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Ben Greenfield Podcast - NAD Special

Matt Titlow [00:00:00]:
Aging is more than just boosting NAD Plus, right? Like, we are a complex system, right? And you just talked about inflammation just a second ago. So how do we actually, like, maintain liver function, right? Insulin sensitivity in the liver, insulin sensitivity in the muscle, these sorts of things that would potentially contribute to a loss of NAD Plus. So I guess we're just trying to say is if you're just interested interested in boosting, which we're not, we're interested in boosting and preventing the degradation. If you're just interested in boosting, then yeah, you just take niacinamide. But we believe that there's an offense and defensive role.

Ben Greenfield [00:00:43]:
All right, folks, if you've been interested in this molecule everybody's talking about, that seems to be kind of controversial, NAD or NR or NMN or whatever you want to call it, you're going to want to tune in to today's show because I have a couple of guys who are really smart when it comes to this stuff. Joining with me to discuss all things NAD. So my first guest is Dr. Michael Roberts. He's a professor in the school of kinesiology at auburn university where he directs the molecular and applied sciences laboratory. And the applied physiology laboratory. So basically, this guy has published over 180 different publications in several prominent physiology and nutrition journals. He edits a lot of these journals.

Ben Greenfield [00:01:29]:
He presents at scientific conferences. And one particular area of expertise for Dr. Michael Roberts is NAD. And he's worked with companies like Compound Solutions and the International Protein Board and kind of searched to advise a lot of these companies that are developing products that might contain something like NAD or NMN or he'll clear up the air about what all those different terms mean. My other guest, because this is a three way, is Matt Titlow, who's the CEO of Compound Solutions. And they actually create and provide unique science backed ingredients to different nutrition companies, including one called Biostack Labs, which I think we're going to mention in today's show. And so I've got some articles at Ben Greenfield Life that I've already written about NAD. I'll link to those.

Ben Greenfield [00:02:21]:
I'll link to everything else that we talk about in today's show. So all of the show notes are going to slash ingredients that's slash ingredients, where you can also see the video of today's episode. So guys, welcome to the show.

Matt Titlow [00:02:40]:
Thanks for having us.

Dr Mike Roberts [00:02:41]:
Yeah, thanks for having us, Ben.

Ben Greenfield [00:02:43]:
Yeah, for sure. By the way, for people who are old school like me, listening to the audio, not watching the video, matt, go ahead and speak up so people know your voice. And then oh, OK. Yep.

Matt Titlow [00:02:54]:
This is all right.

Dr Mike Roberts [00:02:57]:
Yep. This is Mike. Mike Roberts.

Ben Greenfield [00:03:00]:
All right, cool. Coming through my headphones, mike's slightly louder and Matt's more soft spoken. So there. That's how you guys might be able to tell these guys apart. So who would like to take on the massive task of explaining exactly what NAD is and what it's doing on a cellular level? I realize that's a jam packed question, but I'll hand it over to you guys.

Dr Mike Roberts [00:03:22]:
Sure. I guess I can start. Ben sort of a molecular biologist by trade, and I sort of apply that set of lenses to exercise science research. But when you read like an Xfiz textbook, historically you sort of appreciate NAD as an electron carrier. And as you know, cells, they need energy to function. And in order to harness the energy in cells, you need to have cellular NAD plus to carry electrons to the electron transport chain. So you can eventually produce ATP in the cell. And that's kind of the main energy currency of all cellular biochemical reactions.

Dr Mike Roberts [00:04:10]:
So historically I think people would view NAD as kind of this energy transfer molecule. A lot of interesting data has sort of surfaced, I would say since really the early 2000s. Right around 2000 or so. Researchers showed that if you elicit nutrient deprivation, whether that's in vitro, like in a petri dish or in rodents, this can increase longevity. And people started linking that to NAD plus levels increase in certain cells or tissues, things like that.

Ben Greenfield [00:04:52]:
Okay. And by the way, just to interrupt you real quick, if people say NAD, do they really mean NAD plus? Like from a semantic standpoint? Because it sounds to me like NAD plus is the electron carrier. So is there a difference? Like when I'm talking about NAD, am I going to sound dumb hanging around know, smart guys like you if I'm not saying NAD plus instead of NAD?

Dr Mike Roberts [00:05:15]:
No, that's a good question. I typically we say NAD or NAD would be NAD plus, and then NADH would be the reduced form that's carrying the electron to the electron transport.

Ben Greenfield [00:05:28]:
Okay, got it. So when it's carrying an electron, it's NADH, and when it's not carrying an electron, it's NAD plus.

Dr Mike Roberts [00:05:35]:
That's correct.

Ben Greenfield [00:05:36]:
Okay, got it.

Dr Mike Roberts [00:05:38]:
Yeah. So since I'd say the early two thousand s, and there's been a lot of names that some of your more educated listeners probably recognize, right? So David Sinclair at Harvard, lenny Gorete at MIT, charles Brenner, Shanichiro, these folks did a lot of work and what they realized was that, hey, look, things like sirtuin activation occur through NAD plus. Mitochondrial NAD levels are linked to cell survival, mitochondrial function, and the like. Research since then has shown that certain DNA repair enzymes are called parps. They're activated by NAD Plus.

Ben Greenfield [00:06:21]:
What's PARP stand for?

Dr Mike Roberts [00:06:23]:
So that's a PolyADP ribose polymerase and it just AIDS in repairing damaged DNA. Okay. Having this metabolite not only is critical for cell function through energy transfer and ATP production, but then you talk about sirtuin activation, you talk about PARP activation. And these enzymes are also critical for cell survival, mitochondrial function and the like.

Ben Greenfield [00:06:54]:
Okay, got it. So we're not just talking about ATP production or are we talking about the fact that NAD plus as an electron carrier or NADH is the electron carrier, right?

Dr Mike Roberts [00:07:11]:
Yeah. So the molecule itself is carrying the electron in the reduced form, NADH, that's going to have the electron to the electron transport chain.

Ben Greenfield [00:07:20]:
Okay. All right, so when you're talking about sirtuin activation, PARP activation, some of the other functions that you hear about NAD supporting, is all of that just basically stemming down from NAD's ability to help the cell produce more ATP? Or are those functions that are in addition to helping the cell produce more.

Dr Mike Roberts [00:07:40]:
ATP, does that make does make that's a good question, Ben. So it is in addition to because NAD plus can act as a co factor and interact with these enzymes in order to increase their activity.

Ben Greenfield [00:07:52]:
Okay, got it. So even if it's not an electron carrier, even if it's not helping the cell produce ATP, there's other functions like some of these repair and maintenance functions that you're talking about that it's doing as well.

