FoundMyFitness - #050 NAD+ in Aging: Role of Nicotinamide Riboside and Nicotinamide Mononucleotide

Episode Date: November 13, 2019

In this episode, Rhonda describes NAD+ (perhaps one of the most important molecules in the human body), why it is so important for aging, and why it declines with age.    In this episode, you'll discover:  (00:00) Introduction (03:07) Overview of NAD+, a source of cellular energy (09:18) NAD+ fuels PARP and sirtuin enzymes, promoting longevity (12:37) How can I raise NAD+ levels? (17:03) Can NAD+ boosters (NMN & NR) promote cancer growth? (19:15) Making sense of the research so far (27:03) Why not supplement with NAD+ directly? (29:23) Clinical trials investigating nicotinamide riboside are promising (32:42) Recap and concluding thoughts If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Howdy, folks. Today is a special episode. Rather than giving you an interview, in this episode, I'd like to take a shot at instead giving you guys the full lay of the land on a topic we've continually touched on across multiple episodes, which is all things NAD. We've brushed up against this topic in many interviews, the most obvious of which being the conversation I had with Dr. David Sinclair, but also others like a prior episode with Dr. Eric Verdon, both great episodes, which you should definitely listen to. Those episodes were, however, conversations, which means that in each case, while certainly educational, they weren't necessarily structured to strictly be a primer. Today's episode is different. Instead, my goal in this one is to structure it in a way as to give you

an overview that can lay the framework towards your understanding the relevance, the questions that still need to be answered by the field, and also just my sort of concluding thoughts when it's all said and done. Not only on NAD, but also on the so-called NAD boosters, which are the NAD precursors, nicotinamide and nicotinamide mononucleotide. Before we kick this thing off, a quick mention about this episode. It's actually been out for almost an entire week. Surprised? You shouldn't be. This is one of the new elements of the engine that keeps found my fitness not only running, but thriving, by offering a few solid Conc Creek perks for supporting memories. I'm able to keep this podcast free, grow my team, and actually make free found my fitness better than ever before.

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Without further adieu, onto the podcast. Today I'm going to talk about a molecule that has become in recent years extremely relevant to the field of aging. Specifically, I'm referring to NAD Plus, which I will refer to as NAD for short. And some of the related precursor molecules, nicotinamide riboside, often referred to as NR, and nicotinamide mononucleotide, often referred to as NMN. These two precursor molecules are called NAD boosters, which can both be found as consumer-available supplements. Just in case you've never heard of NAD, it's probably one of the most important molecules on the planet, so important in fact that without it, life would cease to exist. The NAD boosters nicotinamide and nicotinamide mononucleotide at very high doses in animal studies

have both been shown to improve the way multiple tissues and cell types age, including skeletal and heart muscle, brain, and stem cells. There have also been two preliminary clinical trials in humans showing nicotinamide ribicide may raise NAD levels in white blood cells, which is pretty darn cool. However, I still think there are many open questions that need to be answered regarding NAD boosters, and I will touch on some of these concerns in this episode. But the possibility that intracellular NAD may be increased from a supplement or several types of supplements is awfully interesting, if not downright exciting, for one simple reason. NAD levels decrease with age and a decrease in NAD levels across a variety of types of tissues is associated with many,

and I mean many, hallmarks of aging. These hallmarks of aging that are associated with age-related changes in the NAD pool, either directly or indirectly include things like loss of proteostasis, mitochondrial dysfunction, glucose intolerance, insulin resistance, cellular senescence, altered epigenetics, and more. This is partly because the availability of NAD promotes DNA repair capacity, while its decline is associated with the accumulation of DNA damaging reactive oxygen species. Another reason is because NAD is required for energy production. So when NAD levels decline, as they do with AAP, age, this results in less energy production in many tissues, like the brain, immune cells, muscle,

etc. That means those organs do not work as well as they once did during youth, when energy levels were maintained. NAD is also required for the activation of a very important family of enzymes involved in longevity called Sertuans. The complete answer to why NAD levels fall with age is still an open question, but there's a few things we do know. As we age, chronic inflammation and immune activation, two processes that consume NAD tend to go up, and with them our need for DNA repair, placing an immense demand on our NAD pool. Meanwhile, our ability to produce and recycle NAD tends to fall with age. We're going to cover a lot of ground in this episode, but I want to start with an overview of NAD. NAD has a very important role in energy metabolism. NAD can be synthesized

in the body from a variety of dietary sources, including the amino acid tryptifers. which is in tons of healthy foods like salmon, spinach, and nuts. And the three forms of niacin, which is vitamin B3, also found in foods like lean meats, legumes, veggies. These three forms of vitamin B3 include nicotinamide, also called niacinamide, nicotinic acid, and nicotinamide riboside. They are commonly referred to as niacin equivalents. But dietary sources of NAD are not the major source of NAD. The major source of NAD is through a recycling mechanism that we will discuss later. The reason for that is because our organs require such large quantities of NAD that it would be impossible to consume enough from our diet. So why do we require such large quantities of NAD?

