Latest / Hardiness with Dr Paul Taylor / Are we on the brink of a breakthrough in healthy aging? A masterclass in NAD+, with Dr Charles Brenner

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Are we on the brink of a breakthrough in healthy aging? A masterclass in NAD+, with Dr Charles Brenner · Hardiness with Dr Paul Taylor

• 0:09
  Speaker 1: Doctor Charge Brenner, Welcome to the podcast.
• 0:11
  Speaker 2: It is a pleasure to be with you.
• 0:13
  Speaker 1: You know, I have been waiting for you or someone
• 0:17
  Speaker 1: like you for a little bit of time, right and
• 0:20
  Speaker 1: for our listeners, for the benefit of it. We are
• 0:23
  Speaker 1: going to talk about all things n A D plus
• 0:27
  Speaker 1: and so NMN and are And some people might be going,
• 0:31
  Speaker 1: what the hell is he talking about? And other listeners
• 0:33
  Speaker 1: are going, oh, yes, I know that the longevity molecules.
• 0:38
  Speaker 1: So you are an expert.
• 0:40
  Speaker 2: There through the molecules of life. You know, there's certainly
• 0:44
  Speaker 2: the molecules of metabolism, the central jewels of metabolism, and
• 0:53
  Speaker 2: probably the most evidence based supplement that has been discovered
• 0:57
  Speaker 2: in the last fifty years.
• 0:59
  Speaker 1: That is a interesting that you say, probably the most
• 1:02
  Speaker 1: evidence best supplement in the last fifty years. Because I'll
• 1:05
  Speaker 1: just set this up for the listeners. So I heard
• 1:09
  Speaker 1: about NAD plus, MN and n R years ago, like
• 1:14
  Speaker 1: lots of people who are into longevity, you know, it's
• 1:17
  Speaker 1: all over the internet, and I had started taking MMn
• 1:23
  Speaker 1: and then I just thought one day, jeez, I haven't
• 1:26
  Speaker 1: actually done my due diligence on this, and I had
• 1:29
  Speaker 1: the little ghost of resveratrol in the back of my goodness.
• 1:35
  Speaker 2: Can we reworkwind and reset the whole thing, because if
• 1:41
  Speaker 2: you saw the itch that I got the first time
• 1:44
  Speaker 2: that you said longevity. Yes, I'm just uncomfortable about the
• 1:49
  Speaker 2: framing from the beginning, and I'm super uncomfortable about the
• 1:55
  Speaker 2: connection with rosveratrol, the framing around certain ruins around people
• 2:01
  Speaker 2: not having to age. They're being single, dominantly acting genes
• 2:07
  Speaker 2: that you know that preserve you know, human life. And
• 2:15
  Speaker 2: i just want to tell you that I'm a metabolism scientist.
• 2:20
  Speaker 2: The stuff I work on, it is real. You know.
• 2:23
  Speaker 2: The NAD system is disturbed in probably a dozen different
• 2:28
  Speaker 2: conditions of metabolic stress that are intrinsically associated with repair
• 2:35
  Speaker 2: and anti inflammatory pathways, resistance to infection, getting through time
• 2:41
  Speaker 2: zone disruption. Now there's an evidence basis not only for
• 2:46
  Speaker 2: anti inflammation, but for healthy aging with peripheral artery disease,
• 2:52
  Speaker 2: which might be the central ten million person presentation of
• 2:59
  Speaker 2: age related disease in the United States. But I'm uncomfortable
• 3:04
  Speaker 2: with a lot of the literature, okay, And so what
• 3:08
  Speaker 2: I'd like to do is if we could take people
• 3:11
  Speaker 2: you know on the journey and start with what NAD is,
• 3:15
  Speaker 2: and how it gets disrupted, and what the use cases
• 3:19
  Speaker 2: of NR is. But I'm not going to be the
• 3:21
  Speaker 2: guy that tells you that you won't age, or you're
• 3:25
  Speaker 2: going to live forever, or that your surtoins are going
• 3:28
  Speaker 2: to be activated. And I'll never recommend resveratrol. And I'll
• 3:35
  Speaker 2: explain the difference between n R and NMN and an
• 3:38
  Speaker 2: A D. But there's there's a lot of misinformation out there.
• 3:42
  Speaker 1: All look absolutely charged. And I didn't mean to connect
• 3:46
  Speaker 1: res vitral to NADA. I was just talking about my experience, right,
• 3:51
  Speaker 1: some of my listeners will have will have heard me
• 3:53
  Speaker 1: talk about this before because I've been taking res virtual.
• 3:56
  Speaker 1: You know, again, it was a molecule tited on the Internet,
• 4:00
  Speaker 1: not in the circles you work in, but it was though.
• 4:03
  Speaker 2: But it did come out of of of major labs.
• 4:08
  Speaker 2: I mean that it came out.
• 4:09
  Speaker 1: Of Harvard, That's true. It came out of Harvard and
• 4:12
  Speaker 1: David Sinclair and then he sold his research to GSK
• 4:17
  Speaker 1: or his company, and then they couldn't replicate the research
• 4:20
  Speaker 1: and all of this. Now, the reason why I just
• 4:23
  Speaker 1: made the connection, right is that I was taking NMN.
• 4:29
  Speaker 1: I'd started taking NMN just based on the idea that
• 4:33
  Speaker 1: it was active in pathways that were important. Right. And
• 4:38
  Speaker 1: then I thought, let me look at the the literature,
• 4:42
  Speaker 1: the human literature on MNN and NR, and it wasn't
• 4:47
  Speaker 1: there at the time, right. And I but I've said,
• 4:50
  Speaker 1: this is something that I'm watching very very closely because
• 4:54
  Speaker 1: NAD and NAD plus and its role in the body.
• 4:57
  Speaker 1: I am completely convinced the bike. I'm just haven't quite
• 5:03
  Speaker 1: made the leap of feast that if it gets low
• 5:06
  Speaker 1: and you can take a supplement and it raises it,
• 5:09
  Speaker 1: is it going to have significantly better outcomes?
