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PUFA Enhance Glucocorticoid (cortisol) Signalling

Discussion in 'Scientific Studies' started by haidut, Nov 2, 2018.

  1. haidut

    haidut Member

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    I posted some studied in the past on the estrogenic and pro-cortisol effects of PUFA, as well as the pro-androgen effects of SFA. One of those studies showed that PUFA increases cortisol synthesis even in the absence of ACTH, which suggests that they may have pituitary hormonal-like effects.
    PUFA Initiate & Promote The Stress Response (ACTH/cortisol), SFA Inhibit It
    Pufa Stimulates Cortisol Production Even In The Absense Of Acth

    Now this study below shows that PUFA, enhance several-fold the gene expression induced by cortisol when that steroid binds with the GR. On their own, PUFA did not demonstrate a direct glucocorticoid effect but were greatly synergistic when a glucocorticoid steroid was present. Perhaps even more interestingly, omega-3 (DHA) was more effective as a glucocorticoid promoter than omega-6 (arachidonic) acid, and the study repeatedly states that the degree of unsaturation matters. The more unsaturated the fatty acid, the more synergistic effect with cortisol it has. The PUFA concentrations used in this study are physiological and easily achieved by a meal that contains at least 1g of PUFA, but higher concentrations/amounts reached a plateau in glucocorticoid enhancing effects.

    Unsaturated fatty acids synergistically enhance glucocorticoid-induced gene expression. - PubMed - NCBI

    "...The effects of polyunsaturated fatty acids, arachidonic acid (20:4) and docosahexaenoic acid (22:6), were studied in the presence or absence of 10-6 dexamethasone (Fig. l). This hormone concentration was chosen as the concentration inducing the maximal increase in luciferase transcription (data not shown). Treatment of HeLa cells with 10-6 M dexamethasone for 24 h resulted in an induction of the MMTV-luciferase transcription by 18.5 + 0.5 (S.E.)-fold over control levels. Treatment with C20:4 or C22:6 alone had no effect on basal levels of luciferase expression. However, when C20:4 or C22:6 was added together with dexamethasone, the hormonal induction was enhanced 1.4- to 2.3- fold (25-42 times the control levels, Fig. 1). The synergistic effect of fatty acids is dose-dependent with a maximal effect obtained at a concentration of 90 uM (EDso: 18 uM) and 60 uM (EDs0:8 uM) followed by a plateau up to 150 uM and 90 uM for C20:4 and C22:6, respectively."

    "...When added with dexamethasone, RU486 effectively antagonized the hormonal induction itself as well as the synergistic effect observed in the presence of the fatty acids, C20:4 or C22:6 (Fig. 2). These results show that the glucocorticoid receptor is involved in the synergistic effect of fatty acids and dexamethasone on luciferase transcription."

    "...Thus, we were prompted to use these two fatty acids to study the biological relevance of this inhibition. This study represents a new approach using a cell culture system that extends and complements our previous results utilizing cell-free cytosols. In the present study, we found that unsaturated fatty acids together with the glucocorticoid receptor and its specific ligand can synergistically regulate expression of a reporter gene under the control of a glucocorticoid-sensitive promoter. Fatty acids by themselves had no effect and the synergistic response to fatty acids was dose-dependent. The glucocorticoid antagonist RU486 significantly decreased the effect of dexamethasone alone as well as the synergistic effect of fatty acid and dexamethasone, suggesting that the glucocorticoid receptor and its ligand are required for the expression of the synergistic effect of fatty acids."
     
  2. jb116

    jb116 Member

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    And yet for decades they push the omega3 market.
     
  3. Vinero

    Vinero Member

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    How much PUFA do eggs contain? I find myself craving eggs for breakfast most days and just fry 2 or 3 in butter. I hope I am not stimulating cortisol production that way. I find it interesting I only crave eggs in the morning when waking up, never later in the day.
     
  4. Dobbler

    Dobbler Member

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    One egg is 0,7g PUFA
     
  5. OP
    haidut

    haidut Member

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    To both @Vinero and @Dobbler - it is the ratio of SFA/PUFA that matters more since the SFA have largely opposite effects to PUFA when it comes to GR, ER, AR and MR interactions. As long as there are at least several grams of SFA co-ingested with the PUFA, the negative effects should be largely negated since the study said the PUFA effects plateau beyound a certain concentration.
     
