This article is intended solely for informational purposes. It is not meant to be taken as, and should not be construed, as medical advice. Any changes to your lifestyle or diet should be done in consultation with your doctor or health care professional.

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, our ability to produce and utilize NAD goes down.

This leaves us more vulnerable to the downside of the aging process ––– and also, according to some evidence, makes us more susceptible to viral infections such as COVID-19. (Harvard University’s Dr. David Sinclair mentioned this association in a recent interview.)  So many people are exploring ways of boosting their NAD as part of a pro-health, anti-aging strategy.

Several forms of vitamin B3, including –––

  1. niacin (NA) (nicotinic acid)
  2. niacinamide (nicotinamide) (NAM)
  3. NR (nicotinamide riboside)
  4. and NMN (nicotinamide mononucleotide)

––– are all aimed at increasing NAD levels in the body, bringing it back to a more youthful level.  (Some other supplements, such as Pau D’Arco, also raise NAD, but by a different mechanism.  B3 in all of its forms works by providing the raw materials which the body then turns into NAD.)

Do these forms of B3 all work? It appears so. All four appear to increase NAD levels when taken as supplements.

But the NAM form (niacinamide, aka nicotinamide) unfortunately has the negative effect of inhibiting one of the key sirtuin genes, i.e., SIRT1. 

So  –– according to Dr. Sinclair –– you can’t just take more NAM and assume that it will slow down the aging process. It will definitely increase your NAD levels, but as it builds up in your cells it may also start actively inhibiting SIRT1 activities –– the opposite of what we want, since the sirtuins are involved with DNA repair and other essential cellular processes that protect us against some of the problems associated with aging.

The other forms of B3 (NR, NMN and niacin) all appear to support SIRT1 activity, not shut it down.

So why do some people still taken NMN? One reason is the cost:

  • NR and NMN are expensive, running over $3 per gram.
  • Niacin is cheap – just a few cents a gram. And it has many benefits the other forms of B3 don’t, such as lowering triglycerides and raising HDL cholesterol.  But it can trigger a flush (caused by blood vessel dilation) which many people dislike. (If you don’t mind the flush, it’s an excellent choice, in my opinion)
  • Niacinamide is also cheap, and does not cause a flush. But it does not lower triglycerides or raise HDL levels. And –– most importantly from an anti-aging perspective –– niacinamide appears to shut down the sirtuin genes.

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 is correct, it could make sense to take NAM for anti-aging. But 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 essentially clogs up the cellular machinery, interfering with SIRT1 and the other sirtuins. Taking NAM may not directly shut down SIRT1, but if it builds up in the body, the SIRT1 gene can shut down.

This is the great advantage of both NR and NMN: they don’t result in a build-up of NAM, so don’t shut down the sirtuin genes.

The NAMPT salvage pathway

The possibility of excess NAM shutting down the sirtuins 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:

  • 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 ice baths (just for cold shock)
  • do HIIT exercise
  • take saunas
  • take NMN along with resveratrol in the mornings
  • take niacin at night along with chromium
  • and to drink a very low-carb juice fortified with dried parsley every morning. 

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