RIP Big Al Fortney

[Stewie]

Genetics isn't always a determinant

Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users

This is within the full-text:

Results Fifty age-matched participants were evaluated and allocated: 20 AAS users (group AASU), 20 AAS nonusers (group AASNU) and10 sedentary men (group SC). Physical characteristics, clinical biomarkers, and hormonal profile are shown in Table 1. Cumulative lifetime duration of strength training, AAS use and types of AAS used are shown in supplementary Table 1 (Supplementary Data). The cholesterol efflux mediated by HDL was significantly lower in AASU compared with AASNU and SC (Fig. 1A). On the contrary, the lag time of LDL oxidation was higher in AASU than in AASNU and SC (Fig. 1B). In addition, AASU had a modified composition of HDL particles with reduced HDL- cholesterol, HDL-triglycerides, HDL-apo AI, and HDL-phospholipids compared with AASNU and SC (Fig. 2A-D, respectively). We found at least 2 coronary artery segments with lipid, fibro-lipid, and/or calcium plaques in 25% of AASU (Table 2). In contrast, none of the AASNU and SC participants had CAD. In those AASU who had subclinical CAD, fibro-lipid plaques were in 58%, followed by 27% with lipid plaques, and 15% with calcium plaques (Table 2). The mean total plaque volume was 274.4 mm3 , with negative index remodelling of 97.8%, and degree of stenosis from 30 to 50% (Table 2). Left anterior descending artery (LAD), circumflex artery (CX),

This study has clinical implications. First, we found that AAS users have decreased cholesterol efflux capacity by HDL, which could be, at last in part, one of the mechanisms associated with subclinical CAD. Second, 25% of young AAS users had signs of subclinical CAD with high-volume coronary plaque and even coronary luminal stenosis that would not be expected in young men. Third, the most-used general cardiovascular risk, the Castelli Index (ratio of TC:HDL cholesterol) and Framingham Heart Study, were worse in AAS users

Supplementary Fig. 1A and B show calcified plaque in the left anterior descending artery (LAD) in a 27-year-old man AAS user, and a mixed plaque in the LAD in a 43-year- old man AAS user, respectively. Moreover, it is interesting to note that one 41-year-old AASU (24 cumulative years of AAS use) had a coronary ulcer in the left anterior descending artery; and one 43-year-old AASU (11 cumulative years of AAS use) underwent cardiac catheterization, but without coronary angioplasty. We found that the time of AAS use was negatively associated with cholesterol efflux mediated by HDL (Fig. 3A), HDL-cholesterol (Fig. 3B), and HDL-apo AI (Fig. 3C). Moreover, the time of AAS use was positively associated with total coronary artery plaque volume (Fig. 3D). Finally, we also calculated 2 different clinical cardiovascular risk scores, both Castelli Index and Framingham Heart Study scores were higher in AASU compared with AASNU and SC. Vascular aging and hs-CRP were also higher in those men who used AAS (Supplementary Table 2). Discussion To the best of our knowledge, this is the first study to assess the effect of illicit use of AAS on the function of HDL as a possible mechanism involved in CAD in young men. We found that AAS users have impaired efflux cholesterol capacity mediated by HDL when compared with that in sedentary men or the weightlifters who did not use AAS. In our cohort, about 1 in 4 weightlifters (25%) who used AAS had signs of subclinical CAD on CT. In contrast, none of the AAS nonusers and the sedentary participants had subclinical CAD.

**broken link removed**

 

[Vlad The Impaler]

Too many guys are playing the blind game with their health. It’s like how Dante says they get bloodwork when they’re off the dangerous doses and get a false sense of security. Simple lipids and kidney panels aren’t enough to know the status of your health. Also, anyone who doesn’t own a good blood pressure monitor doesn’t truly care about their health in my strong opinion. I get pissed off if I even see a systolic BP number above 125.