  6. lvysaur

    lvysaur Member

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    glucocorticoid, estrogen, androgen, and mineralocorticoid receptors?
     
  7. AnonE

    AnonE Member

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    This is gonna sound weird and anti-Peat, but does anyone think it's possible that PUFA can "help" low cortisol or burned out people?

    I do a lot of self experimentation. I have a great but stressful job, sometimes push too hard in the gym, etc. And over the years my go to for those tough nights when I'm just totally dead... is a nice fried rice and maybe some chocolate/ice cream with a movie. Cheap and terrible stuff, but I come back to life!

    Of course the real solution is to not get to This state of burned out in the first place. But when I do, this combination always works, and the fried rice tastes like heaven... I feel much better and I usually get an erection as well (TMI?).

    Basically I think a lot of Peat things are geared towards lowering cortisol, which is great in general, but when it gets too low this can also be problematic during times of stress. Cortisol is necessary to handle stress right?
     
  8. OP
    haidut

    haidut Member

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    Yes.
     
  9. Cirion

    Cirion Member

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    So I guess this explains why people can eat PUFA in a low-stress environment and somewhat get away with it? Meanwhile, that PUFA in anything even remotely resembling any sort of stress at all, will not be tolerated because it exasperates the effects.

    I found myself reading an epic 65 page thread in Dr. Jack Kruse's forum where a huge debate about the pros and cons of PUFA's ensued.

    What I got from the argument is that JK claims that PUFA is not only useful, but necessary for optimal health while living in a low stress environment.

    Even from the man JK himself, he basically admits that the PUFA's would only get you mileage if your environment was good (UV lighting in particular he says, UV index will only be good in the tropics or summer time in temperate zones). But this seems to me to basically be arguing that environment matters more than diet, if I interpreted the whole debate properly. In which case even according to him it shouldn't matter whether you eat a high DHA/EPA diet or if you eat a high carb RP inspired diet because in a low stress environment, I think we all agree that the body can handle all sorts of diets better. Thus, following that line of thought, even if RP's idea of high carb eating is not ideal, it doesn't matter in the context of a low stress environment, and will be tolerated just fine anyway.

    My main gripe with JK then is that if eating higher PUFA requires you to live in the tropics for it to work, and the fact that most of us do not or can not live in the tropics, what good does that do for us average folk? Answer to me - it doesn't do any good, and we're better off eating a diet that can mitigate stress (low PUFA, high sugar/saturated fats) since avoiding blue light, man made EMF, stressful relationships/job, darkness, etc. is simply not possible for most of us.. And that's exactly the counterargument the other guys were fighting back with.

    But, from what I'm seeing, the fact seems to point towards PUFA being neutral at best during a low stress environment (living in the tropics, low stress job, etc) and detrimental during a high stress situation. Thus, I see no reason to consume it personally.
     
  10. Waremu

    Waremu Member

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    I think Jack makes A LOT of assumptions with regards to PUFA and 'low stress environments.' I especially laughed at that part. There are environments that are lower stress than others, but he makes it sound like certain areas (certain tropical parts, etc.) are low-stress environments so much so that it seems to undo potential damage of PUFA. I don't see that, because while colder environments are no doubt more stressful climate-wise, etc., warm environments have their share of stressors too. So there are trade offs. If you lived in certain parts of the tropics, you would be subject to extreme flooding and other types of storms. Even exhaustion due to heat and not enough calories. You would also be subject to animals and enemy tribes hunting you for food. The extreme competition in the warmer climates would likely subject one to a lot of stress. Just look at how much adrenaline one is exposed to when it spikes or shoots up in emergency situations, including soldiers in wartime. Now if you're on the run for prolonged periods of time (which was common) because the population is larger and reproduces faster in warmer climates, and thus there are many enemy tribes nearby, you're likely coming into contact with constant fear or the state of escape from hungry beasts and the enemy tribes. (This oSo in many ways, you're trading off one type of stress for another in each climate. Overall, the warmer climates may still have been better when all stress is taken into account, but I am no so convinced that it was so 'low-stress' that it offset the bad effects of PUFA for the most part. A lot of tropic areas today still eat a relatively lower PUFA diet, where they eat more coconuts and potatoes and shell fish, etc. And you also have viruses and bacteria in exotic locations that can cause stress. I've spent a lot of time in various types of exotic warmer climates and it is not hard at all to get sick from fungi or bacteria, or poisoned by an insect, etc. So it seems Jack focuses more on the climate type of environment without spending the time to take into account what other stressors may came with the "low-stress environment." (At least from what I have seen from him so far).
     
