T Nation

Grapefruit Juice Enhancement?


I saw this interesting article over on yahoo and wondered if GFJ would help enhance the effectiveness of supplements?


WASHINGTON (Reuters) - U.S. researchers said they have identified the compound in grapefruit juice that affects how some drugs are absorbed in the body and said on Tuesday it might be used to help lower dosages for some patients.

Grapefruit juice is known for its effects on drug metabolism and is avoided by some patients while other deliberately take their drugs with the juice.

The reason is an intestinal enzyme called CYP3A, which partially destroys drugs as they are absorbed. Grapefruit juice, like no other fruit juice, interferes with CYP3A, so the body ends up absorbing more of the drug.

Dr. Paul Watkins of the University of North Carolina at Chapel Hill and colleagues say they have identified the substance in grapefruit juice that is responsible -- furanocoumarin.

"It should now be possible to market the furanocoumarin-free grapefruit juice to patients who would otherwise need to avoid grapefruit," Watkins said in a statement.

"In addition, it should be possible to screen new foods for the potential for drug interactions by determining whether they contain furanocoumarins," Watkins said.

"Finally, it may be possible to add furanocoumarins to formulations of certain drugs that tend to be poorly or erratically absorbed to improve their oral delivery."

To test the theory that furanocoumarin was the responsible compound, Watkins and colleagues filtered it out grapefruit juice, which they discovered was then less bitter but otherwise unaltered.

Then they tested 18 men and women taking various drugs on a regular basis including aspirin and birth control pills.

Each fasted in the hospital and got a single dose of the blood pressure drug felopidine, sold under the brand name Plendil, along with either normal grapefruit juice, furanocoumarin-free juice or orange juice.

They then ate and drank normally and blood was taken regularly all day.

In each volunteer, the normal grapefruit juice made between 6 percent to 230 percent more Plendil available in the blood, the researchers reported in the American Journal of Clinical Nutrition. The furanocoumarin-free grapefruit juice and orange juice had no such effect, they reported.


Years ago in MM2K Dan Duchaine recommended drinking canned grapefruit juice to aid in cutting. I did drink it during cutting cycles, but it was combined with an ECA stack and dietary changes, so i'm not sure if it was helpful or not.

Has it been proven/disproven that it helps? Anyone?


hehe... I read, and did, the exact same thing. Seems like I jittered more with the Grapefruit juice.


He was thinking of Naragenin (another constituent of gf juice)which slows the rate that methylxanthines (caffeine and others) are converted to para-xanthines by the hepatic system (liver). The original use was inteh grapefruit diet which used grapefruit to prolong the effects of black coffee's fat burning.


Grapefruit juice (I think) interfears with the breakdown of caffine. For me I keep the BUZZ longer.


The grapefruit juice doesn't interfere with the absorbtion of caffeine. The reduction of the enzyme CYP3A allows more of the caffeine to be absorbed, hence it stays active longer. I've been using gfj for years now with all of the supplements I take. If you take supplements/drugs that attenuate in a short period of time using gfj will slow the rate at which you have to titrate the dosage upward.


correct me if i'm wrong, but the way i read that article is that GFJ helps keep your stomach from destorying a portion of whatever you take in.

so if you are taking creatine, or protien, or whatever sup.. your body will absorb more of it.

or am i mis-understanding what it's saying?

so to me, it would be a good idea to drink a glass of GFJ before taking your supp's?
(but that's going off that article)


This is incorrect.

The most abundant flavanoid in GFJ Naragenin (or to be more accurate naringin which converts in the body to naragenin) is not effecting the absorption of caffeine, its slowing the rate in which the liver converts caffeine to paraxanthine (aka 1,7-dimethylxanthine. Paraxanthine is the major metabolite of caffeine. Although is has stimulatory effects they are less than caffeine. It has been discussed that it offers the same benefits of caffeine but its debatable.

The same occurs with ingestion of gfj (and other concentrated sources of Naringin-naragenin) to other methylxanthines like theobromine and theophylline.

Baily, Grapefruit Juice and Drugs. Clin. Pharmacokinet. 26:91-98, 1994.

Yusof, Naringin Content in Local Citrus Fruits. Food Chemistry. 37:113-121, 1990.

Paraxanthine (metabolite of caffeine) mimics caffeine's interaction with sympathetic control of thermogenesis
A. G. Dulloo, J. Seydoux and L. Girardier
Department of Physiology, University of Geneva, Switzerland.


In a nutshell, grapefruit products where they have been processed enough to provide adequate levels of flavanoids like naringin (naragenin) interfere with some of the enzymes responsible for the breakdown of many nutrients, increasing the blood level of certain compounds by enhancing both their oral uptake and increasing their half-life in the body.

Like the caffeine to paraxanthine issue I spoke about above.


i hear that gfj is great for dieting, although i hadn't heard all of this before. so if i take my supps (creatine specifically) w/ gfj, the acidity won't affect the supp and/or absorbtion much or at all?
i always understood that gfj itself is good for losing weight. what are some good sources for more info about this stuff? or should i just look through medical and health journals?
good info!


I beg to differ.

Interfere - to act in a way that impedes or obstructs.

