Grapefruit Juice and Orals Question

Clamp

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A buddy of mine gave me 4 grams of methylstenbolone for free because it was killing his appetite. I have researched this compound a bit and am planning to incorporate some into my next cycle. My question is: will grapefruit juice prevent the breakdown of methylsten specifically? I know it does this with other orals such as dbol, via inhibiting the CYP3A4 enzyme, but is methylstenbolone metabolized by this same enzyme?
 
A buddy of mine gave me 4 grams of methylstenbolone for free because it was killing his appetite. I have researched this compound a bit and am planning to incorporate some into my next cycle. My question is: will grapefruit juice prevent the breakdown of methylsten specifically? I know it does this with other orals such as dbol, via inhibiting the CYP3A4 enzyme, but is methylstenbolone metabolized by this same enzyme?

Achieve the same results by taking less dianabol? With grapefruit juice it***8217;s possible. At least, you can read this into a review article published by Israeli pharmacologists in the European Journal of Clinical Nutrition.


The Israelis***8217; article is about the relationship between grapefruit and medicines. Scientists came across this at the end of the 1980s when doing experiments with strong-tasting substances. To make the comparison with the placebo group as true-to-life as possible, the researchers added a grapefruit taste to the preparations. Suddenly the levels of medicines being tested were much higher than you***8217;d expect.

Later on it became clear that grapefruit inhibits the enzyme CYP3A4. This enzyme is responsible for breaking down substances in a process that scientists call 6beta-hydroxylation. Medicines that are sensitive to this form of breakdown disappear quickly out of the body.

And still later scientists discovered that grapefruit only inhibits CYP3A4 in the small intestine. The enzyme is also found in the liver, but grapefruit does not affect it there. Less CYP3A4 in the small intestine therefore means that a large group of substances is more easily absorbed by the body.

Since then another protein has been found that is inhibited by grapefruit: P-glycoprotein or P-gp. P-gp is also found in the small intestine and also decreases the absorption of pharmacological substances.

The figure below shows what the effect can be. The graph shows the concentration of the medicine lovastatine broken down by CYP3A4 after drinking large amounts of water ***8211; or large amounts of grapefruit juice.



You reach maximum effect, the researchers say, after drinking a 250 ml glass of grapefruit juice. Four hours after intake, 47 percent of the enzyme has been deactivated. Twelve hours after drinking the juice, the effect was still pretty optimal. Twenty four hours afterwards, a third of the effect still remains.

It is not know which substances cause the effect. The old theory was that it was the work of naringin and its metabolite naringenin. Laboratory tests do not confirm this though. Another theory is that the furanocourmarin bergamottin ***8211; the flavouring in Early Grey tea ***8211; and its metabolite 6',7'-dihydroxybergamottin cause the inhibition, but in laboratory tests the effect was only slight. There are probably several phytochemicals at play, all of which contribute to the effect.

For the researchers, one of the conclusions of their study is that users of CYP3A4-sensitive medicines are better off avoiding grapefruit juice and the whole fruit.

Dianabol

Halotestin

Turinabol
The dosages for these medicines are not based on improved uptake, and if this happens the users may experience more negative side-effects.

In the future, the Israelis add, once the grapefruit-effect is better understood, it may be possible to add the active ingredients to medicines so that dosages, and manufacturers' production costs, can be lowered.

The relevance of this publication for chemical athletes is that certain oral anabolic steroids are also broken down by CYP3A4. In the mid nineties doping hunter Wilhelm Schaenzer published a study on beta-hydroxylation of testosterone , boldenon, methyltestosterone , halotestin, dianabol and turinabol, which had been administered orally to the test subjects.

Schaenzer examined the metabolites in the urine of his human test subjects. He discovered that the 6beta-hydroxylation of boldenone , testosterone and methyltestosterone was negligible, but was important for the breakdown of turinabol, dianabol and halotestin. Between 17 and 46 percent of these hormones leave the body in the 6beta-hydroxylated form.

Source:
Eur J Clin Nutr. 2004 Jan; 58(1): 1-9.
Steroids. 1995 Apr; 60(4): 353-66.
.
 
Found very little info on it including this short interaction list but nothing conclusive yet:

Users who are at risk for anabolic steroid testing will test positive while using methylstenbolone. Always know whether or not you are at risk for drug testing prior to using Pro-Hormones.

