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Stress As The Underlying Cause Behind ALL Chronic Diseases

Discussion in 'Scientific Studies' started by haidut, Sep 13, 2018.

  1. haidut

    haidut Member

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    One of the more controversial of Ray's statements is that chronic stress is the underlying cause of many/most chronic conditions, especially autoimmune ones. In several of his articles he describes the role tissue damage under the influence of cortisol and estrogen play in creating an immune response. That immune response is not "attacking" certain organs but rather simply picks up the debris of damaged/diseased tissue. The cellular debris from the damaged tissue is what alerts the immune system to mount a response. Needless to day, this "cellular debris" theory of autoimmune conditions is not taken seriously in mainstream medical circles. I have personally spoken to a few rheumatologists and neuroendrocrinologists and have been told that these are "old ideas that got refuted back in the 1950s by genetics". Oncologists just laugh (nervously) and refuse to even discuss the idea. Well, it appears the latest studies (like the one below) are resurrecting the "morphostasis" idea of immunity that Peat has mentioned so many times in his articles and interviews, and the special role stress plays in it.
    home_page

    One of more interesting bits from the study below is that the cellular debris from damaged tissue apparently acts like the hormone cortisol and produces the same systemic physiological response as a stressful event. What's shocking is that even a stressful event as short as five (5) minutes in duration was able to trigger this debris-induced response. The study found that this stress-like response and immune overdrive was due to the cellular debris activating one of the TLR receptors, in this case TLR9. Just like its better known cousin TLR4 (endotoxin receptor), the receptor TLR9 can get activated by a number of bacteria, as well as viruses and even malignant cells.
    TLR9 - Wikipedia
    So, if the cellular debris causes an "autoimmune" response by activating TLR9 then in theory one way to dampen that response is by administering a TLR9 antagonist. As many of the forum users know, Peat has mentioned low-dose naltrexone (LDN) as a potentially helpful approach for treating autoimmune conditions. Naltrexone is best known for its antagonism of opioid receptors and TLR4, however it is also capable of antagonizing the response to activating virtually the whole TLR family, including TLR7, TLR8 and TLR9.
    Naltrexone Inhibits IL-6 and TNFα Production in Human Immune Cell Subsets following Stimulation with Ligands for Intracellular Toll-Like Receptors. - PubMed - NCBI

    As the currently accumulated evidence shows virtually all chronic disease have in common chronic activation of one or more of the TLR entities this may explain the benefits of LDN for so many chronic inflammatory conditions, "autoimmune" diseases, neurodegenerative conditions, and even cancer. However, blocking the TLR family of receptors is probably not going to be enough to resolve a conditions for good. For that to happen, the stress response must be stopped too in order to stop the tissue destruction. Substances like thyroid, vitamin D, progesterone, pregnenolone, DHEA, testosterone, aspirin, methylene blue, the *caine anesthetics, etc are among the most fundamentally protective agents that can be administered synergistically with TLR antagonists to hopefully deliver true recovery from a chronic condition.

    Towards the end of the article it becomes quite obvious that the authors think (stress-induced) mitochondrial damage is the underlying reason behind ALL inflammatory responses and thus chronic disease. Sounds like something coming straight from Peat's or Selye's writings. If Selye were to read this study today he would have probably sighed deeply and said (again) "Stress kills, have some respect for it". Hey @Amazoniac, didn't you post this quote somewhere on the site?

    Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury
    Brain's Dumped DNA May Lead to Stress, Depression

    "...This so-called “fight-or-flight” response served our ancestors well, but its continual activation in our modern-day lives comes with a cost. Scientists are starting to realize stress often exacerbates several diseases, including depression, diabetes, cardiovascular disease, HIV/AIDS and asthma. One theory is hoping to explain the link between stress and such widespread havoc by laying the blame on an unexpected source—the microscopic powerhouses inside each cell."

    "...But our fight-or-flight response places extreme demands on the mitochondria. All of a sudden, they need to produce much more energy to fuel a faster heartbeat, expanding lungs and tensing muscles, which leaves them vulnerable to damage. Unlike DNA in the cell’s nucleus, though, mitochondria have limited repair mechanisms. And recent animal studies have shown chronic stress not only leads to mitochondrial damage in brain regions such as the hippocampus, hypothalamus and cortex, it also results in mitochondria releasing their DNA into the cell cytoplasm, and eventually into the blood. The genetic cast-offs are not just inert cellular waste. “This circulating mitochondrial DNA acts like a hormone,” says Martin Picard, a psychobiologist at Columbia University, who has been studying mitochondrial behavior and the cell-free mitochondrial DNA for the better part of the last decade. Ejection of mitochondrial DNA from the cell mimics somewhat adrenal glands’ release of cortisol in response to stress, he says. Certain cells produce the circulating mitochondrial DNA and, as with the adrenal glands, its release is also triggered by stress."

