Hepatoxicty: Fact or Fiction

[K.Biz]

I thought this was a great read. I came across it looking for something else. It was in the steroid forum. But since a lot of people come here for advice on orals I thought it would be a good idea to post this here as well

Props to Nark for all the info

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 weak 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 not 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 livers 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 50mg to 90mg 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.

[Manpretty]

yep read that when nark worte it......that thread had a bunch of arguing in it...lol

[IronAdam]

Thats an interesting article, but I'm not fond of his extroplation techniques comparing rat doasages to would be human dosages, although I see his point. All I know is that when my back starts hurting and my piss gets dark, it's time to drop the oral roids.

[*Narkissos*]

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[IronAdam]

bump

Nark, can you comment on this article? What are your thoughts on oral steroids ? Can we assume that oral steroids will not result in symptomatic hepatoxicity based soley on the studies posted in the article? Are we to believe that the only cases of hepatoxicity from oral steroids are idosynchratic? And does that make taking them any safer? Please elaborate on this as I think many who read the article will simply take away the message that "oral steroids are safe" and some newbs might be inclined to abuse them based on that assumption.

[K.Biz]

Nark, can you comment on this article? What are your thoughts on oral steroids ? Can we assume that oral steroids will not result in symptomatic hepatoxicity based soley on the studies posted in the article? Are we to believe that the only cases of hepatoxicity from oral steroids are idosynchratic? And does that make taking them any safer? Please elaborate on this as I think many who read the article will simply take away the message that "oral steroids are safe" and some newbs might be inclined to abuse them based on that assumption.

Thats not what i was trying to come across with this post, Im sure Nark can elobrate more on it. But that was not my intention of this post at all.

[IronAdam]

Thats not what i was trying to come across with this post, Im sure Nark can elobrate more on it. But that was not my intention of this post at all.

I know that, and I'm not trying to flame you or nark. I'm really just interested in what narks opinions are on it. That and the supplement section is full of newbs that might get the wrong idea about oral steroids . I think its wise to be prudent when doing any oral steroids . Most newbs lack that vitrue.

Something I just realized is that there's no mention of cholesteral, and how orals can effect it. I realize its an article about hepatoxicity, but high cholesteral is terrible for your long term cardiovascular health. The liver can regenerate cells but the heart cannot. A functioning liver only helps a donor recipient if your heart fails. Again, I'm not trying to be a pain in the ass, just offering some talking points.

[Manpretty]

i agree with you iron....i would hate to see someone misinterpert this as saying its ok to abuse oral steroids .

i think for me what the article highlighted is that hepatoxcity associated with a moderately dosed cycles along with a moderated cycle length and more than enough time off (idealistic i know but) is relatively low and somewhat overexaggerated on most boards.

as you may or maynot know i usually dose my cycles on the upper end of acceptable dosing and have gone as far as stacking 2 17aa on more than one occasion. i experienced relatively little sides however only on my first cycle did i have BW done, it was fine at the time. that is not to say im fine now and i do plan on have BW done again in the near future.

what it really comes down to is not being an idiot, some would say im an idiot (tank prolly would say that LOL) but i feel i run cycles as saftly as possible with the addition of ancilliaries and the proper amount of time off cycle which i think is key........dont hit a man while hes down ie let you body recover fully before the abuse starts again.

i mean look at two well know monitors on this site tia and bino. tai is notorious for what i would say is abuse of steriods and specifically oral steroid (he would say heavy use) but is 200+mged of dbol really abuse?? lol from what i know he has rel few probs, i may be wrong, increase BP from hdl and well im not too sure but he dosent seem too concerned lets put it that way.

and then we have bino who i talked to about this very subject not too long ago and he said

"Last bout that got me into trouble was running var for prolly 6 weeks at 100mg ed. Earlier in the same cycle ran halo at 40mg ed for 4 weeks."

Originally Posted by Manpretty
"thats not too crazy do you know if you had existing problems before those cycles?"

Naw I was perfect. I get my blood work done every few months to be safe on and off cycle. But now I have to get blood work done EVERY WEEK just to be sure im stayin healthy cuz my liver cant take anything. I cant even take medications for other problems now because my liver is ****ed.