Dr Mike Roberts [00:08:04]:

Ben Greenfield [00:08:05]:
Okay. All right, got it. How come it got so popular? Because I interviewed Sinclair back in the day, and obviously some people even talked about how I know he might listen to this show, so I'll be nice, but I think some people have said he might have profit motives. Some people are concerned about the whole industry behind NAD just being all about making money that we don't have to supplement with. Like, what do you guys think spikes this whole interest in NAD? Because it seems to be very popular now.

Dr Mike Roberts [00:08:35]:
Yeah, I guess I can jump in. So there's a few sort of milestone publications, right? Some of which was the energy restriction linking it to NAD plus, and then that being linked to longevity. Since then, they've done a lot of different studies. We've done some studies, for instance, showing if we get a muscle biopsy from an older individual, and then if we get a muscle biopsy out of a younger individual and we look at tissue levels of NAD plus with increased age, you're going to show decrements in muscle content. There was a Minnesota study, I think around 2012 or 2013, where they did MRI imaging of the brain. And so obviously you get pretty pictures from that, but you can also do sort of metabolomics. And these researchers showed that brain levels sort of showed this incremental decrease with aging. And again, that would be NAD plus.

Dr Mike Roberts [00:09:38]:
There have been other studies, I think there was one in Australia showing that with skin cells, there's also this linear decrease of NAD plus with aging. So really what's capturing people's attention and imagination is, hey, look, with aging, we see this natural decrement and it seems to be linear in this metabolite, right?

Ben Greenfield [00:10:04]:

Dr Mike Roberts [00:10:04]:
Now you marry that with the fact that we know it can activate enzymes that are needed for cellular maintenance and repair. And again, that's a direct interaction of metabolite with these enzymes. I think it sort of makes sense that people want to increase their NAD levels, be it through diet, exercise, lifestyle modification, or the like?

Ben Greenfield [00:10:30]:
Yeah, that makes sense. It seems to me the surgeon interest has kind of paralleled the surgeon interest in antiaging and life extension, longevity as a whole, which kind of makes sense if it tends to be as depleted as you're saying it is. Based on these muscle biopsies of older people, is it the same, do you know, in men versus women when you're looking at these biopsies and the depletion that happens with age?

Dr Mike Roberts [00:10:52]:
Yeah, that's a good question. My read of the literature seems to be it's not so dependent on sex. It just seems to be a function of.

Ben Greenfield [00:11:07]:
Yeah, but what about other you know, there's this comprehensive article that I recently released at Ben Greenfield Life. And again, I'll link to all this stuff. You go to slash ingredients because we're going to talk about some different ingredients that could help to increase NAD in the body. But in that article, I talked about how some of the stuff I've seen that can deplete NAD probably come as no surprise to people like alcohol or poor sleep or inflammation or insulin resistance. But are all of those similar pathways and this might be kind of a loaded question or are there different pathways via which each of the things that we know are depleting NAD are depleting? It I mean, is it just the cells getting beat up? Or is alcohol doing something different than poor sleep, different than know, different than insulin resistance, for example?

Dr Mike Roberts [00:12:02]:
I think you may have different mechanisms of so, you know, doing this with this line of research with Matt and other colleagues, I started my journey about three years ago. Matt, is that right?

Matt Titlow [00:12:19]:

Dr Mike Roberts [00:12:20]:
And so I said, okay, to your question, why would we want to increase in Ad levels? And then you quickly find, okay, it's linked to longevity. Got it. It's activating these enzymes. Got it.

Matt Titlow [00:12:31]:

Dr Mike Roberts [00:12:34]:
We know Americans, for instance, and really developed countries, they have poor diets. So is this because we don't have enough vitamin B three, which is a precursor right, to cells making NAD? Is that the problem? And my read on the literature is it's not, at least according to the RDA. We'll get into that later. Because it seems like if you supplement with relatively higher levels of B three or NR, whatever, then you're going to see this bump in NAD. But all that being said, I don't think it's at large sort of diet, people not hitting the RDA. Does that make sense?

Ben Greenfield [00:13:17]:
You think that the strip in NAD that we see with age is not because people aren't getting enough vitamin B three?

Dr Mike Roberts [00:13:23]:
That's correct.

Ben Greenfield [00:13:25]:
Okay, so it would be some of these other reasons like alcohol and porcelain.

Dr Mike Roberts [00:13:29]:
Inflammation, then with aging, what's going on? And I can speak to our own research. We published a study a couple of years ago. And we looked at young versus old, and I'd say old, it's about 60 years old. And we showed that muscle tissue NAD plus levels were lower, like 60% lower. Now, these people did not exercise right. We then had them engage with ten weeks of resistance training and we showed a restoration to pseudo youth like levels. So exercise certainly can affect it. We also looked at the enzyme in the muscle that's responsible for generating and maintaining NAD plus levels.

Dr Mike Roberts [00:14:18]:
It's called NAMPT. And we showed that exercise was able to increase the levels of that enzyme. So that's where I think physical activity and if you talk about aging and people just generally being more sedentary, perhaps part of the decrement in muscle at least is related to this decrease in NAMPT enzyme content.

Ben Greenfield [00:14:41]:
Right, okay. Something important there, by the way, though, you said it was ten weeks of resistance training.

Dr Mike Roberts [00:14:46]:
That's right.

Ben Greenfield [00:14:47]:
And then you said physical activity. Do you think it matters like cardio versus weight training when it comes to natural methods to increase NAD?

Dr Mike Roberts [00:14:54]:
I think it's a conserved mechanism across both modalities, to be quite honest with you, because the only study prior to us doing that was done, it was out of ECU, and they were looking at endurance training and they showed that endurance training can elevate muscle NAPT levels. There's some sort of conserved mechanism, and you see this with other things like myostatin. I don't know if you've ever delved into that can of worms, but myostatin is not good for muscle growth.

Ben Greenfield [00:15:27]:
I've Googled myostatin knockout bowl and myostatin knockout dog and myostatin knockout mouse. And that Google image search result will show you some pretty good proof in the streets of what happens when you get rid of myostatin supports muscle growth.

Dr Mike Roberts [00:15:46]:
And to be clear, myostatin, so far as we know, doesn't have any link with NAD. But that's just an example. If you look at something like myostatin, which is a protein your muscle produces if you go out for a run or if you lift weights, there's a conserved mechanism where both modalities will downregulate the production of that gene and protein in muscles. So it seems to be the same with NAMPT, which is the enzyme that's used to maintain cellular NAD levels. Right. That exercise can affect that, I think a big thing. And Matt, you can hit on this, and we've talked about this is inflammaging, right? We've all heard that term and it's been thrown around a lot and I don't like using it because really when you talk about the biomarkers to define inflammaging, you're going to get some differences in opinion there. But here's the deal.

