ArticleLiterature Review

The Role of Nutraceuticals in Male Fertility

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Abstract

Nutraceuticals are food products that that can provide medical or health benefits by preventing or treating disease processes. The high costs associated with assisted reproductive techniques for male infertility have led consumers to find less expensive alternatives for potential treatment. Nutraceuticals are widely available and have many antioxidant properties. This articles reviews the current English literature regarding readily available nutraceuticals and their potential effects on male infertility and potential side effects with excess intake.

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... Los suplementos dietarios impactan no sólo la salud física del individuo, recientemente se ha descrito que pueden mejorar la capacidad fértil, especialmente aquellos productos a base de preparaciones herbales, frutas y vegetales que contienen altas propiedades antioxidantes. (1) El 18,8 % de los norteamericanos reportan usar preparados herbales o productos naturales para tratar sus problemas de salud donde se incluyen los suplementos dietarios. Cada vez es más frecuente el consumo de éstos suplementos para tratar los problemas asociados a la fertilidad aunque no se ha demostrado que potencien un incremento en la tasa de concepción. ...
... Este fenómeno puede ser atribuido a infecciones, inflamaciones, traumas, tabaquismo, agentes industriales, ejercicio extenuante e incremento de la temperatura en la zona pélvica por el uso de bañeras de hidromasaje, baños frecuentes en el turco o sauna y uso del portátil. (1) Los efectos directos sobre la calidad seminal del estrés oxidativo se reflejan en disminuciones en la concentración, la movilidad, la viabilidad, la integridad del ADN espermático e incluso en eventos de suma importancia a nivel reproductivo, como la capacitación espermática y la capacidad de interacción con el oocito. (1,15) Por tanto, es posible sugerir que el uso de suplementos dietarios que disminuyan los daños causados por el estrés oxidativo en la calidad seminal constituye un tratamiento adecuado para tratar los problemas de infertilidad. ...
... (1) Los efectos directos sobre la calidad seminal del estrés oxidativo se reflejan en disminuciones en la concentración, la movilidad, la viabilidad, la integridad del ADN espermático e incluso en eventos de suma importancia a nivel reproductivo, como la capacitación espermática y la capacidad de interacción con el oocito. (1,15) Por tanto, es posible sugerir que el uso de suplementos dietarios que disminuyan los daños causados por el estrés oxidativo en la calidad seminal constituye un tratamiento adecuado para tratar los problemas de infertilidad. (1,2) Los reportes sobre este tema contribuirán a implementar estrategias de bajo costo que ayuden a muchas parejas a alcanzar el éxito reproductivo en aquellos casos donde la infertilidad se asocia al estrés oxidativo, por lo que el objetivo de la presentación de este caso es determinar el efecto del consumo de antioxidantes sobre la calidad seminal. ...
Article
Los suplementos dietarios tales como vitaminas, minerales y antioxidantes mejoran la ingesta de nutrientes. Recientemente se ha descrito que, especialmente aquellos que contienen altas propiedades antioxidantes también mejoran la capacidad fértil. Se presenta el caso de un voluntario de 37 años con posible infertilidad masculina y se desea determinar el efecto del consumo de antioxidantes sobre la calidad seminal. Se realizó evaluación de los parámetros seminales convencionales y funcionales antes y después del uso del suplemento dietario Male Fertility. Se observó que el uso del suplemento dietario incrementó la concentración espermática, el potencial de membrana mitocondrial alto y la capacidad antioxidante del semen; además disminuyó la producción de 1as reactivas de oxígeno, la lipoperoxidación y la fragmentación de la cromática espermática. El suplemento dietario Male Fertility contiene altas concentraciones de vitamina A, C, E, B2, B3, B12, folato, zinc, selenio, acetil L-carnitina, coenzima Q10, L-metionina y licopeno. Se ha descrito que la ingesta de cada uno de estos compuestos tiene efectos positivos sobre la calidad seminal. El reporte de este caso permitió observar que el uso de suplementos dietarios ricos en vitaminas y antioxidantes puede mejorar la calidad seminal a través de la disminución del efecto adverso de las especies reactivas del oxígeno y por el incremento de las moléculas antioxidantes en el plasma seminal.
... Thin Layer Chromatography (TLC). TLC is simple and cheap and it can be used for preliminary identification of known PDE-5I for which the reference standards are available (Patel et al., 2014 (Halsted, 2003) pKa 2 = 3.5 pKa 2 = 6.21 (Hlasney, 2010) pKa 3 = 5.9 (Bailey et al., 2011) Log P 1.65 (Ko & Sabanegh 2014) 1.33 (Fleshner et al., 2005) 1.64 (Regan et al., 2011) Polar surface area 109.13 (Ko & Sabanegh, 2014) 118 (Hlasney, 2010) 74.9 (Regan et al., 2011) Doses available (mg) 25, 50, 100 2.5, 5, 10, 20 5, 10, 20 ...
... Thin Layer Chromatography (TLC). TLC is simple and cheap and it can be used for preliminary identification of known PDE-5I for which the reference standards are available (Patel et al., 2014 (Halsted, 2003) pKa 2 = 3.5 pKa 2 = 6.21 (Hlasney, 2010) pKa 3 = 5.9 (Bailey et al., 2011) Log P 1.65 (Ko & Sabanegh 2014) 1.33 (Fleshner et al., 2005) 1.64 (Regan et al., 2011) Polar surface area 109.13 (Ko & Sabanegh, 2014) 118 (Hlasney, 2010) 74.9 (Regan et al., 2011) Doses available (mg) 25, 50, 100 2.5, 5, 10, 20 5, 10, 20 ...
... 16-45 (Carson, 2004) Duration (hr.) 4 (Bailey et al., 2011;Halsted, 2003) 4 (Hlasney, 2010) 36 (Bailey et al., 2011;Halsted, 2003) Metabolism CYP3A4 (Ko & Sabanegh, 2014) CYP3A4 (Hlasney, 2010) CYP3A4 (Regan et al., 2011) Active metabolites ...
Article
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Erectile dysfunction prevalence globally is noticeably high. This is accompanied by an increase in the use of nutraceuticals for male enhancement. However, the global market is invaded by counterfeit and adulterated nutraceuticals claimed to be of natural origin sold with a therapeutic claim. The objective of this article is to review male enhancement nutraceuticals worldwide with respect to claim, adulterants, and safety. The definition of such products is variable across countries. Thus, the registration procedures differ as well. This facilitates the manipulation of the process, which leads to widespread adulterated and counterfeit products without control. The tele-advertisement and Internet pharmacies aided the widespread sale of male enhancement nutraceuticals, unfortunately, the spurious ones. Finally, based on literature, most of these products were found to be adulterated with active pharmaceutical ingredients (API) and mislabeled as being natural. These products represent a major health hazard for consumers due to lack of clear regulations.
