Study Shows NMN Improves Sleep, Fatigue, Physical Function

The biological clock is an invisible clock in the body, which actually refers to various physiological and biochemical activities in different organisms that change periodically with time. For example, the rhythm of physiological indicators such as blood pressure and body temperature in a 24-hour cycle are all rhythms of day and night changes caused by the rotation of the earth. This rhythmic phenomenon that life on earth shows with the rhythmic movement of the earth is what we usually call the biological clock.

If people don't work according to their biological clock, their work efficiency will be low, and it may lead to other complex diseases such as obesity, diabetes, hypertension, depression and tumors.

As a precursor of NAD+, NMN is inextricably related to the biological clock. The metabolism involved in NAD+ is regulated by the biological clock, and in turn these metabolisms also affect the biological clock. Acetylation enzyme (Sirtuin) plays a decisive role in this. Acetylase (Sirtuin) has been scientifically proven to resist aging and prolong life. It plays an important role in various cellular processes such as aging, so it is also called longevity protein. Sirtuins are present in mammals, consist of 275 amino acids, and have 7 different isoforms (SIRT1-SIRT7). Among them, SIRT1 controls the connection with the biological clock.

NMN produces NAD+ in the body, and NAD+ is the main substrate of SIRT1 protein, which means that NAD+ and SIRT1 are linked to each other, and the level of NAD+ also adjusts the level of SIRT1. SIRT1 can inhibit the transcription of cycle genes (circadian clock genes) to control the operation of the biological clock, which in turn can regulate NAD+ levels through NAMPT (the enzyme that regulates the synthesis of nmn in vivo).

In the experiments, the researchers first monitored the mice's natural activity patterns. Normally, the biological clock of mice is a little shorter than 24 hours, about 23.5 hours; the biological clock of mice lacking SIRT1 in the brain is slightly longer, approaching 24 hours; the biological clock of mice with twice the normal amount of SIRT1 is longer than that of normal mice Slightly shorter; if the SIRT1 level is 5 times normal, it is too short.

The amount of SIRT1 in the brain helps the master circadian clock adapt to seasonal changes in the length of sunlight, and the mice's circadian clock gets closer to 24 hours with age. So is the longer biological clock related to the reduction of SIRT1 content in the brain?

The researchers created a 4-hour jet lag in mice by suddenly changing the light in the lab. Young mice reset their circadian clocks in just two days, adapting to the 'new time zone'; older mice took eight days to reset. Further experiments found that young mice with low levels of SIRT1 in their brains took 4 days to re-adapt; those with high levels of SIRT1 recovered faster than the average old group.

This suggests that SIRT1 is at least related to the ability to reverse jet lag. In addition, they also found that the level of SIRT1 in the brain's biological clock is also closely related to the levels of other important clock proteins.

The 12-week intervention period (August-November 2019) of 6 tablets of NMN (250 mg) in 108 participants at the Institute of Innovative Medicine, University of Tsukuba, with major considerations including sleep quality and fatigue, measured by subjective questionnaires at baseline ( Before the intervention), week 6 (during the intervention), and week 13 (post-intervention), physical performance was assessed only before and after as secondary outcomes.

There was no statistically significant interaction of sleep quality as assessed by the Pittsburgh Sleep Quality Index PSQI. However, there were significant main effects on sleep duration, sleep disturbance score, daytime dysfunction score, sleep quality score and PSQI total overall score. In addition, the effect sizes of sleep latency, daytime dysfunction score, sleep quality score, and PSQI overall total score were the largest among the four groups in the NMN_PM group. NMN had a significant effect on improving the sleep quality of the participants.

This study showed that after 12 weeks of NMN intake, afternoon NMN intake was more effective in improving lower extremity function and reducing sleepiness in older adults, which could further benefit their physical and mental health. Simultaneously increasing NAD+ through NMN intake is expected to improve aging-related mitochondrial diseases, chronic inflammation, oxidative stress, DNA damage, and sirtuin inactivation, which may prevent age-related diseases and physical dysfunction.

Tag: NMN

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