Article

Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: A double-blind randomised clinical trial

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Abstract

Low seminal plasma concentrations of coenzyme Q10 (CoQ10) have been correlated with impaired sperm parameters, but the exact mechanism remains of dominating interest. This randomised, placebo-controlled study examined the effect of CoQ10 on catalase, superoxide dismutase (SOD) and F(2) -isoprostanes in seminal plasma in infertile men and their relation with CoQ10 concentration. Sixty infertile men with idiopathic oligoasthenoteratozoospermia (OAT) were randomised to receive 200 mg d(-1) of CoQ10 or placebo for 3 months. 47 persons of them completed the study. Semen analysis, anthropometric measurements, diet and physical activity assessment were performed for subjects before and after treatment. Independent and paired t-test, chi-square test and ancova were compared outcomes of supplementation between two groups. CoQ10 levels increased from 44.74 ± 36.47 to 68.17 ± 42.41 ng ml(-1) following supplementation in CoQ10 (P < 0.001). CoQ10 group had higher catalase and SOD activity than the placebo group. There was a significant positive correlation between CoQ10 concentration and normal sperm morphology (P = 0.037), catalase (P = 0.041) and SOD (P < 0.001). Significant difference was shown between the mean of changes in seminal plasma 8-isoprostane in two groups (P = 0.003) after supplementation. Three-month supplementation with CoQ10 in OAT infertile men can attenuate oxidative stress in seminal plasma and improve semen parameters and antioxidant enzymes activity.

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... CoQ10 was introduced into animal feeds for the treatment of various OS-induced organ dysfunctions, including cattle (Wafa and El-Nagar 2021), rabbits (Elokil et al. 2019), and birds (Sharideh et al. 2020), horses (Nemec Svete et al. 2021, rats (Delkhosh et al. 2021) and humans (Nadjarzadeh et al. 2014). CoQ10 supplementation enhances testicular function and fertility in aged breeding roosters and heat-stressed rabbits by lowering OS, increasing total antioxidant capacity and testosterone levels, and upregulating testicular melatonin receptors (Elokil et al.2019;Sharideh et al.2020). ...
... Unaltered levels of FSH, LH, and E2 during the experimental time points between CoQ10 supplemented males versus control need to be interpreted cautiously taking into consideration its pulsatile secretions. Contrarily, there was evidence that CoQ10 treatment decreased FSH and LH levels concurrent with elevated prolactin levels and these changes were attributed due to the anti-gonadotropic effects of higher prolactin levels (Nadjarzadeh et al. 2014;Alahmar et al. 2021). This discrepancy may be due to the species and conditions variations. ...
... In this study, there were marked increases in seminal plasma CAT activity and TAC, and a decrease in MDA concentration. These results suggest that CoQ10 supplementation improved seminal antioxidant power with subsequent higher membrane integrity evidenced by lower lipid peroxidation profile which is consistent with a previous study (Nadjarzadeh et al. 2014) and a study conducted in human medicine (Alahmar et al. 2021), roosters (Sharideh et al. 2020), and rats (Delkhosh et al. 2021). In addition, our results appear to indicate that CoQ10 rewarded HS-mediated depletion of seminal antioxidant capacity. ...
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Oxidative stress (OS) is brought on by heat stress (HS), which weakens antioxidant defense and initiates OS. Since mitochondria are the primary source of reactive oxygen species (ROS), HS-mediated OS may be lessened by targeting mitochondria with particular antioxidants. The purpose of this study was to investigate the effect of oral coenzyme Q10 (CoQ10) supplementation on the reproductive performance of goat bucks under HS conditions. Ten mature bucks were randomly separated into two groups and housed in an environment with a high-temperature humidity index (THI: 88.3 to 94.8; summer season). The first group (n = 5) got the baseline diet while the second group (n = 5) received supplemental oral CoQ10 (3 mg/kg BW; CoQ10 group) daily for six weeks. Testicular blood flow parameters (TBF), testicular volume (TV) and echogenicity (TE), nitric oxide (NO), seminal alanine aminotransferase (ALT) and catalase (CAT) activities, total antioxidant capacity (TAC), malondialdehyde (MDA) content, and semen quality traits were all measured. The examinations started a week before (W-1), on the first supplementation day (W0), and weekly for eight consecutive weeks (W1-W8). There were marked (P < 0.05) increases in TBF (W3-W6) and TV, and a decrease in TE (W3-W5) in the CoQ10 group compared to the CON group. Similarly, testosterone (T) and NO levels (W3-W5) in the CoQ10 group were higher (P < 0.05) than those of the control group. The CoQ10 group demonstrated significant (P < 0.05) increases in seminal CAT (W4-W8) and TAC (W2-W6) activities and decreases in ALT (W4-W7) activity and MDA (W5-W8) concentration as compared to the control group. The CoQ10 group showed improvements (P < 0.05) at W3-W6 for sperm progressive motility, viability, and normal morphology and at W6-W8 for sperm concentration. In conclusion, oral CoQ10 supplementation improved testicular hemodynamics, testosterone production, semen quality, and antioxidant capacity in goat bucks during summer heat stress conditions.
... Among all 80 selective articles, 57 RCTs were blinded while the remaining 23 were not blinded. Among the studies included in this review, 13 were conducted in Iran (Safarinejad, 2009;Safarinejad and Safarinejad, 2009;Moradi et al., 2010;Safarinejad, 2011a;Safarinejad, 2011b;Nadjarzadeh et al., 2011;Safarinejad et al., 2011;Safarinejad et al., 2012;Mehni et al., 2014;Nadjarzadeh et al., 2014;Haghighian et al., 2015;Hosseini et al., 2016;Modarresi et al., 2019), 13 in Italy (Izzo et al., 1984;Foresta et al., 2002;Caroppo et al., 2003;Lenzi et al., 2003;Lenzi et al., 2004;Balercia et al., 2005;Foresta et al., 2005; Paradisi et al., 2006;Selice et al., 2011;Colacurci et al., 2012;Paradisi et al., 2014;Farrag et al., 2015;Maretti and Cavallini, 2017), 6 in the United States of America (Haas and Manganiello, 1987;Clark and Sherins, 1989;Gerris et al., 1991;Sigman et al., 2006;Wiehle et al., 2014;Helo et al., 2015), 6 in England (Willis et al., 1977;Pryor et al., 1978;Inton et al., 1979;Badenoch et al., 1988;Scott et al., 1998;Williams et al., 2020), and 4 from Austria (Pusch, 1988;Maier and Hienert, 1990;Imhof et al., 2012;Lipovac et al., 2016) and Germany (Knuth et al., 1987;Krause et al., 1992;Keck et al., 1994;Kamischke et al., 1998) (Yamamoto et al., 1995a;Yamamoto et al., 1995b;Matsumiya et al., 1998), and Greece (Adamopoulos et al., 1997;Adamopoulos et al., 2003;Farmakiotis et al., 2007). Two were from Egypt (Ghanem et al., 2010;ElSheikh et al., 2015), Denmark (Fedder et al., 2014;Jensen et al., 2020), China (Ding et al., 2015;Guo et al., 2015), and Switzerland (Comhaire et al., 1986;Crottaz et al., 1992) and n 1 from Turkey (Çakan et al., 2009), Australia (Baker et al., 1984), Malaysia (Ismail et al., 2014), Nigeria (Mbah et al., 2012), France (Almeida et al., 1985), Saudi Arabia (Suleiman et al., 1996), South Africa (Wong et al., 2002), Finland (Park et al., 2016), Yugoslavia (Mićić and Dotlić, 1985), Canada (AinMelk et al., 1987), Israel (Glezerman et al., 1993), Mexico (Merino et al., 1997), and Scotland (Hargreave et al., 1984). ...
... Pairwise MA results were in the favor of the SERMs (Mićić and Dotlić, 1985;AinMelk et al., 1987;Krause et al., 1992;Çakan et al., 2009;Ghanem et al., 2010;Haje and Naoom, 2015) where the levels of sperm concentration increased to 6.00 million per mL [95% CI 5.27, 6.72; p 0.43] followed by supplements [5.99;95% CI 2.83,9.15; p < 0.00001; I 2 91%] (Wong et al., 2002;Lenzi et al., 2004;Safarinejad, 2009;Nadjarzadeh et al., 2011;Hadwan et al., 2012;Imhof et al., 2012;Safarinejad et al., 2012;Nadjarzadeh et al., 2014;Haje and Naoom, 2015;Lipovac et al., 2016;Alsalman et al., 2018;Jensen et al., 2020) (Supplementary Figure 4). Subgroup analysis of studies examining the effect of SERMs revealed (Mićić and Dotlić, 1985;AinMelk et al., 1987;Krause et al., 1992;Çakan et al., 2009;Ghanem et al., 2010;Haje and , 2003;Caroppo et al., 2003;Paradisi et al., 2006;Selice et al., 2011;Colacurci et al., 2012;Paradisi et al., 2014;Ding et al., 2015;Farrag et al., 2015) where the percentage increase in sperm morphology was maximum [3.68; 95% CI 0.97, 6.39; p < 0.00001; I 2 83%], followed by supplements [1.93; 95% CI 0.43, 3.43; p < 0.00001; I 2 89%] (Wong et al., 2002;Lenzi et al., 2004;Safarinejad, 2009;Nadjarzadeh et al., 2011;Hadwan et al., 2012;Imhof et al., 2012;Safarinejad et al., 2012;Nadjarzadeh FIGURE 4 | Network plots I, II, and III are for primary outcomes whereas IV and V are network plots for secondary outcomes. ...
... To assess the effect of intervention on primary and secondary parameters, twenty-eight studies (Mićić and Dotlić, 1985;AinMelk et al., 1987;Pusch, 1988;Krause et al., 1992;Kamischke et al., 1998;Foresta et al., 2002;Wong et al., 2002;Adamopoulos et al., 2003;Caroppo et al., 2003;Lenzi et al., 2003;Paradisi et al., 2006;Safarinejad, 2009;Çakan et al., 2009;Ghanem et al., 2010;Nadjarzadeh et al., 2011;Selice et al., 2011;Colacurci et al., 2012;Hadwan et al., 2012;Imhof et al., 2012;Safarinejad et al., 2012;Nadjarzadeh et al., 2014;Paradisi et al., 2014;Ding et al., 2015;Farrag et al., 2015;Haje and Naoom, 2015;Lipovac et al., 2016;Alsalman et al., 2018;Jensen et al., 2020) were included for primary outcomes and seventeen studies (AinMelk et al., 1987;Pusch, 1988;Krause et al., 1992;Kamischke et al., 1998;Paradisi et al., 2006;Safarinejad, 2009;Çakan et al., 2009;Selice et al., 2011;Safarinejad et al., 2012;Paradisi et al., 2014;Helo et al., 2015;Jensen et al., 2020) were included for secondary outcomes. NMA was executed to compare the effects of intervention on primary and secondary parameters. ...