... Imbalance between increased reactive oxygen species (ROS) production and decreased antioxidant capacity (oxidative stress) in the male reproductive tract contribute to the infertility and can cause a defect in sperm function. Oxidative stress in the testes or semen can be attributed to infection, inflammation, smoking, industrial exposure, chemotherapy, drugs, and varicocele, as well as leukocytes, which are primary producers of endogenous oxidants in semen [1][2][3][4]. ...
... Over the last years, intensive research has been focused on various antioxidants and their optimal doses and combinations, for more effective and safe treatment of human fertility disturbances [20]. Improvement of sperm parameters after antioxidant therapy of infertile men (with vitamin E, vitamin C, N-acetyl-L-cysteine, carnitine, or CoQ 10 ) may result in higher pregnancy rates [2,24]. Vitamin E as an antioxidant may directly quench free radicals and together with CoQ 10 protect lipid membranes from peroxidative damage [24]. ...
... Vitamin E is able to reduce seminal ROS levels in men with infertility. Combined therapy with vitamin C resulted in improvement of DNA fragmentation yet excessive intake of nutraceuticals can have also negative consequences [2]. ...
Article
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Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme , γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, , and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.
... The North American Veterinary Nutraceutical Council defined nutraceuticals in veterinary medicine as 'substances produced in a purified or extracted form and administered orally to patients to provide agents for normal body structure and function and administered with the intent of improving the health and well-being of animals'. Recently, nutraceuticals have become remarkably popular in both human and veterinary medicine and substances of vegetable origin, minerals and vitamins are available on the market for the management of male infertility (Freitas & De Oliveira, 2018;Ko & Sabanegh, 2014). ...
... Medicinal plants have been used in traditional medicine since ancient times for the management of different diseases including reproductive disorders (Williams & Lamprecht, 2008). Nutraceuticals including herbs, fruits, vegetables and vitamins have been sponsored to ameliorate several aspects of male fertility, including sperm quality, erectile function, and libido (Crimmel et al., 2001;Ko & Sabanegh, 2014). ...
Article
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Nutritional supplements are widely used in the equine industry with the aim of improving horse health, sports or reproductive performances. Over the years, a number of studies have focused on investigating the effects of several dietary compounds on the quality and preservation of stallion semen. This paper reviews the literature available on the use of nutritional supplementation for the improvement of reproductive performance and semen quality in equine species, critically appraising the benefits and negative effects of several compounds found in complementary feeds such as PUFAs from different sources, vitamins and antioxidants, carnitine ad botanical extracts. Different nutraceuticals have been highlighted to improve stallion fertility by providing optimal levels of antioxidants, with the most promising results obtained by the combination of PUFAs and antioxidants that resulted to be essential for the maintenance of normal reproductive functions and the reduction of cryodamage in cooled and frozen equine semen.
... Additionally, recent reports have suggested anti-apoptotic, anti-inflammatory, and gene modulation effects for CoQ10, which could explain the use of CoQ10 for the treatment of other diseases such as ischemic heart diseases, Parkinson's disease, diabetes mellitus, and malignant tumors in addition to infertility [36,38,39]. We [12,35,40] and others [41][42][43] have also detected higher SDF in men with IMI, and these levels were ameliorated by CoQ10 therapy. These findings augment the role of CoQ10 as a gene modulator. ...
Article
Objective: Oxidative stress is a key player in the development of idiopathic male infertility (IMI), and various antioxidants have been used for the treatment of IMI with inconsistent results. Coenzyme Q10 (CoQ10) is a cofactor and an antioxidant that may improve semen parameters and reduce oxidative stress in patients with idiopathic oligoasthenospermia (OA). Therefore, this study aimed to explore the effect of CoQ10 on semen parameters and antioxidant markers in patients with idiopathic OA. Methods: Fifty patients with idiopathic OA and 35 fertile controls were enrolled in this prospective controlled study. All participants underwent a comprehensive fertility assessment. All patients received CoQ10 (300 mg/day) orally once daily for 3 months. Semen parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in patients and controls at the start of the study and after 3 months. Results: Treatment with CoQ10 resulted in increased sperm progressive motility (p<0.05), total motility (p<0.01), seminal TAC (p<0.01), SOD (p<0.05), GPx (p<0.001), and seminal CoQ10 (p<0.001) levels and reduced ROS (p<0.01) in patients as compared to baseline. Sperm concentration and motility were also significantly correlated with antioxidant measures and seminal CoQ10 levels (r=0.38-0.57). Conclusion: CoQ10 therapy (300 mg/day for 3 months) improved sperm motility and seminal antioxidant markers in patients with idiopathic OA. Therefore, CoQ10 could be a promising treatment for patients with idiopathic infertility and may improve their fertility potential.
... Harmless consequences of oral antioxidant at or below the recommended daily doses makes antioxidant supplementation a reasonable treatment regimen before continuing with more invasive and expensive managements such as in vitro fertilization or Intracytoplasmic sperm injection. 17 In this research, we have inspected the effectof a combination of L-Carnitine tartrate, Zinc, Maca Root, Asian Ginseng Lots of Antioxidants Vitamin C, E, Beta Carotene, and Selenium plus CoQ10, B12 as pharmacological treatment boosting semen parameters of cases with IOAT. ...
Article
Full-text available
Background: Fertil Aid for Men is a non-prescription dietary supplement, it's a mixture of multiple antioxidants, vitamins, a blend of herbal ingredients, and amino acid, as L-Carnitine. This research aims to appraise the effectiveness of a mixture of vitamins and antioxidants on seminal fluid parameters in males with idiopathic infertility.
... Since CoQ10 is synthesized in the body, the amount to be taken with the diet is not clear. However, the optimal amount of intake has been determined as 200-300 g per day (87). In addition, it has been reported that plasma samples of adolescent PCOS patients have lower amounts of Gamma-Tocopherol and higher amounts of CoQ9, a product of deficient CoQ10 biosynthesis (88). ...
Article
Koenzim Q10 (CoQ10), benzokinonlardan elde edilen lipitte çözünür bir bileşendir. Koenzim Q10’un oksitlenmiş formu ubiquinonedir ve indirgenmiş formu ubiquinoldür. Koenzim Q10, endojen sentezinin yanı sıra diyete de dâhildir. CoQ10’un diyet kaynakları et, kümes hayvanları, balık, yağ ve fındıktır. Koenzim Q10 in mitokondride enerji metabolizmasında önemli görevleri bulunmaktadır. Ayrıca membrandaki oksidatif hasardan fosfolipitleri, proteinleri ve DNA’yı korur. CoQ10’un antioksidan kapasitesi nedeniyle hastalıklar üzerinde birçok olumlu etkisi olduğu belirtilmektedir. Son yıllarda CoQ10 alımı yaygınlaştı. CoQ10’un kardiyovasküler, nörolojik hastalıklar, diyabet, kadın hastalıkları ve doğum vb. pek çok hastalıkta kullanım ve kullanım miktarını araştıran çalışmalar bulunmaktadır. Bu yazıda CoQ10 un metabolizması, etki mekanizmaları ile sağlık üzerine olan etkilerinin değerlendirilmesi amacıyla yapılmıştır.