Interactions

Users who are on anti-depressant or anti-anxiety medication may experienced increased anxiety/depression while on cycle and during post cycle therapy (pct). Users should avoid using stimulants on cycle as blood pressure may elevate too high and possibly cause nose bleeds or even in some rare cases fainting. In general, avoid starting any new medications while on cycle or just before, if you***8217;re concerned about a possible interaction consult your doctor. Users should also eat a clean diet on cycle and limit their alcohol intake significantly (best option would be to discontinue usage).
 
Found this gem:

All of the above compounds are found, to some extent, in grapefruit juice, and they all share a common mechanism of action: They are 'suicide inhibitors' which bind to the enzyme protein (apoprotein) & degrade it. This is an irreversible reaction which permanently destroys the CYP3A4 enzyme -- so, after a heavy dose of bergamottin, a couple of days might be required for CYP3A4 function to return to normal, as the body needs time to synthesize new proteins.
Bergamottin and its analogs do not appear to affect CYP activity in the liver, in vivo. (ref, ref) Although this fact seems to be rather well-known, I have yet to see a decent explanation. If I had to guess, I would assume that they themselves are quickly metabolized and deactivated in the enzyme-rich hepatic environment.

So the question is: Can these grapefruit juice phytochemicals increase steroid bioavailability? Based on the evidence we have, it seems that the answer is: Yes, but variability will generally be high, and the effect will not be very strong for most people. There are a couple of reasons for this: (1) CYP3A4 is not the only drug-metabolizing enzyme, and hydroxylation generally accounts for only around 40% of the first pass effect. And (2) due to genetic and environmental influences, CYP3A4 expression in the intestine varies widely. People who express it most strongly are most likely to notice this 'grapefruit juice effect.' Those who express it weakly, or even normally, might not notice much of a difference.

In a study using ethinylestradiol, grapefruit juice increased bioavailability by an average of 30%, but there was very wide individual variability. (ref) This seems to be about right.

As mentioned above, CYP3A4-mediated first-pass hydroxylation tends to affect 17a-methylated and non-17a-methylated steroids in roughly the same manner, so CYP3A4 inhibitors also improve the bioavailability of most 'oral' androgens.
...With that said, hepatic CYP3A4 inhibitors (like itraconazole) might make it slightly more difficult for the body to metabolize/detoxify 17a-methylated steroids, which may make them more toxic in themselves. Additionally, CYP3A4 is the enzyme which metabolizes bile acids and transforms toxic/hydrophobic bile acids into much more safe/hydrophilic varieties -- so inhibiting hepatic CYP3A4 can intensify cholestasis. (Luckily this isn't a concern with grapefruit juice!)


So... there you have it. Most of you already knew this, but drinking a glass of grapefruit juice can increase the bioavailability of most oral steroids. This effect is highly variable -- and some people will notice it much more strongly than others -- but the average bioavailability increase will likely be in the 25-40% range.

It is worth keeping in mind that 'F = Fa * Fg * Fh' implies that the 'grapefruit juice effect' and the increase in absorption seen when lipophilic compounds are taken with food are synergystic. 'Fa' increases with absorption, and 'Fg' increases as metabolism in the gut becomes less extensive.

Grapefruit juice only affects CYP3A4 enzymes in the small intestine not the gut where they're also located. I don't think the effect will be particularly great in either case.
 
Thanks doc, I can always count on you to find great info :)

You should drive out to the beach with me. I am throwing a wild college party today and tomorrow. There are plenty of single hot girls and I'm sure Rumpy won't mind sharing you for a bit ;)
 
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A buddy of mine gave me 4 grams of methylstenbolone for free because it was killing his appetite. I have researched this compound a bit and am planning to incorporate some into my next cycle. My question is: will grapefruit juice prevent the breakdown of methylsten specifically? I know it does this with other orals such as dbol, via inhibiting the CYP3A4 enzyme, but is methylstenbolone metabolized by this same enzyme?


This thread is above my IQ level
 
It's worth a shot. Can't really hurt if your only taking the methylstebolone. Don't take it with any other prescription/self-medicated drugs.
 
Thanks doc, I can always count on you to find great info :)

You should drive out to the beach with me. I am throwing a wild college party today and tomorrow. There are plenty of single hot girls and I'm sure Rumpy won't mind sharing you for a bit ;)

Rumpy and I have an agreement where he'll share me if I share with him :D. Sounds like you'll be having some fun with the ladies hahahaha. Thanks for the invite brother :)
 
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