How Pregnenolone And Progesterone Raise Metabolism

Discussion in 'Thyroid and Hormones' started by haidut, Sep 30, 2015.

  1. haidut

    haidut Member

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    I know pregnenolone/progesterone work via multiple mechanisms such as inhibiting serotonin, opposing estrogen, lowering FFA, etc. However, this method caught my eye and I thought I'd share it since many people here have trouble converting T4 into T3.
    As you all know both pregnenolone and porgesterone both reliably raise levels of allopregnanolone. The Wkipedia page for allopregnanolone has this to say about it (among other things).
    https://en.wikipedia.org/wiki/Allopregnanolone

    "...Similarly to many other GABAA receptor positive allosteric modulators, allopregnanolone has been found to act as an inhibitor of L-type voltage-gated calcium channels (L-VGCCs),[13] including α1 subtypes Cav1.2 and Cav1.3.[14] However, the threshold concentration of allopregnanolone to inhibit L-VGCCs was determined to be 3 μM (3,000 nM), which is far greater than the concentration of 5 nM that has been estimated to be naturally produced in the human brain.[14] Thus, inhibition of L-VGCCs is unlikely of any actual significance in the effects of endogenous allopregnanolone.[14] Also, allopregnanolone, along with several other neurosteroids, has been found to activate the G protein-coupled bile acid receptor (GPBAR1, or TGR5).[15] However, it is only able to do so at micromolar concentrations, which, similarly to the case of the L-VGCCs, are far greater than the low nanomolar concentrations of allopregnanolone estimated to be present in the brain.[15]"

    And activating the bile acid receptor has the following effect:
    https://en.wikipedia.org/wiki/Allopregnanolone
    "...One effect of this receptor is to activate deiodinases which convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). T3 in turn activates the thyroid hormone receptor which increases metabolic rate.[3][4]"

    So, for the people that have liver issues, or otherwise trouble with Synthroid or regular Cynoplus, instead of adding T3 (or if you don't react well to it) you can take some pregnenolone and this should increase the conversion of T4 into T3 and raise your metabolic rate. Most endocrinologist agree that high doses of pregnenolone/progesterone cause hyperthyroidism, so I guess this is one of the primary mechanisms.
     
  2. Tarmander

    Tarmander Member

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    When you say most endos agree that high doses of preg cause hyperthyroidism, what doses are they talking about? Grams per day?
     
  3. OP
    haidut

    haidut Member

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    This study used a moderate dose equivalent to about 300mg - 400mg for a human per day.
    viewtopic.php?f=75&t=6902

    Most endos would not recommend taking more than 100mg per day unless the blood levels are very low. The ones I have talked to say it is due to fears of hyperthyroidism and driving estrogen too low due to pregnenolone converting to progesterone. Oral pregnenolone has the same effect on blood progesterone as a direct dose of progesterone about 1/2 the size of pregnenolone. So, taking 100mg pregnenolone is the same as taking 50mg progesterone and that is considered high even for women, if it is taken on a regular basis. Too high a progesterone may impair absorption and bioavailability of some metals.
     
  4. Dean

    Dean Member

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    Any thoughts on how I would use progesterone and pregnenolone together? I've been taking small doses of progest-e together with 5 mg of DHEA morning and night. Haven't noticed a lot yet, positive or negative, other than sleeping better. Maybe a little increased sociability and a bit of a lessening of libido.

    I have some 30 mg Preg. capsules. Could I try one of those midday with DHEA, in addition to the morning and night Progest-e/DHEA?
     
  5. OP
    haidut

    haidut Member

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    I'd up the DHEA dosage to 5mg x 2-3 daily. Your androgens may be low and progesterone is ovewhelming the androgenic effect of the small dose DHEA. If you use pregnenolone a good ratio is 1:1 or 1:2 DHEA:pregnenolone. So if you take a daily total of 15mg DHEA then one capsule of 30mg pregnenolone should be enough.
     
  6. Dean

    Dean Member

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    Thanks Haidut, to be clear I do take 5 mg of DHEA 2-3 x a day with the Progest-e. Not sure how to accurately measure the amount of progest-e I am taking as it doesn't come out in drops even taking it out of the fridge for an hour or so before using. I'm guessing I'm taking 3-5 drops with the 5 mg of DHEA.

    So, the ratio of DHEA:Pregnenolone would be per day, not per dose. I know you've cautioned about taking more than 5 mg of DHEA at a time or 15 mg per day. So, what about taking the progest-e dose morning and night and pregnenolone 30 mg midday. The 5 mg DHEA with each dose of prog or preg?
     
  7. OP
    haidut

    haidut Member

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    I'd take the progesterone and pregnenolone together. Try it out and see i it makes you sleepy or alert. It can go both ways so decide if you want to take int he morning or night. The DHEA can be taken separately. I meant to say the ratio per dose should 1:1 or 1:2 DHEA: pregnenolone and you can take the total daily pregnenolone all at once or if you have smaller capsules take smaller dose with each DHEA dose. The total daily dose of DHEA should not be taken together.
     
