Niacinamide Inhibits Sirtuins. Reason To Not Take Niacinamide?

CoolTweetPete

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Search SIRT on this forum. There are a number of threads opposing the idea that SIRT expression extends life. Peat himself has offered opposition to this idea.

"In the last couple of years there has been a lot of "noise" in the media about how the SIRT-family of genes can extend lifespan when activated by things like exercise or, preferably, by certain chemical compounds like resveratrol (which putatively acts on SIRT-1). Ray Peat has stated his opinion that activating those genes is not likely to lead to life extension and may even be implicated in some cancers. In one is his articles he talks about how niacinamice/nicotinamide (vitamin B3) acts in a way approximately opposite to resveratrol. Also, there are independent studies that found niacinamide silences SIRT-1 and SIRT-2 in high doses. An interesting study came out recently that seems to corroborate Ray's views. It looks like it's niacinamide that actually extends life while resveratrol so far has been a bust (several clinical trials halted due to resveratrol increasing mortality in patients)."

https://raypeatforum.com/forums/threads/sirtuins-and-life-extension.2503/
 

haidut

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Nicotinamide (aka niacinamide) may be a potent promoter of aging. Please see #5 in the following article which also mentions other issues with niacinamide. http://www.anti-agingfirewalls.com/...ging-framework-for-health-and-life-extension/ http://www.anti-agingfirewalls.com/...ging-framework-for-health-and-life-extension/

I have been reading that site before I even knew about Peat. If you read the site extensively you will see that Bruce (its author) acknowledges raising NAD/NADH ratio is one of the most promising anti-aging approaches. And what is the most accessible way to do that? Niacinamide of course. And methylene blue. Either one alone is pretty good but combined they are magic:): Niacinamide protects from the oxidative stress methylene blue can cause if sugar is low in the cell.
 

haidut

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javin

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I've seen a few "niacinamide danger" posts lately.

Hopefully Haidut chimes in on this one as well to set it straight. :D I know he's a big fan of niacinamide.
 

Dasgeistes

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There are studies showing how Niacinamide is a Sirt1 activator in vivo like these:
Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.
Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells. - PubMed - NCBI

Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction.
Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction. - PubMed - NCBI
 

Kyle Bigman

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Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in ...https://www.ncbi.nlm.nih.gov/pubmed/28417163

"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."

Posted this on another thread but would like to get more opinions on this. I think it's important to know whether Ray Peat's advice to take low dosage niacinamide (50-100mg) 2-3x per day would in fact accelerate aging by activating SIRT1. Many people on the forum supplement with niacinamide.
 
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Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in ...https://www.ncbi.nlm.nih.gov/pubmed/28417163

"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."

Posted this on another thread but would like to get more opinions on this. I think it's important to know whether Ray Peat's advice to take low dosage niacinamide (50-100mg) 2-3x per day would in fact accelerate aging by activating SIRT1. Many people on the forum supplement with niacinamide.

Where is Dr. Peat telling people to take niacinamide?
 
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But Peat isn't telling people to take it. It is a possibility and if you do take it, 50mg to 100mg a few times a day is what he said. But it's not like a recommendation.
 

Kyle Bigman

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It would depend on how much of it converts into NAD. Lower doses niacinamide, up to maybe 500mg daily, probably end up mostly as NAD and thus may activate SIRT even though they would inhibit it in the first 4-6 hours after taking. However, higher doses of 750mg+ daily would have predominanly an effect on SIRT as niacinamide instead of NAD and thus likely inhibit it. This is what the study below found - inhibition of SIRT in vivo with HED of about 7.5mg/kg daily.
Long-term Treatment With Nicotinamide Induces Glucose Intolerance And Skeletal Muscle Lipotoxicity

Here is Haidut's response to the study. But this makes me question the low dosage discussed by Dr. Peat.
 

Kingpinguin

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Sirtuins are responsible for converting niacin to niacinamide. In mice where they blocked the effects of niacinamide over expression of sirtuins did not extend lifespan like previously. So the lifespan extension must be due to niacinamide likely by its conversion to NAD+. Reduced sirtuin activity from niacinamide makes sense as the body realizes it does not need to synthesize as much niacinamide from niacin when you supply it exogeniously. Taking nicotinamide is likely the best and safest anti aging supplement you can take. Combine it with sugar consumption and good protein with exercise and you got a strong organism.
 

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