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Pufa Stimulates Cortisol Production Even In The Absense Of Acth

Discussion in 'Scientific Studies' started by haidut, Jan 20, 2016.

  1. haidut

    haidut Member

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    Many people opposing Peat have complained that there is no evidence for PUFA acting on the stress hormones or that oxidizing PUFA is bad for health. Well, this study not only shows otherwise but also demonstrates that a PUFA metabolite is capable of stimulating cortisol synthesis even in the absense of ACTH. This is a common feature of the so-called ectopic Cushing syndrome and the finding is significant since it suggests PUFA can circumvent the normal negative feedback mechanism and the effects of anti-cortisol drugs that aim to suppress ACTH. In the presence of ACTH, the PUFA metabolite boosted production of cortisol even more.
    Needles to say, this effect has great implications for conditions like diabetes and suggests that substances like niacinamide may have indirect anti-stress effect due to the lowering of lipolysis and thus fat oxidation.

    http://www.ncbi.nlm.nih.gov/pubmed/12689852

    "...Oxidized derivatives of linoleic acid have the potential to alter steroidogenesis. One such derivative is 12,13-epoxy-9- keto-10-(trans)-octadecenoic acid (EKODE). To evaluate the effect of EKODE on corticosterone production, dispersed rat zona fasciculata/reticularis (subcapsular) cells were incubated for 2 h with EKODE alone or together with rat ACTH (0, 0.2, or 2.0 ng/ml). In the absence of ACTH, EKODE (26 microM) increased corticosterone production from 5.3 +/- 2.3 to 14.7 +/- 5.0 ng. 10(6) cells. h(-1). The stimulatory effect of ACTH was increased threefold in the presence of EKODE (26.0 microM). Cholesterol transport/P-450scc activity was assessed by measuring basal and cAMP-stimulated pregnenolone production in the presence of cyanoketone (1.1 microM). EKODE (13.1 and 26.0 microM) significantly increased basal and cAMP-stimulated (0.1 mM) pregnenolone production. In contrast, EKODE decreased the effect of 1.0 mM cAMP. EKODE had no effect on early or late-pathway activity in isolated mitochondria. We conclude that EKODE stimulates corticosterone biosynthesis and amplifies the effect of ACTH. Increased levels of fatty acid metabolites may be involved in the increased glucocorticoid production observed in obese humans."

    http://www.ncbi.nlm.nih.gov/pubmed/12530633
    "...In zona fasciculata cells, EKODE stimulated corticosterone production at concentrations of 5 microM or greater, and there was no evidence of inhibition at high concentrations. Stimulation of steroidogenesis was observed after 15 min of incubation and continued for at least 2 hrs. The potential relevance of our findings to the hypertension of obesity is discussed."


    And if this was not enough, these studies show that the same PUFA metabolite stimulates aldosterone production as well.
    http://www.ncbi.nlm.nih.gov/pubmed/14718355

    Another notable finding is that it is not only arachidonic acid that can produce dangerous metabolites. The metabolite found to increase cortisol and aldosterone is a direct derivative of linoleic acid. So, inhibition of downstream metabolites using drugs like aspirin or LOX inhibitors is not enough. Depleting PUFA stores seems to be the only safe path to avoid this cascade.
    "...Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks."
     
  2. hmac

    hmac Member

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    This is really interesting and a good microcosmic example of why people are referring to PUFA as 'hormone-like'. With regards to the metabolism of linoleic acid; would there not be things that inhibited that pathway, and would the lipolysis suppression which is characteristic of aspirin not mitigate the damage in a situation where the organism was not depleted of PUFA?
     
  3. OP
    haidut

    haidut Member

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    I am not aware of any direct inhibitors of that metabolic pathway, but aspirin and niacinamide should have an effect by limiting lipolysis directly. Another approach would be to saturate the tissue lipids by eating high ratio of SFA/PUFA and even if lipolysis occurs this metabolite should not form in high quantities or at all.
     
  4. superhuman

    superhuman Member

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    great find.
     
  5. Tarmander

    Tarmander Member

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    I would be curious how MUFA fits in here. SFA are often mentioned as not having the same cascade like activity as PUFA, but where does MUFA fit in? Does it have like half the inflammation cascade? I ask because I have been doing a lot of chocolate lately, and that has a few grams of MUFA along with SFA.
     
  6. tara

    tara Member

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    I had the impression, from reading Peat, that it's the unsaturated bonds that cause the trouble, and MUFA's have one where PUFAs have two or more. So large amounts of MUFA are not ideal either, but you can get away with a little more MUFA than PUFA? Some of the high MUFA oils, like olive and I don't know about cocoa, may have some beneficial effects as well in small quantities. They are relevant to Randle cycle, so large amounts presumably tend to reduce sugar burning.
     
  7. OP
    haidut

    haidut Member

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    I think Peat said that MUFA are more or less neutral. They don't have the stress-blocking abilities of saturated fat but they also do not server as precursors to arachidonic acid and the inflammatory mediators. Oleic acid seems to have some testosterone boosting qualities due to its effect on the steroidogenic enzymes, and its amide has some GABA boosting and anti-stress properties as well. See below.
    https://en.wikipedia.org/wiki/Oleamide
     
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