  8. bipolarguy

    bipolarguy Member

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    haidut,

    I recall that you wrote that some people who get negative symptoms with low dose pregnenolone seem to be able to tolerate high doses, i.e., over 100mg. Last Summer, I was doing 500mg, daily and didn't notice anything good or bad, so I stopped. Last week, after starting on tiny doses of Thiroyd, I took 300mg of preg with two tablespoons of sugar, then my testosterone shot. Whether it was coincidence, it was the first time, in a long time, that my libido was strong, my mood was good and my erectile function improved, though not great, but it was letting me know it was alive. I believe it might be a synergistic effect, where before, test shots, alone, haven't helped, thyroid, alone didn't help and preg, alone, didn't help.

    I take my shots M,W,F, so tomorrow(Monday), I'll see if I get another positive reaction. My urologist believes my HPTA axis is malfunctioning due to my untreatable ultra rapid cycling bipolar illness, since, even when I had supraphysiologic numbers of total and free testosterone, there wasn't a corresponding improvement in libido/erectile function. I'm waiting and hoping to feel and function like I did 13 years ago, when I was 52. At that time, my function was like it was when I was 30. An aside; back then I was eating raw honey everyday and my wife and I followed a mostly vegan diet, which included lots of soy. I actually felt good eating like that and I was working in a job where I did heavy lifting almost everyday. However, over the past six or seven years, no longer a vegetarian, my digestion and immune function have been declining, which might be related to immune dysfunction and dysregulation that seems to accompany worsening bipolar illness. I don't expect to cure my bipolar illness but I'm desperately trying to reverse this ongoing decline and turn the clock back ten or fifteen years. Also going to give lithium another try. I'll post, weekly or every couple of weeks, how it's going.
     
  9. aguilaroja

    aguilaroja Member

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    Peter Whybrow has for years used "supraphysiologic" doses of T4 to treat "resistant" bipolar illness. AFAIK, he used only T4 and not a T4/T3 combination. Whybrow is a psychiatrist with prestigious appointments and has published these findings for years, including about safety of large doses of T4 for this indication. It may be possible to find a psychiatrist to consider this view and prescribe, or work with you.

    Mol Psychiatry. 2016 Feb;21(2):229-36. doi: 10.1038/mp.2014.186. Epub 2015 Jan 20.
    Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.
    Bauer M1,2, Berman S2, Stamm T3, Plotkin M4, Adli M3, Pilhatsch M1, London ED2, Hellemann GS5, Whybrow PC2, Schlagenhauf F3.

    Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission ... - PubMed - NCBI
    Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction).
     
  10. bipolarguy

    bipolarguy Member

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    aguilaroja,

    Thank you for your post. Dr. Whybrow and I have corresponded several times and he has spoken with my psychiatrist. We tried T4, starting at 50mcg and I ended up with a severe migraine. My psychiatrist didn't want to to continue with the experiment, nor did I and she is also a world class reasearcher at the NIMH. Perhaps I needed compounded T4 without fillers and binders, which tend to cause problems for me. However, I'm tolerating Thiroyd, at least at extremely tiny doses, twice a day.

    I'll be seeing her in April and we're talking another trial with lithium.
     
  11. OP
    haidut

    haidut Member

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    Peat has written before that many of the symptoms of bipolar disorder may actually be due to high ammonia in the brain. This is why lithium is helpful for bipolar - i.e. it chelates ammonia, and it is ammonia that apparently triggers the manic portion of bipolar. Pregnenolone has been studied for bipolar in humans but always as an adjuvant. I think in doses of about 200mg - 300mg daily it has been shown to also reduce glutamate, which is responsible for the depressive portion of bipolar. Biotin, thiamine, zinc and ceylon cinnamon all reduce ammonia. So, you could try combining pregnenolone with vitamin B1, biotin, etc.
    People with bipolar also tend to have very high cortisol and that can also contribute to symptons. Have you had your cortisol tested? Pregnenolone, by inhibiting ACTH may be helping by lowering cortisol as well.
     
  12. bipolarguy

    bipolarguy Member

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    Thank you, haidut. Interesting about ammonia; didn't know that. Reducing glutamate, I know, is a core therapeutic focus in bipolar, lithium being one of the drugs that reduces glutamte. Haven't had a four specimen cortisol, just morning blood draw. Need to discuss that with my psychiatrist. I am taking B1, B2 and zinc. I'm fortunate that my psychiatrist's area of research at the NIMH is psychoneuroendocrinology as relates to addiction and mood disorders. She's quite open minded and eclectic; if I'm willing to try something, she's willing to prescribe it once she researches it.

    You're a walking scientific data base! I enjoy reading what you post.
     
  13. mayweatherking

    mayweatherking Member

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    this is so accurate, even though nearly 2 years ago wow. i noticed when taking progesterone, it for sure can overwhelm the body. i see very obvious and very clear indicators that preg is completely depleted. many times, i will take it, and notice it's anti cortisol effects. even with thyroid use (without preg), the depleted androgens don't even allow thyroid to work right, it pushes you even further into a dark pit of stress.
     
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