Testimonial For Niacin - It Just Works

BigChad

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According to pfeiffer, overmethylators have very low folic acid levels and high copper levels. Personally I dont know how convinced I am of about the copper as of late, but I do know, taking folic acid or methylfolate or anything else that is supposed to help overmethylators has tremendously helped my paranoia/anxiety/sleep issues and emotional bluntness(less blunt emotion). Funnily enough if you look on google one of the "side effects" of folate or folic acid is "depressed or overly excited".

If an undermethylator takes folate, they can become depressed, if an overmethylator does, the opposite happens, excitement. I never got anxiety from methylfolate though I read some are sensitive to the methyl. Thats the best way to describe myself when I take lots of methylfolate(what Im currently taking now), makes me feel like a new person and its not an exaggeration. Gets rid of my strong emotional bluntness. I suppose I am not sensitive to methylfolate's methyl group then others, but you may be. Folic acid may work better for you as to not add more methyl.

Copper and folate do not impact or deplete each other right
I thought folate promotes overmethylation, along with b12 while low levels of either are common in undermethylators
 

redsun

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Copper and folate do not impact or deplete each other right
I thought folate promotes overmethylation, along with b12 while low levels of either are common in undermethylators

Undermethylators are characterized by very high folic acid levels. Overmethylators have very low folic acid levels. That's the major distinction between the two but its not the only one.
 

Curiousman

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NNMT – Methylation of Nicotinamide – Nam

Methylnicotinamide is a “mitohormetic compound” that regulates longevity

Of all of the unusual aspects of Sirtuins and NAD metabolism, N-methylnicotinamide is probably the hardest one to understand. Recent evidence has shown that for the longevity effects of NAD metabolism to occur in nematodes (C. elegans), NAM must be methylated and then used by the gene, GAD-3, to produce low levels of hydrogen peroxide, thereby acting as a “mitohormetic compound”. This low level of hydrogen peroxide induces mitochondrial biogenesis and is necessary for nematode lifespan extension.

Reference: 2013 Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide

This article came out last year and one of the co-authors is David Sinclair.

However, that is not the entire story. There is much more to the story of the methylation of nicotinamide. Most of this has to do with stopping the toxic effects of nicotinamide from occurring, due to the inhibitory effects of Nam on both the Sirtuin enzymes (SIRT1-7) and the PARPs (1-17).

Over 85% of transmethylation reactions occur in the liver, including the methylation of nicotinamide. With the oral intake of nicotinamide, the liver could either methylate the nicotinamide or convert it to NAD. From many studies, it is clear that the liver preferentially methylates nicotinamide, rather than converting it to NAD. The reason why the liver methylates nicotinamide is that high concentrations of nicotinamide cause cell injury and cell death, since nicotinamide inhibits all 7 of the Sirtuins and also inhibits the PARP enzymes (PARP1,PARP2, etc).

For this reason, with oral intake of Nam, serum levels of N-methylnicotinamide increase. Only 15% of nicotinamide methylation occurs outside of the liver. Nicotinamide methylation by NNMT also requires a methyl donor, such as SAMe or trimethylglycine, which is also called betaine. When nicotinamide is methylated, it is then excreted, thereby reducing Nam levels in the body and preventing SIRT/PARP inhibition.

GWAS studies of polymorphisms in the NNMT gene have revealed an amazing association with Non-alcoholic steatohepatitis (NASH). The NNMT gene SNP, rs694539, is a SNP found in the regulatory portion of NNMT gene. The “GG” genotype protects against NASH, with an OR of 0.58. The “AA” genotype increases the risk of NASH with an OR of 7.3. This suggests that methylation of nicotinamide is an important factor in preventing NASH (see references below). This same polymorphism (rs694539) has been linked to bipolar disorder recently. The association was “female gender-specific” and did not influence male bipolar risk.