• 5:12
  Speaker 2: Intend to take a leap of faith. Yes, yeah, And
• 5:16
  Speaker 2: I want you to take a leap with me of evidence,
• 5:19
  Speaker 2: you know. And and and the thing is that the
• 5:26
  Speaker 2: same people that promoted resveratrol are in fact promoting an
• 5:33
  Speaker 2: a man, and a man is actually working. It's It's
• 5:38
  Speaker 2: strange because NMN is n R with a phosphate group
• 5:41
  Speaker 2: on it, but when you take it orally, it goes
• 5:46
  Speaker 2: back to n R before it can get into cells.
• 5:48
  Speaker 2: So MN is weirdly a precursor of n R because
• 5:54
  Speaker 2: then it gets into cells and gets converted to nimn
• 5:56
  Speaker 2: and then nad co enzymes so enemen and are basically
• 6:01
  Speaker 2: working on the same pathways in the body. The folks
• 6:07
  Speaker 2: that brought you, you know, risveratrol as a mass marketed supplement.
• 6:13
  Speaker 2: Of course, it was kind of in the food supply
• 6:15
  Speaker 2: for a long time because it's famously in red wine
• 6:19
  Speaker 2: and it's in peanuts and other stuff. Their use case
• 6:24
  Speaker 2: for it was it activates these genes called sirtuins. Right,
• 6:30
  Speaker 2: Certuins are not conserved longevity genes. They're not even conserved
• 6:36
  Speaker 2: as longevity genes in yeast. As it turns out if
• 6:40
  Speaker 2: you just look at how long yeast cells live without
• 6:44
  Speaker 2: and with the sertu gene, they live longer if they
• 6:47
  Speaker 2: don't have the sertugene. So, even back in yeast that
• 6:53
  Speaker 2: the research was not really sound and it was very
• 6:56
  Speaker 2: selectively presented, and then it didn't really replicate in worms
• 7:03
  Speaker 2: and flies, even though there were some papers in the
• 7:06
  Speaker 2: early two thousands that said that extra copies of certu
• 7:10
  Speaker 2: genes extends lifespan and animals, and as you know, it
• 7:13
  Speaker 2: doesn't work in mice and doesn't work in humans. So however,
• 7:20
  Speaker 2: any D and the four anyd coenzymes, and you know
• 7:24
  Speaker 2: what they are an a D plus, any dh, ADP plus,
• 7:27
  Speaker 2: and an aph. These are the central catalysts of metabolism, right,
• 7:32
  Speaker 2: so they move high energy electrons. We take in food
• 7:37
  Speaker 2: that has calories, protein, fat, and carbohydrate. It gets to
• 7:41
  Speaker 2: be broken down into intermediates like pyravd and alplacated glutorate
• 7:49
  Speaker 2: and the ketyl CoA, and some of it gets fully
• 7:52
  Speaker 2: oxidized generating ATP. Other stuff goes into those intermediate compounds
• 7:58
  Speaker 2: like pyrivate, allen in, alphacita, gluot rate and gets built
• 8:03
  Speaker 2: up into making new lipids, right, making nucleotides that requires
• 8:09
  Speaker 2: the nadph and the NAD system comes under attack in
• 8:14
  Speaker 2: many conditions of metabolic stress. So use case of NAD
• 8:21
  Speaker 2: is basically fighting these conditions of metabolic stress and repleting.
• 8:28
  Speaker 2: We're kind of rebuilding the NAD system inside various types
• 8:34
  Speaker 2: of cells. Hepatocytes, nerve cells, immune cells in order to
• 8:41
  Speaker 2: be able to damp down on overactive innate immune responses,
• 8:50
  Speaker 2: promote DNA repair, promote tissue repair, and just because ultimately
• 8:58
  Speaker 2: we're not interested in improving the health of mice and
• 9:03
  Speaker 2: the laboratory, I'll tell you that there's eight randomized clinical
• 9:07
  Speaker 2: trials that show anti inflammatory activity of NR oral NR.
• 9:13
  Speaker 1: In human beings and humans and jesting.
• 9:16
  Speaker 2: But and I'm going to start mentioning this this more.
• 9:22
  Speaker 2: There's a really important positive result in peripheral artery disease. Okay,
• 9:28
  Speaker 2: And the reason that I'm going to mention this more
• 9:31
  Speaker 2: is the quality of the and the independence of the
• 9:36
  Speaker 2: research group that is running these trials. So this is
• 9:40
  Speaker 2: from Professor McDermott's group at Northwestern University, probably the number
• 9:48
  Speaker 2: one clinical trialists in the area of peripheral artery disease.
• 9:53
  Speaker 2: So you know, ten million US citizens alone, and so
• 9:59
  Speaker 2: hundreds of million, maybe one hundred million around the world
• 10:02
  Speaker 2: have peripheral artery disease. A lot of them are smokers,
• 10:06
  Speaker 2: almost all of them are older. There's signs of you know, atherosclerosis,
• 10:14
  Speaker 2: you know, worse circulation. And at minimum, these people are
• 10:23
  Speaker 2: experiencing pain, loss of mobility, poor recovery from what you
• 10:34
  Speaker 2: and I would consider mild exertion. But if they get
• 10:38
  Speaker 2: a cut or infection, they could get a wounds that
• 10:40
  Speaker 2: doesn't heal, and they could get to a point where
• 10:47
  Speaker 2: something's amputated. Okay. The men typically have a reptile dysfunction,
• 10:53
  Speaker 2: So this is a this is a major age related
• 10:56
  Speaker 2: condition and the type of condition where the primary endpoint
• 11:01
  Speaker 2: in a randomized clinical trial is walking speed. Yeah, what
• 11:06
  Speaker 2: can you do in six minutes?
• 11:08
  Speaker 1: Yeah? Right? And it's just for the for the individuals
• 11:11
  Speaker 1: that the walking speed is clearly something that that is
• 11:17
  Speaker 1: massively influenced by peripheral artery disease because you're just not
• 11:21
  Speaker 1: getting blood flow. So if you can't get proper blood flow,
• 11:25
  Speaker 1: your muscles don't work effectively. So it's one of those
• 11:28
  Speaker 1: things like walking speed is a big predictor of one
• 11:32
  Speaker 1: of the big predictors of how long you're going to live.
