Why DHEA Must Be Taken In Small Doses Only

[narouz]

In a recent interview
Peat said he would take like 2mg.
From that, he said, he would feel a slightly euphoric vibe.

 

[tara]

I just hit 40 and am into natural bodybuilding. My sister inlaw is a Doctor and she freaked out when she heard I was taking DHEA. I was only taking about 10mg a day. After she freaked out, I stopped, but am now wondering if I should go against her advice?

I though natural body building meant doing it without supplementing hormones. I misunderstood?

 

[Iron Man]

Just to clarify...

I do not compete... I consider myself natural, because I am not on the AAS type gear. I did not consider DHEA to be anything that radical until my sister inlaw (a Doctor), freaked out. I was only ever taking 5mg to 10mg per day. My blood results showed that my testosterone level was way down (a long way below the recommended levels), even though I lift weights and was taking DHEA. Not sure what is going on there. I am not sure what to do...
When I get my next blood work done and my Testosterone has not gone up to even average, then I feel the Doc will agree that I am a candidate for androgel or something like that. Personally... I would prefer to keep it natural though.

 

[sladerunner69]

post 87639 Once again, I am amazed at how well Ray's recommendations are backed by science. He has said that taking DHEA is fine and can restore proper youthful hormone balance. However, he cautioned that DHEA should only be taken in doses of no more than 10mg at once and preferably no more than 15mg daily.
Virtually all studies with DHEA used doses 50mg+ daily and the results for men were quite disappointing in terms of hormonal profile as in men DHEA raises estrogen quite a bit while in women it raised mostly DHT. Basically, the opposite effect of what most clinicians try to achieve. These results have convinced the scientific community that DHEA is a non-starter as an HRT for older people.
However, I have posted studies showing DHEA in doses of <15mg daily is quite androgenic and virtually indistinguishable from DHT in terms of anabolic effects.
So, what is the catch? This studies shows the that the estrogenic effects of DHEA start manifesting only at concentrations of 500nM or higher. A single dose of 15mg of DHEA results in concentrations slightly higher than 500nM, so Ray's recommendations at 10mg being the cutoff for non-estrogenic effects seem spot on.
So, DHEA does seem to have a lot of potential if you know how to use it and follow Ray's advice that "more is not better" when it comes to hormone supplementation. Also, doses of 5mg taken 2-3 times a day happen to mimic very closely the physiological levels and hormone metabolism of 20-year old men and women. So, once again, Ray's recommendations make perfect sense even in that context.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364836/

"...Finally, we examined whether the precursor hormone DHEA is taken up into the myotubes in culture and further processed to T or E2. After 5 days of differentiation, myotubes were exposed to 100 nm DHEA, 500 nm DHEA or mock for 6, 24 and 72 h. Myotubes readily took up DHEA into the cells as shown by the increase in the cellular concentration of DHEA (Fig.​(Fig.5A).5A). There were significant group differences at all time points (ANOVA P = 0.001, 0.003 and 0.002, respectively). Cellular DHEA concentration was significantly upregulated already at 6 h in 500 nm DHEA-exposed myotubes when compared to mock (P = 0.002) and continued to be elevated at 24 h (P = 0.004) and at 72 h (P = 0.004), while 100 nm DHEA was not sufficient to increase cellular concentration of DHEA at any time point. Interestingly, the cellular concentrations of T and E2 also increased in response to the DHEA treatment, indicating that their synthesis from DHEA was induced. However, the differences in E2 concentration did not reach statistical significance (Fig.​(Fig.5B).5B). Cellular T concentration was significantly different at 6- and 24-h time points, but not at 72 h (ANOVA P = 0.007, 0.027 and 0.144, respectively; Fig.​Fig.5C).5C). In addition, the gene expression of aromatase was statistically significantly upregulated after 72-h exposure to 500 nm DHEA (P = 0.13), while no significant differences in the gene expression of ESR1,ESR2,GPER, or AR were observed (Fig​(Fig5D5D–H)."

Should ther ebe any need to cycle DHEA, as in take breaks from it? Seems like the androgenic effects would wear off after sometime. Also, would a 205lb male like me be able to handle a few more mg of DHEA topically? I was thinking I should do 10mg x2 a day. I am a post-finasteride-syndrome guy so I have low andro especially low DHT. I need all the DHT I can possibly muster. Thanks.

