Written by Taylor Woosley, Science Writer. A 12-week supplementation of 250 mg NMN, when administered in the afternoon, significantly increased lower limb function through improvements in 5-STS and TUG scores and significantly reduced drowsiness in subjects.

man with weightsFatigue, the overwhelming sense of decreased ability for activity, results from an imbalance in the availability and utilization of resources and is often attributed to disease-specific or cognitive factors 1. Fatigue is common amongst most people but chronic, severe fatigue (persisting longer than 6 months) is associated with functional impairment and a decreased quality of life 2. Around 21.9% of the general population experiences fatigue and the prevalence is even more common in elderly populations, affecting around 40% to 74% of elderly people 3. Another factor that decreases with age is sleep quality, which is often related to a variety of adverse health outcomes, such as depression, anxiety, disability, and mortality 4.

Nicotinamide adenine dinucleotide (NAD+), a crucial metabolite necessary for cellular bioenergetics, DNA repair, and cell survival, has been previously studied as a potential therapeutic approach to reducing fatigue in elderly populations 5. NAD+ is critical for human longevity and naturally declines as we age and NAD+ deficiency leads to biological aging of cells, tissues, and organs 6. Nicotinamide mononucleotide (NMN), an intermediate of NAD+ biosynthesis, acts as a source of cellular energy 7. Previous research on NMN administration has proven its ability to suppress age-associated tissue inflammation, with improvement in mitochondrial functioning in various metabolic organs 8.

In this randomized, double-blind, placebo-controlled parallel-group study, 108 participants were divided into four groups and given an NMN supplement (at different times of day depending on the group) for 12 weeks. Subjects consumed 6 tablets of the supplement (NMN or placebo) once a day with water and had to record their intake over the course of the trial. NMN supplementation contained 250 mg NMN, along with maltitol, crystalline cellulose, silicon dioxide, and magnesium stearate, while placebo contained maltitol, crystalline cellulose, silicon dioxide, and magnesium stearate. The four participant groups were as follows:

Group 1NMN – AM (n=27)
Group 2NMN – PM (n=27)
Group 3Placebo – AM (n=27)
Group 4Placebo – PM (n=27)

Clinical characteristics were gathered, such as BMI, diastolic blood pressure, and heart rate. Subjective sleep quality was obtained using the Pittsburgh Sleep Quality Index and a self-reported sleep diary to assess factors like sleep duration, sleep disturbances, and quality. Subjective fatigue information was obtained using the Jikaki-sho shirabe questionnaire (developed by the Industrial Fatigue Research Committee of Japan Occupational Health) to understand participant’s feelings of drowsiness, pain, and uneasiness. Physical performance was assessed by 5-times sit-to-stand (5-STS), grip strength, timed up and go, and a 5-m walk. The focus of the study was to observe any significant changes in sleep quality and fatigue, with a secondary outcome being noticeable changes in physical performance. After 12-weeks of the study, the significant findings are as follows:

  • Although sleep quality remained similar, there were significant changes noted for sleep duration, sleep disturbance, and daytime dysfunction (p < 0.01).
  • Compared to NMN AM supplementation, significant improvements were noted for NMN PM supplementation in drowsiness (p < 0.01), instability (p < 0.01), dullness (p = 0.03), and total fatigue score (p <0.01).
  • When observing changes in physical performance, a significant improvement was noted for 5-STS (p = 0.04), with the largest improvement observed in the NMN PM group.
  • Furthermore, when evaluating the main effects of time on physical performance, a substantial change was observed in the NMN PM group, with a significant improvement in 5-STS (p < 0.01) and TUG (p < 0.01).

Findings of the study support the use of NMN supplementation to boost NAD+ levels in older adults. Significant findings suggest that the NMN supplementation, particularly when consumed in the PM group, helped aid in reducing inflammation, oxidative stress, and DNA damage. Future studies should observe the effects of higher and lower dosages of NMN to see if further improvement can be achieved. Limitations of the study include the lack of data regarding the subject’s daily diet which could potentially be high in NMN-containing foods, the unobserved potential physiological factors of the participants, and the presence of a placebo effect which was noted for 5-STS, drowsiness, and sleep disturbance scores.

Source: Kim, Mijin, Jaehoon Seol, Toshiya Sato, Yuichiro Fukamizu, Takanobu Sakurai, and Tomohiro Okura. “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 14, no. 4 (2022): 755.

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Click here to read the full text study.

Posted April 12, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Torossian M, Jacelon CS. Chronic Illness and Fatigue in Older Individuals: A Systematic Review. Rehabil Nurs. May-Jun 01 2021;46(3):125-136. doi:10.1097/rnj.0000000000000278
  2. Goërtz YMJ, Braamse AMJ, Spruit MA, et al. Fatigue in patients with chronic disease: results from the population-based Lifelines Cohort Study. Sci Rep. Oct 25 2021;11(1):20977. doi:10.1038/s41598-021-00337-z
  3. Afzali A, Goli S, Moravveji A, Bagheri H, Mirhosseini S, Ebrahimi H. The effect of zinc supplementation on fatigue among elderly community dwellers: A parallel clinical trial. Health Sci Rep. Jun 2021;4(2):e301. doi:10.1002/hsr2.301
  4. Chen HC, Hsu NW, Pan PJ, Kuo PH, Chien MY, Chou P. The Development of a Rapid Classification Scale for Sleep Quality in Community-Dwelling Older Adults – The Yilan Study, Taiwan. Nature and science of sleep. 2021;13:1993-2006. doi:10.2147/nss.S324928
  5. Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD(+) in Brain Aging and Neurodegenerative Disorders. Cell Metab. Oct 1 2019;30(4):630-655. doi:10.1016/j.cmet.2019.09.001
  6. Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol. 2020;8:246. doi:10.3389/fcell.2020.00246
  7. Poddar SK, Sifat AE, Haque S, Nahid NA, Chowdhury S, Mehedi I. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. Jan 21 2019;9(1)doi:10.3390/biom9010034
  8. Yoshino J, Baur JA, Imai SI. NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. Mar 6 2018;27(3):513-528. doi:10.1016/j.cmet.2017.11.002
×