• 11:34
  Speaker 2: Right, you can take you can take every publication on
• 11:40
  Speaker 2: DNA methylation age tests and glycan age tests and other
• 11:49
  Speaker 2: biomarker age tests, and you can put them in one pile, okay,
• 11:55
  Speaker 2: and then you give me a function assay, like a
• 12:02
  Speaker 2: six minute walking speed, and I prefer that functional assay
• 12:06
  Speaker 2: to any forest full. You could cut down an entire
• 12:11
  Speaker 2: forest to pivot to publish the papers on methylation based
• 12:17
  Speaker 2: age tests tests, and they don't matter as much as
• 12:22
  Speaker 2: one good test of walking speed because walking speed is
• 12:26
  Speaker 2: what you what you can do, yes, and walking speed,
• 12:30
  Speaker 2: as you know, if you separate people into quartiles of
• 12:34
  Speaker 2: walking speed. That's fitness, and that's future life expectancy. That's function.
• 12:43
  Speaker 2: That's being able to run after your kids or grandkids,
• 12:47
  Speaker 2: make love to your partner, and you know, do a
• 12:52
  Speaker 2: full day of work or a full day of recreation.
• 12:56
  Speaker 2: Walking speed is life.
• 12:59
  Speaker 1: It's it's it's functional capacity, isn't it? And you know,
• 13:04
  Speaker 1: and it's also strongly related to VO two max, right,
• 13:08
  Speaker 1: which in the data is the strongest predictive of how
• 13:11
  Speaker 1: long you're going to live. Right, And you combine walking
• 13:14
  Speaker 1: speed with grip strength, Oh my god, you can forget
• 13:18
  Speaker 1: about all those other tests, not just the DNA methalations. Right,
• 13:22
  Speaker 1: those two combined are way more predictive of how someone's
• 13:26
  Speaker 1: going to live, even than diabetes, carniorder disease, all of that, if.
• 13:30
  Speaker 2: You would see right right, Yes, so.
• 13:34
  Speaker 1: Sorry, I just wanted to just before we move on
• 13:37
  Speaker 1: to this, I just wanted to quickly sidestep into the
• 13:40
  Speaker 1: DNA methalation clocks, which are again all over the internet
• 13:47
  Speaker 1: in terms of and papers reducing biologically do you know what?
• 13:51
  Speaker 1: And I've got quite interested in those, but do you
• 13:53
  Speaker 1: know what really put me off those Matt Chamberlin, who
• 13:57
  Speaker 1: I'm sure you're pretty aware of who's a you know,
• 14:01
  Speaker 1: a big researcher for thees in the intervention's testing programs.
• 14:05
  Speaker 1: He did and the four major ones that are out there,
• 14:10
  Speaker 1: GRIMMAGE and DNA, and I can't remember the other two.
• 14:14
  Speaker 1: But he did all four of them, and he ordered
• 14:18
  Speaker 1: two tests of each. He got them all delivered at
• 14:20
  Speaker 1: the same time. So he did eight tests, all one
• 14:23
  Speaker 1: after the other, sent them back in under different names.
• 14:27
  Speaker 1: Kit they came back he got eight different biological ages
• 14:32
  Speaker 1: and that's when I went, Wow, this stuff is nowhere
• 14:36
  Speaker 1: near ready in terms of.
• 14:38
  Speaker 2: It's even worse in the laboratory because somebody will do
• 14:45
  Speaker 2: some type of intervention on mice or maybe on people,
• 14:51
  Speaker 2: and then they can test multiple methylation age tests or
• 14:57
  Speaker 2: other type of age kits, and if they want to
• 15:02
  Speaker 2: show efficacy, they could basically choose the one that works.
• 15:06
  Speaker 2: It works, yes, yes, supports their priors, yes yes, yes,
• 15:12
  Speaker 2: but walking speed doesn't lie, just like hips don't lie, right.
• 15:17
  Speaker 1: Just like grip strength and VOTMX.
• 15:19
  Speaker 2: So back to perferal ry disease. Folks that are enrolled
• 15:24
  Speaker 2: in clinical trials of peripheral ry disease, you do a
• 15:29
  Speaker 2: I can't remember how long the studies typically go, maybe
• 15:32
  Speaker 2: thirteen weeks. Don't quote me on that. I'm going to
• 15:36
  Speaker 2: look that one up. But these folks are in decline. Yes,
• 15:41
  Speaker 2: so the placebo arm the walking speed is shorter, you know,
• 15:46
  Speaker 2: in the length of the trial.
• 15:48
  Speaker 1: Because they're naturally declining with the edge. They're older people alone.
• 15:52
  Speaker 2: So McDermott at Northwestern was in She does a lot
• 15:59
  Speaker 2: of things in collaborations with different groups that have different
• 16:03
  Speaker 2: you know, interests, And the group that she was interested
• 16:07
  Speaker 2: in that she collaborated with a year or two ago
• 16:12
  Speaker 2: was at University of Florida. They were interested in NAD Okay,
• 16:18
  Speaker 2: so they wanted nicotinamide rib aside as the intervention. They
• 16:24
  Speaker 2: were funded by the National Institutes on Aging, which had
• 16:30
  Speaker 2: been tremendously influenced by this rosveratrol stuff. Yes, they said,
• 16:35
  Speaker 2: we're going to give you the money, but you can't
• 16:39
  Speaker 2: do two doses of n R against placebo. You have
• 16:44
  Speaker 2: to do nicotinamide ribe aside plus or minus rose a veratrol.
• 16:50
  Speaker 2: Oh really, okay, let me tell you what the result was.
• 16:54
  Speaker 2: Nicotinamide ribe aside met the primary endpoint of increasing walking
• 17:02
  Speaker 2: speed with respect to placebo. They had a longer walking
• 17:06
  Speaker 2: speed than when they started. But more importantly, it's a
• 17:09
  Speaker 2: placebook control trial. So you look at the walking speed
• 17:15
  Speaker 2: at the end of the trial for placebo, which was shorter,
• 17:18
  Speaker 2: versus the walking speed at the end of the trial
• 17:20
  Speaker 2: with nicoten rid ribiside, which was longer, and it met
• 17:24
  Speaker 2: their primary endpoint. It scored positive nicotinamide ribiside plus rosveratrol.
• 17:31
  Speaker 2: Rosveratrol actually degraded the positive effect of NR mc dermott.
• 17:37
  Speaker 2: McDermott published this in Nature Communications. Fast forward to last week.