  11. Cirion

    Cirion Member

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    Well the thought is that somehow UV rays from the sun actually cause benefit from PUFA... but I've seen on this forum that people have noted they actually do better with less PUFA even with sunlight in the picture, and that they tend to get sunburnt from a PUFA laden diet in a high UV index sun. They did also admit though, that their overall metabolism seemed fine with PUFA intake while at the beach or something, but the sunburn aspect alone shows me that we don't want much PUFA regardless. It makes sense when you consider that PUFA's don't like heat, and would quickly oxidize in the presence of sun (heat) -> sunburn since most of our PUFA's are stored in the skin (well more accurately, body fat) to keep it safe and stored away from our bloodstream. Interestingly, the body tends to store many other toxins in our body fat to keep us safe, but that's a topic for another discussion. There's of course the point of contention that SOME pufa is necessary, but if there is a requirement its so low that its essentially impossible to not get it, because virtually every food on the planet has at least trace pufa's in it. Then there's of course the argument for Mead acid which many think replaces the need for PUFA's entirely. This might explain too why we have an epidemic of people who can't tolerate much sunlight without sunburn since our overall PUFA intake is at a historic high. I know I historically can't be out in the sun more than 30-45 minutes without sunburn.
     
  12. Waremu

    Waremu Member

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    Well, let me tell you. There is no one who burned up in the sun as easy as me. I was well known to among all my friends growing up. For the first time since Peating, 4 years in (which is roughly the amount of time that it takes for your body to fully turn over if you begin restricting PUFA), I was on vacation in Florida at a beach in direct sun for hours with no sunscreen on. My GF had none on too. She ate a normal American diet as well. She got extremely red and I did not. Ever since then I have never got red again despite going out in the sun all the time. I now only get a olive colored tan. I never get tomato red. That speaks volumes to me and it agrees with what many have also experienced Peating. So what you said really hits home with my experience. I was like you in that regard -- no more than 30 min out in direct sun.

    But from all the reading I have done and from what Peat has said, PUFA has a more toxic effect on mitochondria when it is readily metabolized instead of stored and eventually released and processed by the liver, etc. I remember Peat saying specifically that PUFA being used as energy was like glass shattering into small pieces to the mitochondria. Thats the analogy he used anyway. So if that is the case, I would think sunlight oxidizing PUFA quickly would have a similar toxic immediate effect. And if so, it would seem to be worse and match up with my experience as well.
     
  13. Cirion

    Cirion Member

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    Nice to hear confirmation.

    How many PUFA's are you doing a day BTW? 4g or less?
     
  14. Waremu

    Waremu Member

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    I try to stay around 2 grams of PUFA or less per 2000-25000 calories. I never go above 4 grams per day. Been eating this way since I began Peating in 2012. I on average get an egg in per day, and my raw milk is grass fed, so even if some of the Omega 3's were truly essential in very small amounts (like Chris Master john says --- but he even agrees to keep PUFA intake low like Peat so they both essentially agree on the main issue of PUFA), I would be getting more than enough despite being very very low PUFA overall. I am more convinced by the Peat argument, however, with regards to PUFA. I have noticed first hand the pro-metabolic effects of PUFA restriction. I used to gain weight on anything over 2100-2400 calories and now I am eating 3500 calories on average and I am leaner than I was. I could probably go to 4000 calories and not gain much if any fat weight too. I will be doing an experiment on that perhaps soon.
     
  15. Cirion

    Cirion Member

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    Excellent. I need to get back to being 100% disciplined with PUFA restriction, and you've more than convinced me. I gained 30 lbs last time trying RP, then quit and dieted the weight off, only to realize I went hypo doing so, came back, gained 70 (!!!) lb, and realized that this time I've been more relaxed with PUFA intake, that's probably why I gained so much. No more PUFA's for this guy... I probably need to try to get not only under 4g but less than 2g or even 1g where I can because I have so much weight to lose. Lowering PUFA will be my weight loss strategy this time NOT purposeful caloric deficit (all that did was tank my metabolism).
     
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