First and foremost, NAD plays a critical role in energy metabolism, critical meaning without it, you can't make energy. NAD participates in back and forth processes of reduction and oxidation, often referred to as redox reactions. These alternating conversions of NAD's oxidized form, which is NAD, to its reduced form, NADH, are crucial for the metabolism of glucose and fatty acids and the formation of ATP. Since both the oxidized and reduced forms of NAD are essential for these linked sets of reactions, cells need to maintain massive concentrations of both NAD and NADH. Basically, without these molecules, not only would we cease to exist, but life.

on our planet would cease to exist. NAD is also a co-factor for many different important enzymes. In this context, a co-factor means something that is required for an enzyme to work. It has to bind the enzyme and this activates the enzyme so it can perform its function. So let's talk about a few of these enzymes. Several of these NAD required enzymes are inside the mitochondria, and this is another way NAD participates in the generation of energy, aside from itself being a type of energetic currency. It also acts as a co-factor for enzymes involved in the production of energy from glucose outside of the mitochondria. This is referred to as glycolysis. Many types of cells use glycolysis as their primary source of energy.

For example, red blood cells do not have any mitochondria, so 100% of the energy they require to perform their function of delivering oxygen and other goodies to other tissues in the body comes from glycolysis. NAD plays a very important role in mitigating DNA damage. You need NAD to repair damage to DNA. That is because NAD is a co-factor for one of the most important enzymes involved in repairing DNA damage called PARP 1. The activation of PARP 1 requires an enormous amount of NAD. For example, excessive DNA damage and subsequent PARP 1 activation have been shown to decrease NAD levels to 20 to 30% of its normal levels. The ability to repair DNA damage

is important for longevity. Lymphoblastoid cell lines established from blood samples of humans who were centenarians, 100 years or older, have significantly higher PARP 1 activity than cell lines established from younger individuals that are 70 years old. Part 1 activity has also been correlated with maximum lifespan in mammals. The higher the PARP 1 activity, the longer the lifespan. For example, the activity of PARP 1 was measured across multiple mammalian species, and the difference in PARP 1 activity between the longest-lived mammals tested, which were humans, and the shortest-lived mammals tested, which were rats, was 5.5.5.5.5.5.5 activity between the longest-lived,

five-fold. So not too much of a surprise, but genomic stability, which relies on NAD in general, and PARP-1 specifically, may be very important for longevity. NAD is required to activate signaling proteins known as Sertuans, which are highly conserved enzymes that play roles in health span and longevity in multiple organisms. Certuans are linked to the regulation of a variety of metabolic processes, like the response to stress and the modulation of lifespan. The way they do this is through epigenetic regulation. Sertouins utilize NAD to remove specific chemical structures called acetyl groups, a process called deacetylation from cellular proteins to control the activation of genes involved in energy metabolism, atophagy, circadian rhythm, DNA repair, cell survival,

and more. When cellular energy levels are low, such as during exercising, fasting, or caloric restriction, NAD levels rise, which also means the ratio of NAD to its reduced form NADH increases, and this serves as a sensor to switch on Certuin expression and subsequent activity. Resveratrol, a naturally occurring compound found in red grapes and other plants, is a potent certuan activating compound, and its beneficial effects on health span, some of which is now showing up in human research, are thought to result from Certuin activation. All right, so that is NAD in a nutshell. It's important stuff. Unfortunately, NAD becomes depleted across various tissues, including including the brain as we age. The brain, skeletal muscle, the heart, these are all tissues with a

