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Niacinamide and Sirt1

niacinamide nicotinamide sirt1

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#1 p75213

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Posted 10 June 2020 - 12:27 PM


Does NAM inhibit Sirt1? This paper argues that while it is an inhibitor invitro this imay not be the case invivo.

 

"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."

 

"To understand better the effects of cellular administration of NAM, we reviewed published literature in which treatment with NAM was used to inhibit SIRT1 and found that the expected inhibitory effect of NAM was either unreliable or muted in many cases. In addition, studies demonstrated NAM administration stimulates SIRT1 activity and improves the functions of cells and organs."

 

https://pubmed.ncbi....xt=Nicotinamide is an inhibitor of SIRT1 in vitro%2C but,be a stimulator in cells.&text=Since the finding that NAM,role in certain cell physiology.

 

 

This paper says that while it is a sirt1 inhibitor at larger concentrations at 5mM it is an activator.

 

"In the cells pulsed with 5 mM NAM, cellular NAD+ concentration increased by close to 40% in 12 h, and this increase was maintained throughout the 21 days of the investigation."


"NAM at 5 mM but Not at Higher Concentrations Causes the Activation of SIRT1 and the Decrease of Mitochondrial Content"


"NAM at a 10 or 20 mM dose caused an increase of [NAD+] to the levels almost identical to that in the cells treated with 5 mM NAM but resulted in an inhibition of SIRT1 activity during the early time period."

 

https://www.ncbi.nlm...les/PMC5471864/

 

It seems the sensible thing would be to aim for a concentration of 5mM.

How does 5mM NAM invtro convert to an appropriate dosage per kg of bodyweight?

 

 

 

 

 


Edited by p75213, 10 June 2020 - 12:28 PM.

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#2 warner

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Posted 14 June 2020 - 01:54 PM

From my research on this topic several years ago, I concluded that 500 mg NAM would result in a peak plasma concentration of just 10 ug/ml after about 30 minutes, which is just 100 uM or 0.1 mM, meaning that, for example, a typical dose of 1000 mg (1g) per day of NAM for skin cancer prevention, taken as 2 x 500 mg NAM about 12 hours apart (half-life = 1 hour), is unlikely to inhibit SIRT activation for any significant time, and, as noted in previous post, likely results in higher NAD+ and greater SIRT activation.


Edited by warner, 14 June 2020 - 02:04 PM.

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#3 p75213

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Posted 15 June 2020 - 04:09 AM

That being the case I'll start to iincrease my dose from 500mg per day to around 800mg. Maybe include 100 - 200 mg of nicotinic acid..


Edited by p75213, 15 June 2020 - 04:57 AM.





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