 

[haidut]

post 118015

post 87639 Once again, I am amazed at how well Ray's recommendations are backed by science. He has said that taking DHEA is fine and can restore proper youthful hormone balance. However, he cautioned that DHEA should only be taken in doses of no more than 10mg at once and preferably no more than 15mg daily.
Virtually all studies with DHEA used doses 50mg+ daily and the results for men were quite disappointing in terms of hormonal profile as in men DHEA raises estrogen quite a bit while in women it raised mostly DHT. Basically, the opposite effect of what most clinicians try to achieve. These results have convinced the scientific community that DHEA is a non-starter as an HRT for older people.
However, I have posted studies showing DHEA in doses of <15mg daily is quite androgenic and virtually indistinguishable from DHT in terms of anabolic effects.
So, what is the catch? This studies shows the that the estrogenic effects of DHEA start manifesting only at concentrations of 500nM or higher. A single dose of 15mg of DHEA results in concentrations slightly higher than 500nM, so Ray's recommendations at 10mg being the cutoff for non-estrogenic effects seem spot on.
So, DHEA does seem to have a lot of potential if you know how to use it and follow Ray's advice that "more is not better" when it comes to hormone supplementation. Also, doses of 5mg taken 2-3 times a day happen to mimic very closely the physiological levels and hormone metabolism of 20-year old men and women. So, once again, Ray's recommendations make perfect sense even in that context.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364836/

"...Finally, we examined whether the precursor hormone DHEA is taken up into the myotubes in culture and further processed to T or E2. After 5 days of differentiation, myotubes were exposed to 100 nm DHEA, 500 nm DHEA or mock for 6, 24 and 72 h. Myotubes readily took up DHEA into the cells as shown by the increase in the cellular concentration of DHEA (Fig.​(Fig.5A).5A). There were significant group differences at all time points (ANOVA P = 0.001, 0.003 and 0.002, respectively). Cellular DHEA concentration was significantly upregulated already at 6 h in 500 nm DHEA-exposed myotubes when compared to mock (P = 0.002) and continued to be elevated at 24 h (P = 0.004) and at 72 h (P = 0.004), while 100 nm DHEA was not sufficient to increase cellular concentration of DHEA at any time point. Interestingly, the cellular concentrations of T and E2 also increased in response to the DHEA treatment, indicating that their synthesis from DHEA was induced. However, the differences in E2 concentration did not reach statistical significance (Fig.​(Fig.5B).5B). Cellular T concentration was significantly different at 6- and 24-h time points, but not at 72 h (ANOVA P = 0.007, 0.027 and 0.144, respectively; Fig.​Fig.5C).5C). In addition, the gene expression of aromatase was statistically significantly upregulated after 72-h exposure to 500 nm DHEA (P = 0.13), while no significant differences in the gene expression of ESR1,ESR2,GPER, or AR were observed (Fig​(Fig5D5D–H)."

Should ther ebe any need to cycle DHEA, as in take breaks from it? Seems like the androgenic effects would wear off after sometime. Also, would a 205lb male like me be able to handle a few more mg of DHEA topically? I was thinking I should do 10mg x2 a day. I am a post-finasteride-syndrome guy so I have low andro especially low DHT. I need all the DHT I can possibly muster. Thanks.

Yeah, in cases of low DHT I would do higher doses of DHEA topically. However, human studies showed that even topical administration raised estrogen when applied at more than 18mg daily. Granted, the study used a single application so 18mg at once may be estrogenic. Doing 10mg topically twice a day should be OK for a male. The total daily dose of oral DHEA for which no estrogenic effects were seen is 0.15mg/kg.

 

[sladerunner69]

Alrighty awesome, I'm going to take a few off and jump back on at 10mg 2x a day. That should do the trick I hope. That 18mg is probably dependent upon total lean body mass so I think I could handle 20-25mg with no estrogenic effects..... thanks for turning me onto this stuff man it's been a total game changer for me

 

[nullredvector]

@haidut what was the mg/kg for the 18mg topical dose? I'm 135kg, at last weigh but I may have lost a little. Ive been doing 15, I might double that spread out.

