DHT Production Depends On Stress

Elephanto · May 30, 2015

http://www.ncbi.nlm.nih.gov/pubmed/19615370

"5alpha-R isozymes (5alpha-R1 and 5alpha-R2) mRNA and protein levels were detected in prefrontal cortex of male and female rats after they underwent environmental stresses, i.e., excessive heat, artificial light, and the sensation of immobility in a small space, similar to those found in common workplace situations. Results showed significantly higher 5alpha-R2 mRNA and protein levels in environmentally-stressed versus control rats."

haidut · May 30, 2015

Elephanto said:
http://www.ncbi.nlm.nih.gov/pubmed/19615370

"5alpha-R isozymes (5alpha-R1 and 5alpha-R2) mRNA and protein levels were detected in prefrontal cortex of male and female rats after they underwent environmental stresses, i.e., excessive heat, artificial light, and the sensation of immobility in a small space, similar to those found in common workplace situations. Results showed significantly higher 5alpha-R2 mRNA and protein levels in environmentally-stressed versus control rats."

Yes, that is true but it seems to be a defensive mechanism so I would not try to use stress to raise DHT levels. Under stress, cortisol activates aromatase (as Peat says) and there is no telling if testosterone or DHEA will convert into estrogen or DHT. I think a safer approach would be to take small doses of DHEA (no more than 5mg per dose, no more than 3 times daily) like Peat does. DHEA is itself an inducer of 5-alpha reductase and when you are NOT under stress and keep the dose low converts mostly into DHT in tissues. It will probably not raise your serum DHT levels but when they did tests on both rats and humans they found that when DHEA is ingested, the level of DHT metabolites increases by several hundred percent, while DHT in serum stays the same. This is one of the reasons leading people to say DHEA is useless as an androgen - not seeing change in serum DHT. But the studies are solid and I am afraid once FDA realizes DHEA is pretty much equal to DHT when taken in lower doses we may see the end of its unrestricted sales.
I posted several other studies showing DHEA is as anabolic as DHT in tissue, and it exerts beneficial effects just like exercise due to its conversion into DHT.
I think this study and the ones I posted demonstrate one of Peat's much debated points - it's tissue levels of hormones that matters and not serum. His famous example was about estrogen but it probably applies to all steroids. I guess if estrogen has some known metabolites, we should be asking the doctor to test for those and not directly for estrogen levels in serum. Some of the later metabolites of estrogen include 2-OH-estradiol, 4-OH-estradiol, 2-methoxy-estradiol, 4-methoxy-estradiol. Unfortunately, I don't know of a lab that would do such tests.
Just my 2c.

Elephanto · May 30, 2015

Well, stress is involved in neurodegeneration and this link with DHT probably explains why, as you can see in the other study I posted about Dickkopf-1. I'll take your word that Dhea mostly raises DHT in tissue.

DHT upregulates the androgen receptor, whereas testosterone downregulates it. It seems like there's no real benefit to DHT itself and one should keep SHBG high to prevent too much conversion of testosterone to DHT (or estrogen, for that matter).

Sure, DHT is more anabolic than testosterone, because it is very pro-survival and anti-longevity. Survivality and longevity are clearly opposed, that's why turtles live long and lions don't. It only makes sense that in a stressful environment, the body gives up longevity to raise its anabolism/survivality and it also makes sense when you see that women live longer than men in environments where they don't have to dominate to survive and the opposite is also true.

Oh and for instance, exercise doesn't necessarily promote anabolism/survivality, it can promote longevity. I haven't seen a study on dht, but I've read one showing that sedentary men have higher igf-1 (a pro-survival and anti-longevity gene) than those who exercise. Endurance training on the other hand raises DHT and cortisol because it is very stressful, but exercice below 40% oxygen capacity is proven to lower basal cortisol and igf-1, raise igfbp-3 and SHBG, and that would indirectly imply that it lowers dht.

miko · May 30, 2015

Elephanto how can you "keep SHBG high" except physical exercise?

Such_Saturation · May 30, 2015

Stress-induced elevation of testosterone concentration in high ranking baboons: role of catecholamines.

