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

[ecstatichamster]

I will note that Dr. Peat has often said that 50mg - 100mg or so of niacinamide a few times a day is a safe dosage. I have never heard him say that people should take 1000mg or dosages like that, although perhaps he has quoted an anecdote here or there on someone doing that.

I was taking high dosages and it made me feel very tired and lowered my blood sugar. I think it's a great idea for a supplement for people on a high carb (high sugar) low fat diet trying to recover from type 2 diabetes as it inhibits lipolysis and is probably safer ongoing and better in some ways than trying to do that with aspirin.

 

[LeeLemonoil]

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.

I‘ve never considered that. Damn it. I sometimes get rather rapid blodpressure-slump from gelatine-hydrolysate, nur Never attributed it to endotoxin.

Is Collagen-Hydrolysat not heated and manufactured enough to prevent the bacterial risk?

 

[nathan10000]

Niacinamide causes insulin resistance which increase serum insulin and glucose, subsequently the high insulin cause hypoglycemia during later phase.

 

[nathan10000]

The study i posted was done on humans and animals.

Here is another study done on animal showing the same conclusion of insulin resistance.

Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induced obesity
Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induce... - PubMed - NCBI

"Our data showed that NAM treatment (100 mg/kg/day for 8 weeks) induced insulin resistance and skeletal muscle lipid accumulation in mice fed regular chow. This observation clearly demonstrates an adverse effect of NAM intake on insulin sensitivity, conflicting with reported therapeutic effects of NAM in T2DM and obesity [10]. In agreement with our results, there are several studies reporting detrimental metabolic effects of NAM at higher dose in rats and humans, one of which suggests that NAM overload induced an increase in plasma MNAM level, resulting in oxidative stress and insulin resistance"

". It should be noted that our study has examined the effects of NAM only at 100 mg/kg/day. This dosage was much lower than that used for inducing detrimental metabolic effects (4 g/kg/day), whereas the duration was similar to each other"

"Moreover, we focus on the healthy mice fed regular chow, instead of mice with type 2 diabetes and obesity. We observed that NAM treatment (100 mg/kg/day for 8 weeks) induced glucose intolerance and increased serum lipids. This effect is partially similar to insulin resistance in type 2 diabetes and obesity"

" Here, we investigated the effects of NAM on lipid content in liver and skeletal muscle. We found no pronounced increase in hepatic lipid storage. Instead, NAM increased lipid content and decreased glycogen content in skeletal muscle."

"Together, it can be concluded that NAM-induced insulin resistance in nonobese mice was associated with skeletal muscle lipid accumulation. In this work, the possible explanation for skeletal muscle lipid accumulation is that NAM reduced the capacity of exogenous FA oxidation and increased TAG esterification."

"NAM also resulted in higher circulating TG and FFA levels compared with control mice"

"Our results demonstrate that chronic NAM supplementation in healthy individuals, although at lower dose than previously reported, is still detrimental to glucose homeostasis and skeletal muscle lipid metabolism."

 

[yerrag]

I‘ve never considered that. Damn it. I sometimes get rather rapid blodpressure-slump from gelatine-hydrolysate, nur Never attributed it to endotoxin.

Is Collagen-Hydrolysat not heated and manufactured enough to prevent the bacterial risk?

I don't know why I don't feel any detrimental effects of high gelatin intake, but maybe I'm just not sensitive enough. If endotoxins are a concern, would it help to take activated charcoal before going to bed so endotoxins can be asdorbed?

Niacinamide causes insulin resistance which increase serum insulin and glucose, subsequently the high insulin cause hypoglycemia during later phase.

I should try increasing intake of potassium, preferably from fruits, to see if the effect of large niacinamide intake can be offset by potassium's insulin-like response, where it facilitates glucose uptake by tissues.

On second thoughts, this may not work. It occurred to me that with high niacinamide supplementation, the NAD/NADH ratio will likely be pumped up, such that the production of NAD will have to be restricted. This restriction will affect the uptake of glucose by tissues, and this will lead blood sugar levels to increase to a point where an insulin response will cause blood sugar levels to go down to hypoglycemic levels. So, the answer would either be to lower the dosage of niacinamide intake, or to increase the reducing rate of NAD. But I think the former would be more practical. I don't know if this makes any sense. What are your thoughts @haidut ?

 

[gilson d dantas]

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.

OK, yerrag. Thank you. Your experiencie is very important to my, to my case [kidney condition, with CKD].
You use the cistatine C to measure the kidney filtration? I use cistatine C and creatinine to monitor my kidney condition and evolution.
What is the best way to do a dry bath of CO2? I´m also trying fo find a rebreathing mask.
I think that as we have a similar problem [CKD] we can change many ideas. I´m thinking to increase niacinamide to 1,2 g daily.

 

[yerrag]

OK, yerrag. Thank you. Your experiencie is very important to my, to my case [kidney condition, with CKD].
You use the cistatine C to measure the kidney filtration? I use cistatine C and creatinine to monitor my kidney condition and evolution.
What is the best way to do a dry bath of CO2? I´m also trying fo find a rebreathing mask.
I think that as we have a similar problem [CKD] we can change many ideas. I´m thinking to increase niacinamide to 1,2 g daily.

