Glutathione
(GSH) and Male Infertility
Improving
Sperm Quality and Morphology
Copyright
© 2002 1Whey2Health
Reproduction Prohibited
► Is
pollution stealing your future?
►
Whey
are anti-oxidants important for sperm quality?
►
Why
is glutathione important for sperm quality and male fertility?
►
How
can glutathione help in the treatment of male infertility?
►
References
on glutathione and male infertility
Is
Pollution Stealing Your Future?
In 1992, E.
Carlsen et al. reported that sperm counts have dropped by half
in the last 50 years while semen volume is 20 percent less (1).
A recent report
from researchers in Aberdeen presented preliminary data that suggests
the sperm concentration of the men seen in their clinic had declined
by 29% over the past 14 years. (2)
Persistent
organic pollutants (POPs) and endocrine-disrupting chemicals from
normal, everyday plastics are known to cause reproductive damage,
as documented in the book "Our
Stolen Future."
Men
who are exposed to high levels of lead may be at increased risk
of becoming infertile
as studies have shown that higher lead levels interfere with the
ability of the sperm to bind to the egg and with its ability to
fertilise the egg. (3)
Exposure to
the common industrial chemical, trichloroethylene (TCE), commonly
found in adhesives, lubricants, paints, varnishes, paint strippers,
pesticides, spot removers and rug cleaning fluids, has been shown
to adversely affect the normal development of sperm and cause
infertility.(4)
Damage in
sperm due to exposure to common chemicals like alcohol, pesticides
in food, has been linked to lowered intelligence and behavioral
disorders in children. (5)
Lifestyle
risk factors that decrease sperm quality include cigarette smoking,
alcohol consumption, chronic stress, and nutritional deficiencies.
You would also want to rule out congenital factors, and health
conditions like prostatitis and diabetes that can affect sperm
production.
Other than
changing your lifestyle and switching to organic foods, there's
not a lot you can do to reduce your exposure to persistent environmental
toxins. There
is, however, a lot you can do to prevent and repair the damage
they cause to your body, through better lifestyle and nutrition.
A number of
nutritional therapies have been shown to improve sperm counts
and sperm motility, including carnitine, arginine, zinc, selenium,
and vitamin B-12. Antioxidants
like vitamin C, vitamin E, glutathione, and coenzyme Q10, have
also proven beneficial in treating male infertility. (6)
Studies show
that anti-oxidant supplementation - glutathione in particular,
can improve sperm quality, and possibly increase your chances
of conceiving.
If you smoke,
drink, are exposed to stress, chemicals, radiation, pesticides
or take medication or drugs that may affect fertility (like Sulfasalazine,
Ketoconazole, Azulfidine, Anabolic steroids, Marijuana), you will
very likely require an anti-oxidant supplement to reverse some
of the damage.
Why are Anti-oxidants Important for Sperm Quality?
Mammalian
spermatozoa are coated by a membrane rich in polyunsaturated fatty
acids. These fatty acids are extremely susceptible to oxidative
damage by free radicals or Reactive Oxygen Species (ROS) by a
process called lipid peroxidation (LPO).
Lipid
peroxidation damages the sperm cell membrane and is considered
to be the key mechanism of this ROS-induced sperm damage leading
to loss of motility, abnormal morphology and reduced capacity
for sperm oocyte penetration and infertility. (7,8)
To protect
sperm from this damage, the body depends on powerful antioxidant
enzymes in the body such as superoxide dismutase (SOD), catalase,
and glutathione peroxidase/reductase (GPX/GRD). The GPX/GRD enzymes
play a central role in the defence against oxidative damage in
human sperm.(7)
Seminal
plasma and spermatozoa possess several antioxidant enzymes, glutathione
peroxidase, glutathione reductase, superoxide dismutase. (9)
It is now
known that some amount of all the antioxidant enzymes, which may
protect spermatozoa from oxidative attack, are also made by the
epididymis during storage. (10)
Why is Glutathione important for Sperm Quality and Male Fertility?
A decrease
in levels of reduced glutathione (GSH) during sperm production
has been shown to cause disruption in the membrane integrity of
spermatozoa as a consequence of increased oxidative stress.(11)
Intracellular
glutathione levels of spermatozoa are shown to be decreased in
certain populations of infertile men.(12)
At the 94th
Annual Meeting of the American Urological Association, andrologists
presented strong clinical evidence that men diagnosed with infertility
have high levels of oxidative stress that may impair the quality
of their sperm.(13,14)
Compared with
a control group, the infertile men in all groups had significantly
higher levels of ROS and lower levels of total antioxidants. In
some groups, higher levels of ROS were associated with lower sperm
counts and defective sperm structure, while lower antioxidant
levels correlated with reduced sperm movement.
Their results
supported previous evidence showing that oxidative stress can
decrease a sperm's life span, its motility, and its ability to
penetrate the oocyst, or egg cell. Up to 40% of men with male
infertility without a known cause have higher levels
of free radical activity in their bodies. (13)
Because men
with high levels of ROS have a seven-fold lower likelihood of
inducing a pregnancy than men with lower levels, researchers
recommend that treatment for infertile men should include strategies
to reduce oxidative stress and improve sperm quality.
How can Glutathione help in the Treatment of Male Infertility?
Glutathione
is not only vital to sperm antioxidant defenses, but selenium
and glutathione are essential to the formation of phospholipid
hydroperoxide glutathione peroxidase - an enzyme present in
spermatids which becomes a structural protein in the mid-piece
of mature spermatozoa. Deficiencies of either substance can lead
to instability of the mid-piece, resulting in defective motility.