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Background. Infertility is an emerging health issue for men. Comparative efficacy of different pharmacological interventions on male infertility is not clear. The aim of this review is to investigate the efficacy of various pharmacological interventions among men with idiopathic male infertility. All randomized control trials evaluating the effectuality of interventions on male infertility were included for network meta-analysis (NMA) from inception to 31 April 2020, systematically performed using STATA through the random effect model. The protocol was registered at PROSPERO (CRD42020152891). Results. The outcomes of interest were semen and hormonal parameters. Treatment effects (p < 0.05) were estimated through WMD at the confidence interval of 95%. Upon applying exclusion criteria, n=28 RCTs were found eligible for NMA. Results from NMA indicated that consumption of supplements increases sperm concentration levels [6.26, 95% CI 3.32, 9.21] in comparison to SERMs [4.97, 95% CI 1.61, 8.32], hormones [4.14, 95% CI 1.83, 6.46], and vitamins [0.15, 95% CI −20.86, 21.15)] with placebo, whereas the use of SERMs increased percentage sperm motility [6.69, 95% CI 2.38, 10.99] in comparison to supplements [6.46, 95% CI 2.57, 10.06], hormones [3.47, 95% CI 0.40, 6.54], and vitamins [−1.24, 95% CI −11.84, 9.43] with placebo. Consumption of hormones increased the sperm morphology [3.71, 95% CI, 1.34, 6.07] in contrast to supplements [2.22, 95% CI 0.12, 4.55], SERMs [2.21, 95% CI −0.78, 5.20], and vitamins [0.51, 95% CI −3.60, 4.62] with placebo. Supplements boosted the total testosterone levels [2.70, 95% CI 1.34, 4.07] in comparison to SERMs [1.83, 95% CI 1.16, 2.50], hormones [0.40, 95% CI −0.49, 1.29], and vitamins [−0.70, 95% CI −6.71, 5.31] with placebo. SERMs increase the serum FSH levels [3.63, 95% CI 1.48, 5.79] better than hormones [1.29, 95% CI −0.79, 3.36], vitamins [0.03, 95% CI −2.69, 2.76], and supplements [−4.45, 95% CI −7.15, −1.76] in comparison with placebo. Conclusion. This review establishes that all interventions had a significantly positive effect on male infertility. Statistically significant increased sperm parameters were noted in combinations of zinc sulfate (220 mg BID), clomiphene citrate (50 mg BID), and testosterone undecanoate and CoQ10; tamoxifen citrate and FSH were shown to improve the hormonal profile in infertile males.
... Men in the CoQ10 group had higher catalase and SOD activity and lower seminal plasma 8-isoprostane concentration than those in the placebo group after the treatment period. Moreover, seminal CoQ10 showed a significant correlation with SOD (r = 0.6, p < 0.005) and catalase (r = 0.3, p < 0.05) after treatment [21]. ...
... The present review demonstrated a general positive effect of CoQ10 supplementation on seminal parameters. As regards CoQ10 monotherapy, sperm motility significantly increased in all the studies evaluated [9,[13][14][15][16][18][19][20][21][22][23] except one [17]. A significant increase in sperm concentration was also reported by some authors [13,16,[18][19][20]23], whereas the effects on normal morphology were lower [9,13,18,19,23]. ...
... As noted above, spermatozoa are susceptible to OS that is generated when seminal fluid scavenging mechanisms are overwhelmed by ROS [4]. CoQ10 supplementation significantly increases seminal coQ10 levels [14,15] and improves the antioxidant capacity of seminal fluid [13,17,18,20,21,23], improving both enzymatic and non-enzymatic germ cell protection systems. This appears critical in protecting sperm DNA from ROS damage, as demonstrated by some authors [11,25,28,29], who reported a significant reduction in the DFI after antioxidant treatment. ...
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Infertility affects 15% of couples worldwide. A male factor is involved in 50% of cases. The etiology of male infertility is poorly understood, but there is evidence for a strong association between oxidative stress (OS) and poor seminal fluid quality. For this reason, therapy with antioxidants is one of the cornerstones of empirical treatment of male infertility. Coenzyme Q10 (CoQ10)—an essential cofactor for energy production with major antioxidant properties—is commonly used to support spermatogenesis in idiopathic male infertility. This systematic review aims to elucidate the usefulness of CoQ10 supplementation in the treatment of male infertility, particularly with regard to semen quality assessed by conventional and advanced methods, and pregnancy rates. All studies report a beneficial effect of CoQ10 supplementation on semen parameters, although randomized controlled trials are a minority. Moreover, the optimal dosage of CoQ10 or how it can be combined with other antioxidant molecules to maximize its effect is unknown. However, CoQ10 is still one of the most promising molecules to treat idiopathic male infertility and warrants further investigation.
... It is an isoprenylated benzoquinone that transports electrons from complexes I and II to complex III in the mitochondrial respiratory chain-regulating cytoplasmic redox potential-protecting cell membrane against lipid peroxidation-induced damage and regulating the mitochondrial permeability transition pores [19]. CoQ10 has two forms: a reduced form ubiquinol and an oxidized form ubiquinone [20]. Safarinejad and colleagues have reported an increase in sperm concentration and motility after CoQ10 therapy [21]. ...
... Safarinejad and colleagues have reported an increase in sperm concentration and motility after CoQ10 therapy [21]. Observations by Nadjarzadeh et al. also support the above findings which reported a reduction in the sperm OS markers after CoQ10 therapy [20]. Other studies, however, reported no improvement in one or more of seminal fluid parameters following CoQ10 therapy [22,23]. ...
... According to Agarwal et al., ROS in semen correlates negatively with all sperm parameters [13] so an increase in TAC and other antioxidant capacity measures may enhance sperm function and fertility potential. In a randomized placebo-controlled study by Nadjarzadeh et al., there was a significant positive correlation between CoQ10 concentration and normal sperm morphology, catalase activity, and SOD after 3 months in infertile men with OAT following CoQ10 supplementation [20]. ...
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Oxidative stress (OS) is a key contributing factor in 30–80% of male infertility cases. To date, several antioxidant treatments have been put forth to manage OS-induced male infertility. This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT). In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months. Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment. The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 0.01) as well as increased progressive sperm motility (p < 0.01 and p < 0.05) and total sperm motility (p < 0.01 and p < 0.05) with CoQ10 and selenium treatment respectively. There was also a significant improvement in TAC (p < 0.01 and p < 0.05) and SOD (p < 0.01 and p < 0.05) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 0.05). Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 0.37–0.76). In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement.
... Therapies with antioxidant compounds or dietary supplements have been widely evaluated as a treatment option for male infertility cases, since nutritional therapies have been shown to improve sperm counts and sperm motility, to quote but two sperm parameters [59][60][61]. Several studies set themselves the objective of examining the effects caused by different types of antioxidant therapies on semen quality in infertile males through a measurement of CAT activity on seminal plasma through exogenous H2O2 degeneration (this can be easily measured by means of spectrophotometry). ...
... Several studies set themselves the objective of examining the effects caused by different types of antioxidant therapies on semen quality in infertile males through a measurement of CAT activity on seminal plasma through exogenous H2O2 degeneration (this can be easily measured by means of spectrophotometry). These studies revealed that catalase activity increased after the administration of antioxidant treatments compared to control samples without antioxidant supplementation [60][61][62]. ...
... In contrast to the positive studies mentioned above, Nadjarzadeh and co-workers reported no beneficial effects on sperm quality derived from the administration of CoQ10 in a small, placebo-controlled trial, despite obtaining a significant increase in catalase activity after the treatment. [61]. ...
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Catalase (CAT) stands out as one of the most efficient natural enzymes when catalysing the split of H2O2 into H2O and O2; H2O2 is one of the reactive oxygen species (ROS) involved in oxidative stress, a process closely related to aging and several health disorders or diseases like male infertility. Some studies have correlated H2O2 with male infertility and catalase with fertility restoration. However, the number of studies conducted with human beings remains scarce. Considering the use of CAT as a molecular target for biochemical analysis, this review summarises the current knowledge on how CAT influences human beings’ male fertility. Thus, three different databases were consulted—Scopus, PubMed and WOS—using single keywords and combinations thereof. A total of 40,823 articles were identified. Adopting inclusion and exclusion criteria, a final database of 197 articles served to conduct this work. It follows from this analysis that CAT could play an important role in male fertility and could become a good target for male infertility diagnosis and monitoring. However, that potential role of CAT as a tool in diagnosis must be confirmed by clinical trials. Finally, guidelines are suggested to reinforce the use of CAT in daily clinical tests for male fertility diagnosis and monitoring.
... The benefits of RJ or CoQ10 supplementation have been demonstrated to alleviate exercise-induced oxidant stress in damaged muscle and enhance various aspects of exercise performance in many but not all studies . Nevertheless, previous studies have most extensively shown that oral RJ or CoQ10 administration has a good safety profile, with no observed adverse effects or toxicity [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69]72,73]. Despite this fact and the possible additive or synergistic effects of using RJ with CoQ10, the influence of their combination on biomarkers of oxidative stress and muscle damage, as well as on exercise performance in athletes remains unexplored. ...
... In addition, the ubiquinol is able to regenerate also vitamins E and C back to their active, fully reduced forms [46,49]. Furthermore, it was reported that CoQ10 increases both MnSOD and CAT activities [69], however the mechanisms of action are currently undefined. Our findings support the hypothesis that the 10-day RJQ supplementation in combination with physical training may be effective aid to attenuate oxidative stress through activation of both enzymatic and non-enzymatic antioxidant defense mechanisms [79]. ...
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Background: Excessive production of free radicals caused by many types of exercise results in oxidative stress, which leads to muscle damage, fatigue, and impaired performance. Supplementation with royal jelly (RJ) or coenzyme Q10 (CoQ10) has been shown to attenuate exercise-induced oxidant stress in damaged muscle and improve various aspects of exercise performance in many but not all studies. Nevertheless, the effects of treatments based on RJ plus CoQ10 supplementation, which may be potentially beneficial for reducing oxidative stress and enhancing athletic performance, remain unexplored. This study aimed to examine whether oral RJ and CoQ10 co-supplementation could improve high-intensity interval exercise (HIIE) performance in swimmers, inhibiting exercise-induced oxidative stress and muscle damage. Methods: Twenty high-level swimmers were randomly allocated to receive either 400 mg of RJ and 60 mg of CoQ10 (RJQ) or matching placebo (PLA) once daily for 10 days. Exercise performance was evaluated at baseline, and then reassessed at day 10 of intervention, using a HIIE protocol. Diene conjugates (DC), Schiff bases (SB), and creatine kinase (CK) were also measured in blood plasma and saliva before and immediately after HIIE in both groups. Results: HIIE performance expressed as number of points according to a single assessment system developed and approved by the International Swimming Federation (FINA points) significantly improved in RJQ group (p = 0.013) compared to PLA group. Exercise-induced increase in DC, SB, and CK levels in plasma and saliva significantly diminished only in RJQ group (p < 0.05). Regression analysis showed that oral RJQ administration for 10 days was significantly associated with reductions in HIIE-induced increases in plasmatic and salivary DC, SB, and CK levels compared to PLA. Principal component analysis revealed that swimmers treated with RJQ are grouped by both plasmatic and salivary principal components (PC) into a separate cluster compared to PLA. Strong negative correlation between the number of FINA points and plasmatic and salivary PC1 values was observed in both intervention groups. Conclusion: The improvements in swimmers' HIIE performance were due in significant part to RJQ-induced reducing in lipid peroxidation and muscle damage in response to exercise. These findings suggest that RJQ supplementation for 10 days is potentially effective for enhancing HIIE performance and alleviating oxidant stress. Abbreviations: RJ, royal jelly; CoQ10, coenzyme Q10; HIIE, high-intensity interval exercise; DC, diene conjugates; SB, Schiff bases; CK, creatine kinase; RJQ, royal jelly plus coenzyme Q10; PLA, placebo; FINA points, points according to a single assessment system developed and approved by the International Swimming Federation; ROS, reactive oxygen species; 10H2DA, 10-hydroxy-2-decenoic acid; AMPK, 5'-AMP-activated protein kinase; FoxO3, forkhead box O3; MnSOD, manganese-superoxide dismutase; CAT, catalase; E, optical densities; PCA, principal component analysis; PC, principal component; MCFAs, medium-chain fatty acids; CaMKKβ, Ca2+/calmodulin-dependent protein kinase β; TBARS, thiobarbituric acid reactive substances; MDA, malondialdehyde.