very high metabolic demand and thus require a lot of NAD. So what happens when you can't meet that metabolic demand? Things start to degenerate and fall apart. They don't work as well. As I mentioned before, NAD depletion has been associated with the hallmarks of aging, such as decrease atopoge, increased DNA damage, increased mitochondrial dysfunction, and dysregulated metabolism. Depletion of NAD may predispose organisms to the development of a variety of age-related diseases, including nerve degenerative disease, such as Alzheimer's disease, and Parkinson's disease, cardiovascular disease, and muscle atrophy. It may also increase the susceptibility to infections, since the immune system requires tons of NAD. In contrast, NAD levels increase under conditions that many of us already think of

as generally health span promoting, such as exercise and also fasting, or in the case of lab rats, full-blown, lifelong caloric restriction. Furthermore, NAD restoration through a variety of different methods has been shown to increase a lifespan in lower-level organisms such as yeast and worms, as well as in rodents. Taking together, these findings suggest that NAD plays a critical role in aging. Specifically, the reduction of NAD levels commonly observed in aging is thought to be a combination of decreased synthesis and recycling, as well as increased consumption and degradation. Increased DNA damage and inflammation as seen in aging may decrease NAD and potentiate aging. So the question that's been on everyone's mind is, can I raise NAD levels in my body?

And if so, will that give me superpowers? Or at the very least, help me to live healthier and free of disease longer? The answer isn't just supplements, though that's a possibility and one some labs are very excited about and pursuing. In fact, NAD levels are heavily influenced by lifestyle and particularly things that cause energy stress, like fasting, caloric restriction and exercise, which all raise NAD. Remember, NAD can be made from things in the diet like triptophan or niacin equivalents, but these niacin equivalents are not the major source of NAD. The reason for that is because the body's demand for NAD exceeds its capacity to produce it from these forms of vitamin B3. So the body recycles nicotinamide using a recycling pathway called the NAD salvage pathway.

This is the predominant source of NAD. Let me explain how we get NAD from this recycling pathway. The consumption of NAD from enzymes that use it generates nicotinamide as a byproduct. Nicotinamide is converted into nicotinamide and subsequently into NAD. There are two important things to know about the NAD salvage pathway. First, nicotinamide has been shown to inhibit the activity of certuans, which is not necessarily a good thing. Second, the enzyme that converts nicotinamide into nicotinamide into nicotinamide mononucleotide is subject to feedback inhibition by NAD levels.

That means at a certain concentration of NAD, nicotinamide will no longer be converted into nicotinamide and subsequently NAD. Rather, it will remain nicotinamide, which is unfortunate because, as I just mentioned, some studies have shown nicotinamide inhibits seretuan activation. Remember, Sertouins are involved in longevity. That means you want them to be activated. The other source of NAD is from nicotinamide ribicide, which is converted into nicotinamide mononucleotide and subsequently NAD.

Both nicotinamide ribicide and nicotinamide mononucleotide are found in low concentrations in many foods, but they are also found in supplements and are referred to as NAD boosters. So let's talk NAD boosters. These two NAD precursors, nicotinamide, and nicotinamide mononuclid, are referred to as NAD boosters because, in supplement form, they have been shown to be well tolerated at high doses and to effectively raise NAD levels and to ameliorate age-associated diseases in rodents. The most extensively studied NAD booster is nicotinamide ribicide. Several animal studies have shown that when nicotinamide ribicide is orally administered at high doses, it can counteract an obesityogenic diet by improving insulin

sensitivity. It can improve endurance and strength. Another animal study showed at high dose nicotinamide ribicide could reverse mitochondrial damage. It could increase mitochondrial biogenesis and reverse muscular atrophy in animals that had a severe muscle wasting disease. Nicotinamide ribosite has also been shown to have positive effects on the brain in animals. It increased neurogenesis. It's decreased cognitive deterioration and amyloid beta production. It's also been shown to increase synaptic plasticity in mice. Nicotinamide mononucleotide has not been studied as extensively as nicotinide ribicide, but there have been several animal studies that have also shown nicotinamide mononucleotide can have health benefits. For example, injection with high-dose nicotinamide mononucleotide

has been shown to counter an obesityogenic diet and improve several markers of metabolic health. High-dose injection of nicotinamide mononucleotide has been shown to improve heart function in animals with heart problems and to improve cognition and memory. and animals with neurodegenerative disease. A long-term study found that dietary administration of nicotinamide mononucleotide mitigated the age-associated physiological decline in mice that have an accelerated aging phenotype. Specifically, starting at five months of age, mice were fed either 100 or 300 milligrams per kilogram body weight, nicotinamide mononucleotide for 12 months.