Dr Mike Roberts [00:16:39]:
We know if you're getting older and you don't exercise and your diet's not good, and we take a blood draw, we're going to see the elevation in certain cytokines, which are just proteins in the blood that are going to promote this low grade inflammation because they trigger immune cells to produce inflammatory mediators. And that's bad for a variety of reasons. It can sort of depress exercise adaptations. Right. There's been obvious cardiovascular issues in terms of atherogenesis and high blood pressure. This, that, and the other. There's metabolic issues with insulin resistance, with low grade inflammation. Well, with inflammaging immune cells, they have a protein that's called CD 38.

Dr Mike Roberts [00:17:31]:
CD 38 is also a consumer, just like parps. And just like sirtuans, CD 38 is a consumer of NAD plus. And so with this inflammaging, you may sort of up the consumption of NAD levels. And that could be one of the reasons as to why you see this decrease not only with aging, but really we're talking about aging and poor lifestyle. Does that make sense?

Ben Greenfield [00:18:01]:
Oh, it totally like, there's this one political commentator I listen to sometimes. His name is Charlie Kirk, and he has this ad on his show where he says, yeah, I fly all over the country. And one of the ways that I've kept myself from feeling as though I've been hit by a truck with however many hundreds of hours of flying the guy does on a near monthly basis, he says, is, I use NAD. And I thought that was interesting that I heard him say that. It's fresh in my mind because I think I heard him running that ad this morning. When I'm low on sleep, when I'm doing a lot of hefty airline travel, when I've been hit with a high amount of inflammation, even though I live a pretty clean lifestyle, NAD seems to help me out a ton. And so there's definitely something going on. I mean, even like lack of sleep or sleep deprivation seems to make a pretty good dent in that too.

Ben Greenfield [00:18:55]:
So it would make sense then coming at it from the other way that inflammation, whether it's from a poor diet or from airline travel or high EMF stress or whatever, could be helped out by restoration of NAD levels. And inflammation could also deplete NAD levels more rapidly. Yeah. Yep.

Matt Titlow [00:19:14]:
Exactly. If I could jump in, this is exactly why we're even collaborating with Dr. Mike Roberts at Auburn, is because at the end of the day, it's not about boosting, because if we're just boosting, we just take niacinamide Nrnmn and be done with it. But it's about the NAD plus pools. Right. Your status. It's about maybe preserving the declination, the decline, the degradation of NAD plus. So it's about playing offense and defense.

Matt Titlow [00:19:45]:
Like, for example, with that NAMPT enzyme, for example.

Ben Greenfield [00:19:49]:
Okay, so offense and defense. When you're saying that, you mean like taking stuff in addition to just vitamin B, three niacinamide?

Matt Titlow [00:19:58]:
That's exactly. Essentially, you want to reduce the degradation while also laying the foundation for a boost. In other words, do you want to just flood the system with Nd plus precursors? And we argue, no, you don't want to do that. It's almost like, hey, do you want to just take, like, a load of niacinamide and smoke a cigarette? Probably not, right? So, anyway, this is what we're trying to do, is play offense and defense so their NAD plus status remains balanced.

Ben Greenfield [00:20:34]:
Okay. I'm actually very interested in that because I was with somebody who's I consider to be pretty smart in the whole nutrition and supplements industry. A few weeks ago, we were walking on the beach, and he's like, Ben, like, all these NAD, NR, NMN supplement companies, they're crap. They're just making a dime. All you need to do is take niacinamide. That keeps your NAD levels restored just fine. Good old dirt cheap vitamin B three. What you're saying is that's just one part of the equation.

Matt Titlow [00:21:02]:
That is, and we're agnostic to that booster. Let's call it niacinamide for half of the equation. I agree with him. Right. So we're agnostic to whether it's NMN, NR, or Niacin even, for that matter. And there are studies there's at least a study showing that they are boosting NAD plus at relatively equal levels. In other words, milligram per milligram.

Dr Mike Roberts [00:21:30]:
Yeah, there was a study in 2020 from a Japanese group, and you can take all of these boosters and you're seeing sort of the same thing. And, Ben, to your point, you can just take the niacinamide, and it's a lot cheaper. And I don't make a buck, by the way, on any of know full disclosure. Right. Obviously, I've consulted with Matt, and it's more scientific advising, but as products go, they sell and other people make money. Man yeah.

Ben Greenfield [00:22:02]:
Okay, so explain this to me just a little bit more about why I couldn't just take niacinamide. Because you said you're boosting and you're, I think, maintaining the pools or at least decrease the amount of degradation of what you're boosting. But what exactly is going on? And then would you say then as a part of this ideal scenario, you take niacinamide, but then you also take some form of NAD?

Matt Titlow [00:22:27]:
So what we believe is that you take something like a substrate, like a niacinamide, for example, but you're also working on the defensive side. You're trying to prevent the degradation. And that's, like, what we'll talk about later probably is like, NAD Three, which contains theocrine, and there are others, because aging is more than just boosting. NAV plus. We are a complex system. You just talked about inflammation just a second ago. So how do we actually maintain liver function, right? Insulin sensitivity in the liver, insulin sensitivity in the muscle, these sorts of things that would potentially contribute to a loss of NAD plus. So I guess we're just trying to say is, if you're just interested in boosting, which we're not, we're interested in boosting and preventing the degradation.

Matt Titlow [00:23:23]:
If you're just interested in boosting, then, yeah, you just take niacinamide. But we believe that there's an offensive defensive role.

Ben Greenfield [00:23:31]:
Okay, yeah, I actually want to hear a little bit more about that. Offensive and defensive role. But before that, back to, I guess, what might be the offensive role. We've already named some things like sleep deprivation, inflammation, too much airline travel, exposure to EMF, insulin issues with probably a link to the diet from that standpoint. But what about ways you could naturally increase it? Because I've heard people talk about stuff like sauna or man, I think fermented foods was another thing I heard one time. But what are some ways that you would naturally increase NAD or even things that you guys would do if you were to say, okay, I couldn't take any supplements at all? How am I going to keep NAD up?

Dr Mike Roberts [00:24:13]:
I think the big one is what we hit upon earlier, and that's exercise. I mean, no question, right? So if you want, Ben, I can send you the article. You could put in your show notes for sure. But in older individuals, which again had around 60% decrements in muscle NAD levels relative to college age individuals, just ten weeks of training, and that was total of 20 training sessions, it restored those levels, and we thought that it operated through that NAMPT enzyme, which is part of the salvage pathway that keeps NAD levels relatively higher. So the big one is exercise, to be clear. Right. The other is I did a little bit of digging into alcohol consumption. There's a guy at UCLA by the name of Sam French where he's proposed in rodents, at least that high blood alcohol levels, which are experimentally induced, will lower liver levels of NAD plus.

