Coenzyme Q₁₀, α-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility

Anna Gvozdjáková, Jarmila Kucharská, Jozef Dubravicky, Viliam Mojto, Ram B Singh, Anna Gvozdjáková, Jarmila Kucharská, Jozef Dubravicky, Viliam Mojto, Ram B Singh

Abstract

Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10, CoQ(10-TOTAL), γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ(10-TOTAL) (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ(10-TOTAL), and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

Figures

Figure 1
Figure 1
Proposed mechanism of coenzyme Q10 and carnitine effect in sperm mitochondria. Acyl-CoA: acyl-coenzyme A; CPT I: carnitine phosphate transpeptidase I; CPT II: carnitine phosphate transpeptidase II; CoQ: coenzyme Q; VDAC: voltage dependent anion channel; ATP: adenosine triphosphate; ADP: adenosine diphosphate; Pi: inorganic phosphate; I, II, III, IV, and V: respiratory chain complexes; H+ proton; e−: electron; Q-cycle: coenzyme Q cycle; cyt c: cytochrome c; NADH: reduced nicotinamide adenine dinucleotide; NAD+: nicotinamide adenine dinucleotide; FADH2: reduced flavin adenine dinucleotide; FAD: flavin adenine dinucleotide; O2 ∙−: superoxide radical; H2O2: hydrogen peroxide; OH: hydroxyl radical; H2O: water; O2: oxygen.

