weltweite
New member
- Awards
- 0
There was a thread posted by Nostrum with several studies on the benefits of androst-5-ene-3β,7β,17β-triol (βAET), which is found in the product Invictus, and other products like from Prototype Nutrition, Iconic Formulations, etc.
I noticed that one of the studies posted seemed to be very concerning for those with visceral fat, chronic inflammation, high cholesterol, and triglycerides.
I want to discuss this study in depth and nitpick at it. I find this especially important because I have used two bottles of transdermal (βAET) and plan to get more... but having a good amount of visceral fat makes me wonder if it is effective based on what the authors of this study concluded.
I will post up my summary of the study and if anyone wants to correct what I write, add to it, or discuss why it is not applicable because there were some methodological flaws in their trials, please do. I want BAET to work since there are very few products that target visceral fat effectively.
My notes on this study:
In healthy people BAET lowered cholesterol. It did not lower cholesterol in elderly people though.
In people that had lots of fat in the blood (triglycerides or cholesterol) there was NO cholesterol lowering effect. It didn’t matter if it was a healthy person or elderly.
BAET didn’t raise Hepatitis B antibodies in old people, which is surprising because it does in old mice.
The study authors think that both of these failures is because BAET was inactivated somehow by pro-inflammatory cytokines in chronic situations. Basically BAET doesn’t seem to work if there is chronic inflammation.
(My thought: High levels of visceral fat is definitely a chronic inflammatory situation that has a pro-inflammatory cytokine profile)
Measurements suggest BAET may become inactivated due to rapid metabolism as seen in primate studies.
This seems consistent because it happens when 17B-HSD is up-regulated (oxidative form of it) and this happens with low-grade systemic inflammation.
The study suggests that BAET may be effective in normal people who do not have chronic inflammation, but in people who do have chronic inflammation, there may need to invent/use a pharmaceutical derivative of BAET that doesn’t degrade and is more stable.
The drug was metabolized rapidly when sublingually administered and also when injected subcutaneously repeatedly, it still did not build up to significant levels in the blood, and was metabolized rapidly.
The study also says BAET may have different disposition in target tissues when comparing normal people with those who have higher lipids, older, or have chronic low-grade inflammation. (Very interesting)
Their data suggests that in inflammatory situations, anti-inflammatory androstenes like BAET may be locally inactivated by perturbation of the otherwise homeostatic in-tracrine network. (Very interesting)
For example, up-regulation of oxidative forms of 17B-HSD would inactivate anti-inflammatory adrenal androgen metabolites such as BAET, while expression and function of the steroid dehydrogenases themselves are regulated by inflammatory cytokine signal transduction pathways and intracellular oxidative potential.
(My thought: So they are saying that these messed up inflammatory signal transduction pathways may resist becoming normal and healthy in their function by the DHEA metabolites.)
They further support their theory by saying that the potent anti-inflammatory activity of 17a-ethynyl-BAET in situations where there is higher inflammation (also has a stronger potency than BAET) , and identification of 17-keto-BAET as a major metabolite support the hypothesis that oxidative 17B-HSD is an important influence. (Interesting)
In their Phase II trials, oxidative steroidogenic enzymes may have reduced exogenous BAET concentrations below therapeutic levels.
They reason that with advancing age, chronic inflammation conditions will not respond to DHEA treatment. This may explain why DHEA and BAET fail to provide any benefit in the context of chronic inflammatory conditions associated with hyperlipidemia and advanced aging.
Tying in with the phase II trials, there was a company that was working on a BAET drug, but appears to have given up on it when I tried to investigate where they were all these years later. That could be for many reasons (funding, politics, economy, new strategies, etc.)
Copy of their conclusion:
In summary, short-term administration of βAET was safe in humans, but the drug appeared to be rapidly metabolized and pharmacokinetics were poor, even with parenteral administration. Cholesterol lowering was observed in normal but not hyperlipidemic subjects, and βAET treatment failed to enhance the response to HBsAg vaccine in elderly subjects. These divergent activities that are reported between rodents and primates may in part be attributed to chronic inflammation, which in addition to differential metabolism provides a basis for the longstanding disparity between these species and the emergence of the “DHEA conundrum” [42]
These observations suggest that natural anti-inflammatory C-19 steroids may be useful to maintain health in healthy individuals, but tissue specific inactivation of natural androstenes in the context of chronic inflammation can result in treatment failure. In these situations metabolically resistant derivatives may be necessary to successfully treat disease.