... The potential association between nutrition and male infertility has attracted increasing attention in recent years. While some researchers have explored the possible association between a single food or food group and fertility parameters [12][13][14][15][16] , others have investigated the relationship between dietary patterns as a whole and infertility and/or abnormalities in semen quality markers [17][18][19] . Despite the importance of information provided by a single nutrient/food analysis, evaluation of the dietary pattern can yield an integrated estimate of both contribution and synergistic effects of some factors and may be used to describe different aspects of a diet 20,21 . ...
Article
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In this case–control study, we aimed to investigate the association between major dietary patterns and fertility status in Iranian men. The study population included 400 newly diagnosed infertile men and 537 healthy individuals without a history of infertility in Yazd, Iran. Infertility was confirmed clinically, based on the World Health Organization (WHO) criteria. Dietary intake was assessed using a 168-item semi-quantitative food frequency questionnaire (FFQ), and dietary patterns were determined based on a principal component analysis. Four major dietary patterns were found in this study, including healthy, Western, mixed, and traditional dietary patterns. After adjustments for potential confounders, men above the median of a healthy dietary pattern showed a reduced risk of infertility compared to those below the median (OR 0.52; 95% CI 0.33–0.83). In contrast, men with greater adherence to Western and mixed dietary patterns were more likely to be infertile (OR 2.66; 95% CI 1.70–4.17 and OR 2.82; 95% CI 1.75–4.56, respectively). Also, there was no significant association between the traditional dietary pattern and the odds of infertility. The present study suggests that greater adherence to a healthy dietary pattern may have an inverse association with the odds of infertility; however, Western and mixed dietary patterns may be associated with an increased risk of infertility.
... A study of 20 infertile patients with high SDF levels treated for 3 months with a preparation containing various antioxidants, including CoQ10, showed that SDF levels significantly decreased and sperm concentration significantly increased [36]. In a study of 20 infertile patients with high SDF levels and low-grade varicocele who were treated for 3 months with a preparation containing CoQ10 and other antioxidants, SDF levels significantly decreased and sperm concentration significantly increased [37]. These results support our finding of a significant decrease in SDF levels when infertile patients with idiopathic OAT were placed on CoQ10 therapy (200 mg/day) [1]. ...
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.
... According to Ko E.Y et al., there are no existing standards as to the optimal oral antioxidant supplement regimen, the dosing of specific agents, or the duration for administering supplements [55]. However, given the rather innocuous side effects at or below the recommended daily allowances, oral antioxidant supplementation may be a reasonable treatment regimen before proceeding with more expensive treatments such as in vitro fertilization or Intracytoplasmic sperm injection [56]. ...
Article
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More than 70 million couples suffer from infertility worldwide. Infertility is defined as not being able to get pregnant despite having frequent, unprotected sex for at least a year. Extraordinary advances have been achieved in the field of male infertility in the last decades. In recent years, the use of antioxidants in treatment of infertile men has been suggested, although there is limited evidence about the influence of nutrition on quality of semen. In this cohort study we aimed to evaluate the effect of Maca, Korean ginseng extract and antioxidants (vitamin C, natural vitamin E, zinc, selenium, L-Arginine, L-Carnitine, L-Methionine and L-Phenylalanine) on a male previously diagnosed with oligoasthenozoospermia, incapable to achieve fertilization of the healthy spouse. The man at age of 30, from Skopje, was supplemented daily with Maca tablets 500 mg three times a day, and once a day with a tablet under a brand name available in Macedonia, consisted of Korean ginseng extract and antioxidants mention above, in a period of four months, from March to July 2017. Semen analysis with microscope phase-contrast was done in andrology laboratory in the policlinic "Bukurest", with 3 days of abstinence was done before starting with the therapy and after. First analyze showed 20% of motile spermatozoa. Second analyze was done 41 days later and showed improvement of motile spermatozoa to 35%, while the last semen analysis was done 83 days after the second sample, which showed significant improvement of motility (50% which meets the criteria of the WHO), morphology, concentration and total number of spermatozoids that classified the man as normozoospermic. We assume that, Maca, Korean ginseng extract and antioxidants intake could improve the quality of semen parameters in men with oligoasthenzoospermia and increase fertility rate.
... Although antioxidants seem quite innocent, they may have potential side effects. Uncontrolled antioxidant therapy may lead to impairment of sperm parameters with a paradoxical effect [35]. The cause of this effect, called "antioxidant paradox," is the need for certain levels of antioxidant and ROS agents for normal cell function because some cells function at a reduced level [36]. ...
Article
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In this study, we aimed to evaluate the effect of oral antioxidant treatment on semen parameters and pregnancy rates in infertile men who underwent varicocelectomy. The study was conducted between January 2016 and January 2018. Subinguinal microscopic varicocelectomy was performed in 90 patients who were referred for infertility and diagnosed with clinical varicocele. The patients were divided into two groups. The first group received antioxidant treatment for 6 months after the operation (n = 62); the second group did not receive treatment after the operation (n = 28). The semen analysis was performed at the time of diagnosis and at 6 months postoperatively. The postoperative treatment semen parameters and pregnancy rates between the two groups were compared. The improvement in total sperm count ( + 45.9% vs + 26.8%), total motile sperm count ( + 50.6% vs + 29.7%), sperm concentration ( + 71.4% vs + 54.5%), sperm count in normal morphology ( + 75.7% vs + 39.9%), and total ( + 28.6% vs + 18.3%) and progressive motile sperm count ( + 60.4% vs + 38.9%) were significantly higher in the treated group than in the untreated group (p = 0.011, p < 0.001, p = 0.008, p < 0.001, p = 0.024 and p < 0.001, respectively). The clinical pregnancy rate in the first group was significantly higher than that in the second group (29% vs 17.9%) (p = 0.029). We concluded that the antioxidant treatment provides an important contribution to varicocelectomy outcomes and improves pregnancy rates.
... Individuals consuming saturated fat frequently were discovered to have 38% lower sperm concentration and 41% lower sperm count compared to the ones who consume it less [5,19]. As polyunsaturated fatty acids (PUFA) are important components of membrane structures of sperm cells and because of their antioxidant features, they play an important role in a successful fertilization by protecting the sperm cells from oxidative stress [5,20]. Also the PUFA are necessary for the plasma membrane fluidity and normal physiological function of sperm. ...
