Endotoxin Causes Cachexia In Cancer; How Statin Drugs Really Work

Discussion in 'Scientific Studies' started by haidut, Mar 22, 2019.

  1. haidut

    haidut Member

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    The title of the post is a bit strange but it is pretty much what the study below found. Just like the SSRI drugs, the mechanism of action of statins is (officially) not really known. The official version for the antidepressant effects of SSRI drugs was that they increase intracellular levels of serotonin. The latter part is true, but that is not what explains the benefits of SSRI drugs. Their lesser known effects on increasing allopregnanolone levels in the brain (by increasing 3a-HSD activity) and lowering cortisol levels (by blocking 5-HT2C receptor) are the real mechanism of action. Obviously, admitting that a supposedly serotonergic drug achieves its antidepressant effects by blocking the 5-HT2C receptor does not sit well with Big Pharma, so the official study continues to be that serotonin helps alleviate depression.
    What does that have to do with statins? Well, a few large trials did appear to show benefit from (some, not all) statins for preventing CVD development. The official story was that this benefit was due to the statins lowering cholesterol levels. However, a lesser known effects of statins that has been kept well-hidden from the public is that some statin drugs are actually antagonists of the endotoxin receptor TLR4. Given the role of TLR4 in virtually all chronic diseases but especially CVD, the observed benefit from statins suddenly become very clear. However, just like in the case of SSRI drugs, that does not mean that suddenly statins become attractive and beneficial drugs. Their negative systemic effects of cholesterol-lowering likely vastly outweigh the benefits these drugs provide by blocking endotoxin.
    And this brings us to the main topic of the study below, which is that TLR4 is apparently crucial for the tissue wasting commonly seen in cancer and known as cachexia. This wasting is actually seen not only in cancer but in a number of other chronic conditions including AIDS, IBD, ALS, Huntington's, and even as part of the general aging process. As the study below found, blocking TLR4 with the statin drug Lipitor (atorvastatin) blocked the sating seen in cancer. There are many other, possibly safer, ways to block TLR4 including with chemicals like ketotifen, cyproheptadine, emodin, etc or even with food like saturated fats, vitamin A, B2, D, etc. Interestingly, both ketotifen and cyproheptadine have successfully been used to prevent/treat cancer cachexia in humans. Given the renewed interest in TLR4 antagonsits, I would not be surprised if both drugs get repurposed and their prices skyrocket. Cyproheptadine is already next to impossible to get even by prescription in most Western countries.
    And last but not least, the study confirmed earlier findings that the porcess of cachexia is associated with the so-called browning of the adipose tissue, which is is also caused by increased adrenaline, exposure to cold, and pretty much any chronic exposure to stress. This is one of the main reasons I kept arguing against cold-exposure thermogenesis as a way to lose fat. It seems to be all the rage now, and is promoted by people like Dr. Chris Kresser.
    https://chriskresser.com/treating-sibo-cold-thermogenisis-and-when-to-take-probiotics/
    For a healthy person, occasional cold exposure is probably OK, but if there is a dormant tumor somewhere in the body this additional stress can likely re-activate it and start the cachectic process.


    https://bv.fapesp.br/en/auxilios/92...n-gastrointestinal-cancer-patients-potential/
    Drug used to control cholesterol found effective against cancer-associated cachexia

    "...TLR4 (toll-like receptor 4) is a protein that plays a key role in pathogen recognition, innate immunity activation and inflammatory responses. Because obesity, similar to cachexia, is associated with systemic inflammation, the authors of the study suspected that TLR4 might be linked to adipose tissue remodeling. "We set out to associate the action of TLR4 with cachexia," Batista said. In a mouse model, the researchers used both genetic ablation and pharmacological inhibition of a receptor similar to human TLR4. They next induced lung cancer in genetically modified mice (without TLR4) and in control wild-type mice (with TLR4). "We found that 28 days after the inoculation of cancer cells in their lungs, the wild-type mice with TLR4 had lost 12% of their body weight, a classic sign of cachexia," Batista said. Cachexia was less severe in mice without TLR4. "These animals lost less weight and muscle mass. They also lived longer, even though tumor growth was the same as in the control group. It's also important to note that no lung metastasis was detected among the genetically modified mice," Batista said. An analysis of adipose cells from the two groups showed that browning had occurred in the control mice with TLR4. This process likely led to accelerated weight loss. "Adipose tissue was less altered in the genetically modified mice without TLR4. In other words, lack of the receptor significantly blocked the adipose tissue browning effect," Batista said."

    "...Atorvastatin is an inexpensive drug widely used to control cholesterol. Research performed in recent years has described the anti-inflammatory effects of atorvastatin, including the downregulation of TLR4 gene expression. The authors of the study decided to use a preclinical model to determine whether atorvastatin affects the development of cachexia in wild-type mice with TLR4 in a similar manner to its effect on genetically modified mice without TLR4. They induced lung cancer in two groups of wild-type mice. In the group not treated with atorvastatin, tumors developed, and symptoms of cachexia were observed. In mice treated with atorvastatin, the result was even better than that in genetically modified mice without TLR4. "Treatment with atorvastatin proved effective in extending survival, attenuating adipose tissue remodeling and reducing tumor growth [by 49.7%] in comparison with a control group not treated with the drug. We showed that atorvastatin had a direct effect on the action of TLR4, which inhibited adipose tissue browning and reduced tumor growth," Batista said."
     
