Nicotinamide riboside (NR) is a promising dietary supplement that may have beneficial effects on human health by increasing nicotinamide adenine dinucleotide (NAD+) levels. However, despite promising results from preclinical studies, human clinical trials have yielded mixed results. In this article, we will review the clinical trials of NR supplementation to date and discuss both the benefits and limitations of its use.
Overview of Clinical Studies on NR
Over the past several years, a number of clinical trials have been conducted to evaluate the efficacy and safety of nicotinamide riboside (NR) supplementation in humans. These studies included a variety of populations, including healthy, obese, elderly, and those with various medical conditions, such as metabolic diseases, heart failure and neurodegenerative diseases.
Most clinical studies have focused on assessing whether NR supplementation increases NAD+ levels in the body, and its metabolic and health effects. For example, studies in healthy volunteers have shown that NR supplementation increases blood levels of NAD+ and related metabolites, suggesting that NR is efficiently converted and absorbed by the body.
Results and Benefits of NR Supplementation
Increased levels of NAD+ and its metabolites
In most clinical studies, NR supplementation has been shown to lead to increased levels of NAD+ and its metabolites, such as nicotinamide adenine dinucleotide (NAAD) and methylnicotinamide (MeNAM), in the peripheral blood. This is important because NAD+ plays a key role in energy metabolism and can support mitochondrial function and DNA repair processes, which is particularly important in the context of aging and age-related diseases.
Reducing inflammation
Several studies indicate that NR can reduce inflammation in the body. For example, studies on people with heart failure showed that NR supplementation reduced levels of certain inflammatory markers, such as interleukin-6 (IL-6) and IL-18, in the peripheral blood. Reducing inflammation may help improve overall health and reduce the risk of chronic diseases such as cardiovascular disease and diabetes.
Potential benefits in neurodegenerative and metabolic diseases
Studies suggest that NR may have beneficial effects on neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis (ALS). In clinical trials in Parkinson's patients, NR supplementation has been shown to increase NAD+ levels in the brain and improve some cognitive functions. Also in ALS, improvements in motor function were observed after NR supplementation, suggesting that NR may have potential therapeutic applications in neurodegenerative diseases.
Clinical Trial Limitations and Challenges
Small sample size and population heterogeneity
Most clinical studies of NR have had relatively small sample sizes, which may affect their reliability and the generalizability of the results. In addition, the diversity of the population (including age, gender, health status and lifestyle) may lead to different responses to supplementation, making it difficult to clearly determine the benefits and risks of NR.
Lack of standardized research protocols
There is a great deal of variability in the doses of NR used, the duration of supplementation and methods of evaluating effects, making it difficult to compare the results of different studies. Different research protocols and lack of standardization can lead to discrepancies in results, which in turn require more rigorous studies in the future.
Limited long-term safety data
Although clinical studies show that NR is generally safe and well tolerated by the body, there are few data on the long-term safety of NR supplementation. More research is needed to understand the long-term effects of NR use, particularly in terms of its effects on metabolism, mitochondrial health and aging.
The results of some studies are contradictory
While some studies show health benefits of NR, others show minimal or no clinical effects. For example, studies on NR's effects on insulin sensitivity and blood glucose levels have been inconclusive, suggesting that NR's effects may depend on the clinical context and specific study conditions.
Future Prospects and Research Needs
Increase sample size and standardize protocols
To obtain more reliable and consistent results, future studies should include larger groups of participants and use standardized research protocols that will allow better comparison of results and more conclusive conclusions.
Research on long-term safety
More research is needed on the long-term safety of NR supplementation to understand its potential side effects and risks associated with long-term use. It is particularly important to focus on populations with various medical conditions and the elderly, in whom NR supplementation may have the greatest benefit.
Research into NR's mechanisms of action
Further research should focus on better understanding the mechanisms through which NR affects health, including its effects on energy metabolism, mitochondrial function and DNA repair processes. A better understanding of these mechanisms may help optimize the use of NR in various clinical contexts.
Summary
Nicotinamide riboside (NR) is a dietary supplement with promising health properties that may raise NAD+ levels and promote metabolic health. Although results from human clinical trials are mixed, there is evidence that NR can reduce inflammation and support mitochondrial health. However, further, more rigorous clinical trials with larger participant groups, standardized protocols and longer follow-up periods are needed to fully assess its benefits and limitations.
Sources:
- What is really known about the effects of nicotinamide riboside supplementation in humans
- Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy
- Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy: Opportunities and Prospects
- Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
- Emerging Role of Nicotinamide Riboside in Health and Diseases
- Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives