Methylated prohormones/steroids and the liver.

[iamthesuperbeast]

Hepatoxicty: Fact or Fiction
by Roy Harper


We all know that the alpha alkylated steroids are hepatotoxic, right….. But, is there actually any truth to this? We’ve been told for years that if you take 17 alpha-alkylated steroids, you will eventually run into liver problems. Never combine 17 aa’s, never go beyond 50mg day, never go longer than 4 weeks, etc. All of this is crap! As I we walk you through some studies, today, you’ll see 17 alpha-alkylated steroids can be hepatotoxic but not to the degree you would think.

To make a steroid hepatotoxic, you need only a small change to a steroid molecule; A strong bond that cannot readily be down broken by enzymes in the liver. This may be a bond at the 17th position, or even at the 1st position (as in methenolone or proviron ). Because the liver cannot easily break the steroid down before it is released in to the blood stream, this also results in the steroid to becoming more orally bio-available.

We can see that the liver has to work harder to break down these steroids. Enzymes in the blood and tissue easily metabolize other steroids such as Testosterone . Commonly, this increase in liver activity has been viewed as a harmful process, but as you will see, this increase is, in and of itself, irrelevant. The liver is THE filter of the human body -- it can figure out what to do with just about anything. The only real problem comes in when one keeps their liver at full blast for long periods of time.

Let’s look at some studies showing the hepatotoxicity of steroids. Here's one of my favorites, a study published in 1979[1]. Essentially, researches did a study of deaths caused by hepatic angiosarcoma (a malignant tumor of vascular tissue in the liver) between 1964 and 1974. Researchers found 131 reported cases of death from hepatic angiosarcoma. Out of the 131 cases, 3.1% (4 cases) were reported to be at all related to the use of androgenic -anabolic steroids. Keep in mind that these 4 people could have liver complications before any steroids were used, aka a genetic disposition. In fact there is no proof, in this study at least, that the anabolic-androgenic steroids even caused the hepatic angiosarcoma.

This is the classic case of associating a cause with an effect, without any evidence, aside from both existing. Furthermore, based on the above numbers, there are only 0.4 cases of hepatic angiosarcoma reported each year, by those using AAS. Now consider the number of people on steroids at this time. Now factor in all the people that don’t know their ass from a hole in the ground when it comes to using AAS, properly. Clearly, this is very week evidence. Lastly there has not been a real increase in hepatic angiosarcoma since the early seventies. Meanwhile, there has been a huge, almost exponential, increase in steroid use during this period.

Another study, that somewhat supports the previous hepatotoxicity case, showed the possibilities of hepatic adenomas(cysts in the liver) caused by androgenic-anabolic steroids [2]. In this study, a Japanese girl was found to have multiple liver lesions after the use of the drug oxymetholone (aka Anadrol ). Most everyone “knows” that Anadrol is linked with liver problems, but a closer inspection into this study shows more.

Apparently, this girl, starting at the age of 14, was diagnosed with aplastic anemia. She was prescribed oxymetholone at 30mg per day. This continued for 6 years until the lesions first appeared. Assuming that the girl was most likely around 100 lbs., this was a pretty heavy dosage. If you extrapolated this data out to a 200 - 250lbs. male, that would be taking approximately 60 - 90mg of anadrol per day for 6 years. Ouch!

The researchers also stated that there were only 17 other cases of hepatic adenomas, found in English literature between 1975 and 1998. They failed to mention the causes of these 17 cases, but there is no reason to believe they were all using 17-AA androgens and 17 is certainly miniscule compared to the number of people who have used them. The authors’ finish off the study by saying the following: "This report may be helpful in identifying the population who is at risk of developing hepatic sex hormone-related tumors." So remember, if you're a small 14-year-old girl taking 30mg of Anadrol per day for 6 years, you may be at risk!