Lol I'm happy when mine is 140

Sent from my SM-G960U using Tapatalk

 

[thethinker48]

Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users



This is within the full-text:















**broken link removed**

As someone with genetically low HDL this is sad


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[DOGGCRAPP]

As someone with genetically low HDL this is sad


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The guys ecstatic that they have high hdl shouldnt be doing backflips either

https://www.sciencedaily.com/releas...2-q9K6aXyjz8zGCvKGo5T0ur7meSuMkzn_JhvXvDThyAE

 

[maldorf]

The guys ecstatic that they have high hdl shouldnt be doing backflips either

https://www.sciencedaily.com/releas...2-q9K6aXyjz8zGCvKGo5T0ur7meSuMkzn_JhvXvDThyAE

Nice find, something I have never heard before. Ill have to ask my cardiologist about this next time I see him. My levels are low though, always have been.

 

[LK3]

Too many guys are playing the blind game with their health. It’s like how Dante says they get bloodwork when they’re off the dangerous doses and get a false sense of security. Simple lipids and kidney panels aren’t enough to know the status of your health. Also, anyone who doesn’t own a good blood pressure monitor doesn’t truly care about their health in my strong opinion. I get pissed off if I even see a systolic BP number above 125.

im gona try n find some middle ground and ask well then what? lol

i dont mean this in a bad way but when we have many people who take the stance that "abuse" is "wrong" , well ok, so then what?

to me, the way we speak almost seems as if we are begging for some sort of outside intervention and we all know that would be "bad" by and large for most, but many would certainly suffer a great deal worse in this case too, if you catch my drift.

so, what do we do as a pro active comunity to try and make tomorrow better?

it sucks to have young guys die, also sucks to have young guys have legal issues, etc.

i think there should be ways to fix both.
im a goofy idealist. lol
i mean this post in a totally possative way, not being dicky.

 

[Stewie]

Nice find, something I have never heard before. Ill have to ask my cardiologist about this next time I see him. My levels are low though, always have been.

Quality over quantity has been discussed a few times in the past. There's a couple other threads other than this one.


https://www.professionalmuscle.com/forums/professional-muscle-forum/134967-raising-hdl-6.html

 

[thethinker48]

The guys ecstatic that they have high hdl shouldnt be doing backflips either



https://www.sciencedaily.com/releas...2-q9K6aXyjz8zGCvKGo5T0ur7meSuMkzn_JhvXvDThyAE

Spot on!

I wish we had a means of testing hdl functionality

But in this game, the rule of averages is something people should really pay attention to.

Is it the end all be all? No, but it’s not good to have when taking supraphysiological doses of hormones that have a negative impact on endothelial function, overall lipid profile which includes dysfunctionality of ldl, triglyc on top of inflammatory responses from hard training, and susceptibility to high bp from the drugs and body weight (thankfully I’m not that big).


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[Rex Feral]

Quality over quantity has been discussed a few times in the past. There's a couple other threads other than this one.


https://www.professionalmuscle.com/forums/professional-muscle-forum/134967-raising-hdl-6.html

Referencing the prior thread posted above r/t tamoxifen and HDL quality vs quantity and tamoxifen's effects on reverse cholesterol transport. None of it may matter if these guys are right. I've performed multiple search combos for CD36/tamoxifen/foam cells etc and I haven't seen this mentioned.

Tamoxifen has been proven in many models to be anti-atherogenic i.e confer protection against atherosclerosis i.e. people and animals on tamoxifen develop less - zero plaque vs if they were not on tamoxifen. Which is why it continues to amaze me that given all the discussions about HDL and plaque how very little tamox is mentioned as a cardioprotective agent. There is the clot risk but at less than 1% with those likely predisposed. Honestly, I believe you have a higher risk of thrombosis with the all the useless therapeutic phlebotomies you people perform, especially within the first 6 months of initiation. Not to mention the phlebotomies confer none of the cardioprotection that tamox does. There is also the ignorance r/t tamox as a carcinogen but these are uterine related so unless you have one of those educate yourself before you make up shit in your mind to worry about.

Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen

These guys say that the anti-atherogenic effect of tamox is due to mechanisms independent of it's effects on the ER. We have always hypothesized that any positive effects tamox may have on preventing CAD were due to it's effects on the lipid profile. But as we've seen we've often been proven more wrong than right as it relates to beliefs about HDL/lipids. There was also some evidence mentioned in the thread referenced above that tamox effects reverse cholesterol transport, impairing cholesterol efflux. But this would be contradictory to it's proven anti-atherogenic effect. But tamox does not confer it's effect on plaque by way of it's increase in HDL.

