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Optimal Dose Of Niacinamide For Stimulating Respiration

haidut

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As many of you know, the Wikipedia page has a warning not to take more than 3g daily as it may elevate liver enzymes. I traced the warning to a few studies with high dose niacinamide using 4g - 6g daily for conditions like HIV and arthritis. However, they did not provide an explanation on why the effect was observed. I kept digging and found a few older references about niacinamide inhibiting respiration in the liver. These studies themselves pointed to a 1951 study which finally provided the answer. It was an in vitro study but it matches the results from other studies so I doubt it is a coincidence.
The 1951 study below shows that using a concentration of 0.5 mM/L niacinamide / nicotinamide or higher inhibited respiration in the liver (see attached image). That concentration of 0.5 mM/L just happens to be achievable in humans by a single dose of 3g niacinamide. Doses lower than that actually stimulated respiration, so niacinamide can have quite a beneficial effect on metabolism when used in the appropriate doses.

INHIBITION OF DIPHOSPHOPYRIDINE NUCLEOTIDE-REQUIRING ENZYMES BY NICOTINAMIDE

"...The presence of 0.5 mM of nicotinamide produced considerable inhibition which was reversed by supplements of DPN. Thus it appeared that nicotinamide at the level tested caused DPN to be rate limiting in the respiration scheme. When at a fixed level of DPN the amount of nicotinamide added was varied from 0 to 10V3 mole, the results presented in Fig. 2 were obtained. It will be noted that the highest level of nicotinamide tested caused considerable inhibition. However, at the low levels some stimulation occurred. This stimulatory effect is compatible with previous observations (2) and is probably due to protection of the DPN from destruction by the DPN nucleosidase. At an intermediary level of nicotinamide the oxygen uptake was almost identical to that with no nicotinamide. At this concentration of nicotinamide a balance between its stimulator-y effect (due to nucleosidase inhibition) and its inhibitory effect was obtained. At higher levels of nicotinamide its inhibitory activities exceeded its stimulatory action and resulted in a net decrease in respiratory rate."
 

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charlie

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Been watching these niacinamide threads with much interest. Thank you for your great work @haidut! :hattip
 

Tarmander

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Awesome find. I almost always run up against a paywall when doing this kind of digging. Thank you for persisting!

I have experimented with a wide range of doses on Niacinamide, and the lower doses being the most effective long term is consistent with my experience. I always loved taking the big bomb of Niacinamide and getting that relaxing, horney, rush for about a day. But the blow-back was negative.
 

NathanK

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I have experimented with a wide range of doses on Niacinamide, and the lower doses being the most effective long term is consistent with my experience.
Dr. Peat would concur.

Ive never felt this mythical sedating feeling others have from taking niacinamide. The one time i tried taking 500mg 3x/day i started getting weird floatie feelings in my head a week or so later.

That was when i read a paper or post that some people (typically prone to parkinsons) cannot break down high doses efficiently in the brain due to a lack of a cofactor (which i forget-ACh maybe) and can cause toxicity. It taught me that 50-150mg/day is more than suitable.
 

whit

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I've always wondered about this one. Niacin has been my go to for years but there were some apprehensions.
Thank you for posting this Haidut it really brings clairity.
Is there a certain brand/source that is preferred?
 

Elephanto

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@haidut

So what's the dose required to achieve optimal stimulation ? Which seems to be around 0.25 mM on the graph.

Also I'd like to know what bodyweight are you using as reference when stating dosage in all studies you post, 60kg ?
 

Drareg

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Dr. Peat would concur.

Ive never felt this mythical sedating feeling others have from taking niacinamide. The one time i tried taking 500mg 3x/day i started getting weird floatie feelings in my head a week or so later.

That was when i read a paper or post that some people (typically prone to parkinsons) cannot break down high doses efficiently in the brain due to a lack of a cofactor (which i forget-ACh maybe) and can cause toxicity. It taught me that 50-150mg/day is more than suitable.

Do you have this paper? Would be interesting to know the cofactor in question.
 

haidut

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@haidut

So what's the dose required to achieve optimal stimulation ? Which seems to be around 0.25 mM on the graph.

Also I'd like to know what bodyweight are you using as reference when stating dosage in all studies you post, 60kg ?

I don't know about optimal, but the cutoff was 0.5mM, which is achievable with 3g niacinamide in humans. Google it - 6g-7g niacinamide are routinely used clinically to reach 1mM concnetrations needed to reduce tumor hypoxia. Not sure about the average weight of the patients but I get they weighed more than 60kg each.
 

DaveFoster

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I don't know about optimal, but the cutoff was 0.5mM, which is achievable with 3g niacinamide in humans. Google it - 6g-7g niacinamide are routinely used clinically to reach 1mM concnetrations needed to reduce tumor hypoxia. Not sure about the average weight of the patients but I get they weighed more than 60kg each.
So given a plasma half-life of 4-5 hours, assuming topical dosing to bypass the liver, do you think 2.5 grams of niacinamide in the morning followed by 1 gram every four hours (which would fall in the 6 gram range you mentioned) should be a ceiling dosage for conditions like generalized anxiety, excessive adrenaline, Cushing's, and the like?
 
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haidut

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So given a plasma half-life of 4-5 hours, assuming topical dosing to bypass the liver, do you think 2.5 grams of niacinamide in the morning followed by 1 gram every four hours (which would fall in the 6 gram range you mentioned) should be a ceiling dosage for conditions like generalized anxiety, excessive adrenaline, Cushing's, and the like?

I think 1.5g - 2g daily should be plenty for everybody. The HIV studies used 2g and 3g and did not find benefit of 3g over the 2g dose.
 

Marg

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Haidut,

Does that 2g dosage apply to cancer patients as well, or do you think that they have to go higher with their dosages?
 

haidut

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Haidut,

Does that 2g dosage apply to cancer patients as well, or do you think that they have to go higher with their dosages?

The studies I posted recently on inhibiting fat metabolism being therapeutic for cancer used the HED of 1.5g - 3g daily. So, given the NAEL of 3g daily for liver enzymes I'd say starting with 1g twice a day and up to 1g x 3 daily should be enough especially if combined with aspirin. If combined with aspirin, which also inhibits lipolysis and fat metabolism/oxidation, probably as "little" as 1g niacinamide would do.
 

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