Dht, testosterone pre workout...
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@sushi_is_cringe
Can you share studies for the three steroids? -
@sushi_is_cringe I have thought about this issue for some time now (DHT derivatives causing hair loss). The standard explanation is quite straightforward: DHT causes hair loss. DHT derivatives are very similar to DHT. Therefore, DHT derivatives also cause hair loss.
That argument is, however, terrible.
That is because DHT does not cause hair loss. How do we know that? Because when DHT levels are the highest (during puberty), there is no male pattern baldness.
I have asked medical doctors about that fact specifically and I have had them reply: "well during puberty, estrogen levels in teenage boys are high to compensate for the high DHT".
I had to stop myself laughing. Aging males are known to have higher levels of estrogen than young males, and aging males are much more likely to be bald than young males. So, it looks like estrogen is not coming in to save the day for the DHT causes hairloss hypothesis.
Nevertheless, there is still the empirical fact that DHT derivatives do seem to cause hair loss (this can be debated -many of the cycles that cause hair loss also contain testosterone derivatives, or are employed during a "cutting phase" which is a time of huge physiological stress which could be a confounding variable- but let's assume it's true).
Am I without an explanation? Do I need to prostrate myself before the altar of the great DHT causes hairloss hypothesis? I don't think so.
My current thinking is that DHT derivatives "cause" hair loss because DHT derivatives cause micronutrient deficiencies that significantly affect the hair follicles that are very sensitive to such deprivations. Such micronutrients as: carnitine, zinc, folate, as well as amino acids like lysine are all "spent" on androgen receptor agonism in skeletal muscle, and so none are left over for the hair. Thus, hair loss results.
Unlike some hypotheses, this one should be testable. A positive test would be if you suffer hair loss from something like anavar, supplement with all the necessary micronutrients for the hair follicles, and observe no hair loss.
A negative test would be a lack of prevention of hair loss in the same scenario.
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@alfredoolivas no im repeating what someone who reads lots of studies is telling me
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@jamezb46 I didn't even know anavar is a dht steroid?
do you think carnitine supplementation is good? same dude recommends it , iirc 4-5g a day
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@sushi_is_cringe @alfredoolivas @jamezb46 how much protein do you guys think is good for 190lb-220lb male bodybuilding on gear? and how much at once per meal. I think 45g of protein + 10g gelatin/collagen peptides, 6 meals, so 270g + 60g protein total per day.
iirc jay cutler claims 5lb of meat a day when he competed, which when it is lean beef and chicken breast is almost 500g protein. in another interview he says 300-400g.
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@sushi_is_cringe
No, carnitine should not be supplemented in my opinion. It blocks uptake of t3 into cells. So it's not good to have in excess but I think its important to have a good amount through diet.
Do bodybuilders typically get enough from their chicken breast, egg whites, and whey protein? No.
Red meat is a much better source.
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@jamezb46 the reason ive heard to take carnitine is to sensitize androgen receptors . the anti t3 thing makes sense cause the guy who says take carnitine subscribes to the hayflick limit theory (lower metabolism = better longevity) which as we know is probably wrong
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@sushi_is_cringe
Well, there are no studies that show that it actually does "sensitize" androgen receptors.
The only study that there is going for it is a single study that showed that after an untrained group of individuals did weightlifting and took l-carnitine, they had increased muscle mass.
But they didn't control for the training effect from the weightlifitng.
That's literally all its got going for it. There are are also studies showing that it increases certain health markers in aging male populations.
But the reason for that is rather simple. Older people, same as sick people, depressed people, are all stuck in fatty acid oxidation and can't do glucose oxidation effectively.
Therefore, since Carnitine enhances fatty acid shuttling into the mitochondria for Beta oxidation, it will help them.
But, what would have helped them even more would have been switching to glucose oxidation.
So, while I believe that carnitine can made a bad situation less bad, I don't think it can make a bad situation good.
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increase not sensitize here
your explanation makes sense
same dude recommends pufa fats for muscle mass so I gotta pick and choose which info is good . their info on gear seems good tho
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@sushi_is_cringe
Ya, well, hyperthyroid people synthesize 4 times more androgens than hypothyroid people, so I guess I’ll choose doing things that move me closer to being hyperthyroid (enhancing glucose oxidation) than those things that move me closer to being hypothyroid (excess carnitine blocks glucose oxidation on multiple levels)
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@sushi_is_cringe
Ya you gotta take everything with a grain of salt these days.
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@sushi_is_cringe Well, find the studies he is referencing and form your own opinion! For example, me and James, didn't find that oxandrolone and caffeine study by ourselves, we are followers of Haidut, that mentioned the study a couple of times, and we each formed our own opinions of the study, rather than taking Haidut's word for granted.
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@sushi_is_cringe Seems good, that's a perfect amount of collagen.
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Well caffeine increases the expression of cAMP, which increases production of ATP, right? So maybe the effect is more global.
The way I was thinking about the effect of increasing the lipophilicity of the cell was that the cell would uptake more lipophilic steroids while excluding more hydrophilic steroids.
So, it would not be fully correct to say that a more lipophilic cell uptakes more steroids, rather it would uptake more lipophilic steroids, androgens among them.
So, if we look at the Log P values of the main steroids:
Estradiol (E2) – LogP ≈ 4.0
Progesterone – LogP ≈ 3.9
Dihydrotestosterone (DHT) – LogP ≈ 3.8
Testosterone – LogP ≈ 3.3
Androstenedione – LogP ≈ 3.0
11-Deoxycorticosterone – LogP ≈ 3.0
Androsterone – LogP ≈ 2.9
Dehydroepiandrosterone (DHEA) – LogP ≈ 2.8
11-Deoxycortisol – LogP ≈ 2.5
Estriol (E3) – LogP ≈ 2.5
Corticosterone – LogP ≈ 1.9
Cortisol (Hydrocortisone) – LogP ≈ 1.6
Aldosterone – LogP ≈ 0.5As you can see, the mineralocorticoids and the main glucocorticoids are the least lipophilic, whereas the androgens and progesterone are more lipophilic.
