Dht, testosterone pre workout...
-
Haidut’s explanation raises some questions: for one, even if caffeine increased cellular uptake of oxandrolone, if we suppose that without caffeine the same amount of oxandrolone was absorbed form the intestines, then wouldn’t a blood test for oxandrolone show the same amount of oxandrolone in the blood in both cases? Could the blood test discriminate between extra cellular and intracellular oxandrolone?
Maybe if oxandrolone were not taken up by cells due to the same extent as they would under caffeine influence, it would be eliminated in the urine quickly, and thus would have been detectable after some time only at amounts 1/20 the amounts seen with caffeine co-administration.
But if caffeine indeed increased cellular uptake, why wouldn’t the same be true with respect to endogenous androgens? Maybe it is true, but there are simply not that many endogenously produced androgens available in a physiological stage when people normally consume caffeine thus only leading to a marginal increase in total androgens inside cells when taking coffee as one normally would.
By what mechanism could caffeine increase cellular uptake of androgens? Well, here’s one thing I know: Lipophilic caffeine derivatives like pentoxifylline and their metabolites are known to be anti-viral agents.
Some anti-viral agents like adamantane are known to work by increasing the lipophilicity of cells, prohibiting the entrance of the virus into the cells.
If caffeine has this same effect of increasing the lipophilicity of cells, then perhaps it increases their uptake on androgens
, which are lipophilic molecules.In time there is life but no knowledge; outside time there is knowledge but no life
-
@jamezb46 Very very interesting, amazing comment.
@jamezb46 said in Dht, testosterone pre workout...:
Haidut’s explanation raises some questions: for one, even if caffeine increased cellular uptake of oxandrolone, if we suppose that without caffeine the same amount of oxandrolone was absorbed form the intestines, then wouldn’t a blood test for oxandrolone show the same amount of oxandrolone in the blood in both cases? Could the blood test discriminate between extracellular and intracellular oxandrolone?
Exactly... that is why the hypothesis of increased bioavailability makes sense but it doesn't at the same time
@jamezb46 said in Dht, testosterone pre workout...:
But if caffeine indeed increased cellular uptake, why wouldn’t the same be true with respect to endogenous androgens? Maybe it is true, but there are simply not that many endogenously produced androgens available in a physiological stage when people normally consume caffeine thus only leading to a marginal increase in total androgens inside cells when taking coffee as one normally would.
By what mechanism could caffeine increase cellular uptake of androgens? Well, here’s one thing I know: Lipophilic caffeine derivatives like pentoxifylline and their metabolites are known to be anti-viral agents.
Some anti-viral agents like adamantane are known to work by increasing the lipophilicity of cells, prohibiting the entrance of the virus into the cells.
Okay here we are getting somewhere I think. The lipophilicity of the cell only determines free steroids affinity for the cell. Not bound steroids. Inside the cell free steroids are the only steroids that can get metabolised by enzymes
If it a cell is more lipophilic - more free steroids will enter the cell - and since more free steroids are in the cell, more will get metabolised.
Therefore; the ratio of a steroid to it's metabolites shows the metabolism of a steroid, and since metabolism of a steroid is determined by the lipophilicty of the cell, the ratio of a steroid to it's metabolite is an indicator for the lipohilicty of the cell?
In the study mentioned, at oxandrolone's maximal concentrations, caffeine decreased the ratio of oxandrolone to it's metabolite epi oxandrolone by 25% (from 10 to 7.5), therefore caffeine increased the metabolsim of oxandrolone by 25%.
So either caffeine induces the enzymes that metabolise oxandrolone, or it increases the lipophilicity of the cell, and free steroids affinity for the cell, causing more free oxandrolone to enter the cell to be metabolised into epioxandrolone decreasing the ratio of oxandrolone to epioxandrolone.
-
@alfredoolivas The enzyme is 17 beta HSD. I want to see evidence for how caffeine affects this enzyme in humans, because a rat study claimed that caffeine increased the expression of the enzyme, but it also claimed that caffeine increased testosterone, which doesn't happen in humans - so I am hesistant to claim that caffeine increases 17 beta HSD activity
-
guys apparently 2.5mg anavar is enough to cause hair shedding for some while studies have proven that in scientific rigor that neither dbol nor halo are proven to cause this
-
@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.
-
@alfredoolivas no im repeating what someone who reads lots of studies is telling me
-
@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
-
@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.
-
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.
-
@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
-
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.
-
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
-
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)
-
Ya you gotta take everything with a grain of salt these days.
-
https://www.youtube.com/shorts/uw7CS04_IZM
jay cutler is kinda peaty ngl
-
@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.
-
@sushi_is_cringe Seems good, that's a perfect amount of collagen.
-
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
-
@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.
