Thread: grape fruit juice makes some gear stronger

I was recently asked about this .. this is a copy and paste of my reply .. Also I dont know if the exact rate of increased absorption can be truly estimated .. ( it will vary from person to person)..


There is evidence that a chemical in grapefruit juice inhibit a cytochrome enzyme known as CYP3A4 .. CYP3A4 is a very important enzyme to degrade things from this system ...

Only certain drugs ( ones that use the CYP3A4 pathway) are effected by grapefruit juice ..

You see MANY steroidal compounds do go by route of CYP3A4 .. which means that you should likely adjust your dose( if using grapefruit juice).. Or you could see GREATLY increased effects .. Keep in mind though as potency is increased. So is the potential of side effects ..

Grapefruit juice is a CYP3A4 inhibitor.... things that require this enzyme for first pass processing dont get processed the same way ..

Grapefruit Juice Drug Interactions

This food-drug interaction was actually discovered by accident. A study that was intending to test the interaction of alcohol and a blood pressure medication used a mixture of alcohol with grapefruit juice to disguise the taste of alcohol for the study. Ironically, alcohol had no effect on the tested medication, but the grapefruit juice seemed to enhance the absorption of the drug. The researchers then confirmed the finding by comparing drug levels when taken with either grapefruit juice or water and found five-fold higher blood levels of the drug when it was taken with juice. Orange juice did not show this effect.

Grapefruit juice inhibits a special enzyme (CYP3A4) in the intestines that is responsible for the natural breakdown and absorption of many medications. When the action of this enzyme is blocked, the blood levels of these medications increase, which can lead potentially toxic side effects from the medications.

Research has suggested that flavonoids and/or furanocoumarin present in grapefruit are the substances that act to block the enzyme in the intestines that normally metabolizes many drugs.

Some medications that interact with grapefruit juice:
-Statins (Cholesterol Lowering Drugs)
-Antihistamines: Terfenadine
-Calcium Channel Blockers (Blood Pressure Drugs):
-Anti-convulsant: Tegretol (Carbamazepine)
-Anxiolytics: Valium (Diazepam)
-Anti-depressant: Sertraline Clomipramine
-Cortico-steroids: Methylprednisolone
-Oestrogens: Ethinyl estradiol
-Anabolic Steroids: Dianabol
-Impotence Drug: Viagra



rapefruit juice interacts with a number of medications. This unusual discovery was made serendipitously in 1989 during an experiment designed to test the effect of ethanol on a calcium-channel blocker.1 The observed response was later determined to be due to the grapefruit juice delivery vehicle rather than the alcohol. In the past decade, the list of drug interactions with grapefruit juice has expanded to include several classes of medication, precipitating a recent advisory from Health Canada.2

The interaction: As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine.4

After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression.5 Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours.6 The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.

Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice–drug interactions.5 An effect is seen with the whole fruit as well as its juice, so caution should be exercised with both.7 The precise chemical compound in grapefruit that causes the interaction has not been identified. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect.8 A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.9

There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability.3 The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.

What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports,10 it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.

Physicians should review medication lists often, with the goal of warning patients about adverse interactions. A list of medicines with which patients should not consume grapefruit is provided in Table 1.3,11,12 In the case of several medications that share the CYP3A4 metabolism pathway, but for which a clinical effect has not been elucidated or is theoretical, patients should be advised to consume grapefruit cautiously and be monitored for toxicity.


pretty cool

Yep,
I tell my patients to avoid grapefruit juice while taking statins because of the same effect.