... Among antioxidant interventions, an important body of literature already reviewed in Littarru et al., 2010 [2], supports the efficacy of CoQ both in improving sperm quality in terms of count and motility, correlated to increasing Q10 levels in spermatozoa. This evidence was confirmed in recent studies showing that ubiquinone [65,66] and ubiquinol [67,68] use in men affected by idiopathic oligoasthenozoospermia, led to improved sperm count, motility and morphology, associated with an increase in spermatic antioxidant defenses quantified as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels and sperm DNA integrity [65,66]. Moreover, Tirabassi et al. [69] demonstrated that 3 months of 200 mg/day CoQ intervention, combined with 2.66 g/day aspartic acid, on idiopathic asthenozoospermia patients, increased CoQ (p < 0.001) and aspartic acid (p = 0.022) levels in sperm cells and seminal fluids, and were associated with significant increases in SOD activity and a significant decrease in oxidative stress markers (NO and DNA damage), the latter showing an inverse correlation with CoQ content. ...
... Among antioxidant interventions, an important body of literature already reviewed in Littarru et al., 2010 [2], supports the efficacy of CoQ both in improving sperm quality in terms of count and motility, correlated to increasing Q10 levels in spermatozoa. This evidence was confirmed in recent studies showing that ubiquinone [65,66] and ubiquinol [67,68] use in men affected by idiopathic oligoasthenozoospermia, led to improved sperm count, motility and morphology, associated with an increase in spermatic antioxidant defenses quantified as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels and sperm DNA integrity [65,66]. Moreover, Tirabassi et al. [69] demonstrated that 3 months of 200 mg/day CoQ intervention, combined with 2.66 g/day aspartic acid, on idiopathic asthenozoospermia patients, increased CoQ (p < 0.001) and aspartic acid (p = 0.022) levels in sperm cells and seminal fluids, and were associated with significant increases in SOD activity and a significant decrease in oxidative stress markers (NO and DNA damage), the latter showing an inverse correlation with CoQ content. ...
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The present review focuses on preclinical and clinical studies conducted in the last decade that contribute to increasing knowledge on Coenzyme Q10’s role in health and disease. Classical antioxidant and bioenergetic functions of the coenzyme have been taken into consideration, as well as novel mechanisms of action involving the redox-regulated activation of molecular pathways associated with anti-inflammatory activities. Cardiovascular research and fertility remain major fields of application of Coenzyme Q10, although novel applications, in particular in relation to topical application, are gaining considerable interest. In this respect, bioavailability represents a major challenge and the innovation in formulation aspects is gaining critical importance.
... In the first retrospective study, Cakiroglu et al. [190] reported significant changes in sperm morphology and motility in 62 patients with idiopathic asthenoteratozoospermia who received 100 mg of CoQ 10 H 2 twice a day for six months. In the second randomized, placebo-controlled study, carried out on 47 infertile males affected by idiopathic oligoasthenoteratozoospermia, Nadjarzadeh et al. investigated the effects of the abovementioned CoQ 10 H 2 administration protocol for 3 months on the expression of catalase and SOD and on the F2-isoprostanes levels in seminal plasma [191]. Besides showing a significant positive correlation between CoQ 10 levels and the percent of morphologically normal spermatozoa, results indicated increased activity of the aforementioned antioxidant enzymes, accompanied by a significant decrease of F2-isoprostanes levels in seminal plasma. ...
... Besides showing a significant positive correlation between CoQ 10 levels and the percent of morphologically normal spermatozoa, results indicated increased activity of the aforementioned antioxidant enzymes, accompanied by a significant decrease of F2-isoprostanes levels in seminal plasma. The authors suggested that the supplementation of CoQ 10 H 2 to infertile males with oligoasthenoteratozoospermia can attenuate oxidative stress in seminal plasma by increasing antioxidant enzyme activity, ultimately improving semen parameters [191]. Surprisingly, a significant improvement in sperm forward motility, sperm density and in total antioxidant capacity was also obtained by Festa et al. [192], who administered a lower dose of 50 mg CoQ 10 H 2 twice a day, for 12 consecutive weeks, to 38 infertile males affected by varicocele. ...
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Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile males, potentially causing permanent oxidative damages to a vast number of biological molecules (proteins, nucleic acids, polyunsaturated fatty acids of biological membrane lipids), negatively affecting the functionality and vitality of spermatozoa. ROS overproduction may concomitantly occur to the excess generation of reactive nitrogen species (RNS), leading to oxidative/nitrosative stress and frequently encountered in various human pathologies. Under different conditions of male infertility, very frequently accompanied by morpho-functional anomalies in the sperm analysis, several studies have provided evidence for clear biochemical signs of damages to biomolecules caused by oxidative/nitrosative stress. In the last decades, various studies aimed to verify whether antioxidant-based therapies may be beneficial to treat male infertility have been carried out. This review analyzed the results of the studies published during the last ten years on the administration of low-molecular-weight antioxidants to treat male infertility in order to establish whether there is a sufficient number of data to justify antioxidant administration to infertile males. An analysis of the literature showed that only 30 clinical studies tested the effects of the administration of low-molecular-weight antioxidants (administered as a single antioxidant or as a combination of different antioxidants with the addition of vitamins and/or micronutrients) to infertile males. Of these studies, only 33.3% included pregnancy and/or live birth rates as an outcome measure to determine the effects of the therapy. Of these studies, only 4 were case–control studies, and only 2 of them found improvement of the pregnancy rate in the group of antioxidant-treated patients. Additionally, of the 30 studies considered in this review, only 43.3% were case–control studies, 66.7% enrolled a number of patients higher than 40, and 40% carried out the administration of a single antioxidant. Therefore, it appears that further studies are needed to clearly define the usefulness of antioxidant-based therapies to treat male infertility.
... Moreover, it also inhibits the production of superoxide ions to protect against OS mediated sperm damage. This explains the result obtained from the studies of Nadjarzadeh, Shidfar et al. 2014 56 where seminal CoQ10 concentration positively correlates with normal sperm morphology and enzymatic enzyme concentrations. It is also evident that at least three-months of CoQ10 treatment at dose of 200-600mg/day, could improve semen parameters, antioxidant enzymes activities in idiopathic infertility patients [56][57][58] Vitamins Carotenoids are a bunch of fat-soluble natural compounds found basically in yellow, ruddy, orange, and pink vegetables. ...
... This explains the result obtained from the studies of Nadjarzadeh, Shidfar et al. 2014 56 where seminal CoQ10 concentration positively correlates with normal sperm morphology and enzymatic enzyme concentrations. It is also evident that at least three-months of CoQ10 treatment at dose of 200-600mg/day, could improve semen parameters, antioxidant enzymes activities in idiopathic infertility patients [56][57][58] Vitamins Carotenoids are a bunch of fat-soluble natural compounds found basically in yellow, ruddy, orange, and pink vegetables. These retinoids are basically vitamin A precursors. ...
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Male infertility is a multifactorial condition which in some cases are presented with unidentifiable underlying causes. Men with idiopathic or non-curable oligoasthenoteratozoospermia as well as with unexplained infertility may be provided with non-hormonal medical treatment which includes the use of anti-inflammatory, antioxidants, fibrinolytic compounds, vitamin supplementation, and oligo-elements, presuming that most of these cases are possibly caused by inflammation and/or oxidative stress. In the case of the known pathogenic mechanisms responsible for male infertility, the treatments include specific antibiotics targeting the exact pathogenic strains, anti-inflammatory drugs targeting particular infections, as well as the use of antioxidants, singly or in combinations to ameliorate the detected oxidative stress. Combined non-hormonal therapies have also shown to improve semen quality. Since there is a lack of consensus regarding the exact dose, duration and effects of non-hormonal treatment on male infertility, this review article aims to present a comprehensive summary of how antioxidants, anti-inflammatory drugs and antibiotics treatment in reproductive tract infections are associated with amelioration of male fertility parameters.
... Accordingly, infertile men display imbalance of the blood oxidation status and the level of reactive oxygen species (ROS) in seminal fluid has been correlated with sperm motility, morphology, and count in astheno-and oligoastheno-teratospermic males [20]. Moreover, reports have linked these factors to sperm DNA fragmentation (SDF), a recurrent disruption observed in idiopathic male infertility [21,22]. As a proof of concept, several authors have investigated the efficacy of antioxidant supplementation (such as L-carnitine, selenium, Coenzyme Q10, ubiquinol, and vitamins C and E) in infertile men, with positive results on sperm quality [23]. ...
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Background: Lifestyle and environmental factors can negatively impact fertility by means of oxidative stress. In this context, antioxidant supplementation therapy has gained much interest in recent years, and different molecules, alone or in combination, have been studied. Objective: The purpose of the present review is to investigate the evidence regarding the efficacy of coenzyme Q10 (CoQ10) and melatonin on male infertility. Methods: A literature search using PUBMED database from 2000 to October 2022 was performed to explore the role of CoQ10 and melatonin on male reproductive function. Conclusions: The analysis involved a narrative synthesis. CoQ10, alone or in combination, appears to reduce testicular oxidative stress and sperm DNA fragmentation and to improve sperm parameters; particularly sperm motility. Moreover, CoQ10 treatment is associated with higher pregnancy rates, both naturally and through assisted reproductive technology (ART). Larger studies are needed to precisely determine its clinical efficacy. Melatonin is a known antioxidant and preclinical studies have shown its ability to modulate reproductive function through hormonal and immune system regulation and sperm cell proliferation. Regardless, clinical studies are necessary to assess its potential in male infertility.
... This finding aligns with our previous studies, which have also shown correlations between CoQ10 levels, SDF, and sperm motility [13,18]. Other studies have also reported similar correlations in men with IMI [42,43]. We could not find studies on the effect of Centrum on SDF, but several studies have explored the impact of different combinations of antioxidants in IMI and reported reductions in SDF levels [44,19]. ...
Article
Objective: Oxidative stress and sperm DNA fragmentation (SDF) have been linked to idiopathic male infertility (IMI). Various antioxidants have been tried to improve semen parameters and fertility potential in IMI patients, but with inconsistent results. The study aimed to compare the effects of coenzyme Q10 (CoQ10) and Centrum multivitamins on semen parameters, seminal antioxidant capacity, and SDF in infertile men with idiopathic oligoasthenospermia (OA). Methods: This prospective controlled clinical study involved 130 patients with idiopathic OA and 58 fertile controls. The patients were divided randomly into two groups: the first group received CoQ10 (200 mg/day orally) and the second group received Centrum multivitamins (1 tablet/day) for 3 months. Semen parameters, CoQ10 levels, reactive oxygen species (ROS), total antioxidant capacity (TAC), catalase, SDF, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin) were compared at baseline and after 3 months. Results: Both CoQ10 and Centrum improved sperm concentration and motility, but the improvement was greater with Centrum therapy (p<0.05). Similarly, both therapies improved antioxidant capacity, but TAC and catalase improvement was greater (p<0.01 and p<0.001 respectively) with CoQ10, whereas ROS (p<0.01) and SDF (p<0.001) improvements were greater with Centrum administration. Centrum therapy was associated with reduced serum testosterone (p<0.05). Conclusion: In conclusion, both CoQ10 and Centrum were effective in improving semen parameters, antioxidant capacity, and SDF, but the improvement was greater with Centrum than with CoQ10. Therefore, Centrum-as a source of combined antioxidants-may provide more effective results than individual antioxidants such as CoQ10 in the treatment of infertile men with idiopathic OA.