... La próstata es una glándula masculina unida a la vejiga responsable de secretar fluido prostático rico en zinc, que representa entre el 25% y 30% del volumen del eyaculado. 3 La principal contribución de las glándulas accesorias es la secreción de proteínas y cofactores, en especial las semenogelinas, liberadas por la vesícula seminal que contribuyen a la viscosidad del semen como una forma de protegerlo hasta que sea depositado en la vagina, donde las calicreinas ayudaran a que la licuefacción se complete y los espermatozoides puedan iniciar su recorrido. 1 ...
Article
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Introducción La prostatitis, término que involucra cuatro categorías de inflamación de la próstata, es considerada una patología enigmática por su complejidad en el diagnóstico e involucra el uso indiscriminado de antibióticos sin obtener evidencia de la infección. El objetivo de esta revisión es describir una patología de mal diagnóstico y de gran magnitud sobre la fertilidad masculina. Materiales y Métodos Se realizó una revisión de la literatura científica a conveniencia en la base de datos PubMed, empleando los términos prostatitis, prevalencia, dolor pélvico crónico y diagnóstico. Resultados La prevalencia de prostatitis varía entre 1,8% y 65% en los estudios evaluados, la prevalencia depende de la metodología empleada y del tipo de población evaluada. Conclusión Se requiere determinar la prevalencia de prostatitis en la población en general, con el fin de mejorar las ayudas diagnósticas y el tratamiento para evitar la propagación de microorganismos.
... The percentage of sperm DNA fragmentation in men taking vitamin C (1 g) and vitamin E (1 g) daily for 2 months was markedly lower than in sperm of men taking placebo (Greco et al. 2005a). Vitamin C may act synergistically with vitamin E to improve sperm quality (Ko and Sabanegh 2014). Infertile men with an elevated percentage of sperm DNA fragmentation whose partners had failed one ICSI attempt were given vitamin C (1 g) and vitamin E (1 g) daily for 2 months. ...
Chapter
Physiological levels of reactive oxygen species (ROS) are required for proper functioning of the male and female reproductive system. However, imbalances between ROS production and antioxidant systems induce oxidative stress, which can jeopardize the quality of the gamete and the developing embryo and cause many pregnancy disorders, such as spontaneous abortion, recurrent pregnancy loss, preeclampsia, fetal embryopathies, and intrauterine growth restriction. This review discusses the adverse effect of ROS-induced oxidative stress in assisted reproductive technologies (ART) outcome, ROS generated in vitro by gametes and embryos, and ROS generated by external sources in the in vitro fertilization (IVF) laboratory and the protocols used, including gamete/embryo handling, composition and pH of culture media, temperature and oxygen concentration during incubation, centrifugation and freeze-thaw protocols, as well as visible light. Studies on oral supplementation of enzymatic and nonenzymatic antioxidants are discussed. Although there is no one antioxidant that is considered the best choice for improving ART outcomes, some antioxidants show promising results. Additional well-designed trials are needed to determine the appropriate type(s) and concentration of antioxidant(s) that would be helpful to infertile patients with various etiologies. Studies are also warranted in the improvement of ART protocols to minimize ROS formation during assisted reproduction.
... Many articles researches and reviews have been reported the efficacy of micronutrients and vitamins supplementation each alone to treat infertility and improve reproductive outcomes in patients with azoosprmia, oligospermia, asthenospermia and unexplained subfertility [14,[21][22][23][24]. However, studies on the effectiveness of different combinations of these microelements in the treatment of men infertility are still very limited. ...
Article
Objective: Over recent decades, there is a growing concern around the infertility problem in Algeria. In the latest census of the health and populations ministry, the infertility affects approximately 10-12% of the couples and in 30% of these cases and the male is the main associated origin. Thus in this research, we attempt to determine the etiology of reproductive failure in infertile men and to assess the effectiveness therapy of Fertimax™ treatment as combination of a specific micronutrients and antioxidants on their semen quality. Methods: Thirty six men consulting for infertility spousal in clinic of assisted reproductive techniques “El Bordj”- Algiers were interviewed, examined for clinical signs and their sperm was analyzed, then after, some of them were subjected to Fertimax™ treatment for six months and their sperm was reanalyzed. Results: The obtained results revealed that Fertimax™ intake for six months can improve significantly all semen parameters including seminal volume and viscosity, spermatozoa number, mobility, vitality and morphology in these patients. Besides, in 33.33% of cases, these treated patients with Fertimax™ have fertilized their partners without recourse to in vitro fertilization process. Conclusion: This wonderful ameliorating role of Fertimax™ may be related to the particularly potent antioxidant properties of its components and thus we recommend this treatment as remedy for patients suffered from subfertility in both sexes.
... In addition, there are no proven therapies to correct any abnormal results. However, given the rather innocuous side effects at or below the recommended daily allowances, oral antioxidant supplementation may be a reasonable treatment regimen before proceeding with more expensive treatments such as IVF or ICSI (138). Repeated semen analysis and ROS testing may be considered 3 months after initiating treatment to evaluate for any changes in semen parameters. ...
Article
Reactive oxygen species (ROS) are an integral component of sperm developmental physiology, capacitation, and function. Elevated ROS levels, from processes such as infection or inflammation, can be associated with aberrations of sperm development, function, and fertilizing capacity. We review the impact of ROS on sperm physiology, its place in infertility evaluation, the implications for reproductive outcomes, and antioxidant therapy. Our systematic review of PubMed literature from the last 3 decades focuses on the physiology and etiology of ROS and oxidative stress (OS), evaluation of ROS, and antioxidants. ROS is normally produced physiologically and is used to maintain cellular processes such as sperm maturation, capacitation, and sperm-oocyte interaction. When ROS production exceeds the buffering capacity of antioxidants, OS occurs and can have a negative impact on sperm and fertility. ROS and antioxidant capacity testing can potentially add additional prognostic information to standard laboratory testing for the infertile male, although its role as standard part of an evaluation has yet to be determined. Elevated ROS levels have been implicated with abnormal semen parameters and male infertility, but the impact of ROS on fertilization rates and pregnancy is controversial. This is partly because of the lack of consensus on what type of patients may be suitable for ROS testing and assay standardization. Routine ROS testing for the infertile male is not currently recommended. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
... Infections and inflammation, smoking, environmental exposure to toxins and heat, anatomic abnormalities such as varicocele and cryptorchidism, may all result in oxidative stress. 1 Oxidative stress leads to the production of reactive oxygen species (ROS). Antioxidants present in seminal plasma and spermatozoa serve to maintain a balance and protect against damage caused by ROS. ...