I haven't herd of cistatine C until now. Thanks! I used creatinine to estimate GFR but I don't trust it. I think it is a very nebulous way of estimating GFR. I like to use 24hr urine test to calculate the creatinine clearance to get an idea of my GFR. Still, it's said that the creatinine clearance overestimates the GFR relative to the eGFR based on serum creatinine, but I couldn't get detailed references. For all I know, eGFR from serum creatinine could be an underestimation of actual GFR, given that the medical system has a vested interest in getting false positives and false negatives.

Is the cistatine C very useful to you?

I bought a dry bath from Carbogenetics when Steve (co2islife) was active in this forum more than a year ago. It's a rubber chamber I slip into and seal my entire body in, and where CO2 is pumped into the chamber, exposing my skin, except my head, to CO2. It allows me to stay exposed to CO2 for a long time, even overnight, to allow the CO2 to penetrate the skin and unto the body. I haven't used it and next week, I hope to begin my trials on it. I have plenty of keloids as well, which is another fibrotic condition. I'm hoping to see my keloids shrink, so that I can get a better idea of its effect on dissolving fibrosis in my kidneys. If it works on my keloids, it is more likely that it will also have an effect on my kidneys. This can later be confirmed by lowered blood pressure readings, which currently is high at 180/120.

Steve also sold me a carbogen breathing machine, which I've used for 1 hour sessions before, where I inhaled 5% carbogen. I didn't see any effect from it, but my test was only for 2 days. Besides, I wasn't too keen on using it as I experienced higher blood pressure when I was practicing Buteyko. Increased control pause times, which indicated higher CO2 blood content, had caused my blood pressure to increase. That was then, and since my body has changed a lot since then, it might respond more favorably to increased tissue oxygenation from increased blood CO2 levels.

You can slowly increased b3 dosage to as much as 30mg/kg of body weight. I was a bit impatient and jumped to that dosage immediately, and it didn't give me any bad reactions. Since b3 increases metabolism, I had experienced higher blood pressure from using it in the past, so I had to be careful not to dose too high on it. But I've since taken a protocol of electrolytes and supplements, and now my blood pressure isn't reacting too much to niacinamide anymore. So I've been fine with taking 2100mg b3 per day. I may dial down the dosage though, as I seem to have low blood sugar effects as of late.

I hope we both get our kidneys better. It's very good we can share our impressions and ideas on this. Good luck to us both!

 

[yerrag]

@gilson d dantas I got my eGFR panel results yesterday. And again, you were right about my cystatin C levels: 1.19 mg/L (reference 0.41-0.99). Serum creatinine at 115.70 umol/L (range 64.0-104.00). eGFR computed at 61 mL/min/1.73 m2. This is just barely above 60, which is considered to be a cutoff point for CKD.

This compares well to the eGFR result based from creatinine only, from earlier: 62.76 ml/min/1.73 m2

These results confirm that I have a low glomerular filtration, and my kidneys could stand to be improved.

However, with a 24 hr urine collection, I'm getting a GFR of 108 ml/min creatinine clearance.It's said that creatinine clearance overestimates GFR by 20%, because the kidney tubules themselves produce creatinine. Factoring for that, I would arrive at a GFR of 86 ml/min.

I think continuing with niacinamide would be a good course to take.

 

[Wagner83]

The study i posted was done on humans and animals.

Here is another study done on animal showing the same conclusion of insulin resistance.

Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induced obesity
Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induce... - PubMed - NCBI

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

 

[Kray]

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.

Can you support your claim for endotoxins in product such as Great Lakes Green Collagen Hydrolysate?

 

[Goobz]

I'm sure this has been discussed before, but...

Wouldn't some of these negative effects be due to the fact that high dose nicotinamide turns off the sirtuins and other NAD+ consuming enzymes via negative feedback?

This is mentioned frequently by the proponents of NR/NMN, as a reason to supplement with those instead.

 

[Mito]

Wouldn't some of these negative effects be due to the fact that high dose nicotinamide turns off the sirtuins and other NAD+ consuming enzymes via negative feedback?

This is mentioned frequently by the proponents of NR/NMN, as a reason to supplement with those instead.

Ray Peat views turning off sirtuins as generally a good thing. Sirtuins And Life Extension

 

[Ingenol]

This is interesting. I've been taking relatively high doses of NMN (sublingual, split throughout the day) and think it may be making me tired/weak.

 

[LeeLemonoil]

The Plasma NAD+ Metabolome Is Dysregulated In ‘‘Normal’’ Aging

Read that thread for additional infos on that topic. I think it is very clear that excess NAD+-precursors including Niacinamide, NR and NMN are dangerous.

 

[Goobz]

Ray Peat views turning off sirtuins as generally a good thing. Sirtuins And Life Extension

Ah I see. Thanks for that, I gave the article on resveratrol a read. I will have to read a bit more to decide fully, but at this stage those ideas don't appear to make a lot of sense to me, given the more recent data on resveratrol. But that's true for his ideas on estrogen in general, so I want to read a bit more first.

But in any case, I'll have to check, but I seem to remember it's not just the sirtuins that get turned off by the nicotinamide off switch

 

[Mito]

Ah I see. Thanks for that, I gave the article on resveratrol a read. I will have to read a bit more to decide fully, but at this stage those ideas don't appear to make a lot of sense to me, given the more recent data on resveratrol. But that's true for his ideas on estrogen in general, so I want to read a bit more first.

A bit more recent discussion on sirtuins here Niacinamide May Treat Brain Cancer (glioblastoma).