Nicotinamide: Cause Of The Causes Of Disease Transitions, Health Divides, And Health Futures?

[LeeLemonoil]

Meat Intake and the Dose of Vitamin B3 – Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?



We will argue that nobody ever systematically checked that pellagra was eliminated globally (dietary supplementation mainly happened in rich countries). Pellagra may be common and misdiagnosed masquerading as ‘environmental enteropathy’, poor cognition, eczema, or general ill health and a lack of well-being or poor homeostasis when under environmental stress with shortened lives.38,39

We also argue that environmental insults from trauma, hypoxia, toxins, stress, or mutations (such as in mitochondrial or DNA-repair genes) may require either lifetime or temporary higher doses than normally recommended (15 mg/d).

Controversially, we suggest that many people in rich countries may be on too high a dose. A hyper-vitaminosis B3 state may be common and, like pellagra, have a wide phenotype that includes the metabolic syndrome, several cancers, and some degenerative or neuro-behavioural disorders.40

Furthermore, we propose that the transition from diseases of poverty to diseases of affluence is due to switching the dose of meat/nicotinamide too fast and too far.41,42 The most recent version of the ‘hygiene hypothesis’ concentrates on reductions in symbiotic/commensal biome diversity acquired early in development, not cleanliness during childhood and common pathogens.43–46 We will discuss how a biochemical switch away from the need to produce nicotinamide ‘in house’ from tryptophan, and the related reduced metabolic need for gut symbionts or tuberculosis (TB) on a better diet so that they are no longer ‘welcomed’ by the immune system is a more plausible explanation for the loss of microbial ‘old friends’. This switch of microbiomes reduces tolerogenic instruction to the immune system further encouraging it to over-react to otherwise irrelevant foreign proteins or self-proteins.47

 

[Wagner83]

They mention 15 mg/day as a dose to treat pellagra but do not mention other doses yet acknowledge certain cases warrant more.

"
Question 4: over and above a rash of immune diseases has the dose of nicotinamide become so high that there is an unrecognised hyper-vitaminosis B3 syndrome?
Nicotinamide is widely viewed as having little serious toxicity at least in the short term.317,318 We suggested nicotinamide toxicity as a causative factor for the Parkinson’s disease, the metabolic syndrome, and some cancers based on direct or indirect measure of high levels of NNMT.53,83,319–333 Too low a dose and nicotinamide can be protective for cancers and Parkinson’s, so we are proposing a double-edged dosage effect.333 As an inducible enzyme, a logical culprit for NNMT overexpression is the dose of nicotinamide – even if other factors such as caloric restriction, stress, and exercise play their part.334,335 Background genetic variation in levels may reflect exposure in earlier generations – certainly, this is true of species as the enzyme is not expressed in herbivores.336 Our original hypothesis for PD was that N-methylnicotinamide resembled the dopaminergic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and so may be toxic at high levels even though beneficial at lower levels. Part of the jigsaw may be that the nicotinamide dose upsets the microbiome that in turn contributes to the proteotoxicity and affects the nicotinic acid receptor.337 Other metabolites may be nephrotoxic.338

Several other plausible mechanisms for nicotinamide toxicity exist whether from excessive inhibition of NAD consumers such as SIRTs or PARPs or consumption of valuable methyl groups depleting the methylome and the epigenome (Figure 30). Recent evidence shows that nicotinamide promotes adipogenesis probably via SIRT inhibition and adipogenic proteins (eg, peroxisome proliferator–activated receptor gamma and FABP4 [fatty acid–binding protein 4]) and is associated with neonatal adiposity – with surprisingly little need for excessive calories or fats.339–342
"
@haidut

 

[haidut]

They mention 15 mg/day as a dose to treat pellagra but do not mention other doses yet acknowledge certain cases warrant more.

"
Question 4: over and above a rash of immune diseases has the dose of nicotinamide become so high that there is an unrecognised hyper-vitaminosis B3 syndrome?
Nicotinamide is widely viewed as having little serious toxicity at least in the short term.317,318 We suggested nicotinamide toxicity as a causative factor for the Parkinson’s disease, the metabolic syndrome, and some cancers based on direct or indirect measure of high levels of NNMT.53,83,319–333 Too low a dose and nicotinamide can be protective for cancers and Parkinson’s, so we are proposing a double-edged dosage effect.333 As an inducible enzyme, a logical culprit for NNMT overexpression is the dose of nicotinamide – even if other factors such as caloric restriction, stress, and exercise play their part.334,335 Background genetic variation in levels may reflect exposure in earlier generations – certainly, this is true of species as the enzyme is not expressed in herbivores.336 Our original hypothesis for PD was that N-methylnicotinamide resembled the dopaminergic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and so may be toxic at high levels even though beneficial at lower levels. Part of the jigsaw may be that the nicotinamide dose upsets the microbiome that in turn contributes to the proteotoxicity and affects the nicotinic acid receptor.337 Other metabolites may be nephrotoxic.338

Several other plausible mechanisms for nicotinamide toxicity exist whether from excessive inhibition of NAD consumers such as SIRTs or PARPs or consumption of valuable methyl groups depleting the methylome and the epigenome (Figure 30). Recent evidence shows that nicotinamide promotes adipogenesis probably via SIRT inhibition and adipogenic proteins (eg, peroxisome proliferator–activated receptor gamma and FABP4 [fatty acid–binding protein 4]) and is associated with neonatal adiposity – with surprisingly little need for excessive calories or fats.339–342
"
@haidut

Given that nicotinamide is the prime precursor of NAD and that it inhibits lipolysis I do not see how it can be a cause of metabolic syndrome or cancer. I even posted a few direct interventional studies where niacinamide can treat advanced liver and even pancreatic cancer. That does not mean one should take as much as one can handle, but I am not aware of any direct study which has showed carcinogenicity or diabetogenicity of B3.

