Charles Brenner is not a scammer. He's a genuine biochemist — the man who discovered nicotinamide riboside back in 2004. He's published hundreds of papers. And when a new study came out showing that his supplement, NR, boosted NAD levels 2.3 times more than its main rival NMN, he was quick to share it on X.
What he didn't share — and what this article examines in detail — is something buried in that same study: metabolic evidence showing that the entire NMN versus NR debate is completely beside the point. This is something the supplement manufacturers on both sides of the debate sincerely hope consumers won't notice. The data, however, tells a clear story about where these expensive supplements actually end up.
Table of Contents
The Backstory
In 2004, Brenner was studying an obscure enzyme called NAD synthetase. He noticed something strange — when you knock this enzyme out in yeast, the yeast should die, because it shouldn't be able to make NAD. But it survived. That meant there had to be an unknown pathway nobody had found yet.
He soon discovered what it was. Nicotinamide riboside, or NR — a molecule naturally present in milk — could be converted directly into NAD through a set of enzymes called nicotinamide riboside kinases [1]. It was an elegant discovery, and it launched an entire industry, because NAD is essential to a host of cellular functions, and deficiency has been linked to aging-related decline.
By 2007, Brenner's lab showed that yeast given NR divided over 23 times instead of the usual 13 [2]. The supplement industry took notice.
Then in 2016, a landmark mouse study took things further. Researchers found that an NAD precursor drove a host of benefits related to aging — enhanced energy metabolism, boosted physical activity, and improved insulin sensitivity, among others [3].
But this study didn't use NR. It used NMN — nicotinamide mononucleotide. And the man behind it? David Sinclair. Who just happened to co-found a company developing NMN as a drug.
So now there were two camps. Brenner and ChromaDex selling NR. Sinclair and his company developing NMN. Both claiming their form of NAD precursor was the one people needed. Both with financial interests in the outcome.
And for years, they've been fighting about it. Brenner has been blunt about his position. In his own words: "NMN doesn't get into cells as NMN. It gets in as NR, and there's a safe source of NR, so why are we still talking about NMN?"
What the latest evidence shows is that this statement needs a significant update — because it applies equally to NR itself.
The New Study
The study Brenner was sharing comes from a research group in Bergen, Norway — an independent team with no ties to any supplement manufacturer. They gave 6 healthy adults 1,200 milligrams per day of both NR and NMN, in a crossover design — meaning each person took both supplements at different times [4].
The effect of NR was decisively stronger. It produced about a 2.3-fold higher increase in NAD levels in the blood compared to NMN [4].
It sounds convincing. Until you realise this was just 6 people. And there's the matter of consistency — the researchers checked how predictable the changes in blood NAD levels were from one measurement to the next in the same people. The responses weren't very consistent, which adds significant uncertainty when trying to pin down the exact impact of each precursor [4].
Just two months before that study was published, a much larger trial appeared in Nature Metabolism — one of the top journals in the field. 65 participants. Randomised. Four groups: NR, NMN, nicotinamide, and placebo. And what did they find? NR and NMN both approximately doubled circulating NAD after 14 days. There was no significant difference between them [5].
So the headline result from the Berven study — the one Brenner was promoting — is contradicted by a study with more than ten times the participants, published in a higher-impact journal.
But it turns out that who wins this debate may not matter at all. Because something else in the Berven data tells a completely different story — one that neither the NR camp nor the NMN camp wants consumers to hear.
The Real Finding
In the Berven study, the researchers didn't just measure NAD. They tracked a whole panel of NAD-related metabolites over time. And one of them — called NAAD — revealed something important.
After 2 weeks of daily use, the data revealed a clear metabolic fingerprint. Baseline levels of NAAD were significantly elevated in those taking NR and NMN [5].
Here is why that matters. The body has multiple routes it can use to build NAD — like different roads leading to the same city. One of those roads starts from nicotinic acid — plain, cheap nicotinic acid, the kind available for a couple of dollars. And NAAD is a landmark that only exists on that particular road. It will never appear if another route is being used.
So if NR were entering cells directly and getting converted straight to NAD — which is a common supplement industry claim — NAAD would never appear at all. It's simply not on that route.
But the significant presence of NAAD after supplementation acts as a fingerprint. It tells you NR and NMN were broken down, converted to cheap nicotinic acid, and then rebuilt into NAD through a pathway called the Preiss-Handler pathway.
And this isn't just one lab's observation. Three independent research groups have now confirmed this mechanism.
In 2022, researchers at Princeton used isotope-labeled NR — a version tagged with atomic markers so they could track exactly where it ended up. What they found was striking. The main route from taking NR orally to impacting NAD levels is through first being broken down into nicotinic acid by bacteria in the gut [6]. When they gave antibiotics to deplete the gut bacteria, NR-derived nicotinic acid was — as the authors wrote — "completely eliminated" [6].