... Although some studies have questioned the benefits of antioxidants in male infertility, inarguable pieces of evidence show that antioxidants alleviate oxidative stress-induced testicular and sperm damage. Vitamins (such as Vitamin C and E), carnitine, cysteine, and carotenoids have been shown to scavenge free radicals and act as energy sources (189)(190)(191)(192)(193). In addition to the free radical scavenging-ability of Coenzyme Q10 (CoQ10), it also serves as an intermediate in the mitochondrial transport (194), thus providing required energy. Folic acid preserves sperm DNA integrity (195), while selenium maintains redox balance and aids sperm motility (196). ...
Article
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Viral infections have been a part of human existence to date, though viruses have posed a huge threat with various outbreaks lately. These threats are associated with reproductive health challenges, especially male infertility. The prime focus of this review is to highlight the mechanisms associated with viral infection-induced male infertility/subfertility and identify new treatment strategies with the aim to preserve male fertility. The reviewed data showed that viral infections stimulate inflammatory responses, resulting in the release of proinflammatory cytokines, which induces oxidative stress. This oxido-inflammatory cycle could continue in a vicious cycle and threaten male fertility. Existing data from human and experimental studies show that viral infection-induced oxido-inflammatory response results in testicular damage, atrophy of the seminiferous tubules and Sertoli cells, and reduced Leydig cell mass. This is accompanied by reduced circulatory testosterone, impaired spermatogenesis, reduced sperm motility, lipid peroxidation, DNA fragmentation and apoptosis of the sperm cells. Based on the available pieces of evidence, antioxidant therapy, in vivo and in vitro , may be beneficial and protects against the potential risk of male infertility from viral infection. It is, however recommended that more clinical studies be conducted to demonstrate the possible protective roles of antioxidants used as adjuvant therapy in viral infections, and in the in vitro treatment of semen samples for those utilizing semen washing and artificial reproductive techniques.
... (200 mg/day) was associated with improvement in semen parameters, and these parameters also correlated with antioxidant capacity . Another clinical trial that involved treatment with CoQ10 (200 mg/day) for 3 months in men with idiopathic oligoasthenoteratospermia (OAT) reported an increment in sperm motility, CoQ10, CAT and SOD (Nadjarzadeh et al., 2014). ...
Article
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Different antioxidants including coenzyme Q10 (CoQ10) have been tried to treat idiopathic male infertility (IMI) with variable results. Therefore, this study aimed to determine the clinical and biochemical predictors of pregnancy outcome and time to pregnancy (TTP) in infertile men with idiopathic oligoasthenospermia (OA) pre‐ and post‐CoQ10 therapy. This prospective controlled clinical study included 178 male patients with idiopathic OA and 84 fertile men (controls). Patients received 200 mg of oral CoQ10 once daily for 6 months. Demographics, semen parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), catalase (CAT), glutathione peroxidase (GPx), sperm DNA fragmentation (SDF) and body mass index were measured and compared at baseline and after 6 months. All participants were followed up for another 18 months for pregnancy outcome and TTP. CoQ10 therapy for 6 months significantly improved semen parameters, antioxidant measures and reduced SDF. The pregnancy rate was 24.2% and TTP was 20.52 ± 6.72 months in patients as compared to 95.2% and 5.73 ± 6.65 months in fertile controls. After CoQ10 therapy, CoQ10 level, sperm concentration, motility and ROS were independent predictors of pregnancy outcome and CoQ10 level, male age, sperm concentration, motility, ROS and GPx were independent predictors of TTP in patients. In conclusion, CoQ10 therapy of 6 months is a potential treatment for men with idiopathic OA. CoQ10 level, male age, semen parameters, ROS and GPx could potentially be used as diagnostic biomarkers for male fertility and predictors for pregnancy outcome and TTP in these patients.
... Moreover, seminal plasma analysis confirmed the already known significant direct correlation between CoQ10 levels and sperm motility and morphology. In their study, CoQ10 supplementation for at least three months attenuated OS in seminal plasma and improved antioxidant enzyme activity [58]. ...
Article
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Background: Infertility, defined as the failure to conceive after one year of regular, unprotected intercourse, affects 50–80 million people worldwide. A male factor is involved in approximately 20–30% of cases. In the etiology of male infertility, the association between poor semen quality and oxidative stress (OS) is well known. High levels of reactive oxygen species (ROS) allow the oxidation of DNA, proteins, and lipids of sperm cells, modifying their vitality, motility, and morphology. Methods: To evaluate the effects of antioxidants on sperm in infertile men, we queried the MEDLINE database (via the PubMed interface) for published studies in the last 10 years (2011–2021). The following keywords were used: “infertility” and -“inositol”, -“alpha-lipoic acid”, -“zinc”, -“folate”, -“coenzyme Q10”, -“selenium”, and -“vitamin”. Results: Inositol regulates OS levels in sperm cells thanks to its role in mitochondrial reactions and is involved in several processes favoring sperm–oocyte interactions. Alpha-lipoic acid (ALA) reduces ROS damage and improves semen parameters in terms of spermatozoa’s motility, morphology, and count. Poor zinc nutrition may be related to low quality of sperm. Supplementation of folate plus zinc has a positive effect on the sperm concentration and morphology. Supplementation with CoQ10 increases sperm concentration, total and progressive motility. Selenium (Se) supplementation improves the overall semen quality and is related to a higher ejaculated volume. Among vitamins, only vitamin B12 shows a positive effect on semen quality; it increases sperm count and motility and reduces sperm DNA damage. Conclusions: In men showing low-quality semen, diet supplementation with antioxidants may improve the sperm quality by alleviating OS-induced sperm damage and enhancing hormone synthesis and spermatozoa concentration, motility, and morphology. Future clinical trials should be focused on the possible association of several antioxidants to take advantage of combined mechanisms of action.
... Ayrıca Koenzim Q10 konsantrasyonu ile normal sperm morfolojisi ve sperm motilite oranlarında da anlamlı korelasyonlar tespit edilmiştir. [15] Lafuente ve ark., yaptıkları sistematik derleme ve meta-analizde 3 plasebo-kontrollü çalışma incelenmiş; koenzim Q10 tedavisinin sperm motilitesi ve semen konsantrasyonlarında anlamlı artışa neden olduğu ancak canlı doğum ve gebelik gelişimine bir etkisinin olmadığı belirlenmiştir. [16] E vitamini, serbest radikaller tarafından lipid peroksidasyonuyla oluşturulan hücre membran hasarını önlemede ve diğer antioksidanların aktivitesini düzenlemede önemli rol oynar. ...
... CoQ 10 is an antioxidant and can protect against free radical-induced oxidative damage [38]. In a randomized double-blind study including 60 oligoasthenoteratozoospermia (OAT) patients, it was reported that the sperm parameters and the antioxidant enzyme activities increased in the CoQ 10 supplementation group [39]. Our study also showed ability transition pore (PTP) on the mitochondria opening decreases the mitochondrial membrane potential, which facilitates cytochrome c release from mitochondria and induces cell apoptosis. ...
Article
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This study explored the effects of coenzyme Q 10 (CoQ 10) on the testicular functions of male mice exposed to cigarette smoke. Eight-week-old BALB/c male mice were divided into the following groups: the AV group (air with a vehicle), the AQ group (air with CoQ 10), the SV group (smoke with a vehicle), and the SQ group (smoke with CoQ 10). The results showed that the CoQ 10 concentrations in the sera and testes were decreased in the groups subjected to smoke but they were improved after the administration of CoQ 10. Neither smoke nor CoQ 10 supplementation affected the serum or testis testosterone concentrations. Regarding the antioxidant system in the testis, the exposure to smoke induced malondialdehyde and hydrogen peroxide production and decreased the catalase and glutathione peroxidase activities. Oral CoQ 10 administration reversed the oxidative damage. In apoptosis, the cytochrome c, c-caspase 9, and c-caspase 3 proteins were increased in the groups exposed to smoke but they were decreased after the CoQ 10 administration. In mitochondrial biogenesis, smoke exposure led to decreases in the PGC1-α, NRF1, and NRF2 levels, but CoQ 10 increased the expressions of these proteins. Additionally, oral CoQ 10 administration improved the mitochondrial copy numbers that were reduced following the exposure to smoke. In summary, CoQ 10 administration reduces smoke-induced testicular damage by regulating the antioxidant capacity, the cell apoptosis, the mitochondrial biogenesis, and the copy numbers in the testes.
... After excluding RCTs with a high risk of bias or without AT prior to sperm analysis, the effects of FSH, hCG, carnitine, SERM plus androgen, and carnitine plus CoQ10 were still significant, while the effects of SERM, SERM plus vitamins, and carnitine plus vitamins were not (Fig. 3). The SUCRA values evaluated for each intervention for overall, excluded RCTs with a high risk of bias, and excluded RCTs without AT prior to sperm analysis are presented in Fig. 4. The optimal intervention for achieving successful pregnancy was carnitine plus vitamins, regardless of the risk bias of the study or without AT prior to sperm analysis (Table 1 [ [25][26][27][28][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]83,84,[86][87][88][89]). The funnel plot indicated a lack of small-study effects for SPR (Fig. 5). ...
Article
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In this study, we used a network meta-analysis (NMA) to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment. Medline, Excerpta Medica Database (EMBASE), Ovid, and China National Knowledge Infrastructure (CNKI), were searched for the period from January 1990 to June 2021 using the keywords “male infertility,” “medical therapy,” “supplement/nutrient therapy,” and related terms. Studies involving randomized controlled trials (RCTs) investigating medicines (mainly follicle-stimulating hormone (FSH), androgen, and clomiphene/tamoxifen) or supplements (mainly zinc, selenium, vitamin C or E, carnitine, coenzyme Q10 (CoQ10), or combined treatment) for idiopathic infertile men were selected for meta-analysis. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) was used for data extraction, and a risk-of-bias tool and grades of recommendation, assessment, development, and evaluation (GRADE) system adapted to the NMA were employed to assess the quality of the evidence. The primary outcomes were live birth and spontaneous pregnancy rate (SPR). The secondary outcomes were sperm parameters (including concentration, progressive motility, and morphology) and side effects. In total, 65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included. A total of 36 studies reported SPR but only three reported live birth rates. The quality of the included studies was found to be moderate to high. Compared with a placebo or being untreated, carnitine plus vitamins significantly improved SPR (relative risk (RR) = 3.7, 95% confidence interval (CI), 1.6–8.5); fatty acids significantly increased sperm concentrations (mean difference (MD) = 12.5 × 10⁶ mL–1, 95%CI, 3.1 × 10⁶–22.0 × 10⁶); and selective estrogen receptor modulators (SERM) plus CoQ10 significantly improved sperm progressive motility (MD = 11.0%, 95%CI, 0.1%–21.9%) and normal sperm morphology (MD = 11.0%, 95%CI, 4.6%–17.4%). The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations, respectively, even after excluding trials at a high risk of bias. Compared with a placebo or being untreated, FSH (RR = 4.9, 95%CI, 1.1–21.3) significantly increased SPR, whereas SERM plus kallikrein increased sperm concentration (MD = 16.5 × 10⁶ mL–1, 95%CI, 1.6 × 10⁶–31.4 × 10⁶), and SERM plus CoQ10 significantly improved sperm progressive motility (MD = 11.3%, 95%CI, 7.3%–15.4%) and normal morphology (MD = 11.2%, 95%CI, 5.4%–16.9%) in men with oligoasthenozoospermia (OA). In terms of side effects, fatty acids and pentoxifylline were associated with foul breath and/or a bad taste (RR = 8.1, 95%CI, 1.0–63.5) and vomiting (RR = 8.0, 95%CI, 1.0–63.0), respectively. In conclusion, the optimal treatment for male infertility for live birth is still unknown. Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in couples with men with OA, respectively. The efficacy of other treatments on pregnancy outcomes warrants further verification.
