Long-term Treatment With Nicotinamide Induces Glucose Intolerance And Skeletal Muscle Lipotoxicity

[REOSIRENS]

About niacinamide... 100mg twice day seemed to be all good to me especially with biotin... 500mg for me seems to be too high and doesn't help... We have to check doses and what we take with... Most of nutrients work good in synergy with others and thr hour you take is important as well

 

[Raincoast]

3grams/day of Niacinamide for three months caused my fasting glucose to become elevated, homocysteine was extremely high.
Return to normal levels after cessation.
Would not take it without keeping an eye on labs. 20mg/day for myself now

 

[Texon]

A number of reasons, the two big ones being that up until now there was really no study on niacinamide and how it affects all of these various biomarkers similarly to Mildronate. To most people, including sports doctors, niacinamide is a puny, ineffective vitamin :)
Second reason is that Mildronate has been in use for decades as performance enhancing drug so a top athlete would likely go with something that is known to work instead of experimenting with vitamins. However, given that Mildronate is now banned by WADA, is somebody in sports were to read this forum they may start spreading the words that niacinamide on its own or especially in combination with inosine may very well give Mildronate a run or its money, and it is also unbannable and probably undetectable even if abused.

Wow I recall trying inosine MANY years ago when I was much younger, and when it was touted as the next big thing. I had to stop because I was getting gouty joint symptoms from it. If anyone experienced something similar or has an idea why this would be, please chime in.

 

[ddjd]

3grams/day of Niacinamide for three months caused my fasting glucose to become elevated, homocysteine was extremely high.
Return to normal levels after cessation.
Would not take it without keeping an eye on labs. 20mg/day for myself now

why does it raise homocysteine?

 

[ddjd]

Wow I recall trying inosine MANY years ago when I was much younger, and when it was touted as the next big thing. I had to stop because I was getting gouty joint symptoms from it. If anyone experienced something similar or has an idea why this would be, please chime in.

so inosine isnt good long term?

 

[Base Ball]

Ive been surprised by the number of people here who have reported not preferring higher doses of niacinamide, and have even had bad reactions to it. I think the stuff is amazing, but I may be a little older than a lot of you, so maybe you need more as you get older. I have known about niacinamide for more than 40 years. Before I heard RP talk about it I was familiar with Hoffer and Kaufman's work with niacinamide. These guys used the stuff on people for years and years, staring in the 1940s with very little reported adverse reactions. Kaufman, who used niacinamide primarily to treat arthritis., made an interesting observation that if the patient's protein was not "adequate" the treatment didn't work as well. (sounds Peaty) He also noticed that more frequent, smaller doses worked a lot better than smaller, larger ones., i.e.. 10, 150 mg doses scattered through out the day was superior to 3, 500 mg doses. In my own experience, I have found that concept true with all the water soluble vitamins, but not necessarily so with the fat soluble ones.

 

[ecstatichamster]

doses of 500mg or more are very sedating for me and make me feel weird

But 50mg to 100mg or so is really nice for me.

 

[Tarmander]

The best dose is to have a bottle of powder, to touch your pinky to your tongue, and then to touch the powder. Take said pinky and put under your tongue. Best dose.

 

[kyle]

people in pain of conditions like depression like to run or drink a lot, and most like both (often to an excess).

I hate running and like booze.

 

[Raincoast]

why does it raise homocysteine?

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives. - PubMed - NCBI

Be aware.

 

[Milena]

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives. - PubMed - NCBI

Be aware.

What would be an excess dose as regards this study. I cannot get the paper. Also, could someone do a layman's analysis, please?

 

[Mito]

What would be an excess dose as regards this study. I cannot get the paper. Also, could someone do a layman's analysis, please?

"Each participant was then orally administered 100-mg nicotinamide."

Here is link to the study: https://www.nature.com/hr/journal/v35/n2/pdf/hr2011151a.pdf

 

[ecstatichamster]

In fact, nicotinamide and its precursor nicotinic acid have long been known to induce glucose intolerance, insulin resistance and liver injury.1,3,18 Recently, our studies found that excess nicotinamide may induce oxidative stress, and suggested that obesity and type 2 diabetes, two major risk factors for CVD, may involve increased niacin consumption.

