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New Cutting Edge Nutrient Nicotinamide Riboside
Submitted by Thorne Research

Nicotinamide adenine dinucleotide (NAD) is a vitamin B-like compound found in all living cells, where it is an essential participant in several life-sustaining metabolic pathways. The best-characterized of these pathways is the Krebs cycle, which is a series of chemical reactions used by cells to convert carbohydrates, proteins, and fats to usable energy.

NAD also plays a role in maintaining the delicate electrochemical balance within cells, as it is capable of shuttling electrical charges between other molecules. In addition, NAD is a necessary cofactor for several classes of enzymes, such as sirtuins, which are intimately involved in DNA repair, stress resistance, and normal cellular aging. Paradoxically, each time a sirtuin performs one of these functions it converts NAD to nicotinamide, a byproduct that actually interferes with the enzyme's function. Consequently, as NAD is consumed and nicotinamide accumulates within a cell, sirtuin activity declines and the cell begins to age more rapidly.

The Obstacles to Making More NAD

Without a doubt, our cells need a lot of NAD to accomplish their day-to-day functions and remain vigorous. Providing more of this important compound through dietary or supplemental means has been the focus of scientific investigation for quite some time. However, the scientists involved in this research have been frustrated by the difficulty of delivering NAD precursors to living cells in sufficient amounts—and in the right form—to be physiologically meaningful.

For example, it is well known that NAD can be produced from L-tryptophan (an amino acid found in many foods), but this is an inefficient and unreliable process; the amino acid is likely to be utilized for other functions in the body. Nicotinamide can also be converted to NAD, but too much can inhibit certain critical processes.

Finally, niacin can be converted to NAD, but this, again, involves an inefficient metabolic pathway and taking large doses causes uncomfortable side effects.

Nicotinamide riboside: The Solution
Nicotinamide riboside (NR), which is simply a nicotinamide molecule attached to the sugar ribose, is the most efficient and direct pathway to NAD production. Nicotinamide riboside can be converted to NAD much more readily than L-tryptophan or niacin. And, unlike nicotinamide, NR does not inhibit sirtuin activity. In fact, NR enhances the function of NAD-consuming enzymes. Furthermore, NR has none of the negative side effects associated with high-dose niacin supplementation.

The issue with nicotinamide riboside— until recently—has been the absence of a commercially viable source. Trace amounts of nicotinamide riboside can also be found in a few foods, such as milk, but no food provides significant levels of NR. This dilemma has been solved with the development of a proprietary process that can now efficiently provide NR in quantities sufficient for widespread commercial use.2 Thorne Research now offers Niacel, containing 125 mg of Nicotinamide riboside.


Potential Clinical Applications for Nicotinamide Riboside
Neuroprotection: Wallerian degeneration is a form of nerve damage associated with Alzheimer's disease, Parkinson's disease, multiple sclerosis, diabetes, cancer chemotherapy, and normal aging. Notably, this type of neuronal degeneration is characterized by the depletion of intracellular NAD. Using mice as study subjects, a team at Washington University School of Medicine in St. Louis, Missouri, has shown that increasing intracellular levels of NAD helps prevent Wallerian-like nerve damage (induced by vincristine, a chemotherapy drug).3

Aging: Scientists have known for some time that caloric restriction prolongs lifespan in certain animals. Researchers investigating the aging process now believe that caloric restriction and sirtuin activation prolong cellular lifespan through similar mechanisms. SIR2, a sirtuin found in yeasts, slows accumulation of abnormal DNA and delays aging and death in these singlecelled organisms. SIRT1, the mammalian equivalent of SIR2, activates regulatory enzymes that prolong the lifespan of cells in higher animals. Both SIR2 and SIRT1 activity are enhanced by elevated levels of NAD. Because sirtuins are inhibited by increasing levels of nicotinamide, NR is a better supplement choice for enhancing NAD levels than nicotinamide. Several studies have explored and confirmed the associations between NAD repletion, sirtuin activity, and increased lifespan.

Obesity: Another exciting area of research involves the apparent connection between sirtuin activity and weight regulation. In the October 2011 issue of Molecular Cell, a group of scientists at San Francisco's Gladstone Institute of Virology and Immunology demonstrated that a highfat diet suppresses the activity of a key mammalian sirtuin, SIRT3, and leads to a decline in fat metabolism, which could contribute to weight gain.4 Presumably, in animals with low SIRT3 activity, reactivation of SIRT3 could reverse this process and help prevent weight gain. In the June 2012 issue of Cell Metabolism, Dr. Carles Cantó and his team provided further evidence that this was, in fact, the case; supplementing mammalian cells and mouse tissue with nicotinamide riboside increased NAD levels and activated both SIRT1 and SIRT3.5 Furthermore, NR supplementation prevented weight gain in mice that had been fed a high-fat diet.

References
1. Belenky P, Bogan K, Brenner C. Trends Biochem Sci 2007;32(1):12-20.
2. Belenky P, Stebbins R, Bogan K, et al. PLoS One 2011 May 11;6(5):e19710.
3. Araki T, Sasaki Y, Milbrandt J. Science 2004;305(5686):1010-1013.
4. Hirschey M, Shimazu T, Jing E, et al. Mol Cell 2011;44(2):177-190.
5. Canto C, Houtkooper R, Pirinen E, et al. Cell Metab 2012;15(6):838-847.
6. Kendrick A, Choudhury M, Rahman S, et al. Biochem J 2011;433(3):505-514.

*This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.


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