... Recent surveys have reported that seminal 8-iso-PGF2α levels were significantly higher in infertile patients than in fertile men [10][11][12]24,25]. In particular, the levels of these compounds were particularly high in patients affected by varicocele, a pathology characterized by sperm immaturity [12,25]. ...
Article
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F2-isoprostanes (F2-IsoPs), stereoisomers of prostaglandin F2α generated by the free radical-induced oxidation of arachidonic acid, have been associated with different male infertility conditions. This study aimed to evaluate the role of seminal isoprostane levels and sperm characteristics in the reproductive outcome and embryo quality of 49 infertile couples. Semen analysis was performed following WHO guidelines. Sperm chromatin maturity was detected using an aniline blue (AB) assay, and DNA integrity was assessed using the acridine orange (AO) test. Seminal F2-IsoP levels were quantified by gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI–MS/MS) analysis. Correlations among variables and their impact on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcome were investigated. F2-IsoP levels are positively correlated with double-stranded DNA sperm (p < 0.001) and negatively correlated with mature sperm chromatin (p < 0.001). Patients with positive outcomes had an increased percentage of sperm with double-stranded DNA, as did patients producing high-quality embryo, who showed higher F2-IsoP levels compared to those detected in the low-quality embryo group. An intriguing relationship between a mild increase in F2-IsoP levels, DNA integrity, and embryo quality seems to indicate that the non-enzymatic oxidation of arachidonic acid can be also a marker of metabolic activity in human semen.
... CoQ10 is an intermediate of the mitochondrial electron transport chain [153,154]. Low seminal plasma/sperm concentrations of CoQ10 have been associated with reduced sperm motility [155]. ...
Chapter
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Within the male reproductive system, oxidative stress (OS) has been identified as prevailing etiology of male infertility. The effects of reactive oxygen species (ROS) on male fertility depend on the dimensions, “modus operandi” of the ROS and the oxido-reduction potential (ORP) of the male reproductive tract. Hereupon, for an adequate response to OS, the cells of our body are endowed with a well-sophisticated system of defense in order to be protected. Various antioxidant enzymes and small molecular free radical scavengers, maintain the delicate balance between oxidants and reductants (antioxidants), crucial to cellular function and fertility. Therapeutic use of antioxidants is an optimal and coherent option in terms of mitigating OS and improving semen parameters. Therefore, recognizing and managing OS through either decreasing ROS levels or by increasing antioxidant force, appear to be a requesting approach in the management of male infertility. However, a clear defined attitude of the experts about the clinical efficacy of antioxidant therapy is still deprived. Prominently, antioxidant such as coenzyme Q10, vitamin C and E, lycopene, carnitine, zinc and selenium have been found useful in controlling the balance between ROS production and scavenging activities. In spite of that, healthy lifestyle, without smoke and alcohol, everyday exercise, reduction of psychological stress and quality well-designed meals, are habits that can overturn male infertility.
... DNA fragmentation can lead to infertility by altering sperm function [50]. Males with a high SDF rate have a substantially lower likelihood of conceiving naturally or via ART procedures [51]. Accordingly, patients with a high percentage of spermatozoa affected by DNA fragmentation have high levels of seminal ROS and decreased antioxidant capacity [26]. ...
Article
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Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.
... Another controlled trial including [32]. The various results from meta-analyses and clinical trials on CoQ10 therapy in men with infertility align with our findings that supplementation with CoQ10 increased seminal CoQ10 levels, sperm motility, and concentration [33]. Generally, controlled clinical trials among men with idiopathic infertility treated with CoQ10 have shown that this treatment leads to a reduction in OS in seminal plasma and lipid peroxidation, as well as an increase in ubiquinol levels and seminal enzymatic antioxidant levels [32]. ...
Article
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Objective: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. Methods: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. Results: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pretreatment values. Conclusion: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.
... Other researcherse valuated the effects produced by different types of antioxidant therapies on semen quality in infertile males via measurement of CAT activity on seminal plasma through exogenous H 2 O 2 degeneration. The results revealed that catalase activity improved after the administration of antioxidant treatments when compared to control samples without antioxidant administration [91][92][93]. ...
Chapter
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Nutritional utilization of antioxidants, such as vitamins C, E, ß-Carotene and micronutrients, such as folate and zinc, have been shown to be critically essential for normal semen quality and reproductive function. However, it is still, a large knowledge gap exists concerning the role of antioxidants on semen parameters and the role in treatment of male subfertility. Therefore, the current review article designed to find out the positive effect of antioxidants on semen quality, alterations in physiological functions of spermatozoa and infertility treatment It is advisable that patients with oxidative DNA disruption should be asked to take a simple course of antioxidants prior to undertaking assisted reproduction treatment (ART). In conclusion, antioxidant may be employed as a potent antioxidant and may improve infertility treatment outcomes with ART.
... As an antioxidant, it scavenges free radicals and prevents the initiation and propagation of lipid peroxidation in cell membranes, also helping with the regeneration of other antioxidants such as tocopherol and ascorbate (Crane, 2001). Its activity as an antioxidant has been studied in different tissues, like the testes (Ognjanovic et al., 2010;Fouad et al., 2011;Nadjarzadeh et al., 2013). As a bioenergetic molecule, it is an essential member of the mitochondrial electron transport chain and has a fundamental role in the production of ATP. ...
Article
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This study was undertaken to assess the effect of a three-minute forced swimming protocol for 50 days, with and without antioxidant administration on sperm morphology in CD-1 mice. Seventy-five mice were randomly allocated to one of the following five groups: no exercise (control group; CG), swimming without antioxidant administration (EX), swimming with trans-resveratrol administration (EX-Resv), swimming with ubiquinol and excipient administration (Kaneka´s ubiquinol) (EX-Ubiq), and swimming with just only the excipient for Kaneka´s ubiquinol administration (EX-Excp). The EX group showed that 53.03±4.83% of sperm had abnormal morphology, with significant differences with regards to CG (46.47±10.57%) (p<0.05). The number of sperm with abnormal morphology decreased in all groups treated with either antioxidants or with excipient; this was most noticeable in EX-Ubiq (p<0.05). The percentage of midpiece and tail, as well as multiple anomalies were greater in EX than in CG (p<0.05). While both antioxidants, as well as the excipient, decreased midpiece and head anomalies, only trans-resveratrol and ubiquinol had an effect on multiple anomalies. Furthermore, only trans-resveratrol had an effect upon tail anomalies. The imposed exercise caused alterations in CD-1 mice sperm morphology, and antioxidant treatment seems suitable to decrease morphological anomalies. Both trans- resveratrol and ubiquinol were effective in decreasing simple as well as multiple sperm anomalies.
... The number of patients included is higher compared to similar placebo-controlled studies of other antioxidants. 32,39,69,70 Astaxanthin group was homogenous because all patients accorded with WHO 2010 criteria for O+A+T. In the placebo group, two-thirds of patients also met the criteria for O+A+T; the average progressive motility of spermatozoa was just above the reference value (33.1 ± 14.7%), but the average total motility of spermatozoa was below the reference value. ...
Article
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Background Higher concentrations of seminal reactive oxygen species may be related to male infertility. Astaxanthin with high antioxidant activity can have an impact on the prevention and treatment of various health conditions, including cancer. However, efficacy studies on astaxanthin in patients with oligospermia with/without astheno- or teratozoospermia (O±A±T) have not yet been reported. Our aim was to evaluate the effect of the oral intake of astaxanthin on semen parameters. Patients and methods In a randomized double-blind trial, 80 men with O±A±T were allocated to intervention with 16 mg astaxanthin orally daily or placebo. At baseline and after three months basic semen parameters, sperm deoxyribonucleic acid (DNA) fragmentation and mitochondrial membrane potential (MMP) of spermatozoa and serum follicle-stimulating hormone (FSH) value were measured. Results Analysis of the results of 72 patients completing the study (37 in the study group, 35 in the placebo group) did not show any statistically significant change, in the astaxanthin group no improvements in the total number of spermatozoa, concentration of spermatozoa, total motility of spermatozoa, morphology of spermatozoa, DNA fragmentation and mitochondrial membrane potential of spermatozoa or serum FSH were determined. In the placebo group, statistically significant changes in the total number and concentration of spermatozoa were determined. Conclusions The oral intake of astaxanthin did not affect any semen parameters in patients with O±A±T.
... However, there are only three RCTs (one underpowered) and none demonstrated a significant effect on LBR (187)(188)(189). For men, there are five RCTs (190)(191)(192)(193)(194). A meta-analysis of three relevant trials concluded that coenzyme Q10 improved sperm parameters but this did not translate into improved LBR or PR (195). ...
Article
There is accumulating evidence demonstrating that positive lifestyle modification and the optimization of the preconceptual period can influence the reproductive potential for both men and women. However, a large percentage of couples attending fertility clinics with potential to improve preconception habits may not always receive appropriate preconceptual advice. Additionally, supplements and adjuncts that promise to increase fertility treatment success rates are marketed to infertile patients despite lack of convincing evidence supporting benefit. This review aims to identify possible associations between lifestyle factors for couples seeking fertility treatment and fertility treatment outcomes and to offer possible explanations of the biological basis of these associations. An electronic search was conducted from 1978 until July 2019 linking preconceptual behaviors for women and men with the outcome of fertility treatment. The literature search explored the importance of numerous factors including smoking, caffeine, alcohol, obesity, physical exercise, recreational drugs, stress, diet, supplements, alternative medicine, environmental factors and pollutants. Some associations were found to be more significant than others. The preconceptual period is undeniably a delicate and important window which should not be overlooked during fertility counseling. Simple lifestyle modifications could positively influence fertility treatment outcomes. Fertility teams, consisting of clinicians, fertility nurses, dieticians, psychologists, exercise advisors and others, should dedicate time to offer evidence-based preconceptual advice and targeted interventions to couples seeking fertility treatment.
... Moreover, the CoQ10 serum level of 2.8 μg/mL from 120 mg per day for three weeks was higher than 2.0 μgl/mL from the study of Safarinejad et al (13) , which used 300 mg per day for 26 weeks. The latter study demonstrated the significant improvement of sperm concentration and motility (13,22,23) . From all of these data, the solubilized form of CoQ10 at the dose 200 mg per day used in the present study for 30 days should be adequately effective to improve sperm motility as compared to the serum level of Bhagavan et al (14) and Safarinejad et al (13) . ...
