Low Dose DHEA Robustly Increases Oxidative Metabolism

[haidut]

I posted another study recently that showed low doses DHEA treatment increased T and DHT levels in rats and had the same beneficial effects as exercise. The human equivalent dose used was <15mg per day.
These studies shows that a low dose DHEA dramatically improves oxidative metabolism in liver and brain. The treatment was for only 7 days and resulted in 2-4 fold increases in metabolism in these tissues. The doses used were lower than the DHT study and in fact the dose equivalent to 15mg for a human had negative effects such as increased liver weight and decreases in some subcomponents of cytochrome C. The lowest dosage used that had good effects (and in some cases had the most positive effect) was equivalent to 2mg - 3mg per day for a human. Even that dose enlarged the liver of the rats in one of the studies but the effects were quite small. Anyways, it seems that Ray is right on his warnings about DHEA and liver/brain. However, it also seems that low doses of DHEA have VERY beneficial effect on oxidative metabolism. So, starting with something like 5mg daily is probably a good way to test its effects. Do not exceed 15mg as that has negative effects on both liver and brain.

http://www.ncbi.nlm.nih.gov/pubmed/16794854
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267683/
http://www.ncbi.nlm.nih.gov/pubmed/17052700
http://www.ncbi.nlm.nih.gov/pubmed/16630690

Quote from one of the studies:
"...In conclusion, the overall results of our present studies point out that DHEA treatment significantly stimulated the respiratory activity in the liver mitochondria from young rats as well as old rats. Although the effects were of lesser magnitude in old rats, the total potential of oxidative energy metabolism increased to a grater extent because of significant dose-dependent increase in the liver weight. The results thus suggest that treatment with DHEA can have beneficial effect on energy transduction potential in liver mitochondria even in the old rats."

 

[charlie]

 

[uuy8778yyi]

where do I apply it ?

on my wrist ?

or scalp if testing hair growth benefits ?

 

[Tarmander]

What I find interesting is the risk of enlargement of liver. Like...this is sold on shelves here in the US at 50mg dosing.

 

[haidut]

post 99184 where do I apply it ?

on my wrist ?

or scalp if testing hair growth benefits ?

The studies used oral administration. Topical would probably work too and for metabolic purposes it does not matter where you apply it. This is not a thread for hair loss so please start a separate one if you need info on DHEA for hair loss issues.

 

[haidut]

post 99201 What I find interesting is the risk of enlargement of liver. Like...this is sold on shelves here in the US at 50mg dosing.

Yep, even 20mg human equivalent dose leads to liver enlargement in rodents, which shows its estrogenic effects. Why would people shoot this stuff like it's candy is beyond me. I think some of the culprits are in the bodybuilder community. They have tried DHEA and found it "mild" so most people take that to mean "benign". It is a hormone after all and it can be as androgenic as DHT if used properly or as estrogenic as estradiol if abused.

 

[sladerunner69]

Yep, even 20mg human equivalent dose leads to liver enlargement in rodents, which shows its estrogenic effects. Why would people shoot this stuff like it's candy is beyond me. I think some of the culprits are in the bodybuilder community. They have tried DHEA and found it "mild" so most people take that to mean "benign". It is a hormone after all and it can be as androgenic as DHT if used properly or as estrogenic as estradiol if abused.

Yes the bodybuilding community is not reknown for it's due dilligence and research.

I have seen an anecdotal reprot where somone using 2-3mg at a time got irritable, and according to the hot flushes he felt in his face, claimed estrogenic symptoms. I am only using small doses of DHEA but am still weary of negative effects as I am with everything. How can I be sure my 5mg doses arent converting much to estrogen?

 

[ecstatichamster]

In real world use in men it elevates estrogen and testosterone both. But takes months for the effects to accumulate. Cycling may help and low dose is best of course. Thanks for these studies @haidut

 

[mirc12354]

In real world use in men it elevates estrogen and testosterone both. But takes months for the effects to accumulate. Cycling may help and low dose is best of course. Thanks for these studies @haidut

And using it along something that would at least partialy prevent aromatisation - DHT, MB, vit. E, aspirin...

 

[cs3000]

These studies shows that a low dose DHEA dramatically improves oxidative metabolism in liver and brain. The treatment was for only 7 days and resulted in 2-4 fold increases in metabolism in these tissues. The doses used were lower than the DHT study and in fact the dose equivalent to 15mg for a human had negative effects such as increased liver weight and decreases in some subcomponents of cytochrome C. The lowest dosage used that had good effects (and in some cases had the most positive effect) was equivalent to 2mg - 3mg per day for a human. Even that dose enlarged the liver of the rats in one of the studies but the effects were quite small. Anyways, it seems that Ray is right on his warnings about DHEA and liver/brain. However, it also seems that low doses of DHEA have VERY beneficial effect on oxidative metabolism. So, starting with something like 5mg daily is probably a good way to test its effects. Do not exceed 15mg as that has negative effects on both liver and brain.
Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy metabolism in the liver mitochondria from developing rats - PubMed
Stimulation of oxidative energy metabolism in liver mitochondria from old and young rats by treatment with dehydroepiandrosterone (DHEA). A comparative study
Effect of dehydroepiandrosterone (DHEA) treatment on oxidative energy metabolism in rat liver and brain mitochondria. A dose-response study - PubMed
Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy metabolism in the cerebral mitochondria. A comparative study of effects in old and young adult rats - PubMed
Quote from one of the studies:
"...In conclusion, the overall results of our present studies point out that DHEA treatment significantly stimulated the respiratory activity in the liver mitochondria from young rats as well as old rats. Although the effects were of lesser magnitude in old rats, the total potential of oxidative energy metabolism increased to a grater extent because of significant dose-dependent increase in the liver weight. The results thus suggest that treatment with DHEA can have beneficial effect on energy transduction potential in liver mitochondria even in the old rats."

