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There are many paridgms in health and nutrition. If there was such a thing as concise and complete, we would known that by now.

I guess the real answer is that everything works, for their intent and purpose, and everything have their downsides. Mixing things up is what I imagine, keeps one the healthiest. If not for our unique physiologys, then for variety and comprehensiveness.

I'd like to hear your opinion on why you think that, however.

I've been posting a number of studies that all point to higher BMIs being more protective against sickness and early death. As Ray has said pretty much. Totally contrary to your belief as stated here.

Many many people on this forum have been down the road you are on. Me included. It feels great for awhile, fantastic, but your can easily run into huge metabolic problems that take years to resolve. Thyroid issue, lower and slower metabolism. This may not apply to you, it's a generality, but often a huge issue because you are advocating a constant high cortisol high free fatty acid regime. That has been shown to lead to insulin resistance and chronic disease including diabetes.

Further, although plenty of thin lean people live healthy lives, LOSING weight to get there is VERY dangerous for most people. The danger of weight loss is vastly under estimated.
 

cyclops

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Further, although plenty of thin lean people live healthy lives, LOSING weight to get there is VERY dangerous for most people. The danger of weight loss is vastly under estimated.

I've been trying to get an answer on this for a while. Why is losing weight so very dangerous for most people. I know PUFA is getting burned and maybe you feel worse while thats going on, but what is the long-term damage of this. If you lose all the fat and then you start eating good, is it really that bad? Losing the fat, I guess somehow screws up your metabolism for a very long time thereafter?
 

DuggaDugga

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I think this thread will ring true for all people who at some in their lives exercised in order to lose weight. Just like fasting, it works great in younger age (<30) but it really masks a bigger metabolic problem and of course badly backfired in the long run. Exercise is a forced/stressed attempt to increase the "calories out" part of the weight maintenance equation. The equivalent, and possibly just as bad, approach is fasting in an attempt to decrease the "calories in" part of the equation. Both are stressful and it has been shown that only people with high RMR are healthy. Neither the artificially raises MR by exercise (adrenaline/cortisol) nor the chronic fasters have been shown to endure lasting health benefits as both of these lower RMR.
As the study below shows, fasting or exercising and then stopping (in the face of unchanged caloric intake), leads to rapid regaining of weight, insulin resistance and obesity. The effects are due to cortisol, which stays elevated after stopping the fasting/exercise due to elevation in 11b-HSD1 expression. I think this is what quite a few people experienced on Peat's diet. Due to their lowered metabolic rate and reliance on cortisol and adrenaline from diets like Paleo and/or chronic exhaustive exercise, these people rapidly regain weight initially post exercise/fasting and struggle with losing it unless they lower their stress hormones and support thyroid. Unless thyroid is addressed and/or excessive cortisol signalling opposed the fasting/exercise needs to be done indefinitely in order to keep the weight off. This would explain why some people here need to endure period long fasts to feel good - once you are in the vicious circle of IR and obesity you either have to keep feeding that cycle or block/lower cortisol to exit it. I think all of these are basic facts that pretty much all of us have experienced personally. I had the same issue back in 2011-2012 and until I reigned cortisol in my weight did not drop. Hey @Jsaute21, @Drareg, @AretnaP, @Dhair, @DuggaDugga and others - I think you will really appreciate this. In light of this I don't know how anybody can view chronic elevation of cortisol (aka stress) as good. Yes, cortisol needs to be reigned in if you want the stress response to stop.

A side note:
As pointed out by one reader this study was on effects of exercise + fasting. However, the study cites other experiments where only exercise was used and the results were pretty similar. See below.
Exercise + Fasting Is Stress, Causes Obesity And IR, And Requires Cortisol Blockade To Reverse

Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric... - PubMed - NCBI

"...Severe caloric restriction (CR), in a setting of regular physical exercise, may be a stress that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In this study, we examined the effect of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adipose tissue mass gain and preserving whole body insulin sensitivity following the cessation of daily running and CR. We calorically restricted male Sprague-Dawley rats and provided access to voluntary running wheels for 3 wk followed by locking of the wheels and reintroduction to ad libitum feeding with or without mifepristone (80 mg·kg−1·day−1) for 1 wk. Cessation of daily running and CR increased HOMA-IR and visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. pre-wheel lock exercised rats and sedentary rats (all P < 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue mass gain was attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that following regular exercise and CR there are GC-induced mechanisms that promote adipose tissue mass gain and impaired metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone."


