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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.
2. 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.
3. There are three fundamental ways of preventing/treating cholestasis:
1. Metabolic induction of hydrophobic bile acid detoxification
2. Stimulation of impaired bile secretion
3. 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.
4. 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.
The bottom line here is this: Oral anabolics/androgens are hepatotoxic. Period. If you are going to use them, I implore you to take sensible precautions. Antaeus shall release a novel and powerful liver-support product in the very near future. In the meantime, there's Thermolife's "Liver Longer" and Primordial's "Liver Juice". Both are cheap enough that there's no excuse not to take them.
Another article:
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How do 17-aa oral steroids cause liver damage?
Despite a lot of discussion on the forums about the "toxicity" of different oral steroids, most users are unaware of the mechanism or implications around these "toxic effects" (which is probably the reason why most users have yet to find an effective cure for the toxic effects).
Let me shed some light on this ambiguous topic.
17-aa steroids are toxic to the liver because they inhibit the excretory functions of the liver. (1-7)
More specifically, the more "liver toxic" a 17-aa steroid is, the more it inhibits the production and flow of bile from the liver.
Bile salts are known as the liver's "cleansing agents" because they act as "soaps" that carry away the toxins and flush them into the intestines for excretion. If the bile flow is restricted in the liver, then the liver cannot rid itself of toxins. When the liver loses its ability to excrete toxins, it creates a buildup of toxins throughout the entire body. (1-13)
This condition is known as cholestasis [Kola-sta-sis]. By definition, cholestasis is a condition where the flow of bile cannot flow from the liver. (1) This is the most common liver condition developed from 17-aa steroids. (1-7)
If a liver becomes cholestatic for too long, the condition can begin damaging liver cells by causing necrosis (premature death of liver cells) from excessive toxin build up in the liver. This can eventually lead to cirrhosis of the liver (development of fibrous scar tissue) when the liver attempts to regenerate the damaged liver cells. This leads to loss of liver function from the replacement of healthy liver cells with fibrous connective tissue. (2)
Although cholestasis is reversible and generally not a lethal condition, it can lead to the more serious problems mentioned above if left untreated -- not to mention costly medical bills.
To avoid serious health complications it's important to protect the liver before it becomes cholestatic or seriously damaged from prolonged cholestasis (which I will explain later).
What are signs that my liver is damaged?
When the liver has been damaged by oral steroids there are certain signs that may become obvious to the user.
Here are some of the most common signs indicating you may have a serious liver issue. Warning signs usually appear in the following order, with the later signs being the most serious -
• Reduced appetite
• Nausea and fever
• Excessive Itchiness
• Yellow eyes or skin (jaundice)
• Very dark urine (dark amber colored)
• Bloody stools
Waiting for all these signs to appear means you have waited too long. You want to take action BEFORE these signs appear. This is why I advise getting full lab values on liver function before, during and after any 17-aa oral steroid cycle. If performing lab tests for liver function, the following values are considered normal.
Normal Values -
Total bilirubin range: 0.3-1.7 mg/dl
Alanine aminotransferase (ALT) range: 10-40 IU/L
Aspartate aminotransferase (AST) range: 10-40 IU/L
Alkaline phosphatase (ALP) range: 34-125 IU/L
Gamma-glutamyl-transpeptidase (GGT) range: 7-32 IU/L
Levels above these normal values doesn't necessarily mean you have liver damage. It is common for healthy weight training athletes or bodybuilders to be slightly outside of the "normal" ALT, AST and ALP values. Therefore these "Danger Values" have been established as more appropriate levels to indicate a serious liver toxicity issue. (1-7)
Danger Values -
Total bilirubin: 10 mg/dl or higher
Alanine aminotransferase (ALT): 50 IU/L or higher
Aspartate aminotransferase (AST): 50 IU/L or higher
Alkaline phosphatase (ALP): 150 IU/L or higher
Gamma-glutamyl-transpeptidase (GGT) range: 50 IU/L or higher
NOTE: Historical research from 17-aa oral steroid induced liver toxicity suggests that lab values higher than the "Danger Values" indicate that you may be suffering from cholestasis (1-7) If your lab values are higher than the "Danger Values" listed above you should discontinue any current oral steroid use and seek medical treatment.
If the above lab tests are not an option, it is possible to get an affordable at home test for bilirubin levels, which can help diagnose a liver damage from a 17-aa oral steroid. There are tests available, such as the TestMedica Liver Home Scan, which can be purchased online for less than $5 per test. Although these home based tests lack accuracy or true diagnosis ability, it can offer a valuable insight about the condition of the liver and is recommended for any steroid user not able to get lab tests done in a clinical setting.
How can I protect my liver?
To prevent cholestasis, the primary condition caused by oral steroid use, it is important to ensure there is ample hydrophilic bile acid available in the liver for the proper clearance of toxins. There are two reliable options for this.
1. The first option is the drug known as Ursodiol - a.k.a. ursodeoxycholic acid. This naturally occurring bile acid is used for its ability to detoxify the liver by clearing out less hydrophilic bile acids and other toxins that cause a toxic build up, such as 17-aa oral steroids. (4,5)
Ursodiol is typically prescribed to patients admitted to the hospital for steroid induced liver toxicity, but unfortunately, it is an expensive prescription drug, and not easily obtainable.
Typical dose - 1000-1200mg/day before, during and after cycle
One more small thing I found someone post on another forum:
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Everytime now that I take an oral AAS, I get massive heartburn within 3 days. I even tried an injectable oral and still got acid reflux within a week. So, I did some research and found some interesting information. This is just a random post I found on Google.
http://www.********.com/forums/archi...p/t-36636.html
Everyone seems to miss what is happening here. If an oral kills your appetite, it is because it is too toxic for the liver. I forget exactly what happens, but to summarize, when the liver is overloaded it causes a slowing of digestion, and a backflow of bile, which is why you also see people complaining of acid reflux on harsh 17aa's. The only way to really cure your appetite is to drop the anadrol. Perhaps next time around run with liv. 52 and alpha lipoic acid?
From what I read, bile helps with digestion. Now, when I take an oral AAS, the pain I get is similar to acid reflu/heartburn, but not exactly. It feels more like the food I eat just sits in my stomach and rots, never digesting. Lets say I eat some tacos on Tuesday, by Thursday morning I am still burping that taste up.That always made me wonder if orals cause heartburn or something similar.
Now read this
http://www.emoryhealthcare.org/liver...blems.html#PBC
In primary biliary cirrhosis, inflammation destroys the bile ducts and prevents bile from escaping the liver. The accumulated bile damages healthy liver tissue, eventually leading to cirrhosis (scarring). As scar tissue replaces healthy liver tissue, the liver loses its ability to function. All this happens very slowly. People with PBC can lead healthy, symptom-free lives for 10 years or more after diagnosis.
Though primary biliary cirrhosis is often asymptomatic, especially early on, the most common symptom is extreme itching, especially in the arms, legs and back. Other symptoms include fluid buildup in the abdomen or legs, jaundice (yellowing of the eyes and skin), or fatty deposits and darkening of the skin under the eyes.
The standard treatment for PBC is a daily dose of a medication called ursodiol. Ursodiol improves liver function and increases life expectancy in people with PBC. Other medications may be indicated for controlling symptoms
I hope this has educated a lot of people! Keep this thread bumped!
