Senolytics ⇒ Questioning Resveratrol - why do we take it?

[RobSmith]

I pose this question as we often here of the noticeable benefits of NMN and NAD+ but there doesn't appear to be much in the way of comment on Resveratrol providing any noticeable benefits.
I was intrigued to find out that one of Dr. Sinclair's companies that he founded called Sirtris Pharmacauticals Inc was acquired by GlaxoSmithkline (GSK) in 2008 for US$720 million and the company was specifically focused on resveratrol formulations and derivatives as activators of the SIRT1 enzyme. The company's initial product was called SRT501, and was a formulation of resveratrol.
However, Studies published in 2009 and early 2010 by scientists from Amgen and Pfizer cast doubt on whether SIRT1 was directly activated by resveratrol and showed that the apparent activity was actually due to a fluorescent reagent used in the experiments.
https://www.jbc.org/content/285/11/8340
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832984/
https://onlinelibrary.wiley.com/doi/ful ... 09.00901.x
GSK/Sirtris terminated development of SRT501 in late 2010. GSK said it was terminating SRT501 due to side effects of nausea, vomiting, and diarrhoea it caused, and because the compound's activity wasn't specific to SIRT1, at some doses it actually inhibited SIRT1, and the compound itself wasn't patentable. The company said at that time that it was focused on two compounds called SRT2104 and SRT2379 that were not resveratrol analogs, had better drug-like qualities, and were more selective SIRT1 activators. In 2013 GSK shut down Sirtris.
https://en.wikipedia.org/wiki/Sirtris_Pharmaceuticals
Going back to Dr. Sinclair's LifeSpan book, he even appears to acknowledges that there is a "controversy" when on Page 296 introducing his team members he says about one of them working to "....resolve the debate about whether resveratrol is working by activating the SIRT1 enzyme...." It's also interesting to read in the book and also posted in the Lifespan newsletter that Dr. Sinclair's father hardly ever takes resveratrol.
Having read extensively in this forum about Oleic Acid also activating SIRT1, and given that we all (and Dr. Sinclair) tend to take the resveratrol with Oleic Acid to aid the absorption, maybe it is just the Oleic Acid that is doing us the benefit.
Although resveratrol is supposedly more potent than Fisetin, maybe Fisetin should be the senolytic supplement of choice, though again, I don't think we have seen positive results of any human studies yet on this either.

I'm sure that consuming the root of Japanese Knotweed (resveratrol) is not doing us any harm, but the costs of all these supplements are noticeable and creep ever higher as we need more and more the older we become.
To spend $720m and then give up..... - Am I missing something or is resveratrol not worth taking?

I'm eager to hear other people's views - in the meantime I might just follow Sinclair Senior's route of "just having a pinch of resveratrol when I think about it", but continuing to have a daily shot of Oleic acid.

[Newage]

Interesting RobSmith.
For sometime now I have only been taking
200 mg of Resveratrol daily with my NMN and NAD+ but increasing my daily intake of Extra Virgin Olive Oil.
I was only acting on “gut instinct” as I do in most cases but maybe there is something to it..

[Fred]

Resveratrol has shown results on fasting blood sugar and inflammatory markers and cerebral blood flow in several human studies. NMN has zero human studies that show any efficacy on any parameters as of this writing...but still, we take a chance on NMN working the same in humans as in rodents.

With resveratrol we actually objectively know it affects human physiology in measurable ways.

Sinclair doesn´t take resveratrol with olive oil. That was my suggestion on this forum and that is what I do. Sinclair just takes it with full-fat homemade yogurt. No olive oil with the resveratrol for Sinclair, he uses it in cooking instead.

(why is this posted under "senolytics"?)

[RobSmith]

Resveratrol has shown results on fasting blood sugar and inflammatory markers and cerebral blood flow in several human studies. NMN has zero human studies that show any efficacy on any parameters as of this writing...but still, we take a chance on NMN working the same in humans as in rodents.

With resveratrol we actually objectively know it affects human physiology in measurable ways.

(why is this posted under "senolytics"?)

Thanks Fred - good to know that there has been some measurable positive effects - I guess they are just the sort of things that no-one will ever notice themselves as having any obvious positive physical feeling. On the NMN side, it appears that so many people have more positive things to say about it in respect to noticeable effects - what probability would you put on that being just a placebo effect?

(as for posting under "senolytics" I had a great deal of trouble just trying to get up the screen to create a new topic - I hadn't even noticed that it was appearing under another heading - I thought a "new topic" was just that)

[NewLifeScience]

well, i know we've been aware of the benefits, and at the very least, the correlation of resveratrol to longer life.

I also am aware the reason some experiments were tricky was that it is essentially the combination of Resversatrol with NMN synergistically that has the maximum benefits.

I think the main benefit is that it is a Sirt1 activator. This is all pretty new, but it is the combination of Sirt activators and NMN that i think has us all taking these substances now.

I don't list citations here, this is something that i feel has been well established in human studies.

[Drdavid]

Here is an article that may help with the resveratrol question

Med Res Rev. 2019 Sep;39(5):1851-1891. doi: 10.1002/med.21565. Epub 2019 Feb 11.
Health benefits of resveratrol: Evidence from clinical studies.
Singh AP1, Singh R2, Verma SS3, Rai V3, Kaschula CH4, Maiti P1, Gupta SC3.
Author information
Abstract
Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

[drkris69]

Great article DrDavid thanks.

[RobSmith]

Thank you Dr. David for adding to Fred's data and giving an overall greater number of reasons for continuing with Resveratrol.

[Fondrees]

I used google scholar a while back to research resveratrol and was surprised at all the studies that showed resveratrol benefitting a number of conditions.

[drkris69]

As Dr. Sinclair says that the Resveratrol is the gas pedal and NMN is the GAS!