Elephanto · May 30, 2015

miko said:
Elephanto how can you "keep SHBG high" except physical exercise?

SHBG is often a marker of insulin sensitivity, so it would be one way of correcting that.

I posted a study about hnf4-a and how it is correlated with SHBG, check it out there are a couple ways to raise it. TNF-alpha and p53 downregulate hnf4-alpha so anything that decrease those two will help. Liver health is important for shbg.

"age (P<0.001) and fiber intake (P = 0.02) were positively correlated to SHBG concentration, whereas body mass index (P<0.001) and protein intake (P<0.03) were negatively correlated to SHBG concentration"

" SHBG was negatively correlated with BMI, fat mass, total IGF-I, free IGF-I, IGFBP3 and leptin"

The thing that raises igf-1 the most is milk. IGF-1 promotes growth, even Peat warns us about growth hormone yet recommends liters of milk which is proven to raise igf-1 more than anything else. Methionine restriction (which Peat recommends) decrease igf-1 and would in part explain higher shbg and lower igf-1 in vegans. Glutathione counter-regulates igf-1.

Correcting leptin resistance is another good way.

Thyroxine (thyroid) increases shbg (and Peat mentions it decreases igf-1).

Cortisol I think usually correlates negatively with SHBG.

miko · May 31, 2015

Thanks. I don't eat dairy becouse my acne/skin - I see improvements on dairy free diet. My SHBG is 24 (11-52).

sugar daddy · May 31, 2015

So you think that it's best to avoid dairy and Methionine (meat, fish, eggs and cheese)

You also suggest that high fibre low protein would be good?

Do you think any of the 'peat' types diets are good because from this post it would seem that you think a vegan diet is healthier.

What's your view that fibre is bad for digestion and causes problems with serotonin etc?
or that we need a reasonable amount of protein (100g protein) for liver function?

Just wondering if you think there's a way to do this (keep shbg high) from a peat perspective.

Such_Saturation · May 31, 2015

Nope we're screwed

Elephanto · Jun 1, 2015

It wasn't meant as a guide but rather some information I collected. It gives hints about what can influence shbg, like dietary fiber usually improve insulin sensitivity but I'm not necessarily recommending it. But the world's blue zones all consume lots of fiber and resistant starch, and not a lot of protein. I also don't think protein directly correlates with shbg, it probably just mean that protein give a greater insulin response than carb, and maybe it comes from having lot of animal fat while eating a high carb meal which would disrupt glucose oxidation. Meat eaters also statistically have higher cortisol (logically if you have more cholesterol available for steroid hormones -> more glucocorticoids) and cortisol is bad for insulin sensitivity. More heme iron is probably another reason why the studies found the negative correlation with protein.

From a Peat perspective, focusing on glucose oxidation is the main point that would help raise shbg. If your liver isn't already optimal, then eating a lot of sugar would be hard to do without driving hnf4-alpha and shbg down, and subsequently developing a fatty liver. I'm still experimenting but right now white rice and potato are my main carb sources and I do better on that and more frequent bowel movements. I think I'm gonna add whey as I want to keep some igf-1 and calcium inhibits igfbp3 (estrogen and high androgen receptor activity do too) and that's bad for hair loss (has to do with excessive keratinocytes and skull growth) you want a low free igf1/igfbp3 ratio and low igfbp2 and 5, high 6. So the logic is to relatively minimize phosphate so you don't need that much calcium to keep parathyroid in check (in term of proteins milk and meats are high in phosphate; gelatin and whey are low).

I'm collecting some info about igfbp-3, it correlates with a lot of pro-Peat stuff except high milk and calcium intakes and lack of exercise, so it's not only about hair loss, I do believe it correlates directly with health. I think the logic in Peat's diet to have that much phosphate so in turn you need a lot of calcium is for the vitamins and minerals found in meat/milk (like vitamin a raises igfbp-3, don't think vegans get a lot of vit a) but you can also supplement and not deal with stuff like advanced glycation end-product, mycotoxins, animal hormones, insulonergic amino acids and high phosphate.