A recent novel theory discussing how “too much NNMT” and “too little NNMT” may both play a role in aging and disease has been proposed. This theory suggests that excess dietary nicotinic acid consumption results in molecular/cellular “methyl consumption” and plays a role in disease. This new theory has been published in Nature and is being taken seriously. The main hypothesis is the increase in “methyl consuming compounds” in our diet contributes to metabolic syndrome and many other “man-made diseases”. Another aspect of this new theory is that NNMT is a “fat accumulation gene” (see references below), since the expression of NNMT is unregulated with increased dietary intake of food, especially foods that are rich in niacin and nicotinic acid. Specifically, the expression of the NNMT gene correlates with the percentage of fat in 20 different mouse strains. The main cause of the up regulation of the NNMT gene is overeating/overfeeding. In fact, Kraus and colleagues recently showed that the administration of methylnicotinamide inhibited NNMT and this increased NAD levels and SAM-dependent gene expression.

References:

This theory has been proposed because of recent studies which show a paradoxical effect occurs when NNMT is over-expressed. When this occurs, the NNMT over-expression results in diet-induced obesity. This has been shown in humans and in animal models. For instance, the NNMT gene is unregulated in fat cells with obesity and T2DM. When the NNMT gene is “knocked down”, it protects against diet-induced obesity.

Source: 30 Major Factors that Control SIRT1 Expression, SIRT1 Activity, and SIRT1-mediated Aging. Part 3 of the series NAD+ an emerging framework for health and life extension - AGINGSCIENCES™ - Anti-Aging Firewalls™
 

Curiousman

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Google : NNMT Inhibitor
 

Curiousman

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Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Obesity in Chinese Han Male College Students

1. Introduction

NNMT is an enzyme which catalyzes the methylation of nicotinamide (NAM) and produces methylnicotinamide (MNA) [1, 2]. Metabolomic works have showed that levels of MNA in urine were correlated with the body mass index (BMI) significantly [3, 4]; thus indicating that NNMT is involved in the regulation of the body fat. Recently, these findings have been supported by multiple evidences. For example, serum MNA was reportedly increased in Chinese obesity population [5] and urinary MNA was found elevated in humans with obesity and type 2 diabetes (T2D), in db/db mice and in obese Zucker rats [4]. These results implicate an increased NNMT activity in obesity. The more direct evidences came from Kraus et al. [6] and Lee et al. [7]. They found that Nnmt knockdown caused a 47% reduction in relative fat mass of mice [6], and NNMT expression is increased in adipocytes of obese population [7].

More than two hundreds of single nucleotide polymorphisms (SNPs) have been identified within human NNMT gene in recent years, and two noncoding region SNPs (rs694539 and rs1941404) have been reported to be significantly associated with some related noncommunicable chronic diseases (NCD), such as hyperhomocysteinemia [8], congenital heart diseases [9], abdominal aortic diseases [10], migraine [11], nonalcoholic steatohepatitis [12], bipolar disorder [13], epilepsy [14], schizophrenia [15], and hyperlipidemia [16]. However, the association between NNMT gene SNPs and the body composition has not yet been reported to date.

Are there any SNPs in NNMT DNA sequence significantly associated with obesity? We check all the candidate genetic association studies (CGASs) on NNMT gene and all the genome-wide association studies (GWASs) on obesity. The results show that no CGAS concerning NNMT gene and obesity has been carried out to date and that no SNP in NNMT DNA sequence has been identified to be significantly associated with obesity in existing GWASs. Theoretically, it is not surprising that NNMT gene is significantly associated with obesity. As the precursor of the NAD+, NAM methylation can directly affect NAD+ levels, because NAM cannot be used in the synthesis of NAD+ if it is methylated by NNMT [17]. NAD+ is essential for the fuel oxidation in our bodies. The competition between NNMT and NAD+ salvage suggests that NNMT gene polymorphisms might affect the fuel oxidation and the storage of fat.


NNMT activation can contribute to the development of fatty liver disease by modulating the NAD+ metabolism

NNMT overactivation decreased the NAD+ content in the liver and also decreased gene activity related to fatty acid oxidation by inhibiting NAD+–dependent deacetylase Sirt3 function.


