 There has been a bit of controversy in the longevity community recently, as some noteworthy work of Harvard scientist and author Dr. David Sinclair, one of the most well-known names in longevity, has been called into question by PhDs and researchers who feel that the data does not back the claims that are being made. We'll explore the root of the disagreements and some possible paths forward in this episode news. In 2003, Dr. David Sinclair published research on yeast in the journal Nature that said, we show that the potent activator resveratrol mimics calorie restriction by stimulating SIR2, increasing DNA stability and extending lifespan by 70%. These appeared to be promising results, and in 2006, Sinclair published another study on resveratrol, this time in mice. The paper was titled, resveratrol improves health and survival of mice on a high calorie diet, and went on to say that resveratrol extends the lifespan of diverse species, and that it produces changes associated with longer lifespan. They argued that, these data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of aging. Based on some of his early resveratrol in SIRT1 activation research, Dr. Sinclair co-founded the biotechnology company Sirtris Pharmaceuticals. This company was purchased by GlaxoSmithKline in 2008 for $720 million. But after that, Dr. Sinclair's research was called into question when other labs had difficulty replicating his results. Eventually, in the wake of clinical trials that didn't go so well, GlaxoSmithKline shut down Sirtris. Still, Dr. Sinclair stood by his work, and resveratrol remained a popular, and in the eyes of many, a promising compound. It was, and still is sold as a dietary supplement, that many take for what they believe are its health and longevity benefits. Among those people was Dr. Brad Stanfield, a medical doctor and YouTuber interested in health span extension, and an increasingly well-known member of the community. In 2020, he posted a video in which he detailed what he thought at the time were the possible benefits of resveratrol and recommended a particular supplement brand. He included affiliate links to these and other supplements in the video description, though this is certainly not uncommon. Later in May of 2021, Dr. Stanfield posted another video in which he apologized to his audience for his previous statements on resveratrol and explained that he had decided to stop taking it. Here's his apology. He then remade this video, publishing an updated version in February of 2022, that he says expands on some crucial points and explores additional research. Here he is summing up his arguments in that video. The foundational idea behind resveratrol is that we want to activate a 2-in-1, but there's no robust data behind that. Resveratrol in normal human cells doesn't activate a 2-in-1 anyway. The only way that it can work is in a very, very, very specific environment that does not match the real world. There's no robust human data supporting resveratrol's benefits in humans, but we do have reproducible data about resveratrol's harms in humans, specifically blunting the positive effects of exercise. And when tested by the meticulous interventions testing program, who did ask Dr. Davidson-Claire's opinion about how to run these experiments, there was no lifespan extension seen. So there's multiple issues with resveratrol. It's poorly absorbed. It's quickly broken down. The idea of activating satuants is shaky at best. Even if we wanted to activate the satuants, it doesn't look like resveratrol does it in a normal human being. And worse than that, resveratrol stresses the cells in such a way that it blunts the positive effects of exercise. So in that way, resveratrol is harmful to humans. Now this is just a summary of his argument, and Dr. Stanfield does include references and sources for those claims, which you can find by watching the full video. Now whether or not he's interpreting those sources correctly, or whether or not they're accurate in the first place, could possibly be debated. Regardless, the information is out there, and I wanted to make sure you had access to it to see it for yourself. For his part, Dr. Davidson-Claire continues to stand by his work. Here he is discussing resveratrol on his new lifespan podcast just weeks before the Dr. Stanfield video was released. I'm actually sitting in front of many pages of notes here. We're going to go deep dive into what is fact and what is not fact, what is known, what is not known, because there's so much misinformation out there, especially with supplements. This is a CERT activator, like the other NAD boosters we've been talking about, works a little bit differently, but like you said, really well studied, and for almost 20 years now, let's start with the animal studies. What do we know? Well, we know, first of all, if you just give it to them in their water supply, it's not going to work. You can't just swallow it and expect it to get in easily. Why not? Well, resveratrol is the equivalent of brick dust. It's really insoluble. If you put it in a glass of water, it'll fall to the bottom. So what you need to do is, we found in both mice and humans, mix it with some food. You can use yogurt, you can use that kind of olive oil, that kind of oily food, and it will dissolve. It's hydrophobic. This is the problem. It's scared of water. And this is actually why you