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Niacinamide Can Cure Liver (and Maybe Pancreatic) Cancer

Discussion in 'Scientific Studies' started by haidut, Jan 19, 2017.

  1. haidut

    haidut Member

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    This study shows that depletion of NAD is a direct cause of the so-called hepatocellular carcinoma (HCC), which is the most common type of liver cancer. People with HCC often develop metastases in the pancreas and in advanced stages, the condition is indistinguishable from pancreatic cancer. Remarkably, not only did treatment with niacinamide completely prevent the development of HCC but it also made the established HCC tumors disappear. Niacinamide also fully protected from pancreatic cancer development. Unfortunately, the study did not look at whether niacinamide would also be able to cure established tumors like it did for HCC. The result of this study remind of another one where niacinamide completely prevented cancer metastases.
    Niacinamide Fully Prevents Breast Cancer Metastasis

    As far as doses - the HED was quite reasonable. The stated dose was 500 mg/kg of diet daily, which translates to 5.5mg/kg bodyweight daily for a human. Duration of treatment was 12 weeks.


    https://www.sciencedaily.com/releases/2014/11/141120123234.htm
    "...The inverse relationship between NAD+ and cancer awakened the curiosity of the researchers: could an increase in NAD+ have beneficial effects on the disease? When the scientists supplemented the diet in genetically modified mice with nicotinamide riboside, a derivative of vitamin B3 that increases intracellular levels of NAD+, they did not observe tumour development. Surprisingly, when they gave this diet to mice that had already developed the disease, the size of the tumours was reduced and they eventually disappeared."

    http://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00392-4
    "...To investigate whether restoring NAD+ pools would prevent dysplastic nodules and tumor formation, 3-week-old hURI-tetOFFhep mice were supplied with a nicotinamide riboside (NR) diet. NR significantly increased hepatic NAD+concentrations (Figure S5A) without affecting liver-to-body weight ratio (Figure S5B). We detected dysplastic lesions and DNA damage in all mutants on chow, but not in those on NR, which also had reduced fibrosis, p53 abundance, and Ser-18 phosphorylation (Figures 5A–5D, S5C, and S5D). Prolonged NR treatment prevented tumor development and reduced ALT levels (Figures 5E–5G). Similarly liver tumors were prevented in 30-week-old homozygous mutants with higher URI levels (Figure S5E). Thus, restoring NAD+ pools protects from hURI-induced DNA damage, preneoplastic lesions, and tumor development. Surprisingly, 12-week-old homozygous mutants with full blown tumors then on 48 weeks of NR regimen showed significant tumor regression (Figures S5F and S5G), and their livers had high levels of cleaved caspase 3 (Figure S5H), suggesting that boosting NAD+ levels may be cytotoxic for tumor cells."

    "...Next, we explored whether other oncogenes had similar effects. Ela-1-myc mice, unlike K-RasG12V mice, develop pancreatic adenocarcinomas with high levels of DNA damage, while pancreatic tumors initiated by K-RasG12V show no signs of replicative stress (Figures S5I and S5J). TOD2 and AFMID were clearly downregulated in Ela-1-myc, but not in K-RasG12Vpancreas (Figure S5K). In 3-week-old Ela-1-myc mice, 4 weeks of NR diet did not affect acinar-to-ductal metaplasia (ADM), but 12 weeks of NR diet decreased ADM and carcinomas formation compared to chow fed mice (Figures S5L–S5O). Importantly pancreatic NAD+ levels were significantly reduced in Ela-1-myc mutants on chow diet, but restored to almost control levels on NR diet (Figure S5P). Thus, oncogene-induced DNA damage has a common bearing on NAD+ levels."
     
  2. Nick Nieves

    Nick Nieves Member

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    How different is nicotinamide riboside from niacinamide? Is it just more effective at raising NAD+ at lower doses?

    Also, are you planning on releasing a pure niacinamide supplement?
     
  3. OP
    haidut

    haidut Member

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    Both niacinamide and NR have to go through the same intermediate called nicotinamide mononucleotide in order to raise NAD levels (see attached image). They have comparable effectiveness in raising NAD, but there is evidence that NR may actually be worse than niacinamide since not only does NR raise NAD levels it also increases NAD consumption through PARP (see study below). This is not desirable as the net effect on long term NAD levels may be nil or even negative. In addition, NR is an activator of sirtuins (SIRT) while niacinamide is a SIRT inhibitor and it also inhibits NAD consumption. The inhbition of NAD consumption together with inhbition of sirtuins is currently in clinical trials for treating cancer.
    Nicotinamide riboside is uniquely and orally bioavailable in mice and humans : Nature Communications
    "...In addition to its role as a coenzyme, NAD+ is the consumed substrate of enzymes such as poly-ADPribose polymerases (PARPs), sirtuins and cyclic ADPribose synthetases1. In redox reactions, the biosynthetic structures of NAD+, NADH, NADP+ and NADPH are preserved. In contrast, PARP3, sirtuin4 and cyclic ADPribose synthetase5activities hydrolyze the linkage between the nicotinamide (Nam) and the ADPribosyl moieties of NAD+ to signal DNA damage, alter gene expression, control post-translational modifications and regulate calcium signalling."

