Endurance exercise causes (peripheral) hyper-cortisol state
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A few months ago I did a post on a pair of studies showing that while cortisol has a negative feedback mechanism centrally, the peripheral feedback mechanism is positive. In other words, a person can have normal or even low blood levels of cortisol and very high cortisol levels in tissues, due to the ability of cortisol to increase the expression of the enzyme 11β-HSD1, which is the rate-limiting step in synthesizing cortisol and is expressed in most organs/tissues. So, the more cortisol one produces (due to stress, fasting carb-restriction, etc) the more one increases the ability to produce even more cortisol. This discrepancy between the peripheral and central feedback mechanism of cortisol is probably a major reason why most endocrinologists still do not want to admit the primary causative role cortisol plays in conditions such as diabetes II – i.e. the blood levels of cortisol in such people are often normal, or even low. However, multiple studies have demonstrated that tissue expressions of 11β-HSD1 are not only predictive of developing obesity/diabetes in the future, but are also predictive of the course of already established diabetes. As a result of this tacit admission that elevated cortisol is pathological for health (especially for metabolic conditions), a number of pharma companies are running clinical trials with 11β-HSD1 inhibitors as treatments for obesity, diabetes, dementia, sarcopenia, and even Cushing syndrome/disease. One of the criticisms I have heard from endocrinologists in regards to the positive feedback mechanism of cortisol peripherally is that most of the evidence so far is from in-vitro experiments. The in-vivo study below may be able to address that criticism by demonstrating that running daily for a few weeks doubled 11β-HSD1 expression in tissues, confirming once again that even “beneficial” stress such as “endurance” exercise is sufficient to cause peripheral state of high cortisol, which probably persists even after the stress/exercise stops since the increased expression of 11β-HSD1 is not known to downregulate on its own. In fact, a number of studies have suggested that once such peripheral hyper-cortisol state is established through increased expression of 11β-HSD1 (specifically through fasting and/or exercise), the only way to reset it back to the original (lower) levels is by using pharmacological interventions such as RU486. However, that is a prescription drug, which is currently out of stock in most suppliers due to political infighting in regards to its abortifacient use. It is also an “estrane” steroids, which means potential for causing unforseen estrogenic effects in specific organs/tissues. Thankfully, aspirin, emodin, and progesterone are also known to downregulate the expression of 11β-HSD1 and in the case of emodin and progesterone, they inhibit the actual activity of 11β-HSD1, and also increase activity of the cortisol-deactivating enzyme 11β-HSD2.
https://doi.org/10.1152/japplphysiol.00652.2016
“…In summary, we report that 6 wk of treadmill training leads to a significant increase in pulmonary corticosterone levels in ob/ob mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. We demonstrate for the first time that exercise training increases pulmonary 11β-HSD1 expression but has no significant effect on pulmonary 11β-HSD2 expression in both lean and ob/ob mice.”
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@haidut Thank you for that.
BTW If anyone wants to know more about this there is an in-depth video with Georgi about it https://youtu.be/PucnCMLLrdo
There is also an extensive interview with Ray about the dangers of high cortisol https://youtu.be/VciTvOAgYxM
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@haidut Thank you for posting this here.
It's difficult to convince people that they could still have high cortisol even though their blood levels are "fine".
I attended a wedding this weekend in a family I have known for over 50 years. I knew most of my friends were low carb. It was tough to see. The men were all bald; some had the shakes; a beloved girl friend was in a wheelchair with MS. At minimum, many of them seemed to have shrinking heads and narrowing chins.
I did get into a conversation with one old male friend. He was super stoked to talk about bio-hacking, but sadly he was ice plunging and low carb. He said he had to because he was T2D. He assured me his cortisol was low because he tests it weekly. It reminded me of when Ray said something like 'many health conscious people were doing the most damage to themselves.' I can't understand why they can't see it themselves. This low carbing is a disaster. -
Fascinating study thank you for sharing Haidut. I guess this would partially explain why so many people after they stop exercising very quickly gain all the weight that they lost.
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@Verdad said in Endurance exercise causes (peripheral) hyper-cortisol state:
Fascinating study thank you for sharing Haidut. I guess this would partially explain why so many people after they stop exercising very quickly gain all the weight that they lost.
Not necessarily but one of the many consequences certainly together with a slowdown of the thyroid and a transition to slow oxidation.
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Franz Kafka had the same observation as Peat. He was involved in various “natural health” movements-Jungborn, in particular- and saw people go from pathologies of disease to pathologies of health: always stressing, torturing their body for some fleeting effect, going totally the wrong direction.
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@haidut So this isn’t something someone can run a test for?
It’s crazy how close to useless blood tests are the more we learn of this stuff
