Glutathione and Your Fertility
"Glutathione, in my opinion, may prove to be one of the most significant factors in why egg quality declines with age.
In every single patient interaction with someone who is trying to conceive (TTC), an overwhelming part of our conversation revolves around egg and sperm quality. In truth, it takes three basic things to make a healthy baby - healthy eggs, healthy sperm, and a healthy uterine environment (complete with the hormonal output necessary to support a pregnancy). But clinically, the biggest obstacle to getting that healthy baby is often egg quality. As you know, women are born with all of the egg cells we’ll ever have. This means they’ve been exposed to absolutely everything we’ve been exposed to over the course of our lives. When we get to be 30, 35, or 40 and decide we’re ready to have children, in many cases those egg cells are no longer operating at their peak potential.
In many patients who I treat at Acubalance, improving the quality of the gametes is our primary target for achieving optimal fertility.
There are several known factors that influence both egg and sperm quality, but oxidative stress is one of the most damaging and the most prevalent. When we test a patient's urine for oxidative stress levels - 9 times out of 10, even if they’re taking antioxidant-rich supplements, levels of ROS come back elevated. This is problematic, because it signals an underlying imbalance that could be blocking the peak performance of eggs and sperm.
In this article, I’m going to review oxidative stress, its role in both male and female fertility, and why glutathione is a keystone in our approach to optimizing fertility.
What is oxidative stress?
Oxidative stress is a type of cellular stress that arises from an imbalance between reactive oxygen species (ROS), and antioxidants within the body.
During normal cellular processes (such as the production of cellular energy, called ATP), ROS are generated as a by-product. This process is kind of akin to how when you burn fuel for your car, it creates exhaust as a waste product. The body has a way of mopping up this exhaust, using antioxidants either derived from food or manufactured within your cells using precursor vitamins and minerals. When there are adequate antioxidants present, ROS have very little opportunity to cause damage - they’re quickly quenched. But in the case of low antioxidant status, ROS can create a lot of cellular damage in the reproductive tract. ROS damage cell membranes, which can hinder fertilization and implantation; they damage mitochondria which produce necessary ATP to nourish the early embryo and facilitate normal separation of chromosomes during cellular division; and they can damage DNA of the sperm, eggs, and reproductive tissues. All bad things when it comes time to TTC.
What creates oxidative stress?
Lots of things can accelerate the generation of reactive oxygen species. A small amount of ROS are actually necessary for certain cellular processes, including egg fertilization and embryo implantation, but what we see most often is an excess amount of ROS that create damage.
Certain lifestyle habits have been shown to accelerate ROS development:
- exposure to environmental toxins (pesticides, plastics, Teflon coating, chemicals in personal care products, etc)
- overconsumption of sugar
- intake of vegetable oils (ie. canola, safflower, margarine)
- chronic high stress, poor stress management
- lack of restful/restorative sleep
- lack of exercise
- poor intake, or absorption, of antioxidants
How does oxidative stress impact fertility?
There’s a large body of evidence that supports the negative influence of oxidative stress on eggs, sperm, embryos, and the uterine environment.
Specific to male fertility:
- small, controlled amounts of ROS are necessary for sperm to be able to function normally and fertilize an egg cell; but research shows that sperm are incredibly sensitive to high levels of ROS
- lipids in sperm cell membranes are easily damaged by excessive ROS
- excessive generation of ROS in the semen, by leukocytes (white blood cells) as well as by abnormal sperm cells, could be a cause of infertility
- the main ROS that impacts sperm, hydrogen peroxide, does so by causing sperm immobilization; very high concentrations of hydrogen peroxide can also result in sperm cell death
This results in the following identifiable changes in sperm quality:
- a reduction in sperm viability (cell death, via damage to DNA)
- decrease in sperm motility (due to instability in the mid-piece affecting propulsion)
- increase in mid-piece morphology defects (this is where the mitochondria are housed)
- increase in sperm DNA fragmentation
- reduction in sperm’s ability to fertilize the egg
- possible contribution to birth defects
Remember that in regards to sperm the question isn’t “how do we get rid of all of it!?”, because we need some ROS present for proper sperm physiology. But when levels are too high (shown via in-office testing), we need to moderate those levels in order to optimize male fertility.
