food sources. A diet rich in anti-oxidants is seen to help patients with low sperm count and motility. 

Great anti-oxidants rich food include:

  • Blackberries                     
  • Blueberries
  • Strawberries                    
  • Cranberries
  • Pomegranate
  • Green tea
  • Dark chocolate                    
  • Cooked vegetables and 
  • Spices such as cumin, turmeric, ginger, and oregano.
Article references
1.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026229/#B7
2.    Agarwal A, Prabakaran SA. Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J Exp Biol. 2005; 43:963–974. [PubMed] 
3.      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988936/


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