Nicotinamide mononucleotide (NMN) is a molecule that has attracted attention for its potential role in improving metabolic functions and slowing aging processes. A landmark study published in Science in 2021 examined the effects of NMN supplementation on muscle insulin sensitivity in pre-diabetic postmenopausal women who are overweight or obese.
Background
In animal models, particularly in rodents, obesity and aging have been shown to disrupt nicotinamide adenine dinucleotide (NAD⁺) biosynthesis, contributing to metabolic dysfunctions such as insulin resistance. NAD⁺ is a crucial cofactor in numerous cellular processes, including energy production and DNA repair. NMN acts as a precursor of NAD⁺ and has been identified as a limiting factor in NAD⁺ biosynthesis in mammals. Studies in mice have shown that NMN supplementation increases NAD⁺ levels and induces metabolic improvements, such as improved glucose tolerance and insulin sensitivity.
Purpose of the Study
The primary goal of this clinical trial was to evaluate whether NMN supplementation could provide similar metabolic benefits in humans, specifically in postmenopausal women with prediabetes and overweight or obesity. The researchers focused on changes in skeletal muscle insulin sensitivity, insulin signaling and muscle remodeling after NMN supplementation.
Study Design and Methodology
The study was a randomized, placebo-controlled, double-blind trial lasting 10 weeks. Twenty-five postmenopausal women with prediabetes and a body mass index (BMI) ranging from 25.3 to 39.1 kg/m² participated in the study. Participants were randomly assigned to two groups: a group receiving 250 mg NMN daily and a placebo group. Major measurements and procedures included:
- Hyperinsulinemic-euglycemic clamp: This technique was used to measure insulin sensitivity by determining glucose uptake into muscle during controlled insulin infusion.
- Skeletal muscle biopsies: Biopsies were taken both in the basal state and during insulin infusion to evaluate changes in insulin signaling and gene expression.
- Body composition: Measurements were performed using dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) to assess changes in fat and muscle mass.
Results
After ten weeks of NMN supplementation, the following findings were reported:
- Improved insulin sensitivity: The NMN group showed a significant increase in insulin-mediated glucose uptake in skeletal muscle compared to the placebo group. This suggests improved insulin sensitivity.
- Increased insulin signaling: Analysis of muscle biopsies showed that NMN supplementation led to increased phosphorylation of key proteins in insulin signaling, such as AKT and mTOR. These changes indicate an enhanced cellular response to insulin.
- Gene expression and muscle remodeling: An upregulation of genes involved in muscle remodeling was observed, including platelet-derived growth factor receptor β (PDGFRβ). This suggests that NMN may contribute to structural and functional improvements in muscle tissue.
Discussion
This study provides the first evidence that oral NMN supplementation can improve skeletal muscle insulin sensitivity in prediabetic postmenopausal women who are overweight or obese. The findings are consistent with previous animal studies and suggest that NMN may be a potential therapeutic intervention for improving metabolic health in humans.
The mechanism behind these improvements appears to lie in the increased availability of NAD⁺, leading to enhanced insulin signaling and gene expression involved in muscle remodeling. Although the results are promising, the researchers stress that further studies are needed to evaluate the long-term effects and safety of NMN supplementation, as well as the optimal dosage and target group.
Conclusion
The findings of this study suggest that NMN supplementation may be an effective strategy to improve insulin sensitivity and possibly reduce the risk of developing type 2 diabetes in pre-diabetic postmenopausal women who are overweight or obese. These results open the door for further clinical trials on the therapeutic applications of NMN in metabolic disorders.
Future Directions
Given the positive results of this study, there are several directions for future research:
- Long-term studies: It is essential to evaluate the durability of the effects of NMN supplementation over longer periods of time and to identify any long-term side effects.
- Dose-response studies: determining the most effective and safest dosing of NMN is critical to developing guidelines for clinical use.
other populations**: Although this study focused on postmenopausal women with prediabetes and obesity, it is important to investigate whether NMN provides similar benefits in younger adults, men, and individuals without metabolic disorders.
- Combination with lifestyle interventions: Another interesting research question is whether NMN supplementation has a synergistic effect when combined with lifestyle interventions such as diet and exercise.
- Potential side effects and safety profile: Although NMN is generally considered safe, further studies should focus on possible long-term side effects and interactions with other supplements or medications.
Critical Evaluation
Although this study provides important insights into the effects of NMN supplementation in humans, there are some limitations and considerations that should be taken into account:
- Small sample size: The study was conducted with only 25 participants, which limits the generalizability of the results. Larger, multicenter studies are needed to confirm the findings.
- Short study duration: With a duration of only 10 weeks, the study provides no information on the long-term effects of NMN use. It is unclear whether the improvements in insulin sensitivity persist over time.
- No comparison with other interventions: It would have been useful to compare NMN with other known methods for improving insulin sensitivity, such as calorie restriction or exercise.
- Variability in response: Although the average results were positive, there may be individual variability in how well NMN works in different individuals. Factors such as genetic predisposition, diet and physical activity may play a role.
Implications for Health and Future Use.
The results of this study suggest that NMN may be a potential supplement for people with prediabetes and obesity, especially in the context of aging and declining NAD⁺ levels. If future studies confirm these findings, NMN could potentially be applied in the prevention and treatment of metabolic disorders.
Nevertheless, caution is warranted. Because NMN is a relatively new supplement, there are not yet comprehensive data on long-term safety. In addition, it is important to remember that supplements are not a substitute for a healthy lifestyle. Diet, exercise and weight management remain the cornerstones of good metabolic health.
Conclusion
This study provides promising evidence that NMN supplementation can improve skeletal muscle insulin sensitivity in postmenopausal women with prediabetes and obesity. This opens new avenues for research into the role of NMN in combating metabolic disorders and age-related insulin resistance.
Nevertheless, many unanswered questions remain. Future research should focus on the long-term effects, optimal dosages, safety and broader applications of NMN in different populations. Only when these questions are answered can NMN potentially become mainstream in the treatment and prevention of metabolic diseases.
With the growing interest in NAD⁺-enhancing therapies and the promise of NMN as an innovative intervention, this area of research may make an important contribution to the future of health promotion and aging research.
Source: Europe PMC