Article
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Background: Pyospermia is a multifactorial disease. There is no ideal treatment, but the most promising treatment modalities are antibiotics and antioxidants. Objective: To evaluate the effects of coenzyme Q10 (CoQ10) on sperm motility of men with pyospermia treated with doxycycline. Materials and Methods: The present study, a double-blinded, randomized, placebo-controlled trial, enrolled 84 men who attended Siriraj Infertility Clinic, Faculty of Medicine Siriraj Hospital, Mahidol University with pyospermia on the initial semen analysis (SA) (T0). The participants were randomly assigned into two groups, group A received oral doxycycline 100 mg twice daily for 14 days plus oral CoQ10 200 mg per day for 30 days and group B received the same dose of doxycycline plus placebo for 30 days. The SA was repeated at 30±7 days (T1) and 60±7 days (T2) after initiating treatment. Results: Of 70 eligible participants, the age of the participants was around 36 years. None of them had symptomatic urethral infection or abnormal urological examination. There was no difference in body mass index, education level, and female infertility factors between groups (p>0.05 for all). Two-thirds of both groups became non-pyospermic after the treatment. There was no difference of total sperm motility between group A and group B (46%; 32% to 55% versus 43%; 33% to 50% at T1 and 46%; 32% to 57% versus 45%; 32% to 53% at T2, p>0.05 for all). Conclusion: A 30-day course of daily oral intake of 200 mg CoQ10 shows no additive benefit on total sperm motility in Thai men with pyospermia treated with doxycycline.
... Максимальное содержание его наблюдается в митохондриях сперматозоидов, обеспечивающих клеточное дыхание и энергию для движения клетки. Nadjarzadeh et al. указали, что на фоне поступления коэнзима Q10 не только улучшаются спермиологические параметры, но и повышается активность каталазы и супероксиддисмутазы [28]. Существует значительная отрицательная корреляция между уровнями коэнзима Q10 и перекиси водорода [29]. ...
Article
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Empirical therapy of male infertility is used as a stand-alone type of treatment in idiopathic infertility, and in other situations can complement basic therapy. There are well-known pathogenetic methods of male infertility treatment applied in case of reproductive gland infection, hypogonadotropic hypogonadism, ejaculation disorders. However, the prospects of empirical treatment of male infertility are not fully clear. Combined antioxidant drugs are very popular, which include a wide range of similar substances. However, their molecules significantly differ from each other in structure, chemical properties and set of biological functions, therefore, there is a number of questions that deserve separate discussion regarding their compatibility with each other. Antioxidants such as various water-soluble and fat-soluble vitamins, coenzyme Q10, zinc and carnitines are widely used in its composition to reduce sperm damage caused by oxidative stress. They are widely available and inexpensive compared to other methods of treatment. Although there are no results of large randomized controlled trials yet, there is some evidence that taking oral antioxidoidants improves the basic parameters of sperm and increases the frequency of childbirth. There are many antioxidant supplements in different dosage forms, with different compositions and modes of use. In this article, we have analyzed the effect of the main antioxidant substances used on semen parameters, the need for their combined use and the role of these substances in the body.
... OPs may induce toxicity to cells by their ability to upregulate ROS production and downregulate antioxidant enzymes [52,53]. Thus, CoQ 10 may play roles in ameliorating OP induced toxicity by acting as a free radical scavenger to mitigate DNA damage and lipid peroxidation from OP-induced oxidative stress, as well as elevating activities of antioxidant enzymes including OP detoxifying enzyme, paraxonase [29,54]. ...
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Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q10 (CoQ10) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ10 status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ10 status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ10 supplementation (5 μM) was able to restore cellular CoQ10 status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ10, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ10 supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ10 deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ10 supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ10 supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.
... Two studies (Balercia et al., 2009;Safarinejad, 2009) had analysed seminal level of CoQ10, but Nadjarzadeh et al., (2011) did not present this data; however, the authors presented these data in their later study on the same patients (Nadjarzadeh et al., 2014). Out of three, two studies reported a significant improvement in seminal plasma CoQ10 level (Balercia et al., 2009;Safarinejad, 2009), while the third reported no significant improvement (Nadjarzadeh et al., 2011 Figure 3 and Table 3). ...
Article
Coenzyme Q10 has shown promise in treating male infertility; however, there are inconsistencies across the published data. We undertook a quantitative meta‐analysis by pooling data from three placebo‐controlled randomised clinical trials (RCTs) in order to evaluate the efficacy of CoQ10 in improving semen parameters. Sperm count, sperm motility, sperm forward motility, sperm morphology and CoQ10 level in the seminal plasma were measured and quantitatively correlated with CoQ10 oral administration. Pooled analysis showed a significant impact of CoQ10 in improving sperm motility and forward motility, without a significant impact on sperm count, sperm morphology, ejaculate volume or seminal plasma level of CoQ10. Efficacy assessment suggested that CoQ10 shows better results at higher doses and when administered for a period of more than 3 months but not longer than 6 months. We conclude that CoQ10 has a profound effect on sperm motility and a meagre effect on all other parameters. Therefore, CoQ10 can be used for treating asthenozoospermic infertility with the dosage and duration depending upon the severity of the disorder and the patient's response to the treatment.
... Aynı zamanda Koenzim Q10 konsantrasyonu ile normal sperm morfolojisi ve sperm motilite oranlarında da anlamlı korelasyonlar tespit edilmiştir. [19] Koenzim Q10 tedavisinin değerlendirildiği 3 plasebo-kontrollü çalışmadan derlenen bir metaanalize göre, tedavinin sperm motilitesi ve semen konsantrasyonlarında anlamlı artışa neden olduğu ancak canlı doğum ve gebelik gelişimine bir etkisinin olmadığı belirlenmiştir. [20] Selenyum Selenyum, hücre zarını oksidatif hasardan koruyan ametal bir elementtir. ...
... Regarding CoQ10 supplementation, A. Mancini et al. (1994) and Nadjarzadeh et al. (2014) reported that CoQ10 levels increased in seminal plasma following supplementation, which attenuated oxidative stress and improved semen parameters. Results of a systematic review showed that despite CoQ10 improved seminal parameters such as sperm concentration and motility, it was not capable of increasing live birth or pregnancy rates (Lafuente et al., 2013). ...
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World population growth and aging are posing unprecedented challenges in sustaining the health of 9.1 billion people that will be occupying the planet by 2050. Although noncommunicable diseases such as cardiovascular and neurodegenerative diseases, cancer, and diabetes are among the top 10 global causes of death, they can be prevented by risk factor reduction, early detection, and adequate treatment. Since a healthy diet along with dietary supplementation could play an important role to reduce morbidity and cut off its associated health care costs, research in the food and nutrition area is required to find solutions to global challenges affecting health. As a result of the healthy living trend, dietary supplements category is growing fast, leading to an urgent need for dietitians, physicians, and policy makers to broaden the scientific evidence on the efficacy and safety of a wide range of active ingredients. Coenzyme Q10 (CoQ10), as the third most consumed dietary supplement, and as a potential candidate for the treatment of various noncommunicable diseases that are among the global top 10 causes of death, has gained interest over years. Scientific evidence regarding mainly CoQ10 efficacy and safety, as well as formulation challenges, is addressed in this review.
... Higher doses of CoQ10 (300 mg twice daily for 12 months) have also been reported to raise conventional sperm parameters and to have a beneficial effect on PR as well [75] (IIb). Accordingly, CoQ10 supplementation has been shown to increase seminal levels of catalase and SOD activity [76]. In contrast with these findings, a randomized, double-blind, placebocontrolled study on 47 infertile patients did not find any difference in conventional sperm parameters after a 12 week-long daily administration of CoQ10 (200 mg), though lower levels of plasma MDA and higher plasma antioxidant capacity were found compared to placebo group [77] (Ib). ...
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Oxidative stress (OS) has been recognized as an important cause of male infertility because it may damage sperm function and DNA integrity. Since antioxidants counteract the action of OS, these compounds are used in the medical treatment of male infertility. This chapter reviews the effects of the main antioxidants used in clinical practice. We used an evidence-based medicine criterion in the attempt to identify the molecules that have the highest clinical efficacy. Some antioxidants have been clearly shown to be effective by many well-conducted studies. These include vitamins C and E, carnitines and coenzyme Q10, which may be considered as a first line treatment. Other molecules, such as glutathione, zinc, lycopene and myoinositol, may be proposed as a second line treatment because their use is supported by a few, but well-designed studies. Lastly, the efficacy of other antioxidants, such as picnogenol, pentoxyfilline, etc., is not yet supported by a sufficient number of studies.
... The human body produces endogenous antioxidants in an effort to prevent the damage caused by ROS [91,92], but this response is not always adequate, resulting in OS. Several studies have shown that exogenous antioxi-dants have the capacity to counteract oxidative damage or OS, improving both sperm motility and DNA integrity for infertile men with OS (Table 3) [87][88][89][90][91][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111]. Indeed, many oral formulations of antioxidants are readily available in the market and are commonly used to treat men with infertility. ...
Article
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Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diag- nose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diag- nosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Chapter
Male infertility is linked to several environmental and mutagenic factors. Most of these factors, i.e., lifestyle, radiations, and chemical contaminations, work on the fundamental principles of physics, chemistry, and biology. Principally, it may induce oxidative stress (OS) and produce free radicals within the cells. The negative effect of OS may enhance the reactive oxygen species (ROS) levels in male reproductive organs and impair basic functions in a couple’s fertility. Evidence suggests that infertile men have significantly increased ROS levels and a reduced antioxidant capacity compared with fertile men. Although, basic spermatic function and fertilizing capacity depend on a delicate balance between physiological activity of ROS and antioxidants to protect from cellular oxidative injury in sperm, that is essential to achieve pregnancy. The ideal oxidation-reduction (REDOX) equilibrium requires a maintenance of a range of ROS concentrations and modulation of antioxidants. For this reason, the chapter focuses on the effects of ROS in sperm functions and the current concepts regarding the benefits of medical management in men with diminished fertility and amelioration of the effect to improve sperm function. Also, this evidence-based study suggests an increasing rate of infertility that poses a global challenge for human health, urging the need of health care professionals to offer a correct diagnosis, comprehension of the process, and an individualized management of the patients.KeywordsMale fertilityFertility impairmentSperm functionFree radicalsOxidative injury
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Background: Oxidative stress (OS) is associated with ferroptosis. Coenzyme Q10 (CoQ10), as an adjuvant treatment, has shown to be beneficial against OS. However, the efficacy of CoQ10 as a therapeutic agent against OS has not been promptly updated and systematically investigated. Methods: A systematic literature search was performed using the Medline, EMBASE, Web of science, Cochrane Central Register of Controlled Trials, CNKI, CBM, Science direct and clinical trial. gov to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. Results: Twenty-one randomized clinical studies met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation increased the levels of antioxidant enzymes [including superoxide dismutase (SOD) (SMD = 0.63; 95% CI: 0.38 to 0.88; p < 0.001), catalase (CAT) (SMD = 0.44; 95% CI:0.16 to 0.72; p = 0.002)] significantly and the levels of malondialdehyde (MDA) (SMD = -0.68; 95% CI: 0.93 to -0.43; p < 0.001) was decreased considerably. However, significant associations were not observed between this supplement and total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity. Conclusion: CoQ10 can improve OS as indicated by statistical significance in CAT and MDA concentrations, as well as SOD activity. Future studies focusing on long-term results and specific valuation of OS parameters are required to confirm the efficacy of CoQ10 on OS. We also believe that with the further research on ferroptosis, CoQ10 will gain more attention. Systematic Review Registration: [ https://inplasy.com/ ], identifier [INPLASY2021120123].