Let's move on to some more useful studies. Take for example a 1995 study that showed the toxic effects of anabolic-androgenic steroids in primary rat hepatic cell cultures[3]. In this study the researchers used the following drugs and dosages:

Steroid
1x10^-8M
1x10^-6M
1x10^-4M

19-nortestosterone
0.002744mg
0.2744mg
27.44mg

Fluoxymesterone
0.003365mg
0.3365mg
33.65mg

Testosterone cypionate
0.004126mg
0.4126mg
41.26mg

Stanozolol
0.003285mg
0.3285mg
32.85mg

Danazol
N/A
N/A
N/A

Oxymetholone
0.003325mg
0.3325mg
33.25mg

Testosterone
0.002884mg
0.2884mg
28.84mg

Estradiol
0.0027424mg
0.2724mg
27.24mg

Methyltestosterone
0.003024mg
0.3024mg
30.24mg


As proof of the hepatoxicity they used Lactate dehydrogenase release, neutral red retention, and glutathione depletion to determine plasma membrane damage, cell viability, and possible oxidative injury, respectively.

What they showed was that the 17 alpha-alkylated steroids, methyltestosterone, stanozolol and oxymetholone, significantly increased Lactate dehydrogenase release and decreased neutral red retention at the 1x10^-4M dosage for 24h. Both methyltestosterone and oxymetholone also showed depleted glutathione at the 1x10^-4M dosage after 2h, 6h and 8h treatments. In other words they increased liver activity. You may also note that the other, non-alkylated steroids showed no significant difference in any levels. All in all this not only shows that 17 alpha-alkylated steroids are directly “hepatotoxic”, but also non-alkylated steroids are note hepatotoxic at all. But is this a real measure of hepatotoxicity? There is yet to be any correlation between the increase of the above-mentioned measurement and “hepatotoxicity”. Obviously, high dosages of the 17 alpha-alkylated steroids are potentially dangerous, but upon closer inspection, the study reveals more.

Take a look, the researchers took cell cultures from the liversse of 60-day-old Sprague-Dawley rats. Not only are rat livers much smaller than human livers, but these were merely cultures. Furthermore, it was the 1x10^-4M concentrations that caused the most changes, but these are approximately 1 to a 1/3 of a full, daily human dosage -- at least for the 17 alpha-alkylated steroids. Even at the 1x10^-6M concentration, there were no significant changes observed. It's apparent that the levels of 17 alpha-alkylated steroids used were potentially toxic, but for a human to take the same amount would be insane. I'm guessing this could translate to maybe 4 grams every 24 hours or 28 grams a week if not more.

What is common so far is we can only prove that any steroid, that is believed to be hepatotoxic, only increases liver activity. I’ll say it again, where is the correlation to hepatotoxicity? We know that if the liver is running at 100% for long periods this may cause complications, but this is akin to any other chemical, which is metabolized by the liver. Ever noticed that liver cancer due to alcoholism takes decades of constant alcohol abuse? It’s apparent that the possibility for hepatotoxicity is there, but for the smart steroid user this is nearly an impossible task.

Another study done in 1999, attempted to show the acute and chronic effects of stanozolol on the liver[4]. In acute treatments of stanozolol, dosages not mentioned, both cytochrome P456 and b5 (microsomal enzymes) levels dropped after 48 hours, and then at 72 hours, levels significant increased. On the other hand, with chronic treatments, time or dosage not mentioned, these microsomal enzymes showed a decrease in levels. Researchers showed that both acute and chronic treatments resulted in "slight to moderate inflammatory or degenerative lesions in centrilobular hepatocytes", but the authors did not note true hepatotoxicity.

How about we look at the other side of the story, the good studies. For instance, in a 1999 study, which looked at the effects of an 8-week cycle of 17 alpha-alkylated steroids[5]. The researchers used fluoxymesterone, methylandrostanolone, or stanozolol on rats at 2mg/kg-body weight, five times a week for 8 weeks. That's 182mg per dosage, for a 200lb man, or 910mg per week. Half of the rats were sedentary and the other were trained on a treadmill.

Levels of NADH-cytochrome c reductase, succinate cytochrome c reductase, and cytochrome oxidase (showing liver activity), increased in the steroid-administered rats, while citrate synthase showed no change. Comparatively, in vitro, the "cytochrome oxidase and citrate synthase activities were insensitive to the AAS, whereas NADH-cytochrome c reductase and succinate cytochrome c reductase activities were partly inhibited."