These animals had improved skeletal muscle function, mitochondrial function, increased energy expenditure, increased bone density, and also decreased insulin resistance. These benefits occurred in a dose in a dose of nicotinamide mononucleotide, the greater the benefit. While this all sounds great, there is another important point that I want to mention. While many animal studies have found that nicotinide ribicide and nicotinamide mononucleotide can ameliorate age-related disease by increasing NAD levels in different tissues, there is always one disease context that throws a curveball. Cancer. In a recent thing, study, nicotinamide mononucleotide was shown to accelerate cancer growth in mice with a type of

pancreatic cancer where pro-inflammatory senescent cells drive tumor growth. When mice were injected with 500 milligrams per kilogram body weight of nicotinamide mononucleotide for 13 days, they exhibited significant increases in precancerous and cancerous lesions in the pancreas. So let's talk about this a little more because nicotinamide mononucleotide's effect on accelerating tumor growth, was dependent on senescent cells, which can disrupt normal tissue functions and, ironically, also drive the progression of cancer over time as well. This is in spite of the fact that senescence is a program that usually prevents cancer more immediately in the short term. The reason this happens is that when cells become senescent, they can secrete molecules that

tend to have the following qualities. They are pro-inflammatory. They're involved in immune activation and evading the immune system. They're involved in growth signaling and also involved in angiogenesis, which plays a role in cancer metastasis. NAD seems to increase this quality of senescent cells, likely because it's being used in terms of energy metabolism. So it's making these cells, even these senescent cells, even more tumorogenic. And while this study only looked at nicotinamide mononucleotized effect on cancer growth, it's quite possible that nicotinamide ribicide may show similar results in this very, very specific context, which is a type of cancer where pro-inflammatory senescent cells drive tumor growth. That does not mean that nicotinamide mononucleotide or

nicotinamide ribicide supplementation will cause cancer or even drive tumor progression in other types of cancer. But I will say it would be nice to see long-term animal studies to confirm. I'm sure those are underway. Now let's focus our attention on whether translation of all this preclinical data to humans is likely. With the exception of the cancer study I just mentioned, much of the preclinical data seems pretty promising. But there are a couple of important points to make with respect to these animal studies that are very relevant for translating this data to humans. First, let's talk about dose. A majority of the rodent studies which used nicotinide ribicide orally used a very high dose of nicotinomide riboside in the range of 400 milligrams per kilogram

body weight, which translates to a human equivalent dose of 32 milligrams per kilogram body weight. So for 180 pound person, that would be approximately 2.6 grams of nicotinamide ribicide per day. We will discuss human studies in a minute, but that is a very high dose, and it is a dose that is orders of magnitude higher that has ever been clinically tested. Regarding the nicotinamide mononucleotide animal studies, the majority of them all used very high dose, about 500 milligrams per kilogram body weight, and typically

it was injected into the abdominal region of animals, which makes it quite difficult to translate findings to humans. The oral dose that was used in the long-term aging study used a dose range. On the low end, the dose was 100 milligrams per kilogram body weight, which is a human equivalent dose of around 8 milligrams per kilogram body weight. So for 180, pound person that translates to about 653 milligrams of nicotinamide mononucleotide, which seems pretty doable. Of course, the mitigation of age-associated physiological decline was much more robust at the high dose of 300 milligrams per kilogram body weight, which is a human equivalent dose of 24 milligrams per kilogram body weight, or approximately 2 grams of nicotinamide mononucleotide per day

for 180 pound person. Again, that's a pretty high dose. The next point of concern is the bioavailability of either nicotinamide ribicide or nicotinamide mononucleotide. The important point to address is whether nicotinamide or nicotinamide mononucleotide can reach other tissues intact and directly form NAD without going through that NAD recycling pathway that I mentioned earlier called the salvage pathway. The salvage pathway would mean that nicotinide or nicotinide or nicotinamide minonucleotide were first metabolized into just nicotinamide before forming NAD instead of directly forming NAD. This is an important point because NAD produced from the salvage pathway is subject to feedback inhibition and therefore cannot raise NAD levels in tissues above a certain level. So let's talk about some details. An animal study using isotope tracers allowed NAD made directly from nicotinamide ribicide

or directly from nicotinamide mononucleotide versus NAD made from nicotinamide via the salvage pathway to be measured. What the study found was that at a low oral dose of around 50 milligrams per kilogram body weight of either nicotinamide or nicotinamide mononotid, they produced very low levels of NAD made directly from those precursors, but only in the liver, not in other tissues. Low levels of nicotinamide-derived NAD, on the other hand, were found in the kidneys, and very low levels of nicotinamide-derived NAD were found in the muscles and also in the brain. The humid equivalent dose of 50 milligrams per kilogram body weight is roughly 4.07 milligrams per kilogram body weight.

