With aging, cell metabolism and function gradually decrease, which is a significant risk factor for several diseases, including cancer, cardiovascular diseases, and the nervous system disorders (1).
The human body comprises 30-40 trillion cells, which all rely on nicotinamide adenine dinucleotide (NAD+) to function correctly. This makes NAD+ an essential determinant of cellular health (2). However, research shows that NAD+ levels declines with age. There is a possibility that NAD+ depletion may play an important role in the development of various age-related diseases such as diabetes, Alzheimer's, obesity, heart disease, and loss of muscle power (2-4).
Within the cell, NAD+ binds to other enzymes and activates cell mechanisms. It also participates in many vital functions. Without NAD+, the human body cannot function properly, and life would not be possible (2).
NAD+ has two critical roles in the human body (5, 3, 2):
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Energy production: NAD+ is critical to cellular metabolism and helps convert food into energy.
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Regulation of numerous cellular processes: As an auxiliary molecule, NAD+, directly and indirectly, affects many cellular functions, including repair of the DNA, gene regulation, and immune function.
While the molecular mechanism involved in the aging process is still poorly understood and a hot topic in the life sciences, scientists are investigating how increasing NAD+ levels in the body through nutrition or supplementation can delay the onset of disease and disability and thus can slow down the aging process and helps to create a healthier and better quality of life.
Ways to maintain and increase NAD+ levels
Generally, having a healthy lifestyle helps to increase the level of NAD+ in the body. Namely, NAD+ levels can be regulated by lifestyle and nutrition approaches such as fasting, caloric restriction, sports activity, low glucose availability, and heat shocks (2-4).
It is not always easy to live a healthy lifestyle due to age or health conditions; In this case, taking supplements such as vitamin B3 is an excellent option to increase the level of NAD+ in the body. In addition, the use of NAD+ precursors can be effective in improving a wide range of diseases associated with NAD+ deficiency, such as infection, cancer, metabolic diseases, acute injury, aging, and aging-related neurological disorders (6,7).
What is nicotinamide riboside, and what are its benefits?
Nicotinamide riboside (NR) is a new generation of vitamin B3 with a unique mechanism of action. Taking supplements containing NR more than other types of vitamin B3 increases the level of NAD+ in the body (7). For example, beer, yeast, and cow's milk contain NR. However, there is a trace amount of NR in these food categories. Recently, NR has been studied much more as one of the precursors of NAD+, and the results of these studies have shown that NR has potential benefits for health in various aspects due to the increase in the level of NAD+ in the body. In addition, the discovery of the relationship between NR and increased lifespan in yeast led to much research on the role of this molecule in reducing the aging process.
The aging process is associated with chronic inflammation and an increase in the number of senescent cells. These factors cause age-related disorders like cardiovascular disease, osteoporosis, and diabetes. Based on scientific research, supplementing with oral NR in older adults and increasing the level of NAD+ reduces inflammatory blood factors and improves muscle function. Also, in cellular studies, NR rejuvenates intestinal stem cells. Cardiovascular diseases are one of the leading causes of death worldwide, and aging is one of its main risk factors. NR reduces aortic stiffness and blood pressure in middle-aged and older adults, and systolic blood pressure and aortic stiffness. On the other hand, in several neurodegenerative diseases, such as Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis, oral NR reduces inflammation and protects nerve cells. Also, taking supplements containing NR in people with Covid-19 improves the recovery time of patients (8).
In addition to the benefits of NR for general health, according to US Federal Food, Drug, and Cosmetic Act, NR is a safe supplement and does not cause flushing (a common complication of niacin or vitamin B3) (9).
References
1. Yang F, et al. Association of Human Whole Blood NAD+ Contents With Aging. Frontiers in Endocrinology. 2022.
2. Chini CC, et al. NAD and the aging process: Role in life, death and everything in between. Molecular and cellular endocrinology. 2017.
3. Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021.
4. Braidy N, et al. Role of nicotinamide adenine dinucleotide and related precursors as therapeutic targets for age-related degenerative diseases: rationale, biochemistry, pharmacokinetics, and outcomes. Antioxidants & Redox Signaling. 2019.
5. Amjad S, et al. Role of NAD+ in regulating cellular and metabolic signaling pathways. Molecular Metabolism. 2021.
6. Trammell SA, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature communications. 2016.
7. Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature communications. 2018.
8. Sharma C, et al. Emerging Role of Nicotinamide Riboside in Health and Diseases. Nutrients. 2022.
9. www.fda.gov/files/food/published/GRAS-Notice-000635--Nicotinamide-riboside-chloride.pdf
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