Introduction
For years, I watched the supplement industry chase the next miracle molecule. CoQ10, resveratrol, alpha-lipoic acid—every few years, another compound promised to reverse aging at the cellular level. Most delivered disappointing results when rigorous trials finally rolled in.
Then came NAD+.
The story was compelling: a coenzyme that declines by 50% or more as we age, leaving our mitochondria starving for the fuel they need to function. Restore NAD+ levels, the theory went, and you restore cellular vitality. Mouse studies showed dramatic results. David Sinclair talked about it on podcasts and at longevity conferences. The supplement market exploded.
I'm taking it. But not because I believe the hype.
I'm taking it because I understand the mechanism, I've looked at what the research actually shows versus what it promises, and I've made a calculated decision even in the absence of gold-standard outcome data. I'm willing to acknowledge what we don't know—including some safety concerns I initially missed.
Here's what I learned that changed my thinking about NAD+, and why the honest answer is more nuanced than either the supplement marketers or the skeptics want to admit.
What Actually Declines (And Why It Matters)
NAD+ stands for nicotinamide adenine dinucleotide. The name doesn't matter. What matters is what it does.
Inside every cell in your body, NAD+ serves as an electron shuttle in the energy production process. When your mitochondria break down glucose and fatty acids to produce ATP—the energy currency your cells actually use—NAD+ is there accepting and donating electrons at multiple steps in the chain. Without adequate NAD+, the whole process slows down. It's like trying to run a factory with half the workers showing up.
But NAD+ does more than shuttle electrons. It activates a family of proteins called sirtuins, particularly SIRT1 and SIRT3. These proteins regulate mitochondrial biogenesis, DNA repair, inflammation, and stress resistance. When NAD+ levels are high, sirtuins work efficiently. When NAD+ drops, sirtuin activity declines, and cellular maintenance suffers.
Here's the part that matters for anyone over 50: NAD+ levels decline dramatically with age. Multiple studies document a 50-60% reduction in NAD+ by middle age compared to youth. In some tissues, the decline is even steeper. Your muscles, your brain, your liver—all running on half the cellular fuel they had at 25.
The question is whether restoring those levels through supplementation actually makes a functional difference.
The Precursor Problem: NMN vs NR
In general, you can't just take NAD+ directly. It's a large molecule that doesn't survive digestion and doesn't cross cell membranes efficiently. Instead, you take precursors—smaller molecules your body converts into NAD+. Unless, of course, you have access to a center that can administer intravenously or otherwise inject it.
The two main precursors are NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside). They enter the NAD+ synthesis pathway at different points, and this matters more than the supplement industry wants you to believe.
NR is one step earlier in the pathway. Once absorbed, it converts to NMN inside cells, then NMN converts to NAD+. NR has been around longer in supplement form, has more published human trials, and until recently was considered the more established option.
NMN enters the pathway one step closer to NAD+. There was debate about whether NMN could enter cells directly or needed to convert back to NR first. Recent research identified a specific NMN transporter protein (Slc12a8) that allows direct cellular uptake. This suggests NMN might be more efficient, bypassing one conversion step.
A 2025 review in Nature Metabolism looked at the latest evidence and concluded that both precursors increase blood NAD+ levels consistently. Both activate the same downstream pathways. The functional differences in humans remain unclear because we don't have head-to-head trials measuring hard outcomes like exercise capacity, cognitive function, or disease markers.
What we do have is biomarker data. And that's where things get interesting—and complicated.
What the Research Actually Shows
To be frank, the evidence is strong for biomarker changes and frustratingly weak for functional outcomes.
A 2022 study published in npj Aging looked at healthy older men (65 years and older, mean age around 71) taking 250mg of NMN once daily for 12 weeks. Blood NAD+ metabolites increased significantly. Muscle biopsy samples showed increased expression of genes related to muscle remodeling. Walking performance improved slightly—participants walked about 4% farther in six minutes, translating to roughly 16-20 extra meters.
For context, clinicians typically consider 25-30 meters the threshold for a meaningful functional improvement in elderly populations. So not a huge difference, it's below what we'd expect to notice in daily activities like grocery shopping or walking to the mailbox.
Another trial in GeroScience (2023) gave 80 healthy middle-aged adults either 300mg NMN daily or placebo for 60 days. NAD+ metabolites rose substantially. The treatment group showed stable biological age markers while the placebo group aged measurably over two months. Intriguing, but biological age clocks are surrogates. Do they predict actual health outcomes? We think so, but we don't have the long-term data yet.
