dylanvib4
Registered
Alright gents, and ladies, something I have noticed lately are more and more posts on what should be used to protect your liver on cycle. So much bro science gets thrown around, as it does with anything aas-related, and for some it's obviously difficult to tell what's right and what's wrong. From what I have been reading, and from people I have personally talked to, I think that a significant amount of people don't understand the gravity of how crucial taking all precautions actually is. Covering all of your bases. In this case, enabling your liver to function properly and preventing damage.
So when we talk about "protecting our liver", what does that actually mean? How does our liver work, and how can we ensure that it continues to work well? What exactly does hepatoxic mean and how can hepatoxicity effect the liver? I have included an article that has been floating around a while below (I DID NOT WRITE THIS, but personally believe it to be extremely beneficial), a great read that answers these questions. But for those lacking the knowledge, or for some reason do not want to read the article below, here is a brief overview.
Your liver is the second largest organ of your body, following skin. I like to think of the liver as a filter. When toxins are created or put into the body, the liver is what separates them from the good stuff such as nutrients and minerals. Bile is created to digest and absorb fats, breakdown cholesterol, and escort waste products out of the body, whether that is through your kidneys and passed in urine or through your feces. Bile is secreted from hepatocytes into the canaliculi (as pictured below), sent to the bile ducts then into gall bladder.
You'll read more about cholestasis below, but overall it is either the obstruction of bile flow, or when bile cannot be secreted and stays in those hepatocytes. Try to imagine all this bad shit going into your body, then staying there and festering due to the inability to be processed. Building up over time. So when you read about dbol, drol, certain methylated compounds being "hepatoxic", it means they can negatively effect bile flow or secretion. As mentioned before, this leads to build up of bile acids that can eventually lead to tissue damage, and the destruction of your bile ducts. Fuck that. In order to maintain healthy function and prevent cholestasis, you want to protect your hepatocytes from toxic effects, stimulate the bile that needs to be secreted, and assist the metabolizing of bile acids. UDCA (ursodeoxycholic acid) and TUDCA (UDCA with Taurine) have both shown to be effective in doing these things. Milk thistle, NAC, and others aren't terrible, but as shown below they do not protect you in the ways UDCA and/or TUDCA do.
Effective doses of TUDCA and UDCA range from 250mg to 500mg daily. I know IMR and RUI carry UDCA (mass spec), and TUDCA is offered in cap form through many companies. Off the top of my head I know of AEGIS by Antaeus Labs and Ar1macare Pro by Olympus labs both carry TUDCA. All in all, caring for your liver and the hepatoxicity of orals put into your body is not something to overlook or underestimate! Please take care of your body, and do so while taking orals by forking up a little extra dough and purchasing UDCA or TUDCA.
If anybody else has anything to add, or if I have made a mistake and can be corrected, please do so! I take the health of all our brothers and sisters on here very seriously. The article is added below, thanks for reading!
-----------------------------------------------BEGIN ARTICLE------------------------------------------------
So when we talk about "protecting our liver", what does that actually mean? How does our liver work, and how can we ensure that it continues to work well? What exactly does hepatoxic mean and how can hepatoxicity effect the liver? I have included an article that has been floating around a while below (I DID NOT WRITE THIS, but personally believe it to be extremely beneficial), a great read that answers these questions. But for those lacking the knowledge, or for some reason do not want to read the article below, here is a brief overview.
Your liver is the second largest organ of your body, following skin. I like to think of the liver as a filter. When toxins are created or put into the body, the liver is what separates them from the good stuff such as nutrients and minerals. Bile is created to digest and absorb fats, breakdown cholesterol, and escort waste products out of the body, whether that is through your kidneys and passed in urine or through your feces. Bile is secreted from hepatocytes into the canaliculi (as pictured below), sent to the bile ducts then into gall bladder.
You'll read more about cholestasis below, but overall it is either the obstruction of bile flow, or when bile cannot be secreted and stays in those hepatocytes. Try to imagine all this bad shit going into your body, then staying there and festering due to the inability to be processed. Building up over time. So when you read about dbol, drol, certain methylated compounds being "hepatoxic", it means they can negatively effect bile flow or secretion. As mentioned before, this leads to build up of bile acids that can eventually lead to tissue damage, and the destruction of your bile ducts. Fuck that. In order to maintain healthy function and prevent cholestasis, you want to protect your hepatocytes from toxic effects, stimulate the bile that needs to be secreted, and assist the metabolizing of bile acids. UDCA (ursodeoxycholic acid) and TUDCA (UDCA with Taurine) have both shown to be effective in doing these things. Milk thistle, NAC, and others aren't terrible, but as shown below they do not protect you in the ways UDCA and/or TUDCA do.
