NMN

Authors:

Faguo Yue, Guanyi Liao, Hong Peng, Jinjun Guo, Li Rong, Tianke Li, Xinsen Zou, Yuchen Xie

Findings:

This review summarizes research on NMN, a NAD+ precursor involved in key biological processes like energy metabolism, aging, and DNA repair. Preclinical studies (mostly rodents) suggest NMN mitigates age-associated physiological decline, improves metabolic health (diabetes, obesity), vascular function, cardiac health, neuroprotection (including in models of Alzheimer's, ischemia, hemorrhage), and shows benefits in models of eye, kidney, sepsis, and fertility issues. Human trials indicate NMN is generally safe (up to 1250 mg/d for 4 weeks, 900 mg/d for 60 days), increases blood NAD+ levels (dose-dependently), and may offer benefits like improved aerobic capacity, muscle insulin sensitivity (prediabetic women), muscle function (older men), and reduced drowsiness (older adults), though evidence is preliminary, sometimes conflicting, and needs more robust, long-term studies. Research specific to digestive diseases (liver, gut, pancreas) shows potential for reducing liver injury/fibrosis/insulin resistance, improving gut barrier function/microbiota balance, and alleviating pancreatitis, but is less developed compared to other areas.

Participants:

Review covers preclinical studies (mice, rats, zebrafish larvae) and human clinical trials (healthy men/women, older adults, postmenopausal prediabetic women, amateur runners, diabetic patients).

Dosage:

Preclinical (rodent models): Doses ranged from 62.5 mg/kg (single dose) to 500 mg/kg/d (i.p. or oral), durations from single dose/3 days up to 12 months. Also mentions 500 mM (5 μL/eye) subconjunctival administration. Human trials: Oral doses ranged from 250 mg/d to 1250 mg/d, durations from 2 weeks to 24 weeks. Dose-dependent increase in blood NAD+ levels noted in humans. Specific examples: 500 mg/kg/d (mice, diabetes/aging/cardiac); 400 mg/kg/d (mice, vascular); 300 mg/kg/d (mice, cognitive); 200 mg/kg/d (mice, oocyte quality); 250 mg/d (humans, multiple trials); 1250 mg/d (humans, safety); up to 900 mg/d (humans, safety/efficacy).

Study Quality Assessment:

Review discusses preclinical studies (animal models) and human clinical trials (some randomized, double-blind, placebo-controlled, parallel-group, multicenter; N=10 to N=108). Mentions methods like RNA-seq, metabolomics, cardiopulmonary exercise tests, physiological/laboratory tests, fundus biomicroscopy, retinal electroretinography, tear volume detection. Acknowledges limitations: results may not fully translate from animals to humans, high doses used in animals, human trials often have small sample sizes/short durations, lack of placebo control in some, potential publication bias/conflicts of interest, conflicting findings, limited long-term human safety data, mechanistic uncertainty (downstream pathways elusive), complex metabolic interactions, tissue-specific metabolism heterogeneity, discrepancies between animal and human results, need for more high-quality clinical studies. Selection criteria for reviewed studies included peer-review, methodological quality (design, sample size, duration, stats), robust designs, use of controls, and consideration of renowned research teams.

All Effects:

Findings:

NMN was shown to be safe, well tolerated, and significantly increased NAD+ levels in blood of middle-aged adults. NMN also had a positive impact on physical endurance in six-minute walk tests, blood biological age, and patient-reported outcomes.

Participants:

80 middle-aged healthy adults

Dosage:

once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN

Study Quality Assessment:

randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial, N=80

All Effects:

Authors:

Brown R et al, Gilley J, Mori V, Nascimento-Ferreira I, Orsomando G

Findings:

A rise in the NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

Authors:

Cheng C-Y

Findings:

The estimated global prevalence of glaucoma is 3.54%, highest in Africa. The number of people aged 40-80 with glaucoma is projected to increase from 64.3 million (2013) to 111.8 million (2040), with disproportionate effects in Asia and Africa.

Participants:

People worldwide aged 40-80 years

All Effects: