Thomas Seyfried, Ph.D.: Controversial discussion—cancer as a mitochondrial metabolic disease?

**Peter Attia** (0:04)
Hey, everyone, welcome to The Peter Attia Drive. I'm your host, Peter Attia.
The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world. And this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peterattiamd.com.
Hello, everyone, welcome to this week's episode of The Peter Attia Drive. My guest this week is Professor Tom Seyfried, who many of you will know, but I suspect an equal number of you will not know.
Tom has come to us through many channels, meaning the requests to speak with Tom have come on many levels. There's been a lot of request through social media, through the site, and of course, based on our discussions with Dom Dagostino, Tom has been in front of mine for quite a while. This is my first time meeting Tom, but I feel sort of like I know him because I've read so much of his work. And Bob Kaplan, who of course you all know as my trusty right-hand guy who lives in Boston, actually takes a course from Tom, and he's taken a course in the past and continues to just wander around Tom's office and just hang out with him overall. So in some ways this felt kind of familiar, though it was my first time meeting Tom. Tom's background is that he's got a Ph.D. in genetics and biochemistry from the University of Illinois. Got that in the mid-70s. And a bunch of other distinctions that I'm not gonna go into because we're gonna link to all of that stuff. He did his post-doc in the Department of Neurology at Yale, and it was there that he first became interested in ketones because of their application in the amelioration of recalcitrant seizures.
As we get into in the episode, that led to his interest in cancer, which is now his focus.
Tom has published over 150 peer-reviewed publications. He's the author of numerous books, textbooks, et cetera, including kind of a treatise on this. So his magnum opus is effectively a book called Cancer as a Metabolic Disease. I probably got my first copy of this a few years ago, and in many ways, that's what sort of felt quite familiar in speaking with him. He's currently a professor at Boston College, and his research today focuses on the mechanisms by which metabolic therapies can manage chronic diseases such as epilepsy, neurodegenerative lipid storage diseases, and above all, cancer.
In this episode, we talk about Tom's background, as I sort of alluded to, his work in epilepsy and how that led him to the interest in caloric restriction and ketosis. We revisit the man, the legend, Otto Warburg, and talk about the Warburg effect and Warburg's point of view on these things. And I do push him a little bit on this because I want to point out that it's not entirely clear amongst people what the Warburg effect really implies and how ubiquitous it is. And I have to be honest with you, I don't necessarily share Tom's views on a number of these things. So I wanted to do my best to sort of represent as many other views as possible, but at the same time, I hope the discussion is helpful. We get into a bunch of the semantics. I knew this was a very technical topic and I know that not everybody has the luxury of listening to this while they're reviewing the show notes. So we do go over the difference between respiration or oxidative phosphorylation and fermentation. It's very important to understand this. So one thing to keep in mind with this podcast and frankly, any of the more technical episodes we do, if you're struggling with a concept, hit pause.
I don't think it's worth sort of going through these, not understanding them. I think it's cool to listen to this, hit pause, go back, hit Wikipedia, ping us with a question on social media or whatever if there's a concept that's stumping you. But this is obviously gonna be one of the more important concepts. If you can't understand the difference between respiration, oxidative phosphorylation, as it were, and fermentation, then a lot of this won't make sense. We also get into this idea of substrate level phosphorylation, a very important concept, and the fermentation of glucose. We also talk a lot about glutamine. This is something that I haven't spent a lot of time talking about in the past. I think I do touch on it a little bit with Dom D'Agostino, but we get into it in much greater fashion. And we, of course, get into ultimately the fundamental question that I think people who are interested in metabolic therapies for questions have to be able to answer, which is, is cancer primarily a metabolic disease, meaning a disease whose origin arrives in the mitochondria or in the metabolic machinery of the cell, or is it primarily a genetic disease where sometimes you will and sometimes you won't sustain mitochondrial damage?