PMID 36482258 The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial Dose-response RCT · GeroScience, 2023 80 people, 60 days - NMN 300, 600, and 900 mg all raised blood NAD+ significantly (highest at 600–900 mg); 6-minute walk distance also rose. Manufacturer-funded (Abinopharm).
Key summary
A 60-day dose-response RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. of 80 healthy middle-aged adults split into placeboAn inert dummy treatment used as the comparison baseline., 300, 600, and 900 mg arms. The primary endpoint, blood NAD+, rose significantly above placebo and baseline in all NMN groups at days 30 and 60 (highest at 600–900 mg), and 6-minute walk distance increased more than placebo at all three doses. HOMA-IR did not differ from placebo. Safety and tolerability were good up to 900 mg. Read with the caveat that some authors are affiliated with NMN manufacturers.
Show original abstract
In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 36740954 Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study RCT · J Clin Endocrinol Metab, 2023 30 people, 28 days - MIB-626 (NMN) improved NAD+, cholesterol, weight, and diastolic BP, but muscle strength, aerobic capacity, muscle fatigability, and insulin sensitivity did not differ from placeboAn inert dummy treatment used as the comparison baseline..
Key summary
A physiologic RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. giving 30 overweight or obese middle-aged and older adults (2:1 allocation) microcrystalline NMN (MIB-626) 1000 mg twice daily for 28 days. NAD+ and its metabolites rose substantially, and total and LDLLow-density lipoprotein cholesterol - the so-called "bad" cholesterol. cholesterol, body weight, and diastolic blood pressure fell significantly versus placeboAn inert dummy treatment used as the comparison baseline.. However, muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ from placebo, and insulin sensitivity, hepatic fat, and intra-abdominal fat did not change. The authors concluded larger trials are needed to test cardiometabolic outcomes - the muscle-function and insulin-sensitivity gains hoped for in anti-aging were not seen here.
Show original abstract
CONTEXT: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. OBJECTIVE: We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions. METHODS: Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. RESULTS: Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference -1.9 [-3.3, -0.5] kg, P = .008); diastolic blood pressure (difference -7.01 [-13.44, -0.59] mmHg, P = .034); total cholesterol (difference -26.89 [-44.34, -9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (-18.73 [-31.85, -5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group. CONCLUSIONS: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 36797393 Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial RCT · Sci Rep, 2023 36 people, 12 weeks - NMN 250 mg/day raised NAD+ metabolism (serum nicotinamide). Arterial stiffness trended down but did not differ significantly from placeboAn inert dummy treatment used as the comparison baseline.. Safe.
Key summary
An RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in which 36 healthy middle-aged adults took 125 mg NMN twice a day (250 mg/day total) for 12 weeks. NAD+ metabolites such as serum nicotinamide rose significantly above placeboAn inert dummy treatment used as the comparison baseline., supporting that NMN raises NAD+ metabolism. Arterial stiffness (pulse wave velocity) trended down in the NMN group but did not differ significantly between groups. Long-term 250 mg/day was well tolerated with no adverse events. The authors went only as far as noting a potential for easing arterial stiffness.
Show original abstract
Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 38789831 Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study RCT · GeroScience, 2024 60 people, 12 weeks - NMN 250 mg/day raised blood NAD+. The primary endpoint (stepping test) did not differ, but secondary 4-m walking time and sleep quality improved vs placeboAn inert dummy treatment used as the comparison baseline.. Manufacturer-funded (Meiji).
Key summary
An RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in which 60 older adults took NMN 250 mg/day for 12 weeks. The primary endpoint, a stepping test, did not differ from placeboAn inert dummy treatment used as the comparison baseline. at 4 or 12 weeks. Among secondary endpoints, at 12 weeks the NMN group had a shorter 4-m walking time than placebo, significantly higher blood NAD+ and metabolites, and better sleep quality (daytime dysfunction and global PSQI). So the headline motor-function measure was unchanged and only some secondary measures improved - a mixed result. Some authors are affiliated with Meiji.
