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Vitamin A Lowers High Cortisol Levels (Cushing Disease)

Discussion in 'Scientific Studies' started by haidut, Oct 14, 2015.

  1. haidut

    haidut Member

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    Several studies, starting with the human one. The scientists used retinoic acid, which is the active form of retinol. Usually, people take vitamin A in the form of retinyl palmitate or retinyl acetate, and then these pro-drugs convert into retinoic acid with an efficiency of about 10%. The lowest dose used in the study was 10mg retinoic acid daily, which would correspond to about 200,000 IU retinyl palmitate or 125,000 IU retinyl acetate daily. Duration of the treatment was 6-12 months but effects were already established by the first month. Side effects were quite minor compared to what a doctor may try to brainwash you with when it comes to high doses of vitamin A.

    http://www.ncbi.nlm.nih.gov/pubmed/22851491
    "...DESIGN: This is a prospective, multicenter study. Seven patients with Cushing's disease (three men, four postmenopausal women) were started on 10 mg retinoic acid daily and dosage increased up to 80 mg daily for 6-12 months. ACTH, urinary free cortisol (UFC), and serum cortisol as well as clinical features of hypercortisolism and possible side effects of retinoic acid were evaluated at baseline, during retinoic acid administration, and after drug withdrawal.
    RESULTS: A marked decrease in UFC levels was observed in five patients; mean UFC levels on retinoic acid were 22-73% of baseline values and normalization in UFC was achieved in three patients. Plasma ACTH decreased in the first month of treatment and then returned to pretreatment levels in responsive patients whereas no clear-cut pattern could be detected for serum cortisol. Blood pressure, glycemia, and signs of hypercortisolism, e.g. body weight and facial plethora, were ameliorated to a variable extent on treatment. Patients reported only mild adverse effects, e.g. xerophthalmia and arthralgias."

    http://www.ncbi.nlm.nih.gov/pubmed/18692856
    http://www.ncbi.nlm.nih.gov/pubmed/11602619
     
  2. Orion

    Orion Member

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    I wonder if this correlates to how accutane works, lowering cortisol and the stress hormones, reducing acne and for some eliminating it.

    I have used accutane and it works, but seems to be a bandaid treatment, doesn't fix whatever was the underlying stress, acne does come back.
     
  3. jb116

    jb116 Member

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    I agree its a band-aid. A friend of mine used accutane 15 years ago and they were not in a good place during the treatment.
    p.s. nice gojira avatar
     
  4. Orion

    Orion Member

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    Esoteric Surgery - "You have the power to heal yourself..." :) That lyric has stuck with me

    Should mentioned that I tried large doses of vitamin A, it had no effect for me. Also I tried the large doses of vitamin B5 as well, it does work, but another bandaid. I guess B5 does something to the stress response 'stack' as well. Any studies with clonidine reducing acne? The more I read on the forum, the acne picture becomes clearer (estrogen, cortisol, adrenaline)...
     
  5. jb116

    jb116 Member

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    When you say large dose A had no effect on you, do you mean as far treating acne? or that there were no real terrible side effects?
     
  6. Orion

    Orion Member

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    Didn't have any side effects, was hoping it would reduce sebum and acne like accutane. Was trying up to 250,000iu per day, no effect. Low dose 5mg of accutane every other day will stop sebum production fully.
     
  7. jb116

    jb116 Member

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    I see..hmm I wonder if different brands would have that much of a difference in effect.
     
  8. m_arch

    m_arch Member

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    Interesting the dry eyes and sore joints are effects of Accutane as well (I went on two separate doses of Accutane in my teens, its mostly gone away). However I still suffer with dry eyes and sore joints which I believe was probably due to the treatment.

    They say that dosing this vit A caused those symptoms?

    When I google "xerophthalmia", it says its a vitamin a deficiency. Not that vitamin A overdose causes it... weird, maan.
     
  9. Giraffe

    Giraffe Member

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  10. OP
    haidut

    haidut Member

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    Actually, the 24h UFC combined with a dexamethasone suppression test is the definitive way of diagnosing Cushing. Similar to the blood serotonin test and 24h urinary 5-HIAA test. Blood cortisol is just a point in time measure and can be influenced by many things like albumin, vitamin intake (especially biotin causing a false elevations), nutrition status, and even infection.
    Blood cortisol does have its use and it can show if elevated it can mean a number of things such as decreased clearance (hypothyroidism and/or liver disease), increased synthesis (many possible reasons including Cushing), or false positive readings due to some other abnormality (even dehydration can cause a false positive).
    Anyways, they used UFC for a reason as it is the more reliable measure of Cushing status.
     
  11. ecstatichamster

    ecstatichamster Member

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    What is the best type of A supplement.
     
  12. Amazoniac

    Amazoniac Member

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    Zeus, where is this from? Does you remembers?
    The only place that I could find such figure is at Stacking the Exchanges, but it's just a speculation based on topical products. Those values are also off.
     
  13. Amazoniac

    Amazoniac Member

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    ..

