Before one considers this protocol below, understand that you may feel ill or nauseated from this protocol.. IMO the best way to utilize ORAL’s is daily, do NOT skip a dose. ALWAYS keep blood serum levels steady, regardless of the half-life receptors will remain active and sensitive if taken daily. Blood serum is important, taking orals on lifting days only and skipping on off days will attribute to less effectiveness and unwanted sides due to spikes, dips and peaks in the blood serum..
The information below is for educational purposes ONLY..
Increase potency of oral steroids ( grapefruit juice increases the bioavailability )
Euro-pharmacies have an addition to a cheap and cost-effective method to help increase the potency and bioavailability of oral steroids.
For some time now, I’ve known about this practice and heard amazing results from people utilizing this protocol, with exceptional results.. I have used this method and seen/felt pronounced effects with the oral I was taking..
This method is also commonly used in the manufacturing process of some pro-hormones, with grapefruit extract added to the binders/fillers!
Grapefruit extract or juice also has this pronounced effect with medications and YES, including steroids!
Grapefruit juice will increase the potency of most oral drugs, including steroids. Here is the article and a blind study
Study-
Does grapefruit juice increase the bioavailability of orally administered sex steroids?
Exciting Objective:
The goal is to determine the extent to which grapefruit juice can enhance the bioavailability of orally administered steroids.
Innovative Design:
They conducted a pilot pharmacokinetics study at the Department of Obstetrics and Gynecology and the Institute of Pharmacology, Medical Faculty, Palacký University, Olomouc, and the Department of Nuclear Medicine, University Hospital, Olomouc.
Cutting-Edge Methods:
They administered 2 mg of estradiol valerate and 100 mg of micronized progesterone to eight healthy postmenopausal volunteers. Samples were collected at various time points after tablet application. The trial was repeated a week later, with tablets swallowed alongside 200 ml of grapefruit juice. Serum levels of estradiol and progesterone were measured using RIA. Statistical analysis was performed using the Wilcoxon nonparametric paired test.
Exciting Results:
The results showed that grapefruit juice slightly increased serum levels of estradiol and progesterone. With a statistically significant increase in estradiol levels 24 hours after tablet application. The mean area under the curve (AUC) of estradiol increased by 117%. While the AUC of progesterone increased by 125%, this was not statistically significant due to individual variability in response.
CONCLUSIONS:
Our results suggest that grapefruit juice may increase the bioavailability of orally administered estradiol and progesterone. The response varies markedly between individuals. This observation may be of some importance also for users of OC and HRT.
Grapefruit juice has been found to interact with a variety of medications. A discovery was made unexpectedly in 1989 during a study focused on the effects of ethanol on a calcium-channel blocker. The surprising outcome was later attributed to the grapefruit juice itself rather than the alcohol. Over the past decade, the number of drugs known to interact with grapefruit juice has grown, leading to a recent warning from Health Canada.
The interaction: Just 250 mL of grapefruit juice can alter the metabolism of certain medications. This interaction occurs due to a shared pathway involving a specific enzyme, cytochrome P450 – CYP3A4 – found in both the liver and the intestinal wall. Research indicates that grapefruit juice primarily affects the intestine.
Upon consumption, a compound in grapefruit binds to the intestinal enzyme. Hindering initial metabolism and causing a sustained decrease in CYP3A4 protein levels. Within 4 hours, a reduction in effective CYP3A4 concentration occurs, with effects lasting up to 24 hours. This leads to inhibited drug metabolism in the intestine and increased oral bioavailability. Even separating the intake of the drug and juice does not prevent interference due to the prolonged response.
Individuals vary in their expression of CYP3A4, with those having higher intestinal concentrations being more susceptible to grapefruit juice interactions. The effects are seen with both the whole fruit and its juice, so caution is advised when consuming either.
There has been some buzz about the potential benefits of adding grapefruit juice to a drug regimen to boost oral bioavailability. However, the tricky part is that each patient may respond differently. But fear not! If we can figure out the specific chemical in grapefruits that inhibits CYP3A4, we might just be able to control this process in a more precise manner.
So, what’s the deal with grapefruit juice and drug interactions? Well, most of the data we have comes from studying a small group of healthy volunteers. Due to this limited information and sporadic case reports, it’s tough to say how this all plays out for individual patients. It seems like the interaction mainly affects oral medications that share the CYP3A4 metabolism pathway, leading to increased bioavailability, higher drug levels in the blood, and potential side effects.
Doctors, it’s time to step up your game! Keep a close eye on your patients’ medication lists and make sure to warn them about any potential grapefruit-related mishaps. Check out Table 1 for a list of medications that don’t mix well with grapefruit. And for those drugs that share the CYP3A4 pathway but don’t have a clear clinical impact. just advise your patients to tread lightly with the grapefruit and watch out for any signs of trouble. Stay sharp, folks!
Grapefruit juice?drug interactions
The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational downregulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice.
Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6′,7′-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.
Introduction
The opportunity for a food-drug interaction is an everyday occurrence. The interaction can be particularly important when total drug absorption is altered. Recently, a chance observation led to the finding that grapefruit juice can markedly increase the oral bioavailability of a number of medications [1]. This article retraces discovery of this novel interaction and reviews the mechanism of action, summaries both studied and predicted medications for an interaction, discusses possible active ingredient(s) in the juice and considers clinical implications
Discovery
Originally, a study was designed to test for an interaction between ethanol and the dihydropyridine calcium channel antagonist, felodipine [2], an analogue of nifedipine. Grapefruit juice was chosen to mask the taste of the ethanol following an assessment of every juice in a home refrigerator one Saturday evening. White grapefruit juice, particularly double-strength juice (single dilution of frozen concentrate), was the most effective. The combination of a non-intoxicating dose of ethanol and felodipine resulted in lower standing blood pressure and a high frequency of orthostatic hypotension compared with felodipine alone in patients with untreated borderline hypertension [2].