Article
Objetivou-se com este trabalho relatar o resultado da suplementação de reprodutores macho criados em Central para a produção de sêmen, submetidos a utilização de um determinado Nutracêutico composto por aminoácidos, vitaminas, antioxidantes e minerais, adicionados a sua dieta, durante um período de sessenta dias e avaliando a produção espermática, para os parâmetros quantitativos e qualitativos para as seguintes características do sêmen: Numero de ejaculados, volume, motilidade, vigor, concentração, Número de Palhetas produzidas, defeitos maiores, defeitos menores e defeitos totais. Ao fim do tempo estimado decorreu-se uma análise comparativa com a produção dos sessenta dias anteriores antes do início do tratamento. Com o cruzamento dos resultados é possível concluir que a produção espermática dos reprodutores tratados com o Nutracêutico apresentara melhoras em sua produção.
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The authors review the literature investigating the role of common dietary supplements that are being marketed as a remedy for male subfertility. They assess the evidence base supporting their use and their potential role in improving semen parameters alongside overall conception and live-birth rates.
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Objective: To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s): Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s): Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s): Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s): Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s): The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71.©2005 by American Society for Reproductive Medicine.).
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L-Arginine is the biological precursor of nitric oxide (NO), which serves as an important signal and effector molecule in animals. This review summarizes some structure-function aspects of the mammalian nitric oxide synthases, which are enzymes that catalyze the oxidation of L-arginine to NO and L-citrulline. These include aspects related to: 1) the chemical transformations of L-arginine during enzyme catalysis, 2) binding of L-arginine or its structural analogs to the nitric oxide synthases, and 3) how L-arginine levels may affect product formation by the nitric oxide synthases and how this can be modulated by structural analogs of L-arginine. J. Nutr. 134: 2748S-2751S, 2004.
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The aim of the study described here was to evaluate any possible effect of L-carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres. One hundred patients received 3 g d−1 of oral L-carnitine for 4 months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by means of a computer-assisted sperm analysis. The results of the study indicate that L-carnitine is able to increase spermatozoal motility, both in a quantitative and in a qualitative manner (per cent motile spermatozoa increased from 26.9±1.1% to 37.7 ± 1.1% [P < 0.001]; per cent spermatozoa with rapid linear progression increased from 10.8 ± 0.6% to 18.0 ± 0.9% [P < 0.001]; mean velocity increased from 28.4 ± 0.6 μm s−1 to 32.5 ± 0.8 μm s−1 [P < 0.001]; linearity index increased from 3.7 ± 0.1 to 4.1±0.1 [P < 0.001], especially in the subgroup of patients with poor rapid linear progression of spermatozoa (per cent of motile spermatozoa increased from 19.3± 1.9% to 40.9± 1.4% [P < 0.001], and per cent of spermatozoa with rapid linear progression increased from 3.1±0.4% to 20.3±1.6% [P < 0.001]) An increase in spermatozoal output was also observed (total number of ejaculated spermatozoa increased from 142.4 ± 10.3 106 to 163.3 ± 11.0 × 106 [P < 0.001]). The authors conclude that oral administration of L-carnitine may improve sperm quality at least in patients with idiopathic asthenozoospermia.
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The objective of this study was to examine the relation between dietary fats and semen quality parameters. Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58-10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= -0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%) higher normal morphology than men in the lowest third (P(trend) = 0.02). In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.
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Coenzyme Q10 (CoQ(10)) is an effective natural antioxidant with a fundamental role in cellular bioenergetics and numerous known health benefits. Reports of its natural occurrence in various food items are comprehensively reviewed and critically evaluated. Meat, fish, nuts, and some oils are the richest nutritional sources of CoQ(10), while much lower levels can be found in most dairy products, vegetables, fruits, and cereals. Large variations of CoQ(10) content in some foods and food products of different geographical origin have been found. The average dietary intake of CoQ(10) is only 3-6 mg, with about half of it being in the reduced form. The intake can be significantly increased by the fortification of food products but, due to its lipophilicity, until recently this goal was not easily achievable particularly with low-fat, water-based products. Forms of CoQ(10) with increased water-solubility or dispersibility have been developed for this purpose, allowing the fortification of aqueous products, and exhibiting improved bioavailability; progress in this area is described briefly. Three main fortification strategies are presented and illustrated with examples, namely the addition of CoQ(10) to food during processing, the addition of this compound to the environment in which primary food products are being formed (i.e. animal feed), or with the genetic modification of plants (i.e. cereal crops).
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There is growing interest in the possible health threat posed by the effects of endocrine disruptors on reproduction. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. The purpose of this review was to examine the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals. Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. However, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology. Further investigation is needed before a firm conclusion can be drawn. In the meantime, caution would suggest that perinatal phyto-oestrogen exposure, such as that found in infants feeding on soy-based formula, should be avoided.
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The objective of the present study was to assess the ascorbic acid (AA) levels in seminal plasma of the fertile and infertile men and to investigate its relationship with sperm count, motility and normal morphology. Semen samples were provided by fertile [smoker (n = 25), nonsmoker (n = 21)] and infertile men [smoker (n = 23), nonsmoker (n = 32)]. A simplified method of reverse phase high performance liquid chromatography (RP-HPLC) procedure using UV detection was applied for the determination of seminal AA. Fertile subjects, smoker or not, demonstrated significantly higher seminal AA levels than any infertile group (p<0.01). Nonsmokers had high, but no significant, mean AA levels in their seminal plasma compared with smokers. Seminal AA in fertile and infertile (smokers or nonsmokers) males correlated significantly with the percentage of spermatozoa with normal morphology (p<0.01). Seminal AA decreased significantly in infertile men. Decrease of seminal plasma AA is a risk factor for low normal morphology of spermatozoa and idiopathic male infertility. Measurement of seminal AA in the seminal plasma of males with a history of subfertility or idiopathic infertility is necessary and can be helpful in fertility assessment.
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To determine whether isoflavones exert estrogen-like effects in men by lowering bioavailable T through evaluation of the effects of soy protein or isoflavone intake on T, sex hormone-binding globulin (SHBG), free T, and free androgen index (FAI) in men. PubMed and CAB Abstracts databases were searched through July 1, 2008, with use of controlled vocabulary specific to the databases, such as soy, isoflavones, genistein, phytoestrogens, red clover, androgen, testosterone, and SHBG. Peer-reviewed studies published in English were selected if [1] adult men consumed soy foods, isolated soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating T, SHBG, free T, or calculated FAI was assessed. Data were extracted by two independent reviewers. Isoflavone exposure was abstracted directly from studies. Fifteen placebo-controlled treatment groups with baseline and ending measures were analyzed. In addition, 32 reports involving 36 treatment groups were assessed in simpler models to ascertain the results. No significant effects of soy protein or isoflavone intake on T, SHBG, free T, or FAI were detected regardless of statistical model. The results of this meta-analysis suggest that neither soy foods nor isoflavone supplements alter measures of bioavailable T concentrations in men.