"...Three weeks of daily running increased 11β-HSD1 protein content 5-fold in epididymal fat and 2.5-fold in subcutaneous (inguinal) fat (Run CR vs. Sed CR, P < 0.05; Fig. 3, A and G). 11β-HSD1 remained elevated 1 wk following the cessation of daily running and CR in the placebo post-WL group vs. the Sed CR group in the epididymal depot (P < 0.05; Fig. 3A). Mifepristone treatment significantly reduced 11β-HSD1 content in epididymal fat during the post-WL period vs. the Run CR and placebo post-WL (P < 0.05; Fig. 3A)."

"...One week of sedentary behavior and ad libitum food intake following 3 wk of daily wheel running and CR impaired glucose tolerance and insulin sensitivity markedly (Fig. 5, A and B). The glucose area under the curve (AUC) increased significantly in the placebo post-WL group (238.3 ± 16.3) vs. the Run CR group (133.1 ± 25.8) (P < 0.05), and this was prevented with mifepristone treatment (139.2 ± 11.2, P < 0.05; Fig. 5A′). The placebo post-WL group had a significantly greater insulin AUC (193.2 ± 33.8) vs. the Run CR group (23.4 ± 6.4), and this elevated response, suggesting severe insulin resistance, was attenuated with mifepristone treatment (72.1 ± 9.2) (P < 0.05 vs. the placebo post-WL group; Fig. 5B′)."

"...There was a significant increase in the placebo post-WL group for fasting glucose (6.12 ± 0.29 mM) and insulin (1.89 ± 0.28 ng/ml) concentrations vs. the Run CR group (4.4 ± 0.22 mM glucose, 0.25 ± 0.05 ng/ml insulin) (P < 0.05, Fig. 5A′′; P < 0.01, Fig. 5B′′)."

"...Previous studies by Booth and colleagues have demonstrated that insulin resistance rapidly develops (within days) in skeletal muscle (32), but not adipose tissue (33), in their rodent wheel lock model. In this study, cessation of daily running and CR resulted in a two- and eightfold increase in glucose AUC and insulin AUC, respectively, in the placebo post-WL group vs. the Run CR group. Remarkably, fasting insulin and HOMA-IR were seven- and tenfold higher in the placebo post-WL vs. the Run CR group. Mifepristone treatment prevented both hyperglycemia and hyperinsulinemia during the OGTT, reduced fasting blood glucose and insulin levels, and prevented the increase in HOMA-IR vs. the placebo post-WL group...Importantly, this hyperinsulinemia induced by the cessation of CR and exercise, paired with maintained adipose tissue insulin sensitivity, may promote rapid adipose tissue regrowth (see below)."

"...We observed a threefold increase in circulating corticosterone levels during the pre-WL period in all of the CR rats. Thus, prior to the wheel lock period, there was systemic hypercorticosteronemia, which may have contributed to the deteriorated metabolic profile and rapid adipose tissue mass gain in the placebo rats once ad libitum feeding was resumed. It is important to note that, although the physically active rats had hypercorticosteronemia and elevated inguinal 11β-HSD1 expression relative to the placebo post-WL group, they had substantially better glucose tolerance and insulin sensitivity and less body fat. Previous studies have suggested that highly trained humans can exhibit basal hypercorticosteronemia (40, 77) as well as systemically elevated 11β-HSD1 activity several days after a single bout of endurance exercise (6). The function of the observed elevations in GC exposure within adipose tissue following exercise is unclear. We speculate that it may be one of the mechanisms underlying the body's physiological drive for fat regain after initial fat mass loss. Collectively, the loss of fat mass and improved metabolic efficiency of peripheral tissues induced by CR and daily exercise, mixed with elevated GC exposure within adipose tissue, may become detrimental only once paired with excessive caloric intake and physical inactivity."