    "...To demonstrate psychological stress can cause mitochondrial DNA to be released by cells, Picard and his team devised a quick stress test. They asked 50 otherwise healthy men and women to deliver a quick speech defending themselves against a false accusation on camera. Afterward the researchers took blood samples from the participants and compared them with blood taken immediately before they were stressed. Even though the stressful task only lasted a total of five minutes, the scientists found participants’ serum circulating mitochondrial DNA levels more than doubled 30 minutes after the test. These results, currently under review, provide the first direct evidence for how bits of mitochondrial DNA floating in our blood may relay stress to other parts of the body, like dominoes tumbling one after another."

    "...Previous studies have provided several clues that suggest circulating mitochondrial DNA is a hallmark of stress. In 2016 Swedish researchers published findings in Translational Psychiatry demonstrating elevated levels of mitochondrial DNA outside the cell in 37 people who had recently attempted suicide. Earlier this year the same group of scientists published another paper in Neuropsychopharmacology showing people with major depression had high levels of circulating mitochondrial DNA, and these levels kept increasing in patients who did not respond well to antidepressant medication."

    "...These studies are all part of an emerging field of research on mitochondrial DNA, where scientists are recognizing that the tiny organelles have effects across a wide range of diseases. “Mitochondrial DNA is probably the most sensitive thing in your body,” says Douglas Wallace, director of the Center for Mitochondrial and Epigenomic Medicine at The Children’s Hospital of Philadelphia. “If your mitochondria are sensing a problem, then all the rest of you is in trouble, too.”"

    "...But how was this inflammation triggered by mitochondrial DNA leaking out of cells? A 2010 Nature paper provided the answer: In it researchers demonstrated the way mitochondrial DNA, when released into the blood after an injury, mobilized a pro-inflammatory immune response. Because of mitochondria’s bacterial origin and its circular DNA structure, immune cells think it’s a foreign invader. When circulating mitochondrial DNA binds to a particular receptor, TLR9, on immune cells, they respond as if they were reacting to a foreign invader such as a flu virus or an infected wound. The immune cells release chemicals called cytokines telling other white blood cells they need to report for duty at sites of infection, inflammation or trauma. Together, this growing understanding of circulating mitochondrial DNA sets a time frame for how psychological stress may lead to widespread inflammation, Picard says. “Mitochondria are the missing link between our psychological state and neurological or other disorders involving inflammation,” he says."
     
  2. Dhair

    Dhair Member

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    So according to these neuroendocrinologists that you have spoken to, Selye's work is now irrelevant basically? If these ideas were rendered useless by genetics research, then there must not be any place for his work whatsoever according to them. I wonder what these people think about PTSD sufferers being successfully treated by hormone replacement therapy and things like that.
     
  3. OP
    haidut

    haidut Member

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    As I mentioned in other threads, most doctors nowadays are remarkably ignorant (for a lack of a better word). The world of medicine is so specialized at this point that most "specialists" know little to nothing outside their field and in a discussion about systemic health can only bring up what they learned in medical school. And the official story in medical school currently is that the environmental hypothesis for chronic diseases was made mostly obsolete by the genetic explanation, and it happened around mid-1950s. I don't know of any medical school in the US or Canada that even teaches the older, environmental hypothesis as a viable theory.
    As far as the new studies showing great results with hormone treatment or other non-genetic methods, the response from doctors is usually the same - i.e. the original diagnosis was wrong and the people that improved did not really have PTSD (or whatever other chronic disease that benefited from treatment). Because, you know, PTSD is chronic and incurable condition with unknown cause just like the majority of other chronic diseases.
    So, aside from ER and surgery, all other doctors are little more than drug dealers that simply prescribe (mostly toxic) drugs to keep quality of life acceptable and numb the pain if there is any, while ensuring the patient will be a client of the medical system for life. Most of them know it too, hence the highest suicide rate of any profession.
    I think @Blossom and @Regina have had some discussions with career doctors, so they can tell you too how it went when you try to bring up anything other than genes as a cause of disease. Not all doctors are bad people, but the good ones can't do much in a system that makes sure that unless they play ball they will be debt slaves for life and possibly the target of a few lawsuits that can end their career.
     
