Nutrition Notes

Nicotinamide Riboside to Support Healthy Aging and Cellular Health

Nicotinamide riboside (NR) is a building block for a critical molecule for cellular health. Nicotinamide adenine dinucleotide (NAD+) is essential for more than 500 biochemical reactions in the human body. Deficiencies in NAD+ have been linked to age-related illnesses.  

Supplementation with NR has been shown to support NAD+ status, healthy aging, mitochondrial health, and healthy sirtuin function. Sirtuins are chemicals associated with antioxidative status and the support of health during the aging process.  

A double-blind, placebo-controlled clinical trial investigated the efficacy of supplementation with NR and pterostilbene (a sirtuin activator found in blueberries) on hospitalized individuals with acute kidney injury. The treatment group (n = 5) consisted of twice-daily titrated doses of NR/pterostilbene: 250/50 mg, 500/100 mg, 750/150 mg, and 1,000/200 mg. NAD+ levels increased by 37% after 2 days. Sirtuin 1 (Sirt1) activation was proposed as a main mechanism of action. 

NR may also help support cardiovascular and respiratory health during the aging process. NR has been shown to promote healthy respiratory function, help reduce mitochondrial reactive oxygen species production, and reduce interleukin (IL)-1β levels in peripheral blood mononuclear cells. NR has also been shown to influence IL-6 levels; upregulated IL-6 levels are associated with chronic heart failure (HF) and acute myocardial infarction. 

A clinical trial exploring the efficacy of NR supplementation involved 19 patients with stage D HF and a mean left ventricular ejection fraction of 20% and 19 healthy individuals. In 5 hospitalized patients, doses of NR escalated from 250 mg twice daily to 1,000 mg twice daily starting on day 3. The study lasted from 5 to 9 days. Study results indicated that supplementation with NR helped support decreased levels in IL-6 and IL-1β and helped support mitochondrial respiration in the hospitalized patients with HF. Because of a short study duration and small sample size, more research is necessary before conclusions can be made.  

NR may also support cellular respiration and mitochondrial function. A 4-week animal study assessed the efficacy of NR supplementation on Sco2 kiko mice. Sco2 is a protein essential for the functioning of cytochrome C oxidase, an enzyme involved in the mitochondrial respiratory chain. The administration of NR resulted in increases in NAD+ and the activation of Sirt1. The transcription of genes related to oxidative phosphorylation were increased along with increases in mitochondrial respiratory chain activity and oxidative metabolism. Motor deficits were also shown to improve. 

NR is believed to have higher neuronal bioavailability due to gene expression in the NR kinase pathway. NR kinase 2 has been shown to be induced after axonal injury in sensory neurons. An animal study administered NR to murine populations after noise exposure. After acoustic trauma, NR was shown to help prevent decreases in cochlear NAD+ levels in a Sirt3-dependent manner

Decreases in the activity of Sirt1 and Sirt2 have been linked to diabetic peripheral neuropathy. In a murine study, NR administration was reported to help protect against sensory and motor neuropathy in prediabetic mice. 

Although more research is needed before clinical conclusions can be made, NR may support healthy aging and cellular health. It may also support mitochondrial function and a healthy response to inflammation.  

By Colleen Ambrose, ND, MAT