Although plasma felodipine concentrations were not different between treatments, they were several-fold higher than observed in other pharmacokinetic investigations with the same dose of drug. A systematic examination for obvious possible causes, such as incorrect dose or drug assay problems, did not resolve this discrepancy and eventually resulted in a pilot project in a single volunteer to judge the role of the juice. Plasma felodipine concentrations were more than five-fold greater with grapefruit juice compared with water .
Grapefruit juice?drug interactions
The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax.
The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with the highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride, and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6′,7′-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.
Introduction
The opportunity for a food-drug interaction is an everyday occurrence. The interaction can be particularly important when total drug absorption is altered. Recently, a chance observation led to the finding that grapefruit juice can markedly increase the oral bioavailability of a number of medications [1]. This article retraces discovery of this novel interaction and reviews the mechanism of action, summaries both studied and predicted medications for an interaction, discusses possible active ingredient(s) in the juice and considers clinical implications
Exploring the twists and turns of felodipine metabolism is like embarking on a thrilling adventure through the body’s pathways. And what better sidekick to accompany us on this journey than grapefruit juice?
The tale begins with a groundbreaking discovery that grapefruit juice, unlike its citrus cousin, orange juice, has the power to triple the mean plasma felodipine area under the curve in borderline hypertensive patients. This results in a rollercoaster of effects, from increased heart rate to a surge in vasodilatation-related adverse events. Grapefruit juice may elevate plasma peak felodipine concentration, but fear not – it won’t mess with the drug’s elimination half-life.
But how does grapefruit juice work its magic? By inhibiting presystemic drug metabolism, of course. This leads to a reduction in the dehydrofelodipine/felodipine AUC ratio and an increase in absolute dehydrofelodipine AUC. It’s like grapefruit juice is playing a game of metabolic hide-and-seek with our bodies, inhibiting one pathway after another.
In a recent twist, a study revealed that grapefruit juice doesn’t just stop at the small bowel – it also takes a swing at the liver’s drug metabolizing enzymes. After just 5 days of grapefruit juice consumption, small bowel enterocyte CYP3A4 and CYP3A5 protein content took a nosedive, leading to a dramatic increase in felodipine AUC and Cmax. It’s like grapefruit juice is the superhero of the metabolic world, swooping in to shake things up.
So, next time you reach for that glass of grapefruit juice, remember – you’re not just quenching your thirst, you’re embarking on a wild ride through the pathways of felodipine metabolism. Cheers to the power of citrus!
The impact of grapefruit juice on CYP3A isoforms goes beyond simple competition for substrate metabolism. It seems that grapefruit juice is playing a sneaky game with our enzymes, decreasing CYP3A4 protein content through a post-transcriptional mechanism. This could involve speeding up CYP3A4 degradation, leaving us in need of some fresh enzyme synthesis to get back to business. It’s like a molecular soap opera!
Research has shown that the effects of grapefruit juice can linger for quite some time. Drinking a glass of juice before taking felodipine can lead to a significant increase in drug levels, with the peak interaction happening between simultaneous consumption and 4 hours prior. The grapefruit juice effect slowly fades away over time, with a half-life of around 12 hours. Even if you sip on some juice a whole day before taking felodipine, you might still see a boost in drug levels.
In some studies, regular grapefruit juice consumption has been shown to have a substantial impact on felodipine levels. Drinking juice three times a day for 5 days can really amp up the drug levels, showing a cumulative effect that can’t be ignored. The variability in the interaction among individuals is quite fascinating, with some seeing no change and others experiencing a six-fold increase in drug levels. It’s like a game of genetic roulette!
So, next time you reach for that glass of grapefruit juice, remember that it’s not just a refreshing beverage – it’s a molecular mischief-maker that can shake things up in your body. Cheers to the power of citrus!
Conclusions
So, drinking a single glass of grapefruit juice can mess with your medications in ways you never even imagined. Who knew that something as innocent as grapefruit juice could have such a big impact on your body? Turns out, grapefruit juice can mess with how your body absorbs and reacts to a whole bunch of different medications, even if you drank it hours before taking your meds. It does this by messing with some enzymes in your small intestine that help break down drugs before they even get into your bloodstream.
This whole grapefruit juice-drug interaction thing is especially important for medications that can have their concentration in your blood doubled, or have a narrow range of effectiveness. If you’re someone with a lot of those enzymes in your small intestine, or if your liver isn’t working so great, or if you already have some other health issues, you might be even more at risk for grapefruit juice messing with your meds.
And get this – your friendly neighborhood grocer isn’t going to ask you about your medical history before selling you that grapefruit juice. So, it’s up to your doctor, pharmacist, or other health pros to warn you about mixing grapefruit juice with your meds.
But hey, maybe someday we’ll figure out exactly what it is in grapefruit juice that causes all this chaos. Then we can start looking at other foods that might do the same thing, or maybe even put that grapefruit juice magic into some new medications. Until then, we’ll just have to keep studying how grapefruit juice messes with our meds when we drink it in normal, safe amounts. Who knew that a random discovery about grapefruit juice making a blood pressure med work better could lead to all this new research and better drug treatments? Life is full of surprises, isn’t it?