All About NAD+
The Science, the Supplements, and What I Found After Trying Nearly All of Them
“I keep getting served NAD ads on Instagram; what does it even do?” — three friends this week.
These days, it feels like everyone’s selling you an NAD+ supplement, but almost nobody actually stops to explain what it is, why you’re losing it, why you even have it in the first place, what it does, or which version actually works. (I’ve tried nearly all of them, don’t worry, we’ll get to that)
NAD+ might be the most talked-about molecule in longevity that almost nobody can actually explain. I know this because I work in this space, I’ve tried many NAD+ products, and when someone asks me “so what should I take?”...my honest answer is longer than they want it to be.
So instead of just telling you what I take (I’ll get there), I want to do something most of these supplement companies skip entirely: explain what NAD+ actually is, why it declines, what that decline feels like, and why the delivery method might matter most.
What NAD+ Is
Nicotinamide adenine dinucleotide. If that doesn’t roll off the tongue, just know this: NAD+ is a coenzyme (a non-protein organic molecule that helps in biochemical reactions) that exists in every single cell of your body, and without it, those cells can’t produce energy.
Your mitochondria (the tiny power plants inside your cells) use NAD+ to convert food into ATP, which is the energy currency your body runs on. No NAD+, no ATP. No ATP, no you.
Think of NAD+ like your phone's battery. When you're young, you wake up at 100% every day and it holds a charge no matter what you throw at it. By your 40s, you're waking up at 60%, and it's draining faster than you can top it off. The phone still works...just slower, dimmer, and it dies at the worst possible time.
But energy production is just the beginning. NAD+ also fuels three critical systems that keep your cells functioning:
Sirtuins (SIRT1 through SIRT7): These are NAD+-dependent enzymes that regulate metabolism, stress responses, DNA repair, and gene expression. Think of them as your cells’ maintenance crew. They can’t clock in without NAD+. Sirtuins are also the enzymes that get activated during fasting and caloric restriction, which is part of why those interventions show up in longevity conversations so consistently.
PARPs (Poly-ADP-Ribose Polymerases): These are your DNA repair enzymes. When your DNA breaks (and it breaks constantly; thousands of times a day), PARPs detect the damage and initiate the fix. They also run on NAD+. The catch: when DNA damage is chronic (from inflammation, poor sleep, UV exposure, or just...(sigh) aging), PARPs go into overdrive and start draining your NAD+ supply faster than your body can replenish it.
CD38: CD38 is an enzyme whose primary job is to consume NAD+. It cleaves it apart. And here’s the kicker...CD38 activity increases as you age. Like…significantly. It’s driven up by inflammation, and it’s accused of being the single biggest reason your NAD+ levels drop over time. CD38 can also degrade NMN directly (a popular NAD+ supplement precursor), which means it can intercept your supplement before it ever becomes NAD+. (Hang on, we’ll get to supplements)
In plain English: NAD+ is the molecule your cells need to make energy, repair DNA, and keep the lights on. Three major systems compete for it, and one of them (CD38) gets hungrier the older you get.
There’s one more thing worth knowing: NAD+ levels oscillate with your circadian rhythm. The enzyme that recycles NAD+ (called NAMPT) is directly tied to your internal clock. Disrupted sleep patterns lower NAD+ levels. So yes, your sleep habits are part of this equation.
When NAD+ Peaks, When It Drops, and What That Feels Like
NAD+ levels are highest in youth. They start declining meaningfully in your 30s and by your 40s and 50s, you may have roughly half the NAD+ you had in your 20s. In skin tissue specifically, the decline can be 50% or more over an adult lifespan.
The decline isn’t just a function of passing years; several things accelerate it simultaneously:
CD38 ramps up with age and inflammation. Senescent cells (the “zombie cells”) release inflammatory signals that drive CD38 expression in neighboring cells. More inflammation, more CD38, less NAD+. It’s a feed-forward loop.
DNA damage accumulates. More damage means more PARP activation, which means more NAD+ consumed for repair. In human skin, PARP activity significantly increases with age and inversely correlates with NAD+ levels.
NAMPT declines. This is the rate-limiting enzyme in NAD+ recycling (the salvage pathway that produces about 90% of your NAD+). Less NAMPT means slower recycling.
Mitochondrial dysfunction creates a vicious cycle. Low NAD+ impairs SIRT3 (the mitochondrial sirtuin), which worsens mitochondrial function, which generates more reactive oxygen species, which damages more DNA, which activates more PARPs. Around and around it goes.
