(Study) Boldenone-mediated hepatorenal impairment in Rats (2021)

[Muay Thai]

wouldn't glutathione (prob inj admin)be the most viable?liposomal I've seen good stuff on

 

[Soalian]

That is quite a high dose of NAC. If taken orally, it does have poor bioavailability. But that's double what I would consider a reasonable (yet still high) dose. Megadosing it like this may cause low-level hypoxia and pulmonary hypertension. I believe it actually reduces the inflammation & can prevent/treat cholestasis, so it's not just merely masking the increase to liver enzymes but in fact preventing liver damage.

I tend to prefer: to start, a reasonable/moderate oral AAS dose, to minimize reliance on compounds for liver toxicity. For very potent orals like Superdrol & methyltren, UDCA/TUDCA. And for more common orals like Anadrol, Anavar, etc. either nothing (not really necessary at a reasonable dose x duration) or milk thistle/silymarin. The latter can also increase bioavailability of other agents that we use if one looks into this, by acting as a P-gp inhibitor, and has other actions beyond being a very effective agent for liver toxicity.

my reservations about NAC use medium and long term, is how it could potentially impair the liver's own adaptative response in response to ROS and oxidative stress, aka subsituting for the endogenous glutathione production under stress, and blunt liver recovery from damage:

Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity


Also, NAC might exert pro-oxidative effects at higher doses (alsal seen with ALA), dosage for antioxidant benefits might follow a U curve:

N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19

"High dose NAC administration (1.2 g daily) is not recommended in healthy individuals who are not exposed to extreme oxidative stress. NAC might actually act as a pro-oxidant and might lower GSH and increase the amount of oxidized GSH."

don't know what your thoughts are about this?

In my eyes, the putative pro-oxidant properties of NAC might be of a HORMETIC nature, eliciting a greater endogenous adaptative response; howver I think in this case the pro-oxiddant properties of NAC would be from another mechanism, independent from its ability to enhance glutathione synthesis.

 

[Doctordave42]

There's nothing unique to boldenone that makes it particularly hepato- nor nephro- toxic, other than its being relatively less estrogenic than T (in vitro data suggests that podocyte cells [part of the glomerulus in the kidneys] express AR & ER; androgens promote apoptosis, whereas estrogens oppose) and, perhaps, the undecylenate ester (trivially in man, perhaps less so in rodent) increases resistance to hepatic breakdown.

On a continuum of toxicity in liver (described by the formula: potency to activate AR * resistance to hepatic breakdown) and kidneys, EQ lies closer to testosterone than trenbolone and rather far from the extreme end of the commercially available androgens, Superdrol and methyltren.

In both instances of liver & kidney toxicity, ascorbate (Vitamin C) acts as a free radical scavenger, decreasing ROS (and increasing NO). Ascorbate thereby ameliorates the ROS production that causes mitochondrial swelling and subsequent apoptosis.

This does not call for you, a human, to take megadoses of Vitamin C because EQ is kidney and liver toxic in rats.

I cannot say it enough: rats are not humans. While we can make some (mechanistic mostly) extrapolations from rodent data to man, talking about any sort of dose-response is folly. Rats are clearly more impacted by parenterally-administered androgens (injected AAS) than man at these doses with respect to hepatotoxicity/liver membrane and cell damage.

Moreover, megadoses of antioxidants blunt the adaptive response to resistance training, essentially blocking this primary stimulus for growth/hypertrophy outright. They likewise blunt many adaptations to endurance training, including endurance training enhancements to antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity.

Guys that blast more than 16 weeks 1x yearly for a few (3+, arbitrarily) consecutive years should be getting annual liver & kidney ultrasounds in addition to echocardiograms, and doing regular (3-6 mo intervals) 24-hr creatinine clearance testing, C-reactive protein, in addition to the standard bloodwork parameters everyone does.