I noticed that one of the studies posted seemed to be very concerning for those with visceral fat, chronic inflammation, high cholesterol, and triglycerides.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102572/7. Phase I and Phase II clinical trials of androst-5-ene-3β,7β,17β-triol
Phase I and Phase II clinical trials of androst-5-ene-3
I want to discuss this study in depth and nitpick at it. I find this especially important because I have used two bottles of transdermal (βAET) and plan to get more... but having a good amount of visceral fat makes me wonder if it is effective based on what the authors of this study concluded.
I will post up my summary of the study and if anyone wants to correct what I write, add to it, or discuss why it is not applicable because there were some methodological flaws in their trials, please do. I want BAET to work since there are very few products that target visceral fat effectively.
My notes on this study:
In healthy people BAET lowered cholesterol. It did not lower cholesterol in elderly people though.
In people that had lots of fat in the blood (triglycerides or cholesterol) there was NO cholesterol lowering effect. It didn’t matter if it was a healthy person or elderly.
BAET didn’t raise Hepatitis B antibodies in old people, which is surprising because it does in old mice.
The study authors think that both of these failures is because BAET was inactivated somehow by pro-inflammatory cytokines in chronic situations. Basically BAET doesn’t seem to work if there is chronic inflammation.
(My thought: High levels of visceral fat is definitely a chronic inflammatory situation that has a pro-inflammatory cytokine profile)
Measurements suggest BAET may become inactivated due to rapid metabolism as seen in primate studies.
This seems consistent because it happens when 17B-HSD is up-regulated (oxidative form of it) and this happens with low-grade systemic inflammation.
The study suggests that BAET may be effective in normal people who do not have chronic inflammation, but in people who do have chronic inflammation, there may need to invent/use a pharmaceutical derivative of BAET that doesn’t degrade and is more stable.
The drug was metabolized rapidly when sublingually administered and also when injected subcutaneously repeatedly, it still did not build up to significant levels in the blood, and was metabolized rapidly.
The study also says BAET may have different disposition in target tissues when comparing normal people with those who have higher lipids, older, or have chronic low-grade inflammation. (Very interesting)
Their data suggests that in inflammatory situations, anti-inflammatory androstenes like BAET may be locally inactivated by perturbation of the otherwise homeostatic in-tracrine network. (Very interesting)
For example, up-regulation of oxidative forms of 17B-HSD would inactivate anti-inflammatory adrenal androgen metabolites such as BAET, while expression and function of the steroid dehydrogenases themselves are regulated by inflammatory cytokine signal transduction pathways and intracellular oxidative potential.
(My thought: So they are saying that these messed up inflammatory signal transduction pathways may resist becoming normal and healthy in their function by the DHEA metabolites.)
They further support their theory by saying that the potent anti-inflammatory activity of 17a-ethynyl-BAET in situations where there is higher inflammation (also has a stronger potency than BAET) , and identification of 17-keto-BAET as a major metabolite support the hypothesis that oxidative 17B-HSD is an important influence. (Interesting)
In their Phase II trials, oxidative steroidogenic enzymes may have reduced exogenous BAET concentrations below therapeutic levels.
They reason that with advancing age, chronic inflammation conditions will not respond to DHEA treatment. This may explain why DHEA and BAET fail to provide any benefit in the context of chronic inflammatory conditions associated with hyperlipidemia and advanced aging.
Tying in with the phase II trials, there was a company that was working on a BAET drug, but appears to have given up on it when I tried to investigate where they were all these years later. That could be for many reasons (funding, politics, economy, new strategies, etc.)
Copy of their conclusion:
In summary, short-term administration of βAET was safe in humans, but the drug appeared to be rapidly metabolized and pharmacokinetics were poor, even with parenteral administration. Cholesterol lowering was observed in normal but not hyperlipidemic subjects, and βAET treatment failed to enhance the response to HBsAg vaccine in elderly subjects. These divergent activities that are reported between rodents and primates may in part be attributed to chronic inflammation, which in addition to differential metabolism provides a basis for the longstanding disparity between these species and the emergence of the “DHEA conundrum” [42]
These observations suggest that natural anti-inflammatory C-19 steroids may be useful to maintain health in healthy individuals, but tissue specific inactivation of natural androstenes in the context of chronic inflammation can result in treatment failure. In these situations metabolically resistant derivatives may be necessary to successfully treat disease.