Specific to female fertility:
Similar to with male fertility, a small controlled amount of ROS is necessary for many female reproductive processes: folliculogenesis (follicle growth), egg maturation, hormonal signaling, fallopian tube function, implantation and integrity of the uterine lining all require a small amount of ROS.
That said, when ROS are excessive, the following results have been seen:
- damage to cell membrane, inhibiting fertilization
- mitochondrial/ATP depletion, possibly leading to higher rates of aneuploidies (abnormal chromosome numbers)
- increased risk of hydatiform molar pregnancies
- fallopian tube issues
- pre-eclampsia (hypertension in pregnancy)
- unexplained infertility
- possible contribution to birth defects
Though fertilization is less likely with cellular membrane damage due to ROS, even when it does occur, the following are more likely in the presence of high levels of ROS:
- fragmentation of the embryo
- implantation failure
- insufficient hormone production to maintain early pregnancy
- altered/impaired placental development
- congenital abnormalities
Women with reproductive conditions like PCOS and endometriosis have been shown to have higher levels of ROS than women without these conditions.
In addition, the follicular fluid of women diagnosed with unexplained infertility has been shown to have higher levels of ROS.
So, no matter your age or your diagnosis (or lack thereof), if you’re TTC, you should check and correct your ROS levels.
Why do you need to know about glutathione?
Remember in the beginning of this article, that I said there is a way that your body naturally mops up all of those ROS? And that the answer to ROS was the use of antioxidants? Here’s why glutathione should be on your radar when you’re TTC:
Glutathione is often called the “master antioxidant” in the human body - it is also a very important contributor to the detoxification pathways and immune system function. The reason that it’s important to consider glutathione in the context of fertility, is that it’s one of our best tools to help you quickly combat excessive levels of ROS.
Luckily, your body makes its own glutathione! Through de-novo synthesis, your body makes glutathione out of 3 precursor amino acids: cysteine, glutamic acid and glycine. You find it both within the fluid of your cells, and in the organelles (like mitochondria) within them.
Unfortunately, as we age, our bodies become less efficient at manufacturing glutathione. This, in my opinion, may prove to be one of the most significant factors in why egg quality declines with age.
Though glutathione is used for many important functions in the body, its most important role regarding fertility is its powerful ability to quench ROS, protecting eggs/sperm and the uterine environment against the damaging effects of ROS expressed above. In addition to this primary protective role, glutathione also does a number of other amazing things for your cells via its impacts on nutrient metabolism and detoxification:
- helps your body recycle other antioxidants (like vitamin C) that act similarly to quench other ROS within the body and the reproductive tract
- plays a role in proper gene methylation (and the subsequent expression of your genes)
- assists with DNA and protein synthesis
- facilitates cell communication and regulated cell death
- supports the immune response
- plays a major role in hormone and environmental toxin detoxification (see our video series on the impacts of environmental toxins on your fertility for more information)
Where’s the research on glutathione and fertility?
While the body of literature regarding glutathione and fertility is not vast, there is a growing body of evidence for its supportive role for couples who are TTC, and even more evidence for the fertility-damaging effects of excessive ROS.