Interesting. While this study does not "call for" us to take megadoses of VC, the basic distillation of information suggests a statistically significant benefit of offsetting renal and hepatic damage in mammalian physiology when boldenone is present. Vitamin C has over 500 known beneficial effects on human physiology from repair of connective/muscular tissue to improving immunity and reducing inflammation. It has virtually NO risks associated with moderate to higher dosages, quite the contrary. The blunting you mention that VC may do to hypertrophy and other radical responses that AAS cause in supraphysiological dosages is a quality factor in begging the body to maintain homeostasis on dozens of different fronts. I will continue to take 1-3 grams of a vitamin c complex regardless, but this is a compelling study which is very supportive of VC supplementation to the scientific minds.

 

[Type-IIx]

Interesting. While this study does not "call for" us to take megadoses of VC, the basic distillation of information suggests a statistically significant benefit of offsetting renal and hepatic damage in mammalian physiology when boldenone is present. Vitamin C has over 500 known beneficial effects on human physiology from repair of connective/muscular tissue to improving immunity and reducing inflammation. It has virtually NO risks associated with moderate to higher dosages, quite the contrary. The blunting you mention that VC may do to hypertrophy and other radical responses that AAS cause in supraphysiological dosages is a quality factor in begging the body to maintain homeostasis on dozens of different fronts. I will continue to take 1-3 grams of a vitamin c complex regardless, but this is a compelling study which is very supportive of VC supplementation to the scientific minds.

By all means, continue. Indeed, megadosing antioxidants may be beneficial in older individuals (aged muscle, increased oxidative stress). I was speaking to individuals that are not old. As I take it you are a "scientific mind," I won't trot out the literature supporting strongly the view that megadosing antioxidant, including vitamin C in particular, attenuates strength gains & the acute mechanisms of skeletal muscle hypertrophy in young adults.

 

[Type-IIx]

what real experience do you have with antioxidants creating a pro oxidant effect? more so what real world even anicdotal have you seen?

im not asking about studies published

what experience have you that shows antioxidants being in any way bad for health or performance?

I work with strength athletes and a few bodybuilders that have experienced it, but I don't come to the forums to share case studies in those I've worked with.

 

[Type-IIx]

my reservations about NAC use medium and long term, is how it could potentially impair the liver's own adaptative response in response to ROS and oxidative stress, aka subsituting for the endogenous glutathione production under stress, and blunt liver recovery from damage:

Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity


Also, NAC might exert pro-oxidative effects at higher doses (alsal seen with ALA), dosage for antioxidant benefits might follow a U curve:

N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19

"High dose NAC administration (1.2 g daily) is not recommended in healthy individuals who are not exposed to extreme oxidative stress. NAC might actually act as a pro-oxidant and might lower GSH and increase the amount of oxidized GSH."

don't know what your thoughts are about this?

In my eyes, the putative pro-oxidant properties of NAC might be of a HORMETIC nature, eliciting a greater endogenous adaptative response; howver I think in this case the pro-oxiddant properties of NAC would be from another mechanism, independent from its ability to enhance glutathione synthesis.

Yes, I concur with this view: that a hormetic dose/response curve exists for these more potent antioxidants (e.g., vitamin C, vitamin E, NAC, etc.)

 

[Soalian]

By all means, continue. Indeed, megadosing antioxidants may be beneficial in older individuals (aged muscle, increased oxidative stress). I was speaking to individuals that are not old. As I take it you are a "scientific mind," I won't trot out the literature supporting strongly the view that megadosing antioxidant, including vitamin C in particular, attenuates strength gains & the acute mechanisms of skeletal muscle hypertrophy in young adults.

problem is with megadosing certain oxidants for buffering oxidative stress in susceptible individuals and populations, that instead pro-oxidant effects might be exerted by a given antioxidant compound, if taken above a certain dose threshold,

thereby adding to the already present systemic oxidative stress load.

Again, the issue is that there's no way to tell accurately when, or whether, for a given compound, the curve shifts from overall antioxidant effects to pro-oxidant effects overall on the body, so that dosage might be tricky and caution advised, especially with "direct" antioxidants such as Vitamin E and Vitamin C

 

[Doctordave42]

By all means, continue. Indeed, megadosing antioxidants may be beneficial in older individuals (aged muscle, increased oxidative stress). I was speaking to individuals that are not old. As I take it you are a "scientific mind," I won't trot out the literature supporting strongly the view that megadosing antioxidant, including vitamin C in particular, attenuates strength gains & the acute mechanisms of skeletal muscle hypertrophy in young adults.