 

[haidut]

@haidut what was the mg/kg for the 18mg topical dose? I'm 135kg, at last weigh but I may have lost a little. Ive been doing 15, I might double that spread out.

There was no mg/kg, it as just a fixed dose of cream regardless of size and the amount of DHEA in it was 18mg. I think even 15mg is plenty for most people. Keep in mind that DHEA converts very easily into estrone, and estrone is the primary indicator of estrogenic activity in the organism, and it is also the primary cause of things like liver disease and spider veins in males.

 

[Kray]

BioMatrix DHEA Drops are made with safe ingredients and the dose per drop is small.
Biotics Research have also 2 DHEA products ( dosage of 2mg or 5mg ) which are safe but not sublingual.

Wilfrid, are you using the BioMatrix DHEA? Directions are sublingual but one other person on the forum uses it transdermally. I know it should be taken with fat so I'm not sure if transderm is the optimal way to go, but maybe under tongue with some fat-containing food?

I'm female and not sure what to make of dose equivalent given (1 drop = 3 mg micronized) and recommended intake of 2 drops x 2/day. I'm 60-ish, postmenopausal and also taking pregnenolone, up to 100mg/day.

 

[Wagner83]

I wasn't sure where to post this, this is the follow up on this bit where haidut discussed a study on "low" doses of T being very suppressive:

me:

Ok, you see prednisone in the same light as cortisol then, I saw it's a corticosteroid.

I thought this could be relevant for "physiological doses" of supps, it's hard to find information on physiological doses of hormones and that's where our and Ray' interests lie.
"
The 10-mg dose of fluoxymesterone that was used is equivalent to 7 to 8 mg of testosterone and thus only slightly exceeds the average testosterone production rate (21). Yet this dose resulted in a 50% reduction in plasma testosterone. [...] Stimulation with either ACTH or HCG intramuscularly causes
increases in plasma cortisol or testosterone within a few hours, and chronic stimulation with smaller doses of each tropic hormone leads to a slower rise in the respective plasma steroid levels. Similarly, doses of corticoid or androgen in the physiologic range cause an approximate 50% decrease
in the secretion of cortisol or testosterone, and this inhibition can be extended by the use of large amounts of corticoid or androgen."

haidut:

Yes, IMO prednisone and fluoxymesterone are the equivalent of cortisol and T in humans and that is why they were used. It would have been better to use bioidentical cortisol and T but I think the results would have been pretty similar. The study does not mention how they were administered but I am guess it was by injection to ensure full availability. If the full dose was injected at once I am not surprised there was a suppression occurred. They say the doses are physiological but that it is in regards to the total daily dose a human produces. No human produces 10mg - 40mg T at once or 20mg cortisol at once. So, the rapid rise in the steroid levels due to injection is likely to lead to suppression. I think a much better approach would have been to use 3mg x 3 daily (for the 10mg flyoxymesterone) and 6mg-7mg x 3 daily for the prednisone to mimic more closely the drawn out daily production.
I think the lesson for all of us is that even physiological doses can cause suppression/imbalance if they are administered all at once. I experienced this first hand with pregnenolone/DHEA and that is why the recommended use for Pansterone is the 5mg/5mg combo taken a few times a day instead of all at once even though 15mg/15mg pregnenolone/DHEA would be considered mild and physiological doses by most endocrinologists. Shows you how much they are in the dark about effect of bolus steroid dose. I shudder at the thought of how many men and women get brutally suppressed when they get treated with T, or cortisol for various conditions, often chronically. That can't be good for healht...
Anyways, I think pregnenolone and progesterone are very important for all people using steroids because while they do suppress excessive cortisol production they do not suppress baseline production, and they also activate the HPG. So, the combination of suppressing excessive adrenal activity combined with stimulation of HPG (which gets suppressed by excess cortisol) is a God-send for all people with hormonal imbalances. The only drawback with pregnenolone and progesterone is that they also have to be used in lower pulsatile doses instead of one large one because in smaller doses they allow pregnenolone to go down the DHEA pathway, while in higher doses they suppress the DHEA pathway and it leads to a build up of both 17-OH-pregnenolone and 17-OH-progesterone, which is a hallmark of conditions like adrenal hyperplasia. It would be interesting to see the effects of 5mg/5mg pregnenolone/progesterone WITHOUT the addition of DHEA. If it works like I suspect then maybe using DHEA won't be needed, which is a better situation as it can be a hit or miss depending on the dose and the person's health.

