DOES NICOTINAMIDE REALLY INHIBIT SIRT1 IN THE HUMAN BODY?

This article is copyright © Nils Osmar 2019.

    • It’s intended solely for informational purposes. It is not meant to be taken as, and should not be construed, as medical advice.
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One question at the heart of the life extension movement has to do with the effects of different forms of Vitamin B3 on the aging process.

Aging is related, at least in some respects, to declining levels of a beneficial compound called NAD in the body. When we’re young, we have lots of NAD. As we age, the supplies of NAD go down.

Supplements like niacin (nicotinic acid), niacinamide (nicotinamide), NR (nicotinamide riboside), and NMN (nicotinamide mononucleotide), are all aimed at increasing NAD levels in the body, bringing it back to a more youthful level.

All forms of B3 increase NAD levels when taken as supplements. (So do some other supplements, such as Pau D’Arco.) But one of the most affordable forms of B3, nicotinamide (also known as niacinamide and NAM) has the negative effect of inhibiting one of the key sirtuin genes, i.e., SIRT1. 

So you can’t just take more NAM and hope it will slow down the aging process. It will increase your NAD levels, but as it builds up in your cells it will start jamming up your sirtuins.

To fix this problem, researchers have isolated two forms of B3 which have been found to support SIRT1 activity, i.e., NR and NMN.

This is great in one sense. But it’s a problem in another because we need about a gram of B3 to get these benefits, and NAM costs a few cents for a 1 gram capsule. NR and NMN cost a few dollars for the same amount. And ultimately, NR and NMN are both converted into NAM. What if it was possible to take NAM without harming the sirtuins? 

According to some researchers, it could be. This study concluded that NAM only inhibits SIRT1 activity in vitro (in a petri dish), but can actually support it in living organisms.  From the abstract: 


“Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology.

“However, once administered to cells, NAM is rapidly converted to NAD+ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD+ increases.

“The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity. This possibility raises a concern on the validity of the interpretation of the results in the studies that use NAM as a SIRT1 inhibitor.”


If this study and some similar recent studies are correct, the antagonistic relationship between NAM and SIRT1 may be overblown. As long as NAM is being converted efficiently into NAD, taking it might be beneficial, not harmful to SIRT1 and other sirtuins. The problem appears to come in when NAM builds up in the cells and is not being converted fast enough into NAD. At that point, NAM interferes with SIRT1 and the other sirtuins.


The NAMPT salvage pathway


This suggests that while providing the building blocks for creating NAD is important, it’s just as important to support the NAMPT pathway, a key enzymatic reaction which prevents excess levels of NAM from building up in our cells. (We have lots of NAMPT when we’re young, but as we age, levels of NAMPT decline and NAM builds up in the cells.)

Several products have been shown to support the NAMPT pathway. This web page lists some key ones as:

  • niacinamide
  • niacin
  • vitamin B12
  • creatine
  • resveratrol
  • magnesium
  • grape seed extract

“… and eat your apigenin!”


Another key ingredient to consider supplementing with is apigenin, a natural compound which has remarkable medicinal qualities. It’s anti-carcinogenic; supports muscle growth; supports endurance; is protective against dementia; and prevents the build-up of an enzyme called CD38. This is important because CD38 destroys NAD in the body.

Apigenin is found in high levels in parsley, particularly organic dried parsley. A teaspoon of dried parsley has as much NAD as an entire cup full of fresh parsley leaves.

My own strategy for maintaining high NAD levels as I age is to do lots of fasting, take hot/cold showers (to trigger heat shock and cold shock), take NMN along with some resveratrol –– and to drink a juice fortified with dried parsley every morning. 

If the notion that NAM can support SIRT1 activity is correct, then those of us who are trying to stave off aging might be able to switch out the NMN for (smaller amounts of) NA and NAM and still get much the same benefit, while saving a few dollars a day, by keeping the NAMPT pathway operating efficiently. 


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