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  • Will Nicotinamide Riboside Be The Next Anti-Aging Pill?

    June 10, 2012: by Bill Sardi

    Say it again:  nicotinamide riboside (nik-oh-tin-amide ry-bo-side).

    In the wake of the many advances and setbacks involved in marketing resveratrol pills, another small vitamin-like molecule enters the anti-aging pill market, that is, if it can be produced economically and be shown to work in humans at a much lower dose than in the animal lab.

    The “new molecule” is a cousin of niacin.  Said to be an incredibly small molecule that is difficult to find in foods (it is found in the whey of milk and beer), its molecular weight is 255.247 Daltons, slightly larger than the red wine molecule resveratrol.  It works on some of the same gene targets as resveratrol, such as SIrtuin1 and Sirtuin 3, and subsequently FOXO1, Pgc1a and SOD, genes known to produce anti-aging effects.

    Is this molecule newly recognized as an anti-aging agent? No, it was panned as an anti-aging agent and molecular mimic of a calorie restricted diet in 2007.  But it has gained considerable public attention recently because of a published paper showing it can limit weight gain in fat-fed laboratory animals and help overcome insulin resistance as well as improve endurance and reinvigorate mitochondria, energy compartments within living cells.  The problem with studies like this is that its benefits are shown in overweight lab animals only.  Humans consuming a normal-calorie diet who are not overweight may not experience a benefit.  Normal-fed lab animals didn’t.  What mankind is still searching for is a pill that would work among healthy individuals to delay the effects of advancing age.

    The molecule is nicotinamide riboside, a cousin of niacin.  The dose used in rodents is equivalent to 28,000 milligrams in a 160-lb (70 kilogram) human (400 mg per kilogram of body weight).  Researchers use mega-doses to ensure a positive effect.  Of course, such a dose in humans would be impractical and totally unaffordable.  Nicotinamide riboside is not available as a dietary supplement ingredient and a company in the dietary supplement field says it has licensed a novel manufacturing process for nicotinamide riboside from Cornell University.  But that company is getting ahead of itself.  It is currently attempting to sell its resveratrol-like pterostilbene product, said to be superior to plain resveratrol, in retail shops and it has not gained profitability yet.

    A larger question is whether there is even a market for anti-aging pills at all.  Surveys have shown that many Americans want to live better, not longer.  Some also fear living longer, depleting retirement funds and contributing to overpopulation.  Most surveys have shown people would try an anti-aging pill, but would be more likely to do so if someone else paid for it, like a health insurance plan.

    So are anti-aging researchers chasing the wind, again?

    No question, nicotinamide will capture the attention and maybe imagination of many.  Whatever, don’t start drinking milk to get some, it can hardly be detected in milk samples.

    Niacin, often used to favorably alter cholesterol profiles, produces a flushing effect that makes it difficult for humans to use in required high doses.  Nicotinamide riboside skips around a cell receptor that causes the flushing and thus produces no known side effects.

    Look, most consumers just want to know, can they eat chocolate cake and not pay the price?  Said another way, does such a pill give license to gluttony?  Let’s not go there.

    Another obstacle is that nicotinamide riboside is likely to be produced synthetically rather than derived from any natural source.  The Food & Drug Administration has been saying synthetic molecules are not food derived and therefore only qualify as drugs, not food supplements.  So its regulatory status is in question.

    Here is the abstract of the recent research study:


    The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity

    Cell Metabolism, Volume 15, Issue 6, 838-847, 6 June 2012
Copyright © 2012 Elsevier Inc. All rights reserved.


    Carles Cantó, Riekelt H. Houtkooper, Johan Auwerx


    • NR efficiently increases NAD+ levels in mammalian cells and tissues
    • NR supplementation increases SIRT1 and SIRT3 activities
    • NR largely prevents the detrimental metabolic effects of high-fat feeding
    • NR enhances mitochondrial function and endurance performance



    As NAD+ is a rate-limiting co-substrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38—both NAD+ consumers—increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.

    For a more in-depth review of this topic, click here.


    Copyright 2012

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