By Sid Shastri, M.Sc., Director of Research and Business, Kaneka North America LLC10.03.23
In the broad universe of benefits mediated by CoQ10, one application is now receiving heightened interest: reproductive health. The market category for reproductive health supplements is now estimated at over $2 billion dollars per year, and is set to grow to nearly $3 billion by the year 2028 (reflecting a CAGR of nearly 8%).1
This growth can be attributed to a rising prevalence of difficulty conceiving, particularly as couples delay childbirth. According to the World Health Organization, 1 in 6 people globally are affected at some point in their life, with a prevalence rate nearly identical between high-income countries and low- and moderate-income countries.2 The needs of this growing, global population elevates the urgency of expanding reproductive health research.
Unexplained inability to conceive is defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse when known causes have been ruled out.
To understand the role that CoQ10 can play in supporting both men’s and women’s reproductive health, let’s take a closer look at the factors involved.
For women under the age of 35, the live birth rate is 43%, but it falls sharply to 6% for women above age 42.5 This age-related decrease is associated with a significant decline in oocyte (egg) quality and quantity; this is called loss of ovarian reserve. That there is an increase in live births when donated eggs are used in aging women demonstrates that the decline in oocyte quantity and quality is an important contributing factor for successful conception.5
The quality of oocytes is greatly impacted by the health of the mitochondria within them. Oocytes are known to contain the greatest number of mitochondria of any cell by one or two orders of magnitude because of the intense energy demands of their development and their role in the reproductive process.5
Researchers have proposed that a decline in mitochondrial function could be one of the driving factors behind the declining quality and quantity of oocytes in older women.6 This is due to two different aspects of mitochondrial function.
The first has to do with the mitochondria’s role in the production of ATP (adenosine triphosphate), the cell’s energy source. The oocyte needs large amounts of energy for the continuous transcription and translation of DNA as it matures. Therefore, it is easy to understand that the proper functioning of the energy-generating mechanisms of the mitochondria can greatly impact oocyte function and quality.7 Both CoQ10 and ubiquinol are an essential part of the electron transport chain, the energy-generating part of the mitochondria. Ensuring adequate availability of CoQ10, particularly for women who have delayed childbirth, can support the cellular energy needs of oocytes and thereby promote reproductive health.
The second aspect of mitochondrial function that impacts oocyte health is the fact that in the process of producing energy, many free radicals are produced. This is similar to a mechanical combustion engine that produces energy, but also exhaust, which contains many free radicals. The oxidative stress these free radicals cause in reproductive tissues has come to be regarded as a predominant factor in the reproductive health of those who are unable to conceive.8-9
The reduced, antioxidant form of CoQ10, called ubiquinol, is the most potent lipid antioxidant synthesized within the body. It plays an essential role in protecting lipoproteins and the cell membranes of the mitochondria from oxidative damage. Ubiquinol acts primarily to prevent both the initiation (“chain-breaking”) and the propagation of lipid peroxidation. It is particularly suited to do this, both because it is already located in the mitochondrial lipid membrane where free radicals are formed from the production of energy, and also because it is constantly regenerated through its activity in the electron transport chain.10
Clinical studies have shown that supplementation with CoQ10 positively impacts oocyte and reproductive health. In a prospective, randomized, open-label, controlled study, 186 women who had difficulty conceiving took 200 mg of CoQ10 or placebo for 60 days before assisted reproductive technology (ART). Those taking CoQ10 had a higher number of retrieved oocytes, a higher fertilization rate (67.49%), and more high-quality embryos compared to controls (all p<0.05).11
In addition, in ex vivo and in vitro studies using oocytes from older women, supplementing the oocytes with CoQ10 resulted in statistically significantly improved mitochondrial bioenergetics (increased complex II + III activity; p<0.001) and significantly increased oocyte maturation rates (82.6% vs. 63.0%; p=0.035), reduced oocyte aneuploidy rates (abnormal number of total chromosomes; 36.8% vs. 65.5%; p=0.020), and reduced chromosome aneuploidy frequencies (missing or extra copies of particular chromosomes; 4.1% vs. 7.0%; p=0.012), compared to controls.12-13
Further studies using ubiquinol will improve our understanding of the reproductive health benefits women can realize.
As with oocytes, sperm activity relies heavily on mitochondrial function and energy production. Clinical research has shown that supplementation with CoQ10 or ubiquinol has a positive impact on sperm health.
