LONGECITY

Hello guys,

 

for those who followed our debate about nicotinamide/niacinamide and nicotinic acid as methyl traper in the past. I just found a study that make all things clear :

 

Niacinamide IS a methyltraper as well, and even a stronger one than nicotinic acid !

 

So people who take nicotinamide riboside or even NMN, dont forget most of it is converted back into basic niacinamide. So if you take dosage above 100mg a day you should play it safe and use all along a B12 supplement or/and betaine HCL

 

here is the study, I love the fact they clearly compared the 2 forms :

 

https://www.ncbi.nlm...pubmed/27567458

 

Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels.

Abstract AIM:

The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine.

METHODS:

Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N¹-methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N¹-methyl-2-pyridone-5-carboxamide during the test period were examined.

RESULTS:

The level of 3-h plasma nicotinamide, N¹-methylnicotinamide, homocysteine, the urinary excretion of N¹-methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N¹-methylnicotinamide (1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM group.

CONCLUSION:

The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification.

Hi Tom, interesting study thanks for posting.
I'm out of the loop with the current debate. So you're saying that we should supplement with B12, specifically the methyl version? And what are the common side effects without these cofactors, fatigue and low energy?

Take 5 methyl folate. Your homocysteine will be forever normalized....

Hi Tom, interesting study thanks for posting.
I'm out of the loop with the current debate. So you're saying that we should supplement with B12, specifically the methyl version? And what are the common side effects without these cofactors, fatigue and low energy?

 You r welcome

 

Yes the methyl form is best indeed

 

Well there are probably lot of factors but the main one is homocystein (=cardiovascular disease)

 

Take 5 methyl folate. Your homocysteine will be forever normalized....

 

yes and no. It is now a few years Im on this topic and you need actually : 5 methyl folate (but never above 400mcg / day) + methyl B12 + B6 (P5P) in an ideal to respect the full methylation cycle.

 

But issue is homocysteine is not the worst. If you decrease homocysteine with those vitamins, your all mortaility risk still high. Why ? One reason is because your homocysteine will be in check but NOT your s adenosyl homocysteine. To decrease the later you need... Betaine in the opposite has a role, so we should maybe add it to the stack as #1 if large dose of NR or NMN are used.

 5 methyl folate (but never above 400mcg / day) 

...unless you are homozygous for the MTHFR SNP  C677T in which case going to at least 800mcg is strongly recommended.

The degradation of nicotinamide consumes betaine anhydrous in the human body which is the same as betaine trimethylglycine. So shouldn't we be supplementing with this form of betaine?

The degradation of nicotinamide consumes betaine anhydrous in the human body which is the same as betaine trimethylglycine. So shouldn't we be supplementing with this form of betaine?

 

Sure the use of betaine hcl is just betaine trimethylglycine with a hcl group added for digestive confort. I believe its a good idea to supplement with one of these if one use NR, NMN, or NA.

Edited by Tom Andre F. (ex shinobi), 20 November 2019 - 10:01 PM.

What is the ratio of betaine to nmn/nr/na? At the moment I'm taking 1:1.

Edited by p75213, 21 November 2019 - 12:45 AM.

Sure the use of betaine hcl is just betaine trimethylglycine with a hcl group added for digestive confort. I believe its a good idea to supplement with one of these if one use NR, NMN, or NA.

Is betaine hcl also a methyl donor? I couldn't find any research to verify that.

What is the ratio of betaine to nmn/nr/na? At the moment I'm taking 1:1.

I still wonder the same.
I experienced a methyl crash using Niacin withou TMG.

What is the math needed for calculating the TMG to NR/NAM/NA ratio?

This also interests me ... is there a correct proportion on the use of Nicotinic acid / Niacinamide and a methyl donor such as DMG / TMG to avoid side effects in the methylation process?

A paper in Medical Hypotheses (2000) recommended the same amount of betaine (TMG) as nicotinic acid in weight to avoid any theoretical methylation issues.

http://www.tahomacli...cin therapy.pdf
Edited by Fredrik, 02 January 2020 - 04:58 AM.

A paper in Medical Hypotheses (2000) recommended the same amount of betaine (TMG) as nicotinic acid in weight to avoid any theoretical methylation issues.

http://www.tahomacli...cin therapy.pdf

 

I have been taking 500mg of TMG with 300 mg or NR a day. Before I started the TMG I could not take more that 125mg of NR every other day. I no longer have the heart pounding, overwhelming effect from NR, and have some benefits from it.

What about choline, though? From the OP, they were investigating NA and NM's effect on betaine and choline. They found that there wasn't a significant difference in choline levels. However, according to the following docs, betaine is a metabolite of choline. What would happen if you just increased your dietary choline along with your doses of NA or NM, versus supplementing betaine? 