Dr Mike Roberts [00:25:20]:
So nothing wrong, obviously, with the occasional drink, but if you're binge drinking all the time, probably not good for the liver NAD plus levels, and that may trickle down to other tissues as well.

Ben Greenfield [00:25:33]:
Right, yeah, I'm glad you brought that up too, that you mentioned binge drinking because most of the studies I've seen on the deleterious effects of alcohol involve an amount of ethanol that would cause someone to become near inebriated. I don't know a lot of health enthusiasts who are doing like me, like a little bit of bitters or a nice digestive, like I've been on a Croatian polenkovatch kick lately. Or IBO libo from Italy, like handcraft or wildcrafted herbs and plants and bitters that have a little bit of alcohol added to them that I'm serving over sparkling water with a little bit of lemon. That's way different than a couple of six pack of beer on a Saturday night or going through like, three fishbowl sized glasses of wine on three different nights of the week when you're stressed out. I really think we have to not use baby talk when it comes to alcohol and have it be black and white. Yes or no? I think the dose, of course, is the poison. The delivery method is the poison. And I personally use NAD and I drink alcohol, but I highly doubt that even my type of alcohol consumption is stripping my body's levels of NAD.

Ben Greenfield [00:26:47]:
That remarkably agreed.

Matt Titlow [00:26:50]:
Yes, agreed.

Dr Mike Roberts [00:26:52]:
So, yeah, those are the big ones. And then you talked about sleep deprivation or jet lag or what have you. I've seen a little bit of literature, and I can't recall any of the authors, but I looked into that, and that's a bit of a chicken, the egg thing, or chicken or the egg thing. Excuse me. Because I know they're trying to use boosters to perhaps restore sleep, but does sleep cause deprivation? So I think there's a little bit of science to be parsed out there.

Ben Greenfield [00:27:21]:
Yeah. Okay, that makes sense. By the way, have either of you guys ever been sleep deprived and just taken a bunch of it's? I know. Matt, you're involved with the cell regen stuff from Biostack labs. That's one that I've taken, like, a double dose of on a sleep deprived day, have either you guys actually done that?

Dr Mike Roberts [00:27:41]:
I've been sleep deprived, but I've not done. I have four kids. Very yeah.

Matt Titlow [00:27:50]:
Yeah. I think we need to try that in your household.

Ben Greenfield [00:27:54]:
You do that's actually, my stack for sleep deprivation is Creatine and NAD and Creatine. They've shown that slightly higher dosages for brain function and sleep deprivation, like ten to 20 milligrams. And then even though I don't know the exact dosages on NAD, usually I just throw in a couple of extra capsules. It is a game changer to stack NAD and Creatine on a sleep deprived day. It's literally almost shocking the amount of extra willpower and brain power you get just from that stack alone.

Dr Mike Roberts [00:28:25]:
Yeah, that's interesting. And this is kind of a left turn, but I've been involved with a lot of Creatine research, and we're showing brain, at least in the rodent model, and there's some human studies, too, that Creatine is good for the brain. But like you said, you probably higher doses. So you typically hear 5 grams per day is kind of the maintenance dose or whatever. Folks like Darren Candel, Scott Forbes. Those guys would say, hey, man, let's go. 710 grams per day to get these added benefits to other tissues besides skeletal muscles.

Ben Greenfield [00:28:55]:
Now, Michael, I think you were saying there's not a huge difference between supplementing with NR or NAD or NMN. Like, let's say you're already using a little bit of Niacinamide, as you've recommended, and then you want to keep levels up, like playing that defensive strategy. Are you saying it doesn't really matter if you use NR, NAD, or NMN?

Dr Mike Roberts [00:29:13]:
Well, to be clear, I've not done those studies. Right, but there was a recent study from Japan in 2021 that did the head to head comparison on I believe it was NR. It was niacinamide. Right. And Matt helped me out there.

Matt Titlow [00:29:31]:
There was.

Dr Mike Roberts [00:29:34]:
Yeah, and they showed that it was like, five or six people. So, caveat being that it's relatively limited in scope, but looking at serial blood draws post consumption, that you would see the same response in the blood with NAD plus levels. So based on that, so far, it seems like all cause the same effect when it comes to boosting the metabolite. But buyer beware, right? I mean, research, it takes years to sort this stuff out. So I think we need a little bit more research to hone in on that because of the limited scope and end size and that sort of thing.

Ben Greenfield [00:30:12]:
Yeah. What do you think about that, Matt?

Matt Titlow [00:30:15]:
I think so far, it seems to be equivalent. So I don't believe that there's a big difference at this time between the three.

Ben Greenfield [00:30:28]:
What about NAD Three? Because I think that's originally how I hooked up with you, Matt, was I interviewed Tony Robbins and Pierre Di mondis, and those guys were like, dude, you got to check out NAD Three. It's one of the best ways to keep levels boosted with oral supplementation. Later on, I connected with Biostack Labs, who was making this cell regen product that has the NAD Three in it. And I think you've helped them out with that product. But what's the deal with NAD Three?

Matt Titlow [00:30:59]:
So this came about from me and the late Dr. Hector Lopez. I don't know if you knew him, a brilliant I did individual. And, yeah, he was connected with Tony and Peter, et cetera. And so I went to Hector with an idea. He and I went back and forth and then came up with N 83. And then he involved his partner, who we are still partners with, tim Zigenflus. Dr.

Matt Titlow [00:31:34]:
Tim Zigenflus. And also I'm involved with Hector Lopez, his wife, Yari Lopez. So what we were thinking is, okay, how do we, again, play a little bit of offense and defense? Right. So on the defensive side, we went to Mike and said, hey, let's just study this at a cellular level. And what we found is what Mike just said earlier, which is an upregulation of the NAMPT enzyme. So just like exercise keeps that, let's call it healthy or functioning, and that is what is converting that substrate, call it niacinamide to NAD plus. This is what we're finding, is that NAD Three is up regulating that enzyme. So when you have that substrate, it converts call it niacinamide in the blood, for example.

Ben Greenfield [00:32:26]:
Okay, so NAD Three is up regulating the NAMPT enzyme, which is allowing for the conversion of something like niacinamide into NAD.

Matt Titlow [00:32:38]:
That's exactly, yes. Okay.

Ben Greenfield [00:32:40]:
And what is NAD? Three exactly?

Matt Titlow [00:32:43]:
NAD Three is made up of three ingredients. One is theocrine. Theocrine is a methyl urate. It looks very structurally similar to caffeine, but has different action. So its different action is mostly, believe it or not, as a dopamine agonist, as well as some lipid metabolism, like in the liver. Right. So kind of liver. And dopamine is kind of its action.