• 17:44
  Speaker 2: You and I are recording this in November. Today is
• 17:48
  Speaker 2: November tenth, and last week McDermott with a number of
• 17:55
  Speaker 2: other collaborators tested mcforman right because wants to test met
• 18:01
  Speaker 2: Foreman in age related conditions.
• 18:04
  Speaker 1: Can I guess fail, Yeah, that foreman. I put net
• 18:11
  Speaker 1: Foreman andres vitral in one of those. It's the old
• 18:15
  Speaker 1: azzie yeah nah, which.
• 18:17
  Speaker 2: Is well, no, met Foreman is a real drug.
• 18:20
  Speaker 3: I mean, so you know, if they have two diabetics,
• 18:25
  Speaker 3: you know, then maybe And I don't understand enough about
• 18:31
  Speaker 3: the mechanisms of action of met Foreman because there's so many.
• 18:36
  Speaker 2: But you know, personally, I'm not about to go out
• 18:41
  Speaker 2: and take a complex one inhibitor. You know something that
• 18:46
  Speaker 2: that you know in some ways impairs my chondral function
• 18:52
  Speaker 2: that has a role in lowering blood glucose because there's
• 18:57
  Speaker 2: a step or two in lukenagenesis that requires mitochondrial activities.
• 19:05
  Speaker 2: But basically, you know, met form bottom line is metform
• 19:12
  Speaker 2: and failed in perferal artery disease. And the same senior
• 19:17
  Speaker 2: author McDermott showed that nicotinride ribside worked. So they're doing
• 19:23
  Speaker 2: you know, they're planning a larger they're roll enrolling a
• 19:26
  Speaker 2: larger trial for NR and Purferle artery disease, and I
• 19:29
  Speaker 2: think that that could be it could be huge. So
• 19:31
  Speaker 2: we have eight positive results on anti inflammatory activity and
• 19:36
  Speaker 2: people we have Perferle artery disease, and there's a number
• 19:39
  Speaker 2: of other trials that are being done in the area
• 19:42
  Speaker 2: of neurodegeneration. Long COVID. We could talk about long COVID
• 19:46
  Speaker 2: because I think by the time you air this podcast,
• 19:52
  Speaker 2: there's going to be a long COVID publication.
• 19:57
  Speaker 1: Interesting before we jump into that, and I do want
• 19:59
  Speaker 1: one to jump into that.
• 20:01
  Speaker 4: I think it's really important charge for our listeners to
• 20:05
  Speaker 4: understand when proper scientists draw start to draw conclusions about
• 20:13
  Speaker 4: research about the efficacy of whatever intervention it is.
• 20:18
  Speaker 1: Now, you have mentioned things that maybe some listeners may
• 20:22
  Speaker 1: have not picked up on, but things like the laboratory
• 20:27
  Speaker 1: that's doing the trial and being a highly regarded laboratory
• 20:32
  Speaker 1: and not just some ship kickers.
• 20:35
  Speaker 2: Also, they have no investment in and R met Foreman.
• 20:38
  Speaker 2: This is they have a thirty year history and trying
• 20:41
  Speaker 2: to help people would prefer our disease.
• 20:43
  Speaker 1: Yes, you know, no industry links, right, which is another
• 20:47
  Speaker 1: big one.
• 20:48
  Speaker 2: I don't know about every single author you know in
• 20:52
  Speaker 2: both of those papers. I know I wasn't involved in them,
• 20:56
  Speaker 2: and that the senior authors are are at nor Western.
• 21:01
  Speaker 1: Yeah. And I think the other thing as well, charges
• 21:05
  Speaker 1: is that different labs doing similar things getting the same results.
• 21:12
  Speaker 1: That's when you start to set up and take notice,
• 21:15
  Speaker 1: right that we're then starting to get an accumulation of
• 21:22
  Speaker 1: good quality evidence as opposed to a lot of the
• 21:27
  Speaker 1: stuff that you see on the internet chided and with
• 21:30
  Speaker 1: some bloody influencer Harvard professor on there talking about why
• 21:35
  Speaker 1: he takes it and all of this stuff. Right, So
• 21:38
  Speaker 1: that's the difference between pseudo science marketing and real science.
• 21:42
  Speaker 1: So now that that's been established, I just want to
• 21:45
  Speaker 1: go back a little bit and explore an a D
• 21:48
  Speaker 1: plus because I mean, you were throwing out lots of
• 21:51
  Speaker 1: terms around metabolism, electron transport chain, just from a simplified
• 21:57
  Speaker 1: perspective for the listeners who may not be up on
• 21:59
  Speaker 1: their bow, biochemistry, just tell us high important nada's in.
• 22:08
  Speaker 2: The body, right, So, I mean, cells can't convert fuels
• 22:14
  Speaker 2: to energy without a transmitter of what are called high
• 22:19
  Speaker 2: energy electrons. And that's fundamentally what nad coenzymes do is
• 22:25
  Speaker 2: that they capture high energy electrons from food oxidation, from
• 22:32
  Speaker 2: burning our fuel. The amazing thing about biological systems is
• 22:37
  Speaker 2: that the energy can be extracted without lighting a match
• 22:44
  Speaker 2: and allowing the high energy electrons to go up in smoke.
• 22:49
  Speaker 2: They're basically the high energy electrons are carried on nad
• 22:55
  Speaker 2: coenzymes and then transmitted to other enzymatic processes that need
• 23:00
  Speaker 2: those electrons. So in order to make lipids and in
• 23:06
  Speaker 2: order to convert RNA nucleotides to DNA nucleotides, in order
• 23:13
  Speaker 2: to make DNA, you need two pairs of electrons. In
• 23:18
  Speaker 2: order to make the carbon carbon bonds and extend a
• 23:22
  Speaker 2: carbon chain to make lipids, or in order to convert
• 23:26
  Speaker 2: a what's called a ribonucleotide to a deoxy ribon nucleotide,
• 23:31
  Speaker 2: you need these these electrons and those are carried on NAD.