So for a 180 pound person, that is approximately 332 milligrams of either nicotinamide riboside or nicotinamide monononucleotide, which is a pretty doable dose, but very little increases in NAD were found, at least in animals at that dose. A higher oral dose was also done, but only for nicotinide ribicide, a dose of 200 milligrams per kilogram body weight of nicotinamide ribicide. showed no difference compared to a low dose in terms of making NAD direct from nicotinamide ribicide in any other tissues other than the liver. However, more of the NAD derived from the salvage pathway was found in the kidney muscle and the brain than at the lower dose. So 200 milligrams per kilogram body weight translates to around a human equivalent dose of 16.3 milligrams per kilogram body weight, which for a 180,

person is about 1.3 grams, which is pretty high. When nicotinide ribicide or nicotinide mononucleotide were given intravenously at varying doses, so 50 milligrams per kilogram body weight, or 500 milligrams per kilogram body weight, directly produced NAD was found in the liver, kidney, and muscle in a dose-dependent manner. However, the only NAD detected in the brain was that which was salvaged from nicotinamide, suggesting that neither nicotinide nor nicotinide mononucleotide cross the blood-brain brain barrier. It is noteworthy that head-to-head comparison of identical doses of injected nicotinamide ribicide and nicotinamide mononucleotide produced more NAD made directly from nicotinamide riboside in the liver, kidney, and particularly in the muscle tissue compared to nicotinamide mononucleotide.

So, what does this all mean? and should we care. What this data from the isotope tracer studies means is that even at very high oral doses, neither nicotinamide ribicide or nicotinamide mononucleotide appeared to directly be transported to other tissues other than the liver, at least again at those doses that were measured. However, nicotinamide ribicide and nicotinamide mononucleotide were converted into nicotinamide, which was then transported to other tissues, and some of that nicotinamide was then converted into NAD. And at the end of the day,

isn't raising cellular NAD levels what is most important anyway. The other animal studies I previously mentioned that showed positive health benefits in tissues like the muscle or the brain were at a very high oral dose of nicotinamide riboside and nicotinamide mononucleotide.

In fact, in some cases, they were double the dose, So they were about 400 milligrams per kilogram body weight. So it's possible that nicotinamide ribicide and nicotinamide mononucleotide can be transported to other tissues other than the liver at very, very high oral doses. That's yet to be shown. However, it's also possible that at very, very high doses, the NAD derived from the salvage pathway was high enough to do something beneficial.

The isotope data also suggests that if nicotinamide ribicide or nicotinamide myononuclotide is administered intravenously, both of those compounds are able to be transported to other tissues and directly form NAD and not be subject to feedback inhibition. This also raises NAD levels in multiple tissues to a much higher concentration than otherwise would be. Of course, IV injection of these NAD boosters is very challenging, to translate to humans. You may be wondering why all the messing around with NAD boosters like nicotinamide ribicide and nicotinamide mononucleotide in the first place? The reason nicotinamide and nicotinamide mononucleotide are popular is because they can be transported into multiple tissue types, including the liver, kidney, muscle, and heart. The brain is the exception.

Neither nicotinamide nor nicotinamide mononucleotide seem to be able to directly cross the blood-brain barrier, but both form nicotinamide, which can be transported into all tissue types, including the brain, where it can then form N-A-D. So why not just go to the source and take or inject N-A-D directly? Well, for starters, NAD has poor bioavailability. Animal studies have shown that upon ingestion, orally administered NAD is primarily digested into the precursor nicotinamide, but also to nicotinide ribicide and nicotinide mononucleotide before being absorbed. While oral bioavailability of NAD is low, the hope is that intravenous NAD infusion may bypass that digestive system. The problem is that no mammalian NAD transporter has been identified,

and with the exception of the brain and the heart, extracellular NAD has not been shown to be taken up into tissues. When NAD was injected into the abdominal region of mice, it was able to raise NAD levels in some brain regions. Similarly, mice that were injected with a high dose of NAD had increased levels of NAD in the heart and also protection from cardiac hypertrophy. This suggests that direct injection of NAD at a high dose may be doing something beneficial, at least in the brain and in the heart. I would like to mention that just because no data exists, that does not mean that NAD delivered intravenously cannot raise NAD levels in other tissues, other than the brain or the heart.

