SIRT1 Is A Key Promoter Of Leukemia And Other Blood Cancers

Discussion in 'Scientific Studies' started by haidut, Jun 14, 2019.

  1. haidut

    haidut Member

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    SIRT1 (one of the sirtuin genes) is currently one of the stars in the nutritional/medical blogosphere. As far as back as 2004, SIRT1 was promoted as a key regulator of longevity and activating this gene was marketed as one of the most reliable ways of increasing lifespan. Resveratrol was lauded as one of the most potent natural SIRT1 activators and Harvard University put out a lot of studies promoting the use of SIRT1 activators, especially resveratrol and its patented varieties which Harvard owned. Dr. David Sinclair, one of the chief SIRT1/resveratrol boffins, went on to launch a company called Sirtris Pharmaceuticals.

    Sirtris Pharmaceuticals - Wikipedia

    The goal of this company was to commercialize the patented resveratrol derivatives and conduct human studies so that those derivatives are ultimately approved as drugs by the FDA. The company was sold for $720mil to GSK in 2008 and was shut down not long after due to increased death rates in active groups from clinical trials with Sirtris' patented resveratrol. Long story short - resveratrol and SIRT1 activation is nothing but a scam. In fact, Dr. Peat released an article calling resveratrol "a scam", which details many of the negative effects of SIRT1 activation in general and resveratrol specifically.
    Don’t Be Conned By The Resveratrol Scam

    Furthermore, for those who don't know, resveratrol is a stilbenoid - naturally occurring molecules with potent estrogenic effects. One of the most (in)famous stilbenoids is Vioxx - the withdrawn COX inhibitor drug that killed quite a few people in the early 2000s, likely due to its potent estrogenicity, and possibly also SIRT1 activation.
    Rofecoxib - Wikipedia

    Yet, the promotion of SIRT1 does not stop and other supplements are still marketed for SIRT1 activation. But why is activating SIRT1 dangerous? One of the core effects of SIRT1 activation is increased beta-oxidation. In other words, activating SIRT1 increases the oxidation of fat and by extension reduces the oxidation of glucose (Randle cycle). I posted several studies on the role of SIRT1 in cancer growth and metastases, and the protective role of SIRT1 inhibitors. I also posted in the crucial role of fat oxidation in cancer progression/metastasis, and the protective role of niacinamide/nicotinamide. Well, the most widely-recognized SIRT1 inhibitor happens to be niacinamide.
    https://raypeatforum.com/community/threads/niacinamide-lowers-fatty-acid-oxidation-by-inhibiting-sirt1.3421/
    Niacinamide Is Anti-estrogenic
    Niacinamide Is Androgenic And Increases Dht Effects/signaling

    And now, the study below corroborates yet again the role of SIRT1 as a cancer promoter. It shows that SIRT1 is overexpressed in chronic myeloid leukemia cells and that its overexpression is key for cancer cells maintaining their "stemness" and thus resistance to chemotherapy. Silencing/deletion of SIRT1 made the cancer easily susceptible to chemotherapy and prevented recurrence after treatment. Furthermore, because the fat-oxidation-promoting role of SIRT1 is so systemic, one would expect SIRT1 overexpression to promote the development of other cancers. That is exactly what the study authors found/claimed as well.

    JCI - SIRT1 regulates metabolism and leukemogenic potential in CML stem cells
    News - SIRT1 plays key role in chronic myeloid leukemia by aiding persistence of leukemic stem cells

    "...In a study published in the Journal of Clinical Investigation, Ajay Abraham, Ph.D., Shaowei Qiu, M.D., Ravi Bhatia, M.D., and colleagues at the University of Alabama at Birminghamshow how the stress-responsive protein SIRT1 plays important roles in maintaining the regenerative potential of CML leukemic stem cells and promoting leukemia development in CML. “Our studies provide a conceptual advance and new biological insights regarding the activity of SIRT1 and its role in CML leukemic stem cells,” said senior author Bhatia. At UAB, Bhatia is a professor of medicine, director of the Division of Hematology and Oncology, and interim director of the O’Neal Comprehensive Cancer Center at UAB. In 2012, Bhatia and colleagues reported that SIRT1 was overexpressed in CML leukemic stem cells compared to normal hematopoietic stem cells, and this overexpression contributed to CML leukemic stem cell maintenance and resistance to tyrosine kinase inhibitors. However, the underlying mechanisms were not known."

    "...Treatment with tyrosine kinase inhibitors is known to suppress leukemic hematopoiesis. When SIRT1-deleted mice were treated with tyrosine kinase inhibitors, the UAB researchers found an even greater suppression of leukemic hematopoiesis. The SIRT1 knock-out also impaired development of CML in the mouse model. Compared with the CML mice without SIRT1 knock-out, the researchers saw significant delays in developing increased numbers of leukocytes and neutrophils, and delayed enlargement of the spleen and time of death. The deletion also reversed redistribution of CML stem cells from the bone marrow to the spleen."

    "...Bhatia says the impact of this study extends to other hematological malignancies, including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. “Our research reveals new knowledge and concepts regarding the role of SIRT1 in metabolic regulation of hematopoietic stem cell and leukemic stem cell maintenance, growth and resistance,” Bhatia said. “This raises the possibility of developing improved strategies to target kinase-independent metabolic alterations.”
     