Furthermore, in vivo, each rat had liver enzyme levels that were within normal range. From this, the researchers determined that the steroid-administered rats, trained or sedentary, did not show "...classical serum indicators of hepatic function". Extrapolating this, 910mg a week for 8 weeks could potentially have little to no effect on the liver in humans.

As for human studies, in 1999 researchers tried to prove that the hepatotoxicity of steroids is overstated[6]. In this study, 15 of the participants were bodybuilders using self-administered steroid dosages and 10 were non-steroid bodybuilders. Serum data was compared to 49 patients with viral hepatitis, and 592 exercising and non-exercising medical students. [

All of the bodybuilders showed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) while gamma-glutamyltranspeptidase (GGT) levels were in the normal range. In comparison, hepatitis patients showed increased ALT, AST, and GGT levels while the control exercising medical students showed increased CK levels. From this, the researchers suggested that it is the correlation between AST, ALT and GGT that shows true liver dysfunction. Keep in mind, we can only guess that the 15 steroid users were using 17 alpha-alkylated steroids, and we do not know what the dosages that were used., but common sense tells us the results are likely relevant.

Last but not least, a simple study done in 1996, showed the long term benefits after taking a 3 month break from steroids[7]. 16 bodybuilders using steroids were compared to 12 bodybuilders that were not. After a three-month drug withdrawal, the researchers showed that levels of liver enzymes, types not mentioned, returned to the same as the non users. Again the dosages are left to the reader’s imagination and we can only guess that the 16 steroid users were using 17 alpha-alkylated steroids.

So what can we conclude from all of this? First off, 17 alpha-alkylated steroids are hepatotoxic in high dosages taken for a long time. On the other hand, short cycles and small dosages appear to be perfectly safe. I suggest that maximum dosages should be 500mg to 900mg per day. They should be cycled for perhaps 8 weeks at a time, and if needed a 3-month break from them should be used. Using the above-mentioned techniques, your liver can be healthy for a long time. Simply put, the hysteria surrounding “hepatoxic” steroids, is based mainly on folk lore.


References:

[1] Lancet 1979 Nov 24;2(8152):1120-3, Hepatic angiosarcoma associated with androgenic-anabolic steroids. Falk H, Thomas LB, Popper H, Ishak KG.

[2] J Gastroenterol 2000;35(7):557-62, Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis. Nakao A, Sakagami K, Nakata Y, Komazawa K, Amimoto T, Nakashima K, Isozaki H, Takakura N, Tanaka N.

[3] J Pharmacol Toxicol Methods 1995 Aug;33(4):187-95, Toxic effects of anabolic-androgenic steroids in primary rat hepatic cell cultures. Welder AA, Robertson JW, Melchert RB.

[4] Arch Toxicol 1999 Nov;73(8-9):465-72, Evaluation of acute and chronic hepatotoxic effects exerted by anabolic-androgenic steroid stanozolol in adult male rats. Boada LD, Zumbado M, Torres S, Lopez A, Diaz-Chico BN, Cabrera JJ, Luzardo OP.

[5] Med Sci Sports Exerc. 1999 Feb;31(2):243-50, Rat liver lysosomal and mitochondrial activities are modified by anabolic-androgenic steroids. Molano F, Saborido A, Delgado J, Moran M, Megias A.

[6] Clin J Sport Med 1999 Jan;9(1):34-9, Anabolic steroid-induced hepatotoxicity: is it overstated? Dickerman RD, Pertusi RM, Zachariah NY, Dufour DR, McConathy WJ.

[7] Int J Sports Med 1996 Aug;17(6):429-33, Body composition, cardiovascular risk factors and liver function in long-term androgenic-anabolic steroids using bodybuilders three months after drug withdrawal. Hartgens F, Kuipers H, Wijnen JA, Keizer HA.

[nsa]

This has already been posted here before.

[iamthesuperbeast]

then why are you still insisting that two low mg methyls are bad?

[macrophage69alpha]

hepatoxicity of these new methylated compounds is unknown. You cannot compare one to the other as their impact on the liver can be completely different. Not knowing the half life and/or the metabolite half life is an indication of what unknowns these compounds are.


also since the neither of the above human steroid studies indicated that the users were using 17aa drugs to assume that they were is a very big mistake.

as a side note tylenol is the main cause of fulminant liver failure, partly because of its use in suicide attempts and partly because of its widespread use.

as to the genetic predisposition issue, of course its an issue, though since its impossible to know whether you are predisposed, its better to assume that you are.

