To All

I originally started this thread with a quote from HealthCentral about the mixing of herbs and medicines and mentioned the problems with grapefruit. I received the following private post which I have received permission to post. The original post was dated Sept 7, 1999.

It is a story to remember and one of the reasons why one must be careful. This man was administered his last rites - well you read the story.

The original post is on the page immediately before this one. Go to Herbs And Drugs: Never Mix, Never Worry

There is a second post below this one and a link to a Grapefruit Juice web site.

Don

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Don,

I am particularly appreciative of your post regarding drug-food, drug-supplement interactions. Let me give you the specifics of the Grapefruit interaction you mentioned.

In April 1996, almost exactly one-year before my CaP was diagnosed, I turned myself in to the emergency room at Alta Bates MC in Berkeley, California. I was suffering from severe hypotension. I spent the following 7 days in ICU, the first 4 days unconscious, with an aortic pump in my heart and mechanical ventilation. I was released without a clue as to what caused my hospitalization. BTW, the bills added up to nearly $100,000. Thank God for Medicare and Blue Cross.

About a month after my release the Contra Costa Times medical columnist, Dr. Donohue, answered a letter from a woman who wrote that she had heard something about an interaction between grapefruit juice and the calcium channel blocker, Procardia (nifedipine). It took my wife a week of pestering to get me to read the column, and when I did, I looked up and said "My God, do you realize that I had consumed about 2 quarts of Grapefruit juice that morning, although over about a 4-hour period?" My situation was aggravated by the fact that I had consumed a large amount of grapefruit juice, and I was taking TWO calcium channel blockers, Procardia XL 60 (nifedipine) and Calan SR 240 (verapamil). In retrospect this was probably too high a dosage of these two medication.

I began to search for answers to this remarkable reaction. I found answers in several places, Dr. Koop's "Self Care Advisor" and a book written by a husband and wife team, Joe and Teresa Graedon, "The People's Guide to Deadly Drug Interactions." Joe and Terry are both pharmacists and have a weekly PBS radio show out of the Carolinas called "The People's Pharmacy." I wrote Joe and told him of my experience. It took about a month to make it from the publisher's office to Joe. He then called me and asked me to be a contributor to his radio show. He then was responsible for two NBC television crews arriving at our doorstep to film the story and a one-page article in "Modern One of the film crews was from NBC Dateline, and the other was NBC Extra. Unfortunately, the first was preempted by the murder of Bill Cosby's son and the second by the mass suicide of the Hale Bopp folks in San Diego. The second was aired at 2:00 am the following morning, however. It gave me an opportunity to tape it at least. My 4 minutes of fame.

The interaction was discovered by two Canadian researchers who were attempting to identify the interaction between Procardia and alcohol. Neither was a drinker so they used concentrated grapefruit juice (added one or two cans of water to the frozen juice instead of three) to mask the taste of the alcohol. They were using themselves as guinea pigs. They noted a remarkable rise in the bioavailability of the calcium channel clocker. To shorten the story, GF juice blocks an enzyme in the liver cytochrome 450 if my memory serves me, causing a 5 to 9 times increase in the blood levels of the drug, resulting in an unintentional overdose. This discovery was reported in the British medical journal, the Lancet, in 1991. The manufacturer refuses to acknowledge the interaction.

My wife and I have dedicated much effort to spread this word. Many physicians still deny it, although it has been reported in a number of health newsletters, including Tufts University and Harvard.

It makes me furious when I see the full-page ads run by the Florida Citrus Growers, stating that GF juice is an important part of a heart-health diet. No caveat, such as "so long as you are not taking calcium channel blockers. In the corner of the ad you will see the logo of the American Heart Association. My letters to them, objecting to this content go unanswered to date.

Again, thank for your comments. It's unfortunate that vitamins, minerals and herbal supplements are not required to prove their safety and efficacy and potential for interactivity, as are medications which require dispensing by prescription, supervised in their research, development, trials and recommended by a physician.

Hope you're able to wade through this long story Don. The priest came to the hospital the night of my admittance, administered the sacrament of healing (used to be called the last rites) and told my wife to prepare herself, I wasn't going to make it. My four children sat by my bedside and talked to me around the clock until I came to. I would like to spare other families from this sort of experience.

I left the hospital on the 16th of April 1996 and no one knew what had brought me there. Had I died that night, as expected, no one would ever have known about the GF/CCB interaction. How many people do you suppose may already have died, mysteriously, from this interaction?

Picked up my PSA yesterday, 6 months after ceasing 22 months of ADT, still <0.1, T = 212, up from 99 in June. So far, so good.

Thank you for your very great contribution to this (CaP) community.

Jack Haines

Orinda, CA

SI + 532

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Here is an exchange of posts made on the Advanced list.

To all,

There is a website dedicated to grapefruit/drug interactions at: Grapefruit Juice

Following is a post I made to them regarding taking gj to moderate HDK adsorbtion and followint that, their response:

I visited your website to get information about interaction of gj with ketoconozole+hydrocortisone which I am taking for prostate cancer. As a layman, I unfortunately cannot determine whether or not your listing of Itraconazole means it may have a beneficial or a non-beneficial reaction to the administration of ketoconazole. I am hoping that it may delay somehow the absorbtion of the ketoconozole into the bloodstream, lessening to some degree the assault on my liver. I am attempting to take this at 1200 mg/day dosages, but am having trouble with elevated liver enzymes, so am currently at 600 mg/day. Any explanation in layman's terms you can offer would be greatly appreciated.

Thank you very much, Gary

THE ANSWER

Thanks for your question Gary.

Ketoconazole is a type of antifungal medication, but for the treatment of prostate cancer, it also affects hormonal production, and can have a antagonistic effect on testosterone, which can sometimes drive some tumors of the prostate.

Actually, ketoconazole has very similar effects to grapefruit juice in many ways, causing an inhibition of metabolism of other drugs.

Grapefruit juice (GJ) is known to inhibit an enzyme system found in the small intestine that metabolizes some drugs prior to absorption into the bloodstream. This system is called CYP 3A4 and does play a role in the metabolism of certain drugs. Drugs that are affected by this interaction are metabolized less than usual when they are taken with GJ, allowing a higher amount to reach the bloodstream, and this will cause higher drug levels, sometimes with increases in clinical effects or side effects.

GJ also has an effect on another system, called p-glycoprotein. In the case of itraconazole, the blood levels decreased, which is unexpected, based on what I just said above. The theory is that p-glycoprotein is more important for itraconazole uptake into the bloodstream, that the amount of itraconazole metabolized by the 3A4 enzymes.

Ketoconazole has not been directly studied with GJ, so its hard to comment on what to expect, but it is possible that it may be significantly affected by GJ too. The second study of itraconazole showed 40% decreases in total drug exposure for itraconazole. In view of using ketoconazole for treatment of your prostate cancer, I would recommend against taking GJ with ketoconazole since it has not been studied, and we don't know the effects. If it does lower the amount of ketoconazole that you are exposed to, it may undercut the benefit you may be deriving on the treatment of the tumor.

With ketoconazole, sometimes liver enzymes can be elevated with no symptoms. If you do experience any of the following symptoms, inform your doctor immediately: unusual fatigue, major loss of appetite, nausea, vomiting, jaundice, dark urine or pale stools.

Thanks for your question. I hope this information is helpful.

Dean Elbe, B.Sc.(Pharm.) Director, PowerNet Design, Ltd.

Grapefruit Juice