So what does this actually feel like? Probably familiar:
Fatigue that sleep doesn’t fully fix. Slower recovery from workouts. Brain fog that shows up in the afternoon and doesn’t leave. Injuries that used to heal in a week now taking three. Skin that looks tired even when you’re not. That general sense of “I used to bounce back faster” that we write off as just getting older.
Not all of that is NAD+ alone, obviously. But the overlap between “things people complain about starting in their late 30s and 40s” and “things that happen when cellular NAD+ drops” is...striking.
In plain English: NAD+ peaks when you’re young and declines steadily from your 30s onward. The drop is driven by inflammation, DNA damage, and an enzyme (CD38) that literally eats your supply. What it feels like is the slow erosion of energy, recovery, and resilience that most of us chalk up to “aging.”
Before You Reach for a Supplement, The Dietary Building Blocks
Your body makes NAD+ from raw materials in food, primarily through two routes. The first is vitamin B3 (niacin and niacinamide), found in high concentrations in poultry, fish, beef, mushrooms, lentils, and whole grains. A single chicken breast or a cup of crimini mushrooms gets you close to your daily B3 requirement (16 mg for men, 14 mg for women).
The second route is the amino acid tryptophan, which your liver converts to NAD+ through the kynurenine pathway. About 60 mg of tryptophan yields the equivalent of 1 mg of niacin. Turkey, eggs, cheese, tofu, and edamame are all solid tryptophan sources.
There are also trace amounts of NMN in foods like broccoli, avocado, and edamame, but we’re talking fractions of a milligram per serving...so, not therapeutic. The bottom line is that a protein-rich diet with plenty of B vitamins gives your body the raw materials it needs to keep the NAD+ production lines running.
It just can’t outpace the decline once CD38, PARPs, and NNMT start pulling ahead.
How Do You Know If You Need to Supplement It?
Unfortunately, there’s no standard blood test for NAD+ that your doctor can order through Quest or LabCorp. It’s not on any routine panel. Jinfiniti Precision Medicine offers the first at-home intracellular NAD+ test (CLIA-certified, measures NAD+ inside your blood cells rather than floating in serum), and they process the vast majority of NAD+ tests worldwide. It runs about $200 per test.
But even Jinfiniti’s test has a limitation: it measures NAD+ in white blood cells. Whether that accurately reflects what’s happening in your muscles, brain, liver, and heart (where the aging biology actually plays out) is still an open question.
I’ll save you $200 and say the practical answer is that if you’re over 35 (40 if you’ve lived a very healthy life) and experiencing the symptoms I just described, your NAD+ levels have almost certainly started to decline. That’s not a guess; that’s what the population data consistently shows across multiple tissue types.
The trickier question is what to do about it, because here’s the catch that sets up the rest of this post: raising NAD+ in your blood is relatively easy. Several supplements can do that reliably. Getting NAD+ into your actual cells, especially skeletal muscle...that’s a different story entirely.
The Precursor Supplement Problem
Here’s the thing: you can’t just take NAD+ as a supplement and have it work. The molecule is too large and too electrically charged to cross cell membranes. For you molecular biology geeks out there: it has two negatively charged phosphate groups and a molecular weight roughly twice that of its precursors. Total no-go.
So almost every NAD+ supplement on the market is actually a precursor: a smaller molecule that your body can absorb and then convert into NAD+ once it’s inside the cell. The question is which precursor (there are many), and whether it actually gets where it needs to go.
The main players:
NR (Nicotinamide Riboside) is the most clinically studied NAD+ supplement on the market with over 35 human trials. It enters cells via nucleoside transporters and gets converted to NMN, then to NAD+. NR doesn’t cause flushing, it’s well-tolerated up to 3,000 mg/day, and it reliably raises blood NAD+ levels by about 60% at standard doses.
NMN (Nicotinamide Mononucleotide) is the precursor David Sinclair made famous, and on paper it makes the most compelling case. It's one enzymatic step closer to NAD+ than NR, so why not skip ahead? Because Charles Brenner, the scientist who discovered the NR pathway, argues that NMN can't actually cross your cell membranes. Your body has to strip it back down to NR before it can get inside the cell, then rebuild it into NMN again once it's in. So you're going for the express train, but your body's putting you back on the local. But not so fast, some research suggests cells may have a specific NMN transporter (SLC12A8), meaning NMN can enter cells directly. To add even more intrigue, the FDA has recently categorized NMN as a pharmaceutical compound. NR did not get that scrutiny. No one disputes the increased NAD+ blood levels seen from regular use of NMN; it’s the efficiency and mechanism that are up for debate.
