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Beware of Pomegranate juice

I have just had a bad experience with it. It is like grapefruit juice as it doesn't get along with some of our medications. They are in the same family, which I didn't know until today. I have been dealing with the side effects of it since Saturday. I am starting to feel better but I thought I better put the word out about it.

hi... will research ... need info

ehhh, hi i'm waves, there, we've been introduced :D

i will research this - i am aware of grapefruit juice reactions with carbamazepine for instance (GF juice to be avoided). but have not seen/heard about pomegranate interactions before. it is used in the case of urinary tract infections, which makes me think kidneys but this is all imagination so far... Mrs D. might know something about this...

anyway, i'll check it out - it would help to know:

what meds are you taking (and how much)?

i hope you will be ok. good idea to raise a flag about this.

~ waves ~ from all over the place

Here is an article I just ran across.

Pomegranate Juice Interacts With Medications

From Cathy Wong,
Your Guide to Alternative Medicine.

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About.com Health's Disease and Condition content is reviewed by our Medical Review Board
The pomegranate, once considered exotic, is now immensely popular. Pomegranate juice is found in almost every grocery store in North America.

But a report published in the September 1 2006 issue of the American Journal of Cardiology suggests that we don't know enough about how pomegranate interacts with common medications.

A 48-year-old man was taking ezetimibe (trade name Zetia) 10 mg a day and rosuvastatin (trade name Crestor) 5 mg every other day for 17 months. Both medications are used to treat high cholesterol.

He began drinking pomegranate juice (200 ml twice weekly) and three weeks later, was admitted to emergency with thigh pain and an elevated serum creatine kinase level (138,030 U/L, normal < 200 U/L). Both are symptoms of rhabdomyolysis, a serious condition that causes the breakdown of muscle fibers and may lead to kidney failure.

Rosuvastatin belongs to a group of medicines called HMG-CoA reductase inhibitors, or ‘statins’. Grapefruit juice is known to increase the risk of statin-induced myopathy, but up until now, there was little information about whether pomegranate juice might also increase the risk.

Pomegranate juice and grapefuit juice, are both known to block the cytochrome P450 3A4 enzyme systems in the intestines. By inhibiting these enzymes, the juices may increase blood levels of many medications.

Potential Pomegranate-Drug Interactions

Antiarrhythmics - Amiodarone (Cordarone), disopyramide (Norpace), quinidine
Calcium channel blockers - Felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia), nimodipine (Nimotop), nisoldipine (Sular)
Statins - Atorvastatin (Lipitor), lovastatin (Mevacor), simvastatin (Zocor)
Immunosuppressants - Cyclosporine (Sandimmune, Neoral), tacrolimus (Prograf)
Protease inhibitors - Saquinavir (Fortovase)

However, pomegranate juice may also interact with medications not on this list. The drugs ezetimibe and rosuvastatin are not thought to be broken down by cytochrome P450 3A4.

Based on the limited evidence about the potential drug interactions, it would be wise to talk with your doctor if you use pomegranate products regularly, and to avoid taking pomegranate products within 72 hours of taking the above medications.

Sources

Hidaka M, Okumura M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Setoguchi N, Arimori K. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metabolism and Disposition. 33.5 (2005):644-8.

Kim H, Yoon YJ, Shon JH, Cha IJ, Shin JG, Liu KH. Inhibitory effects of fruit juices on CYP3A activity. Drug Metabolism and Disposition. 34.4 (2006):521-3.

Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. American Journal of Cardiology. 98.5 (2006):705-6.
Updated: September 19, 2006

I looked this up...

and found conflicting data:

1) http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum
Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice.

2)

Quote:

Drug Metab Dispos. 2007 Feb;35(2):302-5. Epub 2006 Nov 28.Click here to read Links
Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.
Nagata M, Hidaka M, Sekiya H, Kawano Y, Yamasaki K, Okumura M, Arimori K.

School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka City, Miyazaki, 882-8508, Japan. m-nagata@phoenix.ac.jp

In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4'-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9. The addition of 25 microl (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In addition, we investigated the effect of pomegranate juice on the pharmacokinetics of tolbutamide (substrate for
) in rats. Relative to the control group, the area under the concentration-time curve was approximately 1.2-fold greater when pomegranate juice (3 ml) was injected p.o. 1 h before the p.o. administration of the tolbutamide (20 mg/kg). The elimination half-life of tolbutamide was not altered by pomegranate juice administration. These results suggest pomegranate juice ingestion inhibits the intestinal metabolism of tolbutamide without inhibiting the hepatic metabolism in rats. Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.

PMID: 17132763 [PubMed - indexed for MEDLINE]

Only problem here is tolbutamide is not used much anymore.

3) here is a handy chart showing various metabolic pathways:
http://www.healthanddna.com/drugchart.html
The one for pomegranate juice is CYP2C9
Remember, that lists like this are subject to change.

Here is a chart just for grapefruit juice:
http://www.fhma.com/grapefruit.htm

4) here is a paper giving relative potency/effects of various juices:

Quote:

Drug Metab Dispos. 2006 Apr;34(4):521-3. Epub 2006 Jan 13.Click here to read Links
Inhibitory effects of fruit juices on CYP3A activity.
Kim H, Yoon YJ, Shon JH, Cha IJ, Shin JG, Liu KH.