The two caveats are that some of the glucocorticoids like 11-Deoxycorticosterone are more lipophilic, but it is actually well known that the more lipophilic a glucocorticoid is, the less it activates that glucocorticoid "receptor" and the more it behaves like progesterone or allopregnenalone.
In fact, the saturated cortisol derivative 5a,3a tetrahydrodeoxycorticosterone is actually a strong neurosteroid and ligand of GABA receptors, just like alloP and 3a-androstanediol
Also, estrogen is the most lipophilic of them all, however the other lipophilic steroids like DHT and progesterone that greatly outnumber it stop its synthesis and oppose its action.
So, the more lipophilic cell will be full of androgens, progesterone, more saturated and thus less catabolic glucocorticoids, and will exclude the mineralocorticoids and the catabolic glucocorticoids.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 Yes absolutely, thank you for the correction. Oxandrolone is fully saturated so we can expect it to have high affinity to more lipophilic cells?
Edit: it does.
It turns out that caffeine does not increase the conversion of androstenedione into testosterone, which relies on 17-beta HSD, as studies have shown neither androstenedione or testosterone to change after caffeine administration.
So going back to the point, I am ruling out that caffeine increased expression of 17-beta HSD. So the only explanation of why caffeine was able to increase the metabolism of the same dose of oxandrolone, is increased uptake due to lipophilcity?
I asked chat GPT what it thought of this conversation: It said that caffeine may interact with the cytochrome p450 enzymes that metabolise oxandrolone, but this likely isn't the case, as explained. It also said that it may affect P-glycoprotein transporters, increasing the uptake via that mechanism, but that doesn't transport free androgens.
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@jamezb46 said in Dht, testosterone pre workout...:
Well caffeine increases the expression of cAMP, which increases production of ATP, right? So maybe the effect is more global.
What do you mean by this?
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That caffeine increases cyclic adenosine monophosphate levels, which leads to more ATP and thus more cellular energy.
In fact, our friend t3 is thought to increase cellular metabolism in part to this same mechanism, by inhibiting phosphodiesterase, and increasing cAMP levels.
I was considering that as the mechanism by which it could cause cells to be more lipophilic.
[https://pubmed.ncbi.nlm.nih.gov/39626644/]
For example, it's known that t3 supplementation, even given to aging males at 100mcg orally, increases levels of testosterone by about 14% and decreases cortisol by about 16%
Now, I have another study showing that in hyperthyroid women (due to Graves' disease), Testosterone was slightly elevated, but, much more significantly, DHT was way higher.
In fact, in the untreated hyperthyroid women, DHT was about 3.3x the level of normal thyroid women and DHT/T ratio was more than triple that of normal thyroid women.
So, we see that when thyroid hormone is high (aka metabolism is high), cortisol decreases, testosterone increases, and DHT increases even more.
Well, it's almost as if t3 increases the synthesis of steroids in a way that is proportional to their lipophilicity ... remember the LogP values? Cortisol is much more hydrophilic, testosterone more lipophilic, DHT very lipophilic. So, it looks like t3 shifts the balance heavily toward more lipophilic steroids.
So, is it a stretch to say that the lipophilicity of the cell increases when metabolism is high? I don't think so.
So, I think it's plausible to say that anything that increases cAMP levels will increase the lipophilicity of the cell. Caffeine being an agent that does that, that explains why it increases the uptake of oxandrolone.
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@jamezb46 That is a very good thought, good thinking outside the box.
Though, T3 has shown to inhibit and increase steroidogenic enzymes, such as increasing 5-AR, and decrease aromatase - potentially this is due to ATP, but there are mechanisms in play that increase the metabolism of steroids towards more downstream hormones that do not depend on increasing the lipophilicity of the cell. Potentially this is due to ATP
I found two studies that shows that caffeine increases the lipophilicity of the cell, and the lipophilicity of the cell affects testosterone uptake. Caffeine makes the lipid heads more hydrophobic, and this has been shown to increase testosterone uptake, at least in bacteria.
Interaction of Caffeine with Model Lipid Membranes
https://pmc.ncbi.nlm.nih.gov/articles/PMC8450902/#sec5
"In this case, thanks to surface-sensitive techniques, we determined that caffeine molecules are preferentially located in the hydrophobic region of the membrane....if originally present, caffeine molecules lay parallel to the acyl chains in the hydrophobic region of a bilayer. Because of the inclusion of caffeine molecules, the volume available for each phospholipid molecule increases, and this leads in turn to a larger headgroup hydration and a decrease in the total bilayer thickness. "
Hydrophobic Outer Membrane Pores Boost Testosterone Hydroxylation by Cytochrome P450 BM3 Containing Cells
https://www.frontiersin.org/journals/catalysis/articles/10.3389/fctls.2022.887458/full
"Thus, we co-expressed nine genes encoding hydrophobic outer membrane proteins potentially facilitating steroid uptake. Indeed, the application of four candidates led to increased initial testosterone hydroxylation rates."
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Thank you for finding those studies. I'm actually going to use all of this in a separate thread I'll make sometime later that I think some forum members will find quite useful.
If caffeine does indeed increase the lipophilicity of the cell, then because we know that DHT (and I think also testosterone) induce the 5 alpha reductase enzyme, then just by entering the cell in higher abundance, these lipophilic androgens (especially DHT) should increase their own synthesis.
This is a positive feedback loop.
In time there is life but no knowledge; outside time there is knowledge but no life
