Reproductive health poses a significant challenge for millions worldwide.
Globally, one in six people experience difficulty achieving pregnancy in their lifetime.1 Unexplained inability to conceive is defined as a failure to achieve pregnancy after 12 consecutive months of unprotected intercourse when all known causes have been ruled out. In these cases, environmental and lifestyle factors such as stress, smoking, poor diet and pollution may be implicated.
The challenges surrounding conception are complex and impact both sexes. For men, these challenges can be summarised by three key sperm health parameters: low sperm count; decreased sperm motility; and changes in morphology (size and shape). Data show that 50% of cases can be traced back partially or entirely to the male.2
For women, age plays a significant role in the ability to conceive, as the quality and quantity of oocytes (egg cells) diminishes substantially with advancing reproductive age. There is a notable increase in difficulty conceiving observed after the age of 32, and a sharp decline in pregnancy rates after age 37.3 While a man produces new sperm approximately every three months, a woman is born with all the eggs she will ever have, with the number of high quality oocytes becoming fewer and fewer over time.
The inability to conceive can have detrimental effects on a person’s mental and physical health. For mental health specifically, it can be both a cause and an effect. Difficulty conceiving often leads to feelings of stress, loss of control and low self-esteem. Research shows that prolonged levels of high or chronic stress can delay the process of conceiving. It has been reported that women practicing stress management techniques as part of a mind-body program had improved conception rates compared to those that did not participate in such program.4
Effects of oxidative stress on reproductive health
Since reproductive cells have very high demands for energy during the preconception and conception stages, oocytes and sperm rely heavily on having robust mitochondria. Oxidative stress is a major factor that compromises mitochondrial function by causing damage to mitochondrial membranes, DNA, and biochemical pathways. Oxidative stress occurs when there is an excess of free radicals in the body compared to antioxidant capacity. This can be induced by many factors, including aging, poor diet, stress, a sedentary lifestyle, and exposure to toxins.
Reducing the number of free radicals in the body is therefore vital for preconception health. Free radicals are produced in dynamic chemical reactions: as free radicals effectively ‘steal’ an electron from a molecule, the electron-deprived molecule becomes damaged and sometimes even turn into a free radical itself. If antioxidants are in short supply, free radicals begin to overwhelm antioxidants and damage to the body accumulates at a cellular level.
For men, studies show that elevated free radicals in the seminal fluid are found in 30-80% of men who have unexplained inability to conceive (depending on the measuring tool).2 In women, oxidative stress can impact oocyte and follicular development, ovulation and hormone production and chromosomal duplication and/or omission, leading to unsuccessful ovulation, fertilization and embryo development.5,6
Oxidative stress and mitochondrial dysfunction
Importantly, as women age, accumulating oxidative stress may contribute to the decline of the quality and function of oocytes, due to detrimental effects on mitochondria, which play a crucial and complex role in the healthy functioning of cells.5,6 In addition to their role in cellular energy generation, mitochondria also regulate gene expression, particularly relating to inflammatory response, and the mitochondria permeability transition pore (mPTP), which governs the flow of small molecules, a crucial switch for cell life and death. They also participate in a dynamic process of fission and fusion, which seems to be critical to overall cellular homeostasis.7
Research suggests that the decline in mitochondrial function is one of the driving factors behind the accelerated aging of oocytes.7 Oocytes contain the greatest number of mitochondria in any cell in the human body by one or two orders of magnitude due to the intense energy demands of their development and role in the reproductive process.8
Therefore, oocytes are especially reliant on healthy mitochondrial function and are especially susceptible to free radical damage. Because both sperm and egg cells have the greatest numbers of mitochondria, they produce large amounts of reactive oxygen species (ROS), which can cause oxidative damage to cells.
“Mitochondrial dysfunction is now known to be one of the core reasons that the gametes – the reproductive cells, sperm and egg – do not function properly, together with other factors including free radical damage to tissues and the mitochondrial DNA,” says Risa Schulman, Senior Science and Regulatory Advisor, Kaneka.
CoQ10 and ubiquinol’s role in preconception
As more becomes known about the factors which impact reproductive health at a cellular level, the supplement market is aligning with science to support both men and women who want to conceive.
Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain and cellular energy (ATP) production. CoQ10 continually shifts back and forth between being CoQ10 and ubiquinol, a powerful antioxidant form of CoQ10. As we age, our bodies produce less CoQ10 and ubiquinol and supplementing our diet with this nutrient is key.
As the most abundant lipid-soluble antioxidant, ubiquinol is localized to the mitochondrial membrane, where most free radicals are formed, making it the ideal neutralizer to combat oxidative stress and protect mitochondrial health. Ubiquinol is therefore crucial for reproductive health, protecting both sperm and oocyte from oxidative stress and its detrimental effects.