References

    1. Sheweita S. A., Tilmisany A. M., Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Current Drug Metabolism. 2005;6(5):495–501. doi: 10.2174/138920005774330594.
    1. Ko E. Y., Sabanegh E. S. The role of nutraceuticals in male fertility. Urologic Clinics of North America. 2014;41(1):181–193. doi: 10.1016/j.ucl.2013.08.003.
    1. Fariello R. M., Pariz J. R., Spaine D. M., et al. Effect of smoking on the functional aspects of sperm and seminal plasma protein profiles in patients with varicocele. Human Reproduction. 2012;27(11):3140–3149. doi: 10.1093/humrep/des287.
    1. Aitken R. J., Smith T. B., Jobling M. S., Baker M. A., de Iuliis G. N. Oxidative stress and male reproductive health. Asian Journal of Andrology. 2014;16(1):31–38. doi: 10.4103/1008-682x.122203.
    1. Bansal A. K., Bilaspuri G. S. Impacts of oxidative stress and antioxidants on semen functions. Veterinary Medicine International. 2011;2011:7. doi: 10.4061/2011/686137.686137
    1. Aitken J., Fisher H. Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. BioEssays. 1994;16(4):259–267. doi: 10.1002/bies.950160409.
    1. Gvozdjakova A., Kucharska J., Lepies P., Braunova Z., Malatinsky E. Decreased level of sperm coenzyme Q10, mitochondrial respiration and energy production in infertile patients. Therapeutic effect of coenzyme Q10 (a pilot study). Proceedings of the 1st Conference of the International Coenzyme Q10 Association; May 1998; Boston, Mass, USA. pp. 137–138.
    1. Alleva R., Scararmucci A., Mantero F., Bompadre S., Leoni L., Littarru G. P. The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid. Molecular Aspects of Medicine. 1997;18:S221–S228. doi: 10.1016/S0098-2997(97)00040-X.
    1. Mancini A., Conte G., Milardi D., de Marinis L., Littarru G. P. Relationship between sperm cell ubiquinone and seminal parameters in subjects with and without varicocele. Andrologia. 1998;30(1):1–4.
    1. Littarru G. P., Tiano L. Clinical aspect of coenzyme Q10 in relationship with its bioenergetic and antioxidant properties. In: Gvozdjakova A., editor. Mitochondrial Medicine. Amsterdam, The Netherlands: Springer; 2008. pp. 303–321.
    1. Gvozdjakova A., Kucharska J., Lipkova J., et al. Importance of the assessment of coenzyme Q10, alpha-tocopherol and oxidative stress for the diagnosis and therapy of infertility in men. Bratislava Medical Journal. 2013;114(11):607–609. doi: 10.4149/BLL_2013_129.
    1. Zhou X., Liu F., Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pacific Journal of Clinical Nutrition. 2007;16(1):383–390.
    1. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th. Geneva, Switzerland: WHO Press; 2010.
    1. Kucharská J., Gvozdjáková A., Mizera S., et al. Participation of coenzyme Q10 in the rejection development of the transplanted heart: a clinical study. Physiological Research. 1998;47(6):399–404.
    1. Mancini A., De Marinis L., Oradei A., et al. Coenzyme Q10 concentrations in normal and pathological human seminal fluid. Journal of Andrology. 1994;15(6):591–594.
    1. Ruder E. H., Hartman T. J., Blumberg J., Goldman M. B. Oxidative stress and antioxidants: exposure and impact on female fertility. Human Reproduction Update. 2008;14(4):345–357. doi: 10.1093/humupd/dmn011.
    1. Janero D. R., Burghardt B. Thiobarbituric acid-reactive malondialdehyde formation during superoxide-dependent, iron-catalyzed lipid peroxidation: influence of peroxidation conditions. Lipids. 1989;24(2):125–131. doi: 10.1007/bf02535249.
    1. Gvozdjáková A., Kucharská J., Bartolčičová B., Dubravický J., Vořáková M., Lipková J. Effect of Carni-Q-Nol and Mojzis exercise on sperm function and pregnancy. Proceedings of the 7th Conference of the International Coenzyme Q10 Association; November 2012; Seville, Spain. pp. 90–91.
    1. Gvozdjakova A., Kucharska J., Bartolcicova B., et al. Metabolic biomarkers of CARNI-QNol supportive therapy in human fertility disturbances. Proceedings of the BIT's 2nd World Congress of MolMed and BIT's 3rd Annual World Congress of Biomarkers; December 2012; Guangzhou, China.
    1. Gharagozloo P., Aitken R. J. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Human Reproduction. 2011;26(7):1628–1640. doi: 10.1093/humrep/der132.
    1. Carra E., Sangiorgi D., Gattuccio F., Rinaldi A. M. Male infertility and mitochondrial DNA. Biochemical and Biophysical Research Communications. 2004;322(1):333–339. doi: 10.1016/j.bbrc.2004.07.112.
    1. Gvozdjakova A. Mitochondrial ‘spermatopathy’. In: Gvozdjakova A., editor. Mitochondrial Medicine. Amsterdam, The Netherlands: Springer; 2008. pp. 263–266.
    1. Agarwal A., Aponte-Mellado A., Premkumar B. J., Shaman A., Gupta S. The effects of oxidative stress on female reproduction: a review. Reproductive Biology and Endocrinology. 2012;10, article 49 doi: 10.1186/1477-7827-10-49.
    1. Ross C., Morriss A., Khairy M., et al. A systematic review of the effect of antioxidants on male infertility. Reprod Biomed Online. 2010;20:711–723.
    1. Balercia G., Buldreghini E., Vignini A., et al. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertility and Sterility. 2009;91(5):1785–1792. doi: 10.1016/j.fertnstert.2008.02.119.
    1. Safarinejad M. R. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. Journal of Urology. 2009;182(1):237–248. doi: 10.1016/j.juro.2009.02.121.
    1. Tirabassi G., Virgini S., Tiano L., et al. Protective effects of coenzyme Q10 and aspartic acid on oxidative stress and DNA damage in subjects affected by idiopathic asthenozoospermia. Endocrine. 2014 doi: 10.1007/s12020-014-0432-6.
    1. Safarinejad M. R. The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. International Urology and Nephrology. 2012;44(3):689–700. doi: 10.1007/s11255-011-0081-0.
    1. Mancini A., Littarru G. P. Coenzyme Q10 in male infertility. Proceedings of the 7th Conference of the International Coenzyme Q10 Association; 2012; pp. 29–60.
    1. Festa R., Giacchi E., Raimondo S., et al. Coenzyme Q10 supplementation in infertile men with low-grade varicocele: an open, uncontrolled pilot study. Andrologia. 2014;46(7):805–807. doi: 10.1111/and.12152.
    1. Gvozdjakova A. Carnitine. In: Gvozdjakova A., editor. Mitochondrial Medicine. Amsterdam, The Netherlands: Springer; 2008. pp. 357–362.
    1. Thakur A. S., Littarru G. P., Funahashi I., Paikara U. S., Dange N. S. Ubiquinol therapy: sperm parameters and testosterone level. Proceedings of the 7th Conference of the International Coenzyme Q10 Association; November 2012; Seville, Spain. p. p. 131.
    1. Safarinejad M. R., Safarinejad S., Shafiei N. Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. Journal of Urology. 2012;188(2):526–531. doi: 10.1016/j.juro.2012.03.131.
    1. Gvozdjáková A., Kucharská J., Ostatníková D., Babinská K., Nakládal D., Crane F. L. Ubiquinol improves symptoms in children with autism. Oxidative Medicine and Cellular Longevity. 2014;2014:6. doi: 10.1155/2014/798957.798957

Source: PubMed

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