NMN Benefits: The Science Behind This Magical Molecule

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NAD is a co-enzyme, a molecule that helps other proteins and enzymes do their job. One of these jobs is producing energy in mitochondria and reducing oxidative stress.

Source:

Klimova, N., Fearnow, A. & Kristian, T. Role of nad+—modulated mitochondrial free radical generation in mechanisms of acute brain injury. Brain Sciences vol. 10 1–13 Preprint at https://doi.org/10.3390/brainsci10070449 (2020).

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NAD participates in more than 50% of all biochemical reactions in our bodies (2). One of these processes is DNA repair, or keeping the DNA intact.

Source:

Yoshino, J., Baur, J. A. & Imai, S. ichiro. NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metab 27, 513 (2018).

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With time, DNA accumulates errors, or mutations, that if left uncorrected cause diseases like cancer. NAD collaborates with PARP, an enzyme responsible for correcting these errors and keeping the DNA healthy.

Source:

Murata, M. M. et al. NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival. Mol Biol Cell 30, 2584 (2019).

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Furthermore, NAD is a partner of CD38, a protein receptor expressed in plasma cells, and which plays a role in many processes like immune function, cancer and metabolic disease.

Source:

Camacho-Pereira, J. et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab 23, 1127–1139 (2016).

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Another group of enzymes that NAD activates are the sirtuins.

It would be fair to call sirtuins the “proteins of longevity”, as they are well-known for promoting healthy aging and longevity. Sirtuins are instrumental for the proper function of the cells including oxidative balance and DNA repair. As a result, their high activity is necessary for good cardiovascular, cognitive, metabolic and immune functio

Sources:

Imai, S. ichiro & Guarente, L. NAD+ and Sirtuins in Aging and Disease. Trends Cell Biol 24, 464 (2014).

Kane, A. E. & Sinclair, D. A. Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases. Circ Res 123, 868–885 (2018).

6: FRONT!!!!!!!

NAD is crucial for many core pathways in the cell. The enzymes we mentioned earlier compete for the available NAD. If somehow all NAD in our bodies ran out, we would not survive for more than a few seconds.  The problem is that NAD levels drop with age.

Source:

Massudi, H. et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One 7, (2012).

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Reduction in NAD levels leads to a drop in mitochondrial function, sirtuins activity and DNA repair. This leads to an increase in oxidative stress and systemic malfunction, also known as ageing (8) . Consequently, low NAD activity is related to a higher risk of heart disease, Type 2 diabetes, Alzheimer’s disease and accelerated aging.

Source:

Shade, C. The Science Behind NMN-A Stable, Reliable NAD+ Activator and Anti-Aging Molecule. Integrative Medicine • vol. 19 (2020).

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NMN (nicotinamide mononucleotide) is the immediate precursor of NAD. The cell uses NMN to make NAD. The reason we cannot take NAD directly is its big size that makes it hard to get into the cells. NMN is smaller and there is a specific transporter that brings it from the digestive system to blood circulation.

Source:

Grozio, A. et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolism 2019 1:1 1, 47–57 (2019)

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Clinical trials with NMN are relatively recent and mostly included older participants. Yet NMN so far is living up to the expectation. The first human studies showed that NMN supplementation is safe and directly increases NAD levels in the blood.

Sources:

Igarashi, M. et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj aging 8, (2022)

Okabe, K. et al. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Front Nutr 9, (2022)

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Furthermore, 600 or 1200 milligrams (mg) of NMN per day enhanced the aerobic capacity of amateur runners in only six weeks compared to runners that received a placebo.

Source:

Liao, B. et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr 18, (2021)

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Mouse studies show that NAD precursors increase strength and endurance.

Source:

Mills, K. F. et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab 24, 795–806 (2016)

Crisol, B. M. et al. NAD + precursor increases aerobic performance in mice. Eur J Nutr 59, 2427–2437 (2020)

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In another study, NMN showed promise against insulin sensitivity which may lead to type 2 diabetes and is a hallmark of aging. In that trial prediabetic, overweight and postmenopausal women received 250 mg of NMN daily. Ten weeks later, their skeletal muscle was more sensitive to insulin, at levels that compared to 10% weight loss or insulin sensitization treatment.

Yoshino, M. et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science (1979) 372, 1224–1229 (2021)

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Vivo studies where NMN increased insulin secretion and sensitivity in diabetic mice.

Source:

Yoshino, J., Mills, K. F., Yoon, M. J. & Imai, S. I. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab 14, 528–536 (2011).

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The latest clinical trial explored diverse, systematic benefits for NMN. The participants, all older than 65 years old, received 250 mg NMN for 12 weeks. At the end of the study, NMN supplementation in the afternoon improved overall drowsiness and lower limb function.

Source:

Kim, M. et al. 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, (2022)