Article
Background: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. Objectives: To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. Search methods: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, and two trial registers were searched on 15 February 2021, together with reference checking and contact with experts in the field to identify additional trials. Selection criteria: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included men with idiopathic infertility and normal semen parameters or fertile men attending a fertility clinic because of female partner infertility. Data collection and analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes. Main results: We included 90 studies with a total population of 10,303 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing medically assisted reproduction (MAR). Investigators compared and combined 20 different oral antioxidants. The evidence was of 'low' to 'very low' certainty: the main limitation was that out of the 67 included studies in the meta-analysis only 20 studies reported clinical pregnancy, and of those 12 reported on live birth. The evidence is current up to February 2021. Live birth: antioxidants may lead to increased live birth rates (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.07 to 1.91, P = 0.02, 12 RCTs, 1283 men, I2 = 44%, very low-certainty evidence). Results in the studies contributing to the analysis of live birth rate suggest that if the baseline chance of live birth following placebo or no treatment is assumed to be 16%, the chance following the use of antioxidants is estimated to be between 17% and 27%. However, this result was based on only 246 live births from 1283 couples in 12 small or medium-sized studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.22, 95% CI 0.85 to 1.75, 827 men, 8 RCTs, P = 0.27, I2 = 32%). Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, P < 0.00001, 20 RCTs, 1706 men, I2 = 3%, low-certainty evidence) compared with placebo or no treatment. This suggests that, in the studies contributing to the analysis of clinical pregnancy, if the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 15%, the chance following the use of antioxidants is estimated to be between 20% and 30%. This result was based on 327 clinical pregnancies from 1706 couples in 20 small studies. Adverse events Miscarriage: only six studies reported on this outcome and the event rate was very low. No evidence of a difference in miscarriage rate was found between the antioxidant and placebo or no treatment group (OR 1.46, 95% CI 0.75 to 2.83, P = 0.27, 6 RCTs, 664 men, I2 = 35%, very low-certainty evidence). The findings suggest that in a population of subfertile couples, with male factor infertility, with an expected miscarriage rate of 5%, the risk of miscarriage following the use of an antioxidant would be between 4% and 13%. Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal discomfort when compared with placebo or no treatment (OR 2.70, 95% CI 1.46 to 4.99, P = 0.002, 16 RCTs, 1355 men, I2 = 40%, low-certainty evidence). This suggests that if the chance of gastrointestinal discomfort following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 7%. However, this result was based on a low event rate of 46 out of 1355 men in 16 small or medium-sized studies, and the certainty of the evidence was rated low and heterogeneity was high. We were unable to draw conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. Authors' conclusions: In this review, there is very low-certainty evidence from 12 small or medium-sized randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-certainty evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal discomfort, based on very low-certainty evidence. Subfertile couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials studying infertile men and reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.
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The purpose of this experiment was to explore whether coenzyme Q10 (CoQ10) improves the quality of sheep semen stored at room temperature by attenuating oxidative stress. Semen was diluted without (control group), and with antioxidants (5, 50, 250, and 500 μmol/L CoQ10). Sperm kinetic parameters and plasma membrane integrity were determined, and the reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), total antioxidant capacity (TAOC), catalase (CAT), and superoxide dismutase (SOD) activity were evaluated on the fifth day of semen preservation. The results showed that compared with the control group, the progressive motility in the 50 μmol/L group was higher (p < 0.05) within 2–5 days, and the plasma membrane integrity of sperm was higher in the 50 μmol/L group. The ROS content in the 5 and 50 μmol/L groups was reduced. The MDA level was reduced in the CoQ10 supplementation groups (p < 0.05). Additionally, the CAT, SOD, TAOC, ATP and MMP levels in the 50 μmol/L group were higher than those in the control group (p < 0.05). In conclusion, CoQ10 improved the quality of ram semen by alleviating oxidative stress, and 50 μmol/L CoQ10 was the optimum concentration.
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Oxidative stress owing to an imbalance between reactive oxygen species and antioxidants, such as coenzyme Q10 (CoQ10), is a major contributor to male infertility. We investigated the effects of the reduced form of CoQ10 (ubiquinol) supplementation on semen quality in dogs with poor semen quality. Three dogs received 100 mg of ubiquinol orally once daily for 12 weeks. Semen quality, serum testosterone, and seminal plasma superoxide dismutase (SOD) activity were examined at 2-week intervals from 2 weeks before ubiquinol supplementation to 4 weeks after the treatment. Ubiquinol improved sperm motility, reduced morphologically abnormal sperm, and increased seminal plasma SOD activity; however, it had no effect on testosterone level, semen volume, and sperm number. Ubiquinol supplementation could be used as a non-endocrine therapy for infertile dogs.
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It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.
Article
Although coenzyme Q10 (CoQ10) serves as an antioxidant and energy source for spermatozoa when added to stallion semen before cooling or freezing, the effects of feeding CoQ10 on semen quality have not been studied. We assessed the effects of daily oral ingestion of CoQ10-ubiquinol by stallions on their plasma CoQ10 concentrations and semen quality. Seven mature Andalusian stallions ate 1g ubiquinol/day for 4 weeks followed by a 4-week washout period. Four horses initially completed an additional 4-week control period without ubiquinol. Blood was sampled weekly for determination of plasma CoQ10 concentrations. Ejaculates were collected every two weeks and assessed for total motility (TM), progressive motility (PM), and viability (V) after cooling for 24hours (T1), immediate cryopreservation (T2), and cryopreservation after 24hours cooling (T3). Ingesting ubiquinol resulted in an increase in plasma CoQ10 concentration (P < .001). Two weeks of CoQ10-ubiquinol resulted in improved V with all treatments (T1: P = .007; T2: P = .05; T3: P = .01) and PM with T3 (P = .04). In five stallions, TM and PM were also improved for T1 (P = .01 and P = .02, respectively) and TM increased with T2 (P = .03). Overall, semen quality parameters increased within the first 2 weeks of supplementation, plateaued at the end of the 4-week supplementation period and persisted after discontinuing ubiquinol until the end of the sampling period (8 weeks). Feeding 1 g CoQ10-ubiquinol for 4 weeks to breeding stallions improved semen quality after cooling and freezing in 5 of 7 stallions. This could be important for improving reproductive efficiency in stallions.
Article
One of the major causes of defective sperm function is oxidative stress, which limits the fertilizing potential of these cells as the result of collateral damage to proteins and lipids in the sperm plasma membrane. On this point, a derangement of both generation and neutralization of reactive oxygen species (ROS) is a recognized cause of male infertility. Antioxidant protection in sperm has been widely investigated, as well as the sperm composition of fatty acids (FA), which represents the preferred substrate for ROS, most frequently linked to the disease-related infertility. Isoprostanes are compounds derived from free radical-mediated oxidation of FAs. As such, they are considered an index of lipid oxidative damage and lipid mediators. This article discusses the role of isoprostanes as relevant factors both to sperm FA composition and sperm membrane integrity. Additionally, isoprostane’s influence on sperm quality is reviewed. With reference to male reproductive dysfunction, increasing evidence indicates isoprostanes, detectable in biological fluids or sperm membrane, as the specific index of 1) exposure to chemical etiological agents, 2) oxidative damage, 3) reduced antioxidant response, and 4) sperm immaturity. Abbreviations OS: oxidative stress; ROS: reactive oxygen species; PUFAs: polyunsaturated fatty acids; ARA: arachidonic acid, F2-IsoPs; F2-isoprostanes, PLA2: phospholipase A2; NADPH: nicotinamide adenine dinucleotide phosphate; IVF: in vitro fertilization
Chapter
Coenzyme Q10 (CoQ10) intake and supplementation has been directly and indirectly associated with physiological function relative to exercise, aging and reproduction. This chapter describes several significant aspects regarding biochemical properties and mechanism of action of CoQ10 in male and female fertility and reproduction. This effect is mainly through its action as an antioxidant, protecting against oxidative stress by controlling the levels of reactive oxygen species (ROS) associated with reproductive pathologies. Although some studies support the evidence of use of CoQ10 to improve fertility, the available literature is contradictory and conflicting due to lack of standardization regarding type, dosage and time frame of treatment with CoQ10 as well as the bio-specimen, the exercise protocol employed and the assays used to analyze these specimens. However, CoQ10 supplementation seems to be able to improve both male and female gamete physiology, conception and embryo development and pregnancy success, something that may be related to the protecting effect against ROS-related fertility issues. It seems it may, as well, attenuate somewhat the negative impact of age on fertility, though discontinuation of treatment will result in cessation or diminution of such effect.
Chapter
Male and Sperm Factors that Maximize IVF Success - edited by John Aitken April 2020
Article
Oxidative stress is caused by an imbalance between ROS and antioxidants, which plays a significant role in the pathophysiology of many human diseases. There is extensive evidence highlighting the role of oxidative stress in male infertility due to elevated levels of sperm DNA fragmentation and abnormal semen parameters. The use of antioxidants is a potential therapeutic option to reduce ROS and improve semen quality. The appeal is that antioxidants can be easily obtained over the counter and are considered all‐natural and therefore healthy. The hypothesis has been that by decreasing oxidative stress, antioxidants may be used for the treatment of male infertility. While initial studies of antioxidant supplementation suggested a beneficial role in the management of male subfertility, additional research has questioned the benefit of these therapies. The focus of this article is to present recent evidence assessing the viability of antioxidant therapy in the treatment of male infertility.
Chapter
Background: Male factor infertility can be caused by reasons either related or not with total sperm production. The most common cause of male infertility in the first case is idiopathic oligoasthenozoospermia and has been associated with systemic oxidative stress impairing spermatogenesis and reducing the probability of natural reproduction. Additionally, infertility cases where classic seminal parameters are normal are often considered purely idiopathic and affect assisted reproductive technology (ART) results. The most relevant subjacent cause is oxidative stress (OS). Several approaches have been studied to improve OS status in sperm and reproductive outcome. Objectives: To provide the most updated information, global view and interpretation of the relevance and efficacy of antioxidant use in ART, cementing its role in improving intracytoplasmic sperm injection (ICSI) results. Outcomes: There is an important lack of high quality, randomized, placebo-controlled clinical trials for antioxidant therapies in men undergoing ICSI. Although a variety of antioxidant types, doses and combinations have been studied for their effect on classic sperm parameters, generally improving them, only some of those included the measurement of oxidative stress biomarkers in sperm and very few of them included pregnancy as an endpoint of the study. Wider implications: Cumulative evidence points out that oral antioxidant supplementation alleviates the problems that oxidative stress causes in spermatogenesis and sperm quality, although whether or not, and how much this improvement can influence reproductive chances and live birth rates after ICSI is still a controversial issue. Further well-designed clinical research is needed to generate stronger evidence.
Chapter
The etiology of male infertility can often be identified as either genetic, endocrine, or anatomic, and appropriately targeted therapy or alternative conception treatment options can be provided. Idiopathic male infertility is the diagnosis given to patients when no identifiable male infertility factor is found but abnormalities are still present on semen analysis, and this condition is found in 30–40% of all infertile males.
