by Nils Osmar. January 15, 2022
One question that comes up repeatedly in 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 ways to declining levels of a beneficial compound called NAD in the body which is involved in DNA repair and other important functions. When we’re young we have high levels of NAD. As we age our ability to produce and utilize NAD goes down. So many people are exploring ways of boosting their NAD as part of a pro-health, anti-aging strategy.
Ways of Increasing NAD
We can raise NAD in the body by taking vitamin B3 (niacin) or compounds derived from it. They’re precursors, meaning that they provide the raw materials the body uses to make NAD. The ones available as supplements available include:
- Niacin (NA) (nicotinic acid)
- Niacinamide (nicotinamide) (NAM)
- NR (nicotinamide riboside)
- NMN (nicotinamide mononucleotide)
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 or nicotinamide) has the negative effect of inhibiting one of the key sirtuin genes, i.e., SIRT1.
So, according to Dr. David 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. The sirtuins are involved with DNA repair and other essential cellular processes that protect us against some of the problems associated with aging, and are NAD+-dependent to be effective.
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 NAM?
One reason is the cost:
- NR and NMN are a little pricey, running around $1.20 per gram. (However, you do have to shop around to get this price; I’ve seen them on sale for over $12 a gram!) (The kind I buy is the 100 gram bag of NMN powder from DoNotAge.) (ProHealth and Alive by Science are also reputable brands.)
- By comparison, 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) (The time release form of niacin doesn’t cause flushing, but is associated, in large doses, with liver damage.)
- Niacinamide (NAM) 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, it’s the form that 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.
This suggests that 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 article lists some key ones as:
- Vitamin B12
- Grape seed extract
Don’t Forget 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, There is a smaller amount in celery.
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 hot baths and saunas
- take NMN along with resveratrol in the mornings
- take immediate-release niacin in the afternoons (some days) along with chromium