Novel approach to accelerate metabolism could lead to new obesity treatment

By manipulating a biochemical process that underlies cells' energy-burning abilities, investigators have made a novel discovery that could lead to a new therapy to combat obesity and diabetes. The new findings show that reducing the amount of nicotinamide N-methyltransferase (NNMT) protein in fat and liver dramatically reduces the development of obesity and diabetes in mice.



 
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redsun

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Been awhile since I posted an update on here so I thought I'd check in.

I stick to minimized niacin doses nowadays because of the issue that consistent niacin intake empties histamine stores and will lower them over time and keep them low because each subsequent dose will release more histamine before it can build up. If you have read some of my posts, you likely noticed I am a big fan of histamine, so naturally I don't want to empty it out of me. Evidence being I would be way too chilled out and not really accomplishing too much and being unproductive in general, indicating histamine was clearly lowered a lot. Stopping for a few days then starting again with just 250mg once a day works just fine.

If the dose is lower, say 50mg/meal you will not empty histamine and it still will work to replete niacin without lowering histamine too much. I just use 250mg because its convenient so ideally for anyone considering trying it, stick to the lower more consistent doses if possible. Clearly the release of histamine by niacin plays a role in increasing stomach acid that I have experienced so I am grateful that I found this out. Nothing else has worked for smoothing out digestion, nothing really compares. It works because it gets to the root of the issue so again I want to stress to anyone that is having digestive issues to give niacin a shot. I'm glad I did.
 

cihans

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@redsun Hows your niacin experiment goes any update? I’ll try it soon like 500mg - 500mg each meal than gradually lower it to 100mg each meal. Histamine lowering effect is making too much sense. Could you point to your histamine posts if its not a big hussle? I’m curious why you are a big fan of histamine btw
 

ExCarniv

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B Complex by Thorne, game changer for me. I think is due to Thiamine and B3.

The only supplements for me atm are Magnesium and B Complex.
 

redsun

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@redsun Hows your niacin experiment goes any update? I’ll try it soon like 500mg - 500mg each meal than gradually lower it to 100mg each meal. Histamine lowering effect is making too much sense. Could you point to your histamine posts if its not a big hussle? I’m curious why you are a big fan of histamine btw

I do 250mg a few times a week and try to find a better way to optimize digestion without lowering histamine. I don't remember if I ever mentioned it in the other posts, but my digestion was never bad. Niacin was never about fixing digestion, it was about perfecting it and unfortunately it does not do that for me. My guess is optimizing nutrient status for specific nutrients and raising histamine levels is probably what is going to do it. This is what I am currently working on myself as of now.

@redsun Could you point to your histamine posts if its not a big hussle? I’m curious why you are a big fan of histamine btw

I could, issue is when I look back at the posts a lot of them are just a few sentences with tidbits of info about it. So in the end if you search "histamine" with my user you will see all the posts and it will be more useful for you that way.
 

berk

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I did use niacinamide before awhile ago, and I did see improvements with digestion but it was causing weight gain and there was strong drops in blood sugar and I didnt feel that great on it which is why I stopped. Niacin has not fluctuated my weight at all
I have not experienced any fat gain with niacin. Niacinamide yes, but not niacin. I dont think its a serious concern and will likely not happen.
i read a lot about that niacinamide and always want to experimenting with it but i also read couple times that niacinamide hurts/stops fat loss completely.
because now i am try to lose some fat i am afraid for using niacinamide
Do you think niacin don't hurt/stop fat loss?

. Popped a niacin, seems to be more effective than aspirin. Red as hell though lol.
The flush makes me red as hell so I could definitely tell. .
i read a little about these flush but i dont understand what this exactly is.
Its this just body heat that increased by metabolism? or fever? what exactly happens?

I am a big fan of histamine
why are you a fan of histamine?
And if niacin empty histamin storages, this is a good thing for people with allergy's right?

And do you guys also notice a reduce in appetite?
i always have cravings on a low fat, high sugar diet. its makes me crazy, Maybe niacin can reduce this?
 
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redsun

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i read a lot about that niacinamide and always want to experimenting with it but i also read couple times that niacinamide hurts/stops fat loss completely.
because now i am try to lose some fat i am afraid for using niacinamide
Do you think niacin don't hurt/stop fat loss?



i read a little about these flush but i dont understand what this exactly is.
Its this just body heat that increased by metabolism? or fever? what exactly happens?


why are you a fan of histamine?
And if niacin empty histamin storages, this is a good thing for people with allergy's right?

