Dht, testosterone pre workout...
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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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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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Ya you gotta take everything with a grain of salt these days.
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https://www.youtube.com/shorts/uw7CS04_IZM
jay cutler is kinda peaty ngl
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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.
In time there is life but no knowledge; outside time there is knowledge but no life
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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
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Let's put the observation that caffeine doesn't increase testosterone in humans into context in light of the studies I shared about thyroid hormone (which shares caffeine's ability to increase cAMP).
Recall that the hyperthyroid women did not produce significantly more testosterone than the normal thyroid women. In fact, at least at the 95% confidence level the study authors used, the amount of testosterone produced by the hyperthyroid women was not significantly different from that produced by normal thyroid women (0.82 nmol/L +- 0.21) vs (0.77 nmol/L +- 0.26), respectively.
Like I said, however, DHT difference absolutely was statistically significant. Hyperthyroid women had more than 3x DHT of normal thyroid women.
Androsterone and 5 alpha-androstane-3 alpha 17 beta-diol (androstanediol) were also significantly elevated.
Now, there are such things as the "backdoor" and "canonical" pathways of steroidogenesis.
Since the study already admits that hyperthyroidism induces 5 alpha reductase, but testosterone levels were not elevated, and neither was androstenedione, this suggests that the backdoor pathway was being used.
And since androstanediol levels were high also, that suggests that 17 beta HSD 3/5 must also have been induced, for otherwise we would perhaps have expected elevated androsterone but not elevated androstanediol. Likewise 17 beta HSD 6 must have been induced as well to get elevated DHT from the elevated androstanediol.
So therefore the reason that androstenedione and testosterone were not elevated must have been because the progesterone and 17 hydroxy progesterone were mostly going toward dihydroprogesterone and 17 hydroxy-dihydroprogesterone from the induced 5 alpha reductase.
Therefore there were not significant enough amounts of those precursors available to make androstenedione and testosterone.
The difference between rats and humans with regard to caffeine intake is therefore probably due to rats and humans having different pathways for steroidogenesis.
In humans, we can tentatively say that caffeine favors the backdoor androgen synthesis pathway, which supports the idea that it increases the lipophilicity of cells as the backdoor pathway is more lipophilic than the canonical one.
In time there is life but no knowledge; outside time there is knowledge but no life
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@jamezb46 said in Dht, testosterone pre workout...:
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 has been exactly shown in animal studies, DHT increased more than T in this study:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3521899/
"Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe." -
@jamezb46 Maybe, no one knows how significant the backdoor pathway is in humans, and if allopregnanolone or it's precursors, increase DHT in humans.
One could equally say that the reason androstenedione and T weren't as elevated, was that they turned into DHT - any extra androstenedione and T made by the body was turned into DHT and 5a-androstanedione by elevated 5 alpha reductase.
Given that T and androstenedione are the classical, proven, precursors to DHT, I believe this theory, but given there are two pathways to DHT, no one can make conclusions of what was increasing DHT in the steroidgenic enzyme pathway; it's kind of like discusssing about why androsterone rose; was it because 3a androstanediol rose or was it because androstanedione rose? No one knows.
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Any one in the UK got any dht powder for sale?
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@jamezb46 i think your micronutrient deficiency in high androgen state causing hairloss theory is correct
the amount of food required for optimal health is beyond what seems reasonable to normies.
eating clean , whole, “nutritious” foods all day with no junk foods with empty calories, one has to be eating what feels like constantly, every few hours, to hit micronutrient targets. I’ve seen it theorized that copper RDA in usa (0.9mg) is actually up to 10x too low, for example. When I eat mainstream foods like chicken, rice, brocolli, potatoes, I barely hit 2-2.5mg. Only with the addition of seafoods, organ meats, cocoa powders, etc do I get approaching the higher target.
now add athletes/bodybuilders to this. your theory that the androgen receptor agonism requires more nutrients makes sense. also, what happens when someone suffers a major physical or even emotional trauma. their hair falls out, or turns white/grey.
add to that the poor foods people choose, and how this makes it so they can’t eat enough. with bloating and stomach discomfort.
I think calorie and nutrient needs are way higher than commonly thought. The fasting meme and OMAD is mostly a mistake . sure sometimes it’s cool to fast or skip meals but in my opinion many people could do with alot more food, like alot.
ive had this theory that a way for chronic illness sufferers to recover is to aim for basically a bodybuilding lifestyle and diet. with multiple meals per day, anabolic steroids, and training. then once recovered they can stop the gear and by then they will know what food intake is required and also what normal euphoria from day to day living feels like and should feel like
