Why not resveratrol?

I got an interesting question from a reader who wanted to know why “resveratrol” was not mentioned in our book, The Immortality Edge.  Given all the hype that resveratrol continues to get, it’s a fair question. But in that last sentence is the answer, “hype”.  I can remember someone writing in and saying her doctor told her to pick either TA-65 or resveratrol, because one was a telomerase activator and the other (resveratrol) an inhibitor and they should not be taken together, because they counteract each other.  She stopped the TA-65 (no, not because of cost), because she could not imagine life without resveratrol. This is not the first time I have seen or heard of absolute devotion to resveratrol.  Frankly, this kind of almost religious ardor, over a supplement, should be reserved for something that has actually panned out and been proven – like fish oil!

Resveratrol made its reputation based on the “fact” that it activated a class of histone deacetylases (that there, is one of them epigenetic type terms) known as “sirtuins”. Sirtuins were thought to be longevity molecules, for a long time, before cracks in that argument began to appear. Hundreds of millions of dollars were spent on resveratrol research and sirtuin research, in the hopes of finding the “secret molecule of longevity”. As always happens in today’s world, rumors started and the internet bred more and viola; you now have the wonder drug resveratrol, key to the sirtuins, gateway to the same benefits of calorie restriction for longevity…

Now for a little reality check.

Let’s start with the biggest bomb first. Glaxo Smith Kline, a pharmaceutical giant, paid $720 million to aquire Sirtris Pharmaceuticals, a company headed by Harvard resveratrol guru, David Sinclair. While it is not 100% clear what happened afterward, rumor has it, that much of the data provided prior to the sale, including that on resveratrol and its more potent synthetic analogs, could not be reproduced by GSK’s scientists. Then the actual resveratrol-derived compound, that was in clinical trials, caused several cases of kidney failure and that was the end of “resveratrol as a drug”. That, we do know for sure – no rumors.

Next, it was found that resveratrol probably does not directly interact with sirtuins at all, but works via a different class of energy sensors called “adipokines”, making it a metabolic shepherd, not a longevity one; although fixing a sick metabolism might indeed boost longevity, at least to a more normal level than dying prematurely!  This association with an entirely different class of molecules broke the knee jerk association of resveratrol with sirtuins. Or at least it should have! There are still a ton of folks out there, who didn’t get the message and continue to publish outdated and incorrect information about resveratrol and sirtuins.

Next, the whole sirtuin deal came into question. The longevity gains shown with sirtuins were shown to occur only in metabolically stressed animals, not normal healthy ones. Finally, it was recognized, that people who express dramatically higher amounts of sirtuins, because of a genetic aberration, do not live longer than “normal” people. Fortunately, they don’t die younger either. But sirtuins seem to work only when the organism is under stress.  Guess what. Aging is stress. Diabetes is stress. Obesity is stress, so sirtuins remain attractive candidates for intervention into the diseases of aging and improving health span, if not life span. Sooner or later, Big Pharma will have its sirtuin activator.

Now our book, The Immortality Edge, is the first and only book of its kind about telomeres. Resveratrol has been touted as both a telomerase activator and telomerase inhibitor. How can it be both? Well, technically speaking, there is similar information concerning fish oil (Undarti Das et al.). It is possible for compounds to act one way on cancer cells and another on aging or regular “healthy cells”, that are non-cancerous. So far so good, right – I should have put resveratrol in the book. Well, I did a little research on my own, with my friend Dr Bill Andrews, who tests for telomerase activity like no one else! I sent in several samples of resveratrol, from different well-known reputable manufacturers and not one of them had any effect on telomerase, at all.  I believe Bill has tested other samples as well and has NEVER found one iota of telomerase activation from anyone’s resveratrol. In addition, there is a guy out there who purports himself as a “student of longevity”. He had a web site and was selling potential “telomerase activators” and his own brand of resveratrol. This guy was and is very popular and has a forum that many people visit and pontificate in all manners about longevity. His particular brand of resveratrol was toxic to human cells at relatively low concentrations and his telomerase activators didn’t activate squat. Now he sells TA-65, which does work on telomerase, so he finally got it right!

So, is resveratrol toxic? Is it worthless? Generally the answers would be no and no, if you get a reputable brand. But, in spite of the occasional article that comes out claiming it’s a telomerase activator, we could never demonstrate that with commercial brands, nor has there ever been any human testing outside of cultures in a dish. Because of its interaction with adipokines, resveratrol does indeed seem to have some important metabolic benefits, especially if you are fat or diabetic. It may help you be healthier, which is a huge thing. But, it probably won’t help you live longer. I should also mention that, as a plant-based polyphenol, it is a potent antioxidant and I used it long before it was popular, in a sadly now defunct supplement a few of you will remember as Super Wrinkle Guard. So, I am not “anti-resveratrol”. I am simply interested in facts.

The compound we chose in The Immortality Edge is far less known, but at least as interesting to me as resveratrol and its cousin pterostilbene. Instead of coming from red wine, like resveratrol, we chose the polyphenolic extract of the aronia melanocarpa berry, which has the highest polyphenol content, anthocyanins, flavonols and cinnamic acids of all of the berry families, including the much vaunted blueberry! Aronia is not a telomerase activator or a longevity inducer either, but when it is finally studied, it will be found to be more potent in most aspects than resveratrol.

That said, if you like resveratrol and want to keep taking it, do so by all means. Just don’t expect it to function like TA-65.

Doc