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Everyone knows that oral steroids are subjected to a ‘first-pass’ metabolism (first pass meaning before it reaches is a general term which refers to the metabolic reduction of a compound prior to reaching the general circulation). A lot of these metabolic reactions will take place in the liver and small intestine. The liver of course is known for being the drug metabolizing organ of the body but the enzymes are spread out throughout the body, not just with the liver.
Metabolic processes can lead to a deactivation and excretion, or the production of more potent metabolites. So metabolic transformation is not always a bad thing. For example, tamoxifen is converted into the vastly more potent compounds 4-hydroxytamoxifen and endoxifen, biologically-inactive prohormones are converted into active target hormones (Thank you Patrick Arnold for that discovery) and so on.
So knowing this, we know that orally taken steroids are subject to extensive first pass metabolism. Not only does this cause the bioavailability of the oral steroid to go down, but it always converts the active androgens to far weaker or inactive metabolites. This is where the science gets a little more complicated but it’s because of the names of what we will be talking about more than anything else. CYP3A4 (see what I mean) is mainly found in the liver, it is one of the most important enzymes involved in the metabolism of xenobiotics (any chemical which is found in an organism but which is not normally produced or expected to be present, like any sort of pharmaceuticals). CYP3A4 in the intestine plays an important role in the metabolism of certain drugs as well.
The next bit might go a little fast but I want to get this write up posted with as much information on the subject as possible.
So why are we talking about the CYP3A4 enzyme? Because 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.
A comprehensive list of inhibitors can be found here:
Department of Medicine Indiana University, School of Medicine, Department of Medicine
On this list is grapefruit juice, grapefruit juice contains Bergamottin which is a moderate inhibitor (it will increase the bioavailability and subsequently the circulating amount by anywhere from 20-40% as well as increase the clearance time (half life). This alone will help many of you who want to get the most out of your oral steroids. Keep in mind that this will also cause a harsher environment for your liver, so proper liver supports are not only a good idea but will also keep you healthy through all of this.
So how much should you drink? About 250ml (roughly 8 fl oz) or 1 small glass of grapefruit juice will have a lasting effect on the uptake of the orals you are taking. How long varies much like all the science I am pointing out but about 24 hours until you need to drink some more to get the effect, so basically before every time you take an oral take some grapefruit juice (or wash it down with some).
Want to up the stakes and increase the bioavailability even more? Well this can be done as well and relatively safely, take Cimetidine a stomach acid inhibitor (for acid reflux) also known as Tagamet, this is a weak inhibitor of the CYP3A4 enzyme and will increase your uptake on it’s own by about 10% and decrease the clearance time by 20-50%.
And for those of you who just want the cliff notes here is a list
Ways to increase bioavailability and clearance time of your oral steroids
- 250ml grapefruit juice (8 fl oz roughly) before or with your oral steroids will increase availability by 20-40%
- Cimetidine (Tagamet) will on its own increase the availability by about 10%
Metabolic processes can lead to a deactivation and excretion, or the production of more potent metabolites. So metabolic transformation is not always a bad thing. For example, tamoxifen is converted into the vastly more potent compounds 4-hydroxytamoxifen and endoxifen, biologically-inactive prohormones are converted into active target hormones (Thank you Patrick Arnold for that discovery) and so on.
So knowing this, we know that orally taken steroids are subject to extensive first pass metabolism. Not only does this cause the bioavailability of the oral steroid to go down, but it always converts the active androgens to far weaker or inactive metabolites. This is where the science gets a little more complicated but it’s because of the names of what we will be talking about more than anything else. CYP3A4 (see what I mean) is mainly found in the liver, it is one of the most important enzymes involved in the metabolism of xenobiotics (any chemical which is found in an organism but which is not normally produced or expected to be present, like any sort of pharmaceuticals). CYP3A4 in the intestine plays an important role in the metabolism of certain drugs as well.
The next bit might go a little fast but I want to get this write up posted with as much information on the subject as possible.
So why are we talking about the CYP3A4 enzyme? Because 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.
A comprehensive list of inhibitors can be found here:
Department of Medicine Indiana University, School of Medicine, Department of Medicine
On this list is grapefruit juice, grapefruit juice contains Bergamottin which is a moderate inhibitor (it will increase the bioavailability and subsequently the circulating amount by anywhere from 20-40% as well as increase the clearance time (half life). This alone will help many of you who want to get the most out of your oral steroids. Keep in mind that this will also cause a harsher environment for your liver, so proper liver supports are not only a good idea but will also keep you healthy through all of this.
So how much should you drink? About 250ml (roughly 8 fl oz) or 1 small glass of grapefruit juice will have a lasting effect on the uptake of the orals you are taking. How long varies much like all the science I am pointing out but about 24 hours until you need to drink some more to get the effect, so basically before every time you take an oral take some grapefruit juice (or wash it down with some).
Want to up the stakes and increase the bioavailability even more? Well this can be done as well and relatively safely, take Cimetidine a stomach acid inhibitor (for acid reflux) also known as Tagamet, this is a weak inhibitor of the CYP3A4 enzyme and will increase your uptake on it’s own by about 10% and decrease the clearance time by 20-50%.
And for those of you who just want the cliff notes here is a list
Ways to increase bioavailability and clearance time of your oral steroids
- 250ml grapefruit juice (8 fl oz roughly) before or with your oral steroids will increase availability by 20-40%
- Cimetidine (Tagamet) will on its own increase the availability by about 10%