CoQ10 levels have been found to be closely related to sperm quality. A randomized, double-blind, placebo-controlled trial (n=212) evaluated a daily dose of 300 mg CoQ10 over a 26-week period in men with difficulty initiating conception. The increased level of CoQ10 in the seminal fluid (p<0.001) coincided with significant improvement in sperm density and motility (p=0.01). When treatment duration was examined over time (versus baseline), a positive correlation was found for CoQ10 at 26 weeks for sperm count (r=0.46, p=0.03) as well as with sperm motility (r=0.45, p=0.04) and sperm morphology (r=0.34, p=0.04), meaning the longer the treatment with CoQ10, the larger the benefit. A statistically significant improvement in sex hormone levels was also found, which provides a healthier environment for sperm development.16
The same primary investigators conducted a similar study in 2012, this time using ubiquinol. In this study, Safaranijad et al. utilized 150 mg ubiquinol per day (n=228) in the same randomized, double-blind, placebo-controlled format with a similar treatment period of 26 weeks. This study also found a statistically significant increase in sperm counts (28.7± 4.6 x106/ml vs. 16.8±4.4 x106/ml; p<0.005) and sperm motility (35.8% vs. 25.4%; p<0.008) compared to placebo and a positive correlation between length of time on ubiquinol and all of the sperm parameters. Further, investigators found that ubiquinol statistically significantly improved plasma antioxidant activity via antioxidants CAT and SOD as well as improved sex hormone levels. When comparing their two similar studies, the scientists noted that: “Ubiquinol was more effective than CoQ10 in improving sperm count and motility. Sperm density increased by more than 2.5-fold with Ubiquinol compared to CoQ10.”17
Similar results were found by different research groups in an open label18 and a retrospective study,19 both of which used ubiquinol.
These studies and others lay the foundation for our understanding of the benefits of CoQ10 and ubiquinol for reproductive health in both men and women. With well-established safety profiles, CoQ10 and ubiquinol can be recommended as an appropriate adjunct when reproductive health is important.
About the Author: Sid Shastri, M.Sc. is Director of Research and Business at Kaneka North America LLC.
2. World Health Organization, news release April 4, 2023. 1 in 6 people globally affected by infertility: WHO. https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility
3. Ben-Meir A et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell (2015) 14, pp887–895. doi: 10.1111/acel.12368
4. George K and Kamath M. Fertility and age. J. Hum. Reprod. Sci. 2010;3(3):121–123.
5. Bentov, Y et al. Coenzyme Q10 supplementation and oocyte aneuploidy in women undergoing IVF-ICSI treatment. Clin. Med.Insights: Reprod.2014;8:31–36.
6. Ben-Meir A et al. Co-enzyme Q10 supplementation rescues cumulus cells dysfunction in a maternal aging model. Antioxidants 2019;8:58. doi: 10.3390/antiox8030058
7. Kirillova, A, et al. The role of mitochondria in oocyte maturation. Cells. 2021 Sep;10(9):2484.
8. Agarwal A et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol. Endocrinol. 2012 Jun 29;10:49.
9. 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.
10. Ernster L, Forsmark-Andrée P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig.1993;71(8 Suppl):S60-5.
11. Xu Y, Nisenblat V, Lu C, Li R, Qiao J, Zhang 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;16(1):29.
12. Ben-Meir A, Yahalomi S, Moshe B, Shufaro Y, Reubinoff B, Saada A. Coenzyme Q-dependent mitochondrial respiratory chain activity in granulosa cells is reduced with aging. Fertil Steril. 2015 Sep;104(3):724-7.
13. Ma L, Cai L, Hu M, Wang J, Xie J, Xing Y, Shen J, Cui Y, Liu XJ, Liu J. Coenzyme Q10 supplementation of human oocyte in vitro maturation reduces postmeiotic aneuploidies. Fertil Steril. 2020 Aug;114(2):331-337.
14. Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012 Sep-Oct;38(5):576-94.
15. Agarwal A et al. Male Oxidative Stress Infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019 Sep;37(3):296-312.
16. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009:182(1):237–248.
17. Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme Q 10 (Ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2018:188(2):526–531.
18. Thakur AS, Littarru GP, Funahashi I, Painkara US, Dange NS, Chauhan P. Effect of ubiquinol therapy on sperm parameters and serum testosterone levels in oligoasthenozoospermic infertile men. J Clin Diag Res. 2015 Sep;9(9):BC01–BC03.
19. Cakiroglu B, Eyyupoglu SE, Gozukucuk R, Uyanik BS. Ubiquinol effect on sperm parameters in subfertile men who have astheno-teratozoospermia with normal sperm concentration. Nephrourol Mon. 2014 May 10;6(3):e16870.
This growth can be attributed to a rising prevalence of difficulty conceiving, particularly as couples delay childbirth. According to the World Health Organization, 1 in 6 people globally are affected at some point in their life, with a prevalence rate nearly identical between high-income countries and low- and moderate-income countries.2 The needs of this growing, global population elevates the urgency of expanding reproductive health research.