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Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Institute of Medicine has developed a new approach to establish Recommended Dietary Allowances (RDAs) and other nutrient reference values. The new title for these values Dietary Reference Intakes (DRIs), is the inclusive name being given to this new approach. These are quantitative estimates of nutrient intakes applicable to healthy individuals in the United States and Canada. This new book is part of a series of books presenting dietary reference values for the intakes of nutrients. It establishes recommendations for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. This book presents new approaches and findings which include the following: The establishment of Estimated Energy Requirements at four levels of energy expenditure Recommendations for levels of physical activity to decrease risk of chronic disease The establishment of RDAs for dietary carbohydrate and protein The development of the definitions of Dietary Fiber, Functional Fiber, and Total Fiber The establishment of Adequate Intakes (AI) for Total Fiber The establishment of AIs for linolenic and a-linolenic acids Acceptable Macronutrient Distribution Ranges as a percent of energy intake for fat, carbohydrate, linolenic and a-linolenic acids, and protein Research recommendations for information needed to advance understanding of macronutrient requirements and the adverse effects associated with intake of higher amounts Also detailed are recommendations for both physical activity and energy expenditure to maintain health and decrease the risk of disease. © 2002/2005 by the National Academy of Sciences. All rights reserved.
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Nutraceuticals is a broad umbrella term used to describe any product derived from food sources that provides extra health benefits in addition to the basic nutritional value found in foods. The term Nutraceutical is a hybrid of nutrition and pharmaceutical technology, coined in 1989 by Stephen Defelice. In present article an attempt has been made to discuss all aspects of Nutraceuticals- Definition, how they differ from functional food and dietary supplement, classification, marketed products, the pros and cons and future aspects.
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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).
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Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders where proof of efficacy is lacking.
Article
The rat estrogen receptor (ER) exists as two subtypes, ERα and ERβ, which differ in the C-terminal ligand binding domain and in the N-terminal transactivation domain. In this study we investigated the messenger RNA expression of both ER subtypes in rat tissues by RT-PCR and compared the ligand binding specificity of the ER subtypes. Saturation ligand binding analysis of in vitro synthesized human ERα and rat ERβ protein revealed a single binding component for 16α-iodo-17β-estradiol with high affinity[ dissociation constant (Kd) = 0.1 nm for ERα protein and 0.4 nm for ERβ protein]. Most estrogenic substances or estrogenic antagonists compete with 16α-[125I]iodo-17β-estradiol for binding to both ER subtypes in a very similar preference and degree; that is, diethylstilbestrol > hexestrol > dienestrol > 4-OH-tamoxifen > 17β-estradiol > coumestrol, ICI-164384 > estrone, 17α-estradiol > nafoxidine, moxestrol > clomifene > estriol, 4-OH-estradiol > tamoxifen, 2-OH-estradiol, 5-androstene-3β,17β-diol, genistein for the ERα protein and dienestrol > 4-OH-tamoxifen > diethylstilbestrol > hexestrol > coumestrol, ICI-164384 > 17β-estradiol > estrone, genistein > estriol > nafoxidine, 5-androstene-3β,17β-diol > 17α-estradiol, clomifene, 2-OH-estradiol > 4-OH-estradiol, tamoxifen, moxestrol for the ERβ protein. The rat tissue distribution and/or the relative level of ERα and ERβ expression seems to be quite different, i.e. moderate to high expression in uterus, testis, pituitary, ovary, kidney, epididymis, and adrenal for ERα and prostate, ovary, lung, bladder, brain, uterus, and testis for ERβ. The described differences between the ER subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER agonists and antagonists in different tissues.
Article
Summary— A prospective randomised trial was carried out to assess the effect of 6 months' treatment with either clomiphene citrate or vitamin C in 179 men complaining of infertile marriage. There was no significant difference in the wife's pregnancy rates between the 2 treatment groups. In order to detect a subgroup that might respond to clomiphene the results were analysed according to pre-treatment FSH and sperm density, with allowance being made for the result of the wife's tests, but still there was no significant difference in treatment response. Vitamin C would seem a preferable and cheaper alternative treatment for male infertility.
Article
Omega-3 fatty acids found in some foods have a wide-range of health benefits. The omega-3 supplementation results in higher antioxidant activity in human seminal fluid and enhanced sperm count, sperm motility, and sperm morphology. Considerable number of infertile men with idiopathic oligoasthenoteratozoospermia might be benefit from omega-3 fatty acids administration.
Article
Physiological processes are often activated by reactive oxygen species (ROS), such as the superoxide anion (O2–) and nitric oxide (NO) produced by cells. We studied the interactions between NO and O2–, and their generators (NO synthase, NOS, and a still elusive oxidase), in human spermatozoa during capacitation (transformations needed for acquisition of fertility). Albumin, fetal cord serum ultrafiltrate, and L-arginine triggered capacitation and ROS generation (NO and O2–) and superoxide dismutase (SOD) and NOS inhibitors prevented all these effects. Surprisingly, capacitation due to exogenous NO (or O2–) was also blocked by SOD (or NOS inhibitors). Probes used were proven specific and innocuous on spermatozoa. Whereas O2– was needed only for 30 min, the continuous NO generation was essential for hours. Capacitation caused a time-dependent increase in protein tyrosine nitration that was prevented by SOD and NOS inhibitors, suggesting that O2– and NO· also act via the formation of ONOO–. Spermatozoa treated with NO (or O2–) initiated a dose-dependent O2– (or NO) production, providing, for the first time in cells, a strong evidence for a two-sided ROS-induced ROS generation. Data presented show a close interaction between NO and O2– and their generators during sperm capacitation.
Article
Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
Article
High isoflavone intake has been related to decreased fertility in animal studies, but data in humans are scarce. Thus, we examined the association of soy foods and isoflavones intake with semen quality parameters. The intake of 15 soy-based foods in the previous 3 months was assessed for 99 male partners of subfertile couples who presented for semen analyses to the Massachusetts General Hospital Fertility Center. Linear and quantile regression were used to determine the association of soy foods and isoflavones intake with semen quality parameters while adjusting for personal characteristics. There was an inverse association between soy food intake and sperm concentration that remained significant after accounting for age, abstinence time, body mass index, caffeine and alcohol intake and smoking. In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods (95% confidence interval = -74, -8; P, trend = 0.02). Results for individual soy isoflavones were similar to the results for soy foods and were strongest for glycitein, but did not reach statistical significance. The inverse relation between soy food intake and sperm concentration was more pronounced in the high end of the distribution (90th and 75th percentile) and among overweight or obese men. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration.
