Skip to content
NAD+ Picks
← Research
Evidence

Nicotinamide riboside: the best-studied NAD⁺ precursor, and what its trials found

NR raised whole blood NAD⁺ by 22%, 51% and 142% at three doses in a randomized trial. It also failed to change cognition, and failed to alter mitochondrial bioenergetics in aged muscle. Both halves matter.

Rachel Kim8 min read
Whole-blood NAD⁺ increase, by NR doseEight-week randomized trial in overweight adults, within two weeks of starting100 mg+22%300 mg+51%1,000 mg+142%A blood level, not a benefit. The trial was authored in part by the ingredient’s manufacturer.

Nicotinamide riboside — NR — is a form of vitamin B3 that your cells convert into NAD⁺. It is the most-studied compound in this entire category, and if you have read a news article about boosting NAD⁺, the research behind it was probably an NR trial even when the product being advertised alongside it was not NR.

That makes it the right place to see what the science in this field actually looks like when it is done properly, including the parts that did not work. The comparison with the other common precursor is its own question; this page is about NR on its own terms.

The pharmacology is unusually well characterized

The first clinical trial of NR pharmacokinetics gave single doses of 100, 300 and 1,000 mg and found dose-dependent increases in the blood NAD⁺ metabolome. The same paper reported a pilot in one individual whose blood NAD⁺ rose as much as 2.7-fold after a single oral dose, and identified nicotinic acid adenine dinucleotide as a sensitive biomarker of effective NAD⁺ repletion [1].

The chronic dosing study is the one with the cleanest numbers. An eight-week randomized, double-blind, placebo-controlled trial in overweight but otherwise healthy men and women found that 100, 300 and 1,000 mg of NR daily raised whole blood NAD⁺ dose-dependently and significantly — by 22%, 51% and 142% respectively — within two weeks, and held those increases for the rest of the study. There were no reports of flushing, no significant difference in adverse events between NR and placebo, no rise in LDL cholesterol and no disruption of one-carbon metabolism [2].

Two things about that trial matter equally. The numbers are the most specific dose-response data anyone has published for an NAD⁺ precursor. And it was authored by people at the ingredient’s manufacturer, which does not make it wrong but does make it worth naming — the crystalline NR chloride it tested is the branded ingredient sold as NIAGEN, which the paper describes as generally recognized as safe for use in foods and the subject of two New Dietary Ingredient Notifications[2]. That ingredient is what you are buying in Tru Niagen, and it is the reason NR has a settled regulatory position in the United States that NMN does not.

What happened when trials measured tissues instead of blood

A crossover trial gave 1 g of NR daily for 21 days to 12 aged men and sampled skeletal muscle directly. NR raised the muscle NAD⁺ metabolome and depressed circulating inflammatory cytokines — but RNA sequencing showed downregulation of energy metabolism and mitochondrial pathways, and mitochondrial bioenergetics did not change[3]. NR got into aged muscle. It did not make that muscle produce energy differently.

A separate 6-week crossover trial in healthy middle-aged and older adults found chronic NR well tolerated and effective at stimulating NAD⁺ metabolism. On physiological function, the authors were careful: their result was “initial insight”, and they framed blood pressure and arterial stiffness as things future clinical trials should assess [4] — a recommendation for more research, not a finding you can put on a bottle.

The cognition trial

This is the result to read twice, because it is the one the category is least willing to quote. In a placebo-controlled randomized pilot in 20 older adults with mild cognitive impairment, dose-escalated to 1 g daily for 10 weeks, NR produced a 2.6-fold increase in blood NAD⁺ (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse events.

Cognitive scores did not move. The Montreal Cognitive Assessment and the other neurocognitive and psychometric measures remained stable throughout the study, and walking speed improved significantly in the placebo group — consistent with a practice effect from repeated testing — while it did not change in the NR group[5].

So the supplement did exactly what it is supposed to do biochemically, in the population you would expect to have the most room to improve, and the thing people take it for did not happen. That is what a real result looks like, and it is why we treat the benefits evidence the way we do.