I don't think thats a negative effect on liver from DHEA, actually it looks like a benefit

They said the young rats didnt get a liver response , only the aged rats

looking at liver weight as % , u can see the liver weight restored to youth levels.
its a regenerative effect on small livers
https://www.semanticscholar.org/paper/Stimulation-of-oxidative-

(dose was subcutaneous 1mg/kg in rats, so a lot more bioavailable than orally / topically.
and where the 1mg/kg dose effects on mitochondria showed some reversal in young rats , in aged rats it continued to increase benefits)

it continued to be beneficial with higher dose in aged rats because their DHEA levels were low due to old age
(typical reduction in elderly humans is lowering to 10% of youth levels).
so if you know DHEA levels are crashed low or are old aged , by this the 1mg/kg subcutaneous dose is for max effect on liver regeneration & mitochondria,
otherwise the 0.2mg/kg subcutaneous dose is best. or if DHEA levels are somewhere in the middle (i.e 50% less like in colitis) then maybe 0.6mg/kg

400mg as cream vs 100mg orally in humans ,

orally gives a bigger peak with less dose

In 36 healthy older women (60-70yrs), 4g of DHEA cream (10%) or gel (10%) applied on a 30x30cm area were compared against oral administration of 100mg DHEA. Oral administration had a Cmax of 15.6+/-2.5ng/ml (from baseline of 2.3+/-0.3) at a Tmax of an hour, measuring 5.7+/-0.5ng/ml at 6 hours and hitting baseline at 24 hours. The application of a gel or cream reached levels of 8.2+/-2.0nmol/l and 8.0+/-1.2nmol/l at 12 hours, and progressively rose up to 24 hours when the study ceased (higher than baseline values); serum concentrations appeared to cross at 18 hours.[44]
Interestingly, no differences were seen in circulating DHEA, testosterone or estrogen levels between the cream or gel yet the cream resulted in significantly higher androstenedione concentration at 24 hours and topical administration in general favored androgen metabolism more than oral administration.[44] Over 14 days of application, the cream appeared to raise hormones better than the gel and no influence was seen on DHEA-S levels with topical application.[44]

Despite the differences seen in kinetics, the overall bioavailability of topical administration and oral administration in reaching the serum is comparable with minimal differences in AUC, with exception to DHEAS which does not appear to be significantly spiked with topical application;

^ Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women - PubMed
50mg dhea x2 vs 400mg as cream / gel
Serum levels of estrone (E1) and estradiol (E2) did not change following DHEA administration by any of the three formulations, while serum androstenedione (4-dione), testosterone, DHEA sulfate (DHEA-S), E(1)-S, androsterone glucuronide (ADT-G) and 3alpha-androstanediol-G (3alpha-diol-G), increased in all cases,

The present data show that DHEA is transformed into active androgens and estrogens in peripheral intracrine tissues with no or minimal release of the active steroids E(1), E(2) or testosterone in the circulation.


100mg DHEA works basically the same as 400mg as cream in humans

https://ars.els-cdn.com/content/image/1-s2.0-S0960076007001513-gr1.gif

 

[cs3000]

Despite the differences seen in kinetics, the overall bioavailability of topical administration and oral administration in reaching the serum is comparable with minimal differences in AUC, with exception to DHEAS which does not appear to be significantly spiked with topical application;

^ Bioavailability and metabolism of oral and percutaneous dehydroepiandrosterone in postmenopausal women - PubMed
50mg dhea x2 vs 400mg as cream / gel
Serum levels of estrone (E1) and estradiol (E2) did not change following DHEA administration by any of the three formulations, while serum androstenedione (4-dione), testosterone, DHEA sulfate (DHEA-S), E(1)-S, androsterone glucuronide (ADT-G) and 3alpha-androstanediol-G (3alpha-diol-G), increased in all cases,

The present data show that DHEA is transformed into active androgens and estrogens in peripheral intracrine tissues with no or minimal release of the active steroids E(1), E(2) or testosterone in the circulation.
100mg DHEA works basically the same as 400mg as cream in humans
https://ars.els-cdn.com/content/image/1-s2.0-S0960076007001513-gr1.gif

https://ars.els-cdn.com/content/image/1-s2.0-S0960076007001513-gr6.gif
by day 14 it changes and the 400mg is elevated.

baseline DHEA went up 2x in the 100mg oral group , went up ~7x in the 400mg cream group
so pretty much looks equal dosing between oral & topical for blood levels of dhea depending on whats in the cream.
no big differences tho