Alternative Medicine Review 2000 (Feb); 5 (1): 28–38 ~ FULL TEXT
Steven Sinclair, ND, LAc
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<0.0001). Seminal volume decreased from
an average of 3.40 ml to 2.75 ml (p=0.027).6,7 This demonstrates a 20-percent
drop in volume and a substantial 58-percent decline in sperm production
in the last 50 years. Three other recent reports also found semen quality
has declined among donors over the last 20 years. [ 8-10 ]
Because the decline in sperm production is relatively recent, one must
suspect a combination of environmental, lifestyle, and dietary factors
might be interfering with spermatogenesis.
Environmental Risk Factors
Current evidence suggests there may be environmental reasons for deteriorating
sperm quality, including occupational exposure to various chemicals, heat,
radiation, and heavy metals. [ 11,12 ] In addition,
exposure to environmental estrogens and pesticides has been linked to alterations
in spermatogenesis. Lifestyle risk factors are also significant, including
cigarette smoking, alcohol consumption, chronic stress, and nutritional
deficiencies. [ 13 ]
Xeno-Estrogens and Pesticides
Increased exposure to estrogens is thought to be responsible for not
only prenatal testicular damage, but may also contribute to post-natal
depression of testicular function and spermatogenesis. Exogenous estrogens
impact fetal development by inhibiting the development of Sertoli cells,
which determine the lifelong capacity for sperm production.
Circulating estrogens also inhibit enzymes involved in testosterone
synthesis and may directly affect testosterone production.
The synthetic estrogen, diethylstilbestrol (DES), is a well-documented
example of this problem. DES was prescribed from 1945 to 1971 to millions
of women during pregnancy. Male offspring from those women had a higher
incidence of developmental problems of the reproductive tract, as well
as diminished sperm volume and sperm count. [ 5 ]
Synthetic estrogens are still widely used in the livestock, poultry,
and dairy industries. Men wishing to improve their fertility and sperm
quality probably should avoid hormone-containing dairy products and meats
and opt instead for organic or hormone-free foods.
Many commonly-used pesticides, such as organochloride compounds, have
estrogenic effects within the body. Chemicals such as dioxin, DDT, and
PCBs are known to interfere with spermatogenesis. One study which examined
the effect of DDT on male rat sexual development found low levels of DDT
caused degeneration in sperm production, a decrease in the total number
of sperm, and a reduced number of Leydig cells. The authors hypothesize
that DDT acts as an hormonal disrupter, damaging the seminiferous epithelium
and lowering local testosterone levels. [ 14 ]
Nutritional Therapies
Carnitine
The main function of carnitine in the epididymis is to provide an energetic
substrate for spermatozoa. Carnitine contributes directly to sperm motility
and may be involved in the successful maturation of sperm. [ 23 ]
This is especially important since epididymal sperm use fatty acid oxidation
as their main source of energy metabolism, and thus tend to concentrate
carnitine while in the epididymis, as carnitine is necessary for transport
of fatty acids into the mitochondria. [ 24 ]
Low levels of carnitine reduce fatty acid concentrations within the mitochondria,
leading to decreased energy production and potential alterations in sperm
motility.
In a study involving 124 infertile patients, a direct correlation between
semen carnitine content and sperm motility was found. The results also
show a positive correlation between free L-carnitine and both sperm count
and the number of motile sperm per milliliter (P<0.01). [ 25 ]
In one multi-center trial, 100 patients received 3 g/day of oral L-carnitine
for four months. Sperm parameters were assessed before, during, and after
the study. Motility was determined by computer-assisted sperm analysis.
The results clearly demonstrate carnitine has a positive effect on sperm
motility. The percentage of motile spermatozoa increased from 26.9 ±
1.1 to 37.7 ± 1.1 percent. The percent of sperm with rapid linear
progression increased from a baseline of 10.8 percent to 18.0 percent.
Not only did carnitine significantly affect sperm motility, but the total
number of spermatozoa per ejaculate also increased. [ 26 ]
Another clinical study reported similar results with 3 g carnitine given
daily for three months. Thirty-seven of the 47 participants had increases
in sperm motility, rapid linear progression, and total number of sperm. [ 27 ]
In a related study, 20 men with idiopathic asthenospermia (defective
sperm motility) were given acetylcarnitine, 4 g/day for 60 days. While
acetylcarnitine did not affect sperm density or total motility, it did
significantly increase progressive linear sperm motility. It is interesting
to note that gains in sperm motility were sustained in 12 of the subjects
during the four-month follow-up period. Five pregnancies occurred during
treatment, with two more occurring during the four months following the
trial. [ 28 ]
Arginine
The amino acid arginine is a biochemical precursor in the synthesis
of putrescine, spermidine, and spermine, which are thought to be essential
to sperm motility. In 1973, Schachter et al published a study in which
arginine was given to 178 men with low sperm count. Seventy-four percent
of the subjects had significant improvement in sperm count and motility
after taking 4 g/day for three months. [ 29 ]
More recently, researchers in Italy evaluated the clinical efficacy
of arginine in 40 infertile men. All the men had a normal number of sperm
( > 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<.0.05). [ 52 ]
In another study, 10 mg/day of coenzyme Q7 (an analog of CoQ10) was
given to infertile men, with resulting increases in sperm count and motility. [ 53 ]
Clearly, additional studies will be needed to evaluate the possible
role of coenzyme Q10 in the treatment of male infertility.
Vitamin B12
Vitamin B12, in its various forms, has been studied for its effect on
male infertility. Vitamin B12 is important in cellular replication, especially
for the synthesis of RNA and DNA, and deficiency states have been associated
with decreased sperm count and motility.
Methylcobalamin (1,500 mcg/day) was given to a group of infertile men
for a period of 8-60 weeks. They were evaluated periodically by semen analysis,
and standard sperm parameters were increased by 60 percent. [ 54 ]
In another methylcobalamin study, 1,500 mcg/ day was given to 26 infertile
men for a period of 4-24 weeks. Sperm analysis was conducted eight weeks
into the study. Sperm concentration increased in 38.4 percent of the cases
and total sperm count increased in 53.8 percent of the men. Sperm motility
increased in 50 percent of the participants. Serum LH, FSH, and testosterone
levels were unchanged. [ 55 ] When 6000 mcg/day
was given to men with low sperm count, it resulted in a 57-percent improvement. [ 56 ]
Vitamin B-12 (1000 mcg/day) was administered to men with a sperm count
less than 20 million/ml. By the end of the study, 27 percent of the men
had a sperm count over 100 million/ml. [ 57 ]
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