The most comprehensive review came out in Nature Metabolism in 2025. The authors analyzed all available human trials on NAD+ precursors. Their conclusion was measured—more measured than I initially gave them credit for. They state that while NAD+ boosters "consistently increase whole-blood NAD+ levels," human clinical trials have shown "limited efficacy" in producing functional health improvements. They explicitly note the "enigmatic" gap between promising rodent results and disappointing human outcomes.
Compare this to mouse studies, where NMN and NR supplementation extends lifespan by 10-20%, improves glucose metabolism dramatically, and enhances physical performance. Those results made headlines. The human data so far shows biomarker shifts with uncertain clinical meaning.
This gap is critical to understand. It doesn't mean the supplements don't work. It means we're still early in the evidence curve. We have mechanism (strong), biomarkers (improving), and hard outcomes (missing).
The Mitochondrial Connection
If you read my earlier article on mitochondrial health, this is where the pieces connect.
Remember the three specialized mitochondrial populations in heart muscle cells? The subsarcolemmal mitochondria detecting environmental stress, the intermyofibrillar mitochondria producing ATP, and the perinuclear mitochondria regulating quality control through mitophagy?
NAD+ is essential for all three populations. It's required for oxidative phosphorylation in the intermyofibrillar mitochondria. It activates SIRT3, which protects mitochondria from oxidative stress. It supports PGC-1α, the master regulator of mitochondrial biogenesis.
When NAD+ levels drop with age, mitochondrial function declines. When you restore NAD+ through supplementation, you're not adding a foreign substance. You're replenishing a molecule your cells already use, one that's become depleted.
This is why red light therapy and NAD+ supplementation work synergistically. Red light activates cytochrome c oxidase in the mitochondrial respiratory chain. But cytochrome c oxidase requires adequate NAD+ to function optimally. Supporting cellular fuel (NAD+) and stimulating cellular machinery (red light) hit the system from complementary angles.
The question isn't whether NAD+ is important. It clearly is. The question is whether supplementing it produces measurable health benefits.
The Safety Profile (What We Know—And What We're Still Learning)
Before we talk about what to take, let's address safety. This matters because we're talking about long-term use of a supplement without decades of human data.
The good news: NAD+ precursors appear remarkably safe in the doses studied. Multiple trials using NMN at 250-900mg daily and NR at 500-1000mg daily for 12 weeks have found no serious adverse events. The most common side effects are mild: occasional nausea, headache, or flushing at higher doses.
A 2024 safety analysis looked at all published trials collectively. No signals for liver toxicity, kidney dysfunction, or metabolic disruption emerged. Blood markers remained stable.
However, most trials run 8-12 weeks. We don't have 5-year or 10-year human safety data. We're extrapolating from mechanism (NAD+ is already in your body, you're just raising levels) and short-term trials.
Here's where I need to be more diligent than I was in forming my initial thinking: there are legitimate theoretical concerns that deserve discussion, especially for someone my age.
The Cancer Question: More Complicated Than I Initially Understood
The common assumption is that cancer cells "already maximize their NAD+ production" and that supplementation in healthy individuals "doesn't appear to promote cancer." That's oversimplified.
The reality is more nuanced, and the scientific community is genuinely divided.
NAD+ activates sirtuins, which influence gene expression broadly. Some cancer cells do upregulate their own NAD+ synthesis pathways. The theory that they can't benefit from external supplementation sounds reassuring. But it may not be accurate.
Research from Rugang Zhang's lab at the Wistar Institute found that NMN supplementation enhanced cancer progression in mouse models of pancreatic cancer. A 2022 study showed that mice fed NR-enriched diets developed brain metastases from breast cancer at much higher rates than control mice—82% versus 25%.
These findings don't prove NAD+ causes cancer in humans. But they demonstrate that under certain conditions, in certain cancer types, NAD+ supplementation can accelerate tumor growth and metastasis in animals.
Other studies show the opposite. NR suppressed liver cancer metastasis in some mouse models. High-dose NMN showed anti-tumor effects in lung cancer models through different mechanisms.
The picture is genuinely mixed. Cancer type matters. Tissue context matters. The metabolic state of the tumor matters.
Prominent researchers like Peter Attia and Matthew Vander Heiden have called for more research into cancer risk before widespread supplementation. Zhang explicitly cautioned: "We should be cautious and bear in mind the potential downside of NAD+ supplementation."
Here's my current thinking: if you have active cancer or a history of cancer, this is absolutely worth discussing with your oncologist before supplementing. The precautionary principle applies. We don't have enough data to say it's safe, and we have some animal data suggesting potential harm.