Peaterpeater · Jun 8, 2015

Haidut wrote, "DHEA is itself an inducer of 5-alpha reductase and when you are NOT under stress and keep the dose low converts mostly into DHT in tissues."

Haidut, how do you know when your body is "NOT under stress?" I currently have a sore throat with cold-like symptoms and possible thrush.....would that mean my body is under enough stress which would cause supplemental DHEA to convert into estrogen instead of DHT?

haidut · Jun 8, 2015

Peaterpeater said:
Haidut wrote, "DHEA is itself an inducer of 5-alpha reductase and when you are NOT under stress and keep the dose low converts mostly into DHT in tissues."

Haidut, how do you know when your body is "NOT under stress?" I currently have a sore throat with cold-like symptoms and possible thrush.....would that mean my body is under enough stress which would cause supplemental DHEA to convert into estrogen instead of DHT?

Even under stress, if you keep each dose <10mg it should convert mostly into DHT. At least that's what the studies how. The estrogenic effects become a problem with as "little" as 25mg in a single dose.

Peaterpeater · Jun 8, 2015

Thank you for your response Haidut. I agree with the suggestion of keeping DHEA dosing less than 10mg because I have fairly recently taken a dose of 12.5mg (this was before I understood Ray's recommendation) and immediately felt the "shock" like reaction that Ray talks about when Estrogen is massively increased in the body. I want to try low dose DHEA again to increase my chances for conception but I'm afraid to now for obvious reasons. Pregnenolone hasn't seemed to work for me in increasing DHEA. Direct DHEA supplementation has helped me in the past with infertility issues and I was hoping it would help me again the second time around.

haidut · Jun 8, 2015

Peaterpeater said:
Thank you for your response Haidut. I agree with the suggestion of keeping DHEA dosing less than 10mg because I have fairly recently taken a dose of 12.5mg (this was before I understood Ray's recommendation) and immediately felt the "shock" like reaction that Ray talks about when Estrogen is massively increased in the body. I want to try low dose DHEA again to increase my chances for conception but I'm afraid to now for obvious reasons. Pregnenolone hasn't seemed to work for me in increasing DHEA. Direct DHEA supplementation has helped me in the past with infertility issues and I was hoping it would help me again the second time around.

Most human studies show that pregnenolone converts almost entirely into progesterone and allopregnanolone, not much into DHEA. However, taking 500mg pregnenolone for 8 weeks did increase DHEA in humans but not by much. So, for people who want to increase DHEA direct supplementation may be needed. A dose of 5mg taken 2-3 times a day should be more than enough, according to Peat and the studies I have seen.

Nick Ireland · Jun 8, 2015

SHBG is a wild card. It says nothing definitively about hormone status because it has so many factors influencing it's level. This is why TRT docs do not treat on the basis of an SHBG level and are loathe to offer drugs to control it. Sure, winstrol will hammer SHBG down to the 20's or less but the underlying problem remains. I've had SHBG at 83 and cortisol simultaneously at 595. So there is no negative correlation. The fact is that SHBG is a well overplayed serum test. The actual amount of T it can bind, even at 80 or 90 is not significant enough to blunt the overall androgenic or anabolic effect of endogenous T in the average male. This discussion with Bill Roberts discusses the science behind that assertion.
http://tnation.tnation.com/free_online_ ... 8&pageNo=1

SHBG has little to do with cortisol, although cortisol can act as an amplifier for various hormones because it provides the transport and connection facility to their respective sites of action. This is why dudes with low cortisol get little benefit from T therapy and have to boost their cortisol line with pregnenolone or Cortef.

Haidut is right here. Tissue levels are more important than serum markers for this discussion. Certain tissues are capable of holding onto more estrogen than others, the skin for example. However, that level will eventually influence a host of other factors which CAN be detected more easily in the blood like histamine and cortisol. The proof of Ray's tissue assertions lies in the aparent ability of topically applied supplements/drugs to produce more effective results. This is especially true for vitamins E and A, but on balance it would also apply to the commercial T preparation Andgrogel which has a pronounced positive DHT effect ultimately requiring less AI meds - though the lack of gentle titration often leads to sides which should not be blamed on the drug but it's ham fisted application by general physicians.