Niacin (Nicotinic Acid) is the original vitamin B3, available at any pharmacy for pennies. It’s actually the most efficient NAD+ booster for the liver. But it causes the famous “niacin flush” (intense skin redness and tingling from prostaglandin release), which most people hate enough to stop taking it.
NAM (Nicotinamide/Niacinamide) is the other form of B3. No flushing. Cheap. But it directly inhibits sirtuins (the very enzymes you’re trying to activate by raising NAD+), which creates a frustrating paradox: more NAD+ in the tank, but the maintenance crew is on a forced break.
Now here’s where it gets really interesting. A landmark 2026 study from Nestlé and Nature Metabolism put NR, NMN, and NAM head-to-head for the first time in 65 healthy adults. Both NR and NMN approximately doubled blood NAD+ over 14 days. They were statistically equivalent. NAM barely moved the needle.
But the bigger finding was how NR and NMN actually work. The researchers discovered that gut bacteria rapidly break down both NR and NMN into plain nicotinamide, which then gets converted to nicotinic acid (niacin) by the microbiome. It may be that gut-derived niacin is what’s actually driving the blood NAD+ increase for both supplements. Which raises the question of whether you even need the expensive versions.
And then there’s the quality problem. A March 2025 ChromaDex study tested 38 commercial NR supplements. Only 13% met their label claims. 36% contained virtually no NR at all; nine products had zero detectable NR. The brands that passed: Tru Niagen, Elysium, Thorne, Genuine Purity, and Probase Nutrition.
On top of that, a key finding keeps showing up in clinical trials: blood NAD+ goes up with supplementation, but skeletal muscle NAD+ often doesn’t. The gap between what your lab numbers say and what your muscles actually experience is one of the biggest unresolved questions in this space.
The Delivery Methods: I’ve Tried (Almost) All of Them
I’ve been on the NAD+ train for a while now, and here’s what I found, ranked from theoretical worst to best (in my opinion).
NAD+ IV Drips: The One I Skipped
I’ve never done an NAD+ IV, and after everything I’ve learned, I’m glad I didn’t. Here’s why…
NAD+ is too large to cross cell membranes; when you infuse it directly into the bloodstream, it stays extracellular (outside). Your body treats that flood of extracellular NAD+ as a danger signal. Literally. Research published in Frontiers in Immunology has shown that extracellular NAD+ functions as a DAMP (damage-associated molecular pattern), activating purinergic receptors (how cells talk to each other) and triggering an inflammatory immune response. Your body thinks tissue is damaged and races to repair it.
That’s why NAD+ IVs are famously miserable. Every participant in a 2026 Frontiers in Aging study comparing NAD+ IV to NR IV reported moderate-to-severe abdominal cramping, nausea, vomiting, increased heart rate, and chest pressure during infusion. Sessions take 2 to 4 hours because you can’t push the drip faster without making symptoms worse. And about 70% of recipients showed a 3 to 10-fold spike in hs-CRP (an inflammation marker) afterward.
Adding insult to injury, a pilot study found that NAD+ IV didn’t even raise blood NAD+ meaningfully until 24 hours later, and then only by about 2%. Meanwhile, Dr. Eric Verdin, CEO of the Buck Institute for Research on Aging, has said that IV NAD+ is “mostly broken down into nicotinamide” before reaching cells, and you can buy nicotinamide for way less than a fancy IV.
I’ve seen anywhere from $600 to $1,000 per session to sit in a chair for three or four hours feeling terrible, triggering an inflammatory response, and getting something your body immediately dismantles into a molecule that costs five cents.
NAD+ Injections: My Personal Nightmare
I tried NAD+ injections. My entire body went hot. I got an uncomfortable, full-body ache that I can only describe as feeling like every cell was angry at me simultaneously. It was bad, and I hated it. And yes, this was sourced by my longevity doctor in compounded prescription form.
At the time I didn’t understand why. Now I do. Same mechanism as the IV: you’re flooding your bloodstream with a large molecule your body interprets as a danger signal. The heat and ache were my immune system responding to what it perceived as tissue damage. And I didn’t notice any energy benefit. None. Hard pass on this one.