  4. Ulysses

    Ulysses Member

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    Where does mitochon
    The dogma is so entrenched that not even people with Ph.D.s or M.D.-Ph.D.s are permitted to criticize the practice of medicine. Should they dare to try, the medical ideologues will fling their ready-made, rancid-chimp-***t-like-retort that the critic is "just a researcher" or "not a doctor." I've seen it happen. Even though, obviously, a person who dedicates their time to grappling with epistemology and experiment design will be in a better position than your typical overworked M.D. to learn what's true and what isn't.
     
  5. Amazoniac

    Amazoniac Member

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    @haidut, this one?
    Stress is the greatest accelerator of... | Ray Peat Forum


    On almost every thread about the effects of psychological stress I have the impression that you have your job in mind.

    "Universities have now become mostly a mouthpiece of a specific industry. They now produce nothing but exhausted, robotized, and largely uneducated masses ready to assume a soul-crushing, competitive position that usually makes no use of the "knowledge" they acquired as students."​

    This is just one of many, many examples. In some of them your indignation was explicit.

    You're not alone, a lot of people complain about their jobs but stay in them nevertheless. You can argue the obvious, but in many instances people do have alternatives. Of course there's something holding you/them there.


    Part of it I already mentioned elsewhere: it can be a bit scary to all of the sudden reject having someone telling you what to do and direct you in case of mistakes. The person has to take full responsibility over actas.

    By the way, I have talked to a few people commenting that if they had saved the money that they paid on health insurance until this point, they would've a fortune by now. And if anything bad happens (which is their first response to the idea), they will be the ones in charge of deciding how to spend their money, and not how the company forces them to take or leave their offer. Unfortunately most realize this only if they need it, eventually choosing to pay by themselves private physicists despite having the insurance available. But they just can't let go of the sense of security that it provides. Canceling it is assuming responsibility over actions and it can be a stressful thought for someone that is conditioned to something else.​

    Not having annoyance to value all other aspects of life must play a role too. Working by yourself (like Raj) is somewhat meditative because you have more freedom, therefore it's easy for distracting thoughts to affect productivity. Stepping out of your job is a clear separation between duties and hobbies. It's clear to everyone that's self-employed that time is subjective, therefore posting the ponies unpleasant activities can become a habit. The lack of discipline can end up confounding pleasant with unpleasant and everything turns into a mess. He has imposed death lines: news of the letters every 2 months, it's his annoyance that he has to deal with.

    Since you enjoy the quotes..
    The busy bee has no time for sorrow. | Ray Peat Forum


    You also mentioned somewhere that you tend to avoid planning. Is this how it actually works in practice or how you wished it worked? I find it very unlikely to be able to manage a company, family, job, and rap battles on sundays without it.
     
  6. OP
    haidut

    haidut Member

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    It's a bit of a sticky predicament. Can you imagine the riots and vigilante justice that would ensue if the public somehow
    I am no longer at my day job :): Pulled the plug back in 2016, as I mentioned on one of Danny's shows, so I did act upon my perception/thinking of need for change. Personally, my specific position was not that bad but most of the people I worked with at the client site (I worked for a consulting company) matched the description of a zombie pretty well.
    The feeling of indignation you detected was not so much for myself as it was for all the talented people I met as a "forward-deployed consultant" who seemed like they can barely survive another day. While things changed for me, for many of my former clients things seem to either stay the same or have gotten worse. But like you said, there is usually a reason they stay at their job and most of the time it is not fear of freedom. It is usually things like the family barely making ends meet, one person feeds the whole family, the health insurance is vital because one or more people in the family are really sick, the work pays for kids' school/daycare, work pays for an adult to get another degree, etc.
     
  7. ChrisWhewell

    ChrisWhewell Member

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    Just look at most other mammals and consider how their bodies react when they are put under stress, then you have the answer.
     
  8. Amazoniac

    Amazoniac Member

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    I remember when I asked you why not earn money doing what you enjoy, you said that you avoid mixing them. It's a soul-crushing statement if you think of it.

    I still hold that part of it can be fear of freedom. These limitations often appear with people start to pile up things that can make them feel safe instead of backing off to reconsider how they're living. Buying a lot of unnecessary stuff (cars, yachts, etc), settling with someone for lack of options, unwelcomed fetuses, and suddenly they're trapped and it's more than understandable when there are other people depending on them, but it's usually a result of not changing the course early on.
     