And do you guys also notice a reduce in appetite?
i always have cravings on a low fat, high sugar diet. its makes me crazy, Maybe niacin can reduce this?

How you react to niacin/niacinamide is very individual. I would not take either if you are trying to cut fat and don't recommend niacin anymore. Whatever it does its a crutch. Niacinamide can be used that's up to if you want more hormones. It also seems to have mild histamine increasing effects.

Flush is increased blood flow to the skin (vasodilation) caused by certain chemicals. Prostaglandins being one of them. Its not increase body heat from metabolism

Its not surprising to have cravings. I assume you crave fat more or just crave food in general. Healthy fat is very needed for optimal health. I think the best diet to lose weight with is one that still has fat and carbs in it just reduced calories.

The best way to have adequate B3 in the body is to consume foods rich in B3, which is primarily meat. Try to get 25-30mg a day from food. Next up is getting adequate protein (for tryptophan to make niacin), good iron and B6 status. Other vitamins and minerals are necessary to make niacin, I believe B2, zinc... This allows your body to make more niacin if needed instead of giving niacin in unnaturally high amounts.
 
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berk

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Its not surprising to have cravings. I assume you crave fat more or just crave food in general. Healthy fat is very needed for optimal health. I think the best diet to lose weight with is one that still has fat and carbs in it just reduced calories.

The best way to have adequate B3 in the body is to consume foods rich in B3, which is primarily meat. Try to get 25-30mg a day from food. Next up is getting adequate protein (for tryptophan to make niacin), good iron and B6 status. Other vitamins and minerals are necessary to make niacin, I believe B2, zinc... This allows your body to make more niacin if needed instead of giving niacin in unnaturally high amounts.
i eat every day liver and yolks.
if i must believe my cronometer than i got enough vits/mins and protein, but i push this up, seems what happens.
Anyways, tell me, why you love histamine?
 

redsun

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Anyways, tell me, why you love histamine?

Its necessary for optimal brain function and speed. Important for visual processing and vital for environmental observation and detail (dopamine is related to this as well). Low histamine or taking antihistamines tend to impair mathemathical and analytical skills.

Histamine is necessary for drive for a career or motivation to whatever your dream is (doesnt have to necessarily be a dream job), intelligence, libido, emotions, being competitive and driven for life in general. Its involved and needed for many things but it doesnt often act alone. There are many relationships between glutamate, histamine, dopamine, and other hormones and neurotransmitters.

That's a short list of reasoning but there's of course more to it. Hans has a pretty decent article which is a lot more organized than an on the spot post from me.

The High Dopamine & Histamine Personality

i eat every day liver and yolks.
if i must believe my cronometer than i got enough vits/mins and protein, but i push this up, seems what happens.
Anyways, tell me, why you love histamine?
You can be craving fat for the sake of the fat not micronutrients.
 
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I just ate a huge meal and took some niacin (nicotinic acid) and have a huge energy rush (no flushing though), which is amazing since i've been super lethargic lately.

I wondered why it gave me so much energy, moreso than coffee, but in a more natural feeling way, and happen to stumble across this thread.

Kinda bummed to see how awesome niacin was talked about in the beginning of this thread only to see it not being recommended anymore at the end by OP.

My body is telling me to take it, so i'm going to ignore the flip flop recommendation and keep going with it.

I thought histamine wasn't an issue since it's created from other foods. Confused. I eat over a pound of red meat daily so i'm thinking generating more histamine shouldn't be a problem.

Shouldn't we be looking at the net effect of things rather than using hypothesis like "oh in this one study it does this thing that could reduce histamines, so therefore it's bad". (not saying OP is doing this, but just see this a lot on this forum, it's like some logical leap we try and make that rarely pans out in real life)

Meanwhile it has some other unknown effect that balances that aspect out and therefore the net effect is not reduced histamines.