Here’s a summary of the existing research:
-Lenzi et al: 2 months of glutathione therapy (double-blind cross-over trial) in 20 infertile males with unilateral varicocele or germ-free genital tract infection. Treatment was 600mg injectable glutathione daily vs placebo. Positive effects seen on sperm motility (especially forward motility), and sperm morphology
-Agarwal et al: support for the role of excessive ROS impacting sperm quality negativel
-Garrido et al: intracellular glutathione levels are lower when severe sperm morphology issues are present; establishing connection between low % normal morphology and ROS and calling for the role of glutathione supplementation
-Kodama et al: levels of 8-OH-dG (marker of oxidative stress) are higher in male infertile patients than in controls; antioxidant treatment with vitamin C and glutathione resulted in positive effects on sperm concentration, with a significant reduction in sperm 8-OH-dG
-Kodama et al: sperm GSTs (glutathione s-transferase, an enzyme in the glutathione processing family) are essential in the defense mechanism against oxidative stress in sperm cells; further, the female reproductive tract contains extracellular glutathione that would give sperm a survival advantage
-Mukherjee et al: oocytes (egg cells) with higher levels of intracellular glutathione produce healthier and stronger embryos
-Kankofer et al: in younger years, women’s ovaries have higher glutathione levels
-Tola et al: in women undergoing IVF, higher levels of glutathione in a woman’s follicle translated to increased fertilization rates
-Fujii et al: glutathione is shown to be an antiaging antioxidant which could have possible impacts on egg health, one of the cells most affected by the aging process
-Gardiner et al: glutathione can reduce oxidative stress by fighting the formation of damaging free radicals [ROS] in the reproductive system
How do I get more glutathione?
Because of its incredibly reactive nature, it has traditionally been difficult to find ways of increasing the pool of glutathione in the body - taken as an oral supplement, or even via foods that contain it, glutathione is quickly broken down in the digestive tract. It is therefore difficult to increase intracellular glutathione levels in a significant way, and thus affect egg and sperm, with an oral glutathione supplement.
Fortunately, there are a couple of work-arounds. At Acubalance, we administer glutathione via injection to our male and female patients who are TTC. You can either get a glutathione shot (intramuscular injection) or have a push of glutathione during an nutritional IV session. You wouldn’t want to just take glutathione alone, as there are many cofactor nutrients that are necessary to assist in the body’s ability to recycle glutathione and keep levels high for longer. Therefore, we typically recommend having our fertility supportive IVs along with your glutathione, whether you receive it intramuscularly or via IV.
We often recommend starting with a series of 10 weekly IV glutathione sessions, followed by a mitochondrial and glutathione support formula in the form of a nutritional IV drip, for patients who are TTC. At this point, we can help you determine if you should continue them weekly or can to a less frequent maintenance schedule. Read more about our nutritional IVs here.
If you would prefer to receive intramuscular injections (shots) of glutathione, we recommend doing at least 2 nutritional IV therapy sessions, for every 10 weekly intramuscular glutathione shots. These glutathione shots are very quick (they take about 5 mins to administer) and can often be added on to your weekly acupuncture appointments.
Another common recommendation I make to patients, is to begin supplementing with oral NAC (n-acetyl cysteine) while undergoing regular IV glutathione treatments. NAC has been shown to reliably increase glutathione concentration within the cells, and helps elevate the impact of the IV glutathione.
If you’d like to learn more about whether glutathione is right for you and where you’re at in your fertility journey, feel free to book a free 15 minute consult with myself or my naturopathic colleague, Dr Ashley Damm, to discuss!
Dr Kali MacIsaac ND
Naturopathic Doctor in Vancouver, BC
- More info on IV Nutritional Therapy available at Acubalance.
- Laser for Fertility (LLLT/Photobiomodulation) to reduce oxidative stress (ROS) and inflammation to maximize egg quality.
About Dr. Kali MacIsaac – Vancouver Naturopath
Dr. Kali MacIsaac is a registered Naturopathic Doctor (ND) with the College of Naturopathic Physicians of British Columbia. She is a member of the BC Naturopathic Association (BCNA) and the Canadian Association of Naturopathic Doctors (CAND). Prior to medical school, Kali earned an Honours Bachelor of Science degree in Biomedical Science from the University of Waterloo where her passion for healthcare developed. Following this, she attended the Canadian College of Naturopathic Medicine (CCNM) in Toronto, Ontario, for a 4-year accredited naturopathic medicine program.
Dr. MacIsaac works as a general practitioner, and has a clinical focus in digestive health, reproduction and fertility, endocrinology and hormonal balance.