Excess Nicotinamide Induces Reactive Oxygen Species Generation, Insulin Resistance, And Epig

[Terma]

Sorry I had to edit that message, anyway I already posted links to all that stuff elsewhere on the forum.

 

[haidut]

Thanks, I'll look into that.



Thanks. Do you think there are any good reasons not to use rather high doses of glycine to prevent/reverse degenerative conditions such as colitis or liver damage? Several studies have used doses with human equivalents ranging from 20-50g to successfully treat these things.

I prefer gelatin instead of pure glycine, but yes, it should work.

 

[Kartoffel]

I prefer gelatin instead of pure glycine, but yes, it should work.

That was my thinking, too, but I have never found any gelatine that doesn't give me horrible bacterial overgrowth and symptoms associated with endotoxine. I have know many people that have the same problems with gelatine.

 

[LeeLemonoil]

Hom

That was my thinking, too, but I have never found any gelatine that doesn't give me horrible bacterial overgrowth and symptoms associated with endotoxine. I have know many people that have the same problems with gelatine.

How to explain that? Do they feast on Gelatine or is it contaminated?

 

[gilson d dantas]

Interesting finding. I began taking 30mg/kg dosage per day, which amount to 2100mg/day of niacinamide. I needed to use this dosage for a developing chronic kidney disease condition. After 2 weeks, I upped the dosage to 3000mg/day. I immediately felt different, but I couldn't pin it down. I dialed down the dosage the next day, and I felt better. Usually not feeling well meant a disturbance in my blood sugar level, and maybe in this instance it was.

I´m using 600 mg of niacinamide daily trying to fix a chronica kidney disease condition [which results from a prostate tumor, which I´m trying to heal also with other measures]. yerrag, any collateral effects from your high dose of niacinamide?

 

[Mito]

Niacinamide is a methyl sink and, similarly to glycine, will deplete the methyl group pool.

Although niacinamide and glycine both reduce methyl groups, it should be understood that there is a significant difference why each is reducing methyl groups. If the objective is to prevent overmethylation, it seems glycine is probably the better approach. Without getting too deep into the bio chemistry, I thought Chris summarizes the differences well.

“What is the difference between using niacin and glycine to mop up excess methyl groups? The difference is that when you methylate niacin, you do it because you have too much niacin. You don’t do it because you have too many methyl groups. You do it because you have too much niacin. When you methylate glycine, on the other hand, you do it because you have too many methyl groups. You don’t do it because you have too much glycine.

In fact, methylating glycine is only impacted by the number of methyl groups you have and not by how much glycine you have. Methylating niacin is only impacted by the amount of niacin you have, has nothing to do with how many methyl groups you have, unless of course, you’re so deficient in methyl groups that you’re not able to methylate the niacin, but that’s unrealistic. So if you’re consuming niacin over your nutritional needs, you’ll be methylating all of it, and in fact, everyone has methylated niacin metabolites in their urine, even when they’re just eating normal amounts of niacin in the diet, unless they’re deficient.”

https://chrismasterjohnphd.com/2018/10/11/dont-use-niacin-buffer-excess-methyl-groups/

 

[Amazoniac]

Although niacinamide and glycine both reduce methyl groups, it should be understood that there is a significant difference why each is reducing methyl groups. If the objective is to prevent overmethylation, it seems glycine is probably the better approach. Without getting too deep into the bio chemistry, I thought Chris summarizes the differences well.

“What is the difference between using niacin and glycine to mop up excess methyl groups? The difference is that when you methylate niacin, you do it because you have too much niacin. You don’t do it because you have too many methyl groups. You do it because you have too much niacin. When you methylate glycine, on the other hand, you do it because you have too many methyl groups. You don’t do it because you have too much glycine.

In fact, methylating glycine is only impacted by the number of methyl groups you have and not by how much glycine you have. Methylating niacin is only impacted by the amount of niacin you have, has nothing to do with how many methyl groups you have, unless of course, you’re so deficient in methyl groups that you’re not able to methylate the niacin, but that’s unrealistic. So if you’re consuming niacin over your nutritional needs, you’ll be methylating all of it, and in fact, everyone has methylated niacin metabolites in their urine, even when they’re just eating normal amounts of niacin in the diet, unless they’re deficient.”

https://chrismasterjohnphd.com/2018/10/11/dont-use-niacin-buffer-excess-methyl-groups/

Methylate Your Way to Mental Wealth With Dopamine | Chris Masterjohn

"[..]you can have this influx of methionine that comes in, and you can be predisposed to at least transient overmethylation in the sense that if you don’t have the glycine buffer to mop up the extra methyl groups, then you have less control over the level of methylation that’s happening in that moment in the postprandial state.

