Why NAD?
As research reveals more information about metabolism and aging, we increasingly find at the center of this complex web of enzymes and biochemical markers a coenzyme found in all living cells – nicotinamide adenine dinucleotide (NAD). The amount of NAD in the body declines naturally with aging, and in doing so the activities of numerous enzymes are correspondingly decreased.

The sirtuin (SIRT) family of proteins, which rely heavily on the presence of NAD, have been studied for many years for their role in metabolism and aging. To date, seven SIRT protein subtypes have been identified, each of which have a slightly different activity, location, and overall function. Because SIRT activity is dependent on NAD, these two compounds are linked to cellular lifespan, metabolism, and even regulation of inflammation.

Because NAD pools decline naturally during the aging process, SIRT function will decline as well. A decline in SIRT1 activity will impact mitochondrial function in two ways. First, a decline in SIRT1 has been linked to decreases in mitochondrial biogenesis via transcriptional activator PGC1α.

Second, decreased SIRT1 activity leads to decreased mitochondrial function due to a reduction in mitochondrial DNA replication and transcription. Because the mitochondria are the energy powerhouses in every cell of the body, a decline in mitochondrial function has now been linked to many age-associated pathologies, including metabolic syndrome, obesity, neurodegenerative issues, and cognitive decline.

Since one in three adults has metabolic syndrome, the importance of the SIRT family of proteins to metabolism cannot be over-emphasized. A recent study found that individuals with fatty liver who had a specific single nucleotide polymorphism (SNP) for SIRT3 were more likely to progress to metabolic syndrome.

How do we increase NAD?
What can we do to increase NAD in the body? It turns out that recent clinical research has found that nicotinamide riboside (NR) – a newly-researched vitamin B3 analog – can increase NAD levels in healthy humans – indicating that NR crosses into the mitochondria and increases NAD levels.*

How does NR affect metabolism?
The use of NR to increase NAD has been studied in animal models of metabolic syndrome. Because NR leads to increased SIRT1 and SIRT3 activity, the clinical ramifications for human use are extensive, and include:

1. A decrease of fatty liver incidence from a high-fat, high-sucrose diet

2. A decrease in hepatic insult in models of type 2 diabetes

3. An increase in cholesterol metabolism through SIRT1 activation

4. Better weight management in high-fat diets.*

To summarize, NR can increase NAD, which can upregulate SIRT1 and SIRT3.*

Increased SIRT1:
Inhibits hepatic glucose formation in obesity*
Limits hepatic lipid accumulation in the presence of elevated blood sugar*
Promotes the production of good (HDL) cholesterol*
Supports insulin release, improving overall glucose tolerance*
Enhances leptin sensitivity*

Increased SIRT3:
Inhibits lipid accumulation in the liver*
Increases mitochondrial biogenesis in skeletal muscle*
Increases thermogenesis in brown fat stores*


References

Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol 2014;24(8):464-471.

Cantó C, Houtkooper R, Pirinen E, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab 2012;15(6):838-847.

Hirschey M, Shimazu T, Jing E, et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 2011;44(2):177-190.

Imai S. "Clocks" in the NAD World: NAD as a metabolic oscillator for the regulation of metabolism and aging. Biochim Biophys Acta 2010;1804(8):1584-1590.

Sasaki T. Age-associated weight gain, leptin, and SIRT1: a possible role for hypothalamic SIRT1 in the prevention of weight gain and aging through modulation of leptin sensitivity. Front Endocrinol (Lausanne) 2015;6:109.

First human clinical study of ChromaDex's NIAGEN® nicotinamide riboside meets primary endpoint. http://www.news-medical.net/news/20150211/First-human-clinical-study-of-ChromaDexs-NIAGEN-nicotinamide-riboside-meets-primary-endpoint.aspx [Accessed March 9, 2016]