(15,16)
Scavengers,
such as glutathione can be used to treat these cases as they can
restore the physiological constitution of poly-unsaturated fatty
acids (PUFA) in the cell membrane. (17, 18)
In
a double-blind cross-over study of 20 infertile men, treatment
with glutathione led to a statistically significant improvement
of the sperm quality. The study concerned men in whom the
sperm quality was poor due to unilateral varicocele or germ-free
genital tract inflammation - two conditions in which ROS or other
toxic compounds are indicated as causative factors. (19, 20)
Treatment
with glutathione was found to have a statistically significantly
positive effect on, among other things, sperm motility (in particular
forward motility) and on sperm morphology. The findings of these
studies indicate that glutathione
therapy could represent a possible therapeutical tool in cases
where ROS or exposure to toxins is the probable cause of male
infertility. (21)
References
in Glutathione and Male Infertility
- BMJ, 1992,
volume 305
- UK
study shows 29% drop in sperm concentration
5th January 2004; Press release from the British Fertility Society
- Lead
linked to male infertility
6
February, 2003; BBC News, Health
- Common
Industrial Chemical Now Linked To Male Infertility; Chemical
Adversely Affects The Normal Development Of Sperm
2003-03-07; Science Daily
- Damaged
Sperm & Common Chemical Exposure: Links to Links to Learning
Disabilities, ADD and Behavior Disorders by Richard W. Pressinger
- Male
infertility: nutritional and environmental considerations
Sinclair S. [Altern Med Rev 2000 Feb;5(1):28-38] Green
Valley Health, Hagerstown, MD 21742, USA.
- Biochemistry
of the induction and prevention of lipoperoxidative damage in
human spermatozoa
Storey BT. [Mol Hum Reprod 1997 Mar;3(3):203-13]
- Oxidative
stress and role of antioxidants in normal and abnormal sperm
function
Suresh C. Sikka, Ph.D., HCLD [Frontiers in Bioscience
1, e78-86, August 1,1996]
- Studies
on the origin of redox enzymes in seminal plasma and their relationship
with results of in-vitro fertilization
Yeung CH, Cooper TG, De Geyter M, De Geyter C, Rolf C, Kamischke
A, Nieschlag E.
Mol Hum Reprod. 1998 Sep;4(9):835-9.
- Seminal
plasma reduces exogenous oxidative damage to human sperm, determined
by the measurement of DNA strand breaks and lipid peroxidation
Potts RJ, Notarianni LJ, Jefferies TM. Mutat Res. 2000
Feb 14;447(2):249-56.
- Status
of vitamin E and reduced glutathione in semen of oligozoospermic
and azoospermic patients
A. Bhardwaj, A. Verma, S. Majumdar, K. L. Khanduja [Asian
J Androl 2000 Sep; 2: 225-228]
- Glutathione
in spermatozoa and seminal plasma of infertile men
Ochsendorf FR, Buhl R, Bastlein A, Beschmann H. [Hum
Reprod 1998 Feb;13(2):353-9]
- Relationship
between oxidative stress, semen characteristics, and clincial
diagnosis in men undergoing infertility investigation
Pasqualotto FF, Sharma RK, Nelson DR, Thomas AJ Jr, Agarwal
A. [Fertil Steril 2000;73:459-64]
- Oxidative
stress in normospermic men undergoing infertility evaluation.
Pasqualotto FF, Sharma RK, Kobayashi H, Nelson DR, Thomas
AJ Jr, Agarwal A. [J Androl. 2001 Mar-Apr;22(2):316-22]
- Dual
function of the selenoprotein PHGPx during sperm maturation
Ursini F, Heim S, Kiess M, et al. Science 1999;285:1393-1396.
- Selenium
and fertility in animals and man a review
Hansen JC, Deguchi Y. Acta Vet Scand 1996;37:19-30.
- Lipoperoxidation
damage of spermatozoa polyunsaturated fatty acids (PUFA): scavenger
mechanisms and possible scavenger therapies
Lenzi A, Gandini L, Picardo M, Tramer F, Sandri G, Panfili
E. [Front Biosci 2000 Jan 1;5:E1-E15]
- Polyunsaturated
fatty acids of germ cell membranes, glutathione and blutathione-dependent
enzyme-PHGPx: from basic to clinic
Lenzi A, Gandini L, Lombardo F, Picardo M, Maresca V, Panfili
E, Tramer F, Boitani C, Dondero F. [Contraception 2002 Apr;65(4):301-4]
- Glutathione
treatment of dyspermia: effect on the lipoperoxidation process
Lenzi A, Picardo M, Gandini L, Lombardo F, Terminali O, Passi
S, Dondero F. [Hum Reprod 1994 Nov;9(11):2044-50] Laboratory
of Seminology and Immunology of Human Reproduction, University
of Rome La Sapienza, Italy.
- Glutathione
therapy for male infertility
Lenzi A, Lombardo F, Gandini L, Culasso F, Dondero F.
[Arch Androl 1992 Jul-Aug;29(1):65-8]
- Placebo-controlled,
double-blind, cross-over trial of glutathione therapy in male
infertility
Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero F.
[Hum Reprod 1993 Oct;8(10):1657-62
More References:
Environmental
Causes of Infertility
Information provided by Chem-tox.com
Glutathione
as a Treatment for Male Infertility (PDF)
D. Stewart Irvine [Reviews of Reproduction (1996) 1, 6–12]
Relative
impact of oxidative stress on male reproductive function
Sikka SC. [Curr Med Chem. 2001 Jun;8(7):851-62.] Department
of Urology, Tulane University School of Medicine, New Orleans,
Louisiana 70112-2699, USA.
A
rationale for glutathione therapy
Lenzi A, Gandini L, Picardo M. [Hum Reprod. 1998 Jun;13(6):1419-22.]
Department of Medical Pathophysiology, University of Rome La Sapienza,
Italy.
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