T Nation

Grapefruit Juice & Supps/Meds


#1

Okay this is an old subject reasked in regards to grapefruit juice and the effects it has on meds and supps. As we all know grapefruit juice has a substance called bergamottin which inhibits the P450 cytochrome enzyme. This enzyme apparently degrades cetain meds and supps within the intestine. It was discovered that by inhibiting this enzyme the half lives of meds could be increased as well as the amount absorbed. I'm not really all that keen on the subject but I know enough to understand that it in some way acts as an "octane" booster..so to speak.

My questions are: Does the inhibition of the P450 enzyme affect the half life and blood level concentration all meds and supps taken? What is the clearence rate of bergamottin itself..I ask this 'cause say one is on particular meds and they need to be wary of the timing. And lastly should one be worried about long term P450 enzyme inhibition..say if one were to drink grapefruit juice or take bergamottin extract on a daily basis?

I'm curious cause if it does hold true to increasing the efficacy and amount absorbed of most supps (say HOT-ROX) then it would be nice to take less yet with the same effects as a regular dose.


#2

Those are some very good questions. I don't know too much about the P450 enzyme system, only that enzyme activity levels vary from person to person. I think it was found that about 7% of the population lacked sufficient enzyme activity to metabolize the SSRIs.

As for the clearance rate of bergamottin and long term enzyme inhibition, I can't really help you there.


#3

Does the inhibition of the P450 enzyme affect the half life and blood level concentration all meds and supps taken?

No, just those medications and supplements which are partially or fully metabolized by the P450 3A4 and are taken orally. If you take high doses of grapefruit juice, 1.2 L of regular grapefruit juice daily, this can also inhibit the hepatic variant and would impact IV, buccal or transdermal preparation.

What is the clearence rate of bergamottin itself?


The CYP 3A4 inhibition is not solely due to begamottin or its derivative DHB, but other compounds have been implicated such as resveratrol and furanocoumarins. Its specific clearance rate is therefore of little importance, the overall effect on enzyme inhibition seems to be of sufficient importance between 24 to 48 hours. To be on the safe side, you should think that bergottamin could have an effect up to 48 hours.


If you are on a med that interacts with it, it has been shown that taking your grapefruit juice and taking your medication at a different time during the day still has interaction effects. (Some few people are unresponsive to grapefruit juice and it wouldn?t matter to them, but only research labs have access to that kind of equipment to test that possibility).


And lastly should one be worried about long term P450 enzyme inhibition..say if one were to drink grapefruit juice or take bergamottin extract on a daily basis?


Actually there is very little research on that issue, most of it being directed towards the acute effect of P450 3A4 inhibition. However, some preliminary evidence in rats seems to show that long term use could induce the hepatic enzyme (boost in quantity or efficiency of the enzyme) since it has been blocked so much it tries to compensate by making more or making it work better. So yes, there probably is an effect. Would it be reversible, possibly. We have to wait for more research.


I'm curious cause if it does hold true to increasing the efficacy and amount absorbed of most supps (say HOT-ROX) then it would be nice to take less yet with the same effects as a regular dose.


This is one aspect that is being investigated:

Copied and paste from the link below

There is a consideration to make the use of grapefruit juice-drug interaction to improve the drug efficacy and to save cost for expensive medicines. It might be feasible if we have fully understood its mechanism of action, and are also able to control the amount and vari ance of the causative components.

Since there are increased evidence that the causative components differ depending on the drug affected, and under certain conditions, grapefruit juice may also affect hepatic P450[39], it is too impulsive now to apply grapefruit juice into clinical practice.

Guo LQ et al / from the Acta Pharmacol Sin 2004 Feb; 25 (2): 129-136
Review
Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines

http://www.chinaphar.com/1671-4083/25/129.htm

Hope this helps,
AlexH.


#4

Never take grapefruit juice or the concentrated supplements with HOT-ROX. I've gone over this a bit before, but one of the major problems is that it's not selective in terms of the isoenzyme it inhibits. Cyp3A4 yes, but many others, including Cyp1A2 which is a relevant when talking about caffeine and other xanthine metabolism. The other problem is that there's no way to predict to what degree the grapefruit juice will increase peak concentrations of the given compound and this can be very dangerous. As far as I have seen, generally speaking, they'll simply increase peak plasma concentrations, no effect upon half-life, no effect upon time to peak concentration.