I first came across this because CD36 is a new target in pharmacological development and that is what I do for a living. CD36 deficient mice are protected against atherosclerosis. In a nutshell, CD36 expression is essential for the production of foam cells. The formation of foam cells is the first necessary step in the development of atherosclerosis. "our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen." Tamox blocks CD36 expression which is essential for foam cell formation which is essential for plaque formation. This action trumps any effects on lipids or reverse cholesterol transport.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037633#s4

**broken link removed**
Renal disease as well. Tamox has been shown to reverse renal fibrosis as well, this time through its action on the ER. https://academic.oup.com/ndt/article/29/11/2043/1808302

In my mind tamox is on par with tadalafil, metformin, telmisartan in that it is a cheap extremely well studied compound that exhibits multiple benefits through multiple mechansims that are proven to confer benefits to offset the damage incurred by the bodybuilding lifestyle. It is pleiotropic. If you think otherwise, prove it. I assure you the evidence is against you. Don't even get me started on cost effectiveness vs some of the shit you people add that does very little to nothing vs tamox.

Rex.

 

[nothuman]

The 4 times a year that Rex Feral posts never disappoints

 

[Stewie]

Referencing the prior thread posted above r/t tamoxifen and HDL quality vs quantity and tamoxifen's effects on reverse cholesterol transport. None of it may matter if these guys are right. I've performed multiple search combos for CD36/tamoxifen/foam cells etc and I haven't seen this mentioned.

Tamoxifen has been proven in many models to be anti-atherogenic i.e confer protection against atherosclerosis i.e. people and animals on tamoxifen develop less - zero plaque vs if they were not on tamoxifen. Which is why it continues to amaze me that given all the discussions about HDL and plaque how very little tamox is mentioned as a cardioprotective agent. There is the clot risk but at less than 1% with those likely predisposed. Honestly, I believe you have a higher risk of thrombosis with the all the useless therapeutic phlebotomies you people perform, especially within the first 6 months of initiation. Not to mention the phlebotomies confer none of the cardioprotection that tamox does. There is also the ignorance r/t tamox as a carcinogen but these are uterine related so unless you have one of those educate yourself before you make up shit in your mind to worry about.

Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen

These guys say that the anti-atherogenic effect of tamox is due to mechanisms independent of it's effects on the ER. We have always hypothesized that any positive effects tamox may have on preventing CAD were due to it's effects on the lipid profile. But as we've seen we've often been proven more wrong than right as it relates to beliefs about HDL/lipids. There was also some evidence mentioned in the thread referenced above that tamox effects reverse cholesterol transport, impairing cholesterol efflux. But this would be contradictory to it's proven anti-atherogenic effect. But tamox does not confer it's effect on plaque by way of it's increase in HDL.

I first came across this because CD36 is a new target in pharmacological development and that is what I do for a living. CD36 deficient mice are protected against atherosclerosis. In a nutshell, CD36 expression is essential for the production of foam cells. The formation of foam cells is the first necessary step in the development of atherosclerosis. "our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen." Tamox blocks CD36 expression which is essential for foam cell formation which is essential for plaque formation. This action trumps any effects on lipids or reverse cholesterol transport.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037633#s4

**broken link removed**
Renal disease as well. Tamox has been shown to reverse renal fibrosis as well, this time through its action on the ER. https://academic.oup.com/ndt/article/29/11/2043/1808302

In my mind tamox is on par with tadalafil, metformin, telmisartan in that it is a cheap extremely well studied compound that exhibits multiple benefits through multiple mechansims that are proven to confer benefits to offset the damage incurred by the bodybuilding lifestyle. It is pleiotropic. If you think otherwise, prove it. I assure you the evidence is against you. Don't even get me started on cost effectiveness vs some of the shit you people add that does very little to nothing vs tamox.

Rex.

Rex, dude... I've been a-drift at sea for 377 days and 13 hours patiently awaiting a call from you! Good lord man, the least you could have done was sent me a note-in-bottle telling me to hang tight--help is on the way. I'm okay now tho, thanks.

https://www.professionalmuscle.com/...re-you-go-guys-bloodwork-2-5yr-glimpse-3.html

Hopefully Rex sees this, as I'd like to scratch his mind on his thoughts of tamoxifen's impairment of reverse cholesterol transport? As well his clinical use of either levothyroxine or liothyronine with his patients that have subpar lipids?