From elsewhere:
"Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine."

https://www.ncbi.nlm...les/PMC5452175/

Also, see here:
"In the liver, choline is converted to betaine via oxidation steps in the mitochondria by choline dehydrogenase (CDH) (12, 13) and betaine aldehyde dehydrogenase (BADH) (14). A methyl group of betaine is transferred to homocysteine by betaine:homocysteine methyltransferase (BHMT) to generate methionine. Methionine is converted to AdoMet by methionine adenosyltransferase. The liver converts over 60% of free choline into betaine (15), suggesting that choline may play a significant role in methylation reactions. However, an actual contribution of choline to PE methylation has not been demonstrated. This is mainly because many studies of choline metabolism have used choline that contains radioactive methyl groups. Using this radiolabeling technique, the two pools of choline-derived PC, one from the CDP-choline pathway containing the entire choline molecule, and the other from the methylation of PE containing only the methyl groups of choline, could not be distinguished from one another."

https://www.jbc.org/...7/19/17217.full

Also: "Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available."

https://www.ncbi.nlm...les/PMC3798916/

And, finally:
"Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study"
https://www.nature.c...598-017-00773-w
 

What about choline, though? From the OP, they were investigating NA and NM's effect on betaine and choline. They found that there wasn't a significant difference in choline levels. However, according to the following docs, betaine is a metabolite of choline. What would happen if you just increased your dietary choline along with your doses of NA or NM, versus supplementing betaine? 

From elsewhere:
"Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine."

https://www.ncbi.nlm...les/PMC5452175/

Also, see here:
"In the liver, choline is converted to betaine via oxidation steps in the mitochondria by choline dehydrogenase (CDH) (12, 13) and betaine aldehyde dehydrogenase (BADH) (14). A methyl group of betaine is transferred to homocysteine by betaine:homocysteine methyltransferase (BHMT) to generate methionine. Methionine is converted to AdoMet by methionine adenosyltransferase. The liver converts over 60% of free choline into betaine (15), suggesting that choline may play a significant role in methylation reactions. However, an actual contribution of choline to PE methylation has not been demonstrated. This is mainly because many studies of choline metabolism have used choline that contains radioactive methyl groups. Using this radiolabeling technique, the two pools of choline-derived PC, one from the CDP-choline pathway containing the entire choline molecule, and the other from the methylation of PE containing only the methyl groups of choline, could not be distinguished from one another."

https://www.jbc.org/...7/19/17217.full

Also: "Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available."

https://www.ncbi.nlm...les/PMC3798916/

And, finally:
"Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study"
https://www.nature.c...598-017-00773-w
 

Well I don't know. The TMG seems to word for me, so I will keep taking it.

 

Here's another one that's interesting:

 

 

 

Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver. The link between choline, betaine, and energy metabolism in humans indicates novel functions for these nutrients. This function appears to goes beyond the role of the nutrients in gene methylation and epigenetic control. Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders. Changes in plasma concentrations of total homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl group deficiency or nutrient supplementations. Folic acid supplementation spares betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy, particularly in case of folate deficiency, methionine load, or alcohol consumption. Betaine supplementation has a lowering effect on post-methionine load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available.

https://www.research...sferase_Pathway

Every time you rely on a conversion it takes time and some co-factor(s). Add to that some differences in PKs and you have to time it just right to reach your goal.

Since TMG is so cheap, why risk it taking choline and hoping that it will be converted to betaine 1) in enough quantities and 2) in the right time to match and counterbalance NA/NM/NMN effects?

 

What about choline, though? From the OP, they were investigating NA and NM's effect on betaine and choline. They found that there wasn't a significant difference in choline levels. However, according to the following docs, betaine is a metabolite of choline. What would happen if you just increased your dietary choline along with your doses of NA or NM, versus supplementing betaine? 

 

Every time you rely on a conversion it takes time and some co-factor(s). Add to that some differences in PKs and you have to time it just right to reach your goal.

Since TMG is so cheap, why risk it taking choline and hoping that it will be converted to betaine 1) in enough quantities and 2) in the right time to match and counterbalance NA/NM/NMN effects?

 

That's fair. As far as timing is concerned, I don't know how long betaine (directly ingested or converted) sticks around in your body from your diet. As per the following (table 1), a 45g slice of wheat bread will contain about 90 mg of betaine: https://academic.oup...0/3/539/4690529

Sure the use of betaine hcl is just betaine trimethylglycine with a hcl group added for digestive confort. I believe its a good idea to supplement with one of these if one use NR, NMN, or NA.

 

I would suspect the opposite, betaine trimethylglycine being the better option for digestive confort as betaine HCL loweres gastric pH.

 

For people with hypochlorhydria it may be good, but for normal people (and especially ppl with acid sensitive stomach) it may be harmful to take it on a regularly basis.

I just came across an interesting review: 
"Possible Adverse Effects of High-Dose Nicotinamide:Mechanisms and Safety Assessment"
Published: 29 April 2020
https://res.mdpi.com...es-10-00687.pdf

What betaine dosage or ratio should be taken along with niacin say 0.5-1 grams? Don't bread, grain products and vegetables contain enough of betaine? Why more B12 is needed?

Edited by Gediminas Jesinas, 25 August 2021 - 01:37 PM.