suggested that maybe some resveratrol studies that have shown that it doesn't work as well as other studies show, those studies may have involved people who are feeding mice resveratrol without that additional fat. Yeah, that's the case. Some of these studies didn't include food. So Dr. Sinclair appears to be saying that the result of his studies are not flawed, and resveratrol does activate SIRT-1 and leads to positive health benefits, at least when studies are conducted correctly. But these conversations have made their way to Twitter, where there's been some drama. In 2021, Dr. Sinclair tweeted that a study in rats finds long-term ingestion of resveratrol, delays brain aging and preserves the ability to learn, to which a Twitter user replied with Dr. Stanfields why I stopped taking resveratrol video and asked for a comment. To this, Dr. Sinclair responded with two emojis. I'll let you interpret their meaning for yourself. Something similar happened again with Dr. Stanfield's most recent resveratrol video. When a Twitter user shared a link to the video and asked Dr. Sinclair for clarification, Sinclair responded with, It's confusing, I know. Misinformation everywhere. This is helpful. With a link to his 2006 paper, therapeutic potential of resveratrol, the in vivo evidence. At this point, Dr. Stanfield joined the conversation, replying to Dr. Sinclair by saying that's a 2006 paper. Would be nice if you could address the multitude of other papers published since then regarding resveratrol's lack of benefit and likely harm. At this stage, some other noteworthy people also got involved. Jeffrey Flyer, the former Dean of Harvard Medical School where Dr. Sinclair works, quote tweeted Sinclair and said, It's not a good practice to cite a 2006 paper of yours that has been seriously and multiply refuted since then. It really isn't. Flyer's response was signal boosted by both Dr. Stanfield and Dr. Charles Brenner. It's worth noting that Dr. Brenner is deeply involved in nicotinamide riboside and NAD research and is the chief scientific officer of Chromedex, a company which sells supplements for healthy aging. Supplements that, it could be argued, are targeting the same customers that would also or otherwise be interested in resveratrol. As of the recording of this video, Dr. Brenner's pinned tweet is the first of a 10 tweet thread featuring what he calls lowlights of a massive peer review failure that allowed David Sinclair to say things completely unsupported by evidence. Brenner ended this thread by saying that Sinclair's article was plumbing the depths of misinformation. Now there's a lot going on here. I think it's quite possible that well-meaning criticism or questioning could be taken as a personal attack and pretty soon there are rivalries at play or interpersonal disagreements could be manifested publicly in unrelated areas. And we're talking about people who have made or could make millions of dollars with groundbreaking science. And when there's drama, you often hear people say, don't get so caught up in it, it's not life or death. But in many ways, this is literally about life and death. It's no wonder why this matters so much to so many. Ultimately, I'd argue that the goal of everyone involved here should be to attain and share knowledge about how to extend healthy human lifespan and to make sure that those methods are made available so that they can help people. In that case, we're all working towards the same goal and we should do what serves that mission. And I'm not taking any sides here. First of all, I'm not a doctor and I don't work in a research lab. I likely know less about Resveratrol than every person I've mentioned in the story. And lifespan.io, which is the non-profit organization behind Lifespan News, has crowdfunded support for research conducted by Dr. David Sinclair and is currently supporting Dr. Brad Stanfield's Rapamycin trial. I want to see both of these people do great work and continue to popularize science and longevity. So how can we as a community move forward in a productive way? Well, there are a few ideas. Many people have called for a public conversation on this topic, not taking place in Twitter threads, but a direct conversation as face-to-face as possible. Dr. Stanfield has requested that Dr. Sinclair join him on his YouTube channel to discuss this. I'd love for that conversation to happen, but I don't think that's the venue for it. It has to be a neutral third-party platform so that any detractors can't frame it by saying that it's a marketing ploy. We at Lifespan.io are open to facilitating that conversation, but would be just as in favor of another neutral third party hosting it. And if Dr. Sinclair is unable to participate, surely there is someone else who can represent his view. And I understand that this conversation, if it occurs, will not settle the scientific disagreements, but it will at least provide the opportunity for direct arguments and rebuttals and should serve as the best form of both sides of the issue. Perhaps the outcome of this conversation could be both sides coming to an agreement on a study design that they both sign off on that could settle this controversy once and for all. We've supported these researchers before and we'd love to do it again. Ultimately, we want good science with results that can benefit people. That should be what we all want. Let's make it happen.