In this educational YouTube video, Dr. Ashley Frazee breaks down the biology of NAD+ (nicotinamide adenine dinucleotide), why its levels fall dramatically after the age of 40, and evidence‑based strategies to restore it. She explains that NAD+ is a co‑enzyme essential for mitochondrial energy production, fuels sirtuin proteins that regulate repair, inflammation, metabolism, and gene expression, and serves as a substrate for DNA‑repair enzymes (PARPs). Age‑related NAD+ loss is driven by increased consumption (elevated CD38 activity during inflammation and heightened PARP activity from DNA damage) and decreased synthesis/recycling (reduced NAMPT activity). Frazee then evaluates the main delivery methods—high‑dose oral precursors (NMN, NR, liposomal NAD+), injections, and IV infusions—detailing how each bypasses or confronts the liver’s first‑pass metabolism, the “tax” on oral doses, and the practical implications (dose size, methyl‑donor depletion, side‑effects, cost). She advises supplementing high‑dose oral NAD+ with a methyl donor such as trimethylglycine (TMG) to protect methyl pools. The video also debunks the lingering myth that resveratrol is required to activate longevity pathways alongside NAD+. Concluding, Frazee emphasizes that NAD+ is a valuable but not magical tool, recommending lifestyle fundamentals (sleep, exercise, stress reduction) and suggesting that most people can maintain adequate NAD+ without expensive IVs. References to peer‑reviewed studies, a product recommendation (Infiniwell), and a link to her peptide course are provided, along with a standard medical disclaimer.
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Fact, by the time you're 40, your NAD levels are roughly half of what they were in your 20s. And then your cells are less efficient at making energy. Your DNA repair is slower. You have these proteins called sirtuins that regulate nearly everything around how you age. And when NAD levels drop, those proteins are running out of fuel, and then you feel like trash. But guess what? You can fix it. And most people don't understand NAD well enough to believe that. But in this video, I'm breaking down what NAD actually is, Why it drops, and the best ways to get it back based on what the evidence actually supports, so you can get back to feeling yourself. I'm Dr. Ashley Frazee. I work directly for my patients instead of messing around with health insurance, so I've got the time to dive deep into topics like this. I'm gonna be straight with you. If you're lacking energy, NAD+ should be part of your stack. But there's not one person I talk to who really understands what it is, why they need it in the first place, How they should take it, or how much they should pay for it. Is an NAD IV really worth $500? Now, just a quick disclaimer here. I am a doctor on YouTube, but I am not your doctor. Nothing I say here is medical advice. This video is my opinion and is for education only. Talk to your own doctor before starting anything new, especially if you're on medications or have a chronic health condition. All right, let's start with the obvious. What exactly is NAD? Well, NAD stands for nicotinamide adenine dinucleotide. I'm much better at that than I used to be. It's a coenzyme. Coenzyme, meaning it doesn't do things on its own. It helps other enzymes do their job. Its most fundamental role is helping your mitochondria produce your energy. Without NAD+, you cannot make energy. So what's the point in having mitochondria if they don't even work? Like, imagine having a car and not putting gas in it. You're not going anywhere. But energy production is actually the boring part of NAD+. NAD+ is also the required fuel source for something called sirtuins. Proteins that act like cellular supervisors. They help control cellular repair, inflammation, metabolism, stress response, and even which genes get expressed. Sirtuins even protect mitochondrial function. NAD+ also fuels enzymes that repair your DNA when it breaks, called PARPs. Your DNA breaks thousands of times a day from radiation, oxidative stress, and just normal replication errors. Just like AI, your DNA makes mistakes too. So PARPs are enzymes that DNA, and they use NAD to do that. Every time your DNA gets repaired, you're pulling from your NAD stores to do it. This is why aging isn't just wrinkles, it's a resource problem. Your cells are spending more and more energy on maintenance as you get older. And we don't just need NAD for building and repair. Did you know that the older you get, the more senescent cells you have? These are cells that should die and get cleared out, but they don't. That's what senescent means. And the lame The sad part is that they end up becoming inflammatory. When your immune system sees the inflammation, it activates an enzyme called CD38 to help, and CD38 burns through NAD+ like a baby who just discovered sugar. It just burns through your NAD+. If you've ever wondered why stress and inflammation seem to hit harder in your 40s than it did in your 20s, this might be part of the reason. So