In 2025, a Japanese group went even further. They showed that even when you inject NMN or NR intravenously — completely bypassing the gut — the body dumps it into bile, sends it right back to the gut, and bacteria still convert it to nicotinic acid [7].
And the Christen study — the 65-person trial — confirmed this in actual human gut samples. They took fecal samples from healthy adults, exposed them to NR in a lab dish, and watched the bacteria rapidly convert it to nicotinic acid [5].
Here is what is actually happening when someone takes a $60 bottle of NMN or NR. Gut bacteria break it down into nicotinic acid — a form of vitamin B3 available for a few dollars a month. The body then rebuilds that nicotinic acid into NAD through the Preiss-Handler pathway.
Brenner said "NMN doesn't get into cells as NMN. It gets in as NR." He was right about NMN. But the evidence shows the same applies to supplemental NR itself. It doesn't get into cells directly either. It gets broken down to cheap nicotinic acid first.
The entire NMN versus NR debate — which one is better, which one is absorbed more efficiently — is beside the point. They are both like buying a first-class ticket only to end up sitting in the same economy seat.
But maybe none of that matters. Because there's a prior question: does raising NAD levels actually help in the first place?
Does It Even Matter?
A 2025 meta-analysis pooled 10 randomised controlled trials of NMN and NR in adults over 60 — the people who should benefit most if the NAD-decline-with-aging theory is correct. The results were stark: No significant improvement in skeletal muscle index, handgrip strength, gait speed, or chair stand test [8].
The study authors concluded: "Despite positive pre-clinical findings, our results highlight a negligible effect of both NMN and NR" [8].
It's the same story for metabolism — a separate meta-analysis found no significant improvements in fasting glucose, insulin, HbA1c, cholesterol, or triglycerides, despite confirmed NAD increases [9].
But perhaps the right condition simply hasn't been found yet. If NAD metabolism is strained during illness — and NAD levels are boosted in those people — surely a difference would emerge?
That's exactly what researchers tested in long-COVID patients. These are people with brain fog, fatigue, and immune dysfunction — precisely the kind of condition where supporting NAD metabolism should help, if it's going to help at all.
Researchers gave NR to about 60 patients for 20 weeks. Blood NAD+ shot up by 2.6 to 3.1 times. Then they checked cognition, fatigue, sleep quality, anxiety, and depression. Nothing. NAD levels tripled, and not a single symptom improved [10]. If there was ever going to be a functional benefit from boosting NAD, long COVID was the test. And it failed.
NMN and NR reliably raise blood NAD — no one disputes that. But after twenty years and dozens of clinical trials, there is still no demonstration that raising blood NAD translates into anything measurable. Not in muscle. Not in metabolism. Not in the brain. Not even in patients whose NAD metabolism is clearly under strain.
And it's worth noting that NAD decline with age may not be inevitable. A 2022 study found that exercise-trained older adults had NAD levels comparable to young people [11].
The Bottom Line
Brenner was right about one thing. He once said that everyone buying the NMN story is being "hoodwinked." But what the last four years of research show is that the same gut bacteria that convert NMN also convert NR — and turn both into a vitamin available for a couple of dollars a month.
The human data does not support paying a large premium to super-load NAD+ pathways when it isn't translating to functional benefits. Meeting baseline vitamin B3 requirements appears to be sufficient — and nicotinamide, the simple, inexpensive form of vitamin B3, accomplishes exactly that.
From the MicroVitamin range
MicroVitamin includes nicotinamide — the evidence-supported, cost-effective form of vitamin B3 — at a dose aligned with the research discussed above. MicroVitamin.
The bigger picture: the supplement industry benefits when consumers debate which premium form of vitamin B3 is worth $60 a month. Meanwhile, the most evidence-backed approach for supporting NAD levels — the one intervention that actually showed exercise-trained older adults maintaining NAD comparable to young people [11] — doesn't come in a bottle at all. It's regular physical exercise. That single finding reframes the entire NAD supplement conversation.
References
1. https://www.cell.com/cell/fulltext/S0092-8674(04)00416-7
2. https://www.cell.com/cell/fulltext/S0092-8674(07)00390-X
3. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30495-8
4. https://www.cell.com/iscience/fulltext/S2589-0042(26)00139-2
5. https://www.nature.com/articles/s42255-025-01421-8
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC9825113/
7. https://www.science.org/doi/10.1126/sciadv.adr1538
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC12022230/
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC11557618/
10. https://www.sciencedirect.com/science/article/pii/S258953702500567X
