Niacin, Niacinamide And Methylation

Lucenzo01

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May 17, 2016
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I found this on another forum that can be interesting for various forum members having problems with niacin / niacinamide. I hope it helps:
Yes I have read Lynch's claims about methyl sponges, along with those that proliferate on the internet offering advice about methylation.

I simply say what is the mechanism?

It is niacinamide that is cleared by methylation via the enzyme NNMT.

If you look at sites detailing niacin and niacinamide metabolism, there is no enzyme listed that methylates niacin.

See for example the entry in KEGG pathways. If you look in the top left hand section you will see niacinamide being converted to N-methyl nicotinamide via the enzyme NNMT, as I described above.

If you look immediately below niacinamide, you will see nicotinate (aka niacin). It is taken in several directions as part of different metabolic pathways and only one which is terminal or a clearance reaction. This is the conversion to nicotinurate.

I didn't canvas this in my previous post because I didn't want to overcomplicate things. This clearance reaction involves the addition of glycine - ie one of the phase II detox pathways which occur predominantly in the liver and which help the body excrete excess or unwanted metabolic products or exogenous substances.

So excess niacin is glycinated, excess niacinamide is methylated.

So I repeat, if Lynch and others claim that niacin is methylated, how does it happen?

I have no doubt the Lynch is knowledgeable about many things and has been helpful to at least some patients, but on this issue he is wrong.

Here is the thread if you want to read more: Does methyl-absorbing niacin neutralise methyl supplements?
 
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danishispsychic

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i have methylations issues= and when i take niacin on its own its meh... but when i drink my trusty yellow red bull that has b vitamins and taurine as well as niacin- it really does give me wings. no lie.
 
J

jb116

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i have methylations issues= and when i take niacin on its own its meh... but when i drink my trusty yellow red bull that has b vitamins and taurine as well as niacin- it really does give me wings. no lie.
I believe it, because that's how you get from LA to NYC :D
 
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danishispsychic

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actually even my frequent flyer miles have miles. #jetblue #united
 

Runenight201

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Feb 18, 2018
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1,942
After reading up on Niacin and niacinamide, I'm having trouble determining how they exactly differ in the physiological effects. They differ by only one step, as detailed here: KEGG PATHWAY: Nicotinate and nicotinamide metabolism - Reference pathway.

It seems that supplementation of niacinamide should result in either the conversion into niacin or the methylation and subsequent clearance correct? However, only Niacin is associated with the flush, while niacinamide is not. The proposed mechanism can be found on this graphic

upload_2018-10-16_17-27-22.png


It seems that COX-1 and Prostaglandins D2/E2 are necessary for the flush to occur, which is why Aspirin is effective for limiting the flush response from niacin. It would also make sense that eating a diet that supports the reduction of the Prostaglandin E2, by reducing the PUFAs, would also limit the flush response of Niacin. I think I recall reading somewhere that those who are more in need of Niacin are more susceptible to the flush, and this would also make sense, as unhealthier people are going to have higher levels of Prostaglandins in the blood (correct me if I'm wrong here).

So why would niacinamide not cause flush while niacin does, if the pathway only differs by a single enzyme reaction? Could it be that niacinamide can take either two paths, one cleared via methylation and the enzyme NNMT that @Lucenzo01 alluded to, or be converted to niacin. Perhaps the body decreases the amount of niacinamide converted to niacin based on the amount of nicotinamidase enzyme which is needed to facilitate the conversion?

Maybe this is why Peat recommends niacinamide as opposed to niacin, as this two step fork provides a built in safety mechanism to prevent inappropriate amounts of niacin to be exacting its effects.

I've read that only niacin is effective in the beneficial effects of cholesterol while niacinamide was not, but I'm not sure why that would be the case if the only difference between the two is a single step reaction. Perhaps given a chance to either be cleared via methylation or converted into niacin, the majority of it gets cleared, and subsequently not enough is present to effect cholesterol in any meaningful way.

Any input appreciated.
 

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