NR 101: The Basics, Benefits, and Research on Nicotinamide Riboside

With recent regulatory changes, many people are understandably looking for other ways to support their NAD+ stores. Fortunately, there is a viable and effective option—nicotinamide riboside, or NR.

NR is a precursor to NAD+ (nicotinamide adenine dinucleotide), an essential compound that is fundamental to our lives. NAD+ is needed for hundreds of vital reactions that occur each second in every one of our cells. As a coenzyme, NAD+ helps other enzymes to function properly and carry out these life-giving reactions.

However, most people experience a drop in NAD+ activity as they age. Studies show that NAD+ levels can drop by half between the ages of 40 and 60, with an additional decline upon reaching older age. As insufficient NAD+ levels are linked to accelerated aging and age-related conditions, supporting NAD+ levels with age is critical—and one way is with supplemental NR.

The Basics of NR: How It Works

Nicotinamide riboside is part of the niacin (vitamin B3) family. NR participates in the NAD+ biosynthesis pathway. Also known as the “NAD salvage pathway,” this internal recycling program produces NAD+ from inactive forms of nicotinamide, including NR.

Research shows that NR boosts NAD+ levels efficiently, making it a suitable option for supporting NAD+ levels in the body.

Does NR Raise NAD+ Levels? A Look at Recent Research

In research from 2019, healthy overweight adults supplemented with 100, 300, or 1,000 mg of NR for eight weeks. All three doses significantly increased whole blood NAD+. The increases occurred within two weeks and were dose-dependent—meaning the higher doses boosted NAD+ more—with 100, 300, and 1,000 mg of NR increasing whole blood NAD+ by 22%, 51%, and 142%, respectively.

In another study of 70- to 80-year-old men, taking 1,000 mg of NR in the form of Niagen for 21 days safely and significantly boosted the NAD+ metabolome in whole blood and increased a biomarker of NAD+ metabolism in the skeletal muscle.

Top 3 Benefits of Nicotinamide Riboside

1. Supports Heart Health

Boosting NAD+ bioavailability with precursors like NR has been proposed as a strategy for supporting cardiovascular health in aging adults.

One study published in Nature Communications in 2018 found that adults who took 1,000 mg of NR per day for six weeks had a tendency towards reduced blood pressure. Specifically, people with elevated blood pressure had a 9 mmHg reduction in average systolic blood pressure (SBP) after taking NR compared to the placebo.

While that might sound like a small difference, it makes a big impact: every 10 mmHg reduction in SBP is linked to a 20% reduction in the risk of major cardiovascular-related events. This study also found a trend toward reductions in aortic stiffness after taking NR—a strong risk factor for age-related cardiovascular events.

2. Supports Brain Health

NR may also support brain health and cognition, likely due to reducing neuroinflammation. In a 2022 clinical trial, adults with a newly diagnosed neurodegenerative condition were given 1,000 mg NR or a placebo for 30 days.

The researchers found that people taking NR had increased cerebral NAD+ levels, mild clinical cognitive improvement, and reduced activity of pro-inflammatory molecules in the cerebrospinal fluid. The NR treatment also increased the activity of genes involved with mitochondrial function and antioxidant responses.

A review paper looked at the effects of NR in 20 animal- or cell-based models of neurodegenerative conditions. The results showed that NR boosted brain NAD+ levels in mice, supported cognitive performance and behavior, and slowed disease progression in several other models. The mechanisms behind these benefits included reduced neuroinflammation, increased levels of BDNF (brain-derived neurotrophic factor), and elevated sirtuin activity.

3. May Improve Body Composition

As NAD+ is a crucial component of metabolism, supporting its regeneration may also lead to healthier body compositions. One small study examined the effects of 1,000 mg of NR for six weeks on 13 overweight or obese adults. The researchers found that NR supplementation improved skeletal muscle acetylcarnitine metabolism, which is linked to better metabolic flexibility and improved metabolic health.

NR also induced minor changes in body composition and sleeping metabolic rate. These body changes included an increase in fat-free mass with a decrease in fat mass. Notably, these benefits mostly occurred in the females of the study, suggesting that NR may have gender-specific effects on body composition.

However, another study using 2,000 mg of NR daily for 12 weeks showed no significant benefits to body composition or energy expenditure.

NR Safety and Dosing

There are several finished clinical trials on the safety and bioavailability of NR. One study found that 21 days of NR supplementation was safe, bioavailable, and well-tolerated in humans in doses up to 1,000 mg.

Similarly, in animal toxicology studies, rats that took Niagen (a synthetic form of NR) had the lowest levels of adverse effects at 1,000 mg per kg per day, with no observed adverse effects at 300 mg/kg/day. (Note that an animal dose of 1,000 mg/kg/day is not equivalent to a human taking 1,000 mg per day and would equate to a much higher dose.)

While doses of 1,000 mg or even 2,000 mg per day have been shown to be safe and well-tolerated, most NR supplements utilize doses of 300-500 mg per day.

Plus, you can trust ProHealth’s nicotinamide riboside products as we use Niagen, the only clinically proven and science-backed form of NR, and the same form that was used in all of the clinical trials showing benefits to human health markers.

The Bottom Line

NR is an excellent option for supporting NAD+ levels and healthspan with age.

Research has shown that NR is linked to improved cardiovascular and cognitive health—which may be largely due to supporting healthier inflammatory responses—and may also promote healthier body compositions.

While more research on all NAD+ precursors is always needed, NR seems to be a beneficial compound with low risk or possibility of adverse effects.

References: 

Brakedal B, Dölle C, Riemer F, et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022;34(3):396-407.e6. doi:10.1016/j.cmet.2022.02.001

Conze D, Brenner C, Kruger CL. 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. Sci Rep. 2019;9(1):9772. Published 2019 Jul 5. doi:10.1038/s41598-019-46120-z

Conze DB, Crespo-Barreto J, Kruger CL. Safety assessment of nicotinamide riboside, a form of vitamin B3. Hum Exp Toxicol. 2016;35(11):1149-1160. doi:10.1177/0960327115626254

Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. doi:10.1016/j.celrep.2019.07.043

Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Published 2018 Mar 29. doi:10.1038/s41467-018-03421-7

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. Epub 2012 Jul 27. PMID: 22848760; PMCID: PMC3407129.

Nkrumah-Elie Y, Erickson A, Idoine R, et al. Nicotinamide Riboside Supports Brain Health: Assessing the Evidence. Curr Dev Nutr. 2022;6(Suppl 1):798. Published 2022 Jun 14. doi:10.1093/cdn/nzac064.017

Remie CME, Roumans KHM, Moonen MPB, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Am J Clin Nutr. 2020;112(2):413-426. doi:10.1093/ajcn/nqaa072