Matt Titlow [00:33:11]:
It also contains NAD. Three. Also contains wasabi.

Ben Greenfield [00:33:16]:
You mean like wasabi spicy pea wasabi.

Matt Titlow [00:33:19]:
Exactly, yes. And the third. Is a copper one. So it's reduced form, the bioavailable form. And I can go into why if you would like, but that's the makeup of the NAD molecule.

Ben Greenfield [00:33:35]:
I want to know how those things work. So it's wasabi extract theocrine. And what was the last one?

Matt Titlow [00:33:40]:
You said copper one, cooperative copper one.

Ben Greenfield [00:33:46]:
Okay, so why those three?

Matt Titlow [00:33:48]:
So what we were thinking this is me and Hector early on. I said, hey, what about theocrine for kind of like the anti inflammatory action, kind of like cert three activation. So think of liver function, lipid metabolism, this sort of a thing. Kind of like a healthy aging on the anti inflammatory side, the defense. But I said, well, aging is more than that. It's mitochondrial function. What about copper? There's a depletion in soil over the last 50, 60 years, for obvious reasons. And then he's like, yeah, that's cool, but what about something like wasabi like broccoli, these things that have, like, isothiocyanates, these help with antioxidant status and more.

Matt Titlow [00:34:40]:
So it was more about addressing multiple hallmarks of aging versus just saying, you know what, let's reduce all of aging to NAD plus. We all know that's not rational. So it was about trying to take three of these ingredients, combine them together to have to conquer like seven pillars of aging versus just one, for example.

Ben Greenfield [00:35:03]:
Okay, that makes sense. Those three are working in combination. When I'm looking at the cell regen label, though, you've got niacinamide, 125 milligrams of niacinamide. Then you have this NAD three, which makes sense. The wasabi extract, the theocrine and the cooper's niacin. Then there's resveratrol spermidine and black pepper extract in there. Why'd you add those in?

Matt Titlow [00:35:25]:
Right, so that's a Biostack question. But if you are looking at resveratrol, that's obviously extremely famous. People know that from years ago from Sinclair and Sirtuan activation. But also keep in mind that Mike was saying earlier that know are consuming. So, you know, having that substrate in there like a resveratrol is a nice way to preserve NAD plus status without it being consumed. Right. And then when you add in something like a spermidine, we call it youth. You're looking at another pillar of aging, autophagy.

Matt Titlow [00:36:10]:
So we can go into that if we want to, but I don't want to talk too much. But the bottom line is looking at various pillars of aging and why each of those combined into something greater than each of its individual parts.

Ben Greenfield [00:36:24]:
Yeah, I've done podcasts on autophagy before the cellular cleanup, and I think a lot of my audience gets it. And I've talked about spermidine before as well. I was just curious the reasoning behind throwing those in there along with the NAD three, but it seems like a good formulation. It also kind of makes me think a little bit about whether or not you could do this too. I I used to know one doctor, and he told me that he only takes NAD five days on, and then he takes two days off because he doesn't want to overload himself with NAD. And then I came across this study by Nicola Conlin that somebody forwarded to me, and I'll link to it in the show notes. If you go to Ingredients. It's called a systems approach to NAD restoration.

Ben Greenfield [00:37:17]:
And in that article, she goes into the idea that if you have excess inflammation that too much NAD could be bad for you. Or that if you're I think the other argument in there is that potentially if you have poor methylation status, it might also be bad for you. Which I thought was interesting because a lot of people who get NAD IVs feel better if they take a methyl donor prior, like trimethylglycine or Sammy or something like that. But what are your guys thoughts on this idea that too much NAD can be bad for you?

Dr Mike Roberts [00:37:55]:
I can take a stab. So right. If you just look for the magic pill and then you don't change your lifestyle, right? And you're sort of still susceptible to this implementing thing. I mean, you are providing right, if we take the Niacinamide, we boost the NAD plus and cells. Oh, but then, by the way, now we have a substrate for something like CD 38 to consume it and propagate inflammation. That's where I think you can perhaps see a little bit of trouble that's hypothetical, and I haven't read into that. I found a very intriguing research article from the Buck Institute where they had developed mice that didn't have the CD 38 gene and then they showed feeding with precursors, clearly had a conferred benefit. Not sure if they looked at any sort of secondary inflammation status.

Dr Mike Roberts [00:38:56]:
The point being that we have a clear link. CD 38 in immune cells can use this as a substrate that can promote inflammation. You can even search PubMed or Google Scholar and you can see this link between inflammatory bowel disease and people making the argument that substrates for that being N 80 plus could sort of exacerbate that process. So I'm always a big proponent, and I preach this in classes on podcasts, right? I mean, supplements are what they are, and that is we're looking to enhance, but we're not looking as the supplement to cure the ailments that you may or may not have. And that really starts with cleaning up the diet, not drinking as much, not smoking, to Matt's point, and certainly consistently exercising. Once you get into that, in my opinion, once you get into that routine, then from there you start really tinkering with supplements because you've established a nice baseline. Does that all make sense?

Ben Greenfield [00:40:04]:
Yeah. And also based on my understanding of that paper, especially if you have some genetic methylation issues, not only kind of stopping up the leaks of inflammation if they exist, prior to starting into Hefty NAD supplementation, but also addressing methylation issues like getting really good bioavailable folate, avoiding supplements that might contain synthetic folic acid or cereals and grains fortified with synthetic folic acid, and even considering something like organ meat or liver consumption to get really bioavailable methyl groups on board. My takeaway from that paper was don't start taking a bunch of NAD to Band Aid an issue. Instead, use that to support your body, but address inflammation from a wide variety of sources and then make sure that you test and address methylation status.

Dr Mike Roberts [00:40:55]:
Well, here's a little secret, Ben. So we wear a lot of hats, and some of the stuff that we do is just we want to look what exercise does regardless of supplementation. And we worked with a researcher that's really good with DNA methylation arrays. We had people lift weights and we took biopsies like hours afterwards. Exercise can vastly and robustly affect muscle DNA methylation. We did another study showing with aging, for instance, you're going to have mitochondrial DNA in muscle. It is hypermethylated. And that when you exercise.

Dr Mike Roberts [00:41:31]:
And these are older individuals, but you promote chronically this hypomethylation so that you can have mitochondrial DNA replication. You can have mitochondrial DNA transcription to make eventually the electron transport chain protein. So again, it comes down to, I think, exercises first. And I mean, clearly conflict of interest, right? I'm in the school of kinesiology. You have to really do these things from the lenses of, hey, we need to get physically active, and then from there, how can we support the system?

