ABSTRACT
Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40-65 years. The participants received a placebo or daily 300â¯mg, 600â¯mg, or 900â¯mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.
Subject(s)
NAD , Nicotinamide Mononucleotide , Humans , Dietary Supplements , Adult , Middle Aged , Aged , Randomized Controlled Trials as TopicABSTRACT
Background: The objective of the study was to evaluate the effect of Colchicine 0.5 mg and Aspirin 75 mg oral tablets given together on management of moderate COVID-19. Methods: The study was carried out in 122 moderate COVID-19 patients between ages 40-80 years in hospital, instructed to take either 1 tablet of Colchicine 0.5 mg and Aspirin 75 mg each (treatment group), or 1 tablet of Aspirin 75 mg (Control group), twice a day along with standard of care. Result: At the end of treatment, reduction was seen in the treatment group in score of 8-point ordinal scale, troponin, D-Dimer, Hs-CRP from baseline. There was a fall of 51.1% among control arm and 53.4% among treatment arm in 8-point ordinal score. The reduction in mean D-Dimer was 37% in control group and 38.1% in treatment group. The mean reduction in CT severity score in control group was 3.65 and in treatment group was 4.82, and the difference between the two groups was statistically significant (P value = 0.018). Conclusion: It was evident from CT scan scores that the treatment group has shown significant improvement in the reduction of inflammation and other COVID-19 symptoms as compared to the control group. The fall in Ferritin, Hs-CRP and D-Dimer level after treatment were indicative of improvement in internal inflammatory response of body in COVID-19 disease. As increased troponin levels indicate some degree of heart damage, the fall in troponin levels indicated that test treatment improved heart health in COVID-19 patients.
ABSTRACT
In animal studies, ß-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.