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Nicotinamide Riboside

  • Vitamins & Supplements
  • Updated June 7, 2023

Nicotinamide riboside is a form of vitamin B3 that can be converted to nicotinamide adenine dinucleotide (NAD+), an essential compound involved in energy production and other important cellular functions. Research suggests that as we age, the levels of NAD+ in our brains decrease. In initial studies, nicotinamide riboside treatment increased levels of NAD+ in the blood. However, no studies have tested whether nicotinamide riboside can improve cognitive function or prevent age-related cognitive decline. Nicotinamide riboside supplements are generally recognized as safe.

Evidence

No clinical trials have tested whether nicotinamide riboside can improve cognitive function or prevent age-related cognitive decline. Our search identified:

  • 1 observational study on NAD+ levels in the brain
  • Numerous laboratory studies

Potential Benefit

There have not been any clinical trials that have probed whether nicotinamide riboside improves cognitive function or prevents age-related cognitive decline. In a small clinical study of healthy older adults, nicotinamide riboside treatment did not alter biological markers of Alzheimer’s disease or metabolic function [1]. An observational study found that older adults have lower levels of an essential compound, NAD+, in the brain than younger adults [2; 3]. NAD+ plays an important role in cellular metabolism and DNA repair. Nicotinamide riboside treatment can increase levels of NAD+ in the blood [4], but whether it also increases brain levels of NAD+ or exerts benefits on cognition remains to be confirmed. 

In laboratory models of Alzheimer’s disease, nicotinamide riboside treatment prevented cognitive deficits, reduced production of pathological proteins, and prevented brain cell death [5; 6]. In older mammals, nicotinamide riboside may also contribute to the growth and development of neural tissue and neural stem cells [7]. Laboratory studies have shown that boosting NAD+ levels using nicotinamide riboside or other methods [6; 8; 9; 10] may protect the brain and improve age-related disorders such as metabolic disease and diabetes, both of which are risk factors for neurological diseases [11; 12; 13]. 

For Dementia Patients

In a clinical trial of Alzheimer’s disease patients, a combination treatment that included nicotinamide riboside along with other compounds improved cognitive function compared to before the treatment, though patients receiving placebo also showed improvement [14]. Because the intervention included multiple compounds, it is not possible to pinpoint the specific contribution of nicotinamide riboside. Clinical trials testing the effects of nicotinamide riboside in Alzheimer’s patients are currently ongoing.

Safety

Nicotinamide riboside is generally recognized as safe in the US and may be added to vitamin waters, protein shakes, nutrition bars, and other products [15]. The European Food Safety Authority Panel on Nutrition, Novel Foods and Allergens reported that nicotinamide riboside is safe up to 300 mg daily for healthy adults, and up to 230 mg daily for pregnant and lactating women [16]. In the largest randomized controlled trial to date including 140 healthy overweight adults, nicotinamide treatment (100, 300, or 1,000 mg daily) for 8 weeks did not lead to significant differences in side effects when compared to placebo [4]. Side effects included nausea, muscle pain, and sore back.

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 [17]. 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 [18; 19; 20]. 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 supplements are available in capsule form. These products often contain 250-300 mg of nicotinamide riboside per serving. Nicotinamide riboside is also naturally found in some foods (e.g., milk) but in very low quantities.

Learn More

Full scientific report (PDF) on Cognitive Vitality Reports

References

  1. Vreones M, Mustapic M, Moaddel R et al. (2023) Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging cell 22, e13754.
  2. 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.
  3. Ali YO, Li-Kroeger D, Bellen HJ et al. (2013) NMNATs, evolutionarily conserved neuronal maintenance factors. Trends in neurosciences 36, 632-640.
  4. Conze D, Brenner C, Kruger CL (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 9, 9772.
  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. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. Yulug B, Altay O, Li X et al. (2023) Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial. Translational neurodegeneration 12, 4.
  15. Keefe DM (2016) Agency Response Letter GRAS Notice No. GRN 000635.
  16. Efsa Panel on Nutrition Nf, Food a, Turck D et al. (2019) Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. EFSA journal European Food Safety Authority 17, e05775.
  17. Peek CB, Affinati AH, Ramsey KM et al. (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
  18. 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.
  19. Sauve AA (2008) NAD+ and vitamin B3: from metabolism to therapies. The Journal of pharmacology and experimental therapeutics 324, 883-893.
  20. Iqbal J, Zaidi M (2006) Extracellular NAD+ metabolism modulates osteoclastogenesis. Biochemical and biophysical research communications 349, 533-539.