It's possible that extracellular NAD could be metabolized to nicotinamide, and that could be transported to other tissues like muscle and also be converted into NAD. While there is very little pre-clinical data and zero clinical data on direct IV injection of NAD, it does seem like this may also be a good idea or a good area to explore as a potential way to boost NAD levels and tissues. But let's move beyond what is plausible and talk about human data. To date, there is no published evidence of oral nicotinamide mononucleotide supplementation in humans. But there have been two randomized placebo-controlled trials showing that nicotinamide

can increase NAD levels, at least in white blood cells, in a dose-dependent manner. So let's talk about those. In an eight-week-long, randomized double-blind placebo-controlled study involving 120 healthy adults between the age of 60 and 80 years old, a 250 milligram daily dose of nicotinamide ribicide and Terlstilbein, a natural compound found in blueberries that activates certuans similar to resveratrol, increased participants' whole blood NAD levels by 40% compared to their baseline levels just after four weeks. Participants' whole blood NAD levels increased by 90% when taking a double dose, which was 500 milligrams. Those who took the

lower dose exhibited reduced diastolic blood pressure and lower levels of the liver enzyme alanine amino transferase, which is a marker of liver damage. However, it is difficult to know whether nicotinamide riboside, tarostilbin, or both are responsible for the effects on blood pressure and liver health. Previous clinical studies have found that tarotiline reduced blood pressure, at least in adults. Another randomized placebo-controlled trial involving 60 middle-aged and older adults between the ages of 55 and 79 years old demonstrated that a 500 milligram dose of nicotinamide ribicide twice daily for a total of 1 gram per day for six weeks was well tolerated and increased NAD levels in white blood cells by 60%. The study participants also

experienced improvements in blood pressure and aortic stiffness, but these effects were not statistically significant, possibly due to the size of the dose or the relatively small number of people in the study. Nicotinamide ribicide had no effects on metabolic function, motor function, or exercise capacity and performance. That's pretty much it for the randomized placebo-controlled trials. The data seems to indicate that oral nicotinamide ribicide can raise NAD levels in whole blood and in white blood cells, but that it is only a conclusion, that's the only conclusion that can be made. The highest dose tested was one gram per day administered as 500 milligrams twice a day. If we circle back to the animal data on nicotinamide ribicide and all the benefits that were seen,

that was the human equivalent dose of 32 milligrams per kilogram body weight, which is around 2.6 grams per day for 180 pound person. While the short term clinical studies show nicotinamide ribicide given orally is safe, at least in the short term, no long-term studies have been done. It's worth at least a small mention that nicotinamide and nicotinamide mononucleotide both break down into nicotinamide over time, especially in conditions of high humidity or high heat. Somewhat perplexingly, supplemental nicotinamide may even reduce certumin activation. The good news is that overall, if these supplements are kept cold, they are relatively stable, and in most cases, the supplements will contain very little nicotinamide.

So it's a good idea to make sure that these products stay cool as much as possible and get them from a manufacturer to make sure that they have not been laying around in a hot warehouse somewhere longer than necessary. Okay, just to recap, NAD is crucial for our survival. It can be obtained in the diet, but the body recycles it to get most of what it needs. Unfortunately, day-to-day living plus normal aging can cause NED levels to drop. This causes metabolic and mitochondrial dysfunction, as well as many of the other problems and conditions associated with aging, like elevated DNA damage. NAD levels can go up when we exercise or fast, but NAD boosters like nicotinamide ribicide and nicotinominoids. mononuclididid can also increase NAD levels in a dose-dependent manner. However, most of the data on NAD boosters comes from animal studies.

Whether these boosters are effective and safe in humans is still a big question. So, those are my thoughts on NAD in a nutshell. I think the data on the NAD precursors is very promising and exciting, but out of abundance of caution, much more needs to be done before I'm ready to dive in with both feet. That's it for today's episode. Thank you so much for listening. If you would like to learn more about NAD, nicotinamide, and nicotinamide mononucleotide, check out the topic pages my team and I put together. Remember earlier at the start of this podcast about my commitment to make Found My Fitness better than ever before? This is one great example. Now available on my website are deep dive overviews we call topic pages.

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Catch you next time.