  9. Dobbler

    Dobbler Member

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    Good. More redpills, cant get enough of them. (Matrix)
     
  10. OP
    haidut

    haidut Member

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    Yep, the concepts of "learned helplessness" and "chronic unpredictable mild stress" (CUMS) are pillars of animal research and proven to be pathological beyond doubt. Yet, no doctor I have ever talked to is even willing to consider the same may be true in humans. The most common response is "we are not rats". True, but the same ideas have been shown to hold in mice, rabbits, guinea pigs, cats, dogs, monkeys, worms, and even yeast. So if stress is absolutely toxic to all of these organisms, how come humans are assumed to be uniquely immune to stress? With so much evidence for stress causing disease the burden of proof should be on the medical field to show that it does NOT do so in humans. So, the assumption should be that stress IS damaging in humans until evidence to the contrary is found.
     
  11. BrightStar

    BrightStar Member

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    I would say, many people prefer to stay at their present jobs (which can be stressful, boring, etc), because of stability it gives. Many folks do have dependant parent, a chind or some other goal, requiring stable monthly income. Give them 1 billion dollars (figuratively speaking) and their fear of freedom will go away.
     
  12. Amazoniac

    Amazoniac Member

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    That was Zeus' term, I should've used fear of change or of the unknown instead.

    Creating a standard of living that eventually becomes unmanageable is quite common. People tend to correct it by increasing their gainz further, and the stress keeps increasing.

    How many people are there in degrees that they dislike? People that keep a partner around just to avoid loneliness? Having a fetus when feeling that the other will leave? These are all examples that don't involve physiological dependency and people settle due to fear. Choosing the comfortable route is usually what leads people to frustrated lives. But to be fair a yachtless life is worthless.
     
  13. Lejeboca

    Lejeboca Member

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    I'd say that stress is a subjective feeling, except maybe for major catastrophes, such as war or bombing (@bzmazu)
    Besides taming the TLR*'s (on the physical level) and something like meditation (on the spiritual plane) what would be good strategies not to succumb to the feeling of stress? I wonder whether high metabolic rate is one such a defensive mechanism? (Kind of when mitochondria are busy producing energy rather than spewing DNA around :): ?)
     
  14. OP
    haidut

    haidut Member

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    Cell stability and staying intact depends on energy/ATP. Anything that lowers energy production is in effect a stressor. The regular events in life we think of as stress act through the CRH->ACTH->cortisol pathway but if you administer a strong toxin like mercury, cadmium, cyanide, etc it will have the same final effect - interference with energy production and DNA leakage. This is the beauty of the study above. It hints that "stress" is actually anything that leads to DNA leakage, which eventually leads to chronic disease.
    Selye, Warburg, St. Gyorgi, etc all said the same thing - interfere with metabolism in any way and you beget an adaptive response. When the ability to adapt is exhausted, disease starts (or the organism dies if the interference is severe enough).
     
  15. Lejeboca

    Lejeboca Member

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    Thanks, Haidut !
     
  16. Regina

    Regina Member

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    Anecdotally, my neighbors on both sides of me and another one next over have "retired" from careers. They are each only in their early 50's. In each case, they now have loud TV or music playing 24/7. They almost NEVER go outside. When they do, they look like gray zombies. They literally require being saturated and cocooned in constant noise.
    I kindly (I thought) asked my next neighbor if she could turn her sound system (it's a whole house sound system) down after 1am and she said darkly and robotically, "I don't care what you think." I believe her. I remember when she had energy and smiled to her neighbors. I have to believe my block is not unique.
     
  17. Ulysses

    Ulysses Member

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    I don't think it is. The culture is full of subclinical anxious depression that causes people to seek constant distraction from their own thoughts. Imagine doing this for twenty, thirty, or forty years! The longer one goes on like that, the worse the reckoning will be, if and when one finally looks at oneself. Eventually one passes a point of no return.
     
  18. Regina

    Regina Member

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    Yes. In my experience, attempts to coax them out of this state just induce punishing wrath upon the implied suggester that something might not be going well.
     
  19. dfspcc20

    dfspcc20 Member

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    There are analogies of this on the societal level. What happened to "Age of Leisure" the Industrial Revolution was supposed to bring? Never happened. Why not? Because increasing productivity always led to increasing consumption.
     
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