For healthy older adults without cancer history? The risk-benefit calculation is less clear. Most of us at 75 have some precancerous cells or early-stage malignancies we don't know about. Does NAD+ supplementation feed those? We genuinely don't know.
I'm taking it anyway, but with eyes open to this uncertainty. I'm not claiming it's definitively safe. I'm saying the mechanism makes sense for cellular support, and I'm willing to accept unknown risks in exchange for potential benefits. That's a personal choice, not a recommendation.
The Senescent Cell Problem: Something I Completely Missed
When I first researched NAD+ supplementation, I focused on mitochondrial function and missed something important: the interaction with senescent cells.
Senescent cells are cells that have stopped dividing but haven't died. They accumulate as we age—by 75, I have a lot of them. These cells secrete inflammatory molecules (the senescence-associated secretory phenotype, or SASP) that promote aging and disease.
Research published in Nature Cell Biology found that NAD+ supplementation can amplify this inflammatory secretion from senescent cells. The same study showed NMN supplementation enhanced progression of precancerous and cancerous lesions in pancreatic tissue, potentially by empowering senescent cells to create a more tumor-promoting environment.
Researchers at Mayo Clinic explicitly stated that "NAD+ boosting may increase senescence-induced dysfunction" in their 2024 review.
This creates a paradox: NAD+ may benefit healthy cells while potentially making senescent cells more harmful. Some researchers now suggest that senolytics—compounds that clear senescent cells—should be taken before or alongside NAD+ boosters to eliminate the problematic cells first.
I didn't consider this when I started supplementing. I'm now thinking about whether to add a senolytic protocol (quercetin and fisetin are the most studied options) or to cycle off NAD+ periodically to avoid chronic amplification of senescent cell effects.
This is exactly the kind of complexity that emerges when you dig deeper. The mechanism supporting healthy mitochondria might simultaneously empower damaged cells. We're learning this in real-time.
What I'm Taking (And Why, Despite the Uncertainties)
I currently take 500mg of NMN each morning on an empty stomach.
Why NMN over NR? Honestly, it's a coin flip based on current evidence. The Slc12a8 transporter data suggesting direct NMN uptake tilted me toward NMN, but I wouldn't argue strongly against someone choosing NR. Both appear to work.
Why 500mg? Most human trials use 250-500mg daily. Higher doses (up to 900mg) have been studied safely, but the dose-response relationship isn't clear. I'm not convinced that more is better, and I prefer starting conservatively.
Why morning on an empty stomach? NAD+ levels naturally oscillate over 24 hours, peaking during the active phase. Taking it in the morning aligns with circadian biology. The empty stomach is based on one study showing better absorption when not competing with food, though this isn't definitively established.
Am I monitoring the response? Yes. I test biological age markers through TruDiagnostic (DNA methylation-based aging clocks) annually. I track body battery scores on my Garmin Fenix daily—not rigorous, but gives me a sense of energy and recovery trends. I get comprehensive metabolic panels every 6 months, watching liver function, kidney function, glucose, and lipids.
Have I noticed changes? My body battery readings have trended up slightly—averaging 80-85% on waking now versus 75-80% before I started. Is that the NMN? Possibly. Could be sleep improvements, exercise consistency, or placebo effect. I can't isolate cause and effect with n=1.
What I will say: I feel like my recovery from workouts is better than it was two years ago. I'm 75, and I don't expect to feel 50. But I'm training for my 90s, and anything that supports cellular machinery while the research continues to develop feels like a reasonable bet—as long as I acknowledge what I don't know.
The Quality Problem (And How to Navigate It)
The supplement industry has a serious quality control problem, and NAD+ precursors are no exception.
A 2021 analysis by ChromaDex tested 22 commercially available NMN products. The findings were damning: 64% of products contained less than 1% of the claimed NMN content. One product was contaminated with high levels of nicotinamide, a different compound that can inhibit sirtuins at high doses—the opposite of what you want.
A more recent study published in 2024 tested 18 NMN products and found deviation from label claims ranging from +28.6% to -100%. Three products contained no detectable NMN at all.
This isn't unique to NAD+ precursors. The dietary supplement industry has minimal FDA oversight for purity and potency. "Good Manufacturing Practice" standards exist, but compliance varies wildly. What to look for:
Third-party testing. Companies that submit products to independent labs for verification—NSF International, USP, ConsumerLab—demonstrate commitment to quality. Look for certificates of analysis on the company website.
Pharmaceutical-grade sourcing. Some manufacturers disclose where they source their raw NMN or NR. Uthever (from Effepharm) is a well-studied NMN source. ChromaDex (Niagen) is the original patent holder for NR. These aren't the only options, but they have published data behind them.