"...We observed a four- to tenfold increase in relative adipose tissue mass in perirenal, epididymal, and inguinal fat 1 wk following cessation of CR and daily running. Daily mifepristone treatment in the post-WL period attenuated body mass gain and relative adipose mass in perirenal and inguinal depots and partially attenuated epididymal fat rebound. In fact, the absolute masses of all three fat depots were significantly reduced in the mifepristone post-WL group vs. the placebo-treated animals. Previously, it had been shown that mifepristone treatment reduced adipose tissue mass gain and body weight gain in rodent models of diet-induced obesity (3, 28, 56). In addition, 2–4 wk of mifepristone treatment reduced risperidone- and olanzapine-induced weight gain in healthy men (23, 24). This suggests that GCs play a significant role in contributing to fat deposition and weight gain in these studies."

And before everybody starts jumping on the mifepristone (RU486) bandwagon. The study claims that the benefits were due to RU486 inhibiting 11b-HSD1. However, the effects were mixed - in some tissues RU486 actually increased 11b-HSD1, which is highly undesirable. I think a much safer approach would be a combination of progesterone + DHEA, as both have direct anti-cortisol effects systemically (vs. the selective modulation done by RU486). That, and of course supporting thyroid function.
DHEA, In Low Doses, Directly Inhibits Cortisol Synthesis
DHEA Enhances Cortisol Degradation
The Anti-cortisol Mechanism Of Progesterone

Great post. Thanks for constructive contribution as always, @haidut . I'm not sure what else can be done to help demonstrate the negative effects of cortisol aside from individuals taking the time to research it themselves. Virtually any negative health outcome can be linked to cortisol, usually directly. I would challenge others to just head on over to pubmed with the condition of interest and search it along with the keyword "cortisol" or "glucocorticoid".
 

Dhair

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Great post. Thanks for constructive contribution as always, @haidut . I'm not sure what else can be done to help demonstrate the negative effects of cortisol aside from individuals taking the time to research it themselves. Virtually any negative health outcome can be linked to cortisol, usually directly. I would challenge others to just head on over to pubmed with the condition of interest and search it along with the keyword "cortisol" or "glucocorticoid".
I think the role of glucocorticoids in mental health conditions is criminally overlooked as well.
 

DuggaDugga

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I've been trying to get an answer on this for a while. Why is losing weight so very dangerous for most people. I know PUFA is getting burned and maybe you feel worse while thats going on, but what is the long-term damage of this. If you lose all the fat and then you start eating good, is it really that bad? Losing the fat, I guess somehow screws up your metabolism for a very long time thereafter?

Adipose tissue is metabolically active, adipocytes aren't just storage bins like some people seem to think. Biochemistry of adipose tissue: an endocrine organ
Cortisol causes insulin resistance and ultimately the accumulation of fat along the midsection, and adipose tissue increases cortisol release and signaling in a bit of a vicious cycle. Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans
This is why starvation/low-carb diets aren't effective in weight loss, let alone healthy weight loss.
 

DuggaDugga

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I think the role of glucocorticoids in mental health conditions is criminally overlooked as well.
Agreed. I'd recommend Robert Sapolsky's book "Why Zebras Don't Get Ulcers". He does a wonderful job explaining the physiology of stress hormones and their implications in a large variety of conditions, and he does so in a way that's super accessible and stimulating.
https://www.mta.ca/pshl/docs/zebras.pdf
 

cyclops

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Adipose tissue is metabolically active, adipocytes aren't just storage bins like some people seem to think. Biochemistry of adipose tissue: an endocrine organ
Cortisol causes insulin resistance and ultimately the accumulation of fat along the midsection, and adipose tissue increases cortisol release and signaling in a bit of a vicious cycle. Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans
This is why starvation/low-carb diets aren't effective in weight loss, let alone healthy weight loss.