  2. jb116

    jb116 Member

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    Wow, sinclair has a ***t storm headed his way!
    It's sort of comical they want to promote B3 while also promoting something else like resveratroll that has essentially an opposite action.
     
  3. OP
    haidut

    haidut Member

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    Nah, he will be fine. Neither GSK came after him for selling them a turd, nor FDA for promoting false research. I guess the latter is not surprising since FDA believes SIRT1 activation is good. But GSK could have come after him considering Sirtris was a $700mil+ writeoff and they did not. So, either he is very powerful and cannot be touched or Big Pharma has totally lost its mind and blindly invests in snakeoil.
     
  4. jb116

    jb116 Member

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    Those are good points, and I'm certain it's true. But I was referring to his own health! That is, if he is actually taking the crap he promotes.
     
  5. OP
    haidut

    haidut Member

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    I don't think he does. When he was promoting Sirtris back in 2004 they asked him if he takes the patented resveratrol caps. He said "no, too early to say if it works. I drink wine instead". I just LOL-ed when I heard this. It makes GSK look even more stupid but I guess they may have thought it work as a drug where even lethal side effects are acceptable if it is 20% better than placebo for some disease.
     
  6. jb116

    jb116 Member

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    If that's true that he doesn't take it, that is such a joke. So basically he was just a maschot to sell it to the public.
     
  7. Rafael Lao Wai

    Rafael Lao Wai Member

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    This reminded me of this paragraph from one of Peat's articles:
    "There is still a strong division between what people can say in their professional publications, and what they believe. A man who was influential in designating vitamin E as an antioxidant, M.K. Horwitt, complained when the government raised its recommended vitamin E intake by 50%, because it wasn’t supported by new data, and because millions of people get only ten milligrams per day and “are healthy.” But he has been taking 200 mg daily (plus aspirin) for many years. He apparently doesn't have very much confidence in the ideas he advocates publicly. "( from Vitamin E: Estrogen antagonist, energy promoter, and anti-inflammatory)
     
  8. miki14

    miki14 Member

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    A "Chosenite" - well connected.
     
  9. LeeLemonoil

    LeeLemonoil Member

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    I‘d likecto bring this to the debate, not because I take an Anti-Peat or even an Anti-Haidut stance, but because it deserves consideration. Now, I would’nt know how waterproof their reasoning is. And even if Niacinamide is more like a „transient“ Sirt1-inhibitor it doesnt necessarily falsify predating research that Peat bases his Niacinamide view on.

    There is also the possibility that „they“ try to rationalize something to their dogma.


    Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells. - PubMed - NCBI
     
  10. jb116

    jb116 Member

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    Very applicable. I do also however see sinclair's position as even more nefarious.

    @haidut is it also BS that he takes metformin?
     
  11. Goobz

    Goobz Member

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    He does take resveratol and at very high doses. He says every morning he takes resveratrol, metformin and NMN
     
  12. chipdouglas

    chipdouglas Member

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  13. rei

    rei Member

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    He takes something that promotes fat oxidation with 1 that block fat oxidation and one that block mitochondrial activity. Suicide squad.
     
  14. chipdouglas

    chipdouglas Member

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    Since my sole interest lies in the truth, I feel like asking : is there any counter argument to what you posted Haidut ? I'm not emotionally attached to resveratrol or any other substances for that matter. My point is that it doesn't make sense that a scientist like Sinclair would take substances likely to give him cancer.
     
  15. OP
    haidut

    haidut Member

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    Did you read the post in full, including the links I posted on resveratrol and Sirtris? It should answer pretty much all of your questions. The role of SIRT in cancer is undisputed, given their promotion of fatty acid oxidation. None of what I post is "me" saying it. It is all independent evidence.
    Btw, I am not saying Sinclair knew resveratrol causes cancer and still promoted it. AFAIK, he is a firm believer in the mutation theory and as such to him messing with SIRT has no relevance to cancer. But still, I don't think he is clean. The Vioxx fiasco occurred before Sirtris and resveratrol took off and most of the *coxib drugs are based on the stilbenoid skeleton, as is resveratrol. Sinclair knew quite well these drugs are estrogenic and kill yet still promoted his own synthetic version of resveratrol and when GSK started trials with it people died.
     
  16. chipdouglas

    chipdouglas Member

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    Honestly, I haven't read the links, but will - it's far too interesting. Moreover my wife has been taking T-resveratrol for 4 months now. I've told her to stop. You've got a point Haidut. I'm clearly not brushing off what you posted. Like I said, what matters to me most is the truth. I'm glad I came across your post and now I'm worried about my wife...
     
  17. PeatReader

    PeatReader New Member

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    Serious question, why would Peat post the article "Don’t Be Conned By The Resveratrol Scam" to that random blog rather than to his website raypeat dot com? How do we know it's Peat?
     
  18. Rafael Lao Wai

    Rafael Lao Wai Member

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    I don't know why that article isn't on his site, but I'm pretty sure he mentioned the opposite effects of niacinamide and resveratrol in more than one article, and he clearly thinks niacinamide is quite beneficial, so, although this doesn't necessarily prove that that article was written by him, it does indicate that at least Peat's view is that resveratrol isn't good, which is a message contained in that article as well . Also, the writing style looks a lot like the way Peat writes in his other newsletters.
     
  19. chipdouglas

    chipdouglas Member

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  20. ecstatichamster

    ecstatichamster Member

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    this is from an old Dr. Peat newsletter that I read the other day.
     
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