Not sayin it will happen to everyone, but people DO need to exercise caution when using orals and especially if they DO have an existing condition (like you suggested I may have) which this user may."
Bino

so i feel that the problems would arise if a user had an existing condition or one developed in the process of AAS usage. again im going to stress the fact i feel that time off from cycling is the key to preventing liver issus. although this maynot totally prevent all possible problems it for sure will greatly increase the chances you will not have a problem due to the fact the liver is capable of regenerating itself. hopefully the time you take off from aas usage allows the liver to recouperate. we must remember that unforseen issues are all ways a possiblity and therefor must use caution.

[C_Bino]

Thanks for directin me to this thread Manpretty. Like I said before we are all different and anyone can post any study but in the end what does it really tell us...that RATS dont have liver probs with oral steroids , well congratulations but Im not a rat LMAO.
None the less I love reading these studies and do think they are important and educational, but when it comes to ones own health lie Iron said extrapolations from rats are not gonna be my primary source for information. Is hepatotoxicty overrated, no, is it underrated either, no.
Its like the whole smoking argument; some people smoke for 50years and never have a problem, some people have secondhand smoke for a few years and die of lung cancer. So I think caution needs to be exercised when using orals and it is important to monitor liver values. It cant possibly do you any harm to be cautious and for some (like me) it will save them a whole lot of trouble.

Let me give you an example from my real life blood work and feelings over the past few months. Take ALT values for example, regular values should be in the range of 5-30. This is where mine usually fall but are up on cycle, some people go to double that upper limit and show liver problems at say a value of 60. Well my ALT value was 208 during my oral steroid use during the last cycle I ran. I started throwing up after eating and could not even take some medication i was taking for a cough I had because after I took those pills I would throw up, my liver was jus goin down the shitter.
It is recovering now slowly with time but it was a wake up call to me that not only am I not a rat but Im not invincible and I will not touch oral steroids again.

[taiboxa]

yeah, i know 2 people who have surpassed me in orals i.e. either dose or duration.. one would be taking anadrol for 10weeks str8 at a dose im not going to mention here.. and another was getting redy for a strong man comp last october and was running both drol and halo together... both get blood work done usually bi or tri weekly and are FINE..

i my self have never had liver enzymes over 40.. even when im taking truckloads of drop as my preworkout supplement lol.
my father.. hard core smoker and drinker and i MEAN big time drinker! is in his 50's... he goes to the doc to get everything checkd out.. and his is in PERFECT condition not a fuxin thing wrong w/ him.

as for my high blood pressure.. i have had that since i was born, got it from my mothers side... i had trouble getting into the airforce since it was so high i could never pass my physical.. luckily they pulld some strings made up some numbers and took me (and i wasnt on anything back then, weighed bout 185lbs w/ single digit bf)
then u have Bino.. and he dabbles w/ some var and gets a ****d up liver.. i blame it on his canadianismness.. but yeah just goes to show that u cant be too careful and everyone is different.

[Schmidty]

wow...

[notorious_mem]

my last cycle of winztrol and halodrol had me hurting pretty good but 4 weeks later i feel great.im going to chill till atleast may till i cycle again....

[Property of Steroid.com]

If you're running orals, check out my new supplement. Honestly.

I designed it with myself in mind...I have high tryglycerides no matter what I do, and my liver enzymes are never great....take a look at the product write up and see if it'll help you.

As for toxicity from orals, it's real, but overstated.

[Manpretty]

nice....im glad we had both "sides" of the story ill be saving this thread so i can cut and paste when questions arise in the future.

nark any comments?

[Schmidty]

Thanks for directin me to this thread Manpretty. Like I said before we are all different and anyone can post any study but in the end what does it really tell us...that RATS dont have liver probs with oral steroids , well congratulations but Im not a rat LMAO.
None the less I love reading these studies and do think they are important and educational, but when it comes to ones own health lie Iron said extrapolations from rats are not gonna be my primary source for information. Is hepatotoxicty overrated, no, is it underrated either, no.
Its like the whole smoking argument; some people smoke for 50years and never have a problem, some people have secondhand smoke for a few years and die of lung cancer. So I think caution needs to be exercised when using orals and it is important to monitor liver values. It cant possibly do you any harm to be cautious and for some (like me) it will save them a whole lot of trouble.