All kidding aside. This is where I've extracted the info from:

Thoughts... You see something I don't, and/or misinterpreted?

https://www.nature.com/articles/srep32105

It's interesting you touched on CD36, as there's notes and graphs of it within.

The expression of CD36 and NPC1 was not appreciably altered (Supplementary Fig. S7). Preliminary studies showed that apoA-I- and HDL-mediated cholesterol efflux from [3H]cholesterol-AcLDL-labeled primary macrophages was less efficient than from THP-1 macrophages.

However, TAM, but not RAL, impairs M-RCT in vivo. This effect is independent of the decrease of HDL levels caused by SERMs, but it is primarily attributable to the TAM-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. Our data are suggestive of a negative effect of TAM on a major atheroprotective function of HDL that remains to be demonstrated in interventional studies with TAM-treated patients.

Granted it's not conclusive, as that's why I've referenced it in such as "suggestive".



On a side conversation, Rex. Are you or your peers involved with the drug AKCEA-APO(a)-LRx (mRNAi) targeting Lp(a)?



May buy stock in it once it hits the IPO status



I chatted on the phone (Doctor radio) with NYU Langone cardiologist and clinical assistant professor Dr.Howard Weintraub, asking a bit more specifics of this. As well, why isn't there any focus on creating a drug capacitating HDL functionality (increase reverse cholesterol transport)? His quick short response was, "just about everything has failed targeting HDL, -such as niacin." Which I knew that, no shit! My interested is there anything in the works in creating a more efficient drug therapy (miRNA targeting??) on mRCT in combos with LDL targeting therapeutics. Apparently he misunderstood my question.



Speaking of niacin, it's one of those quirky micronutrients that it's functionality on CVD risk reduction is based on the individuals apolipoprotein(a) phenotype. If Lp(a) is being discussed.



There's a couple of anabolics (not that I'm recommending) that has been observed to have quite the statistical effects on lowering effects on Lp(a). Tho, there's lack of multiple replication studies.

 

[emeric delczeg]

Rex, dude... I've been a-drift at sea for 377 days and 13 hours patiently awaiting a call from you! Good lord man, the least you could have done was sent me a note-in-bottle telling me to hang tight--help is on the way. I'm okay now tho, thanks.

https://www.professionalmuscle.com/...re-you-go-guys-bloodwork-2-5yr-glimpse-3.html



All kidding aside. This is where I've extracted the info from:

Thoughts... You see something I don't, and/or misinterpreted?

https://www.nature.com/articles/srep32105

It's interesting you touched on CD36, as there's notes and graphs of it within.




Granted it's not conclusive, as that's why I've referenced it in such as "suggestive".



On a side conversation, Rex. Are you or your peers involved with the drug AKCEA-APO(a)-LRx (mRNAi) targeting Lp(a)?



May buy stock in it once it hits the IPO status



I chatted on the phone (Doctor radio) with NYU Langone cardiologist and clinical assistant professor Dr.Howard Weintraub, asking a bit more specifics of this. As well, why isn't there any focus on creating a drug capacitating HDL functionality (increase reverse cholesterol transport)? His quick short response was, "just about everything has failed targeting HDL, -such as niacin." Which I knew that, no shit! My interested is there anything in the works in creating a more efficient drug therapy (miRNA targeting??) on mRCT in combos with LDL targeting therapeutics. Apparently he misunderstood my question.



Speaking of niacin, it's one of those quirky micronutrients that it's functionality on CVD risk reduction is based on the individuals apolipoprotein(a) phenotype. If Lp(a) is being discussed.



There's a couple of anabolics (not that I'm recommending) that has been observed to have quite the statistical effects on lowering effects on Lp(a). Tho, there's lack of multiple replication studies.

miRNA will become one of the best or the only therapeutic tool for many different diseases.

 

[Stewie]

Yes, sir! It's certainly headed in that direction. As will be pharmacologically targeting specific microbiome. Maybe not be in my lifetime, although that would be awesome to be around for.

