Does Timing Matter? Study Shows Taking NMN Before Bed May Support Physical Performance and Fight Drowsiness More Than Morning NMN
Everybody ages. There is no disputing that we grow older each day we are alive. But the way we age can vary widely from person to person. There’s a broad spectrum of how people feel in their bodies upon reaching “older adult” status. Some may remain spry and strong, while others could start to experience physical decline that contributes to moving less, aching more, and tiring more easily. Up to half of older adults experience fatigue, which is associated with mood changes, physical decline, frailty, cognitive loss, sleep disturbances, and even premature mortality. While many people might think feeling tired is an inevitable part of growing older, recent research has shown that is not the case.
One area of interest is declining levels of NAD+ (nicotinamide adenine dinucleotide) — a molecule needed by every cell in the body to produce energy and keep internal processes running smoothly. Now, researchers out of the University of Tsukuba in Japan show how boosting NAD+ with one of its precursors, NMN (nicotinamide mononucleotide), improves markers of physical function and daytime fatigue. As the first reported trial of its kind in older adults, this research by Kim and colleagues sets the stage for using NMN to support both physical and mental health as we age.
How Mitochondria Fuel Our Muscles
A leading reason why inadequate NAD+ is so tightly linked to physical fatigue is the energy requirements of skeletal muscle — the type of muscle that gives humans the ability to move, stand, jump, run, and even breathe. Skeletal muscle is energetically expensive, meaning it needs higher amounts of energy in the form of adenosine triphosphate (ATP) than most other organs.
To supply this enhanced energy requirement, the ATP-generating powerhouses in our cells — the mitochondria — start to break down fuel sources, like glucose (sugar) or fat stored in the body. Maintaining adequate NAD+ levels inside cells is essential for proper mitochondrial function, as NAD+ is a required cofactor for several enzymatic steps in these energy-creating processes.
Therefore, skeletal muscle health is ultimately dependent on having healthy and functional mitochondria — which, in turn, are dependent on having enough NAD+ around to fuel them. With age or prolonged inactivity, our cells’ mitochondrial function can diminish, leading to a subsequent decline in muscular health and physical energy. As research shows that lower NAD+ levels are detrimental to skeletal muscle health, it’s logical that boosting NAD+ with its precursors, like NMN, could support the internal energy production needed for improving physical energy — which then supports mental energy and fighting fatigue, as well.
Evening NMN Supports Physical and Mental Energy More Than Morning NMN
In this recent 12-week trial published in the journal Nutrients, Kim and colleagues randomly split healthy Japanese adults over age 65 into four groups: one group taking 250 mg of supplemental NMN in the morning before noon (NMN-AM), another taking 250 mg NMN in the evening after 6 pm (NMN-PM), and two corresponding placebo groups. The research team assessed several markers of physical and mental fatigue at baseline, mid-treatment (6 weeks in), and post-treatment (after 12 weeks of supplementation).
The participants who took NMN in the evening exhibited the most significant benefits to fatigue and physical performance, especially in lower limb function. One physical performance test was the 5-STS (5-times sit-to-stand), which measures how quickly one can sit down in a chair and stand back up five times without using their arms. While all groups improved their 5-STS times over the 12 weeks, the NMN-PM group showed the most significant improvements, indicating effectively enhanced lower limb function. Whereas the morning NMN group only reduced their sit-to-stand time from 5.5 seconds to 5.1 seconds, the NMN-PM group improved from 6.3 to 5.3 seconds.
NMN also improved daytime drowsiness the most when supplemented in the evening. Although there was an observed placebo effect (meaning, people who took the placebo pills at night also experienced a perceived benefit to fatigue), the NMN-PM group reduced drowsiness the most. Improving daytime drowsiness through NMN could be meaningful for older adults, as chronic fatigue is more likely to occur with age and cause other comorbidities.
Subjective measures of sleep were not significantly different between the treatment and placebo. However, all four groups reported improvements in sleep duration, disturbances, quality, and latency (the time it takes to fall asleep). These results also suggest that a placebo effect was widely observed in this study, as people who took the placebo perceived sleep-related improvements as well. While the four groups weren’t significantly different from one another, the NMN-PM group did have the largest effect size for sleep latency, sleep latency, and daytime dysfunction. A larger effect size means that those who took NMN in the evening had the most robust relationship to these measures of sleep-related improvements.
Time-Dependent Effects of NMN Reported For the First Time in Humans
This study indicates that supplemental NMN is safe and well-tolerated at 250 mg per day for 12 weeks and supported mobility, lower limb physical performance, and daytime energy levels in this group of people. Further, this is the first known study to look at the timing of NMN and how it alters efficacy. However, it’s worth noting that while these benefits were observed, the findings were not incredibly strong, indicating that more research is needed on this topic.
As the authors conclude, “Therefore, examination of the effects of the time-dependent intake of NMN was considered necessary, and two time zones (morning and afternoon) were set to investigate the optimal intake time to achieve the maximum efficiency of NMN absorption.” They continue, “Collectively, this study suggests that NMN intake in the afternoon is more effective in improving lower limb function and reducing drowsiness in older adults, which could further benefit their physical and mental health.”
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Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. 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. Nutrients. 2022;14(4):755. Published 2022 Feb 11. doi:10.3390/nu14040755