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Male Infertility: Nutritional and Environmental Considerations by Steven Sinclair, ND, LAc ------------------------------------------------------------------------ Abstract Studies confirm that male sperm counts are declining, and environmental factors, such as pesticides, exogenous estrogens, and heavy metals may negatively impact spermatogenesis. A number of nutritional therapies have been shown to improve sperm counts and sperm motility, including carnitine, arginine, zinc, selenium, and vitamin B-12. Numerous antioxidants have also proven beneficial in treating male infertility, such as vitamin C, vitamin E, glutathione, and coenzyme Q10. Acupuncture, as well as specific botanical medicines, have been documented in several studies as having a positive effect on sperm parameters. A multi-faceted therapeutic approach to improving male fertility involves identifying harmful environmental and occupational risk factors, while correcting underlying nutritional imbalances to encourage optimal sperm production and function. (Altern Med Rev 2000;5(1):28-38.) ------------------------------------------------------------------------ Introduction An estimated six percent of adult males are thought to be infertile.1 Infertility is defined by most authorities as the inability to achieve a pregnancy after one year of unprotected intercourse. Conception is normally achieved within 12 months in 80-85 percent of couples using no contraceptive measures; thus an estimated 15 percent of couples attempting their first pregnancy will have difficulty conceiving. While certain cases of male infertility are due to anatomical abnormalities such as varicoceles, ductal obstructions, or ejaculatory disorders, an estimated 40-90 percent of cases are due to deficient sperm production of unidentifiable origin.2 ------------------------------------------------------------------------ Diagnosis and Evaluation While the focus of this article is on specific nutritional and environmental factors, there are other important diagnostic considerations when evaluating male infertility. These include endocrine abnormalities, such as hyper- and hypothyroidism or hypogonadism. Prescription drugs, including phenytoin, glucocorticoids, sulfasalazine, and nitrofurantoin all may have detrimental effects on sperm production and motility.2 A detailed history of exposure to occupational and environmental toxins, recreational drugs and alcohol, excessive heat or radiation, and previous genitourinary infections should be elicited. Concurrent pathologies may also affect sperm production. Hepatic cirrhosis is associated with increased endogenous estrogens, which can suppress pituitary gonadotropin secretion and affect spermatogenesis. In addition, an estimated 80 percent of men with hemochromatosis have some degree of testicular dysfunction. Scrotal temperature is highly regulated by the body, and sperm production is greatly reduced at temperatures above 96º F. Men attempting to improve their fertility should not wear tight fitting pants or underwear (boxer shorts instead of briefs), an should avoid strenuous exercise, hot tubs, and baths. ------------------------------------------------------------------------ Semen Analysis A normal semen sample should have a volume of 1.5-5.0 ml, with greater than 20 million sperm/ml. The number of abnormal sperm should be less than 40 percent, with greater than 30 percent of the sperm sample demonstrating proper motility. Unfortunately, conventional semen analysis is not a highly accurate predictor of fertility. Purvis et al reported, after surveying infertility clinics, that 52 percent of men with a sperm count below 20 million/ml were able to impregnate their partners and 40 percent of men with a sperm count below 10 million/ml were also able to conceive.1 Conventional semen analysis often fails to identify infertile males with "normal" samples and conversely fails to identify fertile males with subnormal semen parameters.3 Another confounding factor is variations in sperm density, motility, and morphology among multiple samples from the same subject. More sensitive tests are available, including the post-coital test, which measures the ability of sperm to penetrate cervical mucus, and the hamster-egg penetration test, which measures the in vitro ability of sperm to penetrate hamster eggs. This test predicts fertility in an estimated 66 percent of cases, in comparison to 30 percent with conventional sperm analysis.1 ------------------------------------------------------------------------ Infection The role of infection in idiopathic male infertility has been underestimated, in particular chronic asymptomatic chlamydial infections.1 Chlamydia can reside in the epididymis and vas deferens, affecting sperm development and fertility. One study suggests approximately 28-71 percent of infertile men have evidence of a chlamydial infection.4 The presence of anti-sperm antibodies may indicate an undiagnosed infection, and is estimated to be a relative cause of infertility in 3-7 percent of cases. In a study designed to examine the effects of antioxidants on anti-sperm antibodies, there was a significant correlation between beta carotene levels and antibody titers, suggesting dietary antioxidants are involved in mediating immune function in the male reproductive system.5 ------------------------------------------------------------------------ Declining Sperm Counts There is a growing body of scientific evidence supporting the idea that sperm counts have declined considerably over the last 50 years. Carlsen et al analyzed a total of 61 studies including 14,947 men from the years 1938 to 1991, for mean sperm density and mean seminal volume. Their results show a significant decline in mean sperm density from 113 million/ml in 1940 to 66 million/ml in 1990 (p 20 million/ml) but had decreased motility which was not due to immunological disorders or infections. Subjects were given 80 ml of a 10-percent arginine HCl solution for six months. Arginine supplementation significantly improved sperm motility without any side effects.30 ------------------------------------------------------------------------ Zinc Zinc is a trace mineral essential for normal functioning of the male reproductive system. Numerous biochemical mechanisms are zinc dependent, including more than 200 enzymes in the body.31 Zinc deficiency is associated with decreased testosterone levels and sperm count. An adequate amount of zinc ensures proper sperm motility and production. Zinc levels are generally lower in infertile men with diminished sperm count, and several studies have found supplemental zinc may prove helpful in treating male infertility.32 In one trial, the effect of zinc supplementation on testosterone, dihydrotestosterone, and sperm count was studied. Thirty-seven patients with idiopathic infertility of more than five-years duration and diminished sperm count received 24 mg elemental zinc from zinc sulfate for 45-50 days. The results were dramatic in the 22 subjects with initially low testosterone levels; a significant increase in testosterone levels and sperm count (from 8 to 20 million/ml) was noted, along with nine resulting pregnancies.33 Fourteen infertile males with idiopathic oligospermia were supplemented with 89 mg zinc from oral zinc sulfate for four months. Serum zinc levels were unaffected, but seminal zinc levels significantly increased. There were also improvements in sperm count and in the number of progressively motile and normal sperm. Three pregnancies occurred during the study.34 Zinc supplementation appears warranted in the treatment of male infertility, especially in cases of low sperm count or decreased testosterone levels. ------------------------------------------------------------------------ Antioxidants Polyunsaturated fatty acids and phospholipids are key constituents in the sperm cell membrane and are highly susceptible to oxidative damage. Sperm produce controlled concentrations of reactive oxygen species, such as the superoxide anion, hydrogen peroxide, and nitric oxide, which are needed for fertilization; however, high concentrations of these free radicals can directly damage sperm cells.35 Disruption of this delicate balance has been proposed as one of the possible etiologies of idiopathic male infertility. ------------------------------------------------------------------------ Vitamin C Studies have shown the concentration of ascorbic acid in seminal plasma directly reflects dietary intake, and lower levels of vitamin C may lead to infertility and increased damage to the sperm's genetic material.36 Fraga et al demonstrated this by reducing ascorbic acid intake in healthy men from 250 mg to 5 mg per day. Seminal plasma levels of vitamin C decreased by 50 percent, with a concomitant 91-percent increase in sperm with DNA damage.37 Cigarette smoking has been documented as having deleterious effects on sperm quality. In a University of Texas study on vitamin C and sperm quality in heavy smokers, 75 men were divided into three supplementation groups; one was given placebo, the other groups received 200 mg or 1000 mg ascorbic acid. While the placebo group showed no improvement, the ascorbic acid groups showed significant improvement in sperm quality, with the greatest improvement occurring in the 1000 mg group.38 In perhaps one of the best studies on vitamin C and male infertility, 30 infertile but otherwise healthy men were given a placebo, 200 mg, or 1000 mg vitamin C daily. After one week, the group receiving 1000 mg/day had a 140-percent increase in sperm count, while there was no change in the placebo group. The 200 mg/day group had a 112-percent increase in sperm count, while both groups demonstrated significant reductions in the number of agglutinated sperm. Most importantly, by the end of the 60-day study every participant in the vitamin C group had impregnated their partner, while no pregnancies occurred in the placebo group.39 ------------------------------------------------------------------------ Vitamin E Vitamin E is a well-documented antioxidant and has been shown to inhibit free-radical-induced damage to sensitive cell membranes.40 In one study, lipid peroxidation in the seminal plasma and spermatozoa was estimated by malondialdehyde (MDA) concentrations. Oral supplementation with vitamin E significantly decreased MDA concentration and improved sperm motility, resulting in a 21-percent pregnancy occurrence during the study.41 In one randomized, cross-over, controlled trial, 600 mg/day vitamin E improved sperm function in the zona binding assay, therefore enhancing the ability of the sperm to penetrate the egg in vitro.42 Nine men with low sperm count and alterations in sperm motility were given vitamin E with the antioxidant trace mineral selenium for six months. Compared to the baseline pre-supplementation period of four months, the combination of vitamin E and selenium significantly increased sperm motility and the overall percentage of normal spermatozoa.43 ------------------------------------------------------------------------ Glutathione/Selenium Glutathione is vital to sperm antioxidant defenses and has demonstrated a positive effect on sperm motility.44-46 Selenium and glutathione are essential to the formation of phospholipid hydroperoxide glutathione peroxidase, an enzyme present in spermatids which becomes a structural protein comprising over 50 percent of the mitochondrial capsule in the mid-piece of mature spermatozoa. Deficiencies of either substance can lead to instability of the mid-piece, resulting in defective motility.47,48 Glutathione therapy was used in a two-month, placebo-controlled, double-blind, cross-over trial of 20 infertile men. The subjects were given either a daily 600 mg intramuscular injection of glutathione or an equal volume of placebo. Glutathione demonstrated a statistically significant effect on sperm motility, especially increasing the percentage of forward motility.49 Sixty-nine infertile Scottish men were given either placebo, selenium, or selenium in combination with vitamins A, C, and E for three months. At the end of the trial, both selenium-treated groups had significant improvements in sperm motility; however, sperm density was unaffected. Eleven percent of the participants in the treatment groups impregnated their partner during the course of the study.50 Another study compared the effects of selenium supplementation in 33 infertile men. They were given either a 200 mcg/day dose of selenium from sodium selenite or a selenium-rich yeast for 12 weeks. While selenium concentration in seminal fluid was increased in both groups, it was markedly higher in the yeast-Se group. Yeast-Se significantly increased glutathione peroxidase activity in the seminal fluid, but failed to produce any improvements in sperm count, motility, or morphology.51 ------------------------------------------------------------------------ Coenzyme Q-10 In sperm cells, coenzyme Q10 (CoQ10) is concentrated in the mitochondrial mid-piece, where it is involved in energy production. It also functions as an antioxidant, preventing lipid peroxidation of sperm membranes. When sperm samples from 22 asthenospermic men were incubated in vitro with 50 microM CoQ10, significant increases in motility were observed. CoQ10 (60 mg) was given to 17 infertile patients for a mean 103 days, and although there were no significant changes in standard sperm parameters, there was a significant improvement in fertilization rate (p


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