    Предполагам, че най-точният метод е когато ретинолът [☣] е етикетиран, но все още може да бъде предизвикателен, защото зависи от анализираната тъкан, състоянието или въпросното животно, дозата, и т.н.

    По-долу са дадени примери за разлики в скоростта на използване. Както можете да отбележите, локализираното преобразуване може да работи независимо от циркулиращите нива.

    - Chemistry and Biology of Synthetic Retinoids (978-1-351-07063-8)

    "Endogenous RA has been purified from rat tissue and rigorously identified.7 In two separate experiments, pools of retinol in rat tissues were radiolabeled by oral administration of [3H]retinyl acetate (Expt. 1) or [3H]retinol (Expt. 2) for 5 d. Both the route of administration and the amount dosed (4 mcg/day/rat) were physiological. RA and retinol were extracted from kidney and were purified by elution through multiple HPLC systems. The specific activities of retinol and RA recovered in each experiment were similar (Table 1) and were much less than the retinol dosed, demonstrating that the RA was derived from the total pool of endogenous retinol."

    upload_2019-4-26_7-49-0.png
    10^8 | 10^9
    10^6 | 10^7
    10^6 | 10^7

    "RA has an elimination half-life as short as 3 h in culture.[4-17] Moreover, RA is notorious for sticking to plastic. Both factors would rapidly lower the effective RA concentration in media and result in an underestimation of RA biological potency."

    "Two complimentary approaches have been taken in this laboratory to study the biogenesis of RA from retinol, the parent endogenous retinoid. Homogenates have been used to evaluate co-factor requirements, to study the characteristics of enzymes and to determine the tissue distribution of RA synthesis activity.[17] Cells in culture have been used to examine RA synthesis relative to the other routes of endogenous retinoid metabolism and to determine what regulates RA concentrations.[18]

    A spectrum of vitamin A-dependent tissues converts retinol and retinal into RA.[17] RA synthesis from retinol was detected in homogenates of rat adrenal, testes, liver, lung, kidney, and small intestinal mucosa, but not spleen (Table 2)."

    upload_2019-4-26_7-49-8.png

    "Several established mammalian cell lines also convert retinol into RA, including cells derived from human carcinomas, dog and pig kidney, mouse teratocarcinoma, and rat ileum, hepatoma, and osteosarcoma (Table 3).[11]"

    upload_2019-4-26_7-49-14.png

    "Note the substantial rate of RA synthesis from 10 \tM retinol, a near physiological concentration for several tissues. This rate of synthesis would appear to be sufficient to saturate cellular-retinoic acid binding protein (CRABP) and to provide the concentrations of endogenous RA measured in tissues (Table 4)."

    upload_2019-4-26_7-49-22.png

    "These data suggest that retinoid target tissues meet their RA needs predominantly by synthesis in situ, rather than by sequestering blood-borne RA, which has been synthesized at limited distal sites."

    "In rat liver, small intestinal mucosa and kidney, the activity converting retinol into RA was recovered in the post-mitochondrial supernatant (P + S fraction). Separation of this fraction into microsomes (P) and cytosol (S) showed that the activity in kidney is predominantly cytosolic, and the major, but not exclusive subcellular locus in liver and intestine is cytosol. This is interesting because cytosol is the locus of the two cellular retinoid-binding proteins, cellular retinol-binding protein (CRBP) and CRABP."

    "There is no obvious relationship, however, between the presence or concentrations of CRBP and CRABP in tissues and their ability to synthesize RA (Table 2).[21,23]"​

    Това е сериозен токсин за околната среда, трябва да започнем да го третираме като такъв, особено защото очевидно замърсява тъканите ни.

    Трябва също да вземем под внимание, че този токсин се съхранява и освобождава малко наведнъж, така че експозицията ще бъде по-голяма от очакваното. Няма значение дали тъканите могат само да метаболизират определена сума в даден момент, това е въпрос на мобилизация.

    Не съм запознат с никаква дискусия за ефективността на преобразуването на цялото тяло.

    --
    - Biogenesis of Retinoic Acid from β-Carotene
     
  14. OP
    haidut

    haidut Member

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    The person who posted this on StackExchange has a study linked to his original comment but it seems to have been removed. The study below found similar effectiveness between retinol and retinoic acid, which suggests the conversion efficiency is much higher or retinol is capable of acting on RAR similarly to retinoic acid.
    https://onlinelibrary.wiley.com/doi/pdf/10.1111/jocd.12193

    I prefer the latter option. :): It reminds me of Peat's discussion on vitamin D and how the medical industry fraudulently claims only calcitriol (1,25-OH) is the "active" vitamin D but according to Peat all intermediates like D3, D2, etc are active at the VDR. So, maybe the same is true of vitamin A.
     
