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Exercise + Fasting Is Stress, Causes Obesity And IR, And Requires Cortisol Blockade To Reverse

Discussion in 'Scientific Studies' started by haidut, Sep 30, 2017.

  1. haidut

    haidut Member

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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
     
  2. dibble

    dibble Member

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    Youve titled this thread exercise/calorie restriction when in reality the study was based on exercise plus calorie restriction. There is a fundamental difference.

    There are countless studies showing the benefit of regular exercise. Just dont overdo it.

    I think exercise is an area where Peat is a little under read.
     
  3. milk_lover

    milk_lover Member

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    What if the exercise is fun? I pretty much enjoy playing soccer, tennis, ping pong, etc., It really makes me appreciate the value of our brains.. Those activities make me think fast and react with my muscles fast to a certain situation in order to yield the best outcomes.
     
  4. OP
    haidut

    haidut Member

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    You are right, it was both CR + exercise. I will change the title. But if you look at the third to the last quote they cite other studies that also found exercise to lead to IR and obesity (post-cessation) and those studies did not combine exercise with CR. Here are the links.
    Sustained rise in triacylglycerol synthesis and increased epididymal fat mass when rats cease voluntary wheel running. - PubMed - NCBI
    Alterations in insulin receptor signalling in the rat epitrochlearis muscle upon cessation of voluntary exercise. - PubMed - NCBI

    Peat does talk about exercise and I also mentioned it in a few of Danny's podcasts - basically it should be stimulating activity, preferably resistance training, and done at a level where you can hold a conversation while doing it. More than that and you are hyperventilating.
     
  5. OP
    haidut

    haidut Member

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    I just responded to that without knowing you asked the same question, see above.
     
  6. TubZy

    TubZy Member

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    Agreed, especially with the last sentence, one of the reasons why people gain so much weight when switching to peat in the beginning IMO.
     
  7. dibble

    dibble Member

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    Im an utter novice at reading studies so excuse me if Ive read these incorrectly but what Im taking from the latter two you have highlighted is that a) if you don't exercise your insulin sensitivity decreases b) growing rats need to exercise for optimal muscle development. If anything an argument for exercise?
     
  8. tca300

    tca300 Member

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    Or.... because they eat too much, foods that stimulate metabolism, stimulate hunger, and many overshoot their needs because of that.
     
  9. Westside PUFAs

    Westside PUFAs Member

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    Studies were done on rats not humans for those that don't value rat studies. Rat studies are garbage. The human being is a completely different organism.

    Of course you should never exercise while fasting. That is retarded. Also, a human in ketosis in a rested state from water-only fasting is different than just caloric restriction and exercsie.

    Peat has said that sprinting is "probably okay.."

    Positive Peat Quotes On Exercise

    .
     
  10. evo21

    evo21 Member

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    We've known for a long time that Exercise and Fasting are stressful, and that chronic stress leads to disease.

    What we want to do is to lower the baseline level of stress (at rest), and use Exercise and Fasting (and other stressful experiences) as hormetic stressors, followed by proper recovery to go back to homeostasis.
    A good way to know when we are properly recovered is by testing HRV (Heart Rate Variability).

    We need to balance rest and stress to maintain good health. Too much of either is bad.
     
  11. OP
    haidut

    haidut Member

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    I disagree. People are insulin sensitive when metabolism is good and RMR is high. No need for fasting or exercise. If you do start exercising you then have to keep that routine otherwise you end up getting obese and insulin resistant. If you became obese without chronically overeating then you have an endocrine problem which will not be solved by fasting or exercise. You can "manage" it for some time if you are willing to do the exercising/fasting indefinitely and be guaranteed to crash at some point when you can't handle the stress load any more. Also, exercising has been shown to NOT be healthy in the long run as with advancing age you rely more and more on cortisol/adrenaline to sustain such activity. What is healthy is having high RMR, not maintaining higher MR by stress. I would absolutely NOT take this as argument FOR exercising. That is what the newer study in this thread did - took rats who were healthy and subjected them to exercise + CR and found that it made the rats IR post-cessation due to cortisol elevation. Btw, in the second study above - the sedentary group was the leanest without any exercise or fasting.
    "...Total running distance (103.6 ± 2.0 km), average daily running distance during the third week (5.7 ± 0.1 km), and distance run on the last day (day 21; 6.1 ± 0.4 km) did not differ among groups with wheel access. Initial body mass (71.9 ± 0.5 g) did not differ between groups. Final body mass was lower in SED (186.3 ± 3.9 g) than in WL5, WL29 and WL53 (199.0 ± 3.0, 208.9 ± 2.5 and 212.3 ± 3.3 g, respectively). Average daily food intake and food intake on the night before the animals were killed was also lower in SED (14.8 ± 0.3 and 16.0 ± 0.4 g) than in WL5 (17.9 ± 0.3 and 21.4 ± 0.5 g), WL29 (17.0 ± 0.4 and 19.5 ± 0.5 g), and WL53 (17.9 ± 0.3 and 20.9 ± 0.4 g). Data for running activity, body mass and food intake are not shown."
     
  12. OP
    haidut

    haidut Member

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    Agree with the first part. As far as exercise - resistance type is probably best. No need for hormesis by running and elevating FFA.
     
  13. OP
    haidut

    haidut Member

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    Sprinting is basically the same as resistance training, which nobody denies is good. Also, look at the discussion with dibble. They cited other studies with the same findings and without fasting, only exercise.
     
  14. Thoushant

    Thoushant Member

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    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

    Fig 5, 4: Run-CR had better glycogen and insulin, blood sugar than Mifepristone wheel lock.
    Fig 6: Run-CR had lower AM corticosterone levels than Sed-CR, and postwheel lock placebo had lower than mifepristone..

    So if you have an active lifestyle, don't just suddenly stop.
     
  15. dibble

    dibble Member

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    Body mass not fat mass. I assume they had less developed muscles due to the lack of exercise caused by living in a cage with a locked wheel. I dont think we would encounter sedentary rats in the real world.
     
  16. Peatful

    Peatful Member

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    Anecdotal "evidence" of this...
    ~90% of The Biggest Loser contestants one year later (or sooner)...
     
  17. OP
    haidut

    haidut Member

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    Yes, I agree. But that is the point though. If you are healthy then do NOT start exercising either otherwise you will have to keep it up indefinitely and eventually the crash will come as I mentioned in my post to dibble and then you will become insulin resistant. Also, raising MR through stress/exercise/fasting has been shown to increase mortality and morbidity in the long run. What is healthy is having a high RMR (aka resting MR), which depends on thyroid and low PUFA stores.
    This whole exercising/fasting thing is right up there with drugs like PPI and SSRI. Once you are on them you'd better keep that routine or all hell breaks loose. And then when hell does break loose the version from your doctor is "well, we all get sick eventually and die, nothing you can do about that". The first one can definitely be avoided to a large degree.
     
  18. OP
    haidut

    haidut Member

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  19. Peatful

    Peatful Member

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  20. Tarmander

    Tarmander Member

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    We have mentioned lots of ways to break that cortisol cycle, but I think the best ways must address digestion in some way. Just lowering stress hormones doesn't do it if the small intestine is not addressed. This narrows down a lot of the plethora of treatments to things like cypro or cascara
     
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