Beneficial Effects of N-acetylcysteine for Improving Seminal Plasma Parameters in Infertile Men

 

H. GUNAWAN SUBRATA

Medical Doctor, International Speaker, Jakarta, Indonesia.

 

Introduction

Eighty million people worldwide are affect­ed by the inability to have children. Delayed conception affects 15% of couple­s trying to conceive and male factors subfertility accounts for up to 50% of the cases. A review by Tremellen 2008 notes that one man in 20 will be affected by subfertility.

Some of 30% to 80% of male factor subfert­ility cases are said to be due to the damaging effects of oxidative stress. Oxidative stress occurs when reactive oxygen species (ROS) overcome the semen’s natural antioxidant defences and cause cellular damag­e. Some studies have suggested that sperm production and quality has decreased over the past few decades. The increased level­s of ROS are thought to be due to environmental factors such as high temperature, electro-magnetic radiation, pesticides and pollution; and lifestyle factors of advanced age, alcohol consumption, smoking, stress, obesity, and poor diet. Other factors include infections, autoimmunity and chronic disease.

Spermatozoal membranes are rich in poly-unsaturated fatty acids and are susceptible to oxygen damage from lipid-peroxidation. Abnormal spermatozoa and contaminating leucocytes generate ROS.

Antioxidants that are naturally found in semen include vitamin E, and C, superoxide dismustase (SOD), glutathione, thioredoxin/. These antioxidants act as free radical scavenge­rs that help to overcome ROS. Subfertile men have been identified as having lower levels of antioxidants in their semen compared to fertile men.  A study by Bykova 2007 showed that  ROS levels were significantly higher in infertile sperm samples when compared with healthy controls and that the infertile men who provided these samples may benefit from an antioxidant supplement.

ROS are thought cause fertility problems in two ways, by firstly damaging the sperm membrane thus affecting the sperm motility and the ability of the spermatozoa to break down the oocyte membrane; and secondly by altering the sperm DNA. Spermatozoal DNA integrity is one of the major determinants of normal fertilization and embryo growth in natural and assisted conception. Indeed, many men with normal seminal parameters may have a high degree of sperm DNA damag­e and this correlates with a poor chance of natural conception.

Polyunsaturated fatty acids (PUFAs) are sources of antioxidants and are commonly taken in the community as nutrional supplemen­ts. PUFAs have varying effects in male fertility. They provide antioxidants and also increase the plasma fluidity of the sperm membrane which acts to assist with conception, however this fluidity makes the sperm susceptibility to reactive oxygen species (ROS) and lipid peroxidation that can damage the sperm. Wathes states that “It appears that PUFAs are two edged swords – some are essen­tial, but too many are potentially harmfu­l”.

An open study Comhaire attempted to overcome the double edged sword of essential fatty acid supplements by also treating the subfertile men in their study with antioxidant supplements of Acetylcysteine or beta-carotene and alpha-tocopherol.    

 PUFAs are classified into omega-3, omega-6 and omega-9. Omega-9 is synthesised by animal but omegas-3 and 6 need to be supplemented in the diet. The main sources of omega-6 are vegetable oils. Sources of omega-3 are vegetable and fish oils.³⁸

Antioxidants are widely available and inexpen­sive when compared to other fertility treatment. The patients with oxidative stress may benefit from the strategies to reduce oxi­dati­ve stress and treatment with anti­oxidan­t.

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