[iamthesuperbeast]

it was stated in the article that not all were 17aa so who is assuming they were. And you are exactly right that the hepatotoxicity of these new methyls are unknown, they are not shown by any study to cause liver damage.
I am not saying that they are completely safe i will most certainly be using my milk thistle and ala. But i am just tired of the people who post only negative info about things with nothing to support there arguement.
When someone asks a question they want information not a biased opinion.

[iamthesuperbeast]

Some of the bloodwork done by testers at Designer Supplements.

As some of you may know we had some of our testers get blood work done while using some of the new products in hopes to provide some insight as to how are bodies react while using these compounds.

Methyl-14ADDiol has been tested alone as well as being stacked with M1T and M5AA. M14ADDiol seems to be a very mild compound as thought. There was no significant rise in liver enzyme values while being used at a dose of 30mgs per day, this helps suggest it does not have a strong influence on liver values. When 20mgs M14ADDiol is stacked with 10mgs M1T per day, these were some of the values from one of our testers. Also suggesting that by lowering the overall amount of Methyl compounds but stacking 2 together you can get a great effect but without much stress on the liver.

protein, total 7.7
albumin 4.8
globulin, calculated 2.9
a/g ratio 1.7
bilirubin, total 0.5
bilirubin, direct 0.1
alkaline phosphatase 44
ast 44 normal (2-50)
alt 75 normal (2-60)

The results were the almost exactly the same when using 30mgs M14ADDiol and 20mgs M5AA 1 hour preworkout on workout days only.

ast 42 normal (2-50)
alt 70 normal (2-60)

Methyl-14ADDiol seems to be an excellent choice for first time users of 17a-methyl ph’s or for more experienced users who know their bodies well enough to be able to stack 2 compounds together. Methyl-14ADDiol can be used for both bulking as well as dieting depending what type of diet and exercise program is being followed.



Here is the baseline as well as the first couple days after 3mgs Methyl Dien™ use. I will try to update the blood work as it comes in.

Baseline: AST 49, ALT 51; LDH 213; Cholesterol 103; HDL
42.2; ALP 76; GGT 17; TBIL 0.9; DBIL 0.2; ALB 4.0; Testosterone 629.56;
Cortisol 7.43; Progesterone 0.48; Prolactin 9.06; PSA 0.44; LH 19.13;
Estradiol 69.03; FSH 4.71

Day 2 while ON: AST 54; ALT 60; LDH 204; Cholesterol 104; HDL 47.4; ALP
68; GGT 21; TBIL 1.2; DBIL 0.2; ALB 4.0; Testosterone 800.12; Cortisol
17.16; Progesterone 0.85; Prolactin 10.14; PSA 0.42; Estradiol 118.91;
LH 16.79; FSH 5.63

Another tester had his blood done as well, the results were similar to those above, most will need to watch Cholesterol instead of liver values. Although Cholesterol levels usually return to normal post cycle.

[nsa]

Designer supplements is biased in their research, of course they are going to claim that methylated compounds aren't that bad on the liver, they make methylated compounds.

[Sir Foxx]

Hey NSA,

Sledge is beyond reproach. His rep is stellar on the boards so don't make accusations that you can't back up or have any proof of.

[nsa]

They are definately biased, they sell the stuff.

[Sir Foxx]

Sledge is not biased. He is an honest bro who tells it like it is regardless of how it might affect his bottom line. Think before you speak.

[nsa]

Is sledge the one who is admistering the test? No.

[Sir Foxx]

Sledge owns the company. He is the one who had his testers go to the Dr. and get the tests. You think the Dr.s are going to falsify the tests to help Sledge out? You don't know the guy or how he operates. So stop making accusations you can't back up.

[daman1]

Children, settle now! We are allowed to voice an OPINION. It is not necessary to tell someone to "think before they speak" or other derogetory comments. It will not get you far on this site.

[Sir Foxx]

It might help if the opinion was based on fact.

[nsa]

All your saying is your opinion of sledge, its not fact.