Effective doses of TUDCA and UDCA range from 250mg to 500mg daily. I know IMR and RUI carry UDCA (mass spec), and TUDCA is offered in cap form through many companies. Off the top of my head I know of AEGIS by Antaeus Labs and Ar1macare Pro by Olympus labs both carry TUDCA. All in all, caring for your liver and the hepatoxicity of orals put into your body is not something to overlook or underestimate! Please take care of your body, and do so while taking orals by forking up a little extra dough and purchasing UDCA or TUDCA.
If anybody else has anything to add, or if I have made a mistake and can be corrected, please do so! I take the health of all our brothers and sisters on here very seriously. The article is added below, thanks for reading!
-----------------------------------------------BEGIN ARTICLE------------------------------------------------
A few words on the hepatotoxicity of 17a-methylated androgens/anabolics 1. 17a-methylated androgens/anabolics are hepatotoxic. The liver toxicity of steroids is an under-researched field, but there seems to be a strong correlation between how easily the body can metabolize a steroid & its toxicity. Metribolone -- a truly excessively toxic compound -- is often referred to in the literature as a 'non-metabolizable androgen'. (1, 2, 3, etc.) Mibolerone, another deadly-toxic anabolic steroid, is also effectively 'non-metabolizable': The main metabolite of mibolerone in humans is... unchanged mibolerone. And by a very wide margin.
Methylstenbolone, which is resistant to 17b-HSD and 3b-HSD, is obviously difficult for the body to clear. It should therefore be no safer, no less toxic, than Superdrol or M1T -- compounds which share very similar traits.
The word "cholestasis" gets thrown around a lot, but it can mean two very different things: The physical obstruction of hepatic bile flow -or- the impairment of bile secretion. In the former case, there is a mechanical block in the bile duct system; in the latter, bile is held in hepatocytes or cholangiocytes as it cannot be secreted. In both cases, what happens thereafter is that the retained hydrophobic bile salts -- which are strongly cytotoxic -- lead to cellular injury, then apoptosis, then necrosis, often followed by an inflammatory reaction and tissue fibrosis. This tissue damage, if advanced enough, can physically destroy bile ducts, worsening the condition.
The obstruction of bile flow is typically not something you'd experience after exposure to any toxin; it is the almost exclusive domain of inherited or autoimmune diseases which leave fibrotic lesions or scar-tissue in the liver, such as cystic fibrosis, primary biliary cirrhosis, and so on. Exposure to oral anabolic compounds can, however, result in the second form of cholestasis -- bile retention in hepatocytes -- thus the enlarged hepatocytes observed after their use.
Cholestatic liver damage is caused by bile acid accumulation... But not all bile acids are toxic. Generally speaking, the fewer hydroxyl groups they bear, the more hydrophobic and cytotoxic they are. Hence lithocholic acid is markedly cytotoxic, deoxycholic acid is very slightly cytotoxic, and cholic acid is essentially non-cytotoxic. Treatment #1 would involve hastening the metabolic conversion of the more toxic bile acids to hydrophilic, less toxic compounds --- or increasing the synthesis of hydrophilic bile acids from cholesterol, which would decrease the cytotoxicity of the entire bile pool as a whole. This can seemingly be achieved with the oral administration of ursodeoxycholic acid (UDCA), which has been reported to activate the PXR/SXR nuclear receptor in hepatocytes, which then activates bile acid–metabolizing enzymes. It is reasonable to assume that Tauroursodeoxycholic acid (TUDCA), the taurine conjugate of UDCA, should have the same effect.
As for #2... Bile secretion at the level of the hepatocyte is carried out by a group of transporter proteins: The bile salt export pump (BSEP), the phospholipid export pump (MDR3), the canalicular bilirubin conjugate export pump (MRP2), and a chloride-bicarbonate anion exchanger (AE2) for bicarbonate excretion. BSEP is the driving factor behind bile-acid dependent secretion, and MRP2/AE2 are the major forces behind bile-acid-independent bile secretion. Hydrophilic bile acids such as UDCA & TUDCA (and even, partially, cholic acid) have been shown to increase expression of BSEP mRNA; they activate BSEP coactivators by binding to the Farnesoid X Receptor (the "bile acid receptor"); they phosphorylate the BSEP protein via a Ca+/PKCa-mediated mechanism; lastly, they stimulate Cl -/HCO3 - exchange via this same PKCa induction, thus increasing AE2 levels. Taken together, the above effects drastically enhance secretion of potentially toxic bile acids.