Let me give you an example from my real life blood work and feelings over the past few months. Take ALT values for example, regular values should be in the range of 5-30. This is where mine usually fall but are up on cycle, some people go to double that upper limit and show liver problems at say a value of 60. Well my ALT value was 208 during my oral steroid use during the last cycle I ran. I started throwing up after eating and could not even take some medication i was taking for a cough I had because after I took those pills I would throw up, my liver was jus goin down the shitter.
It is recovering now slowly with time but it was a wake up call to me that not only am I not a rat but Im not invincible and I will not touch oral steroids again.

thats some scary shit

[*Narkissos*]

and some newbs might be inclined to abuse them based on that assumption.

The fact of the matter is noobs will abuse anything regardless of the information provided.

Additionally, disclaimers account for zilch when it comes to noobs searching for jusitification of an unhealthy practice.

e.g.

Alcohol consumption.

Research indicates that alcohol is heptatoxic, neurotoxic.. and additionally, directly toxic to the cells of the testes.

Still, with all that information pointing to an obvious conclusion, noobs will look at the anecdotal info they glean from buddies.. or from observing others and come to the conclusion that it's ok to drink on cycle.. and on pct.

..'because Arnold did it..and look how good he looked'.

etc.

My opinions on orals and hepatoxicity?

I'd refrain from commenting..solely on the grounds that my opinion may be misconstrued.. and manipulated by a noob to strengthen their sense of justification in their choice(s).

Anyway..that being said:

Hepatoxicity as a whole is over-rated in my honest opinion.

This isn't to say that the potential for damage should be shrugged off as hype.. rather that with all parameters of personal health and genetic predisposition being optimal, oral use is not a problem.

Oral use...

'Use' being the operative term.. not abuse, as it is so commonly interchagned with.

Now for the argument of oral-only v.s. inject-only or inject + oral... where do my thoughts lie?

Firstly.. all of the above are acceptable protocols.

Oral-only being limited by the previously mentioned factors such as health and genetic predipositions etc.

Also.. duration.

It would be illogical to promote a long-term heavy-dose oral-only cycle.

illogical and irresponsible.

That being said, a moderate dose, moderate duration oral-only cycle, all of the above conditions being congruent and conducive to such, is no problem.

I see people getting tied up in the debate(s) without a leg to stand on.

The toxicity of a cycle depends on the toxicity of the individual compounds.. as well as the cumulative toxicity they generate.

Cumulative toxicity is derived from duration as well as content.

It would be illogical to argue that an oral-only cycle is more toxic than an oral + inject cycle..simple because of its nature.

e.g.

Cycle 1

Weeks 1-8: 100 mg Anavar Ed

v.s.

Cycle 2

Weeks 1-8: 50 mg prop Ed
Weeks 1-6: 50 mg Winstrol Ed


Sorry.. but by all account cycle 2 would be more toxic

Hell.. toss in tren in the mix:

Cycle 3:


Weeks 1-8: 50 mg prop Ed
Weeks 1-6: 50 mg Winstrol Ed
Weeks 1-6: 50 mg tren-a ED

and the over-all systemic toxicity jumps a bundle.

Honestly i think people need to look at cycling logically.

..and, don't put blind faith in what you read.

in the end you can only know how your body responds to what by trying it.

Additionally, you've gotta determine what constitutes acceptable risk... and what your exact goals are per cycle.

i see so many saying: "if you'd just like to gain 5 lbs.. why cycle?"

I'd say: "if those are your goals..why not?"

Feasibility:

It will take the average person 8-12 months to add 5 lbs of lean muscle tissue... so balking at a 5 lb gain of pure muscle is simply idiotic imo.

viva la winstrol cycle.

-Narkissos

[number twelve]

great posts

[*Narkissos*]

bump