General Research - Ancillaries

[Sicsemptyran]

I thought I would create a thread where I just generally post anything I find interesting, and if others do, then great. Shoutout to @egruberman for sending me down the cholesterol rabbit hole recently.

Currently am running an experiment on myself with bempedoic acid, a relatively newer drug that is quite expensive if you get it through mainstream pharmacies as its branded form Nexletol or the combo pill with ezetimibe called Nexlizet. While the main effect of bempedoic acid is to lower LDL (and ApoB), the Phase III trials had some eyebrow raising effects to me.

For one, incidents of diabetes/hyperglycemia in the treatment group were lower than placebo, entirely the opposite of what we see from statins. In addition, hematocrit was 1.6% lower in the treatment group as compared to placebo, with erythrocytes being 1.8% lower.

To me, this sounds like it would be damn near a perfect drug for bodybuilders. Lowering of LDL, mitigating erythropoietic effects, not impacting insulin sensitivity (and possibly improving it), all without the negative muscle pain from statins. There are some small side effects, such as raising uric acid, as well as a warning regarding tendon rupture. That said, in reading the studies, the tendon ruptures are likely not drug related and frankly not a worry of mine based on the data.

Am 2 weeks into this experiment and will report back with my own results and bloodwork changes when I get them!

(Multiple edits for dumb little spelling mistakes, really should have read this before posting)

 

[egruberman]

That said, in reading the studies, the tendon ruptures are likely not drug related and frankly not a worry of mine based on the data.

I skimmed through the clinical trials and incidence of tendon rupture was in all cases also coincident with a high-dose statin.

hematocrit was 1.6% lower in the treatment group as compared to placebo, with erythrocytes being 1.8% lower.

This, I missed. It may have some explanation for my reasonable looking hematocrit on my unreasonable looking anabolic load.

 

[Sicsemptyran]

I skimmed through the clinical trials and incidence of tendon rupture was in all cases also coincident with a high-dose statin.

Absolutely. I understand the medical reasoning of testing so many of these new drugs on people who are already pursuing standard-of-care (max dose statins), but it really can cloud the data. One benefit to the bempedoic acid trials is they had the arm which was done in people who swore off statins, showing yet another study in which lowering LDL improves cardiovascular outcomes independent of mechanism.

This, I missed. It may have some explanation for my reasonable looking hematocrit on my unreasonable looking anabolic load.

I was very surprised by this, and there does not seem to be a great mechanistic explanation for it as statins do not have the same effect. Interestingly, among all the study participants, it was an incredibly reliable effect. If you take bempedoic acid, you can expect a drop in your hematocrit.

It's conveniently small enough to be clinically insignificant for most older individuals where I'd be worried about that, but large enough where it could put a ceiling on us who use AAS or drop us from a level where we have some slight unease to one where we do not bat an eye at it.

Terribly interesting and promising adjunct to our stockpile in my opinion. Especially so for those who refuse to touch statins either for legitimate side effects or dogma. Nexilizet (BA + Ezetimibe) could still lower risk substantially.

 

[egruberman]

I'm glad you made this topic. I'm of the opinion that bempedoic acid is under-utilized in the bodybuilding community.

 

[Sicsemptyran]

So 4 weeks into the experiment - Here are my current results going from just ezetimibe to BA and ezetimibe. AAS is currently 250mg/testosterone weekly.

Change from the averages of my last 4 bloodworks (I get blood every ~4 weeks)
LDL 100 -> 74
HDL 69 -> 69
Trigs 51 -> 34
Hematocrit 52.4 -> 49.4 (!!!)

All other markers were completely unchanged or unremarkable. Theoretically BA takes 6-8 weeks to show maximum efficacy, so will have to see what the end result is.

 

[egruberman]

Change from the averages of my last 4 bloodworks (I get blood every ~4 weeks)
LDL 100 -> 74
HDL 69 -> 69
Trigs 51 -> 34
Hematocrit 52.4 -> 49.4 (!!!)

That's excellent!

 

[Sicsemptyran]

Let me start by saying I'm not suggesting this means people should use SARMs, but I am a fan of all research on anabolic agents, as it reduces the stigma and has the potential to incentivize research into drug classes that have been completely untouched by pharma for years.

In this study, participants were given very low doses of enobosarm/ostarine while taking a GLP-1, and showed 71% less lean mass loss while achieving an additional 27% fat loss.

This could be very interesting, because if approved this would be a non-controlled, oral anabolic agent that would potentially increase the amount of the general population using anabolics and also incentivize pharma to create newer, more effective anabolic agents. Top line data and announcement below.

https://ir.verupharma.com/news-events/press-releases/detail/225/veru-announces-positive-topline-data-from-phase-2b-quality

Cross posting into my general research thread (though this is less of an ancillary). Interesting nevertheless.

 

[Sicsemptyran]

Update to the continuing bempedoic acid experiment, decided to get bloodwork only 4 weeks after my last test (I’m impatient) and things couldn’t be going better.

Now currently on 300mg of testosterone cypionate weekly for those past 4 weeks from 250mg, my numbers are as follows:

LDL 100 -> 74 -> 64
VlLDL 11 -> 10 -> 10
HDL 69 -> 69 -> 64
Trigs 51 -> 34 -> 41
Hematocrit 52.4 -> 49.4 -> 48.2
HsCRP .64 -> .92 -> .32

Everything else is completely unchanged. Really couldn’t be happier with how bempedoic acid is working for me, and considering I’m a guy who even with obscenely strict diets couldn’t budge my LDL below ~180, to have ezetimibe and BA get me down to a 3rd of that is really all one could ask for.