3 can be complicated, but I will explain briefly: Certain toxic bile salts activate the Fas Death Receptor on hepatocytes. This leads to a cascade of dozens of protein interactions & ultimately to cell death. TUDCA, UDCA, and certain other compounds can diminish Fas–induced apoptosis, but, as far as I am aware, the exact mechanism is not known at this time. Fas activation here is not ligand-dependent, so the 'obvious' mechanism is out the window. The mechanism could, however, involve activation of the EGFR, which activates MAPK & the MAPK-mediated 'survival pathway' in hepatocytes; it might also involve inhibition, somewhere along the line, of the proapoptotic proteins Bax and Bid.
Silymarin and silybin, the milk thistle extracts, are very strong antioxidants and free-radical scavengers in hepatic tissue. They impede hepatic lipid peroxidation, increase glutathione concentrations, and even have anti-inflammatory and tissue-regenerative properties... Other plant-extracted compounds, such as celastrol, have similar effects... But while these extracts are excellent to take for general liver health, they are weak protection and not an appropriate treatment for cholestasis, as they do not appear to impact bile acid secretion/metabolism at pharmacologically-relevant doses. Silymarin did increase bile secretion and improve bile acid metabolism in rats -- but that effect was primarily noticed at a dose of 100mg/kg, administered via i.p. injection (100% bioavailability), and therefore doesn't have much bearing on humans who take much smaller amounts orally (~10% bioavailability). ...But Primordial Performance's "Liver Juice" is silymarin/silybin attached to an excellent delivery complex, and should be quite effective if taken 3x/day. It is the best milk thistle supplement out there, in my opinion.
NAC is also a fine antioxidant and glutathione-booster, but it suffers from poor bioavailability & is usually very underdosed in commercially-available supplements... So I wouldn't bother with it.
Sanofi-Aventi (or is it just 'Sanofi' these days?) manufactures the popular phospholipid-complex product "Essentiale" and "Essentiale Forte". The phosphatidylcholine therein has been shown to help protect hepatic cell membranes against the damaging effects of chenodeoxycholic acid, can inhibit lipid peroxidation, and can induce cytochrome P450, which stimulates the metabolic clearance of bile acids... So there's a reason that it's the most popular OTC liver support in Europe and Asia... But "Essentiale" can be hard to find in the USA -- and, on its own, I don't believe that it is totally adequate protection for users of oral androgens.
And Liv-52? Mostly a waste of money. A blend of mild antioxidants is all there is to it.
Methylstenbolone, which is resistant to 17b-HSD and 3b-HSD, is obviously difficult for the body to clear. It should therefore be no safer, no less toxic, than Superdrol or M1T -- compounds which share very similar traits.
- Liver injury due to oral anabolic use typically manifests itself as cholestasis. Hepatotoxicity induced by oral anabolic compounds tends to be characterized by enlargement of periportal hepatocytes, impairment of bile flow & dramatically increased serum levels of AST, ALT and GGT. In other words, cholestasis... but let's examine this a little bit further.
The word "cholestasis" gets thrown around a lot, but it can mean two very different things: The physical obstruction of hepatic bile flow -or- the impairment of bile secretion. In the former case, there is a mechanical block in the bile duct system; in the latter, bile is held in hepatocytes or cholangiocytes as it cannot be secreted. In both cases, what happens thereafter is that the retained hydrophobic bile salts -- which are strongly cytotoxic -- lead to cellular injury, then apoptosis, then necrosis, often followed by an inflammatory reaction and tissue fibrosis. This tissue damage, if advanced enough, can physically destroy bile ducts, worsening the condition.
The obstruction of bile flow is typically not something you'd experience after exposure to any toxin; it is the almost exclusive domain of inherited or autoimmune diseases which leave fibrotic lesions or scar-tissue in the liver, such as cystic fibrosis, primary biliary cirrhosis, and so on. Exposure to oral anabolic compounds can, however, result in the second form of cholestasis -- bile retention in hepatocytes -- thus the enlarged hepatocytes observed after their use.
- There are three fundamental ways of preventing/treating cholestasis:
- Metabolic induction of hydrophobic bile acid detoxification
- Stimulation of impaired bile secretion
- Protection of hepatocytes from the toxic effects of hydrophobic bile acids and/or inhibition of hepatocyte apoptosis.