Show original abstract
The study evaluated how ingestion of nicotinamide mononucleotide (NMN) for 12 weeks by older adults affected blood nicotinamide adenine dinucleotide (NAD +) levels and physical function, particularly walking function. Information concerning sleep, and stress was also collected as secondary endpoints. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 60 participants were randomly allocated into a placebo group or NMN group. Members of the NMN group consumed 250 mg/day NMN for 12 weeks. Motor function tests, blood NAD metabolite analysis, and questionnaires were conducted at the start of the study and 4 and 12 weeks after intake. This trial was registered at umin.ac.jp/ctr as UMIN000047871 on June 22nd, 2022.At primary outcome, at both 4 weeks and 12 weeks, the NMN and placebo groups had no significant differences in a stepping test. At secondary outcomes, after 12 weeks of NMN intake, the NMN group had a significantly shorter 4-m walking time than the placebo group as well as significantly higher blood levels of NAD + and its metabolites. A significant negative correlation was observed between the change in the 4-m walking time and the change in blood NAD + , N1-methyl-2-pridone-5-carboxamide (2-PY), and N1-methyl-4-pridone-3-carboxamide (4-PY) at 12 weeks. The NMN group had improved sleep quality at 12 weeks relative to the placebo group as evidenced by lower scores for "Daytime dysfunction" and "Global PSQI" on the Pittsburgh Sleep Questionnaire. No adverse effects related to test substance consumption were observed. Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 34238308 Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study RCT · J Int Soc Sports Nutr, 2021 48 people, 6 weeks - with training, medium (600) and high (1200 mg) NMN raised oxygen uptake and ventilatory-threshold power vs control. But absolute VO2max and peak power did not change in any group.
Key summary
An RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. of 48 amateur runners in Guangzhou split into placeboAn inert dummy treatment used as the comparison baseline., 300, 600, and 1200 mg arms, combined with 6 weeks of training. The medium and high dose groups improved oxygen uptake, percentage of VO2max, and power at the first and second ventilatory thresholds more than controls. However, the authors noted that absolute VO2max, O2-pulse, VO2 relative to work rate, and peak power did not change from baseline in any group after 6 weeks. They concluded the improvement may reflect better oxygen utilization by skeletal muscle - with the caveat that the headline VO2max showed no clear benefit.
Show original abstract
BACKGROUND: Recent studies in rodents indicate that a combination of exercise training and supplementation with nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials analyzing this. OBJECTIVE: This study investigates the effects of a combination of exercise training and supplementation with nicotinamide mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness in healthy amateur runners. METHODS: A six-week randomized, double-blind, placebo-controlled, four-arm clinical trial including 48 young and middle-aged recreationally trained runners of the Guangzhou Pearl River running team was conducted. The participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo). Each group consisted of ten male participants and two female participants. Each training session was 40-60 min, and the runners trained 5-6 times each week. Cardiopulmonary exercise testing was performed at baseline and after the intervention, at 6 weeks, to assess the aerobic capacity of the runners. RESULTS: Analysis of covariance of the change from baseline over the 6 week treatment showed that the oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the medium and high dosage groups compared with the control group. However, there was no difference in VO2max, O2-pulse, VO2 related to work rate, and peak power after the 6 week treatment from baseline in any of these groups. CONCLUSION: NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle. TRIAL REGISTRATION NUMBER: ChiCTR2000035138 . ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 33888596 Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women RCT · Science, 2021 10-week RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in prediabetic overweight postmenopausal women - NMN raised muscle insulin sensitivity (clamp) and muscle insulin signaling. Small, single-population.
Key summary
A 10-week double-blind, placeboAn inert dummy treatment used as the comparison baseline.-controlled RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in prediabetic overweight/obese postmenopausal women. In the NMN group, insulin-stimulated glucose disposal (measured by hyperinsulinemic-euglycemic clamp) and skeletal muscle insulin signaling (AKT and mTOR phosphorylation) increased, while placebo did not change. Expression of muscle-remodeling genes also rose. It is an often-cited positive result, but as a single small study limited to one population (postmenopausal women), it does not readily generalize to the broader population.
Show original abstract
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239). ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 35215405 Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study RCT · Nutrients, 2022 108 people, 12 weeks - the afternoon NMN 250 mg group showed the largest effect size for lower-limb function (5-times sit-to-stand) and daytime drowsiness. Results depended on time of day (afternoon).