• 23:36
  Speaker 2: So under conditions where the NAD system comes under attack,
• 23:44
  Speaker 2: the mitochondria kind of hangs on to its NAD coenzymes
• 23:49
  Speaker 2: longer than the than the cytosol does, but ultimately all
• 23:53
  Speaker 2: of metabolism can become compromised. And then because NAD is
• 23:58
  Speaker 2: also used to repair DNA and to detoxify free radical species,
• 24:05
  Speaker 2: it's really central, you know, to repair and to you know,
• 24:10
  Speaker 2: maintenance of cellular health. And and now we can measure
• 24:14
  Speaker 2: its effect on human health because you know, in chronic
• 24:19
  Speaker 2: inflammatory conditions you have these things like IL ten and
• 24:25
  Speaker 2: ASLE six that are that are elevated and and initially
• 24:32
  Speaker 2: in response to an infection, you get an inflammatory response
• 24:36
  Speaker 2: that's supposed to help your tissues heal. But in older people,
• 24:42
  Speaker 2: as you know, they circulate these inflammatory markers all the
• 24:46
  Speaker 2: time and it's kind of contraindicated. So by suppressing the
• 24:55
  Speaker 2: the hyperactive inflammatory system and R can base get cells
• 25:01
  Speaker 2: and tissues to focus more on productive healing rather than
• 25:07
  Speaker 2: just spewing out in plammatory markers.
• 25:10
  Speaker 1: And so basically our rough layman's translation of all of
• 25:15
  Speaker 1: that charge is that if you don't have a NAD,
• 25:19
  Speaker 1: magic shit doesn't happen in your sales to allow you
• 25:23
  Speaker 1: to still be alive.
• 25:24
  Speaker 2: Right, So it is, I mean, it is amazing what
• 25:27
  Speaker 2: biology does when we think, you know, let me show
• 25:32
  Speaker 2: mad respect to human longevity, okay, because you know, you
• 25:37
  Speaker 2: and I can probably both expect to live into our nineties,
• 25:43
  Speaker 2: you know, with some vigor, Okay, And that's just amazing
• 25:49
  Speaker 2: because if we live till ninety five and we could
• 25:54
  Speaker 2: reproduce when we were fifteen, that's eighty years of keeping
• 25:59
  Speaker 2: are stuff together. I mean, that's an amazing thing. Eight decades.
• 26:06
  Speaker 2: Yeahs reproductive, because the way that animals are built and
• 26:10
  Speaker 2: evolve is you get to reproductive capacity, Yeah, compete for mating, yes,
• 26:21
  Speaker 2: create some offspring, and then you're not that useful.
• 26:26
  Speaker 1: Now, that's right, And the major, the major driver of
• 26:30
  Speaker 1: your genome is not about you. It's about survival of
• 26:34
  Speaker 1: the species, isn't it so?
• 26:36
  Speaker 2: Right?
• 26:36
  Speaker 1: So basically you're talking about an eighty year upside after
• 26:41
  Speaker 1: we've actually done the job that our genome months.
• 26:44
  Speaker 2: The most West didn't reproduced when we were fifteen, but
• 26:50
  Speaker 2: we could have and and and and it is. It
• 26:57
  Speaker 2: is remark so because people ask these questions like when
• 27:01
  Speaker 2: does aging begin, Well, aging begins probably with fertilization of
• 27:05
  Speaker 2: the of yes, and aging is not the enemy, right
• 27:10
  Speaker 2: because if you didn't have a developmental program to age
• 27:14
  Speaker 2: from fertilization to you know, birth to growth and puberty,
• 27:24
  Speaker 2: you know, you wouldn't have been a functioning human. That
• 27:29
  Speaker 2: the part of aging that people have a problem with is,
• 27:34
  Speaker 2: you know, age related decline. You know, after you're beyond
• 27:40
  Speaker 2: reproductive capacity and you're finding that it's harder to you know,
• 27:46
  Speaker 2: maintain muscle mass and it's harder, but your brain is
• 27:51
  Speaker 2: probably still maturing if you're male, certainly until you're thirty
• 27:56
  Speaker 2: or you know, I'm sixty for now and still making
• 28:02
  Speaker 2: mistakes that I think I might be able to avoid.
• 28:05
  Speaker 2: So we'd like to be able to have productive maturation
• 28:10
  Speaker 2: for a long period of time. And what we're going
• 28:13
  Speaker 2: for is mastery, right and being able to take care
• 28:17
  Speaker 2: of yourself and others. And so humans are extremely good
• 28:22
  Speaker 2: at aging. Humans are better at aging than gorillas, which
• 28:26
  Speaker 2: you would not expect from our size because gorillas are
• 28:30
  Speaker 2: bigger than us. The general rule is bigger body, longer
• 28:36
  Speaker 2: life spiking, right, But humans live longer than gorillas. And
• 28:42
  Speaker 2: then women are even the biggest head scratcher because women
• 28:51
  Speaker 2: reach a menopause at an average age of fifty one,
• 28:56
  Speaker 2: so they're no longer reproductively viable, but in their sixth, seventh, eighth,
• 29:03
  Speaker 2: and ninth decade are actually healthier than men, right, and
• 29:09
  Speaker 2: have a better life expectancy than men post menopause, which
• 29:13
  Speaker 2: evolution can't explain other than to say that grandmothers are
• 29:18
  Speaker 2: really really important again for the survival of the species.
• 29:24
  Speaker 1: Yes that you.
• 29:25
  Speaker 2: Know human human you know children human babies and children
• 29:30
  Speaker 2: are pretty inept as as animal offspring go, right, Like
• 29:36
  Speaker 2: if you've seen videos of giraffes or horses being born,
• 29:41
  Speaker 2: and like watch for ten minutes for something remarkable to happen,
• 29:48
  Speaker 2: like as soon as it gets up and as belly
• 29:51
  Speaker 2: is not on the ground, it might still be dripping wet,
• 29:55
  Speaker 2: it's going to run. Yeah, that's just astonishing.
• 30:02
  Speaker 1: It takes us three years to do that, right, and
• 30:07
  Speaker 1: and probably the limit limiting factors that are brain size.
• 30:10
  Speaker 1: But now, as you were talking, about all of that
• 30:14
  Speaker 1: and talking about the nady and its central role in metabolism,
• 30:19
  Speaker 1: and straight away in my head, I'm going boom, boom boom,
• 30:22
  Speaker 1: I'm going hallmarks of aging. You know, some of my
• 30:26
  Speaker 1: listeners will be familiar with the nine hallmarks of aging
• 30:30
  Speaker 1: that then get upgraded to the twelve hallmarks of aging.
• 30:33
  Speaker 1: But straight away I'm going DNA rapair that's the hallmark
• 30:36
  Speaker 1: of aging. So inflammation that's another hallmark of aging. Stem Oh,
• 30:42
  Speaker 1: there you go. So I was going to say mitochondrict function.
• 30:46
  Speaker 1: Then you have stem cell meeting. So there's there's four already.
• 30:50
  Speaker 1: And you know if probably if we had the entire
• 30:52
  Speaker 1: list in front of us and went through it, there'd
• 30:54
  Speaker 1: probably be another view. So that really does emphasize its
• 31:00
  Speaker 1: importance in the aging process. Are in overall healthy, right,
• 31:08
  Speaker 1: And like you say, I don't think we're going to
• 31:11
  Speaker 1: get escape velocity, but what we can do is age better, right,
• 31:16
  Speaker 1: And I think that we're definitely on the custom.
• 31:19
  Speaker 2: So let's think about the challenges of living in twenty
• 31:22
  Speaker 2: twenty five, twenty twenty six, right, So long COVID right
• 31:26
  Speaker 2: is out there? Yes, you know, this is a real thing.
• 31:30
  Speaker 2: It's probably kind of heterogeneous. So what do you get
• 31:34
  Speaker 2: when you enroll people in a trial for long COVID?
• 31:37
  Speaker 2: Do they all have exactly the same disease? They all
• 31:41
  Speaker 2: have exactly the same presentation? Maybe not, but there's a
• 31:45
  Speaker 2: kind of positive result that's that's that's coming out now. Wow,
• 31:51
  Speaker 2: So let's not dump on on Harvard, you know, entirely
• 31:56
  Speaker 2: because the study was done at mass General Hospital, and
• 32:03
  Speaker 2: and and study material was provided by Niagen Biosciences. I
• 32:08
  Speaker 2: was a middle author of the paper. I'm a you know,
• 32:11
  Speaker 2: chief science advisor of Niagen. I don't work for Niagen,
• 32:15
  Speaker 2: but I do consult for them. And but this study
• 32:21
  Speaker 2: was done by really good clinical trialists. And you know,
• 32:27
  Speaker 2: of course, the gold standard result would be would be
• 32:31
  Speaker 2: the kind of thing that was just reported for perferal
• 32:34
  Speaker 2: artery disease, Right that you have a placebo group, and
• 32:38
  Speaker 2: you have the intervention group, and you have a pre
• 32:42
  Speaker 2: specified endpoint, which in the case of prefer artery disease
• 32:46
  Speaker 2: was the six minute walk test, and the intervention group,
• 32:51
  Speaker 2: the n R group, was demonstrably better right than the
• 32:56
  Speaker 2: placebo group. Now, but there's other things that you can
• 33:00
  Speaker 2: look for as well, particularly when the disease doesn't present
• 33:05
  Speaker 2: exactly the same in every person. Right, So you have
• 33:09
  Speaker 2: the beginning measurements of executive function, fatigue, sleep quality, depression,
• 33:17
  Speaker 2: and then you have the end of study measurements of
• 33:21
  Speaker 2: the same thing executive function, fatigue, sleep and depression, and
• 33:25
  Speaker 2: then you can see whether place EBO move the needle
• 33:30
  Speaker 2: or NR moved the needle in the same individuals. Right. So,
• 33:35
  Speaker 2: early days of clinical trials for long COVID didn't meet
• 33:41
  Speaker 2: the endpoint of placebo controlled results, again potentially because of
• 33:47
  Speaker 2: a lot of individual variability. But when you look at
• 33:52
  Speaker 2: times zero versus end of trial, the NR participants had
• 33:58
  Speaker 2: improvements in executive function, improvements in sleep quality, lower depressive scores,
• 34:06
  Speaker 2: and lower severity of fatigue, and the Paciba group did not. Wow,
• 34:11
  Speaker 2: So it's looking pretty promising. And I'm excited because we
• 34:18
  Speaker 2: have a safe, you know, clinically tested, patented, you know
• 34:26
  Speaker 2: supplement that is being conservatively you know, offered to the
• 34:33
  Speaker 2: public where the same exact material is available to medical
• 34:38
  Speaker 2: researchers in these clinical trials. Right, That's not the case
• 34:42
  Speaker 2: for NMN. Right, most of the men out there is
• 34:49
  Speaker 2: not doesn't meet the label claims, Like ninety percent of
• 34:53
  Speaker 2: the NMN stuff that is sold doesn't actually have men
• 35:00
  Speaker 2: in it or the amount of nmen that it says
• 35:02
  Speaker 2: of the label. Uh, the chemistry doesn't really make sense
• 35:07
  Speaker 2: to deliver n amen because it has to be converted
• 35:10
  Speaker 2: to n R.
• 35:10
  Speaker 1: But that was hard of the differences in in in
• 35:15
  Speaker 1: that and n R. So sorry, I just finished what
• 35:18
  Speaker 1: you said, and Net's come back to that.
• 35:20
  Speaker 2: Well, I mean the company, there's a company that is
• 35:24
  Speaker 2: testing and a man is a drug, and that's good,
• 35:26
  Speaker 2: that's I'm glad that they're they're doing that, and I'm
• 35:29
  Speaker 2: sure that their material is safety tested and you know,
• 35:35
  Speaker 2: shown to be safe and humans. In fact, I've seen
• 35:38
  Speaker 2: some evidence of that in the in the literature. But
• 35:41
  Speaker 2: when when consumers go online to get an amen supplement,
• 35:47
  Speaker 2: there's no real telling what they're getting. On the other hand,
• 35:53
  Speaker 2: the these eight randomized clinical trials of showing anti inflammatory activity,
• 35:59
  Speaker 2: the positive clical trials showing peripheral artery disease improvement and
• 36:03
  Speaker 2: walking speed, and the newly released trial of long COVID
• 36:08
  Speaker 2: where within group, if you took an R you have
• 36:11
  Speaker 2: improvements in executive function, lower fatigue, better sleep quality, lower depression.
