supplements

Nicotinamide Riboside

  • Vitamins & Supplements
  • Updated February 13, 2018

Nicotinamide riboside is a form of vitamin B3 that can be converted to the essential coenzyme NAD+. Research suggests that as we age, the levels of this coenzyme in our brains decrease, potentially leading to age-related diseases [1]. In initial studies, nicotinamide riboside treatment appears to increase levels of the coenzyme, extend lifespan, and reduce cognitive deficits [2]. While it holds promise, there are gaps in the existing evidence and the safety and potential benefit in humans is unknown.

Evidence

Very few studies of nicotinamide riboside use in humans have been published. Our search identified:

• 0 meta-analyses or systematic reviews
• 3 clinical trials for safety
• 1 observational study on NAD+ levels in the brain
• Several preclinical studies

Potential Benefit

Since age is the greatest risk factor for Alzheimer's disease and dementia, supplements that slow aging-related processes may also slow progression of these diseases. An observational study found that older adults have lower levels of the coenzyme NAD+ in their brains than younger adults [3][4]. This coenzyme is involved in cellular metabolism and DNA repair. Nicotinamide riboside can be converted to NAD+ in our bodies and may boost its levels.

Some preclinical studies have suggested that nicotinamide riboside may protect our neurons. Nicotinamide riboside use was associated with fewer cognitive deficits, reduced production of beta-amyloid plaques, reduced levels of tau tangles, and fewer cell deaths [5][6]. In older mammals, it may also contribute to the growth and development of neural tissue and neural stem cells [2]. Boosting NAD+ levels using nicotinamide riboside or other methods [6-9] also appears to protect the brain and improve aging-related disorders such as metabolic disease and diabetes, both of which are risk factors for cognitive diseases [10][11][12]. No studies have confirmed the benefits of nicotinamide riboside in humans, though ten clinical trials are now in progress.

For Dementia Patients

There are no published studies on the effect of nicotinamide riboside in dementia patients and no evidence that people with Alzheimer's disease also have reduced levels of NAD+. Some preclinical studies suggest that nicotinamide riboside can improve cognitive function and reduce production of beta-amyloid plaques [5] but the scientific rationale is stronger for prevention than treatment of dementia.

Safety

No serious side effects or safety concerns have been identified for nicotinamide riboside. A toxicology report from a supplement manufacturer states that no adverse effects were observed for doses up to 1000 mg/kg in rodents, which is higher than the standard supplement dose [13]. One eight-week study in elderly people reported no serious adverse effects using a combination of nicotinamide riboside and pterostilbene, although it did increase LDL cholesterol levels in overweight individuals [14]. However, safety has not yet been confirmed in humans, particularly for long-term use.

There are a few theoretical concerns with artificially raising NAD+ levels. Normal NAD+ levels appear to fluctuate naturally throughout the day, so artificially increasing them may disrupt healthy circadian signaling [15]. Additionally, depleting NAD+ levels has been proposed as a treatment for cancer, inflammation, and cardiovascular disease, and one study suggests that NAD+ may accelerate the breakdown of bones [16][17][18]. But there is currently no evidence to substantiate these risks with nicotinamide riboside supplementation.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Nicotinamide riboside is available as an over-the-counter dietary supplement (e.g., Niagen®). A supplement manufacturer recommends a dose of 100–250 mg taken before the first meal of the day.

Nicotinamide riboside is also available in combination with pterostilbene, an antioxidant that is closely related to resveratrol (e.g., Basis from Elysium Health), at a dose of 250 mg of nicotinamide riboside and 50 mg of pterostilbene per day. Although there is a theoretical rationale for combining the two supplements, no scientific studies have directly tested whether the combination is more effective than nicotinamide riboside alone.

Learn More

Scientific American examines the growing use of a nicotinamide riboside supplement in "Beyond Resveratrol: The Anti-Aging NAD Fad."

Media release for a clinical trial planned to assess nicotinamide riboside in college football players: "Thorne Research Announces Clinical Study to Assess Nicotinamide Riboside on Brain NAD+ in College Football Players"

References

  1. Imai SI, Guarente L (2014) NAD and sirtuins in aging and disease. Trends in cell biology.
  2. Zhang H, Ryu D, Wu Y et al. (2016) NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352, 1436-1443.
  3. Zhu XH, Lu M, Lee BY et al. (2015) In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences of the United States of America 112, 2876-2881.
  4. Ali YO, Li-Kroeger D, Bellen HJ et al. (2013) NMNATs, evolutionarily conserved neuronal maintenance factors. Trends in neurosciences 36, 632-640.
  5. Gong B, Pan Y, Vempati P et al. (2013) Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-gamma coactivator 1alpha regulated beta-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Neurobiology of aging 34, 1581-1588.
  6. Wang X, Hu X, Yang Y et al. (2016) Nicotinamide mononucleotide protects against beta-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res 1643, 1-9.
  7. Turunc Bayrakdar E, Uyanikgil Y, Kanit L et al. (2014) Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Abeta(1-42)-induced rat model of Alzheimer's disease. Free Radic Res 48, 146-158.
  8. Long AN, Owens K, Schlappal AE et al. (2015) Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC neurology 15, 19.
  9. Wu MF, Yin JH, Hwang CS et al. (2014) NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary rat cortical neurons. Free Radic Res 48, 794-805.
  10. Canto C, Houtkooper RH, Pirinen E et al. (2012) The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism 15, 838-847.
  11. Lee HJ, Hong YS, Jun W et al. (2015) Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes. J Med Food 18, 1207-1213.
  12. Yoshino J, Mills KF, Yoon MJ et al. (2011) Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell metabolism 14, 528-536.
  13. Conze DB, Crespo-Barreto J, Kruger CL (2016) Safety assessment of nicotinamide riboside, a form of vitamin B3. Hum Exp Toxicol.
  14. Dellinger RW, Santos SR, Morris M et al. (2017) Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD(+) levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis 3, 17.
  15. Peek CB, Affinati AH, Ramsey KM et al. (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
  16. Montecucco F, Cea M, Bauer I et al. (2013) Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: rationales, controversies, clinical experience. Current drug targets 14, 637-643.
  17. Sauve AA (2008) NAD+ and vitamin B3: from metabolism to therapies. The Journal of pharmacology and experimental therapeutics 324, 883-893.
  18. Iqbal J, Zaidi M (2006) Extracellular NAD+ metabolism modulates osteoclastogenesis. Biochemical and biophysical research communications 349, 533-539.