Where NR is being taken seriously as a drug

Parkinson’s disease, mostly. A double-blinded phase I trial gave 1,000 mg of NR or placebo to 30 newly diagnosed, treatment-naive patients for 30 days; NR was well tolerated and produced a significant but variable increase in cerebral NAD levels measured by phosphorus magnetic resonance spectroscopy, with altered cerebral metabolism and mild clinical improvement in the subgroup whose brain NAD actually rose[6]. A follow-up safety trial randomized 20 people with Parkinson’s to 1,500 mg twice daily or placebo for four weeks, found no moderate or severe adverse events, augmented blood NAD⁺ up to five-fold, and recommended extending the dose range to 3,000 mg per day in phase II [7].

Those are phase I trials in a disease population, run by academic neurologists. They are not evidence that a healthy person should take NR, and the dose range they explored sits far above what any retail product sells — which is worth holding in mind when a marketing page cites them. We keep the full list of doses used in published trials on the dosage page.

The honest summary

NR raises NAD⁺ in humans, dose-dependently, with published numbers and a real short-term safety record — more than any other product in this category can say. It has not been shown to improve cognition, and it did not alter mitochondrial bioenergetics in aged muscle when someone looked. The interesting clinical work is in neurology, at doses nobody is selling.

If that reads as a lukewarm endorsement, it is an accurate one — and it still places NR ahead of everything more expensive. An oral precursor costs a fraction of an injection or an IV drip, neither of which has a controlled outcome trial of its own. In this category the evidence ranking runs opposite to the price ranking, and NR is the clearest illustration of it.

Frequently asked

What is nicotinamide riboside?
A form of vitamin B3 that your cells convert into NAD⁺. It is the most heavily studied compound in the NAD⁺ category, and much of the research quoted on products that are not NR was in fact done with NR.
How much does nicotinamide riboside raise NAD⁺?
In an eight-week randomized, double-blind, placebo-controlled trial in overweight adults, daily doses of 100, 300 and 1,000 mg raised whole blood NAD⁺ by 22%, 51% and 142% respectively within two weeks, and the increases held for the rest of the study. A separate pharmacokinetic study reported a rise of as much as 2.7-fold after a single oral dose in one individual.
Does nicotinamide riboside improve memory or thinking?
In the trial that tested it, no. A placebo-controlled randomized pilot in 20 older adults with mild cognitive impairment produced a 2.6-fold increase in blood NAD⁺ at 1 g daily, while the Montreal Cognitive Assessment and other neurocognitive measures remained stable throughout. Walking speed improved in the placebo group, consistent with a practice effect, and did not change with NR.
What is Niagen, and is it the same as NR?
Niagen is a branded crystalline form of nicotinamide riboside chloride made by ChromaDex. The eight-week dose-response trial above tested that ingredient, and was authored by people affiliated with the manufacturer. The paper describes Niagen as generally recognized as safe for use in foods and the subject of two New Dietary Ingredient Notifications, which is why NR has a settled US regulatory position that NMN does not.
Is nicotinamide riboside safe?
The short-term record is good. The eight-week trial found no flushing and no significant difference in adverse events versus placebo, with no rise in LDL cholesterol. A high-dose safety trial gave 1,500 mg twice daily for four weeks to people with Parkinson's disease with no moderate or severe adverse events. Those are weeks-long studies in small groups, not a long-term safety record.

Sources

  1. [1] Trammell SA, Schmidt MS, Weidemann BJ, et al. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans Nature Communications. PMID 27721479
  2. [2] Conze D, Brenner C, Kruger CL. (Funding/affiliation: ChromaDex and Spherix Consulting — the ingredient manufacturer) (2019). Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults Scientific Reports. PMID 31278280
  3. [3] Elhassan YS, Kluckova K, Fletcher RS, et al. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures Cell Reports. PMID 31412242
  4. [4] Martens CR, Denman BA, Mazzo MR, et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults Nature Communications. PMID 29599478
  5. [5] Orr ME, Kotkowski E, Ramirez P, et al. (2024). A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment GeroScience. PMID 37994989
  6. [6] Brakedal B, Dölle C, Riemer F, et al. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease Cell Metabolism. PMID 35235774
  7. [7] Berven H, Kverneng S, Sheard E, et al. (2023). NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease Nature Communications. PMID 38016950

Where to get it

Oral NAD⁺ precursors (NR and NMN)

The cheapest route with the strongest human data — and the one we earn nothing from.

Compare providers →

More in Evidence