Nicotinamide riboside clinical trials
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Nicotinamide Riboside Clinical Trials: Safety and Tolerability
Multiple clinical trials have shown that nicotinamide riboside (NR) supplementation is generally safe and well-tolerated in humans, even at high doses. Studies in healthy overweight adults, obese men, and individuals with Parkinson’s disease have reported no serious adverse events or significant differences in mild adverse events between NR and placebo groups, even at doses up to 3000 mg per day for several weeks to months Dollerup2018Conze2019Berven2023+1 MORE. These findings support the development of a tolerable upper intake limit for NR based on human data .
Nicotinamide Riboside and NAD+ Metabolism
NR supplementation consistently increases NAD+ levels in blood and tissues. Clinical trials in healthy middle-aged and older adults, overweight individuals, and people with Parkinson’s disease have demonstrated significant, dose-dependent increases in NAD+ and related metabolites, with some studies reporting up to a 5-fold increase in blood NAD+ Martens2018Conze2019Berven2023+1 MORE. However, there is a lack of standardization in how NAD+ changes are measured and reported, making direct comparisons between studies challenging .
Effects on Metabolic Health and Insulin Sensitivity
Despite promising results in animal studies, NR supplementation in obese, insulin-resistant men did not improve insulin sensitivity, glucose metabolism, or body composition over 12 weeks . Similarly, in overweight adults, NR did not negatively affect cholesterol or 1-carbon metabolism, and no significant changes in body composition were observed . These results suggest that while NR is safe and increases NAD+ levels, its effects on metabolic health in humans may be limited or require further investigation in different populations Dollerup2018Conze2019.
Inflammation and Immune Markers
Preliminary evidence from clinical trials indicates that NR may reduce certain markers of inflammation, particularly in populations with higher baseline inflammation or compromised NAD+ status, such as older adults or those with chronic diseases. Some studies reported significant reductions in circulating and gene expression levels of inflammatory markers like IL-6, IL-18, IFNB, and CXCL10, though effects on other markers such as TNF-α were inconsistent Kwon2022Brakedal2022. More research is needed to clarify which inflammatory pathways are most affected by NR and how these effects vary by dose and participant characteristics .
NR in Neurodegenerative and Chronic Disease: Parkinson’s Disease, Glaucoma, NAFLD, and PAD
Clinical trials are exploring NR’s potential as a neuroprotective therapy. In Parkinson’s disease, NR supplementation was well-tolerated, increased cerebral NAD+ levels, altered brain metabolism, and was associated with mild clinical improvement and reduced inflammatory cytokines Brakedal2022Berven2023. A large, ongoing trial is investigating whether NR can slow optic nerve degeneration in glaucoma patients, with primary outcomes focused on retinal nerve fiber layer thinning .
In non-alcoholic fatty liver disease (NAFLD), a combination of NR and pterostilbene (NRPT) was safe and led to significant reductions in liver enzymes (ALT, GGT) and toxic lipid ceramide 14:0, suggesting a potential benefit in lowering hepatic inflammation, though no significant change in liver fat was observed .
For peripheral artery disease (PAD), NR supplementation for six months improved walking distance compared to placebo, with no added benefit from combining NR with resveratrol. These results suggest NR may help improve physical function in PAD, but larger trials are needed to confirm these findings .
Personalization and Future Directions
Current clinical trials have not yet established how individual factors such as age, gender, BMI, or health status influence response to NR supplementation. There is a need for standardized outcome measures and analyses to enable personalized dosing and to identify responders and non-responders . Future studies should focus on these aspects to maximize the clinical benefits of NR.
Conclusion
Nicotinamide riboside supplementation is safe, well-tolerated, and reliably increases NAD+ levels in humans. While its effects on metabolic health are limited in some populations, NR shows promise in reducing certain inflammatory markers and may have therapeutic potential in neurodegenerative diseases, NAFLD, and PAD. More research is needed to clarify its clinical benefits, optimal dosing, and the populations most likely to benefit.
Sources and full results
Most relevant research papers on this topic
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects.
Nicotinamide riboside supplementation (2000 mg/d) appears safe but does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men.
Assessment of Clinical Research Outcomes for Personalizing Nicotinamide Riboside Dosing
Personalizing nicotinamide riboside dosing is crucial for effective supplementation, as current clinical trials lack standardization and individual response data.
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