Nicotinamide riboside (NR)

What it is

NR belongs to the vitamin B3 family, which also includes nicotinic acid and nicotinamide. In the body it is converted to NAD+, an important coenzyme in all cells that is needed by the sirtuins, among others. According to EFSA, NR is also a source from which nicotinamide, and thus niacin, becomes available.

As a preparation, NR is almost always sold as synthetic nicotinamide riboside chloride. The first clinical study in humans appeared in 2016. A critical review counted 25 published papers by 2023, an unusually high number for a longevity supplement.

How it is supposed to work

The idea comes from animal research. According to studies, NAD+ falls with age, and in animal experiments NAD precursors improved metabolism, for example insulin sensitivity and fatty liver. If the NAD+ level rises again in humans, so the hypothesis goes, cells could produce energy better, repair DNA damage better and dampen inflammation.

The first step of this chain is well supported in humans. In an 8-week placebo-controlled study, NAD+ in whole blood rose by 22, 51 and 142 percent with 100, 300 and 1,000 mg of NR, after just 2 weeks, and then remained stable. In a study of 30 Parkinson's patients, NAD rose measurably in the brain, although to varying degrees. A pharmacokinetic study showed that the blood level only reaches a plateau after about 2 weeks and is elevated in the brain after 4 weeks. Whether the higher level in muscle, liver or blood vessels triggers the hoped-for effects is the open part of the chain.

What the studies show

NR in overweight and insulin resistance 2018

40 men with obesity aged between 40 and 70 took 2,000 mg of NR per day or placebo for 12 weeks. Insulin sensitivity, measured with the elaborate clamp method, did not improve, and neither did glucose production, fat breakdown, energy expenditure or body composition. No serious side effects occurred, and the safety values remained normal. The primary endpoint was thus missed.

Dose and NAD increase 2019

Overweight but otherwise healthy adults received 100, 300 or 1,000 mg of NR or placebo for 8 weeks. NAD+ in whole blood rose in a dose-dependent manner by 22, 51 and 142 percent. Side effects were no more frequent than under placebo, and there was no flush. The branded raw material was tested, whose safety the study was meant to demonstrate.

NADPARK in Parkinson's disease 2022

30 newly diagnosed, not yet treated Parkinson's patients took 1,000 mg of NR or placebo for 30 days. NR was well tolerated and measurably raised NAD in the brain, measured with magnetic resonance spectroscopy. Inflammatory messengers in serum and cerebrospinal fluid fell. It was a phase I study on safety and feasibility; efficacy cannot yet be derived from it.

Critical review 2023

Two researchers who had themselves been involved in several NR studies evaluated all 25 human studies published up to that point. Their conclusion: oral NR has so far shown few clinically relevant effects, and the literature tends to overstate findings. Highlighted positively are indications of less inflammation and potential in individual serious diseases.

High-dose safety study NR-SAFE 2023

20 people with Parkinson's disease received 1,500 mg of NR twice daily or placebo for 4 weeks in a double-blind design, 10 per group. The primary endpoint was safety: moderate or severe side effects did not occur, and mild ones were no more frequent than under placebo. NAD+ in the blood rose up to 5-fold. The Parkinson's scores improved, although this was also related to a shorter interval since the last levodopa dose, and homocysteine initially rose slightly.

Where the data stop

The leap from a higher NAD+ level to better health has not yet succeeded in humans. In the metabolic studies, insulin sensitivity, blood sugar, liver fat, mitochondrial function and blood pressure mostly did not change. One study found slightly more fat-free mass and a higher sleeping metabolic rate, but no effect on inflammatory markers. The lower blood pressure in older people observed in an early study was not confirmed in other studies. For aging itself, that is frailty, disease burden or lifespan, there are no data; the longest published studies lasted 6 months.

The most important open question concerns Parkinson's disease. The phase III study NOPARK with 410 participants in early disease was completed on June 17, 2025, but results can be found neither in the registry nor as a publication. Until then, the positive signals from small phase I studies remain a hypothesis.

Status, approval and legal

Nicotinamide riboside chloride has been authorized in the EU as a novel food since 2020. The basis was an EFSA assessment from 2019 that classified NR in food supplements as safe up to 300 mg per day for healthy adults, and up to 230 mg for pregnant and breastfeeding women. EFSA did not confirm an extension to meal replacements and beverage powders as safe in 2021, because the safety margin for infants was too small. There are no specific health claims for NR, but NR counts as a source of niacin. There are no medicines containing NR. NR is not on the WADA prohibited list for 2026.

Safety

NR has been well tolerated in the studies so far, even at high doses over several weeks. Isolated mild complaints have been described, and in one high-dose study a slight initial rise in homocysteine. NR does not cause a flush like nicotinic acid. EFSA considers up to 300 mg per day safe for healthy adults, and up to 230 mg for pregnant and breastfeeding women. For nicotinamide, into which NR is partly converted, the upper limit is 900 mg per day. EFSA at the same time points to experimental indications that very high intakes far above requirements could have side effects, and considers a reassessment of this limit possible. Long-term data over more than 6 months are missing. For people with cancer there are no data; here, intake belongs in the hands of a physician.

Sources

• Damgaard & Treebak, Sci Adv 2023
• Conze et al., Sci Rep 2019
• Dollerup et al., Am J Clin Nutr 2018
• Remie et al., Am J Clin Nutr 2020
• Martens et al., Nat Commun 2018
• Brakedal et al., Cell Metab 2022 (NADPARK)
• Berven et al., Nat Commun 2023 (NR-SAFE)
• ClinicalTrials.gov NCT03568968 (NOPARK)
• EFSA NDA Panel, NR chloride as a novel food, EFSA Journal 2019
• EFSA NDA Panel, extension of use of NR chloride, EFSA Journal 2021