Metabolomics, NAD+, and cancer metabolism | Josh Rabinowitz, M.D., Ph.D.

**Peter Attia** (0:11)
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Now, without further delay, here's today's episode. My guest this week is Josh Rabinowitz. Josh is a professor of chemistry and integrative genomics at Princeton University where his research focuses on a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. He's also the director of the Princeton branch of the Ludwig Institute for Cancer Research and a member of the Rutgers Cancer Institute.
Josh earned his MD and PhD in biophysics from Stanford, which is how we met. We were in the same graduating class, although he of course started earlier because he did two degrees.
In between earning his MD and PhD and joining the faculty at Princeton, Josh worked at Alexa Pharmaceuticals as the co-founder and vice president of research, a topic that we actually touch on in this podcast. Josh is the inventor of over 160 patents, including five drug products that are in the FDA-sanctioned clinical testing pipeline. He has received numerous awards, including an NSF Career Award, an NIH Pioneer Award, and was distinguished as an Allen Distinguished Investigator in 2019
This is a pretty technical episode, I'm not gonna lie. And we really focus on three things, metabolomics, NAD specifically, and of all of its precursors and movements, and cancer metabolism. We opened the discussion talking about metabolism, metabolomics, and fluxomics. And this includes a pretty in-depth conversation around glucose, glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. From there, we speak in more detail on the electron transport chain and the Krebs cycle, and what the implications are, both with respect to drugs and nutrition. This is an important segue then into the second major pillar of our discussion, which is that around NAD. Most of you have heard of NAD. We certainly got a lot of questions about NAD, and not so much about NAD as we do probably more about their precursors, NR and NMN. We've also had previous podcasts where we've discussed this, including episodes with David Sinclair and Rich Miller. So in this discussion, we talk about the intravenous use of NAD, the oral use of the precursors, and I'll just give you a little spoiler alert, or I'll try not to spoiler alert it, but I'll point you to something, which is I learned something pretty significant in this episode that I have historically been saying, incorrectly, for some time. So if this is a topic that's interesting to you, and you've heard me speak on it before, you might want to listen to this because I'm going to come into a big correction. We end our conversation talking about cancer metabolism, and particularly one way in which cancer metabolism and immunotherapy might intersect. So without further delay, please enjoy my conversation with Josh Rabinowitz.
Josh, great to see you again. It was about three years ago, I think it was the last time we saw each other in person at some sort of conference in New York. A cancer metabolism conference, I think, right?

**Josh Rabinowitz** (3:40)
The New York Academy of Sciences, I think.

**Peter Attia** (3:43)
And we somehow wound up at some kind of mediocre bar in Brooklyn, and it might have been the dorkiest concentration of people talking about autophagy and metabolomics and all sorts of things. There was...

**Josh Rabinowitz** (3:56)
That was actually the AACR Brooklyn Conference, that's true.

**Peter Attia** (4:02)
Well, you know, it's really funny. Just recently, I've interviewed a few of our classmates from med school, Max Dean and Carl Desiroth. And I think Carl and I were reminiscing about how you, me and Carl all started our surgical rotation together in the same day. It's almost 25 years ago, and I remember it like it was yesterday, when we were all sitting in the room, practicing sewing with our big, goofy knots and things like that, before we all got divided up into our surgical rotations. Do you remember that?

**Josh Rabinowitz** (4:27)
I definitely remember you. I really do not remember Carl from those days, but I certainly remember you practicing a lot while I looked and said, oh, I guess that's what you're supposed to be doing if you want to become a surgeon. The thing I remember most clearly is being in surgery with you, and it was like the very end of surgery rotation, finally being given the bovey, immediately making a mistake.