 

[emeric delczeg]

Yes, sir! It's certainly headed in that direction. As will be pharmacologically targeting specific microbiome. Maybe not be in my lifetime, although that would be awesome to be around for.

It will happen in your life time.

 

[LATS]

Referencing the prior thread posted above r/t tamoxifen and HDL quality vs quantity and tamoxifen's effects on reverse cholesterol transport. None of it may matter if these guys are right. I've performed multiple search combos for CD36/tamoxifen/foam cells etc and I haven't seen this mentioned.

Tamoxifen has been proven in many models to be anti-atherogenic i.e confer protection against atherosclerosis i.e. people and animals on tamoxifen develop less - zero plaque vs if they were not on tamoxifen. Which is why it continues to amaze me that given all the discussions about HDL and plaque how very little tamox is mentioned as a cardioprotective agent. There is the clot risk but at less than 1% with those likely predisposed. Honestly, I believe you have a higher risk of thrombosis with the all the useless therapeutic phlebotomies you people perform, especially within the first 6 months of initiation. Not to mention the phlebotomies confer none of the cardioprotection that tamox does. There is also the ignorance r/t tamox as a carcinogen but these are uterine related so unless you have one of those educate yourself before you make up shit in your mind to worry about.

Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen

These guys say that the anti-atherogenic effect of tamox is due to mechanisms independent of it's effects on the ER. We have always hypothesized that any positive effects tamox may have on preventing CAD were due to it's effects on the lipid profile. But as we've seen we've often been proven more wrong than right as it relates to beliefs about HDL/lipids. There was also some evidence mentioned in the thread referenced above that tamox effects reverse cholesterol transport, impairing cholesterol efflux. But this would be contradictory to it's proven anti-atherogenic effect. But tamox does not confer it's effect on plaque by way of it's increase in HDL.

I first came across this because CD36 is a new target in pharmacological development and that is what I do for a living. CD36 deficient mice are protected against atherosclerosis. In a nutshell, CD36 expression is essential for the production of foam cells. The formation of foam cells is the first necessary step in the development of atherosclerosis. "our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen." Tamox blocks CD36 expression which is essential for foam cell formation which is essential for plaque formation. This action trumps any effects on lipids or reverse cholesterol transport.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037633#s4

**broken link removed**
Renal disease as well. Tamox has been shown to reverse renal fibrosis as well, this time through its action on the ER. https://academic.oup.com/ndt/article/29/11/2043/1808302

In my mind tamox is on par with tadalafil, metformin, telmisartan in that it is a cheap extremely well studied compound that exhibits multiple benefits through multiple mechansims that are proven to confer benefits to offset the damage incurred by the bodybuilding lifestyle. It is pleiotropic. If you think otherwise, prove it. I assure you the evidence is against you. Don't even get me started on cost effectiveness vs some of the shit you xpeople add that does very little to nothing vs tamox.

Rex.

Great post rex... at what does do you recommend nolva and tadalafil? Just curious..

 

[Kaladryn]

The above view of tamoxifen is rather optimistic and leaving out a lot of contradictory research.

Understanding the genotoxicity of tamoxifen?

And btw, balls are just ovaries on the outside (and tamoxifen is carcinogenic to more than just ovaries for that matter) and there is no reason to worry about blood clotting on tamoxifen unless you are a postmenopausal woman...

I use tamoxifen, but sparingly, I certainly wouldn't want to be on it long term.

 

[nothuman]

I’d like the know the cons of using tamoxifen long term based on the research

 

[Kaladryn]

I’d like the know the cons of using tamoxifen long term based on the research

You aren't going to find any because of the purposes the drug is generally used for, the closest thing you are going to find is evidence of its somewhat mild toxicity, not really a concern for someone who has cancer.

 

[Elvia1023]

I use 20mg tamoxifen for certain periods. I have been on it about 6 weeks now and plan to use it during my entire blast. Like with anything there are many unknowns and many contradicting posts. I definitely think for on cycle support it's up there with the best. I also use tadalafil on most blasts as well. At the moment also 80mg telmisartan (which gives me a weird side effect) and 500mg metformin.