NAD+ is simultaneously the fuel for your energy system, the substrate for your longevity proteins, and the repair currency for your DNA. And that's why people are excited about it. And that's also why when it drops, things go very wrong. Now that you see how important NAD+ is, let me recap what actually happens to NAD+ as you age, why it drops. It's a little more complicated than the internet wants to admit. The short version is that as you age, you're consuming more NAD+ and making less Of it. Your expenses go up, but your income goes down. CD38 is the main culprit on the consumption side. NAMPT is the main issue on the synthesis side, and I'll explain that. But remember CD38, the enzyme your immune system activates during inflammation? Well, the problem is you tend to express more of it as you age. So more inflammation means more CD38, and more CD38 means more NAD gets Burned up. Same story with PARPs. More DNA damage with age means that PARPs are working overtime and every repair costs NAD+. And then there's another problem. Your body also gets worse at recycling NAD+. You have this enzyme called NAMPT. I just said that. It helps rebuild NAD+ from broken down pieces. It's recycling it. But NAMPT activity drops with age. Just happens for all the same reasons that anything drops with age. Inflammation, stress, mitochondrial dysfunction, etc. Now you're not only spending more NAD+, but you're getting worse at replacing it. Okay, you get the picture. You have less NAD+ the older you get and the more stress you encounter. So now what? How do you top it off? Well, the great debate is how to take NAD+: orally versus injections versus IVs. And I'll give you a secret: they all work. But that doesn't help you choose, does it? So let me break down how and why they all work, and maybe you can make the best choice for you. Let's start with oral NAD+. Or pills. So any pill you take must survive passage through your gut, including the digestive enzymes and the acid in the stomach. But anything absorbed by your gut doesn't go straight to your tissues. It has to take a mandatory detour through the portal vein straight into the liver. And this is called first-pass metabolism. Now think of your liver as the most metabolically demanding, overworked factory in your entire body. It's constantly detoxifying, processing, and filtering things. And because it works so hard, the liver is absolutely starving for NAD+ all the time. And to feed itself, the liver is packed with that NAMPT, that NAD+ recycling enzyme. And the NAMPT in the liver, well, it's kind of like a fleet of recycling trucks. Its job is to grab any raw NAD+ precursors that come floating in from the gut, haul them inside, and immediately build them into NAD+ for the liver's own private use. And what this means for the rest of your body? Well, because the liver is so greedy and has so many recycling trucks waiting at the border? Well, the liver takes a massive cut. It aggressively hoards and consumes the vast majority of any oral NAD+ that you take to fuel its own heavy workload. And only a fraction of what you swallow actually survives the liver detour to make it out into the rest of your system. And this is why with oral NAD+, the dose should be really high. You might swallow 400 milligrams of NMN, like This one, which I like, and the link for this one in particular is in the description. But just remember, your liver steps in like a corrupt border guard and takes a 70% tax for itself and leaves the rest for your body to fight over the crumbs. And when I learned this, I simply asked, well, can you just overpay the taxman? And the answer to that is yes. And again, this is exactly why oral doses have to be high. But there is a catch to this tax strategy. When you overpay the taxman, it creates a lot of waste. And when your liver processes a surplus of NAD precursors, it has to tag the leftovers with methyl groups or carbon groups. And this is so that your body can pee them out. If you do this day after day, you can rapidly deplete your body's internal methyl donor pools, which you need for things like your mood, your DNA health, and clearing out things like homocysteine, which having high levels of that is Bad for you. So if you're going to take high-dose oral NAD+ to beat the liver tax, you should consider looking into something called TMG or trimethylglycine to use alongside NAD+ to act as a methyl donor. It's like an insurance policy, keeps the liver from bankrupting the rest of your system. Okay, now for a bit of a marketing war. NMN or NR or liposomal NAD+, which one is best? Every supplement company swears that theirs is the way, but what's the actual difference? Well, NMN is basically one step away from NAD+. You can think of it like partially assembled furniture. Your body still has a little bit of work to do to convert it to NAD+, but not much. And for years, scientists thought that NMN had to be broken down into something called NR before your body could absorb it. But the newer research suggests that certain tissues, especially