Cholestatic liver damage is caused by bile acid accumulation... But not all bile acids are toxic. Generally speaking, the fewer hydroxyl groups they bear, the more hydrophobic and cytotoxic they are. Hence lithocholic acid is markedly cytotoxic, deoxycholic acid is very slightly cytotoxic, and cholic acid is essentially non-cytotoxic. Treatment #1 would involve hastening the metabolic conversion of the more toxic bile acids to hydrophilic, less toxic compounds --- or increasing the synthesis of hydrophilic bile acids from cholesterol, which would decrease the cytotoxicity of the entire bile pool as a whole. This can seemingly be achieved with the oral administration of ursodeoxycholic acid (UDCA), which has been reported to activate the PXR/SXR nuclear receptor in hepatocytes, which then activates bile acid–metabolizing enzymes. It is reasonable to assume that Tauroursodeoxycholic acid (TUDCA), the taurine conjugate of UDCA, should have the same effect.
As for #2... Bile secretion at the level of the hepatocyte is carried out by a group of transporter proteins: The bile salt export pump (BSEP), the phospholipid export pump (MDR3), the canalicular bilirubin conjugate export pump (MRP2), and a chloride-bicarbonate anion exchanger (AE2) for bicarbonate excretion. BSEP is the driving factor behind bile-acid dependent secretion, and MRP2/AE2 are the major forces behind bile-acid-independent bile secretion. Hydrophilic bile acids such as UDCA & TUDCA (and even, partially, cholic acid) have been shown to increase expression of BSEP mRNA; they activate BSEP coactivators by binding to the Farnesoid X Receptor (the "bile acid receptor"); they phosphorylate the BSEP protein via a Ca+/PKCa-mediated mechanism; lastly, they stimulate Cl -/HCO3 - exchange via this same PKCa induction, thus increasing AE2 levels. Taken together, the above effects drastically enhance secretion of potentially toxic bile acids.
3 can be complicated, but I will explain briefly: Certain toxic bile salts activate the Fas Death Receptor on hepatocytes. This leads to a cascade of dozens of protein interactions & ultimately to cell death. TUDCA, UDCA, and certain other compounds can diminish Fas–induced apoptosis, but, as far as I am aware, the exact mechanism is not known at this time. Fas activation here is not ligand-dependent, so the 'obvious' mechanism is out the window. The mechanism could, however, involve activation of the EGFR, which activates MAPK & the MAPK-mediated 'survival pathway' in hepatocytes; it might also involve inhibition, somewhere along the line, of the proapoptotic proteins Bax and Bid.
- Recommendations I strongly recommend TUDCA or UDCA to anybody considering a cycle containing oral androgens, for what should by now be obvious reasons. They are extremely potent at preventing or reversing 17aa-androgen-mediated liver damage. There's really no excuse not to take them, in my opinion, and I would advise you not to run a cycle if you can't afford them. Oral androgens can send you straight to the ER if the right precautions are not taken, & your health is much more important than a few more pounds of here-today-gone-tomorrow muscle.
Silymarin and silybin, the milk thistle extracts, are very strong antioxidants and free-radical scavengers in hepatic tissue. They impede hepatic lipid peroxidation, increase glutathione concentrations, and even have anti-inflammatory and tissue-regenerative properties... Other plant-extracted compounds, such as celastrol, have similar effects... But while these extracts are excellent to take for general liver health, they are weak protection and not an appropriate treatment for cholestasis, as they do not appear to impact bile acid secretion/metabolism at pharmacologically-relevant doses. Silymarin did increase bile secretion and improve bile acid metabolism in rats -- but that effect was primarily noticed at a dose of 100mg/kg, administered via i.p. injection (100% bioavailability), and therefore doesn't have much bearing on humans who take much smaller amounts orally (~10% bioavailability). ...But Primordial Performance's "Liver Juice" is silymarin/silybin attached to an excellent delivery complex, and should be quite effective if taken 3x/day. It is the best milk thistle supplement out there, in my opinion.
NAC is also a fine antioxidant and glutathione-booster, but it suffers from poor bioavailability & is usually very underdosed in commercially-available supplements... So I wouldn't bother with it.
Sanofi-Aventi (or is it just 'Sanofi' these days?) manufactures the popular phospholipid-complex product "Essentiale" and "Essentiale Forte". The phosphatidylcholine therein has been shown to help protect hepatic cell membranes against the damaging effects of chenodeoxycholic acid, can inhibit lipid peroxidation, and can induce cytochrome P450, which stimulates the metabolic clearance of bile acids... So there's a reason that it's the most popular OTC liver support in Europe and Asia... But "Essentiale" can be hard to find in the USA -- and, on its own, I don't believe that it is totally adequate protection for users of oral androgens.
And Liv-52? Mostly a waste of money. A blend of mild antioxidants is all there is to it.