Matt Titlow [00:42:01]:
Right? I'd also like to jump in and say, didn't you study when you were studying NAD Three? We obviously found that it didn't hypo or hypermethylate. Right? It was quite balanced. But didn't we look at another NAD plus precursor and it was hypermethylating? In other words, to Ben's point, you can overdo it, I guess to Ben's point. Right. So, yeah, exercise may recover that, but that was something that we actually did to make sure that we were not hypermethylating. But you could because we actually tested and it did.

Dr Mike Roberts [00:42:50]:
Just for the listeners, a study we did, and this was in collaboration with Tim Zigginfus and late great Hector Lopez, but there was a placebo group involved and there was NAD Three. And then we have a little bit of preliminary data with NAD Three plus a precursor, but we're still sort of analyzing that. Long story short, we put out sort of the early work with just placebo versus N 83 groups. These are humans. We had baseline sort of pre intervention blood draws where we isolated the PBMCs, which is immune cells, for lack of a better term, from the blood. And then after supplementation, which was twelve weeks, we again took those cells from the placebo and the NAD Three group, and we did DNA methylation arrays and we saw less erratic methylation. Now, what does that mean? Right. So over the intervention, there was less hypermethylation of the DNA in these immune cells.

Dr Mike Roberts [00:43:48]:
And there was less hypomethylation relative to the control group. So that's interesting. The other thing we did was we did a technique that's called transcriptomics. So you can look at all of the messenger RNAs that are being expressed in those cells. There were a lot of them. There's not like one or two. I can say, hey, these are critically important. Some were affected in a positive light that were related to DNA repair.

Dr Mike Roberts [00:44:18]:
But when you take this list of differentially expressed mRNAs through the intervention between the NAD three group and the control group, and you do sort of this in silico technique on the computer saying, okay, this basket of mRNAs, what does this represent? There were a couple of things that I thought was really interesting, one of which was we see this reduction in er stress and that's potentially because it's predicted through these mRNA signatures, right?

Ben Greenfield [00:44:49]:
You mean endoplasmic reticulum stress?

Dr Mike Roberts [00:44:52]:
That's right. Yeah. Sorry. So endoplasmic reticulum stress, which if it becomes dysfunctional with aging, that can cause cellular apoptosis, cell damage and the like, right? Mitochondrial damage, you name it. So that was interesting. Another one which I was like, what's going on here is that the mRNA signature n 83 versus control with that intervention was predicted to lower mRNA transcription in these cells. So I thought initially, this is not good, we need mRNA transcription, right, just for the cell to function. We'll find out.

Dr Mike Roberts [00:45:27]:
Did a little bit of digging there and this is like 2023 science, but aging researchers are saying one of the reasons why cells may age is that we have sort of this abarant and uncontrolled mRNA transcription. It's almost like this situation where there's not tight regulation and so we have too much mRNA transcription. So again, found that interesting. Can I link an ingredient in NAD three to that effect? That's what we're continuing to do with Matt, right, is saying, hey, let's go back to the drawing board, let's do this in vitro, let's see what's going on. But this is part of what Matt's talking about, which is lowered inflammation. Another thing was improved blood lipids. And we thought that operated through the liver. And then know, using this PBMC model in humans, we're seeing unique gene expression signatures which are leading us to the next step in terms of research.

Ben Greenfield [00:46:23]:
Yeah, that makes sense. What about the idea that what's it called a taphylactic response when you start to get used to something that you're taking, which I think might also be a reason that that doctor was telling me he goes five days on, two days off with his NAD supplementation. You think there's any reason for that? You think that the body can get used to oral NAD supplementation? Like any feedback loops or anything like that, that you guys have heard of?

Dr Mike Roberts [00:46:48]:
Are there feedback loops? I'm not aware of any data on feedback loops. Can you consume too much researching just the precursors alone? If you go to the NIH's website for the Office of Dietary Supplements. Once you start getting to pretty high doses, so we're talking about over a gram per day, you can have side effects like GI distress. Certain liver enzymes are actually elevated in the blood, which would indicate that you have tissue damage. You can certainly have hypotension and things of that nature. So I think, yes, you can take too much, like people that are enthusiasts are, you know, NAD plus. We need to boost that as soon as possible. Let me take double, triple the dose.

Dr Mike Roberts [00:47:44]:
Not a good idea, in my opinion, with the precursors in terms of these defensive mechanisms. Right. What Matt's speaking to? We just don't have the data, to be quite honest. I mean, I think that's an interesting area of study, but what I can say is, based on the human work we've done, we didn't see any of the sort of clinical signs of tissue damage. When you get blood draw at the doctor's office, for instance, you get a lot of tissue enzymes that would indicate as to whether or not you're seeing muscle damage, liver damage, kidney damage. None of that stuff popped off the charts over a twelve week study. But I don't know. Matt, did you want to add to that?

Matt Titlow [00:48:31]:
No, I agree. I think over consuming isn't really a good idea. Yeah, what? You said over consuming is not a good idea.

Ben Greenfield [00:48:43]:
Yeah, well, the other thing that obviously people do massive doses via IV. I've done that before. I've done many nadivs. I've probably done like, I don't know, close to 50 of them over the past maybe seven years or so. And that's 1000 migs, sometimes 1000 migs plus. I've talked about this before on my podcast. I've used NAD patches, like, to do the slow delivery of 500 to typically like 800 milligrams transdermally. There's one company called Ion Layer that makes those.

Ben Greenfield [00:49:17]:
I've even done NAD suppositories. I've done that for like, long haul plane flights before. There's one company called Mitozen where I've gotten NAD Suppositories. What do you guys think of some of these alternate routes of NAD delivery, whether it's IV or transdermal or rectal? Have you guys messed around with that at all? Do you have any opinion on it, Matt?

Matt Titlow [00:49:42]:
Honestly, it feels over engineered. I'm not necessarily against it. What I'm just thinking to myself is if that study that Mike mentioned from 2020 showed Nrnmn and Niacinamide increased NAD plus, then why are we taking it rectally or IV or anything else? Or if you can exercise and keep things balanced, or you can take, like, NAD regen, why? It just feels over engineered, I guess is my point.

Ben Greenfield [00:50:19]:
I don't know. The claim I've heard is better cellular uptake when you bypass oral administration. That pep argument.

Matt Titlow [00:50:26]:
Yeah, but I guess it's like creatine. It's already bioavailable. Do you want it more bioavailable? I guess. How much more bioavailable is that? Is that oral administration. So let's say lacking in bioavailability to the point where you're not boosting or feeling well, well, then obviously you'd go that IV or rectal route.

