What the human data actually says about NAD+...and why what you're buying might not be what you think.
I spent three days in March surrounded by NAD+ researchers in Copenhagen, and my overall take is this: the science is real, the hype is ahead of it, and the most important signals right now are in specific disease contexts rather than general wellness.
Nowhere is that more true than in neurodegenerative disease.
But before we get there, I need to back up and make sure we’re all speaking the same biological language. Because there is a lot of confusion in the marketplace about how these molecules actually work, and some of that confusion is being actively exploited.
A quick (and important) refresher: how NAD+ and NR actually get into your cells
I wrote a detailed explainer on this in a previous post (linked here), so I’ll keep this high-level, but it’s worth revisiting because it matters enormously for evaluating the products you’re seeing marketed.
NAD+ is a large, charged molecule that lives and does its work inside your cells, primarily inside the mitochondria. It cannot cross the cell membrane directly. There is no transporter for intact NAD+ into most cells. So when NAD+ appears in your bloodstream, whether from an IV infusion or from the breakdown of a supplement, it doesn’t just cross into your cells and go to work. It has to be broken down first into smaller precursor molecules (primarily NR and NMN), which can then enter cells through specific transporters and be reassembled into NAD+ intracellularly.
Where is the human data - expert panel, Copenhagen 2026
This is why straight oral NAD+ supplements (and low dose infusions/injections) are a waste of money. Your body simply can’t use it directly.
Oral NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), on the other hand, are smaller precursor molecules that do have specific cell transporters. NR enters cells via equilibrative nucleoside transporters (you don’t need to remember that, just know: there is a biological door for it). Once inside, it gets converted to NMN and then to NAD+ through a series of enzymatic steps. This is why NR and NMN have the most robust human data for actually raising intracellular NAD+ levels. They can get where they need to go.
When it comes to IV administration, the story is more nuanced. IV NR bypasses the gut entirely and delivers NR directly into the bloodstream, where it can be taken up by cells through those same transporters faster and more efficiently than oral supplementation. IV NAD+, however, presents a different problem: NAD+ in the extracellular space (outside the cell, in the blood) is recognized by the body as something of a distress signal. Enzymes called CD38 and CD73 rapidly break it down in the bloodstream. This degradation process is actually what causes the nausea, flushing, chest pressure, and GI distress that many people experience during IV NAD+ infusions. Our first study (more below) documented this extensively. The infusion has to be run slowly, over two to six hours, precisely to manage these reactions. It’s not dangerous, but it is genuinely uncomfortable for many people, and it raises real questions about bioavailability.
What our first study actually found
My lab’s published paper in Frontiers in Aging (Reyna et al., 2026) is the first human study to directly compare IV NAD+ and IV NR in a controlled, real-world setting. The primary focus of this first manuscript was safety and tolerability. We were establishing the basic pharmacological profile of both infusions in a population that actually uses these therapies in a wellness context, not just in a research lab.
The tolerability findings were clinically meaningful. The IV NAD+ group reported significantly more side effects during the infusion period, consistent with the extracellular distress-signal mechanism I described above. We’re talking about real symptoms: nausea, flushing, chest tightness, GI discomfort, that required the infusion to be run slowly and required active management. IV NR, by contrast, was substantially better tolerated, which is consistent with its more direct cellular uptake pathway bypassing that extracellular breakdown step.
We also tracked metabolic markers, body composition, and early biomarkers relevant to aging. The full outcomes picture from this cohort is actually what I’ll discuss more in Post 3, because the most interesting findings involve what happened over the following 30 days of continuous biometric monitoring. But the tolerability data alone makes a clinically important point: IV NAD+ and IV NR are not interchangeable. They behave differently in the body, they feel different during administration, and understanding those differences matters for anyone considering these therapies.
The brain data: where the human signal is actually meaningful
NAD+ is not just an energy molecule. It’s a cofactor for a family of enzymes (i.e. sirtuins, PARPs, CD38) that regulate DNA repair, inflammation, mitochondrial function, and gene expression. All of those processes are directly implicated in neurodegeneration. As NAD+ levels decline with age (and they do, significantly), the brain’s capacity to repair damage, manage oxidative stress, and maintain mitochondrial health declines with it.