me:

thought they used fluoxymesterone to be able to differentiate it from T and see how much natural production was suppressed, if they can't tell the difference between the two then the total (fluoxymesterone + natural T) drop in plasma levels is even more of a concern. As for the doses they used, from what I see they did not use 10-40 mg of T, just the equivalent of 7mg (which may be a lot at once but far less than the current weekly protocol lol).

haidut:

The fluoxymesterone is basically T with some fluoride, It is even weaker than T both as an androgen and anti-catabolic steroid, so I am not even sure why a steroid like that exists except to mimic the effects of T while not being as extensively and quickly metabolized as T. Here is what the study says about doses used:
"...Fluoxymesterone (9a-fluoro-1 1,8-hydroxy-17amethyltestosterone), a synthetic androgen 70 to 80% as potent as testosterone, was given to four men at dose levels of 10 mg and 40 mg daily for 3 days. The data, summarized in Figure 3, show that the lower dose of fluoxymesterone resulted in a 50%o decrease in plasma testosterone levels."

In general, ANY true androgen (i.e. capable of displacing T or DHT from their androgen receptor binding) will decrease T synthesis due to negative feedback. Fluoxymesterone is one such steroid, especially when used in higher doses. Androsterone can also do it if taken in doses (100mg+ daily) as shown by the old study on hirsute women - i.e their T dropped by their DHEA increased. Btw, the Leydig cells have androgen receptors and thus the negative feedback can happen even without affecting the pituitary much. This has been observed in people whose pituitary has been taken out. So, I would be careful with high dose androgens and if used I would always combine with either pregnenolone or pregnenolone/DHEA as a way to keep steroid synthesis going. Both pregnenolone and DHEA stimulate the Leydig cells and also increase activity of the 3b-HSD and 17b-HSD enzymes.

me:

if 7-8mg of T leads to 50% suppression, then how can you recommend 10-15mg of a more downstream metabolite as a physiological dose that wouldn't lead to suppression or issues?

haidut:

I don't recommend 10mg - 15mg. I think it is an upper bound and most people probably do best on around 3mg-5mg, including estrogen inhibition but not too much inhibition to affect libido. T is a stronger androgen than androsterone, about 3 times stronger. So, to achieve the same suppressive effects, a single dose of 20mg - 30mg androsterone would be needed. I have never recommended anybody use such a dose and even the 10mg - 15mg won't come close to is when taken in divided doses of say 5mg each (which is what I have always said should be done, similar to DHEA). Peat also said that 10mg - 15mg would be the safe range, but he also said it in a context of treating cancer and neurodegenerative disease, so again, for healthier people the daily dose should probably be lower. When combined with pregnenolone/DHEA the suppressive effects of both T and androsterone decrease because pregnenolone/DHEA stimulate steroid synthesis downstream so their opposing effects cancel/attenuate each other. But still, 5mg androsterone is probably plenty for anyone unless they have a very serious issue like Peat mentioned.

me:

OK , what do you mean by pregnenolone/DHEA stimulate steroid synthesis downstream? Do you simply mean they are converted to downstream steroids until androsterone (so may help correct some of the potential imbalances) or do you mean they stimulate leydig cells to produce steroids?

An other question, why don't you use it most days of the week? I think anyone would benefit from it, like what you (and others) reported on muscles, voice, mood etc..

haidut:

Both, as per one of my other messages:
"...So, I would be careful with high dose androgens and if used I would always combine with either pregnenolone or pregnenolone/DHEA as a way to keep steroid synthesis going. Both pregnenolone and DHEA stimulate the Leydig cells and also increase activity of the 3b-HSD and 17b-HSD enzymes."