Patches: Nothing
I tried NAD+ patches. I didn’t notice a thing. In fairness to me, the science backs this up. NAD+ has a molecular weight of about 663 daltons; the general rule for passive transdermal penetration is that molecules over 500 daltons don’t cross intact skin. There are zero peer-reviewed human clinical trials showing patches raise blood NAD+ levels. The marketing claims aren’t supported by published data. I don’t even remember which brand I tried, but it’s a moot point, isnt it.
NAD+ Nasal Spray: The One I Made My Sister Try
I didn’t try this one myself, but I made my sister the guinea pig. The theory is sound on paper: the nasal mucosa is highly vascular, so spraying NAD+ into your nose bypasses the digestive system and first-pass liver metabolism entirely. Some researchers believe the nasal route may also offer direct brain access via the olfactory nerve pathway, which would make it uniquely interesting for cognitive symptoms specifically. Note that this is by prescription only. Please do not buy this version off the internet.
My sister’s report: when she remembered to use it consistently, her brain fog improved noticeably (yes, I see the irony). The science on intranasal NAD+ in humans is still in progress, but so far most of the cognitive benefit data comes from preclinical models showing NAD+ reduces neuroinflammation and improves learning and memory. Maybe with prolonged use she’d remember to use it!
NR: Solid Science, Subtle Results, Will Test Again
NR is the most researched NAD+ precursor on the market. 35+ human trials. Clearly safe at doses up to 3,000 mg per day. It reliably raises blood NAD+ by about 60%, and longer-term studies (4+ weeks) have shown it can even raise NAD+ in the brain.
I tried the gold standard brand, TruNiagen (created by the aforementioned Charles Brenner) recently…took it for about a month at the bottle’s recommended dose of 500mg. I didn’t notice a dramatic, obvious difference in how I felt day to day. That doesn’t mean it wasn’t doing something at the cellular level; blood NAD+ definitely goes up, the science is solid. But in terms of subjective energy, recovery, or anything I could point to and say “that’s the NR”...it was subtle at best. It’s worth noting that my NMN experience (coming up next) was at 1,000mg so maybe if I’d pushed it to a gram I would have felt more. Something I’ll probably revisit one of these days. Again, NR has one of the most studied safety profiles around, so if you’re looking to dip a toe into raising your NAD+ levels, this is a solid place to start.
NMN: Where This All Started for Me
NMN was actually my entry point into the whole NAD+ world. About five years ago, my longevity doctor put me on 1,000 mg a day; I suspect the dose came from David Sinclair’s recommendation. And honestly, it worked. I felt a noticeable lift in energy. So the debate above aside, my subjective experience on NMN at that dose was very real. Whether that was the NMN itself, or my gut bacteria converting it to niacin, or just the fact that I was flooding my system with enough precursor material to move the needle...I can’t say for sure, but I felt it.
I take Do Not Age’s Pure NMN (they also make an NR) because they are a research-focused formulation company whose compounds are also used by research labs. I trust the brand enough that I asked for a reader code: YBM takes 10% off. This is what I take when I’m off a 5-amino 1MQ cycle…keep reading for more on that. Sourcing of anything you ingest is important, but since NMN is classified as a pharmaceutical, it’s especially important here.
Niacin: The Surprise Skin Win
This one’s a bit sideways. In the summer and when traveling to warm places, I take Heliocare Advanced, which is a pill-form sunscreen…yes, that’s a real thing, and yes, it works. One of these Mondays I’ll do a post about skinspan. This product contains 300 mg of niacin along with a proprietary Fern-block compound. What I notice each time is that my skin starts glowing.
Niacin is the original, no-frills NAD+ precursor. Your liver converts it into NAD+, and it may actually be the molecule that NR and NMN ultimately get converted into by your gut bacteria. The downside is the famous niacin flush (skin redness and tingling), but at 300 mg in a formulated product, I didn’t experience it. What I did notice was visibly better skin, which makes sense because skin is one of the tissues where NAD+ decline is most dramatic (50%+ over a lifetime) and niacin is the most efficient liver-pathway NAD+ booster available. Shout out to my Brazilian dermatologist for this one.
5-Amino 1MQ: The Dark Horse
This is the one most people have never heard of, and it’s my favorite by a wide margin. 5-amino 1MQ isn’t an NAD+ precursor at all. It works through a completely different mechanism: instead of adding NAD+ precursors, 5-amino 1MQ blocks the enzyme (NNMT) that’s been draining your NAD+ supply in the first place.