OP it would be nice if you could further clarify why you went from thinking it was so amazing, to thinking its' not good to take anymore.

My bloating issues are making me super ******* depressed and to have some hope that niacin could potentially fix it made my day.
 

redsun

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I just ate a huge meal and took some niacin (nicotinic acid) and have a huge energy rush (no flushing though), which is amazing since i've been super lethargic lately.

I wondered why it gave me so much energy, moreso than coffee, but in a more natural feeling way, and happen to stumble across this thread.

Kinda bummed to see how awesome niacin was talked about in the beginning of this thread only to see it not being recommended anymore at the end by OP.

My body is telling me to take it, so i'm going to ignore the flip flop recommendation and keep going with it.

I thought histamine wasn't an issue since it's created from other foods. Confused. I eat over a pound of red meat daily so i'm thinking generating more histamine shouldn't be a problem.

Shouldn't we be looking at the net effect of things rather than using hypothesis like "oh in this one study it does this thing that could reduce histamines, so therefore it's bad". (not saying OP is doing this, but just see this a lot on this forum, it's like some logical leap we try and make that rarely pans out in real life)

Meanwhile it has some other unknown effect that balances that aspect out and therefore the net effect is not reduced histamines.

OP it would be nice if you could further clarify why you went from thinking it was so amazing, to thinking its' not good to take anymore.

My bloating issues are making me super ******* depressed and to have some hope that niacin could potentially fix it made my day.

The release of histamine can be very energizing but not in the increased noradrenaline way which is what caffeine mostly does.

Long term use of it at super high doses would present with possible liver issues. Of course you can just use lower doses but in the end a big part of why I no longer am for it is I am tending to avoid the use of drugs for fixing things. And yes in this context, vitamins are considered drugs when used at unnatural doses and have certain known effects like any other drug.

It did fix the things I said it fixed to a degree in the OP but in the end my MAIN issue specifically with niacin that made me stop taking it was taking it made me too chilled out and unmotivated (but not unhappy and depressed, just too uncaring to the point of not giving a single **** about anything serious like school or life progression). It was nice initially because I was tensed up a lot but then I couldnt care for anything and that was a problem. I cant just check out of life and live happily ever after but thats what I wanted to do.

Another aspect that I havent mentioned in this thread that can explain energy improvements and mental wellbeing as well as improved gastrointestinal function:

Niacin is needed for making steroid hormones, and this includes the hormones that help retain electrolytes like aldosterone, progesterone, cortisol (can bind to aldosterone receptor)... So if you suck at retaining electrolytes because low steroid hormones you can have indigestion problems because electrolytes are needed for gastric juice. It also acutely raises histamine as I said by releasing it which can stimulate stomach acid production. Increased hormone production can also of course help energy and mental wellbeing.
 

Luann

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so @redsun, what is going on with individuals who experience pain after histamine-rich foods?
how are we supposed to avoid migraines etc... are we processing it wrong, or lacking other nutrients or something? interested to find out.
 

redsun

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so @redsun, what is going on with individuals who experience pain after histamine-rich foods?
how are we supposed to avoid migraines etc... are we processing it wrong, or lacking other nutrients or something? interested to find out.

It depends on the individual. People who are histadelic or very close (elevated histamine but not insanely elevated) may be reacting to high histamine food. I assume you mean you don't react well to fermented foods? Histadelics are not known for food intolerances. Histapenics (low histamine) do have food intolerances, some can react to almost anything depending on severity.

People confuse this and think because they react to foods that means they have a histamine problem, and they are right but they think its too much. Actually, histamine is too low. High histamine will largely prevent food intolerances.

Only issue really is heartburn and ulcers because gastric acid secretion is so strong and constant (so is their hunger, they often constantly eat throughout the day). Extra histamine from foods can worsen histamine symptoms in histadelics and cause headaches and migraines.

Do you have many food intolerances? If so that can lead to reactions as digestion is poor. Low histamine individuals have poor digestion (weak secretions) and as such have problems with many foods.

I dont know if you have high histamine, you can look at symptoms of histadelia and histapenia and see where you fit better. If your histamine is truly excessive you can try lowering it through various means.
 
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