The supplements or the placebo was taken once daily after a meal as a complex agent in capsule form. 20 patients ages 29–78 years were enrolled, and after 6 men withdrew, 13 concluded the study without adverse events. The mechanism by which RSV improves cryopreserved sperm functions may relate to activation of AMPK, which is mainly localized in the post-equatorial region of the sperm head and the entire flagellum 34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,52,53. In the present randomized, double-blind, placebo-controlled crossover pilot study, men with ED (Sexual Health Inventory for Men SHIM score below 16) despite the on-demand use of PDE5i received a placebo for 1 month or the active treatment (L-citrulline 800 mg/day and transresveratrol 300 mg/day) for another month without washout before crossover (Figure 1). In this randomized, double-blind, placebo-controlled crossover pilot study, men with ED (Sexual Health Inventory for Men SHIM score below 16) despite on-demand use of PDE5i received a placebo for 1 month or the active treatment (L-citrulline 800 mg/day and transresveratrol 300 mg/day) for another month. In conclusion, we propose that resveratrol has a positive effect on male reproductive function by triggering a penile erection, as well as enhancing blood testosterone levels, testicular sperm counts, and epididymal sperm motility. The in-vivo study measured reproductive organ weights, blood testosterone levels, testicular histopathology, sperm counts, as well as the epididymal sperm motility and deformity of male ICR mice given an oral dose of resveratrol (50 mg/ kg) for 28 days. Table 1 summarizes the main studies exploring the effects of RSV on human conventional and biofunctional sperm parameters. We investigated the efficacy of a supplement drink containing testofen, L-citrulline, resveratrol, and caffeine in improving sexual function, especially libido, in men with sexual dysfunction. We recruited 20 patients who visited our clinics specializing in sexual function to particpate in this randomized, double-blind, placebo-controlled crossover pilot study. Contrarily, at physiological concentrations, resveratrol induces vasodilation, and consequently decreases hypertension and cardiovascular diseases risk . Yan et al. suggest that resveratrol act by preventing the expressions of endothelial nitric oxide synthase, vascular endothelial growth factor, and suppressing phosphorylation of p38 in rats with diabetes-related myocardial infarction . Resveratrol showed beneficial effect in heart failure by improving left ventricle function, decreased cardiac hypertrophy, contractile dysfunction and remodeling, interstitial fibrosis, and the level of plasma BNP . Cisplatin, a cancer chemotherapy agent against ovarian, bladder, testicular, and many other cancers, high risk of nephrotoxicity is reduce by Resveratrol . Resveratrol has also shown promise as part of combination therapy, particularly in breast cancer . Whilst research is limited to animal studies, it is definitely an areas of interest that warrants further investigation. The decrease in estrogen allows more room for testosterone to flourish therefore indirectly elevating it. Not only did it decrease its action, but also decreased production of estrogen at mRNA levels too. Resveratrol appears to boost male hormone levels by directly increasing T levels, and secondly by decreasing aromatization. The actual process of testosterone and other anabolic hormones converting to estrogen is called aromatization – something any man would want to avoid. It has also been claimed to increase lifespan, although this is anecdotal and not backed up by science. The bioflavenoid content of the nutrient has also been shown to decrease fat cell production, meaning that it may help long-term improve body composition. However, it is imperative to mention that these studies were done in healthy populations, and that may vary in sick patients. Otherwise, at doses of 2.5 g or more per day, side effects may occurs, like nausea, vomiting, diarrhea and liver dysfunction in patients with non-alcoholic fatty liver disease . All the above highlighted studies show the pivotal role of dose-dependency and aging in resveratrol-induced responses towards health benefits. In addition, resveratrol may increase ovarian follicular reserve and prolong ovarian life span, serving as a potential anti-aging agent . Pterostilbene is a methoxylated derivative of resveratrol that showed antibacterial activity against drug-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) superior of pterostilbene compared to resveratrol (8~16-fold). Resveratrol showed antiviral activity by inhibiting the Pseudorabies virus replication and effectively increase the growth performance and reduce the mortality of Pseudorabies virus-infected piglets . Resveratrol showed antibacterial activity against Gram-positive bacteria and time-kill assays showed that its effects were due to its bacteriostatic action . RSV alone slightly but significantly decreased the percentage of spermatozoa with abnormal chromatin compactness, did not have any significant effect on LPO, and decreased the percentage of spermatozoa with elevated mitochondrial superoxide production. Finally, BaP significantly increased LPO and the production of mitochondrial superoxide. Metabolically activated BaP increases ROS production and consequently the oxidative stress, resulting in increased lipid peroxidation, and caspase, and endonuclease activation 43,44. The authors concluded that RSV could have a role as a ROS scavenger in presence of increased oxidative stress, such as during cryopreservation or IVF-ICSI . RSV was particularly effective in preserving sperm chromatin texture, but it was not able to fully preserve acrosome, the most fragile sperm organelle. The authors evaluated the motility of swim-up selected spermatozoa to test the effect of different RSV concentrations (from 6 to 100 µM).