Nutrients. 2020 May; 12(5): 1501.
Published online 2020 May 21. doi: 10.3390/nu12051501
PMCID: PMC7285147
PMID: 32455696

Two Faces of Vitamin C—Antioxidative and Pro-Oxidative Agent​

this study got me thinking. With the effect on iron metabolism, I am going to look further into any contributing effect that supplemental VC may have in men over 40, on HRT, that develop erythrocytosis/hemochromatosis/polycythemia. Great material Type IIx

 

[LK3]

I work with strength athletes and a few bodybuilders that have experienced it, but I don't come to the forums to share case studies in those I've worked with.

well this is exactly what i want to know.
saying you dont come here to talk about that sounds a little like a copout.

all these studies are hypothetical in reality and mostly mental masturbation.

i had more then 100 pages of threads deleted to protect the identity of service guys who put this stuff to the test in about the most demanding situations there are. besides info from very sick people and top level endurance athletes. only positive results were seen. to the extent of them being unbelievable.

i have not worked with anyone who had negative results. other then not being able to handle side effects.

those side effects seem interesting to me as i think its part of the adaptation process.

im probably the only one here who has injected high doses of antiox for more then a decade, so it makes me real curious when people say things that are totally different from my real experience.

to me it sounds like docs who read a paper and think thats life. in rats, in test tubes and in limited normal person experience that is only backed up by paper, not real world results.


id really like to hear some of those.

 

[LK3]

problem is with megadosing certain oxidants for buffering oxidative stress in susceptible individuals and populations, that instead pro-oxidant effects might be exerted by a given antioxidant compound, if taken above a certain dose threshold,

thereby adding to the already present systemic oxidative stress load.

Again, the issue is that there's no way to tell accurately when, or whether, for a given compound, the curve shifts from overall antioxidant effects to pro-oxidant effects overall on the body, so that dosage might be tricky and caution advised, especially with "direct" antioxidants such as Vitamin E and Vitamin C

lets wait and hear on the real world stuff, as i have never seen it.
just words on paper by dudes in white coats who prob dont push the envelope in anything besides mail boxes.

 

[Love_to_Bodybuild]

Lots of different views, and insights here on anti oxidants . Lovin' both of these.

 

[Type-IIx]

well this is exactly what i want to know.
saying you dont come here to talk about that sounds a little like a copout.

all these studies are hypothetical in reality and mostly mental masturbation.

i had more then 100 pages of threads deleted to protect the identity of service guys who put this stuff to the test in about the most demanding situations there are. besides info from very sick people and top level endurance athletes. only positive results were seen. to the extent of them being unbelievable.

i have not worked with anyone who had negative results. other then not being able to handle side effects.

those side effects seem interesting to me as i think its part of the adaptation process.

im probably the only one here who has injected high doses of antiox for more then a decade, so it makes me real curious when people say things that are totally different from my real experience.

to me it sounds like docs who read a paper and think thats life. in rats, in test tubes and in limited normal person experience that is only backed up by paper, not real world results.


id really like to hear some of those.

"high dose antioxidants" (surely you don't claim to have come up with these compounds and have used them all by your lonesome?)... "adaptation process"... Those are just a couple of the scientific concepts you allude to in this very post, while claiming to abhor science. So, when it comes to your pet issue (antioxidants and performance) you choose to pick and choose the merits of "real world" vs. "scientific" knowledge as it suits you? And you talk to me about "copouts."

Might I suggest that megadosing antioxidants might be expected to benefit performance in those you've listed:
those with systemic infection/illness (antioxidants would be anticipated to often help these people due to reducing oxidative stress)
high level endurance athletes
and your athletes, perhaps

Due to overtraining? Perhaps if they were on properly designed training programs they wouldn't derive apparent benefit from crushing ROS?

