Posts made by jamezb46

@Corngold

You are correct. All cigarettes are required by law to contain flame retardants. You want to be inhaling flame retardants? BIG NO

@Korven

They contain nicotine, which is converted to niacinamide in the body. Since niacinamide raises NAD+ levels, nicotine should too.

In fact, I found a study purporting to show just that.

https://pubmed.ncbi.nlm.nih.gov/36797299/

@VehmicJuryman

Ya, that's right. Seldom in nature are there truly unique properties. If something exists, it's usually on a continuum that contains many other realities.

Ex. Coffee is not the only source of caffeine, rather, the methylxanthines are pervasive in nature.

Similarly, the indigestible "insoluble fibers" are pervasive.

Turnips probably have them too, just based on their similarity to carrots.

@Korven

Maybe your body wants the NAD+ boost.

So maybe Niacinamide would work. Actually the combination of 250-500 mg niacinamide with 3-5 mg methylene blue should be really potent at increasing NAD+/NADH ratio.

So, if after doing that for a few days, you don't have the cravings, you might have satisfied a physiological desire.

On the other hand, you could try nicotine in its pure form. One company that make products with it is:

https://pixotine.com/?gad_source=1&gclid=CjwKCAiArKW-BhAzEiwAZhWsIC9ypbxooo67Bnza_T6FP5QsNSetk9DOfvwO5b6zL2tmcnseludpyBoCCygQAvD_BwE

@Jennifer

Thanks for sharing.

@oliveoil

As I was using my old-school CASIO FX-300MS calculator, I realized that it was basically exactly what I was looking for. If only my desktop worked like it did.

I tested it out at, unsurprisingly, it has no backlight. The screen is invisible in the dark.

If only they could make desktops like the old handheld calculators. Would be extremely cool and retro.

@Jennifer

Does your thyroid atrophy with those dosages?

@alfredoolivas

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.

@alfredoolivas

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.

@alfredoolivas

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.

@alfredoolivas

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 ≈ 0.5

As 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.

@Mauritio Whenever I go for a walk and see a pine tree or pine shrug, I pick of some of the needles, crush them between my fingers and smell it as I walk.

Probably the same effect.

@sushi_is_cringe

Ya you gotta take everything with a grain of salt these days.

@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)

@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.

@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.

@bioenergetical Try magnesium and riboflavin.

@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

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.

@alfredoolivas

Half life is 16 hours, so it might cause insomnia if taken in the evenings.

However, you could take advantage of the fact that caffeine is known to increase the peak concentration (20x with Anavar) as well as clearance time of orals that are administered with it.

https://www.adop.pt/media/4114/Oxandrolone_excretion_effect_of_caffeine_dosing_.pdf

The above study shows that 300mg caffeine taken at the same time as oxandrolone caused the oxandrolone levels in blood to skyrocket and then decrease to almost zero in 8 hours. So, the study authors note that the concentration of oxandrolone mirrored that of the caffeine.

So, let’s say your workout is at 5pm. You could take the caffeine and Tbol at 4, have your workout, then after take theanine, taurine, or glycine to help calm you down before bed.

That way you can hopefully metabolize most of the caffeine before bed (maybe at midnight?) or at least mitigate the effects of the caffeine on the CNS at that time while getting a boost from the tbol.