It is well-established that infertility in both males and females has been gradually increasing over several decades, with one couple in every six affected – and many requiring assisted reproductive technology in order to become parents.
The causes of infertility are not well-understood but it is known that many factors are involved. In this article, we focus on the upstream biochemical factors identified as major contributors to infertility together with therapeutic options.
Cellular Defences in Fertility
It is becoming increasingly apparent that deficits in the inbuilt cellular mechanisms protecting us against environmental and metabolic stresses significantly contribute to infertility. Protective mechanisms become even less efficient as we age, a factor shown to impact the normal development of both the ova and the sperm. This is especially true for modern couples delaying pregnancy-planning by a decade when compared with the generation before them. Even with younger couples, one or both partners may be unaware that their cellular defences are compromised and that an oxidative burden impacts their health.
The newer science of Nutrigenomics has uncovered ways to beneficially influence our endogenous cellular defence mechanisms.
How does Nutrigenomics enhance cellular defences?
Where 20th century nutritionists focused largely on micronutrients to effect changes in biochemical pathways, 21st century Nutrition Science encompasses the added benefits of potent food-derived molecules capable of significantly impacting the simultaneous expression of the hundreds of genes associated with cellular defences.
Nutrigenomics takes the practice of Clinical Nutrition to an entirely new level in the way it directly targets key biochemical pathways governed by genes that clinicians can now readily influence.
Redox imbalance in fertility
Evidence is mounting to support a strong link between uncontrolled oxidative stress and infertility. A 2019 study showed that low expression of the primary antioxidant enzyme Superoxide dismutase increases the likelihood of errors occurring as the female egg matures. The findings indicate that a major factor in female infertility is age-induced oxidative damage that results in the development of such dysfunctional ova.
Impact of oxidative stress on female fertility
Animal studies have also indicated that increased intracellular oxidative stress can potentially impair luteal formation and progesterone production. This Japanese research group suggested that SOD plays a crucial role in both the luteal function and the maintenance of fertility in females.
SOD on pregnancy rates of women undergoing intrauterine insemination
Many couples now rely on multiple rounds of assisted reproductive technology to achieve a pregnancy, a situation which makes it imperative that the woman’s redox environment is not hostile to the fertilisation process.
A 2017 clinical trial used a combination of melon-derived SOD and gliadin to increase cellular SOD activity. The purpose of the study was to determine whether there was any increase in pregnancy rates in women undergoing intrauterine insemination. The SOD/gliadin complex was shown to provide better ovarian stimulation response and increased pregnancy rates in these patients.
These outcomes showed that when SOD is upregulated nutrigenomically, there are measureable benefits to conception and in achieving pregnancy.
The impact of SOD on Oocytes
The relationship between SOD and the function of ova was demonstrated in a 2004 trial where higher SOD activity in oocytes resulted in good fertilization rates, more likely to result in a healthy pregnancy.
SOD and the Sperm
Men with lower sperm quality are known to exhibit lower SOD activity, a factor sometimes linked to environmental stressors increasing the levels of ROS in the body.
Another study confirmed that the activity of SOD in the seminal plasma of men with reproductive disorders was lower compared with fertile men. In some men carrying SOD gene polymorphisms, sperm concentration and quality can both be adversely affected. Nutrigenomic upregulation of SOD and the other primary antioxidant enzymes may assist in these cases.
An animal study concluded that the possible protective effects of SOD on sperm parameters are that it preserves the antioxidant and intracellular enzymes.
‘Old’ Science and Infertility
Twentieth century Nutrition Science assumed that oxidative stress could be countered by direct-acting antioxidant vitamins. Many large-scale clinical trials have not been able to demonstrate a protective benefit of the antioxidant vitamins A, E, C and beta-carotene in preventing chronic disease and in some studies both vitamin E and beta-carotene exacerbated lung cancer in smokers and cardiovascular disease.
Although it may seem intuitive to use antioxidant vitamins to address the redox imbalances associated with infertility, 21st century science indicates otherwise and a recent review of studies using antioxidants concluded that there were too few studies and that those available showed that the supplements probably made no difference, although there was some evidence for benefit in males.
When comparing the ability of the direct-acting antioxidant vitamins with the endogenous antioxidant enzymes in quenching radical species, the differences are obvious. An antioxidant enzyme such as SOD can quench literally millions of ROS per second, whereas an antioxidant vitamin can quench just one or a few ROS per molecule.
Other Lessons from Nutrigenomics
Nutrigenomics has taught us something else of great importance. Human cells activate their own defences in response to a stressor of some kind; that stressor could be a toxin, a free radical species, UV radiation or similar. This makes sense because cells make protective molecules as they need them. Imagine what might happen when a large dose of antioxidant vitamins floods the cells; this sudden antioxidant effect can mask the signals the cells need to activate the production of antioxidant enzyme like SOD.
Better understanding of how cells use stress signals to activate their defences makes it very clear why the ‘old’ science led to so many failed antioxidant trials.
New Science Brings New Hope
The melon-derived compound that combines SOD and gliadin is a potent activator of the three primary antioxidant enzymes, SOD, Glutathione peroxidase (GPx) and Catalase (Cat). As the patented combination, GliSODin, a few milligrams of gliadin per 250 mg of the SOD-rich melon extract is the mild stressor required to activate cellular synthesis of SOD, GPx and Cat.
GliSODin has been extensively studied to show that 250 mg of SOD/gliadin is capable of approximately doubling the activity of the three enzymes over a 28-day period. These effects have been confirmed in clinical trials, including a trial showing significant benefit in reducing atherosclerosis with this single intervention.
Following Nature’s lead in dealing with the stressors that threaten healthy reproductive function seems an obvious approach in helping couples dealing with the heartbreak of infertility. The new science of Nutrigenomics heralds that change.
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