Avoid proprietary blends. If the label says "NAD+ boosting blend" without disclosing exact amounts of each ingredient, walk away. You can't assess dosing or quality without knowing what you're actually getting.
Expect to pay. Quality costs money. If you see 500mg NMN capsules for $15 per month, that's a red flag. Legitimate pharmaceutical-grade NMN costs $50-100 monthly at therapeutic doses. NR tends to run $40-80 monthly. If it's dramatically cheaper, question what you're actually getting.
I use a brand that provides third-party testing certificates and sources from Uthever. I'm not promoting specific companies here—do your own research, check certificates of analysis, and prioritize quality over price.
What About the Other "Longevity" Supplements?
Since we're talking about NAD+, let me address the compounds often stacked with it: resveratrol, quercetin, fisetin.
Resveratrol gets marketed as a sirtuin activator that works synergistically with NAD+. The truth is more complicated. A 2025 meta-analysis of 11 randomized controlled trials found no significant effect of resveratrol on SIRT1 gene expression, protein levels, or serum concentrations in humans. The sirtuin activation seen in yeast and mouse studies doesn't reliably translate to humans at achievable doses.
That doesn't mean resveratrol has zero benefits—some trials show modest improvements in glucose metabolism and blood pressure—but the "longevity molecule" claim is overblown.
Quercetin and fisetin are marketed as senolytics, compounds that clear senescent cells. Given what I just learned about NAD+ potentially amplifying senescent cell dysfunction, this combination suddenly seems more relevant. Mouse studies are promising. Human data is sparse. A few small trials suggest potential benefits for markers of cellular aging, but we're far from proof.
I take resveratrol although I am somewhat inconsistent. If I run out it may take me a while to remember to reorder. I'm now considering adding quercetin and fisetin specifically to address the senescent cell concern. I do want to see more human data and I am alert and watching for that. Supplements are expensive especially if you only buy from trusted producers and not the cheapest thing you see on Amazon. Functional outcome trials are very expensive to conduct. As I discussed most trials in this country are geared for short exposure on the order of 8-12 weeks. It is impossible to see functional outcomes unless you study for many years. That would justify expansion of the list of needed supplements. Just as I believe supplements are warranted, remember that the number one source of micronutrients should be your diet. Avoid processed food. Eat clean.
The Honest Bottom Line
At 75, I'm not chasing immortality. I'm chasing function. I want to stay strong enough, sharp enough, and energetic enough to live independently and train for my 90s.
NAD+ supplementation sits in an uncomfortable middle ground. The mechanism is sound—cellular fuel declines with age, restoring it should support mitochondrial function. The biomarker data is encouraging—blood NAD+ metabolites rise, biological age markers stabilize in some studies. But the functional outcomes we actually care about—strength, endurance, cognitive performance, disease prevention—lack definitive evidence.
And the safety picture is more complicated than I would like. The cancer data is genuinely mixed. The senescent cell interaction is a legitimate concern that deserves more research. The long-term data doesn't exist yet.
I made the decision to supplement anyway. Not because I'm certain it works, but because the risk-benefit calculation makes sense to me given what I know now. The short-term safety profile looks good. The cost is manageable. The mechanism directly addresses a known age-related deficit. And I'm willing to be part of the generation that experiments while the long-term data accumulates.
But I'm also willing to stop if new evidence suggests I should. I'm tracking biomarkers. I'm staying current on the research. I'm acknowledging the gaps in our knowledge rather than pretending they don't exist.
This isn't for everyone. If you're waiting for gold-standard randomized controlled trials showing NMN prevents dementia or extends lifespan, you'll be waiting years, possibly decades. If you need reassurance about cancer safety before supplementing, the data isn't there yet. If you have active cancer or significant cancer history, the precautionary principle suggests waiting for more evidence.
If you're comfortable supplement based on strong mechanisms, improving biomarkers, and acceptable short-term safety while accepting genuine uncertainty about long-term outcomes and cancer interactions, this might be worth considering.
What I won't do is oversell it. I won't claim it's reversed my biological age or made me feel 50 again. I notice better recovery. My objective tracking shows slight improvements. Whether that's NAD+, better sleep, consistent exercise, or placebo effect, I can't say for certain.
But here's what I know: my mitochondria need fuel. NAD+ is that fuel. Levels decline by half as we age. Restoring them makes mechanistic sense even in the absence of perfect data and in the presence of theoretical risks I'm choosing to accept.
The research will catch up. Until then, I'm making an informed bet on supporting my cellular machinery with the best evidence currently available, while staying honest about what we don't know.