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

[nathan10000]

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."

 

[nathan10000]

"Previous studies showed that NAM administration (2 g/day, 2 weeks) caused a decrease in insulin sensitivity in IDDM patients despite increased insulin secretion, suggesting that the use of NAM in IDDM may lead to insulin resistance in humans"

"Excess NAM intake leads to homocysteine-related cardiovascular disease"

 

[ReSTART]

100mg/kg/day seems quite high.

 

[nathan10000]

thats mice dosage, its much lower if convert to equivalent human dosage.
8.3 mg/kg/day

 

[What-a-Riot]

i think that converts to 16.66 mg/kg human dose

 

[nathan10000]

"NAM-treated mice did not differ significantly from control mice in body weight, body composition or the weight of fat depots. Our findings suggest that chronic treatment with NAM results in systemic insulin resistance without obesity in mice fed a regular chow diet."

 

[nathan10000]

"It is noteworthy that NAM is also a substrate for nicotinamide Nmethyltransferase (NNMT), which methylates NAM to produce N(1)-methylnicotinamide (MNAM). Recent studies have suggested that NNMT activity and plasma MNAM levels are linked to dietinduced obesity and diabetes in rodents and humans"

 

[nathan10000]

[ moderator edit: same study as above, threads merged ]

"Due to the fact that NAM-induced insulin resistance was not accompanied by obesity, we assessed the lipid content in skeletal muscle and liver. Skeletal muscle TAG levels were higher in NAM treated mice compared with controls, but this difference was not significant in liver (Fig. 2A)

Further, there was a significant decrease in muscular and hepatic glycogen content in NAM-treated mice" (fulltext)

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

 

[sladerunner69]

That's why you have to eat plenty of sugar on niacinmide. There was similar thread about niacinmide causing one to become hypoglycemic, because it powerfully boosts the metabolism and glucose consumption. For some people the effect is too strong, and they get a headache which I think would be brain glycogen depletion perhaps. Additional consumption of sugar would likely help, but some people who are not yet fully adapted can not utilize ingested sugar efficiently enough to compensate for the effects.

 

[nathan10000]

It doesnt boost metabolism but decrease oxidation. Eating sugar is not going to help with other side effect of niacinamide such as
1. increase TG and FFA
2. increase insulin resistance
3. lipid accumulation in the skeletal muscle
4. reduced FA oxidation
5. increase homocysteine-related cardiovascular disease
6. increase nicotinamide Nmethyltransferase which is linked to development of diabetes

 

[nathan10000]

Decrease of glycogen with niacinamide is not due to lack of carbohydrate but suppression at the level of genes. So "eating sugar" wont help to increase glycogen. Excessive of sugar will only increase TG accumulation.

 

[Mountain]

Lol what's your beef with niacinamide? You made your account like 2 days ago and have already made two anti-niacinamide threads, both of which cite the same journal article.

 

[nathan10000]

I had been regularly following up this forum for months. Recently, I found that interesting article. I am just letting people know the potential side effects of long term niacinamide in obese/ non obese individual. Its up to the reader to come up with their own conclusion in the end. Just watch out the glucose level, don't want ending up with diabetes eventually....

 

[Wagner83]

Sorry but how do they come to their conclusions on healthy humans from their 8 weeks study done on mice ?
Also :

Regular chow is composed of agricultural byproducts, such as ground wheat, corn, or oats, alfalfa and soybean meals, a protein source such as fish, and vegetable oil and is supplemented with minerals and vitamins. Thus, chow is a high fiber diet containing complex carbohydrates, with fats from a variety of vegetable sources. Chow is inexpensive to manufacture and is palatable to rodents. In contrast, defined high-fat diets consist of amino acid supplemented casein, cornstarch, maltodextrose or sucrose, and soybean oil or lard, also supplemented with minerals and vitamins. Fiber is often provided by cellulose. Chow and defined diets may exert significant separate and independent unintended effects on the measured phenotypes in any research protocol.

Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induce... - PubMed - NCBI
How do mice do on high starch , fiber and PUFAs diet? Am I wrong or did Vollkheimer show all the negative effects and inability of mice to process such starch?

Other remarks:
-They promote the virtues of resveratrol.
-The mice somewhat adapted to a high fat diet by improving their fatty acids oxidation.
-Since they say nicotinamide is essential for ATP synthesis I don't get this quote : "NAM impaired mitochondrial respiration capacity and energy production in skeletal muscle"
-See this study too (same journal):
Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes

 

[Such_Saturation]

side effect

reduced FA oxidation

this forum sometimes

 

[haidut]

Can somebody please provide a link to the full study or post it here? I would like to see the materials and methods function. If you block/inhibit lipolysis clearly you'd be dependent on glycogen for energy, so I see nothing abnormal about these effects in the title. But I want to see the full study before I comment more.

 

[Drareg]

Sorry but how do they come to their conclusions on healthy humans from their 8 weeks study done on mice ?
Also :

Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: compared to diet-induce... - PubMed - NCBI
How do mice do on high starch , fiber and PUFAs diet? Am I wrong or did Vollkheimer show all the negative effects and inability of mice to process such starch?

Other remarks:
-They promote the virtues of resveratrol.
-The mice somewhat adapted to a high fat diet by improving their fatty acids oxidation.
-Since they say nicotinamide is essential for ATP synthesis I don't get this quote : "NAM impaired mitochondrial respiration capacity and energy production in skeletal muscle"
-See this study too (same journal):
Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes

Your making too much sense,you will be labelled dogmatic Peat follower soon.

Keep in mind China is where a lot of niacinamide is produced,it's hugely profitable(billions)and the competition is heating up with producers.
It's a good thing the producers are based in China as its a fair and open society and the government would not try to Influence big business in any way whatsoever with threats of misinformation to hurt prices unless they pay more for example,the lysine and citric acid scandals were one off occurrences.

 

[Drareg]

"Due to the fact that NAM-induced insulin resistance was not accompanied by obesity, we assessed the lipid content in skeletal muscle and liver. Skeletal muscle TAG levels were higher in NAM treated mice compared with controls, but this difference was not significant in liver (Fig. 2A)

Further, there was a significant decrease in muscular and hepatic glycogen content in NAM-treated mice" (fulltext)

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

Hi,
How do your explain all the studies that show the opposite?
What's your take on them compared to this one study you posted?

 

[paymanz]

It doesnt boost metabolism but decrease oxidation. Eating sugar is not going to help with other side effect of niacinamide such as
1. increase TG and FFA
2. increase insulin resistance
3. lipid accumulation in the skeletal muscle
4. reduced FA oxidation
5. increase homocysteine-related cardiovascular disease
6. increase nicotinamide Nmethyltransferase which is linked to development of diabetes

these are almost true for niacin , but not niacinamide.

 

[Rad]

Here's the file.

Oops, wrong file and can't upload right one. Getting error message.