Thank you this is very helpful. Couple more questions, if you don't mind.

-Could you define insulin resistance in a simple way?

-I guess you're a believer that if someone has fat to lose, following a Ray Peat inspired method and doing it very slowly is the best option?
 

RedStaR

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A lot of the discussions are missing a key hormone to my amazment, the most important arguably.

Leptin.
 
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Great post. Thanks for constructive contribution as always, @haidut . I'm not sure what else can be done to help demonstrate the negative effects of cortisol aside from individuals taking the time to research it themselves. Virtually any negative health outcome can be linked to cortisol, usually directly. I would challenge others to just head on over to pubmed with the condition of interest and search it along with the keyword "cortisol" or "glucocorticoid".

Some people have probably been poisoned by past cortisol use and now refuse to believe it is really not that good for the brain (or any other tissue for that matter) :):
The fact that is elevated in EVERY mood disorder and suppressing it is now hailed as treatment for all of them should be enough to give people a pause. And if it is not good for the brain, how can it be good for anything else?!?
 
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I think the role of glucocorticoids in mental health conditions is criminally overlooked as well.

It is not overlooked but rather criminally underpublicized. Same with serotonin. Pfizer sells a ton of SSRI drugs every year while at the same time running multiple clinical trials with the serotonin antagonist terguride to reverse the effects of serotonin and cortisol on every tissue. They know quite well what is going on - i.e. they sell both the poison and remedy (like that Prodigy song form the 90s goes). How is this not a crime against humanity is beyond me.
 
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RedStaR

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Some people have probably been poisoned by past cortisol use and now refuse to believe it is really not that good for the brain (or any other tissue for that matter) :):
The fact that is elevated in EVERY mood disorder and suppressing it is now hailed as treatment for all of them should be enough to give people a pause. And if it is not good for the brain, how can it be good for anything else?!?

Cortisol, like inflammatoom, is good, and part of the body's stress response.

Chronic cortisol release is bad, like chronic low-grade inflammation. What I mean by that is, the problem is more upstream, whereby cortisol is only but a stress response. Stress response, or simply stress, is what should be improved.

When it comes to mental disorders, the correct keyword here was mental resilience. I'll look for a recent conference that was done on this topic, between stress, inflammation, and mental disease.
 

DHT

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Cortisol, like inflammatoom, is good, and part of the body's stress response.

Chronic cortisol release is bad, like chronic low-grade inflammation. What I mean by that is, the problem is more upstream, whereby cortisol is only but a stress response. Stress response, or simply stress, is what should be improved.

When it comes to mental disorders, the correct keyword here was mental resilience. I'll look for a recent conference that was done on this topic, between stress, inflammation, and mental disease.
totally agree with you. Anything chronically gonna hurt you one day. You need to cycle everything like day and night same with cortisol if you have chronically elevated levels you re gonna take dmg from it. Same with exercise . Your body needs exercise also after exercise he need food and a break to regenerate.
 

RedStaR

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Here it is, a conference from the Library of Congress last year.

The interest is from the first speaker, Philip W. Gold.



Some parts of the transcript here. He touches only lightly on the stress response, and in the context of depression:



