Scientists have shown that resveratrol rescues erectile function in aged rats, most probably by activating SIRT1, and that it can work in synergy with the existing erectile dysfunction treatment tadalafil .
A molecule of discord
Resveratrol, a plant-derived chemical of the polyphenol family, was once considered one of the most promising anti-aging molecules. David Sinclair’s lab at Harvard University showed that resveratrol works by activating SIRT1 , a protein thought to be protective against various diseases of aging .
Sinclair’s research eventually led to a huge 720-million-dollar deal with GlaxoSmithKline, but a few years later, GSK reluctantly shut the program down due to various problems. Currently, there is an open controversy about resveratrol, involving several prominent figures in the field, the gist of which you can get from this Lifespan News video.
Yet, resveratrol was not abandoned, and numerous studies have documented its various beneficial effects, some of which may be unrelated to SIRT1 . This should not come as a surprise, since many other polyphenols, such as quercetin and curcumin, have shown strong anti-aging potential.
It would be safe to say that the question of whether resveratrol indeed activates SIRT1, and whether such activation is beneficial for lifespan and healthspan, is currently debated. In this new study, a group of Chinese scientists contributes to the discussion in an interesting way.
Rats have the same problem
The researchers decided to analyze the effect of SIRT1 activation by resveratrol on erectile dysfunction in aged rats (apparently, humans are not the only mammals suffering from age-related loss of erection). Sixty-eight 20-month-old rats were divided into four groups: a control group, a resveratrol group, a group that was given the SIRT1 inhibitor nicotinamide (NAM), and a group that was given a combination of resveratrol and tadalafil, a known treatment for erectile dysfunction.
In this study, 8-week-long resveratrol supplementation led to a significant amelioration of erectile dysfunction and coincided with an increase in SIRT1. In the NAM group, SIRT1 levels were lower, and erectile dysfunction was more severe than in the controls. Finally, the fourth group showed the best results, which led the researchers to believe that resveratrol and tadalafil work in unison against erectile dysfunction.
The researchers also analyzed histological changes in the rats’ penises. Resveratrol supplementation led to a significant increase in smooth muscle and endothelial tissue in the corpus cavernosum, which is indicative of better function. Yet again, NAM supplementation delivered the opposite results, while tadalafil reinforced the resveratrol-related gains.
Nitric oxide (NO) levels are negatively correlated with erectile dysfunction. In this study, resveratrol supplementation increased NO levels. This might be the mechanism behind the synergy between resveratrol and tadalafil, since drugs like tadalafil need a minimum amount of NO in order to work. One study has shown that SIRT1 promotes vascular relaxation (hence, erectile function) by activating the NO-producing enzyme nitric oxide synthase, which might also have contributed to the overall effect .
Erectile dysfunction has also been linked to oxidative stress. The researchers checked for two markers of oxidative stress: the antioxidant enzyme SOD, which eliminates free radicals, and MDA, which is indicative of tissue damage, and found that resveratrol supplementation had a positive effect on the levels of both (that is, it increased SOD levels and decreased MDA levels). In the context of oxidative stress, the advantage of the combination treatment was less pronounced than in other experiments but still significant. Overall, the benefits of resveratrol were shown to be statistically significant across all the experiments.
A safer ED drug?
This is not the first study of its kind. A previous one found that resveratrol reduces erectile dysfunction in rats that was induced by diabetes , another problem that these rodents seem to share with humans. According to the researchers, those previous findings, as well as their own, point at resveratrol as a potentially effective treatment for erectile dysfunction that is also safer than the current ones.
This study has some limitations. First, although the researchers did employ a SIRT1 inhibitor, it would be interesting to also see SIRT1 activation by other means, in order to be sure that resveratrol indeed works via this pathway. Second, a group treated with tadalafil alone could have provided a deeper insight into the supposed synergy between tadalafil and resveratrol.
This interesting study appears at a time when resveratrol’s beneficial effects and its ability to activate SIRT1 are under discussion. Although this cannot be considered an ironclad proof, and more research is needed, this study shows that in a rodent model, resveratrol does activate SIRT1, which leads to the amelioration of erectile dysfunction.
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 Yu, W., Wang, J., Dai, Y. T., Wang, B., Xu, Y., Gao, Q. Q., & Xu, Z. P. (2022). Modulation of SIRT1 expression improves erectile function in aged rats.
 Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., … & Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444(7117), 337-342.
 Elibol, B., & Kilic, U. (2018). High levels of SIRT1 expression as a protective mechanism against disease-related conditions. Frontiers in endocrinology, 614.
 Pollack, R. M., Barzilai, N., Anghel, V., Kulkarni, A. S., Golden, A., O’Broin, P., … & Crandall, J. P. (2017). Resveratrol improves vascular function and mitochondrial number but not glucose metabolism in older adults. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(12), 1703-1709.
 Mattagajasingh, I., Kim, C. S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S. B., … & Irani, K. (2007). SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proceedings of the National Academy of Sciences, 104(37), 14855-14860.
 Fukuhara, S., Tsujimura, A., Okuda, H., Yamamoto, K., Takao, T., Miyagawa, Y., … & Okuyama, A. (2011). Vardenafil and resveratrol synergistically enhance the nitric oxide/cyclic guanosine monophosphate pathway in corpus cavernosal smooth muscle cells and its therapeutic potential for erectile dysfunction in the streptozotocin-induced diabetic rat: Preliminary findings. The journal of sexual medicine, 8(4), 1061-1071.
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