 

[Terma]

I guess the tryptophan disposal from low B3 diet makes sense. Paul Jaminet argued against supplementing B3 and will eat up that article, if he still cares. From the chronic infections angle, with tryptophan.

I never supplement niacinamide more than once a day and not every day. I still use it, just avoid constant exposure. In a sense I see their points.

I happened to see this one not long ago, which your article has as a reference: https://www.nature.com/nature/journal/v508/n7495/full/nature13198.html [Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity] seems if you knockdown NNMT you get higher levels of NAD+ (and SAM) and more oxygen uptake, though I assume from fat oxidation mostly. And according to them prevent obesity and diabetes [based on their mouse experiment]. They say polyamine flux has major role in metabolism, but Ray Peat looks down on them in one his articles; don't know much about it under that name.

 

[Wagner83]

Given that nicotinamide is the prime precursor of NAD and that it inhibits lipolysis I do not see how it can be a cause of metabolic syndrome or cancer. I even posted a few direct interventional studies where niacinamide can treat advanced liver and even pancreatic cancer. That does not mean one should take as much as one can handle, but I am not aware of any direct study which has showed carcinogenicity or diabetogenicity of B3.

In one of the generative energy podcast you said the only supplement you were using daily was niacinamide, but recently I've seen you mention methylene blue, not niacinamide. What was the reason you quit using the niacinamide daily? I felt better on it but experienced sleep issues and (I think) more body fat.
Is there an upper limit under which you think it is safe when taken daily?

 

[haidut]

In one of the generative energy podcast you said the only supplement you were using daily was niacinamide, but recently I've seen you mention methylene blue, not niacinamide. What was the reason you quit using the niacinamide daily? I felt better on it but experienced sleep issues and (I think) more body fat.
Is there an upper limit under which you think it is safe when taken daily?

Both niacinamide and methylene blue can replenish NAD stores. I used to take niacinamide to address liver issues, endotoxin and excessive lipolysis but I found I don't need to take it daily any more as things improved. As far as NAD, MB achieves the same in smaller doses, and I use niacinamide only if I have been under a lot of stress and feel like FFA are getting high and glycogen low - i.e. chills, fatigue and slowed thinking. Niacinamide may have antiinflammatory effects in higher doses that MB does not. Same with skin - niacinamide has benefits for the skin that I don't think MB has.

 

[sladerunner69]

Both niacinamide and methylene blue can replenish NAD stores. I used to take niacinamide to address liver issues, endotoxin and excessive lipolysis but I found I don't need to take it daily any more as things improved. As far as NAD, MB achieves the same in smaller doses, and I use niacinamide only if I have been under a lot of stress and feel like FFA are getting high and glycogen low - i.e. chills, fatigue and slowed thinking. Niacinamide may have antiinflammatory effects in higher doses that MB does not. Same with skin - niacinamide has benefits for the skin that I don't think MB has.

Do you know of any mechanism (or just anecdotal reports) where niacinimide in higher doses decreased dopamine? 500mg I usually handle fine and is calming, but taking 1-2grams through the day I believe has a sedative effect and maybe is lowerring dopamine as well as serotonin. I'm not exactly sure what could be happening exactly. Could just be an intense suppression of stress hormones. I have ehard other people report that niacinimide/aspirin stalled their fatloss programs, perhaps because they are blocking lipolysis? You mentionned niacinimide has the ability to help excrete fats through the liver though, in a generative energy.

 

[haidut]

Do you know of any mechanism (or just anecdotal reports) where niacinimide in higher doses decreased dopamine? 500mg I usually handle fine and is calming, but taking 1-2grams through the day I believe has a sedative effect and maybe is lowerring dopamine as well as serotonin. I'm not exactly sure what could be happening exactly. Could just be an intense suppression of stress hormones. I have ehard other people report that niacinimide/aspirin stalled their fatloss programs, perhaps because they are blocking lipolysis? You mentionned niacinimide has the ability to help excrete fats through the liver though, in a generative energy.

Niacinamide is a GABAa (not a typo) agonist and in higher doses acts like a benzodazepine. So that would explain some of the sedation. I posted a few threads about this on the forum. Search for "niacinamide xanax".

 

[sladerunner69]

Niacinamide is a GABAa (not a typo) agonist and in higher doses acts like a benzodazepine. So that would explain some of the sedation. I posted a few threads about this on the forum. Search for "niacinamide xanax".

Great thanks! I'll look into it.

What about the fatloss though? Have you ever encounterred bodyfat build up with it?

 

[haidut]

Great thanks! I'll look into it.

What about the fatloss though? Have you ever encounterred bodyfat build up with it?

No fat build up, but slower fat loss at higher doses.