• 36:17
  Speaker 2: That's done with niagen okay, which is the same material
• 36:21
  Speaker 2: that consumers can get. Now, clinical trials are usually done
• 36:24
  Speaker 2: at like a gram okay, pa, Right, so consumer doses
• 36:29
  Speaker 2: might be three hundred milligrams, but people take you know,
• 36:33
  Speaker 2: three tablets and three capsules and they're at a clinical level.
• 36:37
  Speaker 1: And now that what you just said, I don't. I
• 36:42
  Speaker 1: want to make sure that our listeners understand the importance
• 36:44
  Speaker 1: of that, and I want to explore why it. So basically,
• 36:48
  Speaker 1: what you're saying is the animeen that they'll they'll use
• 36:51
  Speaker 1: in clinical trials, and even there's a question mark around
• 36:54
  Speaker 1: the metabolism of that, but that that that stuff is
• 36:59
  Speaker 1: not the same is a lot of the stuff that
• 37:01
  Speaker 1: you will buy.
• 37:04
  Speaker 2: It can't be the same because because there there's a
• 37:08
  Speaker 2: company that has a patent on the crystal form of
• 37:15
  Speaker 2: NMN that is they company?
• 37:20
  Speaker 1: Is that company?
• 37:22
  Speaker 2: Is that if it's in measure measure bio attack. Yeah,
• 37:26
  Speaker 2: and so well, you know, I think that it's good
• 37:34
  Speaker 2: that they're doing you know, careful clinical testing of a
• 37:39
  Speaker 2: pure beta and AMN. But the problem is that if
• 37:46
  Speaker 2: people are trying to get that same material, they can't
• 37:51
  Speaker 2: because when when a company decides to do a drug trial,
• 37:58
  Speaker 2: then they're not supposed to release that material as a supplement.
• 38:04
  Speaker 2: There have been a number of FDA rulings on this,
• 38:07
  Speaker 2: but in the in the case of the way Niagen
• 38:10
  Speaker 2: was introduced, the company then called chromot X now called
• 38:15
  Speaker 2: Nigen Bioscience first got FDA notifications that this is a
• 38:23
  Speaker 2: new dietary ingredient and generally regardless safe it could be
• 38:26
  Speaker 2: sold as in a food or supplement that means over
• 38:30
  Speaker 2: the counter, and then subsequently that material can be tested
• 38:36
  Speaker 2: as a drug. OK, But generally the ruling is it's
• 38:41
  Speaker 2: called the Dshay law d s h e A. The
• 38:47
  Speaker 2: Dshay Law says that if something is initially being tested
• 38:51
  Speaker 2: as a drug, you can't just go out and buy
• 38:54
  Speaker 2: it because that would basically it's you don't know that
• 38:58
  Speaker 2: it's safe. Right. You can't go out and buy things
• 39:01
  Speaker 2: that fail in clinical trials due to safety or loss
• 39:06
  Speaker 2: about non efficacy.
• 39:09
  Speaker 1: So touchards the other brands of n R that are
• 39:14
  Speaker 1: so how does an individual because there's a lot of
• 39:18
  Speaker 1: grandfathering of research, right, So one particular supplement that maybe
• 39:25
  Speaker 1: it may be a herb that's picked at a particular
• 39:28
  Speaker 1: time of year in a particular place and it has
• 39:32
  Speaker 1: done a randomized control trial and has efficacy. And then
• 39:36
  Speaker 1: you'll find other supplement companies with similar things, but turns
• 39:41
  Speaker 1: out that their herb is growing in a different place
• 39:44
  Speaker 1: and it has different qualities, and it's picked at a
• 39:47
  Speaker 1: different time of year and it's not the same. So
• 39:51
  Speaker 1: is this the case with n R with the trials
• 39:56
  Speaker 1: it's all an ar that's out there pretty much.
• 40:00
  Speaker 2: Is it all Nigen, No, it's probably not all Niagen.
• 40:05
  Speaker 2: There are a couple of other companies that actually used
• 40:10
  Speaker 2: to buy Niagen from chromon x slash Nigen Bioscience and
• 40:15
  Speaker 2: then went their own way, and you know, are selling
• 40:24
  Speaker 2: stuff that I can't really vouch for. I mean, I
• 40:26
  Speaker 2: haven't seen the safety data behind it. They certainly don't
• 40:31
  Speaker 2: have the safety dossier that that Nigen has. They're not
• 40:36
  Speaker 2: used in very many clinical trials, if at all. And
• 40:44
  Speaker 2: so the Nigen Blue bottle is kind of the safety
• 40:49
  Speaker 2: tested way to go if someone wants to test to
• 40:52
  Speaker 2: see whether you know, this has anti inflammatory activity for them.
• 40:56
  Speaker 1: And this is the key thing for individi Jels is
• 41:00
  Speaker 1: that if you're going to take a supplement because you
• 41:03
  Speaker 1: think it's it's having an impact and you've seen studies
• 41:07
  Speaker 1: published on it. You want to make sure if you
• 41:10
  Speaker 1: possibly can, that you're getting the exact supplement that was
• 41:14
  Speaker 1: used in the clinical trial, because others can be completely different.
• 41:18
  Speaker 1: I think that's something that a lot of people don't understand.
• 41:22
  Speaker 1: A lot of lay people don't understand, like the Amiga
• 41:25
  Speaker 1: three fatty acids that you can buy in chemist Warehouse,
• 41:28
  Speaker 1: which is a big, massive chain over here that does
• 41:32
  Speaker 1: a lot of cheap stuff, like like a lot of
• 41:34
  Speaker 1: that can be rancid shit, and it's very different to
• 41:37
  Speaker 1: some of the Amiga three fatty acids that are used
• 41:39
  Speaker 1: in clinical trials. I know which one I want, right,
• 41:43
  Speaker 1: That's really important I think for for people to understand. So,
• 41:49
  Speaker 1: I mean we've we've talked about that that clinical clinically proven,
• 41:55
  Speaker 1: and that that difference from if we go back again
• 42:01
  Speaker 1: and talk about nad plus, so the methods of getting
• 42:06
  Speaker 1: in so there's a lot of intravenous infusions of nad plus.
• 42:12
  Speaker 1: My understanding is that when you infuse nad plus, it's
• 42:17
  Speaker 1: got to go to the liver and then it's converted.