Ben Greenfield [00:50:52]:
Yeah, well, I think originally a lot of the IVs were used for addiction and detox. And maybe it's just because that high of a dose, as you were talking about earlier, Mike, wouldn't be that well tolerated orally from a gastrointestinal distress mean. Maybe that's why if certainly higher doses might help with detox or with know, that type of thing, that maybe the IVs were favored by a lot of these functional medicine doctors and then later picked up by the biohacking community. But originally, just because you can't take that massive dose without gastric distress.

Dr Mike Roberts [00:51:30]:
Yeah, and the one thing to consider, too is NAD plus itself. To your point, you can't orally ingest it. It's not going to be bioavailable. It's tricky to get across. So it's not fat soluble. Right. It's not going to just diffuse across a cell membrane. And transporter wise, there's not a good transporter system to get it across to.

Dr Mike Roberts [00:51:50]:
That's why you take the precursors. So the precursors can get into the cell and then the enzymes can use it to make NAD Plus.

Matt Titlow [00:51:58]:
To Ben's point is that it is that you might take it just because let's say you're inflamed. You're not exercising and you don't have the NAMPT enzyme to be so to Ben's point, it is lacking in bioavailability orally because you don't have the mechanism. Because you're inflamed, let's just say. And an IV is.

Dr Mike Roberts [00:52:27]:
Think this sort of speaks to I'm not trying to talk over you, Matt, but I think I'm trying to loop in my thoughts to what you're saying, which is and you brought up creatine. I think that's a beautiful example. Hey, man, look, creatine monohydrate works. Everyone's excited now. How can we improve? How can we improve, how can we improve? And so we sort of go through this as a research community, as a nutritional supplement marketing standpoint. There's sort of this long march towards let's improve delivery, let's improve bioavailability, let's inject, let's do this, let's do that. But really, it's like, look, man, Creatine monohydrate works. Should we have stopped there? Is there a point of diminished return? These are things that you have to consider when you're thinking about this stuff.

Dr Mike Roberts [00:53:15]:
And to Matt's point, so far as we know, just a niacinamide on the offensive side seems to be plenty good. I don't know if we're going to get into it and I don't know much about it, but like, NMN, which is another precursor, right, was a supplement. No longer a supplement because the pharmaceutical companies took interest in that.

Ben Greenfield [00:53:45]:
You just shot down my idea for preloaded syringes full of Creatine monohydrate that you could ship out to somebody's house. Thanks a lot for that. But that thing you just mentioned about the pharmaceutical industries is interesting. I saw that, like, you can't get NMN anymore. So what exactly happened?

Dr Mike Roberts [00:54:05]:
Matt probably knows more than I do on that front.

Matt Titlow [00:54:08]:
Yeah, apparently some pharmaceutical companies said that they had filed an ind and prior to it becoming a supplement and pharma one. So far that's essentially the short story.

Ben Greenfield [00:54:21]:
So you think there's going to be some pharmaceutical coming down the pipeline that's basically really overpriced NMN? That you could get covered by insurance or something like that?

Matt Titlow [00:54:29]:

Dr Mike Roberts [00:54:32]:

Ben Greenfield [00:54:32]:
I'm shocked. I'm shocked.

Dr Mike Roberts [00:54:36]:

Matt Titlow [00:54:37]:
First time ever.

Ben Greenfield [00:54:39]:
Yeah. I know I'm spitballing a few random questions at you guys, but this is another thing I've been wondering about. I find NAD very stimulating. Like I mentioned, I've been taking the Biostack NAD Regen stuff that you helped to formulate, Matt. And if I take that at night, I'll have a hard time know. Same thing if I'll do like a NAD suppository on a long haul flight, I don't sleep so well. It's almost like too stimulating. Have you guys ever seen research that looks into circadian rhythmicity in NAD or even just the best time of day and way in which to take it? Like with a meal? Without a meal.

Ben Greenfield [00:55:14]:
What's gold standard if you have this stuff as far as how to dose it and time it?

Dr Mike Roberts [00:55:21]:
Matt, any thoughts on that?

Matt Titlow [00:55:23]:
So I was thinking first I was thinking about within NA three is theocrine, which is a dopamine agonist. It also has been shown to elevate mood, focus and energy. Almost like remember Hector used to talk about allosteric modulation. Essentially it's a slight adenosine inhibitor like caffeine is, but it's a light one. So I think between it's like light adenosine inhibition, it's dopamine activation for mood motivation.

Ben Greenfield [00:55:56]:
Right. And since adenosine increases sleep drive, that might be why if I take the Biostack lab stuff too late in the day, it might be overstimulating for me.

Matt Titlow [00:56:05]:
It could be particularly the dose that you're taking. You asked a second question, which was I lost it. Pardon me?

Ben Greenfield [00:56:14]:
Do you take it with a meal? Without a meal? Morning, afternoon? Has there ever been any research on that?

Matt Titlow [00:56:20]:
No, I would just be surmising. Any thought, Mike?

Dr Mike Roberts [00:56:24]:
If you want. Yeah, and I'm trying to think back to the twelve week study we had done in the humans. I want to say it was in the morning, and I also want to say that it was taken with breakfast, but I'll have to check.

Matt Titlow [00:56:41]:
As a general rule, I would just take it in the morning, generally speaking.

Ben Greenfield [00:56:46]:
Okay. Have either of you guys done the IVs? Like just seeing what that feels like?

Matt Titlow [00:56:52]:
No. I need to come over to your house, apparently. I feel like decked out.

Ben Greenfield [00:57:00]:
I did a 1000 MiG push IV of it once in about eleven minutes with a garbage can next to me for the overstimulating gastric distress. But normally it's like a two to four hour sit with the drip IV and even then, unless you're taking methyl donors like Trimethyl glycine is probably the most popular one beforehand. You still have a pretty large amount of butterflies in your stomach when you're doing it, but I feel this, and a lot of people do as well. You feel pretty unstoppable for a few days after that. Massive of a dose of NAD via IV.

Matt Titlow [00:57:33]:
But you have to take it with TMG with betane, you're saying?

Ben Greenfield [00:57:37]:
If you want to stave off some of the it almost feels like excess sympathetic nervous system stimulation. During might be, I don't know, depletion of methyl groups or poor uptake or what, but a lot of doctors co administer a methyl group along with it.

Matt Titlow [00:57:53]:
There we go from the prior conversation just a few minutes ago, is you're an N of one, but maybe that's it is that you hypermethylate on over consumption of NAD precursors and just take Betane with it if you want to go big.

Ben Greenfield [00:58:10]:
Yeah, that's interesting. What about any new research happening on NAD as far as things that it might help with or delivery mechanisms or anything like that? Is there anything coming down the pipeline that you think would be cool for my listeners to know about?

