High dose Niacinamide, what are the cofactors

[Candeias]

I have to use high doses of Niacinamide to correct a problem, last time I was doing fine until I put too much stuff for my liver, I got up to 3 grams with no problems.

But what is essential to take to avoid problems of excess of undermethylation and high homocysteine? Does anyone have experiences with this?

As far as I know I don't have serious genetic/enzymatic problems.
Thanks


___________________________________________
Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives - Hypertension Research

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and...

www.nature.com

 

[Candeias]

As I understand it uses SAM to methylate Niacinamide into N-methylniacinamide, which leads to more SAM being produced and increasing consumption of all the nutrients and co-factors behind it. I think the ideal context was to increase SAM with cofactors/nutrients, as SAH is toxic. Figure 1

Figure 2
Interconversions between SAMe and other one-carbon cycle intermediates

 

[Candeias]

Metabolism of S-adenosylmethionine

 

[Candeias]

Therefore the depletion of SAM by excess Nicotinamide causes an increase in Norepinephrine and Epinephrine, if the homocysteine loop becomes compromised for any reason. Vitamin B6 converts excess homocysteine to cysteine.

I just don't understand how Nicotinamide increases Homocysteine, can someone explain to me?

 

[Candeias]

S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule
"Methionine concentrations are closely related to homocysteine metabolism. When methionine is needed, homocysteine is remethylated by methyltetrahydrofolate, but when methionine is in excess, catabolism of homocysteine via cystathionine β-synthetase (EC 4.2.1.22) is accelerated (24). This regulatory mechanism has been studied in some detail. Womack and Rose (25) first showed that cysteine could replace ≈70% of the dietary requirement for methionine. Later, Finkelstein and Martin (26) studied the enzymatic basis for this methionine-sparing effect of cysteine. Replacement of methionine with cysteine resulted in a marked decrease in hepatic concentrations of cystathionine β-synthetase. In other studies, the same authors showed that feeding excess methionine to rats resulted in decreased hepatic concentrations of methionine synthetase and increased concentrations of betaine–homocysteine methyltransferase, methionine adenosyltransferase (MAT; EC 2.5.1.6), and cystathionine β-synthetase (26). These studies showed that the partitioning of homocysteine between the transsulfuration and methylation pathways is finely regulated by the tissue concentrations of substrates and effector metabolites."

 

[Candeias]

Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats

Vitamin B-6 Normalizes the Altered Sulfur Amino Acid Status of Rats Fed Diets Containing Pharmacological Levels of Niacin without Reducing Niacin's Hypolipidemic Effects

Homocystinuria


I can only come to the conclusion that, somehow, Niacinamide lowers B6, causing the enzyme Cystathionine-β-synthase, which is used when methionine and homocysteine are in excess, to not work properly due to the low level of B6.

 

[profwormbog]

I'll give you a non-science response based on my own experience earlier this year. I had issues with high homocysteine (15.5) after taking only 250mg niacinamide daily for many months, in the absence of other B vitamins, to lower triglycerides. It successfully lowered them from 174 to 60, but created methylation issues. I had to take a methyl-B complex (b2, b6, b9, b12, tmg) alongside it daily for three months to get it down to 8.1. There are various threads on the forum around this topic, but like many I had to learn the hard way. My takeaway was to make sure you balance your Bs. Personally, I think my issue was depleted riboflavin over p5p as I was out in the sun a lot this past summer.

 

[Candeias]

I'll give you a non-science response based on my own experience earlier this year. I had issues with high homocysteine (15.5) after taking only 250mg niacinamide daily for many months, in the absence of other B vitamins, to lower triglycerides. It successfully lowered them from 174 to 60, but created methylation issues. I had to take a methyl-B complex (b2, b6, b9, b12, tmg) alongside it daily for three months to get it down to 8.1. There are various threads on the forum around this topic, but like many I had to learn the hard way. My takeaway was to make sure you balance your Bs. Personally, I think my issue was depleted riboflavin over p5p as I was out in the sun a lot this past summer.

And did you continue to take B3 along with the others?

The B3-related increase in homocysteine is undoubtedly related to the depletion of B vitamins. Probably also betaine, being one of the main methyl donors. I'm also sure it consume copper, I was craving liver and cocoa after taking up to 4 grams of Nicotinamide, possibly exacerbating a longstanding low copper, boosting metabolism has caused my beard to lose pigmentation in recent years.

What symptoms did you have?

 

[Inaut]

I use MSM so I’m hoping I get enough methyl groups from it. I’m taking about 300-500mg of niacinamide daily and have noticed skin irritation. I’ve also been consuming a lot of chocolate which may be causing histamine issues?

 

[profwormbog]

And did you continue to take B3 along with the others?

The B3-related increase in homocysteine is undoubtedly related to the depletion of B vitamins. Probably also betaine, being one of the main methyl donors. I'm also sure it consume copper, I was craving liver and cocoa after taking up to 4 grams of Nicotinamide, possibly exacerbating a longstanding low copper, boosting metabolism has caused my beard to lose pigmentation in recent years.

What symptoms did you have?

I take a lower dose of B3 daily (50-100mg) and B-complex every other day. And yes, my copper/ceruloplasmin have been low for some time. I cannot stomach liver or organ meats and am allergic to shellfish, so I don't have many options. I do a few tsps of cacao powder daily and a copper glycinate supplement which probably won't do much. My zinc was on the higher end of the range, so I have ceased zinc supplementation as well.

Was doing my quarterly round of out-of-pocket labs back in July and discovered it was high -- there were no symptoms I could really pinpoint at the time. Will get all these tested again in 2-3 months.

 

[Candeias]

I use MSM so I’m hoping I get enough methyl groups from it. I’m taking about 300-500mg of niacinamide daily and have noticed skin irritation. I’ve also been consuming a lot of chocolate which may be causing histamine issues?

I don't know much about histamine and cocoa, I think I only get skin reactions when my liver is damaged.

 

[cremes]

I take 3 grams (divided) of niacin daily to lower my cholesterol. In addition, I take a B-complex and make sure to eat foods that are methyl donors. So my diet includes beets, berries, and black tea.

I've only been doing this for 6 weeks so it's probably too early to run into any issues of B depletion.

 

[Candeias]

I take 3 grams (divided) of niacin daily to lower my cholesterol. In addition, I take a B-complex and make sure to eat foods that are methyl donors. So my diet includes beets, berries, and black tea.

I've only been doing this for 6 weeks so it's probably too early to run into any issues of B depletion.

With niacin there is not so much this problem, because not everything converts to niacinamide.
I don't know about black tea and berries, but liver, legumes, and leafy greens/kale are some of the few things that are high in folic acid. Beetroot has choline and folic acid so it's great.