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

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 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

“…Clinical benefits of NMN supplementation in mouse models have shown doubled running endurance on aging mice [ 6 ], restored cognition in Alzheimer’s disease rat model [ 7 ], and reversed vascular dysfunction in old mice [ 8 ]. However, human clinical trials with NMN are limited [ 9 – 17 ]. The first human clinical trial confirmed that NMN supplementation was safe up to 500 mg/day and plasma concentrations of NAD metabolites were significantly increased, but the changes of plasma NAD concentration were not mentioned, and the trial was an open-label single oral dosing with only 10 healthy male participants [ 9 ].…”

“…A 6-week RCT with healthy amateur athletes with 300, 600, and 1200 mg/day NMN oral regimens concluded that exercise plus NMN supplementation was significantly and dose-dependently increased aerobic capacity but found no impact on physical strength when compared to exercise alone [ 16 ]. Another RCT on the effects of the time-dependent intake (morning or afternoon) of NMN on sleep quality, fatigue, and physical performance in older adults was conducted with 250 mg/day NMN oral treatment for 12 weeks [ 17 ]. The trial found that only drowsiness and lower limb function in the afternoon NMN-treated group were significantly improved among the many trial end points measured.…”

Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan

“…Furthermore, 250 mg of daily NMN supplementation was shown to be well tolerated, efficacious when increasing NAD+/NADH ratio, and improved muscle function in aged but otherwise healthy men [68]. NMN supplementation has also been implicated in improving circadian paraments in older adults, where 12 weeks of 250mg daily NMN supplementation led to improvements in sleep quality, as measured through the PSQI, fatigue, and physical performance [69]. Having established the safety and efficacy of NMN supplementation to increase NAD+ levels in the body, numerous trials analyzing the effects of NMN on health, aging, and disease are constantly emerging.…”

New horizons in life extension, healthspan extension and exceptional longevity

“…To date, published studies of NR have mostly evaluated its bioavailability [ 33 ], whereas there have been some recent studies of NMN that have evaluated clinical outcomes in older adults. A 12-week period of treatment with NMN reduced drowsiness and improved leg function in older people [ 34 ]. A randomised clinical trial in 25 obese postmenopausal women found that 10 weeks of NMN compared to placebo was associated with improved insulin sensitivity in muscle but not liver or adipose tissue [ 35 ].…”