"And as I mentioned, we know that depression is a dysregulation of the stress response and I'll talk with you a bit about what the stress response is all about. We first presented this in a two-part series in the New England Journal of Medicine entitled "Clinical and biochemical manifestations of depression, Relation to the neurobiology of stress." And what is the stress response? Say you're being chased by a bear and you fear for your life. The first of fear-related behaviors and anxiety and these are essential for survival. Without them, there is not sufficient motivation to escape the threatening stimulus. There is a very extensive central nervous system apparatus for generating anxiety deep in the brain and it sends many, many fibers to the cortex to announce the conscious experience of fear. But the cortex sends relatively few wires down to the anxiety center and for that reason, we can't really persuade ourselves not to be afraid or not to be anxious and that's the price we pay, I think, for survival. But I think it's one of the tragedies of human evolution. There is a decreased capacity for pleasure and the reason for that or one of the reasons for that is to prevent distraction along the way since the attention must be focused only on the threatening stimulus. Similarly, there's an inflexible mood and cognition. The mood should not be bouncing around and cognitive style is really very fundamental either programs that had been generated during past stressful experiences or somewhat instinctive responses. Stress hormone production is always an invariable part and I'll be talking a bit about some of these stress hormones, cortisol and norepinephrine. There is redirection of fuel to the bloodstream and the brain and this increases plasma glucose which the brain-- the stressed brain needs in order to mount an effective stress response. It occurs through insulin resistance. And I can talk a little bit about that later on. I'm going to show you some data. There is premonitory inflammation. And so when we are stressed, whether it's psychological stress or whether it's a physical stress, there is a premonitory activation in the inflammatory response. And presumably, that occurs perhaps to prime the system to respond to a possible injury that is inflicted by the stressful situation. And there's also similarly an activation of coagulation as a stay against plasma hemorrhage so that the body is ready for this before it happens. Inhibition of neurovegetative program for one of these-- again, these occur in order to prevent distraction or the wasting of calories on programs that are not essential. So that if you're being chased by a bear or if you're very stressed, you won't stop and eat. You won't stop and look at a beautiful scene. You won't stop to rest. You won't stop to sleep. You won't stop to participate in sexual activity. All of these are suspended during the acute stress response. And there is something called-- increased neuroplasticity and neurogenesis. We just learned that not long ago...


...There is-- Inflammation is activated during depression really rather considerably and there's some data to suggests that not only it may be premonitory but that it may even occur and predate the onset of the depression. Insulin resistance, so blood sugar rises to help the stressed brain. Increased blood clotting. And these events occur even during psychological stressors, just as powerfully as if when we're chased by a dangerous animal. Inhibition of the growth hormone and reproductive endocrine systems to save energy for the stress response. And there's a marked decreased in depression of neuroplasticity and neurogenesis which are not very much involved in a depressive pathophysiology. So, melancholic depression, this really is a rendition of virtually exactly to what I had earlier showed as what transpires during a stress response. Fear-related behaviors, the inflexible mood and cognition, stress hormone production, redirection of fuel to the bloodstream and brain, inflammation and coagulation, inhibition of neurodegenerative functions, here, decreased neurogenesis and neuroplasticity, and there is insufficient termination of the stress response. It gets stuck as it were in the on position. Here is a schematic of the brain. If you look at the green area, sort of in the center to the left, that's called the subgenual prefrontal cortex which Wayne Drevets discovered was significantly reduced in size and its activity is abnormal in patients with familial major depression. These are people who are depressed and who have first degree relatives who are depressed. And this plays a very important role in the depressive syndrome and during the stress response. It regulates and restrains the amygdala fear system and hopes to-- and is working properly. It prevents being maladaptive levels of high anxiety. It plays a large role in self-assessment on how we feel about ourselves. It estimates the likelihood of punishment or reward. It modulates the pleaser and the reward centers. It restrains cortisol secretion and norepinephrine secretion. And in patients with familial depression, it's reduced by as much as 40%...

...CRH is released from the brain, stimulates the anterior pituitary just outside of the brain, and that stimulates the secretion of cortisol. But it's the brain that drives cortisol secretion and its secretion is highly elevated with depression. We've now finally nailed down that depression is really a full-blown systemic neurodegenerative disease rather than a simple chemical imbalance....patients with depressive illness lose approximately seven years of life, much is untreated hypertension predictably shortens a life. Now I'm going to talk a little bit about CRH which is the main driver of cortisol. It actually does many things in addition to driving cortisol and I don't think it's core abnormality in depression but it confers many of its observable features. And if you give it centrally to experimental animals it induces fear-related behaviors, anxiety, and increased vigilance, inflexible mood and cognition, the hypercortisolism and increased norepinephrine secretion. It produces the enzyme resistance, the proinflammatory state, and increased coagulation. And it inhibits food intake, sleep, sexual activity and the endocrine program [inaudible] growth and reproduction. Now here's a study that we did sort of an ambitious study to really get a good picture with this where we put lumbar drains in where you would do a spinal tap and left in there for 30 consecutive hours. The neurosurgeons would do this after all much all neurosurgical procedures, the incidence of infection is virtual nil and there are virtually no side effects. And what we saw is cortisol was elevated around the clock in the upper left even while people slept so that this anxiety and hyperarousal does not require consciousness...