 

[LK3]

"high dose antioxidants" (surely you don't claim to have come up with these compounds and have used them all by your lonesome?)... "adaptation process"... Those are just a couple of the scientific concepts you allude to in this very post, while claiming to abhor science. So, when it comes to your pet issue (antioxidants and performance) you choose to pick and choose the merits of "real world" vs. "scientific" knowledge as it suits you? And you talk to me about "copouts."

Might I suggest that megadosing antioxidants might be expected to benefit performance in those you've listed:
those with systemic infection/illness (antioxidants would be anticipated to often help these people due to reducing oxidative stress)
high level endurance athletes
and your athletes, perhaps

Due to overtraining? Perhaps if they were on properly designed training programs they wouldn't derive apparent benefit from crushing ROS?

no dude, im not claiming to have come up with anything. i have just been a lab rat for a bunch. the things i did have not ever been readily available they were made by a friend who is no longer here.

i have however done far more of this than anyone i know of. probably i know the majority that has real experience with this.

i in no way abhor science. in fact im asking you about something you are talking about like you know it. so im asking what it is that you know and have seen.

im not sure what or where my copout might be, there was tons of stuff here still is if you dig for it but some of the best stuff was deleted. that stuff was posts by other people who tried these things for various reasons. none were normal people. i dont think people come to pro muscle to be normal either.

ill agree that heavy antiox is probably not the best thing for bodybuilding purity but for someone to push more then what is normal i have seen and others that i know of have seen results that simply blow away aas or any other combos i can think of.

when i say adaptation process im talkign about the sometimes very sever side effects that can come with this. adaption is them going away. never have i come close to experiencing these side with oral sups like nac and ala and list of who knows how many things.

ideas on this came from scientific studies that a handful of crazy people went out and made there own things ( that no one else to my knowledge has duplicated ) to try and go after ideas that were taken from those studies.

since then the people who know the most have died or gone very mia all under strange circumstance and we have a world wide health epidemic. mnsod is no longer availbe aside form places like sigma aldich and there prices make it unthinkable. nac is also on the chopping block.

now we have all this talk of antiox being pro ox from people who have not really even tapped what antiox capacity could be. nac just doesnt get you there. its nice if the otehrs are around but maybe its 10%

for how many years did many docs say aas dont work?
now docs say antiox are bad?

all im really doing is poking to see what you really know or have seen in real life. the things i have seen and have had contact from others about are to the extent of being unbelievable.

i started posting on my person experiances with this around ten years ago here as the things i and others were doing with this was blowing away the known performance enhancement combos. this wasnt some guy doing bechpress, it was guys going through elite military training and top tier endurance athletes. people with cancer, people with als, people with ms and all sorts of other heavy conditions that normal medicine doesnt do a good job with.

all talking about basically impossible results.

in this case you are saying too much nac could be bad. i have seen in person with my own 2 eyes a young girl who was sick in the care of docs taking 3 different meds drop all stay with high dose nac, i forget exact dose but min 1.2g ed for idk a 50lb kid go from being sick all the time to not missing a day of school for 3+ years.


these are things that i have seen.

im always opén to the possibility of being wrong or of new info coming along.

here you are saying something new/different all im saying is lets see something more then some studies. studies often can often have bias results. main stream seems heavily biased. docs generally are very main stream.

you said to have seen or know of more, all i did is ask what you saw.

 

[Soalian]

That is quite a high dose of NAC. If taken orally, it does have poor bioavailability. But that's double what I would consider a reasonable (yet still high) dose. Megadosing it like this may cause low-level hypoxia and pulmonary hypertension. I believe it actually reduces the inflammation & can prevent/treat cholestasis, so it's not just merely masking the increase to liver enzymes but in fact preventing liver damage.