I think because steroids build up one should take a break from them every once in a while. I used to use Pansterone every day but as my health improved I find that I need it mostly after some type exhaustion event or very high stress. The rest of the time I seem to get the steroids I need from diet and metabolism. I eat a lot of egg yolks, as I mentioned before.

 

[boxers]

Im curious to see if anyone actually increased DHEAS level from taking DHEA such small amounts.. taking 50mg barely increases my DHEAS levels.

 

[Lyall]

What are people’s thoughts on taking higher dose DHEA and a AI to reduce conversion to estrone?

 

[haidut]

What are people’s thoughts on taking higher dose DHEA and a AI to reduce conversion to estrone?

That's the rationale behind mixing it with progesterone or pregnenolone, or taking aspirin with it. If you react well to pharma AI drugs then those could probably be tried as well.

 

[jack_zen]

@haidut :
I have low T and started to take 25 mg pregnenolone once and 5 mg DHEA twice a day (both oral)

Furthermore my doctor prescribed me a compounded cream consisting of 1,5% T, 1,0% progesterone. It also contains some Vitamin E. He advised to take 0.2-0.5g of the cream per day.

So if I use 0.5g of the cream this should be 7.5mg T and 5mg progesterone.
I use it since a few days on scrotum to improve absorption. But I don't know what the absorption rate is. I find information varying from 10-50% absorption from compounded testo-creams.

What do you think about my approach to raise my T levels and how would you dose the cream to get best benefits and minimal supression?
According to your older posts it would be better to split dose to 3 smalller doses right?

I also started my own topic here, if you prefer to answer there:
https://raypeatforum.com/community/threads/low-dose-testosterone-without-shutdown.24821/

thank you :)

 

[BigChad]

Awesome! If you are willing to experiment try adding 30mg - 60mg zinc daily to the DHEA regimen for added effect. Take zinc on empty stomach as absorption is inhibited by food.

do you still recommend this dosage of zinc? in the email repository thread Ray mentioned that zinc if supplemented should be limited to 10mg or less. I developed copper and iron deficiency symtpoms just from regularly supplementing 20mg zinc a day (with another 15mg or so from diet-ground beef/lamb). Although I didn't eat liver or oysters so my dietary copper and iron intake would have been lower than someone regularly eating liver and oysters

 

[TheBeard]

Just to clarify...

I do not compete... I consider myself natural, because I am not on the AAS type gear. I did not consider DHEA to be anything that radical until my sister inlaw (a Doctor), freaked out. I was only ever taking 5mg to 10mg per day. My blood results showed that my testosterone level was way down (a long way below the recommended levels), even though I lift weights and was taking DHEA. Not sure what is going on there. I am not sure what to do...
When I get my next blood work done and my Testosterone has not gone up to even average, then I feel the Doc will agree that I am a candidate for androgel or something like that. Personally... I would prefer to keep it natural though.

Tara was answering Renky

Is Renky your second handle?

 

[haidut]

do you still recommend this dosage of zinc? in the email repository thread Ray mentioned that zinc if supplemented should be limited to 10mg or less. I developed copper and iron deficiency symtpoms just from regularly supplementing 20mg zinc a day (with another 15mg or so from diet-ground beef/lamb). Although I didn't eat liver or oysters so my dietary copper and iron intake would have been lower than someone regularly eating liver and oysters

I never recommended this dose zinc as a daily regimen. It was suggested simply as an experiment (as the comment itself says) to see if it would inhibit aromatase and increase DHEA conversion into DHT.

 

[BigChad]

I never recommended this dose zinc as a daily regimen. It was suggested simply as an experiment (as the comment itself says) to see if it would inhibit aromatase and increase DHEA conversion into DHT.

Great. Bit off topic but would it be possible to message you. I wanted to ask something about tocotrienols and vitamin e

 

[nbznj]

Estrone is a really weak estrogen, AIs are trash anyway.

Don’t conflate XENOestrogens with E1/E2

 

[TheBeard]

Estrone is a really weak estrogen, AIs are trash anyway.

Don’t conflate XENOestrogens with E1/E2

Why would one have to not conflate them? Do they differ in their behavior? If so by what mechanism and magnitude?

You can't just spit "facts" like that, not back them up and just leave