What is NR?

Key Takeaways

  • NR is a unique form of vitamin B3 that effectively boosts NAD+ levels in whole blood, brain, and skeletal muscle.
  • NAD+ is essential for energy production, DNA repair, and healthy aging, but naturally declines with age and metabolic stress.
  • NR is found naturally in trace amounts in foods like milk, brewer’s yeast, bananas, and oranges, but is available in much higher doses through supplements.
  • NR is more effective than NAD+ because NAD+ is a large molecule that cannot efficiently enter cells.
  • NR is a superior NAD+ precursor compared to niacin, nicotinamide, and nicotinamide mononucleotide. 
  • Oral NR supplementation is clinically proven to safely increase NAD+ levels, supporting mitochondrial, brain, heart, and muscle health.

What Is Nicotinamide Riboside and Why Is It Important?

Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3, a family that also includes niacin (nicotinic acid) and nicotinamide (niacinamide or NAM). Vitamin B3 is essential for supporting energy metabolism, cellular repair, and overall health.

NR’s vitamin activity, as a precursor to NAD+, was first discovered by Dr. Charles Brenner in 2004. When vitamin B3 is consumed—whether through diet or supplementation—it is converted into NAD+ (nicotinamide adenine dinucleotide), a crucial coenzyme that supports cellular vitality and function. NAD+ plays a central role in energy production, DNA repair, and regulating cellular metabolism.

As a precursor to NAD+, NR is a compound that the body can efficiently convert into NAD+. By acting as a building block, NR helps replenish and maintain NAD+ levels, thereby supporting cellular energy production and repair.

Where Is NR Found Naturally?

Nicotinamide riboside (NR) naturally occurs in trace amounts in foods, such as:

A recent comprehensive analysis identified wild chicory, banana, and orange as having the highest NR content among common foods. Smaller amounts of NR were also detected in capers, cilantro, leeks, spinach, eggplants, avocados, moringa, bell peppers, and tomatoes.

However, the levels found in food are too small to meaningfully impact NAD+ levels. For example, while NR naturally occurs in milk, you’d need to drink around 87 gallons to match the amount in a typical 300 mg supplement. Similarly, you’d have to consume nearly 1,500 twelve-ounce glasses of craft beer to reach the same dose. This is why NR supplements have been developed to provide higher, clinically relevant amounts to support NAD+ production and cellular health.

Is NR Bioavailable, and How Does NR Boost NAD+ Levels?

NR is highly bioavailable, efficiently absorbed through the digestive tract, and transported into cells via specialized nucleoside transporters known as equilibrative nucleoside transporters (ENTs).7 Once inside the cell, NR is converted into NAD+ through a two-step pathway involving the enzyme nicotinamide riboside kinase (NRK). This efficient pathway bypasses enzymes like nicotinamide phosphoribosyltransferase (NAMPT), which tend to decline with age, making NR a particularly effective NAD+ precursor in aging or metabolically stressed cells.

Extensive preclinical and clinical research shows that oral NR supplementation significantly and dose-dependently boosts NAD+ levels and NAD+ flux—the rate at which cells produce and use NAD+. Over 15 human clinical studies have confirmed that NR safely and effectively increases NAD+ levels and/or NAD+ flux in multiple biofluids and tissues, including whole blood, white blood cells, brain, and skeletal muscle, underscoring its strong absorption and bioavailability.

Importantly, NR’s ability to elevate NAD+ levels in white blood cells is particularly meaningful because these cells have a nucleus, like most cells in the body. This makes white blood cells a reliable, noninvasive marker indicating that NR elevates NAD+ inside cells, rather than simply increasing NAD+ levels in the blood plasma outside the cells.

Daily supplementation with NR at 300 mg has been shown to increase blood NAD+ levels by over 50% within two weeks. Higher doses, such as 1,000 mg, can raise NAD+ levels by up to 150%, with these increases maintained over time, demonstrating its dose-dependent effectiveness.

Why Not Just Take NAD+ Directly?

Despite its importance, taking NAD+ as a supplement or intravenously is not effective. One of the main challenges with taking NAD+ directly is its limited stability and bioavailability. NAD+ degrades rapidly when exposed to light, heat, and water, potentially making both oral and intravenous administration difficult., An FDA briefing document concluded that NAD+ is unlikely to remain stable in capsule form under typical storage conditions.

In addition, NAD+ is a large, phosphorylated molecule that cannot pass through cell membranes intact. It must first be broken down into smaller precursor molecules, such as NR, before it can be absorbed and converted into NAD+ inside the cell.

Finally, because a single NAD+ molecule is more than twice the molecular weight of most NAD+ precursors like NR, an equivalent dose of NR contains more than twice as many molecules, making it a potentially more efficient source for boosting NAD+ levels.

Learn more about why direct NAD+ supplementation isn’t effective. 

How Does NR Compare to Other NAD+ Precursors?

Nicotinamide riboside (NR) is one of several NAD+ precursors—including niacin, nicotinamide, and nicotinamide mononucleotide (NMN)—each metabolized differently in the body and characterized by distinct biological effects and safety profiles.

Niacin

Niacin increases NAD+ levels through the Preiss–Handler pathway. However, this pathway is less efficient, requiring multiple enzymatic steps and significant cellular energy. At low doses, niacin commonly causes uncomfortable skin flushing, and at high doses, it can lead to liver toxicity.

Nicotinamide

NAM does not cause flushing, but it inhibits sirtuins—NAD-dependent enzymes essential for mitochondrial function and cellular repair. NAM is converted into NAD+ via the salvage pathway, which depends on the enzyme NAMPT. Unfortunately, NAMPT levels decline with age, making this pathway less reliable over time.

