5 replies to this topic

[Phoebus]

seems Nicotinamide supplementation oxidizes betaine in the liver. Thus perhaps we should all be supplementing with betaine and/or SAM-e

 

what do you think? 

 

 

 

Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy

 

Abstract

High-dose niacin has versatile and substantial efficacy for the treatment of hyperlipidemias, but its utility is compromised by various side effects, the most serious of which is liver damage. It is proposed that this hepatotoxicity reflects the high demand for methyl groups imposed by niacin catabolism, leading to a reduction in hepatic levels of S-adenosylmethionine (SAM). Depletion of the hepatic SAM pool has likewise been shown to mediate, at least in part, the hepatotoxic effects of ethanol, methotrexate, and niacinamide. If niacin does indeed decrease SAM, a likely consequence would be a counterproductive elevation of plasma homocysteine.

https://www.scienced...306987799910113

 

and here 

 

 

 

The nicotinamide-treated rats had higher hepatic and renal levels of 8-hydroxy-2'-deoxyguanosine, a marker of DNA damage, and impaired glucose tolerance and insulin sensitivity when compared with the control rats. Nicotinamide supplementation increased the plasma levels of nicotinamide, N1-methylnicotinamide and choline and decreased the levels of betaine, which is associated with a decrease in global hepatic DNA methylation and uracil content in DNA. Nicotinamide had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions (nicotinamide N-methyltransferase and DNA methyltransferase 1), for homocysteine metabolism (betaine-homocysteine S-methyltransferase, methionine synthase and cystathionine β-synthase) and for oxidative defence (catalase and tumour protein p53). It is concluded that nicotinamide-induced oxidative tissue injury, insulin resistance and disturbed methyl metabolism can lead to epigenetic changes. The present study suggests that long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities.

https://www.ncbi.nlm...pubmed/23768418

Edited by Phoebus, 07 June 2018 - 02:31 PM.

[Oakman]

What does 'High Dose Niacin" mean?  Generally in the 1-15 gram range according to a review of studies for hyperlipidemia. Although Niacin has this side effect, does NR/NMN have the same effect or not is the question. At least in the studies I've seen (up to 1 gram as I remember for NR), that side effect was not mentioned. Interesting point though and something to watch for.

 

"Hepatotoxicity

Niacin in doses above 500 mg daily causes transient, asymptomatic elevations in serum aminotransferase levels in up to 20% of people.  The elevations are rarely greater than 3 times the upper limit of the normal range and usually resolve spontaneously even with continuation of the drug.  The effect is partially dose related and is more common with doses above 3 g/day.  In some patients, there is an overall decrease in serum proteins synthesized by the liver and, in some instances, coagulopathy with an increase in prothrombin time and decline in serum albumin, coagulation factors and apolipoproteins.  These changes resolve rapidly upon stopping therapy and may not recur with lower doses."

Edited by Oakman, 07 June 2018 - 03:36 PM.

[mike888]

Hi@all, maybe you have ideas about a special cocktail

 

Just by chance through Corona Patent search i found a citation about 3 component product with nmn+tmg+h2o2.

Note, that they are proposing a pretty hight dosage of about  2 times 3,5g nmn   

 

Here are the details

 

• Nicotinamide Mononucleotide (NMN) dosage -- 2.38 x 10^-4 moles / Kg body weight / day
• The betaine dosage -- 5.82 x 10^-4 moles / Kg body weight / day
• The Hydrogen Peroxide (H202) dosage -- 2.34 x 10^-5 moles / Kg body weight / day

 

alternatively to h202 the recommend

• The Sodium Hydrogen Sulfide (NaSH) dosage -- 3.02 x 10^-6 moles / Kg body weight / day

 

I wonder if anybody has an opinion about this cocktail.

 

Best mike888

[mike888]

here is a sketch about the proposed mechanism attached

 

[joesixpack]

here is a sketch about the proposed mechanism attached

I don't have the knowledge to comment on the cocktail. However, I take 300mg NR, and 500mg TMG. Until I started the TMG I could not tolerate more than 150mg of NR. I think TMG is a good idea.

[Gediminas Jesinas]

What should be betaine dosage when taking niacin, for example 1g? Betaine does come from grain food and vegetables also, however that is not enough not to put stress in body pool?