Science Update

Recent Phase 1 Trial Explores Role of NR to Support Neuronal Health During Aging

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder associated with brain changes, deficits in motor function, nonmotor symptoms, and cognitive decline. Age, family history, and environmental factors are major risk factors for PD. Inflammation, mitochondrial dysfunction, and oxidative damage have been linked to PD. In recent research, the molecule nicotinamide adenine dinucleotide (NAD+) has been shown to exhibit potential neuroprotective effects and support healthy aging.  

NAD+ is found in every living cell and plays a role in more than 500 reactions in the body, including gene expression, stress response, and DNA repair. Deficiencies of NAD+ have been linked to certain age-related diseases. Nicotinamide riboside (NR) is a variation of vitamin B3 (niacin) that functions as a building block for NAD+. 

A recently published double-blind phase 1 clinical trial by Brakedal and colleagues explored the efficacy of supplementation with NR on parameters related to PD. The study involved 30 participants who were recently diagnosed with PD and were treatment-naive. Participants received either 1,000 mg of NR daily or a placebo for 30 days. NR was shown to increase levels of cerebral NAD+ through phosphorus magnetic resonance spectroscopy measurements and biomarkers from cerebrospinal fluid. Cerebral metabolism was also shown to be influenced by NR and was reported to be related to increases in brain NAD+ levels.  

In the central nervous system, decreased levels of certain pro-inflammatory cytokines, including interleukin (IL)-1β and IL-12 were observed in the NR group. NR was also reported to help support biochemical processes relating to the function of mitochondria, lysosomes, and proteasomes. The authors report that NR may also attenuate epigenomic dysregulation associated with PD through the regulation of histone acetylation.  

In the study by Brakedal and colleagues, NR was also shown to significantly influence the expression of over 50 genes, including KLF2 in muscle tissue. KLF2 is linked to the induction of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is associated with supporting antioxidative status. NR was also associated with the upregulation of genes associated with a cellular response to oxidative stress, mitochondrial respiration, and protein degradation. 

Study strengths include patient retention, treatment adherence, and all adverse events, which were reported to be unrelated to NR. Study limitations include a relatively small sample size and short time of observation. Further studies need to be conducted before clinical conclusions can be determined.  

NR has been shown to support healthy NAD+ levels, mitochondrial function, and healthy aging. It may also support a healthy response to neuroinflammation and neuronal DNA damage and may help support healthy aging. 

By Colleen Ambrose, ND, MAT