    "...Nam without conversion to NAD+. Interestingly, of three NAD+precursor vitamins provided in bolus at equivalent oral doses, Nam provided the least increase in ADPR (Fig. 5j). Whereas the area under the curve (AUC) of the Nam-driven rise in hepatic NAD+ indicated a ∼50% advantage of Nam over NA (Fig. 5b), there was a >50% deficit in Nam-driven ADPR accumulation versus NA (Fig. 5j). This is consistent with the idea that high-dose NA, though not an ideal hepatic NAD+precursor, is effective as a cholesterol agent whereas Nam is not44because high-dose Nam inhibits sirtuins1. Notably, NR is active as a cholesterol-lowering agent in overfed mice30."
     

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  4. superhuman

    superhuman Member

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    Interesting. I thought esp high dose niacinamide would increase liver enzymes and cause problems?
     
  5. OP
    haidut

    haidut Member

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    You'd have to take more than 3g daily for months to get this effect and even then it is not clear that the niacinamide was toxic as it only elevated liver enzymez to less than 2x the upper limit and there was no evidence of tissue pathology. Broda Barnes said that this elevation of liver enzymes to less than 2x upper limit is actually a sign of liver working well and not a sign of liver injury. The dose used in this study was <500mg daily for most people and in those doses niacinamide was shown to reverse liver damage.
    Low Dose Niacinamide Prevents NAFLD / Cirrhosis
     
  6. superhuman

    superhuman Member

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    Yeah thats great. Im currently only doing 50mg 3x a day so maybe i should try and increase it since i have some signs of a slower or lower then optimal liver and kidney function
     
  7. chispas

    chispas Member

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    This is exactly the protocol I suggested to a friend after being told that she needed surgery for NAFL disease. She had ultrasounds done that demonstrated the extent of the problem. After six months of taking 500mg B3 a day (the pain had vanished within two weeks of commencing the dose) she had a follow up scan, which showed nothing but a healthy liver, and this was reflected in her blood tests, which normalised. The specialist was angry that she used B3, and said it was quackery. The specialist had put her on a diet low in sugar, and recommended she stop drinking Coke. He must have been applying the "try to kill the patient" treatment!

    She still takes B3 today as a preventative because she consumes a lot of oily fish as part of her traditional islander diet. She continues to have no problems, and no longer eats a low sugar diet.
     
  8. OP
    haidut

    haidut Member

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    If B3 was quackery than what was the disappearance of the NALF? Divine intervention?
     
  9. What-a-Riot

    What-a-Riot Member

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    i'd call b3 divine. god's own vitamin
     
  10. OP
    haidut

    haidut Member

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  11. Tarmander

    Tarmander Member

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    Does niacinamide have a crystalline structure? Whenever I spill the powder it reminds me of fine fiber glass
     
  12. chispas

    chispas Member

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    You see, the disappearance of the NAFL correlated precisely to the disappearance of a repayment the specialist hoped to make towards his luxury car. There's no way those two phenomena are linked, so quackery must be responsible!
     
  13. PUTFOT

    PUTFOT Member

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    What's the ideal dosage to skyrocket that GABA?
     
  14. MigFon

    MigFon Member

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    I've had an 11 mm nodule disappear from my liver last year, either HCC or a metastasis from testicular cancer in 2015. 4 g of niacinamide daily was part of the protocol.
     
  15. OP
    haidut

    haidut Member

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    I think it does. When I dissolved in DMSO and leave out in the cold it forms crystals inside the bottle. Other supplements simply precipitate as a cloudy residue, but niacinamide does not.
     
  16. OP
    haidut

    haidut Member

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    What does GABA have to do with the study above? Niacinamide does not raise GABA as far as I know, it acts as GABAa agonist.
     
  17. OP
    haidut

    haidut Member

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    Amazing! What else were you taking? Vitamin K and caffeine maybe?
     
  18. MigFon

    MigFon Member

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    I took about 4g of Aspirin, 4 g niacinamide, 30drops of lapodin 3x per day, 1 grain of tyromax, 15 mg of kuinone 3x per day, 40 drops mitolipin, 20 mg progesterone 2x per day, Vitamins A, D, E, some Methylene Blue and some Turkey Tail Mushroom supplement, and I think that was about it.

    As far as caffeine is concerned, I brewed some really strong coffee and tried to drink as much as I could (up to 300mL, but it varied a lot from day to day), however, coffee/caffeine supplements really upset my intestines and I think my glycogen stores suck, so I was really limited on the amount an how often I could drink.

    Perhaps some of the supplementation doesn't make much sense, but as soon as I found out about the nodule I tried to soak up as much information from this forum as possible, and this protocol was the best I could come up with on such short notice.

    I don't know what did it, but something seemed to have worked.

    I would like to thank you personally because your posts were invaluable, as well as the idealabs supplements.

    Thank you very much Sir.
     
  19. High_Prob

    High_Prob Member

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    I am confused: Isn't agonizing Gaba the same as increasing it? (I promise this will not become a Gaba thread, this just threw me off)
     
  20. High_Prob

    High_Prob Member

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    Nevermind...I understand now
     
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