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

Discussion in 'Scientific Studies' started by nathan10000, Feb 8, 2017.

  1. nathan10000

    nathan10000 Member

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    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."
     
  2. OP
    nathan10000

    nathan10000 Member

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    "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"
     
  3. ReSTART

    ReSTART Member

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    100mg/kg/day seems quite high.
     
  4. OP
    nathan10000

    nathan10000 Member

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    thats mice dosage, its much lower if convert to equivalent human dosage.
    8.3 mg/kg/day
     
  5. What-a-Riot

    What-a-Riot Member

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    i think that converts to 16.66 mg/kg human dose
     
  6. OP
    nathan10000

    nathan10000 Member

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    "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."
     
  7. OP
    nathan10000

    nathan10000 Member

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    "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"
     
  8. OP
    nathan10000

    nathan10000 Member

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    [ 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
     
  9. sladerunner69

    sladerunner69 Member

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    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.
     
  10. OP
    nathan10000

    nathan10000 Member

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    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
     
  11. OP
    nathan10000

    nathan10000 Member

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    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.
     
  12. Mountain

    Mountain Member

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    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.
     
  13. OP
    nathan10000

    nathan10000 Member

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    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....
     
  14. Wagner83

    Wagner83 Member

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    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
     
  15. Such_Saturation

    Such_Saturation Member

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    this forum sometimes
     
  16. haidut

    haidut Member

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    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.
     
  17. Drareg

    Drareg Member

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    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.
     
  18. Drareg

    Drareg Member

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    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?
     
  19. paymanz

    paymanz Member

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    these are almost true for niacin , but not niacinamide.
     
  20. Rad

    Rad Member

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    Here's the file.

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