Dr Mike Roberts [00:58:24]:
Well, so a little spoiler alert, right? With the teocrine and the wasabi and the Cooperas Niacin, we're doing an in vitro study on human liver cells, and we're looking at it more from a cellular resiliency autophagy. We're also some of those legacy markers. So we're looking at cellular NAD plus levels. And so that's done. That study was a contract through Compound Solutions. We're currently disentangling that data in terms of other stuff. Matt, do you all have anything in the hopper?

Matt Titlow [00:59:02]:
Of course. And what we think is like more big picture on longevity. I mean, it was on the front of The Economist a couple of weeks ago. They said like, living to 120, it's arguably the most influential magazine in the world. So this is not going anywhere. And we don't think it's just like settled on NAD three because we're going to keep going, right? Because we will do that. But I think it's all these other pillars of aging. Now we have twelve, so it seems silly that something like boosting NAD plus could be the one key when we have twelve pillars of aging.

Matt Titlow [00:59:38]:
So if you look at like Dysbiosis, for example, we're always talking about autophagy, we're always talking about senescence, we're talking about like methylation status, et cetera, et cetera. But the twelveTH is now Dysbiosis. So how in the world does the gut interact with insulin sensitivity, for example, or mitochondrial function, which is obviously super correlated to aging? So I think the answer to the question is yes, we'll keep study NAD three, but we'll also be looking at combinations thereof.

Ben Greenfield [01:00:14]:
Yeah, I actually just did a pretty interesting podcast. It came out a few days ago with Colleen Cutcliffe, who makes an Acromantia based product. We talked about the gut metabolism axis and the gut brain axis. And, yeah, it is pretty interesting how we're seeing amongst the many dozen or so pathways of aging, that Dysbiosis plays a pretty significant role, which, obviously, again, when you look at functional medicine and they often begin to treat disease in the gut or in the mouth or in the colon, the small intestine, the stomach et of kind of makes sense. So there's another person I interviewed named Sandra Kaufman who kind of like, rank prioritizes different supplements based on staving off the degradation of some of these pathways. And I think NAD plays a pretty significant role in her book as well. Although it's interesting, I think the top of the totem pole, based on all of her clusters of factors and research, I think was like, astaxanthin, which is like a pretty potent antioxidant. So it's really interesting.

Ben Greenfield [01:01:10]:
I just love to keep my finger on the pulse of all this. And obviously, and I've said this before on podcasts, NAD is kind of like near the top of the totem pole for me, not only because I live a pretty hard charging lifestyle, and I'm on planes and often sleeping less than I'd like to, et cetera, and hence my NAD Creatine stack that I favor. But I just feel good when I use this stuff, and this cell regen seems pretty well formulated. Anything else you guys want to share in the last couple of minutes as far as NAD or anything else that you found or you think is important to know?

Dr Mike Roberts [01:01:43]:
We've sort of talked about this, so I hopefully don't sound like a broken record, but I am intrigued with aging and NAD. And I heard a really good friend who's also a researcher. He said, at some point in your career, mike research is going to become me search, right? And I'm now 42. I'll go and exercise, but things ache a little bit more, so a little bit more heightened inflammation after the fact, and I just don't recover as well. So I've been intrigued with aging. I think we hit a lot of high points, which is clearly this metabolite NAD. Plus there's a lot of solid ground to suggest that, hey, man, it's going down with aging. I'm also interested in cellular senescence.

Dr Mike Roberts [01:02:33]:
Personally, I think that's sort of a big area of research that's starting to pop out. So, like Nathan Labrassier, he's doing a lot of good work with Davis England. They're over in Mayo Clinic with skeletal muscle specifically. But are senescent cells hanging around in the tissue, are they really causing a lot of havoc? And are they blunting exercise adaptations? Are they causing anabolic resistance, for instance, as well? Because they're secreting pro inflammatory cytokines in the tissue. So that, to me, is what gets me, really. You know, Matt hit on seeing any we're seeing anti inflammatory effects with teocrine. Not only us, but a lot of literature out there published today to show that so there's a lot of integration between my own interests and Matt's interests where we'll continue to pursue some mechanisms.

Ben Greenfield [01:03:34]:

Matt Titlow [01:03:36]:
And I'd say simply, melding cellular, and let's call it chemical to make a better healthy aging. In other words, starting with autophagy and mitophagy and how to get rid of these, how to make nice copies for cell renewal so they don't become senescent. Right. Starting there and adding in things like NAD Three and other exercise and things of this sort I think is a cocktail. I think is the big picture that I think you have been explained in numerous occasions and your guests, and I just want to reiterate a cocktail versus a singular ingredient or yeah, yeah, I.

Ben Greenfield [01:04:26]:
Think that was a big takeaway from that massive article I released a few weeks ago on NAD. I know a few people I think that you were involved with, Matt, helped contribute to that article. I'll link to if you go to cause yeah, I get deep know, sauna practices and fermented food and some of the exercise protocols that Mike was talking about, the ins and outs of the cell regen stuff, NAD Three and a lot more. So if you want, like that deep nerdy propeller hat scientific dive, also check out that article. And from what I understand, you can even get AI or GPT or whatever these days to read it to you, so you don't have to read it. So ingredients is where I'll link to that. Mike and Matt, I'll link to all your stuff as well. And I think I've got a discount code somewhere for the cell regen from Biostack, which I've been stacking along with the cell shield, which we don't really have time to go into now, but I think it's a pretty good one to combo in my pantry and y'all look to all that slash ingredients.

Ben Greenfield [01:05:28]:
Hey guys, this has been fun. Super insightful. Thanks for fielding all my dumb questions about NAD.

Dr Mike Roberts [01:05:33]:
You're good. Hey, man, can I get one shout out here? My wife, Ben, she loves you. Actually, I told this before I signed on. So I was doing a postdoc in Missouri. We met there. She's a lawyer, super smart, driving back to see her folks in Kansas City, listened to a podcast and she's like, have you heard this guy? I'm like, no. Who's this? This is back in 2011, ben Greedfield. I'm like, oh, okay, cool.

Dr Mike Roberts [01:06:00]:
Kristen Roberts, my wife.

Ben Greenfield [01:06:03]:
That's awesome. Way back in the day. Old school, dude, that's awesome. All right, well, cool. I'll link to that 2011 podcast in the show Notes as well for people who want to hear my high pitched zip pox teenage voice podcasting. No, I'm joking. I'm actually almost 42 myself, Mike, so thanks for the warning on the post exercise soreness. I'll be ready for it.

Ben Greenfield [01:06:23]:
All right, guys, well, thanks so much, folks. This has been Mike Roberts and Matt titlo. I've been talking. To along with me, Ben Greenfield, signing out from again. Show notes or ingredients so you can take a deeper dive into all these fantastic ingredients for upping your own NAD and keeping it from being depleted. All right, Mike and Matt, I'll talk to you later, guys.