Article
The aim of this systematic review was to quantify the efficacy of L-carnitine (LC) and/or L-acetyl-carnitine (LAC) in nutrition treatment for male infertility according to present clinical evidence. Biomedical databases were searched to collect related clinical trials and nine relevant randomized controlled trials (RCTs) were included. The quality of the RCTs was assessed based on their performance in randomization, blinding, and allocation concealment. The meta-analysis compared LC and /or LAC therapy to placebo treatment found significant improvement in pregnancy rate (OR = 4.10, 95% CI (2.08, 8.08), p< 0.0001), total sperm motility (WMD = 7.43, 95% CI (1.72, 13.14), p = 0.04, forward sperm motility (WMD = 11.83, 95% CI (0.49, 23.16), p = 0.04) and atypical sperm cell (WMD = -5.72, 95% CI (-7.89, -3.56), p< 0.00001). However, no significant difference was found in the sperm concentration (WMD = 5.69, 95% CI (-4.47, 15.84), p = 0.27) and semen volume (WMD = 0.28, 95% CI (-0.02, 0.58), p = 0.07). In conclusion, the administration of LC and/or LAC may be effective in improving pregnancy rate and sperm kinetic features in patients affected by male infertility. However, the exact efficacy of carnitines on male infertility needs to be confirmed by further investigations.
Article
Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. To perform a meta-analysis of the dose-response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials. 135,967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d). PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied. 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available. 9 of 11 trials testing high-dosage vitamin E (> or =400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10,000 persons (95% CI, 3 to 74 per 10,000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was -16 per 10,000 persons (CI, -41 to 10 per 10,000 persons; P > 0.2). A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. High-dosage (> or =400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult. High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
Article
Background: Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm and 1 man in 20 will be affected by subfertility. Antioxidants are widely available and inexpensive when compared to other fertility treatments and many men are already using these to improve their fertility. It is thought that oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress. Pentoxifylline, a drug that acts like an antioxidant, was also included in this review. Objectives: This Cochrane review aimed to evaluate the effectiveness and safety of oral supplementation with antioxidants for subfertile male partners in couples seeking fertility assistance. Search methods: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO and AMED databases (from inception until January 2014); trial registers; sources of unpublished literature and reference lists. An updated search was run in August 2014 when potentially eligible studies were placed in 'Studies awaiting assessment'. Selection criteria: We included randomised controlled trials (RCTs) comparing any type or dose of antioxidant supplement (single or combined) taken by the subfertile male partner of a couple seeking fertility assistance with a placebo, no treatment or another antioxidant. Data collection and analysis: Two review authors independently selected eligible studies, extracted the data and assessed the risk of bias of the included studies. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates, adverse events, sperm DNA fragmentation, sperm motility and concentration. Data were combined, where appropriate, to calculate pooled odds ratios (ORs) or mean differences (MD) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods. Main results: This updated review included 48 RCTs that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy, one enrolled men with a varicocoele, and one recruited men with chronic prostatitis. Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial avenues or university grants. Thirty-three trials did not report any funding sources.A limitation of this review was that in a sense we had included two different groups of trials, those that reported on the use of antioxidants and the effect on live birth and clinical pregnancy, and a second group that reported on sperm parameters as their primary outcome and had no intention of reporting the primary outcomes of this review. We included 25 trials reporting on sperm parameters and only three of these reported on live birth or clinical pregnancy. Other limitations included poor reporting of study methods, imprecision, the small number of trials providing usable data, the small sample size of many of the included studies and the lack of adverse events reporting. The evidence was graded as 'very low' to 'low'. The data were current to 31 January 2014.Live birth: antioxidants may have increased live birth rates (OR 4.21, 95% CI 2.08 to 8.51, P< 0.0001, 4 RCTs, 277 men, I(2) = 0%, low quality evidence). This suggests that if the chance of a live birth following placebo or no treatment is assumed to be 5%, the chance following the use of antioxidants is estimated to be between 10% and 31%. However, this result was based on only 44 live births from a total of 277 couples in four small studies.Clinical pregnancy rate: antioxidants may have increased clinical pregnancy rates (OR 3.43, 95% CI 1.92 to 6.11, P < 0.0001, 7 RCTs, 522 men, I(2) = 0%, low quality evidence). This suggests that if the chance of clinical pregnancy following placebo or no treatment is assumed to be 6%, the chance following the use of antioxidants is estimated at between 11% and 28%. However, there were only seven small studies in this analysis and the quality of the evidence was rated as low.Miscarriage: only three trials reported on this outcome and the event rate was very low. There was insufficient evidence to show whether there was a difference in miscarriage rates between the antioxidant and placebo or no treatment groups (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I(2) = 0%, very low quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, use of an antioxidant would result in the risk of a miscarriage lying between 1% and 13%.Gastrointestinal upsets: there was insufficient evidence to show whether there was a difference in gastrointestinal upsets when antioxidants were compared to placebo or no treatment as the event rate was very low (OR 1.60, 95% CI 0.47 to 5.50, P = 0.46, 6 RCTs, 429 men, I(2) = 0%).We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as not enough trials compared the same interventions. Authors' conclusions: There is low quality evidence from only four small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low quality evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage but this is uncertain as the evidence is of very low quality. Data were lacking on other adverse effects. Further large well-designed randomised placebo-controlled trials are needed to clarify these results.
Article
Effective medical treatments of infertile men with idiopathic oligoasthenoteratospermia (OAT) have yet to be determined. This study considered two major aims: (i) to measure the changes in semen parameters, omega-3 fatty acids (FA) compositions and anti-oxidant activity; (ii) to determine if the administration of omega-3 FA affect semen quality in infertile men with OAT. Two hundred thirty-eight infertile men with idiopathic OAT were randomised to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), 1.84 g per day (EPAX 5500TG; Lysaker, Norway), or placebo for 32 weeks. The semen parameters were assessed according to WHO criteria, and the EPA and DHA concentrations were determined in red blood cells (RBCs), seminal plasma and sperm cells at baseline and 32-week treatment period. Of randomised subjects, 211 (88.7%) completed the full 32-week randomisation period. The anti-oxidant status of seminal plasma was also evaluated by measuring the superoxide dismutase (SOD) and catalase-like activity. In the total group of participants, all EPA and DHA levels in RBC, and seminal plasma, were statistically significantly correlated with those in spermatozoa (both P = 0.001). A significant improvement of sperm cell total count (from 38.7 ± 8.7 ' 10⁶ to 61.7 ± 11.2 ' 10⁶, P = 0.001) and sperm cell concentration (from 15.6 ± 4.1 ' 10⁶ per ml to 28.7 ± 4.4 ' 10⁶ per ml, P = 0.001) was observed in the omega-3 group. A significant positive correlation was found between the EPA and DHA in seminal plasma and the semen parameters. Seminal plasma EPA and DHA concentrations were positively correlated with seminal plasma SOD-like and catalase-like activity (both P = 0.001). In seminal plasma, both SOD-like and catalase-like activity were positively correlated with sperm count, sperm motility, and sperm morphology. Oligoasthenoteratospermic men with low levels of EPA and DHA may benefit from omega-3 FA supplementation. Further studies are warranted to shed more light on this important issue.