Key summary
An RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in which 108 older Japanese adults were split into morning/afternoon × NMN/placeboAn inert dummy treatment used as the comparison baseline. groups and took 250 mg once a day for 12 weeks. Significant interactions were seen for five-times sit-to-stand (5-STS) and drowsiness, and the afternoon NMN group showed the largest effect size for 5-STS (d = 0.72) and drowsiness (d = 0.64). The authors concluded that afternoon NMN improved lower-limb function and reduced drowsiness in older adults. The dependence on time of day and the splitting into subgroups limit interpretation.
Show original abstract
Deteriorating sleep quality and physical or mental fatigue in older adults leads to decreased quality of life and increased mortality rates. This study investigated the effects of the time-dependent intake of nicotinamide mononucleotide (NMN) on sleep quality, fatigue, and physical performance in older adults. This randomized, double-blind placebo-controlled study evaluated 108 participants divided into four groups (NMN_AM; antemeridian, NMN_PM; post meridian, Placebo_AM, Placebo_PM). NMN (250 mg) or placebo was administered once a day for 12 weeks. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Fatigue was evaluated using the "Jikaku-sho shirabe" questionnaire. Grip strength, 5-times sit-to-stand (5-STS), timed up and go, and 5-m habitual walk were evaluated to assess the physical performance. Significant interactions were observed between 5-STS and drowsiness. 5-STS of all groups on post-intervention and drowsiness of the NMN_PM and Placebo_PM groups on mid- and post-intervention showed significant improvement compared with those in pre-intervention. The NMN_PM group demonstrated the largest effect size for 5-STS (d = 0.72) and drowsiness (d = 0.64). Overall, NMN intake in the afternoon effectively improved lower limb function and reduced drowsiness in older adults. These findings suggest the potential of NMN in preventing loss of physical performance and improving fatigue in older adults. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 36443648 Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study RCT · Geriatr Gerontol Int, 2023 14 older men with diabetes, 24 weeks - NMN 250 mg/day was safe but did not improve grip strength or walking speed vs placeboAn inert dummy treatment used as the comparison baseline. (null primary endpoint).
Key summary
A 24-week placeboAn inert dummy treatment used as the comparison baseline.-controlled, double-blind RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. in 14 men aged ≥65 with diabetes and reduced grip strength (<26 kg) or walking speed (<1.0 m/s). NMN 250 mg/day was safe with no serious adverse events, but the primary endpoints, grip strength and walking speed, did not differ between groups, and no exploratory indicators differed significantly (only borderline trends in frailty prevalence and central retinal thickness). The authors explicitly stated that 24 weeks of NMN was safe but did not improve grip strength or walking speed. A major limitation is the very small sample of 14.
Show original abstract
OBJECTIVE: Nicotinamide adenine dinucleotide regulates various biological processes. Nicotinamide mononucleotide (NMN) increases its intracellular levels and counteracts age-associated changes in animal models. We investigated the safety and efficacy of oral nicotinamide mononucleotide supplementation in older patients with diabetes and impaired physical performance. METHOD: We carried out a 24-week placebo-controlled, double-blinded study of male patients with diabetes aged ≥65 years with reduced grip strength (<26 kg) or walking speed (<1.0 m/s). The primary end-points were to determine the safety of NMN oral administration (250 mg/day), and changes in grip strength and walking speed. The secondary end-points were to determine the changes in various exploratory indicators. RESULTS: We studied 14 participants aged 81.1 ± 6.4 years. NMN was tolerable without any severe adverse events. The changes in grip strength and walking speed showed no difference between the two groups: 1.25 kg (95% confidence interval -2.31 to 4.81) and 0.033 m/s (-0.021 to 0.087) in the NMN group, and -0.44 kg (-4.15 to 3.26) and 0.014 m/s (-0.16 to -0.13) in the placebo group, respectively. There were no significant differences in any exploratory indicators between the two groups. However, improved prevalence of frailty in the NMN group (P = 0.066) and different changes in central retinal thickness between the two groups (P = 0.051) was observed. CONCLUSION: In older male patients with diabetes and impaired physical performance, NMN supplementation for 24 weeks was safe, but did not improve grip strength and walking speed. Geriatr Gerontol Int 2023; 23: 38-43. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ 