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Androstenediol Increases Thymus and Spleen Size by a Factor of 4, and Protects Against Viruses

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Hip, May 3, 2016.

  1. Hip

    Hip Senior Member

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    In a murine study, the supplement androstenediol (AED) was found to increase the weight of the immune organs the thymus and spleen by over 4 times when given to mice infected with coxsackievirus B4 (a virus commonly associated with ME/CFS).

    Although the thymus and spleen of mice not infected with CVB4 did not grow in size when AED was administered — AED only caused an increase in organ weight of infected mice.

    Here is an image taken from the study showing the increase in spleen size in CVB4-infected mice given AED:

    The Large Increase in Spleen Size in CVB4-Infected Mice Given AED
    Androstenediol increased spleen.png

    Gonads also increased in weight by over 4 times under AED treatment, whereas the increase of the lungs and the liver was about 200% and 85% respectively.

    AED had a powerfully protective effect against infection: in CVB4-infected mice not treated with AED, necrosis and calcification of the heart is seen within 14 days. But in CVB4-infected mice given AED, it was found that AED completely protects the heart tissue from virus-induced necrosis and calcification.

    AED is naturally found in the body: AED is a metabolite of the hormone DHEA. But AED is 100 times more effective than DHEA at helping mice survive otherwise lethal infection with CVB4.

    AED also helps protect against Gram positive and Gram negative bacterial infections, parasites, influenza infections, and herpes simplex 1 & 2 infections. What's more, AED can also counter the effects of stress-mediated immune suppression.

    More info can be found in this paper: Protective Effects of DHEA and AED against Viral, Bacterial and Parasitic Infections, Loria RM and Ben-Nathan D. 2011.



    Dr John Richardson mentioned the potential of AED for ME/CFS in his book on ME/CFS and enteroviruses (on page 225).

    This paper by Dr Roger Loria finds that a similar supplement called androstenetriol (AET) is even more potent than androstenediol (AED) in its protective effects against infection.

    Both AED and AET are classed as β-androstene steroids. These β-androstene steroids are highly unusual, in that they up-regulate immunity. Normally steroid hormones (like cortisol) down-regulate the immune response. But β-androstenes like AED and AET boost immunity, and also counteract the immunosuppressive effects of cortisol. Ref: 1

    β-androstenes increase Th1 cytokines such as IL-2, IL-3, and interferon. Similar to hydrocortisone, β-androstenes suppress inflammation — but without causing immune suppression. Ref: 1

    AED fights herpes simplex virus 1 by up-regulating interferon alpha production. Ref: 1



    Unfortunately, the FDA banned androstenediones such as androstenediol (AED) in 2004, on the basis that they are converted in the body to testosterone which is an androgenic and anabolic steroid (reference here).

    However, AET (which is more powerful than AED) is available as a supplement product called 5-AT from Core Nutritionals.

    The oral bioavailability of AET is poor, thus AET is best taken transdermally.
     
    Last edited: Nov 30, 2016
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  2. Little Bluestem

    Little Bluestem All Good Things Must Come to an End

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    Is a 200% increase in lung size a good thing?
     
  3. Hip

    Hip Senior Member

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    I am not sure, but if this supplement cures me of ME/CFS, the 400% increase in gonad weight it produces will be very handy for the spree of amorous activity I am sure to engage in when my health returns!


    Joking aside, note that first of all, this is an animal study, so it's results may not translate to humans. Secondly, this increase in organ size only appeared in animals in the midst of a fierce acute viral infection that would normally be fatal for them. ME/CFS patients generally are not suffering from fierce acute infections; the infections we have tend to chronic and often low-level "smoldering" ones.


    That said, it still is quite amazing that in animals at least, these various organs can increase so significantly in weight within such a short time of two weeks, as a result of being given the supplement AED during a viral infection.

    What is also extraordinary is the degree of protection that AED confers on infected organs. If you look at the full paper of this study on AED, it shows in pictures the remarkable way that AED protects the pancreas from viral damage from coxsackievirus B4. This is what a normal healthy pancreas looks like:

    This Is What A Healthy Pancreas Looks Like
    Healthy pancreas.jpg

    Then if you look at the two images below (which are from figure 3 of the study), you can see that in image (a) on the left, the coxsackievirus B4 infection has destroyed the pancreatic cells of the mouse (the acinar cells and islet of Langerhans).

    Whereas in image (b) on the right, you can see how these pancreatic cells were protected from destruction by the same virus, when a mouse was given AED at a dose of 320 mg/kg. Note that coxsackievirus B has been associated with type 1 diabetes.


    LEFT: Pancreatic Cells Destroyed By CVB4. RIGHT: Pancreatic Cells Protected From Destruction By AED
    AED Protected Pancreas.jpg

    Note that AED is not itself antiviral, so the protective effect of AED on organs comes from the way AED modulates the immune response.​
     
    Last edited: Nov 30, 2016
  4. Mary

    Mary Senior Member

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    @Hip - this is really interesting - are you going to try using AET transdermally?

    I will say the increase in organ size in general with mice is a little scary, but can't imagine the same happening in humans.
     
  5. Dufresne

    Dufresne almost there...

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    I was just about to crack off a joke about the gonads but it seems I was too slow.

    Fascinating stuff. I've been throwing everything and the kitchen sink at a babesia infection and still haven't triumphed. Perhaps this androgen is worth a try. Babesia is known to become a real problem for those who've undergone a splenectomy, so I assume enhancing this organ's function might be particularly helpful. I'm going to do some research on all this. Thanks.

    @Hip, do you think a transdermal could be made from the product you linked to?
     
  6. Hip

    Hip Senior Member

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    @Mary @Dufresne
    I have ordered some AET from the above link, but it has not arrived yet in the UK (I read online that this supplier is slow in responding).

    But when it does arrive, I will try to find some oil that AET readily dissolves in (like perhaps Johnsons Baby Oil), which I can then apply to my skin. This I hope will lead to good transdermal absorption.


    You are not going to get AET dissolving in water, because it says here that the water solubility of AET is 0.191 mg/mL, which according to Table 1 in this article corresponds to only "very slightly soluble".

    This water insolubility is I expect also why AET has poor oral bioavailability (poor oral bioavailability is often due to lack of water solubility).
     
    Last edited: May 4, 2016
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  7. Mary

    Mary Senior Member

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    @Hip - this reference talks about the 5-AT (AET) product having much of its effect from suppressing the release of cortisol. https://www.corenutritionals.com/5-at

    I know that many of us have problems with low cortisol, so wanted to get your thoughts on this issue --
     
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  8. Hip

    Hip Senior Member

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    That's a very good point. The general trend in ME/CFS is definitely to have both lower cortisol levels throughout the 24 hour cortisol cycle, as well as a blunted (lower) cortisol awakening response (see this post for refs).

    Although there are also ME/CFS patients who seem to have high cortisol levels. Unfortunately I have not actually had my cortisol tested as yet.


    I can't find in Professor Roger M. Loria's numerous published studies on β-androstenes anywhere where he says that AED or AET suppress the actual release of cortisol; but Loria does say that these β-androstenes counteract the immunosuppressive effects of cortisol.

    For example, see Loria's study which concluded:


    So one can speculate that potentially, AET may have more benefits for ME/CFS patients with high cortisol, because AET will counteract the immune suppressing and Th2-inducing effects of cortisol, which may then allow for viral clearance.

    Incidentally, although in general I think the idea that ME/CFS is psychologically-caused is nonsense, I do think there may be rare ME/CFS cases where, because of a learned behavioral stress response, the individual tends to respond in a stressful way to life's stressors. This stressful response then may raise cortisol, and thereby suppress immunity and prevent clearance of viral infections. These are the sort of people who may do well on psychological therapies such as Reverse Therapy which teaches patients not to respond so stressfully.

    But something like AET might work just as well for stressed patients, because AET will counter the immune suppression caused by cortisol release.
     
    Last edited: May 4, 2016
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  9. Mary

    Mary Senior Member

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    @Hip - I think severe long-term stress was a major factor in my developing ME/CFS. It was very slow onset, taking some 13 years from when my health first started to go south until I started crashing. And there were early childhood factors which I know helped create an inadequate stress response.

    However, I've been meditating faithfully for many years, no longer have the stress I used to and so on, but my ME/CFS remains unchanged. I think stress damaged my immune system for viruses which then did damage (including Coxsackie B). Several years ago I tried a protocol, I forget the name of it, but it was probably something similar to Reverse Therapy and it did nothing for me. I have low NK cell function and so on.

    So I'm seriously considering trying the product you linked. It just sounds so intriguing and too good to be true but it least it doesn't cost an arm and a leg! :D Thanks for bringing this to our attention --
     
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  10. Little Bluestem

    Little Bluestem All Good Things Must Come to an End

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    @Hip, interesting that you/they should mention the pancreas. I read somewhere that pancreatitis is the 4th leading cause of death in pwME.
     
  11. Mary

    Mary Senior Member

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    @Hip - well, I got the 5-AT several days ago. I've been taking 2 a day, one with breakfast and one with lunch, today is my 6th day. I haven't noticed anything, good or bad, and I'm glad no bad reaction at least so far. I was a little concerned about it possibly making me more tired through lowering cortisol, but I am hoping you are right in that perhaps it doesn't lower cortisol itself, but rather counteracts the effects of cortisol.

    I determined my dose with muscle testing done by myself and my chiropractor, which I know means less than nothing (a negative number!) to you, but it has been helpful to me on many occasions - But I don't want to start a debate here! :whistle: The bottle itself says to take 2 to 3 a day, and not to exceed 4.

    I know you said absorption is difficult and transdermal might be the best method but I'm being very cautious here.

    FWIW, the bottle says to take it for 4 to 8 weeks, but not longer than 8 continuous weeks without a 4-week break.

    Here's an article I posted awhile back when I wrote about BCAAs helping recovery from PEM: http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=41341

    and this excerpt I find intriguing in terms of the 5-AT, wondering if the 5-AT is able to normalize this metabolic pathway, since it was first activated for immune system stimulation:

    So we will see - do keep us posted how you do when you try it --
     
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  12. PatJ

    PatJ far and free I gaze

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    From the linked page:
    Does this mean that high cortisol could be a cause of fat and muscle loss for those of us who have lost a lot of weight and can't gain it back? I'm stuck at 110 pounds no matter how much, or what I eat (being 5' 10" and male this means I'm emaciated.)

    And could high cortisol also be a cause of reactive hypoglycemia during the day by over-regulating blood sugar and forcing it lower than it should be? I need to eat 10 small meals during the day to keep my blood sugar stable, but I can go all night without food until 4am when I need to start eating again.

    I've never had my cortisol tested and won't be able to for quite awhile (I'm partly bedbound due to low-bp and don't have a doctor.)
     
  13. Mary

    Mary Senior Member

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    @PatJ - The answers to your questions may be yes, I don't know for sure. There is a connection between high cortisol and a catabolic state where you would eventually lose muscle. Here's an article that has more info: https://www.drlam.com/blog/catabolic-state-adrenal-fatigue-syndrome-part-1/11116/

    It sounds like you really need a doctor, though even if you were able to get to one, finding a good one can be very difficult - have you tried taking salt to raise your BP? And a craving for salt and low BP can be indicators of adrenal fatigue.
     
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  14. PatJ

    PatJ far and free I gaze

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    That link was very useful. I'm still reading through the pages. I fit almost all the symptoms of being in a clinical catabolic state.

    I should have known it wouldn't be as simple as suppressing high cortisol (by taking the supplement discussed in this thread.)

    Doctors haven't been much help so far. My adrenals used to be in such poor shape that anything I tried to raise BP such as salt, licorice etc. would lead to aching adrenals. After taking liposomal vitamin-c for the past few months I think my adrenals are doing a little better. Now I can take large amounts of salt without adrenal ache but it doesn't raise my BP. I think most of the salt heads out of my body via frequent urination.