Cleverly, the oral oil based T capsule Restandol uses the lymphatic system to deliver the hormone and avoid the first pass of the liver - and it is not liver toxic. The lymphatic system is the same delivery vehicle for our topical Peat friendly supps. Few people know this, but Restandol can be applied topically also. A single capsule is listed as 40mg T. But the actual molecular weight is 25mg. At an absorption rate of 20%, that's 5mg from a single capsule - exactly the amount Ray recommends to top up T to youthful levels without compromising endogenous production. Haidut's suggestion of small, split doses of DHEA works because it is not upsetting the balance of hormones - it is subtly adjusting them by acting within feedback limits.

I have learned to ignore many serum markers - because they are not telling the real story. The blood is only a physical transport - we never hear about the half lives of drugs in tissues, because nobody really tests or knows that specific imformation despite it's importance.

Nick Ireland · Jun 8, 2015

It's also proposed that Restandol's rapid 'feel good' effects on the gut and brain are because of it's ability to quickly increase DHT. Perhaps DHT rises in stressful situations to directly buffer stress effects - physically and paychologically.
A nice intro to DHT:
http://www.bodybuilding.com/fun/reform8.htm

Guys on DHT meds (where appropriate) look better, feel more confident and relaxed, have more energy. Those changes happen faster than those boosting exclusively with T and an AI and avoid many of the pitfalls associated with the latter. DHT has been successfully used an antidepressant and a fertility drug. Surely then, it's effects are the retention and prolongation of youth?

haidut · Jun 8, 2015

Nick Ireland said:
SHBG is a wild card. It says nothing definitively about hormone status because it has so many factors influencing it's level. This is why TRT docs do not treat on the basis of an SHBG level and are loathe to offer drugs to control it. Sure, winstrol will hammer SHBG down to the 20's or less but the underlying problem remains. I've had SHBG at 83 and cortisol simultaneously at 595. So there is no negative correlation. The fact is that SHBG is a well overplayed serum test. The actual amount of T it can bind, even at 80 or 90 is not significant enough to blunt the overall androgenic or anabolic effect of endogenous T in the average male. This discussion with Bill Roberts discusses the science behind that assertion.
http://tnation.tnation.com/free_online_ ... 8&pageNo=1

SHBG has little to do with cortisol, although cortisol can act as an amplifier for various hormones because it provides the transport and connection facility to their respective sites of action. This is why dudes with low cortisol get little benefit from T therapy and have to boost their cortisol line with pregnenolone or Cortef.

Haidut is right here. Tissue levels are more important than serum markers for this discussion. Certain tissues are capable of holding onto more estrogen than others, the skin for example. However, that level will eventually influence a host of other factors which CAN be detected more easily in the blood like histamine and cortisol. The proof of Ray's tissue assertions lies in the aparent ability of topically applied supplements/drugs to produce more effective results. This is especially true for vitamins E and A, but on balance it would also apply to the commercial T preparation Andgrogel which has a pronounced positive DHT effect ultimately requiring less AI meds - though the lack of gentle titration often leads to sides which should not be blamed on the drug but it's ham fisted application by general physicians.

Cleverly, the oral oil based T capsule Restandol uses the lymphatic system to deliver the hormone and avoid the first pass of the liver - and it is not liver toxic. The lymphatic system is the same delivery vehicle for our topical Peat friendly supps. Few people know this, but Restandol can be applied topically also. A single capsule is listed as 40mg T. But the actual molecular weight is 25mg. At an absorption rate of 20%, that's 5mg from a single capsule - exactly the amount Ray recommends to top up T to youthful levels without compromising endogenous production. Haidut's suggestion of small, split doses of DHEA works because it is not upsetting the balance of hormones - it is subtly adjusting them by acting within feedback limits.

I have learned to ignore many serum markers - because they are not telling the real story. The blood is only a physical transport - we never hear about the half lives of drugs in tissues, because nobody really tests or knows that specific imformation despite it's importance.