Here’s how NNMT works: every time your body uses NAD+, one of the byproducts is nicotinamide (NAM). Normally, NAM gets recycled back into NAD+, but NNMT diverts NAM away from that recycling process by methylating it into a waste product (1-methylnicotinamide) that gets excreted. NNMT activity increases with age, particularly in fat and muscle tissue, which means your recycling system gets less efficient right when you need it most.
In plain English: Instead of pouring more water into a bathtub with the drain open, 5-amino 1MQ plugs the drain.
5-amino 1MQ also preserves SAM (S-adenosylmethionine), your body’s primary methyl donor, because NNMT competes for the same methyl groups. So you’re protecting two important metabolic resources with one compound. This is extremely valuable to people like me who have an MTHFR variant (80% of you reading this also have it, btw), and why taking creatine also helps. See this post for more on that.
But back to 5-amino 1MQ (it is a mouthful, isn’t it?)…I felt it immediately. And I mean immediately. Do not take this in the afternoon or you will not sleep. The first few days, the energy was almost overwhelming; like someone turned the voltage up on my entire system. It levels out after about 3 days, but the initial hit is unlike anything I’ve experienced from any other NAD+-related compound. And it wasn’t just me. Other people I know…subscriber and longevity aficionado Trish Tang Golumbic, for one, described the same experience. Please note that we both sourced this through a longevity doctor through a compounding pharmacy. Also important to note: this one must be cycled. The most common recommendation is 4 to 6 weeks on, 2 to 4 weeks off. I spend longer in the off-cycle than the on-cycle, more like 3 months off. The idea is to prevent your body from adapting to the NNMT inhibition and to maintain sensitivity to the compound.
The science is early but compelling. A 2024 study in Scientific Reports found that 5-amino 1MQ improved grip strength in aged mice to a greater degree than vigorous exercise alone. When combined with exercise, the improvements were additive. Another study showed it to shorten muscle recovery time, increase intracellular NAD+ levels 1.2 to 1.6-fold, and reduce fat cell size by 30 to 40% without diet changes.
The caveat: there are no published human clinical trials. Zero. The mechanism is well-understood and well-published in journals like Frontiers in Pharmacology and Biochemical Pharmacology, but the human data just isn’t there yet. This is the same gap BPC-157 lives in (more on that here); compelling animal data, strong mechanism, real-world anecdotes, but no human studies. If that’s a dealbreaker for you, I understand. For me, the mechanism made sense, the preclinical data was solid, and the experience spoke for itself.
In Case You Skimmed
NAD+ is the coenzyme every cell needs to make energy, repair DNA, and maintain itself. It declines starting in your 30s, accelerated by inflammation, DNA damage, and an enzyme called CD38 that literally consumes it.
You can’t take NAD+ directly as a supplement; the molecule is too large to enter cells. Every “NAD+ supplement” is actually a precursor (NR, NMN, niacin) that your body converts.
NR and NMN both raise blood NAD+ by about the same amount. A 2026 study found your gut bacteria may convert both into plain niacin before they do anything, which raises questions about whether the expensive versions are worth it.
NAD+ IVs are expensive, miserable, trigger inflammation, and your body breaks the NAD+ down before it can enter cells. NAD+ injections gave me a full-body ache and did nothing for energy. Patches have zero clinical evidence.
5-amino 1MQ takes a different approach entirely: instead of adding more precursors, it blocks the enzyme (NNMT) that drains your existing NAD+. I felt the difference immediately and it’s the only NAD+-related compound that gave me an obvious, undeniable energy response.
Quality matters. 87% of NR supplements tested in a 2025 audit failed to meet label claims. If you’re investing in NAD+ supplementation, buy from companies with third-party testing.
NAD+ supplementation isn’t a silver bullet, and the science is still catching up to the hype. But the biology is real, the decline is real, and for me, finding the right approach to supporting it has been one of the more noticeable changes in how I feel day to day. If you think NAD+ supplementation might work to improve your days, try out which method works best for you, and see how you feel by next Monday.
See you then,
Susan
Longevity In The Wild
A friend and subscriber (who shall remain nameless) recently admitted she takes her kids to McDonald’s more often than she’d like. I respect the honesty. I also warned her she was going to end up in this section.
The answer nobody wants to hear: meal prep. Even a little. Organic chicken nuggets in the freezer. An air fryer and a bag of potatoes with sea salt. Frozen fruit for smoothies. It doesn’t have to be a whole thing; it just has to be there so that when the 5 PM panic hits, the path of least resistance isn’t a drive-thru, it’s a freezer with a plan.