Does Resveratrol Really Activate Sirtuins?
The proposition that resveratrol can activate sirtuins, those so-called “longevity genes”, is widely held as true in the scientific literature, but the time has come to reevaluate that claim. Watch Dr. Brad Stanfield show evidence to the contrary.
One of the most highly visible proponents of resveratrol is Dr. David Sinclair, a tenured Professor of Genetics at Harvard Medical School and an expert researcher in the field of longevity. Back in the early 2000s, his lab indicated that resveratrol could activate sirtuins.
Based on the promise of those results, Dr. Sinclair co-founded a biomedical company called Sirtis Pharmaceuticals, which was purchased by the pharmaceutical giant GlaxoSmithKline for $720 million, from which Sinclair reportedly earned about $8 million.
Turns out that Glaxo couldn’t reproduce the results gotten by Dr. Sinclair’s lab, and after several years of trying, shut down the company.
As I wrote in the post Why Trans-Resveratrol Is The Best Resveratrol Supplement:
Sirtis sought to make drugs that act on sirtuins, a class of proteins that scientists believe play a role in aging, programmed cell death, and other key cell processes. It all looked good until it wasn’t. Glaxo shut down the company nearly five years after its acquisition.
Sirtris co-founder Dr. David Sinclair, a geneticist at Harvard Medical School, headed studies that indicated resveratrol and related compounds can activate sirtuins. For reasons as clear as mud, apparently, Glaxo and Sirtis couldn’t make good on the investment aimed at creating a resveratrol-like drug that activated sirtuins.
Dr. Sinclair got a lot of flack after Sirtis was shut down. He still thought that his lab’s experiments were accurate, and after licking his wounds for awhile after the Glaxo fiasco, went back to the lab and again produced similar results as before, which was that resveratrol did activate two of the seven sirtuins; namely, SIRT1 and SIRT2.
However, there still was a problem — other labs couldn’t reproduce Sinclair’s result that resveratrol activates sirtuins. And that brings us to Brad Stanfield, a young medical doctor practicing
medicine in New Zealand and producing well-researched videos that explore longevity science on his YouTube channel, Extend Healthspan.
Like me, Dr. Stanfield believed that resveratrol did just what Dr. Sinclair says it does. Like Dr. Sinclair, Dr. Stanfield and I consumed resveratrol (actually, the trans-resveratrol form), and extolled its purported virtues. But unlike Dr. Sinclair, Dr. Stanfield and I are no longer convinced that resveratrol works as advertised, and consequently, we stopped taking it. Dr. Sinclair has not.
So, who is right — Sinclair or Stanfield?
I think this is an important question to answer. Not just to get to the truth about resveratrol, but to get insights about how someone with the truly admirable credentials and notoriety of Dr. Sinclair can publicly admit to the word that he — and his science — was wrong. Or, at least debate the matter with those, like Dr. Stanfield, who have challenged Sinclair’s assertions that resveratrol can activate sirtuins.
For the nitty gritty on all this, I encourage you to watch Dr. Stanfield’s videos below that will show you why he has reversed course about resveratrol in the videos below.
But first, why give a hoot about resveratrol to begin with?
What Is Resveratrol, And Why Should I Care About It?
If you’re not taking resveratrol and don’t intend to, or you’ve never heard about it, well, perhaps only your intellectual curiosity may lead you to wonder about what all the fuss is about.
Resveratrol is a stilbenoid, a type of natural phenol, which is mildly toxic and produced by numerous plants in response to ultraviolet radiation, injury, fungal or bacterial infection. Resveratrol is concentrated in the skin and seeds of these plants, and is thought to offer a remarkable range of beneficial biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties.
The commonly recognized problem with resveratrol has not been about whether it truly can activate sirtuins (those longevity genes), but that it’s not well absorbed into the bloodstream. So, all of the therapeutic benefits attributed to it are encumbered by its low bioavailability, and therefore its potential health benefits are blunted. The workaround regarding availability was to use a particular form of reseveratrol called trans-resveratrol, which is better absorbed.
OK, so now you have a form of resveratrol that’s bioavailable — especially if you consume it with a dietary fat, such as yogurt or olive oil — but that still leaves unanswered the question about whether resveratrol does all the benefical health benefits attributed to it, such as to activate sirtuins?
Dr. Stanfield offers evidence that resveratrol does not activate sirtuins, as you’ll soon see in the videos below.
Resveratrol Does Not Activate Sirtuins, Says Dr. Stanfield’s Evidence
This is what Dr. Stanfield covers in his first video:
2003 paper published by Dr. Sinclair’s lab indicated that resveratrol is a potent activator of sirtuin 1 (SIRT1) of the seven sirtuin genes (also referred to as enzymes or proteins). This was done in a petri dish.
In 2006, the Sinclair lab published a paper that indicated that resveratrol improves health and survival of obese mice on a high-calorie diet. It was this discovery that led GlaxoSmithKline to purchase Sirtis.
In a paper published in 2011, researchers tried to replicate the Sinclair lab’s results, and found that when the genetic background of the subjects were standardized, and appropriate controls were used, there were no benefits seen for either worms or flies. They also found that the benefits from calorie restriction had nothing to do with the SIRT2 gene, leading the researchers to conclude that resveratrol did not activate sirtuins.
At time stamp 3:22 in the video below, in an interview with Peter Attia, MD, biogerontologist Dr. Matt Kaeberlein agrees that resveratrol can activate sirtuins in yeast, but not in the other life forms studied — and furthermore, whether activated or not, lifepan extension was not observed, as indicated by the Sinclair lab. Dr. Kaeberlein goes on to say that “nobody to my knowledge has ever been able to replicate that initial study from the sinclair lab where they claimed lifespan extension from resveratrol”.
Finally, a 2020 paper using the latest CRISPR technology found that resveratrol does not activate SIRT1; moreover, there is published research indicating that resveratrol might increase cholesterol levels and blunt the beneficial effects of exercise.
Now that you’ve got the basics of the story, watch Dr. Stanfield’s video where you can get more details and see the studies cited:
Click here for list of Dr. Stanfield's references
https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… https://pubmed.ncbi.nlm.nih.gov/12939… https://xconomy.com/boston/2013/03/12… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… https://pubmed.ncbi.nlm.nih.gov/16286… https://www.youtube.com/watch?v=T1ACc… https://www.youtube.com/watch?v=jOE7V… https://pubmed.ncbi.nlm.nih.gov/19843… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… HTTPS://PUBMED.NCBI.NLM.NIH.GOV/32755… https://www.frontiersin.org/articles/… https://www.fiercebiotech.com/r-d/upd… https://pubmed.ncbi.nlm.nih.gov/28182… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.ncbi.nlm.nih.gov/pmc/arti… https://www.youtube.com/watch?v=edrIE… https://www.youtube.com/watch?v=g8bXY…
Dr. Sinclair Responds To Dr Stanfield’s Resveratrol Video
This is short and not so sweet.
Dr. Sinclair did respond to this fracas over his resveratrol/sirtuin research, but as you’ll see, it was unhelpful.
If you’re confused by this review of resveratrol’s effect on sirtuins, know that I’m in the same boat.
I admire Dr. David Sinclair and his extensive body of work in the field of gerontology. I’ve written positively about him.
Nonetheless, Dr. Brad Stanfield’s review of the research casts doubt on Sinclair’s assertion that resveratrol activates sirtuins, and this needs to be addressed, either by Dr. Sinclair himself, someone from his lab, or someone who has been able to replicate Sinclair’s findings.
Until there’s a conclusion to this controversy that supports the use of resveratrol in order activate sirtuins, I will not continue taking it. Perhaps you should do the same.