Excellent points!
Speaking of tissue levels of various hormones - I would love to see some more reliable studies but like you said, there aren't many out there. For a hint on the discrepancy between blood and tissues, I will just mention that brain and muscle levels of pregnenolone have been found to be 50-100 times higher than plasma levels. Also, substances like methylene blue and DHEA have been found to have really long half-life in brain and liver. Methylene blue has been shown to have half life of at least 30 hours in the brain, and some people as high as 80 hours. DHEA has a half life of a few weeks in the brain.
So, people taking even <1mg methylene blue or <5mg DHEA per day will elevate their tissue/brain levels over time and this probably explains the beneficial effects form the microgram dosages of methylene blue some people are taking as well as the anabolic effects from small doses of DHEA.

haidut · Jun 8, 2015

Nick Ireland said:
It's also proposed that Restandol's rapid 'feel good' effects on the gut and brain are because of it's ability to quickly increase DHT. That's probably the effects of allopregnenolone for which DHT is essential. Perhaps DHT rises in stressful situations to directly buffer stress effects - physically and paychologically.
A nice intro to DHT:
http://www.bodybuilding.com/fun/reform8.htm

Guys on DHT meds (where appropriate) look better, feel more confident and relaxed, have more energy. Those changes happen faster than those boosting exclusively with T and an AI and avoid many of the pitfalls associated with the latter. DHT has been successfully used an antidepressant and a fertility drug. Surely then, it's effects are the retention and prolongation of youth?

Peat has said that in his opinion testosterone is almost as dangerous as estrogen. He said he thinks dysregulation of testosterone metabolism is the primary cause behind diseases like ALS. In light of that, he has told people over email that supplementing DHT would be much safer than T even though he also said that small doses of T can be beneficial as well.

Elephanto · Jun 8, 2015

Nick Ireland said:
It's also proposed that Restandol's rapid 'feel good' effects on the gut and brain are because of it's ability to quickly increase DHT. That's probably the effects of allopregnenolone for which DHT is essential. Perhaps DHT rises in stressful situations to directly buffer stress effects - physically and paychologically.
A nice intro to DHT:
http://www.bodybuilding.com/fun/reform8.htm

Guys on DHT meds (where appropriate) look better, feel more confident and relaxed, have more energy. Those changes happen faster than those boosting exclusively with T and an AI and avoid many of the pitfalls associated with the latter. DHT has been successfully used an antidepressant and a fertility drug. Surely then, it's effects are the retention and prolongation of youth?

5-a reductase is essential to convert progesterone to allopregnenolone, but that doesn't mean DHT is essential. If one has a high shbg, not much testosterone would be converted to DHT and it would not interfere with 5-a reductase's ability to produce allopregnenolone. about the prolongation of youth, old men have higher dht and lower testosterone than young men, so that's false.

haidut · Jun 8, 2015

Elephanto said:
Nick Ireland said:

It's also proposed that Restandol's rapid 'feel good' effects on the gut and brain are because of it's ability to quickly increase DHT. That's probably the effects of allopregnenolone for which DHT is essential. Perhaps DHT rises in stressful situations to directly buffer stress effects - physically and paychologically.
A nice intro to DHT:
http://www.bodybuilding.com/fun/reform8.htm

Guys on DHT meds (where appropriate) look better, feel more confident and relaxed, have more energy. Those changes happen faster than those boosting exclusively with T and an AI and avoid many of the pitfalls associated with the latter. DHT has been successfully used an antidepressant and a fertility drug. Surely then, it's effects are the retention and prolongation of youth?

Click to expand...

5-a reductase is essential to convert progesterone to allopregnenolone, but that doesn't mean DHT is essential. If one has a high shbg, not much testosterone would be converted to DHT and it would not interfere with 5-a reductase's ability to produce allopregnenolone. about the prolongation of youth, old men have higher dht and lower testosterone than young men, so that's false.

Since pregenolone converts mostly into progesterone and from there into allopregnanolone, would you say pregnenolone increases 5-AR? Some people get a highly androgenic effect from a combination of pregnenolone and DHEA. DHEA increases 5-AR and if pregnenolone does the same it would explain the big spikes in DHT people get with this combination.

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DHT Production Depends On Stress

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