Safarinejad MR, 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 atudy. J Urology. 2012 Aug; (188): 526-531.
Double-blind, placebo-controlled, randomized study
Two hundred twenty-eight healthy men, ages 25–44 years old with primary, idiopathic infertility for at least 2 years were studied. Male factor infertility was defined by sperm morphology less than 14% using Kruger strict criteria, sperm concentration less than 20 x 106/mL (oligozoospermia), and sperm motility less than 50% (asthenozoospermia). All participants had oligoasthenozoospermia on at least 2 semen samples that were obtained 1 month apart prior to initiating the treatment medicine. Participants were randomly assigned to 1 of 2 groups. Participants were excluded if they had a history of cancer requiring chemotherapy or radiation, cryptorchidism, varicocele, genital tract surgery, karyotype abnormality, or a body mass index 30 kg/m2 or greater.
Study Medication and Treatment Protocol
The treatment group (n=114) received 200 mg ubiquinol by mouth per day for 26 weeks, while 114 men in the control group received a placebo by mouth each day for 26 weeks. All participants were then followed for 12 weeks after discontinuation of their medicine. The participants were instructed not to take any other medications or supplements that could affect spermatogenesis during the study.
Primary Outcome Measures
A semen analysis was performed to assess changes in sperm concentration, sperm motility, and sperm strict morphology at baseline, every 4 weeks during the treatment phase, after the 26-week treatment phase, and every 4 weeks for 12 weeks after discontinuation of the treatment medicine. At each follow-up point, 2 semen samples were obtained 1 week apart and the results were averaged. Seminal fluids were evaluated for catalase and super oxide dismutase activity every 4 weeks, at the end of the 26-week treatment phase and at the end of the 12-week off-treatment phase.
When comparing semen parameters at baseline and after the 26-week treatment phase, average sperm concentration increased in the ubiquinol-treated group by 15%, 43.7%, and 81.6% (P=0.005) at 8, 16, and 26 weeks, respectively. Sperm motility increased in the ubiquinol-treated group with statistical significance by week 12 of treatment; the average increase in motility in the treatment group was 18%, 26.5%, and 31.7% (P=0.008) at weeks 12, 20, and 26, respectively. Sperm morphology also improved in the ubiquinol-treated group compared to the control group with an 18.3%, 21.1%, and 24% (P=0.01) increase in strict morphology in the treatment group at 16, 20, and 26 weeks, respectively. Mean levels of catalase and superoxide dismutase activity in the seminal fluids were higher in the ubiquinol-treated group (422 and 54.7 U/mL) (P=0.02 for both) than in the placebo group (311 and 36.5 U/mL) after the 26-week treatment phase. Evaluation after the 12-week off-drug phase demonstrated a gradual reversal in semen parameter improvements with discontinuation of ubiquinol, although the difference between sperm concentration in the treatment and the control group remained statistically significant after the 12-week off-drug period. No adverse events or side effects were reported by any of the participants.
Infertility affects 15% of couples, with a contributing male factor in 40% of cases.1 Of these cases, 30% are considered idiopathic, meaning standard clinical and laboratory evaluations do not elucidate a cause.2 Oxidative stress mediated by reactive oxygen species (ROS) is a well-known yet overlooked causative factor in male infertility.3–5 At physiologic levels, ROS in seminal fluid are necessary for normal reproductive function and in promoting sperm capacitation and acrosomal reactions;6 at higher levels, ROS have been shown to have a significant adverse effect on sperm function by impairing spermatogenesis and decreasing sperm quality.7,8 Mature spermatozoa are encased in a polyunsaturated lipid membrane, which is easily oxidized in the presence of ROS. This oxidative damage impairs the integrity of spermatozoa membrane thereby harming sperm morphology and motility.9,10
Men with idiopathic oligoasthenozoospermia are often treated empirically with medications and supplements that have variable efficacy or are not well studied. Many are referred for assisted reproductive techniques, which are expensive and not without risks to the female partner. This study, as well as several other studies on antioxidant therapy for male infertility, supports the use of ubiquinol, the reduced form of coenzyme Q10 found predominantly in serum and tissue, as an effective treatment for oligoasthenozzopsermia.11–16 Ubiquinol supports cellular bioenergetics by providing fuel for the high-energy expenditure needed for sperm motility while protecting against oxidative stress to the vulnerable spermatozoa lipid membrane.
While this study lacked long-term follow-up and evaluation of pregnancy rates with treatment, the statistically significant improvement in semen parameters, lack of adverse reactions and side effects, as well as relative affordability of antioxidant treatment in comparison to assisted reproductive techniques should warrant consideration for infertile men desiring a more natural approach to achieving pregnancy with their partner. Research demonstrating the negative effects of ROS on male fertility with complementary findings showing improvement in semen parameters with antioxidant treatment should support the use of antioxidants—namely ubiquinol—as etiologic treatments and not simply “supplements.”
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- Agarwal A, Sekhon LH. Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified? Indian J Urol. 2011.;27(1):74-85.
- Mahfouz R, Sharma R, Sharma D et al: Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil Steril. 2009. 91:805.
- Meeker JD, Godfrey-Bailey L, Hauser R. Relationships between serum hormone levels and semen quality among men from an infertility clinic. J Androl. 2007;28:397-406.
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- Mahfouz R, Sharma R, Sharma D et al: Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil Steril. 2009;91:805.
- Agarwal A, Sekhon LH. Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified? Indian J Urol. 2011;27(1):74-85.
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- Saleh RA, Agarwal. Oxidative stress and male infertility: from research to clinical practice. J Androl. 2002;23:737-762.
- Aileva R, Scaramucci A, Mantero F, Bompadre S, Leoni L, Littarru GP. The protective role of ubiquinol-10 against formaltion of lipid hydroperoxides in human seminal fluid. Mol Aspects Med. 1997;18:5221-5228.
- Balercia G, Arnaldi G, Fazioll F, et al. Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozzospermia. Andrologia. 2002;34:107-111.
- Balercia G, Mantero F, Armoni R, Principato G, Regoli F. Oxyradical scavenging capacity toward different reactive species in seminal plasma and sperm cells. A possible inflice on kinetic parameters. Clin Chem Lab Med. 2003;41:13-19.
- Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, Littarru GP. Coenzyme Q10 supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Fertil Steril. 2004;81:93-98.
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- Yanashita S, Yamamoto Y. Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of oxidative stress. Annal Biochem. 1997;250:66.