...Increased cortisol secretion has multiplicity of effects. Every cell in the body has a cortisol receptor. Sympathetic nervous system activation, the insulin resistance causes much physiologic morbidity and the increased clothing. Let me show you some data that we've done looking at insulin resistance. I'll describe insulin resistance a little bit. I hope this seems clear. Insulin is a hormone that secreted-- that causes glucose to exit the bloodstream into the cell and if you lack insulin you have diabetes. And so, blood does not get into the cells and instead, it builds up and you have very high blood sugars. During stress and in depression, we get slightly insulin resistance, so what happens is that the insulin doesn't really promote as much glucose transported into the cell. It builds up in the blood supply and high glucose levels go to the brain which doesn't need insulin to transport glucose across the neuron. And for that reason insulin resistance is a clever way to increase plasma glucose acutely and to promote optimal brain function during distress. And we see that in our depressed patients who are remitted, they're not suppressed any longer, they have increased plasma insulin levels. The insulin is going up and up trying to get the glucose into the cell. It does manage to do it completely and the plasma glucose levels are elevated in patients with depression. They're not abnormally elevated. The insulin levels don't get abnormal, 100, 110. So, here, it's really 90s or a low 90s but it's significantly higher than we see in healthy controls who are matched for BMI, age, and gender....

...Then we see elevated fasting triglycerides and total cholesterol in remitted patients with major depression. They have high triglycerides. They're not outside the normal range which is about over 160, they have high cholesterol not outside the normal range but it's 185 compared to the total cholesterol in very closely matched controls. And next is a compound call adiponectin which is very essential for insulin sensitivity. I won't go into this in detail. But adiponectin promotes insulin sensitivity and its levels are reduced completely in patient with major depression around the clock at every time point. One of the things that happens during depression because of high cortisol levels and at the top of that sphere, high insulin level, high IL-6 which promotes inflammation. And that increases the secretion of adipose tissue but a special form of adipose tissue which intraabdominal, we call it visceral fat. And visceral fat is a very active biochemical machine. And on there right there, you see it makes a variety of proinflammatory compounds that cause inflammation. IL-6 for the side with receptor, you don't need to know these, TNF-alpha resistant and so forth. And actually, the levels of the circulating proinflammatory compounds correlate with BMI. So, if you have child who's moderately overweight, they're in a proinflammatory state. And anyone who's overweight or obese is in a proinflammatory state and that confers along the mobility. It goes all along with obesity. The insulin has a variety of-- it's elevated in depression, a variety of negative effects. It promotes inflammation and it stimulates the sympathetic nervous system, it produces bad liquids and increases clotting. Now, this is some studies we've done, there are many others done by others that show inflammation in patients with major depression. And there-- the inflammation story in depression is very exciting, really. It's present in a very large percentage of depressed patients. It's present in the bloodstream, it increase stimuli compounds that stimulate inflammation, and there is increased inflammation in the brain. And this seems to precede the major depression. So some people feel that inflammation may be a primary trigger to depression and some have used antiinflammatory compounds and with mix results, but there have been several which show that they have antidepressive effects. This is an around the clock study we did with plasma IL-6 which is a proinflammatory compound. It's elevated around the clock in our patient...

