Scientists have shown that resveratrol rescues erectile function in aged rats, most likely by activating SIRT1, and that it may work synergistically with the existing treatment for erectile dysfunction, tadalafil. .
A Molecule of Discord
Resveratrol, a plant-derived chemical from the polyphenol family, was once considered one of the most promising anti-aging molecules. David Sinclair’s lab at Harvard University has shown that resveratrol works by activating SIRT1 a protein believed to protect against various diseases of aging .
Sinclair’s research eventually resulted in a whopping $720 million contract with GlaxoSmithKline, but a few years later GSK reluctantly shut down the program due to various issues. Currently, there is an open resveratrol controversy involving several prominent figures in the field, the gist of which you can get in this Lifespan News video.
Yet resveratrol has not been abandoned, and numerous studies have documented its various beneficial effects, some of which may be unrelated to SIRT1. . This should come as no surprise, as many other polyphenols, such as quercetin and curcumin, have shown strong anti-aging potential.
It would be safe to say that whether resveratrol actually activates SIRT1, and whether such activation is beneficial for lifespan and health, is currently under debate. In this new study, a group of Chinese scientists contribute 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 received nicotinamide (NAM), a SIRT1 inhibitor, and a group that received a combination of resveratrol and tadalafil. , a known treatment for erectile dysfunction.
In this study, resveratrol supplementation for 8 weeks led to a significant improvement in 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 controls. Finally, the fourth group showed the best results, leading 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 resulted in a significant increase in smooth muscle and endothelial tissue in the corpora cavernosa, indicating better function. Again, NAM supplementation provided the opposite results, while tadalafil enhanced resveratrol-related gains.
Nitric oxide (NO) levels are negatively correlated with erectile dysfunction. In this study, resveratrol supplementation increased NO levels. This could be the mechanism behind the synergy between resveratrol and tadalafil, since drugs like tadalafil need a minimal amount of NO to work. A study showed that SIRT1 promotes vascular relaxation (therefore erectile function) by activating the NO-producing enzyme nitric oxide synthase, which may also have contributed to the overall effect .
Erectile dysfunction has also been linked to oxidative stress. The researchers looked for two markers of oxidative stress: the antioxidant enzyme SOD, which scavenges free radicals, and MDA, which indicates tissue damage, and found that resveratrol supplementation had a positive effect on levels of both ( that is, it increased SOD levels and decreased MDA levels). In the setting of oxidative stress, the benefit of the combination treatment was less pronounced than in other experiments but still significant. Overall, the benefits of resveratrol were found to be statistically significant in all experiments.
A safer ED drug?
This is not the first study of its kind. A precedent found that resveratrol reduced erectile dysfunction in rats induced by diabetes , another problem these rodents seem to share with humans. According to the researchers, these earlier findings, along with their own, indicate that resveratrol is a potentially effective treatment for erectile dysfunction that is also safer than current treatments.
This study has certain limitations. First, although the researchers used a SIRT1 inhibitor, it would be interesting to see SIRT1 activation in other ways as well, to be sure that resveratrol is working through this pathway. Second, a group treated with tadalafil alone might have provided deeper insight into the supposed synergy between tadalafil and resveratrol.
This interesting study comes at a time when the beneficial effects of resveratrol and its ability to activate SIRT1 are under discussion. Although this cannot be considered ironclad proof, and further research is needed, this study shows that in a rodent model, resveratrol activates SIRT1, leading to improvement in erectile dysfunction.
 Yu, W., Wang, J., Dai, YT, Wang, B., Xu, Y., Gao, QQ and Xu, ZP (2022). Modulation of SIRT1 expression improves erectile function in aged rats.
 Baur, JA, Pearson, KJ, Price, NL, Jamieson, HA, Lerin, C., Kalra, A., … & Sinclair, DA (2006). Resveratrol improves health and survival in 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 endocrinology614.
 Pollack, RM, Barzilai, N., Anghel, V., Kulkarni, AS, Golden, A., O’Broin, P., … & Crandall, JP (2017). Resveratrol improves vascular function and mitochondria count, but not glucose metabolism in the elderly. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(12), 1703-1709.
 Mattagajasingh, I., Kim, CS, Naqvi, A., Yamamori, T., Hoffman, TA, Jung, SB, … & Irani, K. (2007). SIRT1 promotes endothelial-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 ameliorate the cyclic nitric oxide/guanosine monophosphate pathway in corpora cavernosa smooth muscle cells and its therapeutic potential for erectile dysfunction in streptozotocin-induced diabetic rats: preliminary results. The Journal of Sexual Medicine, 8(4), 1061-1071.