Nicotinamide Mononucleotide (NMN) 

Although NMN is a precursor to NAD+, its phosphate group prevents it from entering cells efficiently. NMN must first be converted into NR before it can cross the cell membrane. Furthermore, as of November 2022, the United States (U.S) Food and Drug Administration (FDA) stated that NMN is excluded from the definition of a dietary supplement, meaning it cannot be legally marketed as one in the U.S.

Why Nicotinamide Riboside Is Superior

NR stands out for its efficiency, cellular accessibility, and favorable safety profile:

  • Efficient NAD+ Synthesis: NR enters cells directly and is converted into NAD+ through a streamlined, two-step pathway involving the NRK enzyme, which is widely expressed across tissues. This bypasses the NAMPT-dependent salvage pathway required for NAM.
  • No Flushing, Even at High Doses: Unlike niacin, NR does not cause flushing. Clinical studies have shown that NR is well-tolerated even at doses up to 3,000 mg per day, with no flushing reported.
  • Supports Sirtuin Activity: NR does not inhibit sirtuins like NAM. In fact, research suggests NR may enhance sirtuin activity.

A Closer Look at the Science 

Preclinical studies continue to reveal that NR and NAM are not interchangeable. NR supplementation has been uniquely associated with improved skeletal muscle function, protection against heart failure, and expansion of hematopoietic stem cells—effects not seen with NAM. Moreover, in models of metabolic stress and viral infection (e.g., SARS-CoV-2, Zika), cells have been shown to selectively use NR to restore NAD+ levels. In mice lacking the ability to metabolize NR, susceptibility to disease increased, and NAM was unable to compensate.

While further research is needed to fully understand the unique properties of NR compared to other precursors, these findings suggest that under conditions of metabolic stress, cells specifically require and seek out NR to maintain adequate NAD+ levels.

Benefits of Nicotinamide Riboside Supplementation

Nicotinamide riboside (NR) supplementation has emerged as a promising NAD+ precursor with a growing body of research supporting its impact on a variety of health areas. By raising NAD+ levels across, NR may help address some of the key drivers of aging and support whole-body vitality.

  • NAD+ Boosting: Multiple human studies have shown that oral NR supplementation can increase NAD+ levels in whole blood, blood plasma, white blood cells, skeletal muscle, and the brain.13,15,16,27,29
  • Supports Healthy Aging: As we age, NAD+ levels naturally decline in tissues such as the brain, skin, and muscles.46–48 This decline contributes to oxidative stress, impaired DNA repair, and mitochondrial dysfunction—all of which accelerate cellular aging. By restoring NAD+ levels, NR supports mitochondrial health, cellular energy, and cellular repair.9,16,17 It can help address biological root causes of aging, making it a proactive strategy for healthy aging and longevity.
  • Increases Cellular Energy and Supports Repair: NAD+ is essential for energy production (in the form of ATP) and for activating repair enzymes like PARPs and sirtuins. These enzymes play a vital role in DNA maintenance, stress responses, and metabolic regulation. Without adequate NAD+, cells are less equipped to generate energy or repair daily damage. Supplementing with NR replenishes NAD+ stores, helping increase energy metabolism and support the body’s repair systems.9,16,22
  • Supports Brain Health: The brain is a high-energy organ that depends on efficient mitochondrial function and steady NAD+ levels to maintain brain function. With age, NAD+ levels in the brain decline. With aging, cerebral NAD+ declines, potentially impacting neurological function. Research shows NR can increase NAD+ levels in the brain,22,27 helping support a healthy brain.
  • Supports Muscle Health: Skeletal muscles require NAD+ and healthy mitochondria to generate the energy needed for movement and strength. NR has been shown to increase mitochondrial biogenesis in muscle cells,23 supporting muscle energy metabolism and overall muscle health.
  • Supports Heart Health: The heart is one of the most metabolically active organs in the body. It requires constant ATP production, driven in part by NAD+. NR supplementation has been linked to reductions in systolic blood pressure and arterial stiffness13—two key indicators of cardiovascular health. By supporting mitochondrial function in cardiac tissue, NR may help support long-term heart health and resilience.

While the current evidence is promising, continued research is needed to fully understand the long-term effects of NR supplementation in diverse human populations. Nonetheless, these findings highlight NR’s potential as a tool for enhancing cellular health and supporting healthy aging from the inside out.

Is Nicotinamide Riboside Safe?

NR is widely regarded as safe and well-tolerated in humans.9 Across published clinical studies, no adverse effects have been directly attributed to NR supplementation, even at high doses.

NR has been extensively evaluated for both safety and efficacy at doses ranging from 100 mg to 3,000 mg per day in humans.16,24 These studies consistently demonstrate that NR is well-tolerated and produces a reliable, dose-dependent increase in NAD+ levels without clinically significant side effects.

To date, there are currently no known interactions or contraindications associated with NR supplementation. Its safety and efficacy continue to be validated in ongoing human trials.

Conclusion

NR is a scientifically validated NAD+ precursor that safely and effectively supports cellular energy, repair, and healthy aging. Its unique metabolic pathway and safety profile make it a promising tool for combating age-related NAD+ decline.

Unlike NAD+ itself, which is large and poorly absorbed, NR offers a bioavailable and efficient path to restoring NAD+ levels—especially under metabolic stress or during aging, when NAD+ naturally declines. While the Recommended Dietary Allowance (RDA) for vitamin B3 prevents deficiency, emerging science suggests that higher levels—particularly in the form of NR—may help maintain optimal cellular function and delay the onset of age-related physiological decline.

With more than 35 clinical studies already published and many more underway, the science supporting NR continues to grow.

To stay informed, explore registered ongoing and completed clinical trials on NR and browse published studies for the latest findings.

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