In animal models, restoring NAD+ levels has shown striking neuroprotective effects like reducing amyloid accumulation, attenuating neuroinflammation, improving cognitive function. The mechanistic case for why NAD+ replenishment might protect the aging brain is genuinely strong.
The human data is more nuanced, but it is getting more compelling.
The most discussed clinical programs at the conference involves NR supplementation in PAD (peripheral artery disease), Parkinson’s disease, and rare genetic disorders. There is compelling, published, peer-reviewed data here. I was particularly intrigued by the neurodegenerative clinical work. Studies have shown that oral NR can suppress inflammatory activation in Parkinson’s patients in a measurable way that correlates with improved NAD+ levels in blood. This is not a subjective “I feel better” finding. This is biochemical target engagement translating into a downstream inflammatory signature change in a disease population.
Is this a cure? Absolutely not. Is it disease modification? We don’t know yet. The trials are still relatively small and short. But it is a real signal. And for a disease as devastating and as poorly served by current therapeutics as Parkinson’s, a real signal is worth following with rigor and urgency.
On the cardiovascular (PAD) side, early proof-of-concept studies have shown modest blood pressure reduction, improved arterial compliance in older adults, and suppression of inflammatory markers. These aren’t headlines yet, but they’re consistent with the mechanistic story and worth watching as larger trials get underway.
The buyer beware section
Okay. Here is where I put on my “no hype, just science”, because what I’m this frustrates me about my industry.
The NAD+ supplement market is projected to grow from roughly $200 million in 2021 to over $500 million by the end of this decade. That kind of growth attracts innovation. It also leads to products that are, to put it charitably, scientifically implausible. I want to flag two categories that I think deserve specific scrutiny.
First: products that cannot work based on basic biology. A new product making the rounds right now is a subcutaneous NAD+ “smart pen”. It’s essentially a self-injectable device that delivers NAD+ under the skin. I understand the appeal. It sounds cutting-edge. But here is the problem: subcutaneous NAD+ has the same fundamental limitation as IV NAD+. NAD+ in the extracellular space cannot cross the cell membrane directly. It needs to be broken down first into precursors. Delivering it (especially in very small doses) under your skin instead of into a vein doesn’t solve the cellular uptake problem. It just adds a different route to the same biochemical dead end, while also triggering the same kind of extracellular degradation. At $599-1000 per cartridge, you deserve to know that the biological rationale for subcutaneous NAD+ delivery improving intracellular NAD+ levels is not supported by the current science. Any improvements people feel are most certainly placebo.
Second: products that don’t contain what they claim to contain. Niagen Biosciences (formerly ChromaDex, the company that developed the Niagen NR ingredient used in our Restore Labs research) recently published a market surveillance analysis of 39 NR supplements commercially available in the United States. The findings were striking: only 13% of the products tested actually met or exceeded their label claims for NR content. Thirty-six percent had significantly less NR than claimed. And 36% had virtually no NR at all — below 1% of the labeled amount, which the researchers describe as “virtually none.”
The formats most likely to fail were high-water-content products: softgels, gummies, and liquids. This makes biochemical sense. NR is unstable in the presence of water. It degrades rapidly in an aqueous environment, which means that a gummy or a liquid NR product sitting on a shelf may have lost most or all of its active ingredient before it ever reaches you. All nine high-water-content products in the analysis contained less than 1% of their labeled NR content. Not less than claimed. Less than 1% of claimed.
The practical upshot: if you’re buying oral NR or NMN, it matters enormously what form you’re buying, who made it, whether there is third-party testing, and whether the active ingredient is listed as a patented, verified form. Capsules or tablets from a manufacturer with verified third-party testing and batch-level certificates of analysis are the formats most likely to actually contain what’s on the label. Gummies, liquids, and softgels are probably a waste of your money.
The bottom line
There is some very compelling, still emerging, data on NR and NMN supplementation to enhance NAD+ intracellularly, with some clinical outcomes to keep an eye on.
The biology of how these molecules reach your cells matters enormously. NAD+ itself cannot do it directly, which is why precursors like NR and NMN are what the science actually supports. And the supplement marketplace has a significant quality and plausibility problem that you need to know about before spending your money.