Glycine is going to take up a methyl group and become sarcosine, or it’s gonna take up two methyl groups and become dimethylglycine, and you may pee that out in your urine, or you may salvage it through various pathways where you can eventually get those methyl groups back into the regular system where they could actually recycle homocysteine.

But in general, I think it’s helpful to think of glycine as mainly getting peed out in the urine because if you have some problem of overmethylation, then that’s essentially what it’s gonna do. It’s gonna waste your glycine, and if you don’t have that glycine there, it’s gonna predispose you to rampant overmethylation."

 

[Terma]

Yeah Chris is probably right regarding GNMT and the way he words it make its safety more obvious. However, glycine is also part of creatine synthesis in liver and synthesis of compounds and tissues that require methionine (as well as cysteine in glutathione), and when in these cases glycine becomes rate-limiting, then adding glycine lowers available methionine. Also his comment about sarcosine's fate says basically nothing without studies of its quantification (someone please provide), similar to how dosages of niacinamide were shown to be crucial in Amazoniac's threads.

----------

Because Travis isn't here I'll leave a criticism in his place that I mentioned:

We also found that excess nicotinamide disturbed the monoamine neurotransmitters degradation and DNA methylation by competing for the biological methyl-donor, betaine in the body.

We don't have the full study so their reasoning can't be examined, but Travis warned that the link between SAMe (~betaine) and DNA methylation is usually an assumption made (well, he believed in it a little more than that).

Alternatively what happens here is high-dose niacinamide does affect the liver's methylation cycle, but in cells the DNA methylation loss is through another mechanism. If that were the case, possibly other forms of B3 or other substances would work just fine instead, working through something else like SIRT, ROS, excess polyamines, etc. no idea yet.

Finally the impacts of DNA methylation itself are now debated (not sure if @Travis saw this):
Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation
Thread by @G_Devailly: "I've seen a lot of tweets about this preprint by Frod et al.: "Frequent lack of repressive capacity of promoter DNA methylation identified t […]"

We find that DNA methylation is frequently insufficient to transcriptionally repress promoters. Furthermore, DNA methylation deposited at promoter regions associated with H3K4me3 is rapidly erased after removal of the zinc finger-DNMT3A fusion protein.

(I think the second link agrees with the second sentence but not the first, didn't really read it)

Yet another problem: Probably DNA methylation is being confused for Histone methylation - Wikipedia by random people, which has repressive effects but also pro-transcriptive activity.

In other words methylation "good or bad" is severely reductionist here, not even knowing what it's really doing let alone whether those things are good or bad (though it certainly does manufacture a few pro-metabolic products in the short term).

I'd also point out that glycine usually reduces ROS (glutathione/other). Although I'm not sure it's the most appropriate in this case, it would perhaps counteract bad effects of the niacinamide.

 

[Kartoffel]

How to explain that? Do they feast on Gelatine or is it contaminated?

Gelatine is made from dead skin. Skin cells divide and die rapidly. They are a perfect breading ground for gram-negative bacteria that release LPS when they die. I think gelatine can be a very harmful thing when your intestine is leaky to begin with.

 

[Terma]

On top of that I would say that I would not really recommend restricting [the methylation cycle, beyond a point], either intentionally or by force of other choices - without also supplementing or ingesting some of the end-compounds produced using SAMe, such as as CoQ10 (perhaps this is why Vitamin K filled in for it evolutionarily?! There's a thought).

[Yes, because if you only have leaves to eat, you get no methionine->CoQ10 but tons of Vitamin K to make up for it.]

[I am so high right now (Canada), THC + Cocoa powder + beta-alanine + energin = my air has become wool]

 

[Terma]

@haidut Here's a new one for you: "Cannabis Enhancer". You could ruin the entire alcohol industry in Canada and Colorado in one single blow. Think about it.

 

[Terma]

@haidut Think of how much fun you'd have developing this!

 

[Kartoffel]

Hom


How to explain that? Do they feast on Gelatine or is it contaminated?

Maybe I would try gelatine again, if I could get my hands on some of that low endotoxin stuff. I bet it would be expensive though...

Biol Pharm Bull. 2007 Feb;30(2):237-41.
Development of low endotoxin gelatin for regenerative medicine.
Kanayama Y1, Aoki C, Sakai Y.
Author information
Abstract
The basic concept of tissue engineering, an actively applied technology in regenerative medicine, is the coordination between cells, scaffolds, and proliferation factors. Collagen and gelatin are materials that have mostly been used as scaffolds because of their excellent affinity for cells, they are biodegradable, and their ability to form gel. However, very few of the collagen or gelatin preparations used as tissue engineering material have been prepared with low levels of endotoxin, which may trigger fever, shock and a fall in blood pressure even in very minute quantities. Therefore we decided to decrease the content of endotoxin in gelatin so that this biomaterial is not harmful to the body but still maintains its properties, namely, bioaffinity and biodegradation for use in the fields of cell culture and regenerative medicine. In this paper, we describe a method whereby endotoxin could be removed from gelatin solution by using an ultrafiltration membrane with a molecular weight cut-off of 100 kDa and low endotoxin gelatin, endotoxin activity in 0.1% gelatin solution was below 0.03 EU/ml, was obtained as the resulting filtrate solution.