I tend to prefer: to start, a reasonable/moderate oral AAS dose, to minimize reliance on compounds for liver toxicity. For very potent orals like Superdrol & methyltren, UDCA/TUDCA. And for more common orals like Anadrol, Anavar, etc. either nothing (not really necessary at a reasonable dose x duration) or milk thistle/silymarin. The latter can also increase bioavailability of other agents that we use if one looks into this, by acting as a P-gp inhibitor, and has other actions beyond being a very effective agent for liver toxicity.

tangentially, in relation to TUDCA/UDCA being used for improved bile flow and clearance, when used with possibly cholestatic-inducing drugs (aka oral steroids in this case),

my concern would be that, by allowing forced bile clearance and relieving cholestatic bile obstruction by facilitating hepatic bile flow when it's blocked, the forced clearance might lead to ruptured bile ducts, and other complications.

Then again, I don't know how much truth there'd be to those concerns, and whether or not TUDCA use would be best for during cycle alongside orals, or post-cycle, when cholestatic bile flow impairment would be alleviated

 

[Soalian]

tangentially, in relation to TUDCA/UDCA being used for improved bile flow and clearance, when used with possibly cholestatic-inducing drugs (aka oral steroids in this case),

my concern would be that, by allowing forced bile clearance and relieving cholestatic bile obstruction by facilitating hepatic bile flow when it's blocked, the forced clearance might lead to ruptured bile ducts, and other complications.

Then again, I don't know how much truth there'd be to those concerns, and whether or not TUDCA use would be best for during cycle alongside orals, or post-cycle, when cholestatic bile flow impairment would be alleviated

therefore, you may watch out when using TUDCA/UDCA along in cycle, with c19 alkylated oral steroids, because of the potential for cholestasis with biliary obstruction.

In that case, use of TUDCA/UDCA during cycle might be detrimental, due to its choleretic effects:

Is ursodeoxycholic acid detrimental in obstructive cholestasis? A propos of a case of malignant biliary obstruction

Ursodeoxycholic acid aggravates bile infarcts in bile duct–ligated and Mdr2 knockout mice via disruption of cholangioles

Differential effects of norUDCA and UDCA in obstructive cholestasis in mice

 

[Type-IIx]

therefore, you may watch out when using TUDCA/UDCA along in cycle, with c19 alkylated oral steroids, because of the potential for cholestasis with biliary obstruction.

In that case, use of TUDCA/UDCA during cycle might be detrimental, due to its choleretic effects:

Is ursodeoxycholic acid detrimental in obstructive cholestasis? A propos of a case of malignant biliary obstruction

Ursodeoxycholic acid aggravates bile infarcts in bile duct–ligated and Mdr2 knockout mice via disruption of cholangioles

Differential effects of norUDCA and UDCA in obstructive cholestasis in mice

That first study (the relevant one) shows that UDCA is efficacious for (chemotherapy-induced) cholestasis with (complete) biliary obstruction in man.

There is some hypothetical risk that hasn't been borne out that it may disrupt biliary integrity.

Again, in my view it's a potent drug usually unnecessary, but seems most appropriate with Superdrol & methyltrienolone use.

 

[jaxino]

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role


So, it looks like there's yet another recent study on there that seems to be showing the deleterious effect of Boldenone on health markers, specifically kidney and liver health...

I've been wondering if all those results could be transferred to other specific AAS, or whether there are attributes to Boldenone that makes it specifically toxic, among all the other AAS.

Thoughts?

Use EQ do bloods, evaluate.

It's not rocket science.....

 

[Love_to_Bodybuild]

Again, in my view it's a potent drug usually unnecessary,

I thought tudca is a potent supplement for last, alt liver enzymes? Tudca is a drug?

 

[MasteroniPepperoni]

I thought tudca is a potent supplement for last, alt liver enzymes? Tudca is a drug?

Udca is a pharmaceutical. I believe they can sell tudca because they attached taurine to it

 

[Type-IIx]

I thought tudca is a potent supplement for last, alt liver enzymes? Tudca is a drug?

As @MasteroniPepperoni says, UDCA is a drug. TUDCA is taurine-conjugated UDCA and is the primary UDCA metabolite. TUDCA is not quite as efficacious, but is comparable. Specifically, both are satisfactory in the dissolution of gallstones, improving GGT values (but UDCA > TUDCA), and tolerability (but UDCA >> TUDCA).