Unexplained inability to conceive is defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse when known causes have been ruled out.
To understand the role that CoQ10 can play in supporting both men’s and women’s reproductive health, let’s take a closer look at the factors involved.
Female Reproductive Health
One of the most important factors in unexplained inability to conceive is the age of the woman, with increased prevalence of difficulties at age 32 and dramatically increased prevalence after age 37.3,4For women under the age of 35, the live birth rate is 43%, but it falls sharply to 6% for women above age 42.5 This age-related decrease is associated with a significant decline in oocyte (egg) quality and quantity; this is called loss of ovarian reserve. That there is an increase in live births when donated eggs are used in aging women demonstrates that the decline in oocyte quantity and quality is an important contributing factor for successful conception.5
The quality of oocytes is greatly impacted by the health of the mitochondria within them. Oocytes are known to contain the greatest number of mitochondria of any cell by one or two orders of magnitude because of the intense energy demands of their development and their role in the reproductive process.5
Researchers have proposed that a decline in mitochondrial function could be one of the driving factors behind the declining quality and quantity of oocytes in older women.6 This is due to two different aspects of mitochondrial function.
The first has to do with the mitochondria’s role in the production of ATP (adenosine triphosphate), the cell’s energy source. The oocyte needs large amounts of energy for the continuous transcription and translation of DNA as it matures. Therefore, it is easy to understand that the proper functioning of the energy-generating mechanisms of the mitochondria can greatly impact oocyte function and quality.7 Both CoQ10 and ubiquinol are an essential part of the electron transport chain, the energy-generating part of the mitochondria. Ensuring adequate availability of CoQ10, particularly for women who have delayed childbirth, can support the cellular energy needs of oocytes and thereby promote reproductive health.
The second aspect of mitochondrial function that impacts oocyte health is the fact that in the process of producing energy, many free radicals are produced. This is similar to a mechanical combustion engine that produces energy, but also exhaust, which contains many free radicals. The oxidative stress these free radicals cause in reproductive tissues has come to be regarded as a predominant factor in the reproductive health of those who are unable to conceive.8-9
The reduced, antioxidant form of CoQ10, called ubiquinol, is the most potent lipid antioxidant synthesized within the body. It plays an essential role in protecting lipoproteins and the cell membranes of the mitochondria from oxidative damage. Ubiquinol acts primarily to prevent both the initiation (“chain-breaking”) and the propagation of lipid peroxidation. It is particularly suited to do this, both because it is already located in the mitochondrial lipid membrane where free radicals are formed from the production of energy, and also because it is constantly regenerated through its activity in the electron transport chain.10
Clinical studies have shown that supplementation with CoQ10 positively impacts oocyte and reproductive health. In a prospective, randomized, open-label, controlled study, 186 women who had difficulty conceiving took 200 mg of CoQ10 or placebo for 60 days before assisted reproductive technology (ART). Those taking CoQ10 had a higher number of retrieved oocytes, a higher fertilization rate (67.49%), and more high-quality embryos compared to controls (all p<0.05).11
In addition, in ex vivo and in vitro studies using oocytes from older women, supplementing the oocytes with CoQ10 resulted in statistically significantly improved mitochondrial bioenergetics (increased complex II + III activity; p<0.001) and significantly increased oocyte maturation rates (82.6% vs. 63.0%; p=0.035), reduced oocyte aneuploidy rates (abnormal number of total chromosomes; 36.8% vs. 65.5%; p=0.020), and reduced chromosome aneuploidy frequencies (missing or extra copies of particular chromosomes; 4.1% vs. 7.0%; p=0.012), compared to controls.12-13
Further studies using ubiquinol will improve our understanding of the reproductive health benefits women can realize.
Male Reproductive Health
For men, the reasons for inability to conceive are poorly understood and often lack any specific cause. Of infertility cases, 30-50% can be traced back solely or partially to a male factor,14 which is commonly manifest in the quality and quantity of sperm, including low sperm count, poor sperm motility, and abnormal sperm shape. This can be due to advanced age and genetics, as well as environmental pollutants and lifestyle factors, such as a poor diet, high stress, and a sedentary lifestyle that induces oxidative stress. Indeed, 1 in 3 men with inability to conceive have elevated free radicals in the seminal fluid.15As with oocytes, sperm activity relies heavily on mitochondrial function and energy production. Clinical research has shown that supplementation with CoQ10 or ubiquinol has a positive impact on sperm health.