• 42:20
  Speaker 1: I can't remember whether it's an or whatever. It's converted
• 42:23
  Speaker 1: in the liver.
• 42:24
  Speaker 2: It's actually even worse than that. So it causes a
• 42:30
  Speaker 2: painful inflammatory reaction when it's when it's given by IV,
• 42:37
  Speaker 2: because the body thinks that there's some infection somewhere and
• 42:42
  Speaker 2: some cells are busted open. You don't normally circulate high
• 42:50
  Speaker 2: levels of NAD or ATP, or you don't generally circulate
• 42:57
  Speaker 2: mitochondria or chromosomal DNA. All of those things in circulation
• 43:02
  Speaker 2: can cause an inflammatory reaction. So NED is actually breaking
• 43:07
  Speaker 2: down in the bloodstream to NR, and then as NR
• 43:11
  Speaker 2: it can get into cells.
• 43:13
  Speaker 1: So it's a really expensive way and painful way of
• 43:19
  Speaker 1: getting some.
• 43:20
  Speaker 2: N R right and which you can get orally and
• 43:23
  Speaker 2: for which there's now hundreds of registered clinical trials attesting
• 43:28
  Speaker 2: its oral efficacy, including you know, ten eleven twelve trials
• 43:33
  Speaker 2: that we talked about that that are positive that said,
• 43:37
  Speaker 2: there are people that have sworn by the effects of
• 43:42
  Speaker 2: intravenous NAD, and so Niagen developed something called nigen plus,
• 43:50
  Speaker 2: which is a pharmaceutical grade n R that can be
• 43:54
  Speaker 2: delivered IV. And so it turns out it's three or
• 44:00
  Speaker 2: four times as fast because it can basically go in
• 44:05
  Speaker 2: without you know, without a painful reaction. There's not a
• 44:11
  Speaker 2: huge amount of scientific literature on it, other than there's
• 44:17
  Speaker 2: an initial report I think on the med Archives that
• 44:21
  Speaker 2: that shows that it did increase volunteers blood na D.
• 44:27
  Speaker 2: That's not too surprising that it was more rapidly administered
• 44:32
  Speaker 2: than intravenous na D. And so the good thing about
• 44:37
  Speaker 2: it is that it's available for use, it's available for
• 44:41
  Speaker 2: clinical testing. Now there's a lot of interest in its
• 44:46
  Speaker 2: potential activity as something that could curve cravings for opiates,
• 44:54
  Speaker 2: like a black market, gray market use of intravenous n
• 44:58
  Speaker 2: a D in drug recovery clinics, this stuff.
• 45:03
  Speaker 1: Like this, Wow, that's that's that's fascinating stuff. And very
• 45:07
  Speaker 1: quickly because I need to go to the airport, which
• 45:11
  Speaker 1: is very annoying because I'm loving this conversation. Talk about
• 45:15
  Speaker 1: its role in neuro degenda to the diseases, right, and
• 45:20
  Speaker 1: do you know of any clinical trials currently being done
• 45:23
  Speaker 1: looking at NAD plus or precursors or yes.
• 45:28
  Speaker 2: So there's a large trial in Norway on Parkinson's. There's
• 45:34
  Speaker 2: some trials in the US on my cognitive impairment. Most
• 45:38
  Speaker 2: of the people probably have early Alzheimer's that are enrolled
• 45:43
  Speaker 2: in those trials, and we're going to get the the
• 45:46
  Speaker 2: The trials from the early phase Parkinson's were promising enough
• 45:54
  Speaker 2: that the Norwegian government gave everybody niagen at the end
• 46:00
  Speaker 2: of the trial, so the folks that were on placebo
• 46:03
  Speaker 2: were able to get nigen because there appeared to be
• 46:07
  Speaker 2: improvements in cerebral blood flow. We know some of the
• 46:11
  Speaker 2: mechanisms by which NAD comes under attack in neurons. Ironically,
• 46:17
  Speaker 2: NMM accumulation in neurons is one of the bad actors,
• 46:24
  Speaker 2: and NMN turns on an enzyme called sarm one, and
• 46:28
  Speaker 2: then sarm one degrades NAD into cyclic adp ribos, which
• 46:34
  Speaker 2: mobilizes calcium and activates calpains and leads to neurodegenerative you know, collapse.
• 46:43
  Speaker 2: So NR has some strong potential in neuroprotection. And but
• 46:49
  Speaker 2: the you know, the clinical trials are the biggest clinical
• 46:53
  Speaker 2: trial is just being completed now in Norway.
• 46:59
  Speaker 1: Wow. That that is fascinating stuff. And so I'll watch
• 47:02
  Speaker 1: this space on that because you know the theory. I'm
• 47:06
  Speaker 1: sure you can talk about the theory all day long.
• 47:08
  Speaker 1: NAD plus is very important in the human brain as well,
• 47:12
  Speaker 1: and when it drops, bad shit happens, right, which I
• 47:18
  Speaker 1: think you've done a very good job charge of educating
• 47:22
  Speaker 1: our listeners both on the importance of NAD in terms
• 47:27
  Speaker 1: of metabolism as a as A as a A basically
• 47:32
  Speaker 1: a key driver of metabolism. But I think what has
• 47:37
  Speaker 1: also been great is helping people to understand the research
• 47:42
  Speaker 1: and what to look out for, not just with with
• 47:44
  Speaker 1: this particular supplement, but with any supplement. I think that's
• 47:48
  Speaker 1: been gold for the listeners to really understand that from
• 47:51
  Speaker 1: a somebody who's at the coalface doing research and we.
• 47:56
  Speaker 2: Want to over deliver and underpromise. And it was safety
• 48:02
  Speaker 2: first from the from the earliest days of nicotina white
• 48:07
  Speaker 2: ribside testing by Nigen Bioscience, And you know, at this
• 48:12
  Speaker 2: point there's a clinical track record and a safety track
• 48:15
  Speaker 2: record that I think that consumers can be confident in.
• 48:21
  Speaker 1: And and I have not got enough confidence that it's
• 48:26
  Speaker 1: buying onto my supplement lists. There's not many people who
• 48:30
  Speaker 1: can do that, who can sway me from sitting on
• 48:32
  Speaker 1: the fence to I mean, but I A mean, so
• 48:38
  Speaker 1: thank you very much. This has been awesome pleasure