NAD+hi all

walkersimonis
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hi all

Post by walkersimonis » Tue Jul 28, 2020 1:18 am

It is the general belief that nicotinamide inhibits sirt1. However the authors of this paper argue that while NAM 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."

It seems the sensible thing would be to aim for a body concentration of 5mM. Now how does 5mM NAM invitro convert to an appropriate dosage per kg of bodyweight?


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jocko6889
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Re: hi all

Post by jocko6889 » Wed Jul 29, 2020 4:09 pm

walkersimonis wrote:
Tue Jul 28, 2020 1:18 am
It is the general belief that nicotinamide inhibits sirt1. However the authors of this paper argue that while NAM 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."

It seems the sensible thing would be to aim for a body concentration of 5mM. Now how does 5mM NAM invitro convert to an appropriate dosage per kg of bodyweight?
I think some NAM at smaller doses probably does activate Sirt1, but the problem when you get older is that the salvage pathway needed to upconvert NAM to NAD+ begins to break down because of the NAMPT bottleneck. NAMPT is the enzyme needed for conversion of NAM to higher forms and we produce less of this enzyme as we age. This is why higher forms like NMN that don't require NAMPT work so much better. No upconversion is needed.
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ALIVEBYNATURE
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Re: hi all

Post by ALIVEBYNATURE » Wed Jul 29, 2020 6:39 pm

If you are low in NAM, it might be useful to take some.

But the body does not like excessive levels of NAM, and will methylate it to MeNAM, which is then excreted in urine.

Adding more NAM just increases demand for methyl groups.

Everyone here knows that as we age, NAD+ levels decrease dramatically.

Also, NAM levels increase! Older people have too much NAM already.

So it seems likely to be counterproductive to take NAM for most people.
Drdavid
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Re: hi all

Post by Drdavid » Wed Jul 29, 2020 7:01 pm

ALIVEBYNATURE wrote:
Wed Jul 29, 2020 6:39 pm
If you are low in NAM, it might be useful to take some.

But the body does not like excessive levels of NAM, and will methylate it to MeNAM, which is then excreted in urine.

Adding more NAM just increases demand for methyl groups.

Everyone here knows that as we age, NAD+ levels decrease dramatically.

Also, NAM levels increase! Older people have too much NAM already.

So it seems likely to be counterproductive to take NAM for most people.
Great point!
canadahealthy
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Joined: Tue Aug 20, 2019 5:31 pm

Re: hi all

Post by canadahealthy » Sat Aug 01, 2020 7:19 pm

ALIVEBYNATURE wrote:
Wed Jul 29, 2020 6:39 pm
If you are low in NAM, it might be useful to take some.

But the body does not like excessive levels of NAM, and will methylate it to MeNAM, which is then excreted in urine.

Adding more NAM just increases demand for methyl groups.

Everyone here knows that as we age, NAD+ levels decrease dramatically.

Also, NAM levels increase! Older people have too much NAM already.

So it seems likely to be counterproductive to take NAM for most people.
This is an important clarification, between NAM and NAD+/NMN.
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