Until recently conditions such as varicocele, undescended testes, infections, obstructive lesions, cystic fibrosis, trauma, and tumors were the only known causes of male infertility. Those men who did not fall into any of these groups were described as having “idiopathic” infertility as the cause has only recently been identified.
However, over the past decade it has become clear that the principal cause of idiopathic male infertility is an underlying pathological condition known as “oxidative stress”.
Oxidative stress is a well known biological state that occurs when there is an imbalance between the body’s production of excessive reactive oxygen species (also known as free radicals) and an insufficiency of internal and dietary-derived antioxidants to counter the adverse effects of the these potentially harmful molecules.
Although all cells may be damaged during episodes of oxidative stress, spermatozoa are particularly susceptible to free radical damage.
Reactive oxygen species (ROS) are environmental pollutants as well as by-products of the body’s energy production and other cellular activities. Although some cellular ROS do fulfill important physiological functions when produced in excess they can affect both the quality and quantity of sperm.
Under normal circumstances seminal fluid contains antioxidants that control the damaging effects of ROS; but if excessive quantities of the latter are produced an imbalance occurs and the ROS inflict damage to the sperm cell walls and sperm DNA. This leads to the production of poor quality sperm and results in infertility.
Moreover, such DNA-damaged sperm may cause miscarriages, produce offspring with conditions such as achondroplasia (dwarfism) and trigger childhood cancers.
Two of the aggravating factors associated with idiopathic male infertility are infection and inflammation. Even low grade, “hidden” genito-urinary infections cause inflammation and an associated increase in the number of leukocytes (white blood cells) in the male reproductive tissues. Both contaminating leukocytes and abnormal sperm cells contribute to an increase in the production of ROS and oxidative stress that further compromises normal spermatogenesis.
Other causes of oxidative stress associated with male infertility are smoking, aging, pesticides, exogenous estrogens, heavy metals and diseases such as diabetes.
TREATMENT OF INFERTILITY CAUSED BY OXIDATIVE STRESS
It goes without saying that one should first eliminate the treatable causes of oxidative stress such as diabetes, infections, smoking etc. Once that has been done there are laboratory tests that can determine whether or not oxidative stress exists in the seminal fluid.
However it is important to note that ROS can have both beneficial and detrimental effects on spermatozoa. The ratio of quantities of ROS produced to those neutralized by antioxidant compounds will decide whether a given sperm function will be helped or hindered.
As various antioxidant compounds work at different stages of the oxidative process it is unlikely that taking large doses of one “strong” antioxidant alone will make much impact. In fact large doses of any antioxidant may actually aggravate the situation as certain ROS like hydrogen peroxide are essential signaling molecules without which normal immune function is compromised.
We recommend, therefore, that large doses of one or two antioxidant vitamins such as vitamin C, E and Beta-carotene are not taken without careful consideration. Instead a diet rich in antioxidant containing foods such as spices, fruit and vegetables provide a wide variety of natural antioxidant compounds. In fact spices have the greatest antioxidant activity of all food types (American Journal of Clinical Nutrition July 2006) and should be added to all meals or taken as a balanced spice-based supplement.
Keith Scott MD
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