Chapter
Oxidative stress has an integral role in the pathophysiology of most human diseases. With a rapidly aging population, increased attention and study have been directed toward the use of antioxidant therapy. The appeal is that these agents are considered “natural” substances and are associated with a healthy diet. The hypothesis has been that decreasing oxidative stress may prevent disease processes such as cancer or coronary heart disease. Since much of the general population are relatively healthy patients, it is critically important that these supplements are free of toxicity and side effects. While initial studies of antioxidant supplementation suggested a beneficial role in disease prevention, more recent clinical trials and a meta-analysis have questioned the benefit of these therapies. Several studies have suggested that excess supplementation may in fact be harmful. Recent attention has also focused on the use of antioxidants for the treatment of male infertility. The focus of this chapter is the potentially harmful effects of antioxidant therapy.
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Background: Sperm cells extracted from testes (TESE) have poor chromatin quality and motility. Various substances are used in the laboratory to increase sperm motility and improve the ART outcomes; however, there are few research which considered improving both sperm motility and chromatin quality. Objective: The aim of this investigation was to evaluate the improvement of the testicular sperm motility and chromatin quality exposed to L-carnitine (LC) and L-acetyl-carnitine (LAC), which are normally concentrated in testis and epididymis, compared with Pentoxifylline (PF), which used for sperm motility enhancement in IVF procedures. Materials and Methods: TESE samples from 30 male mice divided into four parts. The sperm samples were added to Ham' F10 (control) or the media contained 1.76mM of LC, LAC or PF), then, the samples were kept in the room temperature for 30, 90 and 180 min. At each time step, sperm motility and chromatin quality were assessed. Chromatin quality was evaluated by chromomycin A3 and aniline blue. Statistical analysis was performed using one way analysis of variance (ANOVA). A p-value less than 0.05 were accepted as a statistically significant difference. Results: The results showed LC, LAC and PF significantly increased the sperm motility. However, sperm chromatin quality only improved significantly by administration of LC and LAC. Conclusion: Administration of LC and LAC to the testicular sperm samples can lead to improve both sperm motility and chromatin quality. It may be because they can mimic in vivo sperm condition during late spermatogenesis.
Article
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There is growing evidence that damage to spermatozoa by reactive oxygen species play a key role in male infertility. The aim of this study was to assess seminal plasma free 8-Isoprostane levels in men with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia compared to normozoospermic males and its correlation with seminal parameters. The case group consisted of men with asthenozoospermia (n=15), asthenoteratozoospermia (n=16) and oligoasthenoteratozoospermia (n=15). The control group consisted of 16 males with normozoospermia. After Purification of Free 8-Isoprostane by affinity column, its concentration was measured by enzyme immunoassay method. Free 8-Isoprostane evaluation showed significantly greater values in the total case group (n=46) versus control group (18.23±3.56 vs 2.6±0.38 ng/ml). In each case group free 8-Isoprostane also showed a significant increasing compared to normozoospermic males. Free 8-Isoprostane showed an inversely significant correlation with sperm motility and sperm morphology. Lipid peroxidation could have significant role in etiology of sperm abnormalities. Measurement of 8-Isoprostane can be used as a specific biomarker for assessing lipid peoxidation in sperm.
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Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations. We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation. Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation. Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010). Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.
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8-Isoprostane is a potential in vivo marker for oxidant burden, but its usefulness in induced sputum of smokers and chronic obstructive pulmonary disease (COPD) has not been investigated. The current study investigated 58 subjects comprising 11 never-smokers, 11 ex-smokers, 13 healthy current smokers and 23 COPD with stage 0-III disease (according to the Global Initiative for Chronic Obstructive Lung Disease criteria). 8-Isoprostane was determined from induced sputum by enzyme immunoassay. Sputum 8-isoprostane levels were similar in the never-smokers and ex-smokers, but were elevated in the healthy smokers compared with nonsmokers, and in those with stage I-III COPD. Sputum 8-isoprostane levels could not differentiate nonsymptomatic smokers from those with Stage 0 COPD. There was a correlation between sputum 8-isoprostane level and lung function parameters (forced expiratory volume in one second/forced vital capacity and sputum neutrophils. In conclusion, sputum 8-isoprostane levels correlate with the severity of chronic obstructive pulmonary disease. However, they do not appear to differentiate healthy smokers from those who are at risk of developing chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease stage 0).
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Our objective was to review all published trials of coenzyme Q10 for hypertension, assess overall efficacy and consistency of therapeutic action and side effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study and eight open label studies. In the randomized controlled trials (n=120), systolic blood pressure in the treatment group was 167.7 (95% confidence interval, CI: 163.7-171.1) mm Hg before, and 151.1 (147.1-155.1) mm Hg after treatment, a decrease of 16.6 (12.6-20.6, P<0.001) mm Hg, with no significant change in the placebo group. Diastolic blood pressure in the treatment group was 103 (101-105) mm Hg before, and 94.8 (92.8-96.8) mm Hg after treatment, a decrease of 8.2 (6.2-10.2, P<0.001) mm Hg, with no significant change in the placebo group. In the crossover study (n=18), systolic blood pressure decreased by 11 mm Hg and diastolic blood pressure by 8 mm Hg (P<0.001) with no significant change with placebo. In the open label studies (n=214), mean systolic blood pressure was 162 (158.4-165.7) mm Hg before, and 148.6 (145-152.2) mm Hg after treatment, a decrease of 13.5 (9.8-17.1, P<0.001) mm Hg. Mean diastolic blood pressure was 97.1 (95.2-99.1) mm Hg before, and 86.8 (84.9-88.8) mm Hg after treatment, a decrease of 10.3 (8.4-12.3, P<0.001) mm Hg. We conclude that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects.
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Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.
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To evaluate the effectiveness of coenzyme Q(10) treatment in improving semen quality in men with idiopathic infertility. Placebo-controlled, double-blind randomized trial. Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy. Sixty infertile patients (27-39 years of age) with the following baseline sperm selection criteria: concentration >20 x 10(6)/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study. Patients underwent double-blind therapy with coenzyme Q(10), 200 mg/day, or placebo; the study design was 1 month of run-in, 6 months of therapy or placebo, and 3 months of follow-up. Variations in semen parameters used for patient selection and variations of coenzyme Q(10) and ubiquinol concentrations in seminal plasma and spermatozoa. Coenzyme Q(10) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, baseline and after treatment, of seminal plasma or intracellular coenzyme Q(10) and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q(10) had a statistically significant higher probability to be responders to the treatment. The exogenous administration of coenzyme Q(10) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.
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Studies of the kinetics of the proton- or hydrogen-transfer reactions concerning vitamin E in solutions and in micellar dispersions by means of stopped-flow and absorption spectroscopy indicated that proton tunneling plays an important role in the antioxidant and regeneration reactions that are advantageous in vivo but not as a part of the harmful prooxidant action.
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In a randomized, placebo-controlled, double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men. Ejaculate parameters included semen volume, sperm concentration and motility, and sperm count and viability. Thirty-one patients without genital infection but with asthenozoospermia (<50% motile spermatozoa) and normal or only moderately reduced sperm concentration (>7×106 spermatozoa/ml) (according to WHO criteria) were examined. To investigate the influence of the epididymal storage period on semen parameters, the patients were asked to deliver two semen samples with abstinence times of 2 and 7 days both before and at the end of vitamin treatment. After randomization, the patients received either 1000 mg vitamin C and 800 mg vitamin E (n = 15) or identical placebo capsules (n = 16). No changes in semen parameters were observed during treatment, and no pregnancies were initiated during the treatment period. Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate. Prolonged abstinence time increased ejaculate volume (P < 0.05), sperm count (P < 0.05), sperm concentration (P < 0.05) and the total number of motile spermatozoa (P < 0.05).
Article
Context Oxidative stress may play a role in the development or exacerbation of many common diseases. However, results of prospective controlled trials of the effects of antioxidants such as vitamin E are contradictory.Objective To assess the effects of supplemental vitamin E on lipid peroxidation in vivo in healthy adults.Design Randomized, double-blind, placebo-controlled trial conducted March 1999 to June 2000.Setting A general clinical research center in a tertiary referral academic medical center.Participants Thirty healthy men and women aged 18 to 60 years.Interventions Participants were randomly assigned to receive placebo or α-tocopherol dosages of 200, 400, 800, 1200, or 2000 IU/d for 8 weeks (n = 5 in each group), followed by an 8-week washout period.Main Outcome Measures Three indices of lipid peroxidation, urinary 4-hydroxynonenal (4-HNE) and 2 isoprostanes, iPF2α-III and iPF2α-VI, measured by gas chromatography/mass spectrometry and compared among the 6 groups at baseline, 2, 4, 6, and 8 weeks, and 1, 3, and 8 weeks after discontinuation.Results Circulating vitamin E levels increased in a dose-dependent manner during the study. No significant effect of vitamin E on levels of urinary 4-HNE or either isoprostane was observed. Mean (SEM) baseline vs week 8 levels of iPF2α-III were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects taking placebo; 165 (19.6) vs 234 (30.1) pg/mg for those taking 200 IU/d of vitamin E; and 195 (26.7) vs 213 (40.6) pg/mg for subjects taking 2000 IU/d. Corresponding iPF2α-VI levels were 1.43 (0.6) vs 1.62 (0.4) ng/mg of creatinine for subjects taking placebo; 1.64 (0.3) vs 1.24 (0.8) ng/mg for those taking 200 IU/d of vitamin E; and 1.83 (0.3) vs 1.94 (0.9) ng/mg for those taking 2000 IU/d. Baseline vs week 8 levels of 4-HNE were 0.5 (0.04) vs 0.4 (0.05) ng/mg of creatinine for subjects taking placebo; 0.4 (0.06) vs 0.5 (0.02) ng/mg with 200 IU/d of vitamin E; and 0.2 (0.02) vs 0.2 (0.1) ng/mg with 2000 IU/d.Conclusions Our results question the rationale for vitamin E supplementation in healthy individuals. Specific quantitative indices of oxidative stress in vivo should be considered as entry criteria and for dose selection in clinical trials of antioxidant drugs and vitamins in human disease.
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The purpose of this study was to investigate the effect of coenzyme Q10 supplementation on oxidative stress and antioxidant enzyme activity in patients with coronary artery disease (CAD). This was an intervention study. Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery or receiving percutaneous transluminal coronary angioplasty (n = 51) were randomly assigned to the placebo group (n = 14) or one of the two coenzyme Q10-supplemented groups (60 mg/d, n = 19 [Q10-60 group]; 150 mg/d, n = 18 [Q10-150 group]). Intervention was administered for 12 wk. Patients' blood samples were analyzed every 4 wk for plasma coenzyme Q10 concentrations, malondialdehyde (MDA), and antioxidant enzyme (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase) activity. Forty-three subjects with CAD completed intervention study. Plasma coenzyme Q10 concentration increased significantly after coenzyme the Q10-150 intervention (P < 0.01). The MDA levels were significantly lower than baseline in the Q10-150 group at week 4 (P = 0.03). The Q10-150 group had significantly lower MDA levels than the placebo group at week 8 (P = 0.03). With respect to antioxidant enzyme activity, subjects in the Q10-150 group had significantly higher CAT (P = 0.03) and SOD (P = 0.03) activity than the placebo group at week 12. The plasma coenzyme Q10 concentration was significantly correlated with MDA levels (r = -0.35, P = 0.02) and CAT (r = 0.43, P = 0.01) and SOD activity (r = 0.39, P = 0.01). The ratio of plasma coenzyme Q10 to total cholesterol was significantly correlated with SOD activity (r = 0.39, P = 0.02). The ratio of plasma coenzyme Q10 to low-density lipoprotein was significantly correlated with CAT (r = 0.35, P = 0.04) and SOD (r = 0.45, P = 0.01) activity. H