  2. CLASH

    CLASH Member

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  3. Zpol

    Zpol Member

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    Wow, thank you Haduit for pointing this out! I know a lot of people on statins and SSRI's, I'm sure many of us do.
    Would there be any way of offsetting the cholesterol lowering negatives of statins? I suppose thyroid supp's and/or a general pro-thyroid diet (lots of OJ, ice cream, eggs, hydrogentated coconut oil, no PUFA, etc), anything else? Unfortunately, people are never going to stop taking statins despite the fact there are healthier and just as effective alternatives so I'm to figure out some ways to offset the negatives and maintain the positives. In fact statins may even become more widely Rx'd for IBS-C and SIBO-C as well ...
    Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders.
     
  4. jb116

    jb116 Member

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    But @haidut doncha know vit A is poison now :wacky:
     
  5. OP
    haidut

    haidut Member

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    Yes, if it makes it to the colon and can reduce bacteria count there that would be another beneficial mechanism but still related to endotoxin.
     
  6. OP
    haidut

    haidut Member

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    Not that I know of as statins also deplete CoQ10. So, the combination of low CoQ10, low cholesterol, and low downstream steroids are hard to address in combination and we probably don't know of many other pathways statins affect in a bad way. I would only consider a statin as a worst case option.
     
  7. danielbb

    danielbb Member

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    I have a history of serious heart disease that I believe has been reversed by 1) eliminating PUFA 2) Processed food 3) Added iron to substances such as flour, 4) and Soy. I've lost lots of weight and can walk up and down huge hills for miles without tiring. My Doctor is just about ready to take me off blood pressure medication so that is a sign my heart is working well in addition to my stamina. With respect to statins, he takes them himself as a prophylactic measure against heart disease even though he is in good shape and has no history of heart disease himself. I am skeptical but he told me a good reason to take statins is they have anti-inflammatory properties. That caught my attention so I researched using statins and anti-inflammatory and did see legitimate studies talking about this effect. Low-dose aspirin therapy (81 mg) (typical for heart patients) is another anti-inflammatory that I also use. I have been taking low dose statin (10 mg) (Crestor - rosuvostatin) 3 days per week on Monday, Weds. and Friday per a negotiation with him. No side effects that I can notice. He claims there are hundreds of studies supporting his views on statins. I am trying to split the baby here. I'll admit I am skeptical. My LDL was 107 without statins and for heart patients, they like to keep it below 70. It is what it is now (my next physical is in November) because I am not planning on increasing my dose beyond what I mentioned here. My triglycerides are low (40ish) and many do not mention that when discussing overall heart health. I also no longer drink alcohol and I believe this has also helped to improve my blood profile. Blood pressure which is hugely linked to the disease, seems to be highly related to our weight. As my weight has come off (I have the same pant size and weight as high school and I am 58 years old), my blood pressure has dropped accordingly. I am not beating my chest about anything I've talked about here, but wanted to share openly some of my concerns and progress toward hopefully beating this dreaded disease. I believe that proper diet and moderate exercise has healed me the most and as far as I can tell.
     
  8. Zpol

    Zpol Member

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    Thank you for your input.

    Glad you have noticeable improvement. I'm looking for as much success stories as I can find with for heart disease so I can follow suit in regards to my fiance. He suffered a heart attack at age 40 (two stents put in). He won't stop taking statins but he will take supplements and dietary measure to offset the negatives, but I'm at a loss as to what to recommend. Currently, I prepare all his food (RP style) and I've got him taking magnesium glycinate, vit C, and famotidine. He takes baby aspirin in addition to statins and levothyroxine per the doctor. His G.P. doctor said to not bother with coQ10. Your doctor's thought process for himself mirrors what most people taking statins think. They use the drug as safety net so they can have their unhealthy lifestyle; that's dangerous thinking. But for you and people who already have serious heart disease... what then? The statins may actually help and the side effects may actually be less damaging than the disease. I'm quite sure cortisol is an issue too. In addition to pro-thyroid diet, keeping cortisol and adrenaline low are probably the only other factors that could mitigate the side effects. Trying to get him and anyone else these days to eat breakfast in order to lower cortisol is like pulling teeth.
     
  9. Sativa

    Sativa Member

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    Statins are pretty savage to the body, and are sure to undermine biological coherence.
    What you are calling 'side effects' are actually the primary effects. Statins are probably one of the top anti-peat drugs, along-side SSRI's lol!

    Anyway... I'm basically saying that statins will never provide any benefits (except, eg - minor anti-endotoxin effects as Haidut mentioned).

    At least, take Statins with CoQ10 lol, and maybe squalane, which is directly related to cholesterol. squalane is used to make all the important neuro-steroids Peat talks about.
     
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