What is incorrect is the suggestion that naringin is responsible for the effects and that the reduction of the intestinal CYP3A4 protein by furanocoumarins is not. The studies you posted are outdated. Here is a more current one that refutes your statments in both this quoted post and your follow up post.



LOL that's not what I said or meant. I was discussing a point you made not 'refuting' the original points as you state. Also that study you quote is poor, the total number of subects and methodology is weak.

Rather than just trash what I said and come back with the cliched 'oh the studies are old' one, why not take some time to explain your reasons (like I did) rather than blow a load of smoke around your reply.


"The most abundant flavanoid in GFJ Naragenin (or to be more accurate naringin which converts in the body to naragenin) is not effecting the absorption of caffeine,its slowing the rate in which the liver converts caffeine to paraxanthine (aka 1,7-dimethylxanthine. Paraxanthine is the major metabolite of caffeine. Although is has stimulatory effects they are less than caffeine. It has been discussed that it offers the same benefits of caffeine but its debatable.

The same occurs with ingestion of gfj (and other concentrated sources of Naringin-naragenin) to other methylxanthines like theobromine and theophylline.


Also just let me get this clear....this block I just re-posted...are you saying its wrong this bit or does that not fit in with you trying to debunk what I said just for the sake of it ?


Lets not turn this into a pissing contest. In essence you and I are in agreement.

What we disagree on is the mechanism of action. The grapefruit effect is not a new phenomenom to me. I've been familiar with its effects since 1990. I initially assumed that it was the naringin that caused the effect and the studies at the time all suggested probable correlation. All the new studies suggest furanocoumarins supress intestinal CYP3A4 proteins allowing for greater absorbtion of certain compounds. Interestingly, according to the studies that I have read CYP3A4 is also found in the liver, but it is not suppressed by grapefruit juice.

The following link is a news report of a study published in the American Journal of Clinical Nutrition on May 9th. I don't think the AJCN would publish a poor, methodologically weak study. This is just one of many you will find supporting the current hypothesis that it is supression of intestinal CYP3A4 by the furanocoumarins in grapefruit juice that increases the absorption of certain drugs.


This is a moot point as more caffeine is absorbed through the intestinal track allowing a higher concentration of it to make its way to the liver thus increasing the strength/duration of the caffeine regardless of naringin's slowing of the conversion rate in the liver. A simple way to test this is to take a caffeine tablet with water and record the effect. A day later (ensuring that all the variables are controlled, ie: timing of last meal before ingestion, time of day, etc.) take a caffeine tablet with grapefruit juice and record this effect. If your assertion is correct caffeine's effects will be slightly diminished, but prolonged. If my assertion is correct you will notice an increase in caffeine's effects as well as duration. You can get back to me with the results of this test if you choose to do so.

...and trying to debunk what you said? It was you that suggested my reponse to Phileaux was incorrect. I stand by my original post.

Lastly, in response to the original poster Blitzkrg ... yes your assumption is correct, but realize that gfj's effectiveness varies depending upon the drug/supplement you are taking with it. Absorption rate increases between 8% and 937% have been recorded with various drugs, so be extremely careful. Do not use it with any drug to which adverse effects have been observed. A simple search on the internet will provide you with this info.


I actually did something similar with people for an assignment, the results were conjecture and partial nonsense.

Get some T-Nationers to try it again though, but they'd have to abstain from caffeine for 48hrs before to get the best result each test.


I thought the largest concentrations were found in the liver. With the intestines and other instances are lesser, I also thought CYP3A4 was the most abundant of all the CYPs in the liver.


As part of the cytochrome p450 enzymes it is found in the largest concentrations in the liver, but the furanocoumarins work by suicide inhibition of the CYP3A4 proteins in the intestinal track.

Recently, results of an investigation by Lown et al. (1997) gave further support to this
hypothesis. In this in vivo study, consumption of grapefruit juice t.i.d. for 5 days resulted in a mean 62% reduction in small intestinal enterocyte CYP3A4 protein content and a 3-fold and 5- fold increase in felodipine AUC and Cmax, respectively. In contrast, no changes occurred in small-intestine levels of CYP3A4 mRNA, or liver CYP3A4 activity as measured by the erythromycin breath test (ERMBT), in small-intestine levels of P-gp, or in colon levels of
CYP3A5. Further, intestinal CYP2D6 and CYP1A1 protein content remained unaltered.

It was concluded from the decreased CYP3A4 expression in the gut wall that the grapefruit-juice effect is not only based on competitive inhibition. Because small intestine CYP3A4 mRNA
was not altered, grapefruit juice probably reduced CYP3A4 protein content by a post transcriptional mechanism, possibly by accelerated CYP3A4 degradation through mechanism based (suicide) enzyme inhibition. Thus, the restoration of CYP3A4 activity would require de novo enzyme synthesis (Lown et al. 1997).

Lown et al.
Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein
expression. J Clin Invest 1997;99:2545-53

Stig, I have read similar conclusions in about 5 studies. Hopefully this one example will be adequate as I currently have limited time and reading another large document for reference is out of the question.


would this same principle apply to protien absorption? understanding o% of the science i would like to know.


im going to start mixin my creatine with it!


'If' it helped in the manners described above the fact is acidic would present probs. It was thought in the past that neutralising the stomach acid a little by taking ant-acids before taking creatine would benefit uptake. But I don't know that much about it.