the gut, may actually absorb NMN directly. But the bottom line is that human studies show NMN reliably raises blood NAD+ levels. And then let's talk about NR, because you can get NR in a supplement too. Well, NR is basically NMN's smaller cousin. It's one extra step away from becoming NAD+. But because it's smaller, some researchers think that it gets into cells more easily. But here's the funny part. When scientists finally compared NMN and NR head-to-head in humans, they performed really similarly, which means that the giant war between NMN and NR supplementation, well, it's more marketing than biology. And there's a third kind of oral NAD+. Which is liposomal NAD+. And I think this is interesting, and I want to think it works because I've taken liposomal NAD+ quite a bit myself. Well, liposomal technology basically wraps NAD+ in a little fatty protective bubble, almost like bubble wrap for like fragile cargo. And the goal of this is to help the NAD+ survive digestion, bypass the liver, and potentially reach tissues more intact. It's very compelling science, And recent studies have shown that the technology actually works. But there are still a lot of unknowns around manufacturing and whether the liposomes are surviving everyday packaging and distribution. But now let's talk about shots or NAD injections. A lot of people think shots are more potent, but it's really just that you get to skip the gut and bypass the liver tax. So if that's what you want, go for it. But you still need to know that injecting NAD doesn't mean it gets straight into the tissues just like that intact. NAD+ is simply too big to cross into your cells on its own. Whether you inject it into your hip or swallow it in a capsule, your body still has to chop it down into smaller precursors to get it inside the cellular wall. But some people just like shots. Then there's IV NAD+ infusions. When you take NAD+ via an IV, the same story applies here. Your body still must first break it down into NMN or NR, import it, and recycle it back into NAD+. Inside the cell, and this takes a couple of hours. The argument for getting an NAD IV is really about whether you are recovering from something like a viral illness or chronic inflammation, and your body has just burned through its stores and like nothing's left. In those circumstances, IV NAD could potentially act like a biological rescue mission, forcing a large amount of raw materials into the tissues that desperately need it. But beware of the cost. Of the IV. Not only financially— these will run you $200 to $600 per treatment— but also the notorious side effects, which are chest tightness or feeling like an elephant is sitting on your chest, nausea, intense flushing, and a feeling like your body just wants to crawl out of its own skin. The first time I ever had one of these, the nurse flooded the IV line on accident, which meant that we couldn't see how fast the IV was running, and an IV that was supposed to take 2 hours went through me in about 30 minutes. What a ride! These side effects are caused by NAD degradation products binding to receptors and high levels of free nicotinamide forcing your blood vessels to dilate and your smooth muscles to violently contract all at the same time. It's like an uncomfortable circus in your body. I actually took an NAD injection in my arm the other day and had those symptoms in just my arm for about an hour. It was weird. So you can get these side effects from the injections too. Just be aware. Now, we can't talk about NAD+ without addressing one of the biggest myths on the internet, that you have to pair it with resveratrol to activate your longevity genes. Look, I know this was the gold standard advice for about a decade, but the actual science has completely moved on. Do you actually need resveratrol with NAD+ supplements? No. But supplement companies still put it in there, and there's a long story to that, but the answer is no. Okay, if you've made it this far, here's my take. NAD+ is one of my favorite supplements. I think most people need it because the older you get, the less you have. But you need it for so many things. And while the delivery methods matter, most people probably don't need expensive IVs to support healthy NAD+ levels unless your body is just wrecked. And I've met people like that. But remember the basics: prioritize sleep, Exercise, lower your stress, be a good human. NAD+ isn't magic, but it is one of the ways that your cells keep the lights on. I have linked the peer-reviewed studies that we discussed today and that I pulled a lot of this information from down in the description, along with the supplement that I take from Infiniwell. And if you want to go ahead and dive deeper into the hard science of longevity, cellular pathways, and things like peptides without the general influencer sales pitch, check out my full course on peptides at courses.drafrasey.com. If like this video, please hit like for me, subscribe to my channel, and share this video with a friend who might need it. I hope you have the best day.