Article
Oxidative stress contributes to defective spermatogenesis leading to male factor infertility. The aim of this study was to review the current literature on the effects of various antioxidants to improve fertilisation and pregnancy rates. The sources of literature were Pubmed and the Cochrane data base. Reviewing the current literature revealed that Carnitines and vitamin C and E have been clearly shown to be effective by many well-conducted studies and may be considered as a first line treatment. The efficacy of antioxidants, such as glutathione, selenium and coenzyme Q10 has been demonstrated by few, but well-performed studies, and may be considered second line treatment. There is, however, a need for further investigation with randomised controlled studies to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the need to determine the ideal dose of each compound to improve semen parameters, fertilisation rates and pregnancy outcomes.
Article
To date, there have been few systematic studies of the antiplatelet and/or anticoagulant effects of natural products. According to the Natural Medicines Comprehensive Database, approximately 180 dietary supplements have the potential to interact with warfarin, and more than 120 may interact with aspirin, clopidogrel, and dipyridamole. These include anise and dong quai (anticoagulant effects); omega 3-fatty acids in fish oil, ajoene in garlic, ginger, ginko, and vitamin E (antiplatelet properties); fucus (heparin-like activity); danshen (antithrombin III-like activity and anticoagulant bioavailability); and St. John's Wort and American Ginseng (interference with drug metabolism). Other supplements, such as high doses of vitamin E (vitamin K antagonist activity), alfalfa (high-vitamin K content), and coenzyme Q10 (vitamin K-like activity), may affect blood clotting, which is dependent on vitamin K. Studies are needed to understand the role of various dietary supplements in thrombosis and their interactions with standard anticoagulants and antiplatelet drugs.
Article
In addition to its role as a component of the mitochondrial respiratory chain and our only lipid-soluble antioxidant synthesized endogenously, in recent years coenzyme Q (CoQ) has been found to have an increasing number of other important functions required for normal metabolic processes. A number of genetic mutations that reduce CoQ biosynthesis are associated with serious functional disturbances that can be eliminated by dietary administration of this lipid, making CoQ deficiencies the only mitochondrial diseases which can be successfully treated at present. In connection with certain other diseases associated with excessive oxidative stress, the level of CoQ is elevated as a protective response. Aging, certain experimental conditions and several human diseases reduce this level, resulting in serious metabolic disturbances. Since dietary uptake of this lipid is limited, up-regulation of its biosynthetic pathway is of considerable clinical interest. One approach for this purpose is administration of epoxidated all-trans polyisoprenoids, which enhance both CoQ biosynthesis and levels in experimental systems.
Article
In earlier studies, we have established that l-arginine enhances motility and metabolic rate in spermatozoa of goat, bull and mouse. In the present study this work was extended to human sperm cells obtained from the semen samples of asthenospermic patients, which are characterised by low motility. The metabolic rate was followed by monitoring the glucose consumption (1-(13)C glucose as substrate) and the production of lactate in sperm cells, using (13)C NMR. The stimulatory effect of l-arginine was neutralised on adding an NO-synthase inhibitor like N(omega)-nitro-L-arginine methyl ester. On the other hand, the inactive d-enantiomorph did not affect the stimulatory effect of l-arginine. This strongly suggests that L-arginine acts through the NO signal pathway. We also demonstrated that the stimulatory effect of L-arginine was inhibited in the presence of anion channel inhibitors like 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid, 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone. Furthermore, bicarbonate supplementation was found to be essential for the action of L-arginine. These observations indicate that L-arginine induces NO synthesis and stimulates motility and metabolism only when an active anion transport system is present.
Article
The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.
Article
Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens.
Article
To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements. We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of included studies published from 1966 through October 2009. The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions. Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B(12), vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events. Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.
Article
The fundamental role of coenzyme Q(10) (CoQ(10)) in mitochondrial bioenergetics and its well-acknowledged antioxidant properties constitute the basis for its clinical applications, although some of its effects may be related to a gene induction mechanism. Cardiovascular disease is still the main field of study and the latest findings confirm a role of CoQ(10) in improving endothelial function. The possible relation between CoQ(10) deficiency and statin side effects is highly debated, particularly the key issue of whether CoQ(10) supplementation counteracts statin myalgias. Furthermore, in cardiac patients, plasma CoQ(10) was found to be an independent predictor of mortality. Studies on CoQ(10) and physical exercise have confirmed its effect in improving subjective fatigue sensation and physical performance and in opposing exercise-related damage. In the field of mitochondrial myopathies, primary CoQ(10) deficiencies have been identified, involving different genes of the CoQ(10) biosynthetic pathway; some of these conditions were found to be highly responsive to CoQ(10) administration. The initial observations of CoQ(10) effects in Parkinson's and Huntington's diseases have been extended to Friedreich's ataxia, where CoQ(10) and other quinones have been tested. CoQ(10) is presently being used in a large phase III trial in Parkinson's disease. CoQ(10) has been found to improve sperm count and motility on asthenozoospermia. Moreover, for the first time CoQ(10) was found to decrease the incidence of preeclampsia in pregnancy. The ability of CoQ(10) to mitigate headache symptoms in adults was also verified in pediatric and adolescent populations.
Article
Fatty acid (FA) composition of the spermatozoa may be an important determinant of fertility. The aim was to evaluate polyunsaturated fatty acid (PUFA) composition of the blood plasma and spermatozoa in infertile men with idiopathic oligoasthenoteratozoospermia (OAT). Eighty-two infertile men with idiopathic OAT and seventy-eight fertile men defined according to semen concentration and proven fertility were enrolled in the study. The semen parameters were assessed according to World Health Organization criteria; three omega-3 fatty acids--alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and two omega-6 fatty acids--linoleic acid (LA) and arachidonic acid (AA) concentrations were measured in blood plasma and spermatozoa; and the seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were also assessed. Proven fertile men had higher blood and spermatozoa levels of omega-3 FAs compared with the infertile patients. The ratio of serum omega-6/omega-3 fatty acids was significantly higher in infertile (14.8+/-4.3) patients compared to fertile controls (6.3+/-2.2) (P=0.001). Additionally, levels of AA were higher and the omega-3 index (EPA+DHA) was lower in infertile subjects than in fertile controls (all P values<0.05). Infertile men had higher mean AA:DHA ratio and AA:EPA (6.4+/-2.9 and 12.0+/-4.9, respectively) than fertile men (3.3+/-1.8 and 6.7+/-2.6, respectively) (both P=0.001). A strong negative correlation was found between the AA:DHA and AA:EPA ratios and total sperm count (r=-0.62, P=0.001 and r=-0.64, P=0.001, respectively), sperm motility (r=-0.63, P=0.001 and r=-0.61, P=0.001, respectively), and sperm morphology (r=-0.61, P=0.001, and r=-0.59, P=0.002, respectively). Infertile men had lower concentrations of omega-3 FAs in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 FA supplementation as a therapeutic approach in infertile men with idiopathic OAT.