 

[haidut]

@haidut Think of how much fun you'd have developing this!

Sure, it would be fun and it would be inviting so much anger and scrutiny from the FDA. I would rather not mess with the alcohol and cannabis industry. Besides, what would be the health benefit

Although niacinamide and glycine both reduce methyl groups, it should be understood that there is a significant difference why each is reducing methyl groups. If the objective is to prevent overmethylation, it seems glycine is probably the better approach. Without getting too deep into the bio chemistry, I thought Chris summarizes the differences well.

“What is the difference between using niacin and glycine to mop up excess methyl groups? The difference is that when you methylate niacin, you do it because you have too much niacin. You don’t do it because you have too many methyl groups. You do it because you have too much niacin. When you methylate glycine, on the other hand, you do it because you have too many methyl groups. You don’t do it because you have too much glycine.

In fact, methylating glycine is only impacted by the number of methyl groups you have and not by how much glycine you have. Methylating niacin is only impacted by the amount of niacin you have, has nothing to do with how many methyl groups you have, unless of course, you’re so deficient in methyl groups that you’re not able to methylate the niacin, but that’s unrealistic. So if you’re consuming niacin over your nutritional needs, you’ll be methylating all of it, and in fact, everyone has methylated niacin metabolites in their urine, even when they’re just eating normal amounts of niacin in the diet, unless they’re deficient.”

https://chrismasterjohnphd.com/2018/10/11/dont-use-niacin-buffer-excess-methyl-groups/

Good point, but niacinamide was shown by the study in this thread to directly reduce DNA methylation. So, it looks like niacinamide would work as well.

 

[Terma]

@haidut BETTER: "Cannabis brain [protector]"! ([probably can't write that legally?])

What are the health benefits?

Harm Reduction

 

[Terma]

@haidut This is EVEN BIGGER!!! This is Harm Reduction! That's the entire policy of the Liberal Party of Canada for the Cannabis push! You could decide the next election!

 

[haidut]

@haidut This is EVEN BIGGER!!! This is Harm Reduction! That's the entire policy of the Liberal Party of Canada for the Cannabis push! You could decide the next election!

I am not sure I want to get in the middle between a psychotropic drug industry and a government agencies. Nothing to be gained and everything to be lost.

 

[Terma]

@haidut I might be high but I think I'm being serious here: Why don't you setup a second startup company? You have all the head up on how to do it. Who else in the world could do this right now other than a rival [objectively worse] or shady supplement company? You could be the "Name Canadians Trust Since 2019". Health Canada would ******* love you! [The Liberals would ******* love you!] Brand name in pharmacies! This is big!!!

 

[Terma]

@haidut If that doesn't work, go to Canada and setup a deal with https://aphria.ca/

@haidut Put Niacinamide in it!!! "[...] with Niacinamide" right on the cover! It's like literally the thing you've always wanted!

@haidut Admit it, this is a good sell!!

@haidut If that fails, then you could even make your whole slogan a joke by advertising this now: "The Name Canadians Trust Since 2019". Pot smokers would ******* love you!!!

@haidut Also on front of box: "[...] by Dr.Peat Medical Enterprises" OR "Dr. Ray Peat-approved" You can transform his legacy!!!

@haidut Make enough to fund to your own anti-aging and niacinamide trials and drug trials all the way through the system!!! "The Dr. Peat Foundation"

 

[yerrag]

I´m using 600 mg of niacinamide daily trying to fix a chronica kidney disease condition [which results from a prostate tumor, which I´m trying to heal also with other measures]. yerrag, any collateral effects from your high dose of niacinamide?

I'm not sure that it's solely attributable to niacinamide, but I've seen my waking heart rate increase to 62 from 54, with my spO2 decreasing from 99 to 97, indicating higher tissue oxygenation. I also noticed that my urine foam has increased, but the surface tension is lower such that the vesicles are much smaller. I started on this on New Year, and I'll end it on Jan 28, for 4 weeks of it. That was the duration of the study in the thread of haidut I posted earlier. I'm also using near infrared light targeted at my kidneys, exposing my back to 2000 joules/cm2 of the infrared radiation. Shortly, I'll begin CO2 bath therapy, starting out in 1-hour durations to eventually sleeping in it overnight. Since I think my CKD has a fibrosis element to it, I'm thinking also of using some proteolytic enzymes such as serrapeptase.