Research demonstrates a link between an increase in oxidative stress and declines in sperm health, oocyte quality and, especially in women 35 and older, ovarian reserve – an indicator of a woman’s reproductive potential.
Kaneka Ubiquinol® – supporting preconception health
A landmark paper published in 2019 exploring clinical practice guidelines for men with unexplained inability to conceive represents a significant advance in understanding the importance of oxidative stress in male preconception health.2
“The paper was authored by close to 100 reproductive health clinicians and researchers from around the world who believe there is overwhelming evidence that oxidative stress is associated with male unexplained inability to conceive” says Schulman. “They created the term ‘male oxidative stress infertility’, or MOSI, and referenced ubiquinol as one of the antioxidants that can be used to combat oxidative stress and promote beneficial effects on sperm concentration, motility and DNA integrity in these cases.”
Two studies in male subjects reveal that Kaneka Ubiquinol® had a positive impact on male reproductive health. In an open-label, six-month study of 60 men with oligospermia, Kaneka Ubiquinol® 150 mg vs placebo was found to increase total sperm count by 53% (P<0.05), total sperm motility by 26% (P<0.05) and absolute numbers of rapidly swimming sperm increased 41% (P<0.05).9
Also, in a retrospective 6-month study of 62 men with asthenoteratozoospermia (low sperm motility and abnormal sperm morphology but normal sperm count), Kaneka Ubiquinol® 100 mg twice daily vs placebo was shown to increase fast-moving sperm from 5.7% to 11.5% and improve sperm morphology from 2.6% to 3.1% (P<0.001).10
Research in women has to date been done using CoQ10 in subjects undergoing assisted reproductive technology. In women undergoing IVF, pretreatment with CoQ10 yielded more retrieved oocytes (P<0.002), higher fertilization rates (67.49%; P<0.005), more high-quality embryos (P<0.05), fewer cancelled embryo transfers (p=0.04), and more available cryopreserved embryos (18.42% vs. 4.3%, P=0.012). Research on the effects of ubiquinol in women’s reproductive health is underway.11
With over a decade of manufacturing in the US, Kaneka Ubiquinol® has a well-established safety profile as demonstrated by extensive clinical trial data. It has been shown to be 2-4 times better absorbed than conventional CoQ10.12,13 For those already using CoQ10 in reproductive health supplements, switching to Kaneka Ubiquinol® offers enhanced absorption and readily available antioxidant benefits. Also, consumers can supplement with ubiquinol while pursuing standard reproductive health treatments. As a unique, lipid-soluble antioxidant backed by scientific research, ubiquinol supports both men and women who want to conceive.
These statements have not been evaluated by the Food and Drug Administration. The product is not intended to diagnose, treat, cure, or prevent any disease.
References
2. Agarwal A, Parekh N, Selvan MKP, et al. Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37(3):296-312.
3. Ben-Meir, A.; Burstein, E.; Borrego-Alvarez, A.; et al. (2015). Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging cell, 14(5), 887–895.
4. Mayo Clinic. Infertility and stress.
5. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018 Aug 20;16(1):80.
6. Zhu Z.; Xu W.; and Liu L. Ovarian aging: mechanisms and intervention strategies. Medical Review 2022 Nov; 2(6):590–610.
7. Zhang D, Keilty D, Zhang ZF, Chian RC. Mitochondria in oocyte aging: current understanding. Facts Views Vis Obgyn. 2017 Mar;9(1):29-38. PMID: 28721182; PMCID: PMC5506767.
8. Bentov Y, Casper RF. The aging oocyte - can mitochondrial function be improved? Fertil Steril. 2013 Jan;99(1):18-22.
9. Thakur AS, et al. Effect of Ubiquinol therapy on sperm parameters and serum testosterone levels in Oligoasthenozoospermic infertile men. J Clin Diagn Res. 2015;9(9):BC01-BC03
10. Cakiroglu B.; Eyyupoglu SE.; Gozukucuk R, et al. Ubiquinol effect on sperm parameters in subfertile men who have astheno-teratozoospermia with normal sperm concentration. Nephro Urol Mon. 2014;6(3):e16870.
11. Xu Y, Nisenblat V, Lu C, Li R, Qiao J, Zhen X, Wang S. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reprod Biol Endocrinol. 2018 Mar 27;16(1):29.
12. Miles MV, Horn P, Miles L, et al. Bioequivalence of coenzyme Q10 from over-the-counter supplements. Nutr Res. 2002;22:919-929.
13. Langsjoen PH, Langsjoen AM. Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone. Clin Pharmacol Drug Dev. 2014;3(1):13-17.
