INHIBIT CD38

“We did a full human, double blind, placebo controlled crossover study. This is, you know, a gold standard in terms of trial design. In this clinical study, not only did we measure NAD levels, so we show that NAD significantly increases. After seven days, it continues to rise. But more importantly, we showed that you can switch back on that NAMPT enzyme. The other thing was biological age. So we saw a reversal of biological age. This was measured using the GlyconAge test, of one point two six years in twenty eight days as well.”

“I have always had this theory that surely this must be triggering some sort of inflammatory reaction, and that's why when people have NADIVs, they normally don't feel the best. You know, you feel sick, heart palpitations, things like that. And I've always had this as a theory. And in the last couple of months, this theory has been proven because there's a paper that's been released. It's in a preprint at the moment. I actually saw the data presented at a conference for the first time that showed within NAD IVs in a human clinical trial that it actually causes an inflammatory reaction. So they saw an increase in white blood cells, neutrophils, cytokines.”

“NAD itself is, when you look at its function, obviously, it's a really interesting molecule that it has such a diverse range of beneficial effects. But the really cool thing about it is that intersection of where it sits between energy production on one side and repair and maintenance and switching on a lot of pathways on the other side. So NAD sits at this really neat intersection between sensing the energy of the cell and almost sensing the environment to then decide in how the cell's gonna react.”

“If you look, there's a clinical study done on NR, and what they show is that if you increase the dose of NR and measure how much NAD that turns into, basically, as the dose goes up, it gets to a certain point where it plateaus. Then it doesn't matter how much more NR or how much more raw material you give the cell. The level of NAD just is flatlined. But they also measured the the amount of methyl nicotinamide, and that just goes up, up, up, up, up. It's like we're going into the drug space where we're taking a drug to fix the side effect of another drug.”

“If you look at anything that causes an energy stress, so exercise, fasting, both of those things naturally switch on NAMPT because what does that do? That increases NAD production. On the flip side, if you look at a lot of people's lifestyles, we are sedentary way more than we ever should be, way more than evolution designed our bodies to be. And we're also eating a lot more often and a lot more calorific foods than, again, our bodies were ever designed for. So one of the theories is that the reason that people are becoming much more chronically depleted in NAD is simply our lifestyles.”

“Rutin actually is a direct activator of NAMPT, so it directly switches on its expression. And then the other one that we use is alpha lipoic acid. And alpha lipoic acid is an indirect activator. The way that this works is it actually switches on something in our cells called AMPK, which is an energy sensor that tells ourselves to produce more NAMPT.”

“For one cycle of CD38 enzymatic activity, it uses around 100 molecules of NAD just for one cycle. For something like the DNA repair enzymes or the sirtuins, they use about six or seven. So you can see that a very small increase in inflammation can have a huge impact on NAD levels.”

“When scientists realize that NAD actually declines with age quite substantially, so it's estimated a half every 20 years, and this is from birth. So even by the time you're 20, it's half, then by the time you're 40, it's half again. What they realized was that, okay, this molecule that's actually very important for keeping our repair switched on, declines significantly with age, so why don't we prevent this decline?”

“When scientists realized that NAD actually declines with age quite substantially, so it's estimated a half every 20 years, and this is, this is from birth. So even by the time you're 20, it's halved, then by the time you're 40, it's halved again. What they realized was that, okay, this molecule that's actually very important for keeping our repair switched on, declines us significantly with age, so why don't we prevent this decline?”

“We know that one of the most prolific NAD consuming enzymes in our cells is something called CD 38. And CD 38 is basically an enzyme that triggers inflammatory responses in the cells. And just to put it into perspective of how much it consumes, so if you imagine, again, NAD is a fuel. So for one cycle of CD38's enzymatic activity, it uses around a 100 molecules of NAD just for one cycle. For something like the DNA repair enzymes or the sirtuins, they use about six or seven. So you can see that a very small increase in inflammation can have a huge impact on NAD levels.”

“We saw a reversal of biological age. This was measured using the glycan age test of 1.26 years in 28 days as well. So we know that this is improving all around cellular health. In this study, we didn't measure any sort of clinical outcomes in terms of disease status, but we saw significant reduction in levels of GSP in just 28 days.”

“The main reason why NAD declines is because that main enzyme, that NAMPT enzyme in the salvage pathway that makes and recycles NAD from these precursors declines with age. It's kind of like, if you go in a factory and saw production's gone down, you realize that the machines weren't working; there's no way that you would think it would just be a good idea to just keep on loading the factory with raw material and hope you're gonna get more NAD out at the end.”

“This Apigenin is actually a really, really good inhibitor of CD38. And that's important for two reasons. The first, we don't want to waste NAD, but perhaps the even more important reason is when you are boosting NAD, everyone's boosting it because they want it to switch on repair or activate the sirtuins. But the reality is that if you have any inflammation in your body, CD38 has what we call a high affinity for NAD and will grab it before the beneficial things even get a look in.”

“The big sort of, gaping hole in this precursor theory was the main reason why NAD declines is because that main enzyme, that NAMPT enzyme in the salvage pathway that makes and recycles NAD from these precursors declines with age. So it's kind of like if you go in a factory, you saw production's gone down, you realize that the machines weren't working, like, there's no way that you would think it would just be a good idea to just keep on loading the factory with raw material and hope you're gonna get more NAD out at the end.”

“Very quickly, we realized that's not a possible way because it's very unstable. It it gets degraded in the gut. By the time you even put it in your mouth, there's probably no NAD left because it degrades just in a bottle. So, yeah, it it what's crazy is the amount of companies on Amazon still selling, you know, the highly pure, purely certified NAD, which will just not have any NAD in it by the time it gets to your house.”

“There's a paper that's been released that showed within NAD IVs in a human clinical trial that it actually causes an inflammatory reaction. So they saw an increase in white blood cells, neutrophils, cytokines. You put in a huge amount of an intracellular molecule outside the cell, the body's going to think, what the heck has happened? Is there a trauma? Is there some damage? And it elicits an unspecific inflammatory reaction to deal with whatever the perceived stress is.”

“If you are ignoring these problems and you are ploughing loads of precursors into the cell, whether that's oral NR or IV NR or it's NMN, that will be getting made into NAD, it will be getting used once, it will be getting broken down in nicotinamide, and then this nicotinamide is just building up and building up because your cells can't do anything with it. And then the methylation problem starts to happen.”