 

[Photon]

BA is more expensive than ezetimibe or a statin, which is probably why it isnt used much. It probably wont do as much as a statin either. Now.. how are you getting that HDL up so high? Ive never been able to get mine above 60

 

[Sicsemptyran]

BA is more expensive than ezetimibe or a statin, which is probably why it isnt used much. It probably wont do as much as a statin either. Now.. how are you getting that HDL up so high? Ive never been able to get mine above 60

Definitely, for most it seems to be less effective. That said, from the Indian sources you're looking at ~$25-30/month which is pretty negligible. If that ever dries up I'd probably still cough up the $450/month for BA, but I'm lucky that I'm in a position to do so. The hematocrit lowering effects of BA referenced in the study I posted in my original post (and I'm seeing in myself) is pretty incredible.

As for the HDL, wish I could tell you. My TT is ~2500 on 300mg/week as I'm quite a hyper responder, and it just does not touch my HDL whatsoever. I definitely take care of myself and do my cardio, used to be a competitive runner, but not anymore than tons of the folks on this forum. Unless I'm running orals I've never seen it budge below 60-70.

 

[AlexDavis43]

The evidence on increasing HDL is much weaker than that on lowering apoB.

Worded another way, if you have naturally high HDL, you hit the genetic lottery and have a certain amount of protection. It is unknown if pharmaceutically increasing HDL provides similar protection.

 

[Sicsemptyran]

The evidence on increasing HDL is much weaker than that on lowering apoB.

Worded another way, if you have naturally high HDL, you hit the genetic lottery and have a certain amount of protection. It is unknown if pharmaceutically increasing HDL provides similar protection.

I'd argue it's almost been definitively shown at this point that pharmaceutically increasing HDL does not provide similar protection. We really do not know much about HDL at this point it seems. My wife has an HDL regularly around 110-115 which is almost certainly a bad thing, but as with everything else HDL no one really knows why!

Can be a good gauge of insulin resistance in natties -> If your HDL is low you're probably insulin resistant and vice versa, but not sure it shows much in enhanced lifters.

@egruberman I imagine knows a lot more about HDL. I consider myself nearly autistically educated on biology and pharmacology due to my profession and own interests, but he clearly has gone even deeper down that lipid rabbit hole than I.

 

[Sampei]

The evidence on increasing HDL is much weaker than that on lowering apoB.

Worded another way, if you have naturally high HDL, you hit the genetic lottery and have a certain amount of protection. It is unknown if pharmaceutically increasing HDL provides similar protection.

I wonder if it's better to have naturally high HDL and decrease LDL with meds or it's better to just have naturally low LDL but average if not low HDL.

Never saw my HDL better than 45 on AAS even on TRT but I have ridiculously low LDL without any cholesterol meds

 

[AlexDavis43]

I'd argue it's almost been definitively shown at this point that pharmaceutically increasing HDL does not provide similar protection. We really do not know much about HDL at this point it seems. My wife has an HDL regularly around 110-115 which is almost certainly a bad thing, but as with everything else HDL no one really knows why!

Can be a good gauge of insulin resistance in natties -> If your HDL is low you're probably insulin resistant and vice versa, but not sure it shows much in enhanced lifters.

@egruberman I imagine knows a lot more about HDL. I consider myself nearly autistically educated on biology and pharmacology due to my profession and own interests, but he clearly has gone even deeper down that lipid rabbit hole than I.

It's interesting to consider very high natural HDL as a marker of underlying pathology. Otherwise your wife hit the genetic lottery (although high HDL is generally more protective for men than women).

 

[Sicsemptyran]

It's interesting to consider very high natural HDL as a marker of underlying pathology. Otherwise your wife hit the genetic lottery (although high HDL is generally more protective for men than women).

It’s unfortunately being more readily recognized as pathological once you get that high (sadly, obviously would like my wife to have hit the good genetic lottery). The current theory is that it’s the body’s response to it being fundamentally unable to transport cholesterol correctly with HDL so it overproduces.

Prior to using AAS I was always in the 75-79 range religiously, never budged out of that range.

 

[AlexDavis43]

I wonder if it's better to have naturally high HDL and decrease LDL with meds or it's better to just have naturally low LDL but average if not low HDL.

Never saw my HDL better than 45 on AAS even on TRT but I have ridiculously low LDL without any cholesterol meds

The question there is if it's better have always had naturally low LDL or had higher LDL that was lowered to the same level (or lower).

LDL is sometimes described as an area under the curve thing. If you had high LDL then lowered it with drugs, the person who never had high LDL in the first place is likely going to do better.

But there are loads of studies on cardiovascular endpoints where lowering LDL is beneficial.

 

[egruberman]

The question there is if it's better have always had naturally low LDL or had higher LDL that was lowered to the same level (or lower).

As you stated, it's about the area under the curve. Atherosclerotic plaque will accumulate when LDL/ApoB is sufficiently high in concert with other inflammatory conditions. There's plenty of evidence that young people, teenagers and 20 somethings with hyperlipidemia already have plaque burden. This evidence comes from autopsies and such following accidental death, for folks of that age, usually from car accidents.

As for HDL, it serves as reverse cholesterol transport and is helpful in lowering LDL. It can also have anti-inflammatory and antioxidant effects as well as improve endothelial function. All of these benefits occur with HDL in range. When it is out of range, particularly when it's greater than 100mg/dL that can lead to some pathological effects. Generally speaking, as was already mentioned, this is the product of certain genetic mutations that lead to poor cholesterol metabolism.