  15. Amazoniac

    Amazoniac Member

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    It can be true:
    - All-trans-retinol is a ligand for the retinoic acid receptors. (posted on the thread against your Poisonil)


    What's interesting is that the effects on skin appear to be unrelated to irritancy:

    - Retinoid Therapy for Photoaging (Rittié; this link will be broken in 57 days :crystalball:) - :moneybag: Pfeizzer

    "Despite extensive evidence demonstrating beneficial effects of topical retinoids in preventing and treating the clinical aspects of photodamaged skin, the detailed molecular basis of this activity remains elusive. Initially, irritation and scaling were thought to be the mechanism underlying retinoid-induced repair. However, several lines of evidence have dispelled this notion. First, two concentrations of tretinoin, 0.025% and 0.1%, were compared for their efficacy and irritancy [7]. Used once daily for 11 months, the two concentrations of tretinoin improved photoaged skin to similar extents, but 0.1% tretinoin was significantly more irritating. Second, topical retinyl palmitate (0.15%) induces skin irritation without demonstrating any advantages over placebo in treating photoaging [75]. These results demonstrate that irritation can be separated from efficacy, although irritation is an inherent side effect of poisonoid therapy (see below)."
    "The ability of poisonoids to restore collagen formation is thought to be the main underlying mechanism by which the appearance of photodamaged skin is improved [45]. RA increases TGF-b in mouse skin [77,78]. Since TGF-b is a major fibrotic cytokine, its induction by RA may underlie the ability of RA to induce collagen synthesis. However, the rôle of TGF-b in repair of photodamaged human skin remains to be investigated."

    "Studies of poisonoid-mediated collagen induction in photodamaged human skin have been hampered by the lack of a suitable in vitro model. In vitro cultures of dermal fibroblasts constitutively produce high levels of collagen, which cannot be substantially increased by RA. As mentioned above, culturing fibroblasts in a collagen gel pretreated with human MMP-1 results in downregulation of collagen, as is observed in photodamaged skin [49]. Whether RA can restore collagen formation in this model remains to be determined."

    "Dermal ECM is a complex matrix composed of many structural components besides type I [one] and type III [three] collagens. Many ECM components have been reported to be altered in photodamaged skin, including elastin [79], anchoring fibrils, proteoglycans, and glycosaminoglycans [80]. It is possible that the mechanisms by which poisonoids improve dermal ECM involves action on deveral dermal components in addition to collagen. For instance, RA increases fibrillin I, a component of microfibrils that are associated with elastic fibers [81]. RA also increases hyaluronic acid content of porcine skin [82] and in human skin organ culture [83]. Finally, it should be noted that, by stimulating collagen formation, RA would be expected to improve interactions between fibroblasts and ECM, which are impaired in photoaged dermis (Fig. 13.1)."​

    Found this when searching for 'non-poisonoid thickening' agents:



    But I don't think that topical applications are reliable for having an idea of such efficiency in the body. It has been quite difficult to find information on this.

    Here's what your friend from Stacking the Exchanges posted:


    And another publication that's also by Joseph Napoli:


    I might not try to interpret this because it's going to be challenging, I have a kitten video awaiting for me and there's a great risk of not leading anywhere practical. However, from the units alone you can tell that it those values are off.

    When applied on skin, cells are exposed to a concentrated and static dose, with the toxin being unbound. Therefore skin cells are forced to metabolize any amount used, which is not based on demands (unlike what happens in the body).

    It could be interesting to look at how the detoxifying enzymes are expressed across the intestines (for handling greater amounts as well) in relation to the skin, but it's still a different situation because the toxin exposure from foods or supplements is either as carottenoids or esterified poisonols. And contrary to the skin, excess that manages to be adsorbed is stored and only metabolized little by little.

    There is a peak of poison A in circulation after a heavily contaminated meal, but for the most part the blood is kept at a steady concentration.

    If (for example) a guru has 30 mcg/100 ml of poisonol circulating in blood..

    - Structure and function of the body (978-0-323-34112-7)

    upload_2019-4-27_15-24-0.png

    ..and if the heart pushes 70 ml of blood on every such contraction, cells in the body are bathed in a similar amount that's being renew'd very often (I wonder if it varies throughout the day) and it's kept this way to the best of its abilities.

    But the main point is that the difference in the concentration then can be high:
    • Blood: 0.3 mcg/g
    • Skin: 0.1 % all-the-trans-poisonoic acid/poisonol (as in the experiment): 1000 mcg/g
      • The pomade will be applied on the skin, without moving, until it's metabolized. This is why more concentrated products are in the form of cream instead of gel, otherwise the delivery is even faster and it's too harsh: brutal irritation.
    So it's an unrealistic scenario. If I find by chance something relevant, I'm going to produce a tag, but meanwhile I remain doubtful.

    By the way, being assertive is zo 2018. The new trend is never positioning yourself and masking uncertainty with the idea of contextual balance; you can't be accused of being wrong because it always depended.
     
  16. LeeLemonoil

    LeeLemonoil Member

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  17. Blossom

    Blossom Moderator

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    You forgot to cite your source. (Blossom 2019)
     
  18. Amazoniac

    Amazoniac Member

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    I don't follow trends, I have that as essence.
     
  19. Blossom

    Blossom Moderator

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    You are the trend. :p:
     
  20. DaveFoster

    DaveFoster Member

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    Tagging me and then removing the tag so I have to read the entire thread to find the relevant point only to find that there is none.

    Sly, very sly.
     
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