CoQ10 levels have been found to be closely related to sperm quality. A randomized, double-blind, placebo-controlled trial (n=212) evaluated a daily dose of 300 mg CoQ10 over a 26-week period in men with difficulty initiating conception. The increased level of CoQ10 in the seminal fluid (p<0.001) coincided with significant improvement in sperm density and motility (p=0.01). When treatment duration was examined over time (versus baseline), a positive correlation was found for CoQ10 at 26 weeks for sperm count (r=0.46, p=0.03) as well as with sperm motility (r=0.45, p=0.04) and sperm morphology (r=0.34, p=0.04), meaning the longer the treatment with CoQ10, the larger the benefit. A statistically significant improvement in sex hormone levels was also found, which provides a healthier environment for sperm development.16
The same primary investigators conducted a similar study in 2012, this time using ubiquinol. In this study, Safaranijad et al. utilized 150 mg ubiquinol per day (n=228) in the same randomized, double-blind, placebo-controlled format with a similar treatment period of 26 weeks. This study also found a statistically significant increase in sperm counts (28.7± 4.6 x106/ml vs. 16.8±4.4 x106/ml; p<0.005) and sperm motility (35.8% vs. 25.4%; p<0.008) compared to placebo and a positive correlation between length of time on ubiquinol and all of the sperm parameters. Further, investigators found that ubiquinol statistically significantly improved plasma antioxidant activity via antioxidants CAT and SOD as well as improved sex hormone levels. When comparing their two similar studies, the scientists noted that: “Ubiquinol was more effective than CoQ10 in improving sperm count and motility. Sperm density increased by more than 2.5-fold with Ubiquinol compared to CoQ10.”17
Similar results were found by different research groups in an open label18 and a retrospective study,19 both of which used ubiquinol.
These studies and others lay the foundation for our understanding of the benefits of CoQ10 and ubiquinol for reproductive health in both men and women. With well-established safety profiles, CoQ10 and ubiquinol can be recommended as an appropriate adjunct when reproductive health is important.
About the Author: Sid Shastri, M.Sc. is Director of Research and Business at Kaneka North America LLC.
References
1. Delve Insight. Fertility Supplements: Market Insights, Competitive Landscape, and Market Forecast -2028. 2023 report. https://www.marketresearch.com/DelveInsight-v4028/Fertility-Supplement-Insights-Competitive-Landscape-33356097/2. World Health Organization, news release April 4, 2023. 1 in 6 people globally affected by infertility: WHO. https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility
3. Ben-Meir A et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell (2015) 14, pp887–895. doi: 10.1111/acel.12368
4. George K and Kamath M. Fertility and age. J. Hum. Reprod. Sci. 2010;3(3):121–123.
5. Bentov, Y et al. Coenzyme Q10 supplementation and oocyte aneuploidy in women undergoing IVF-ICSI treatment. Clin. Med.Insights: Reprod.2014;8:31–36.
6. Ben-Meir A et al. Co-enzyme Q10 supplementation rescues cumulus cells dysfunction in a maternal aging model. Antioxidants 2019;8:58. doi: 10.3390/antiox8030058
7. Kirillova, A, et al. The role of mitochondria in oocyte maturation. Cells. 2021 Sep;10(9):2484.
8. Agarwal A et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol. Endocrinol. 2012 Jun 29;10:49.
9. 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.
10. Ernster L, Forsmark-Andrée P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig.1993;71(8 Suppl):S60-5.
11. Xu Y, Nisenblat V, Lu C, Li R, Qiao J, Zhang 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;16(1):29.
12. Ben-Meir A, Yahalomi S, Moshe B, Shufaro Y, Reubinoff B, Saada A. Coenzyme Q-dependent mitochondrial respiratory chain activity in granulosa cells is reduced with aging. Fertil Steril. 2015 Sep;104(3):724-7.
13. Ma L, Cai L, Hu M, Wang J, Xie J, Xing Y, Shen J, Cui Y, Liu XJ, Liu J. Coenzyme Q10 supplementation of human oocyte in vitro maturation reduces postmeiotic aneuploidies. Fertil Steril. 2020 Aug;114(2):331-337.
14. Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012 Sep-Oct;38(5):576-94.
15. Agarwal A et al. Male Oxidative Stress Infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019 Sep;37(3):296-312.
16. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009:182(1):237–248.
17. Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme Q 10 (Ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2018:188(2):526–531.
18. Thakur AS, Littarru GP, Funahashi I, Painkara US, Dange NS, Chauhan P. Effect of ubiquinol therapy on sperm parameters and serum testosterone levels in oligoasthenozoospermic infertile men. J Clin Diag Res. 2015 Sep;9(9):BC01–BC03.
19. Cakiroglu B, Eyyupoglu SE, Gozukucuk R, Uyanik BS. Ubiquinol effect on sperm parameters in subfertile men who have astheno-teratozoospermia with normal sperm concentration. Nephrourol Mon. 2014 May 10;6(3):e16870.