Something about this whole study really stinks. I don't think these "facts" have long been known. When Discussions and Abstracts say stuff like this they tip the hand that the investigators are heavily biased.

The ACTUAL results show a VERY modest increase in homocysteine. And conflicting numbers on epinephrine. The word "significant" doesn't mean it's MUCH, but that it's perceived statistically to be "true" or "likely to be true."

There are probably HUNDREDS of studies that show benefits of niacinamide on the liver and tissue:

The protective effect of niacinamide on ischemia-reperfusion-induced liver injury
After administration of niacinamide (10 mM), liver injury was significantly attenuated, while blood ATP content was reversed. In addition, MG, TNF-α and NO release was attenuated. These results indicate that niacinamide, presumably by acting with multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.

Niacinamide Abrogates the Organ Dysfunction and Acute Lung I... : Journal of Cardiovascular Pharmacology
Niacinamide exerts protective effects on the organ dysfunction and Acute Lung Injury caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

I could go on and on and on and on...

 

[Milena]

Something about this whole study really stinks. I don't think these "facts" have long been known. When Discussions and Abstracts say stuff like this they tip the hand that the investigators are heavily biased.
...
I could go on and on and on and on...

Thanks :)

 

[ddjd]

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives. - PubMed - NCBI

Be aware.

ive been taking 3 grams a day and i did notice some pains around my heart. not even kidding...

 

[ecstatichamster]

remember there may be reasons for higher dosages but Ray suggests around 50mg to 100mg per day I believe.

 

[Mito]

remember there may be reasons for higher dosages but Ray suggests around 50mg to 100mg per day I believe.

He has also said 125mg 3 or 4 times/day (200-500mg/day) is a safe dose and up to 1000mg/day is probably safe.

 

[Texon]

so inosine isnt good long term?

For some reason I personally just did not handle it well.

 

[Texon]

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives. - PubMed - NCBI

Be aware.

This is certainly true. I have personal experience with this. It is due to certain problems with methylation genetics which seem to be made worse by stressors of various kinds. I am still looking for an optimal solution after 5 years or so.

 

[Regina]

All good points. I think the main reason of increased FAO from endurance exercise causing NAFLD is that the fat that goes to the liver for excretion has estrogenic effect due to being mostly PUFA. On the other hand, fully saturated fat was shown to reverse even terminal cirrhosis. So, if you can somehow provide SFA to the liver while exercising then it should not be that bad. The beneficial effects of exercise are mostly due to increased thermogenesis, but it is done in a bad way - i.e. through increased adrenaline and conversion of the white into brown fat. The so-called "cold thermogenesis" has pretty much the same effect as "exercise". As soon as exercise starts to break down muscle it is no longer beneficial due to the increase of cysteine, methionine and tryptophan in the blood. And once it leads to increased adrenaline, that leads to increased availability of tryptophan in the brain and thus increased serotonin synthesis. The increase in serotonin in the brain is what makes you tired during (and after) exercise and is called the "central fatigue hypothesis". It has been shown to occur even in people with plentiful energy reserves or ones being fed by an IV while exercising. So, the point with any activity (at least to me) is this - while it is glycogen-bound and mentally stimulating/fun it is likely beneficial. Once it gets into the stage of adrenaline/lipolysis/tryptophan/serotonin/etc it is no longer good. For most people this means 10min - 30min of activity. Only very young and healthy people have glycogen reserves to depend on for hours.
Finally, the desire to regularly exercise that many people report and use to argue with Peat is actually a type of "addiction". Exercise has some dopaminergic effects initially and a ton of opioid activity due to the endorphins being released. So, quite a few of people that fanatically exercise are probably self-medicating for some type of physical pain or mental trauma. It is not a coincidence that so many people with depression like to run. Aside from the publicized effects of running on BDNF (which are mostly due to the "fun" factor in exercise and stop sharply when you overdo it), those endorphins can really blunt pain for many people. The same is true of drinking and once again, it is not a coincidence that people in pain of conditions like depression like to run or drink a lot, and most like both (often to an excess).

Advice worth a second read! Yep. 30 minutes is awesome amount of training.
I wish I could take half a class! But I don't think that will fly.