    The only consistent way to raise my BP, at least a little, is to use compression stockings.
     
  15. Mary

    Mary Senior Member

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    @PatJ - have you ever tried an adrenal glandular? Close to 20 years ago my chiropractor who does muscle testing said my adrenals were wiped out - I was weak as a kitten and knew nothing about adrenals at that time. He gave me Drenatrophin PMG by Standard Process, I had to take probably 3 times the regular dose, but within a couple of days my energy started to pick up. My adrenals are still my Achilles heel, but are in much better shape. I still take a low dose of a glandular, and extra pantothenic acid, the B vitamin which is crucial for adrenal health.

    The chiropractor also said I was catabolic - I'd never heard the term before but as I recall he basically said I was using my muscles for fuel --
     
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  16. Hip

    Hip Senior Member

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    I received my androstenetriol (AET) a few days ago also, and have been applying it transdermally, by opening up the capsule, dissolving the contents into a small amount of Baby Oil poured into the palm of my hand, and then applying the oil on the skin of my legs. I am using doses of 25 mg to 50 mg daily.

    It may be a coincidence, but the first thing I noticed with transdermal AET is that it rapidly boosted my emotional responses. One my ME/CFS symptoms is flat emotions (a CCC-listed symptom), which means for example that when I watch a romantic, emotional or melodramatic film on the TV, I have a poor emotional response, and am not emotionally moved by the story (but I used to be sucker for a good romantic movie). And generally, I don't feel much emotions in my body, nor in my social interactions. ME/CFS turned me into Mr Spock.

    However, after transdermal AET, I found I starting thinking and responding to things a little more emotionally; and then when I caught an old romantic film on the TV late last night, it actually brought me to copious tears throughout the film — a very rare occurrence in my normally emotionally dried out state.

    Whether this ramping up of emotional responses is just a coincidence, or one of those flash-in-the-pan responses to drugs or supplements that is not sustainable or repeatable, we shall see over the next few days.

    In any case it was completely unexpected, because I have not read anything about a connection between AED / AET and emotions.
     
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  17. Mary

    Mary Senior Member

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    Interesting @Hip in a couple of ways - I'd never heard of a flat emotional response being an ME/CFS symptom, but I don't doubt it. And then very interesting if the AET is affecting that.

    I realized this afternoon I am dragging more than I should be. I had been fighting a sinus bug for several weeks, and then am somewhat better but I'm tired now in a different way and am wondering if it's the 5-AT. It could be lowering my cortisol, or it could be a herx reaction if it is ramping up my immune system. I am probably going to cut it out for a few days and see what happens.
     
  18. Hip

    Hip Senior Member

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    Because AET is an immunomodulator that boosts the Th1 antiviral response, it is possible AET could increase fatigue by ramping up the immune response against viruses, just like immunomodulators such as oxymatrine that make you feel worse before you feel better. I am also feeling a little more tired today.
     
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  19. Mary

    Mary Senior Member

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    Hi @Hip - well, I do believe the AET is definitely doing something to me. I am quite tired, and somewhat spacey, similar to when I detoxed mercury - arggh! Not unbearable, but it's pretty strong so I am going to cut it out for probably 2 days to see how I do. I am hoping that it's my immune system, as you suggested.

    I know we are guinea pigs and some people would be horrified by it, but I keep thinking of doctors who experimented on themselves with vaccines and so on and how no progress would have been made, or it would have come decades later, and I've been crashing for almost 2 decades and sick for longer than that so WTH - see, I told you I was spacey! :sluggish:

    Hope you are doing okay --
     
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  20. PatJ

    PatJ far and free I gaze

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    I've tried a couple of adrenal glandulars and didn't notice much difference, but maybe I just haven't been taking enough. I just checked into Drenatrophin PMG, and Drenamin and found this message on the pureformulas web site:
    So that's not an option for me at the moment. I've got some Vitacost "Adrenal Stress Combat" capsules that include adrenal cortex and "adrenal polypeptide fractions", and I have some Thorne Adrenal cortex. I'll start taking the Thorne in addition to the Vitacost ASC and see how I feel.
     
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