Walsh's hypothesis and the NAD recipe revisited

[nandixon]

Yes, I guess the only problem with nicotinic acid is the flush. It's certainly cheaper than NR. I have read somewhere that oral NR is cleaved to niacinamide in the intestines anyway. It's hard to get a clear picture.

Yes, I get an uncomfortable flush from "niacin" (nicotinic acid) even at just 25mg. No noticeable beneficial effect at that dose.

Niacinamide, on the other hand, is very slightly energizing (mostly mentally) at 125mg. But it causes additional tiredness at higher doses. (I used to use 500mg at night to help with sleep a few years ago.)

 

[adreno]

500mg Niacinamide gives me problems after a few days. 250mg is tolerable, but 125mg might be even better.

I will probably try the suggestion from the longecity thread above, i.e. resveratrol to kickstart NAMPT, followed by B3 a few hours later to boost NAD.

 

[Kimsie]

Well, sirt activity uses up NAD, so I agree with @nandixon that it must be the latter.

What I meant was "Is the lowered sirt1 causing lower NAD indirectly by activating or deactivating pathways that lead to lower NAD?" In other words does this create a vicious cycle in some people?

It's confusing because although sirt1 silences expression, sometimes it silences something that is silencing something else and so it activates the something else indirectly.

 

[nandixon]

I didn't see anything suggesting that low SIRT1 could lead to low NAD+, so my guess is that it doesn't seem there's a (known) loop.

There are factors (like, e.g., microRNA's) that can can lower both SIRT1 and NAD+ at the same time, but the two lowerings are independent of one another.

 

[nandixon]

@Kimsie
I don't know if this is of any interest to you, but while looking for a potential vicious cycle/loop situation I noticed a couple of 2009 articles that describe how SIRT1, together with CLOCK (one of my worst genes), binds to the NAMPT promoter region for circadian rhythm purposes.

If SIRT1 was acting as a promoter of NAMPT expression in the following diagram then that might seemingly lead to a potential vicious cycle. But it acts as a suppressor, so it wouldn't:

[Fig.4]C) Scheme of the transcription-enzymatic interplay by which the circadian machinery governs the intracellular levels of NAD+. The NAD+-dependent deacetylase SIRT1 is thereby controlling the oscillatory synthesis of its own coenzyme.

Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1
(Full text available here.)

Also see the closely related article:
Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis

 

[Gondwanaland]

together with CLOCK (one of my worst genes)

Would you like to add to the CLOCK gene thread? I see there is a lot of "disagreement" between my husband's SNPs and mine and I would like to learn more about it.

 

[adreno]

This is from the Journal of Orthomolecular Medicine (and so must be taken with a grain of salt), but it states that the niacin flush is indicative of (dependent upon) NAD status. If this is correct, it would mean that my NAD levels are okay, as I do have a severe flush reaction. Do your son flush when taking niacin, @Kimsie ?

A reduced niacin-mediated flush is increasingly accepted today as a positive diagnostic indicator for schizophrenia. Schizophrenics that were successfully treated with high dose niacin (nicotinic acid) therapy by Dr. Abram Hoffer in the 1950s recovered from their otherwise previously reduced flush response simultaneous with recovery from schizophrenia. Significantly, some schizophrenics also recovered after high dose nicotinamide treatment, a different nicotinamide adenine dinucleotide (NAD) precursor that does not cause a flush response. Whether the niacin-flush response is first due to replenishment of NAD deficiency or due to a restoration of polyunsaturated fatty acid levels thus restoring niacin-flush competence is not mutually exclusive.

It is possible that nicotinic acid is first dedicated to intracellular NAD synthesis at the expense of the flush response until the schizophrenic's immediate needs for NAD are finally met. Then the nicotinic acid, rather than entering the cell through transporters, instead becomes available to bind GPR109a, on the surface of the cell thus mediating the flush pathway. Moreover the restored NAD levels may also revive the biosynthetic pathway required for generation of the known niacin-flush vasodilatory molecules PGD2, PGE2, PGI2, and thromboxane A2.

http://connection.ebscohost.com/c/a...-arginine-glutamine-may-provide-added-benefit

 

[Kimsie]

@Kimsie
I don't know if this is of any interest to you, but while looking for a potential vicious cycle/loop situation I noticed a couple of 2009 articles that describe how SIRT1, together with CLOCK (one of my worst genes), binds to the NAMPT promoter region for circadian rhythm purposes.

If SIRT1 was acting as a promoter of NAMPT expression in the following diagram then that might seemingly lead to a potential vicious cycle. But it acts as a suppressor, so it wouldn't:

View attachment 9813

Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1
(Full text available here.)

Also see the closely related article:
Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis

Thanks! That's a very interesting article.

 

[Kimsie]

This is from the Journal of Orthomolecular Medicine (and so must be taken with a grain of salt), but it states that the niacin flush is indicative of (dependent upon) NAD status. If this is correct, it would mean that my NAD levels are okay, as I do have a severe flush reaction. Do your son flush when taking niacin, @Kimsie ?


http://connection.ebscohost.com/c/a...-arginine-glutamine-may-provide-added-benefit

I don't know of anyone who doesn't flush when taking niacin, except for people who take at least 1 gram 3 times a day or more.

It's just a question of how much niacin it takes to flush. Sometimes the flush comes at a much higher dose than at other times. Our experience is that if the person is having a reaction to something, such as a food reaction, it takes a lot more niacin to flush than when they are not. I assume that this is due to the role that NAD+ has in getting rid of the acetaldehyde product in the pathway to get rid of histamine. So I guess that the flush is dependent on NAD+ status in a sense.