THE GRAPEFRUIT EFFECT

Since I joined the forum, a few weeks ago, I've asked numerous questions. Some have met with helpful/informative/amusing answers but quite a few have been left hanging in the air. Of the latter, there is one on a topic I believe to be so important that I feel I should flag it again. In my first ever posting here, on 29th Nov, in the thread "Recovering from radical nephrectomy" I put the question:

4. Has anyone been warned of "The Grapefruit Effect" (that is the dramatic potentiation of some medicines and the attenuation of others by grapefruit juice - so that the effective dosage of your meds. gets screwed up)?

No-body seemed to be aware of this phenomenon - a little surprising since if you put a search into Google in terms like 'the grapefruit effect' you'll get something approaching 20 million sites - which should offer enough to even the most voracious reader. I offered a url for a succinct account of the key facts.

http://www.eurekalert.org/pub_releases/2008-08/acs-nrt072308.php

To save members the bother of hunting anything down, here are a couple of excerpts from different websites to give you the general idea.

PHILADELPHIA, Aug. 19, 2008 — Scientists and consumers have known for years that grapefruit juice can increase the absorption of certain drugs — with the potential for turning normal doses into toxic overdoses. Now, the researcher who first identified this interaction is reporting new evidence that grapefruit and other common fruit juices, including orange and apple, can do the opposite effect by substantially decreasing the absorption of other drugs, potentially wiping out their beneficial effects.
The study provides a new reason to avoid drinking grapefruit juice and these other juices when taking certain drugs, including some that are prescribed for fighting life-threatening conditions such as heart disease, cancer, organ-transplant rejection, and infection, the researcher says. These findings — representing the first controlled human studies of this type of drug-lowering interaction — were described today at the 236th National Meeting of the American Chemical Society.

and

Grapefruit juice boosts drug's anti-cancer effects

April 20, 2009

In a small, early clinical trial, researchers at the University of Chicago Medical Center have found that combining eight ounces of grapefruit juice with the drug rapamycin can increase drug levels, allowing lower doses of the drug to be given. They also showed that the combination can be effective in treating various types of cancer.

For two decades, pharmacists have pasted do-not-take-with-grapefruit-juice stickers on various pill bottles because it can interfere with the enzymes that break down and eliminate certain drugs. This interference makes the drugs more potent. In data presented at the AACR 100th Annual Meeting 2009, the Chicago researchers examine ways to exploit this fruit's medication-altering properties.

"Grapefruit juice can increase blood levels of certain drugs three to five times," said study director Ezra Cohen, MD, a cancer specialist at the University of Chicago Medical Center. "This has always been considered a hazard. We wanted to see if, and how much, it could amplify the availability, and perhaps the efficacy of rapamycin, a drug with promise for cancer treatment."

This trial was designed to test "whether we could use this to boost rapamycin's bioavailability to the patient's advantage, to determine how much the juice altered drug levels, and to assess its impact on anti-cancer activity and side effects," he said.


Later in the article this is stated:

"This study showed that substances known a furanocoumarins, plentiful in some forms of grapefruit juice, can decrease the breakdown of rapamycin. This makes the drug reach higher levels in the bloodstream, two to four times the levels seen without a juice boost, and thus increases the amount of the drug that reaches its targets.

"That means more of the drug hits the target, so we need less of the drug," said Cohen.

Many of the newer cancer medications, precisely focused on specific targets, are now taken as pills rather than intravenously. Some of these drugs, including rapamycin, can cost thousands of dollars a month. Hence, "this is an opportunity for real savings," Cohen said. "A daily glass of juice could lower the cost by 50 percent." "

It doesn't take much imagination to realise that drastically reducing the cost of an adjuvant therapy will make it much more likely that we can get it and that it will amplify the resources available for more R & D to make continuing progress - this at a time when AstraZeneca is announcing large job losses because, following Pfizer, it has disastrous pipeline problems (no drugs in the pipeline to replace the money-spinners on which their patents are about to run out). Eli Lilly is also, seemingly, approaching a potentially catastrophic patent cliff-edge.

I don't know whether the multiplier effect of the grapefruit juice, leading to lower drug doses, will also help reduce the side effects - wouldn't it be great if it does?

I am sure there are members here taking meds. that are affected by grapefruit juice and it would seem a smart move to consult appropriate experts to ensure that this effect is being taken into account.

Finally, another factor of truly huge importance for some drugs is the time of day they are taken. With some meds. the effect of diurnal/circadian rhythms (i.e. our body clocks) is such as to make a really large difference in their efficacy depending on when in the day they are taken. There is a burgeoning new area of science called chronopharmocology which addresses such issues.

I don't know how much variability there is between individuals in these phenomena and anyone who can educate me on the issue will command my gratitude.