...These are in patients who are no longer depressed and not on medication and they have high levels as you see on the right there, CRP, this compound that predicts coronary artery disease and they have high levels of something called serum amyloid A. There is a peripheral CRH that we've shown and it comes out of sympathetic nerve terminals. And it is proinflammatory. It stimulates white cells and it stimulates a cell called the mast cell which contains-- it's a bag of proinflammatory compounds that can do great harm if uncontrolled. And IL-6, one of the proinflammatory compounds has a whole variety of other effects. These things all influence one another. They are synergistic in their actions, the positive feed back loops. Nature has really designed this system so that you can really get the stresses ramped up in dire emergency. But I think that provides the context for being so much depressive illness because depression apparently affects 16% of the American population at one time during their lives. Now, why my patients with major depression be inflamed, this is speculative on my part. But there is a new form of inflammation which has been described called parainflammation. And it occurs in the context of stimuli to which we're not exposed in our early evolution. And so, it become inflamed in this context during at old age, which was not present long, long ago during overfeeding or obesity and underactivity with disruption of the ordinary light-dark cycle with artificial lighting with synthetic chemicals and drugs and so forth. And I suggest again speculatively that major depression may be apparent inflammatory disease. Because early in our evolutionary history, we may not have experience, the everyday multiple small stressors that are incurred in our everyday social interactions or living in chronic conditions. There are several markers for parainflammation that we're looking for to see if we can verify that this process is transpiring in patients with major depression...

...And we've shown that these patients have those stress hormone levels, have increased indices of inflammation, have decreased activity of the growth hormone or reproductive axes, and they have increased heart disease. I'm going to close this with a concept that people becoming more interested in and I think will have more biological markers for in the next few years, but it's the concept of resilience. The American Phycological Association defines resilience as the process of adapting well in the face of adversity, tragedy, trauma, threats, and even significant sources of threat. Then what confirms resiliences? There are genetic factors. If one identical-- in identical twins, if one has PTSD, the other twin has a 40% chance of having it. So even though they share 100% of their genes, there's not a 100% of concordance. So 60% of it is environmental. Repeated childhood trauma to uncontrollable stressors. And people that study children who were housed in institutions and those who were adopted later, they study them, they were more anxious, and they did bring scans on them, and they had amygdala-- amygdalae that were increased in size and activity. On the other hand, mild to moderate controllable stress early in life can have an inoculating effect. Such experience leads to increased neuroplasticity and neurogenesis, and increases the size of the subgenual prefrontal cortex. An enriched, nurturing environment and early life with exposure to manageable novelty increases resilience later in life. Positive emotion, optimism, loving caretakers, flexibility, the capacity to reframe adversity, and strong social support also increase resiliency. And finally altruism, commitment to a valid cause, a capacity to extract meaning from adverse situations, and a tolerance for emotional pain and sadness promote resiliency as well. And people are developing a panel of biomarkers for resiliency that hopefully can-- will be validated in the years to come."
 
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Dhair

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Cortisol, like inflammatoom, is good, and part of the body's stress response.

Chronic cortisol release is bad, like chronic low-grade inflammation. What I mean by that is, the problem is more upstream, whereby cortisol is only but a stress response. Stress response, or simply stress, is what should be improved.

When it comes to mental disorders, the correct keyword here was mental resilience. I'll look for a recent conference that was done on this topic, between stress, inflammation, and mental disease.
It seems like you're splitting hairs here.
I think it would be more accurate to say that cortisol and the stress response has a purpose, not that it's intrinsically good.
After all, if the problem is indeed insulin resistance in the brain, then the the stress response needs to be stopped before any healing can take place. This is why focusing on "receptor sensitivity" is useless for the purpose of actually getting better.
 
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RedStaR

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It seems like you're splitting hairs here.
I think it would be more accurate to say that cortisol and the stress response has a purpose, not that it's intrinsically good.
After all, if the problem is indeed insulin resistance in the brain, then the the stress response needs to be stopped before any healing can take place. This is why focusing on "receptor sensitivity" is useless for the purpose of actually getting better.

I did not imply that cortisol is intrinsically good, for the simple fact that nothing in your body is intrinsically good. They all do their purpose, but a balance is most healthy, whether that's cortisol, testosterone, histamine, glutamate, potassium, muscle, or adipose tissue.

The brain cannot be insulin resistant. Perhaps you meant something else.
 

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