Department of Pharmacology, Inje University College of Medicine, # 633-165, Gaegum-Dong, Jin-Gu, Busan 614-735, South Korea.

There have been very limited reports on the effects of commercial fruit juices on human CYP3A activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum, and wild grape. White grapefruit, pomegranate, and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC(50) values of all fruit juices tested were reduced after preincubation with microsomes in the presence of the NADPH-generating system, suggesting that a mechanism-based inhibitory component was present in these fruit juices, as in the case of grapefruit. The results suggest that, like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant.

PMID: 16415112 [PubMed - indexed for MEDLINE]

5) And there is a difference between enteric enzymes and liver enzymes:

Quote:

Drug Metab Dispos. 2005 May;33(5):644-8. Epub 2005 Jan 26.Click here to read Links
Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats.
Hidaka M, Okumura M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Setoguchi N, Arimori K.

Department of Pharmacy, Miyazaki Medical College Hospital, Kiyotake-cho, Miyazaki-gun, Japan. yshidaka@med.miyazaki-u.ac.jp

In this study, we investigated whether components of pomegranate could inhibit CYP3A-mediated drug metabolism. The ability of pomegranate to inhibit the carbamazepine 10,11-epoxidase activity of CYP3A was examined using human liver microsomes, and pomegranate juice was shown to be a potent inhibitor of human CYP3A. Addition of 25 microl (5.0% v/v) of pomegranate juice resulted in almost complete inhibition of the carbamazepine 10,11-epoxidase activity of human CYP3A (1.8%). The inhibition potency of pomegranate juice was similar to that of grapefruit juice. In addition, we investigated the in vivo interaction between pomegranate juice and carbamazepine pharmacokinetics using rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.5-fold higher when pomegranate juice (2 ml) was orally injected 1 h before the oral administration of the carbamazepine (50 mg/kg). On the other hand, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the injection of pomegranate juice. These data suggest that pomegranate juice component(s) impairs the function of enteric but not hepatic CYP3A. Thus, we discovered that a component(s) of pomegranate inhibits the human CYP3A-mediated metabolism of carbamazepine. Furthermore, pomegranate juice alters the carbamazepine pharmacokinetics in rats.

PMID: 15673597 [PubMed - indexed for MEDLINE]

And there is some concern that data is not forthcoming in humans as much as rats. There may be differences there too.

It took a LONG time for data to be compiled on grapefruit juice. Since pomegranate has become popular, it will take a long time to get really good data on that one too. Since there is not a definitive answer it is best to avoid pomegranate if you are on Rx medications.

This link explains some of the above PubMed papers into clear English:
http://www.netwellness.org/question.cfm/44966.htm

I wonder how much a doctor really knows or understands about complex drug metabolism, so it is best if YOU look up stuff as well yourselves. I have found many doctors rather clueless on this topic.
And of course the studies do not include data on genetically "slow metabolizers". These are people who don't metabolize drugs like the majority.

In response to the article that fibrowendy posted about Crestor and Zetia... Crestor has been found to not
be metabolized normally in genetically "slow metabolizers". This includes many Asians, and about 10% of the rest of the
population. Many people had toxicity from Crestor until FDA sent out letters to doctors to LOWER doses in this
group or not use this drug. So that may be a factor in that report.
Crestor is the most toxic statin, and during trials there were deaths on it....a rare event. So I suspect some additive
situation with it.

I personally don't think pomegranate juice is going to be a huge problem, but something to watch in any event.

I agree. But after my issues with the juice, it will be one I will stay away from.

If you don't mind revealing...

What drug was affected for you fibrowendy?
Send me a PM if you don't want to post. I am curious, and will keep it
confidential. (I may be able to help someone else, with this issue in the future).

I drink grapefruit juice all the time, but I don't see any of my meds on that list.

Nikko:hug:

I take Verapamil and Klonopin -- both of these are effected by grapefruit juice.

I suspect that they are also effected by other citrus too. But I got a "D" in high school chemistry and can't figure out these studies on my own.
And I can't trust drs to give me good advice either.
Good freaking luck getting a dr who knows anything about food and med reaction. http://www.thesmilies.com/smilies/happy/rotfl.gif

I like Pomegranate juice. I suspect, in my case, that I can drink a little of it now and then but not regularly.

M.

SOME citrus - but not all

lime
SOUR orange or Seville oranges
possibly bergamot
have similar metabolic effects as does grapefruit, whereas

lemons
sweet orange varieties
appear to be safe.

tangerines and hybrids i don't recall reading about.

also, the effect on meds metabolism appears less related to originally the originally indicted flavonoid, but rather to the action of contained fumarocoumarins(hmm?), also present in smoke, smoked and charred foods (makes ya think about the "bitter" quality of these indicted citrus. These may affect UGT processes (a different enzyme system than the CYP group) as well - aside from the CYP interactions earlier mentioned. However those mechanisms, are, to me, not well understood. i can't recall yet if the article talked about the UGT processes wrt smoking. The effects i do know of regarding smoking pertain to the CYP interactions i.e. 1A2 increases olanzapine clearance but now i'm rambling waaaaaaayy off topic.

most of this stuff is the post-short-term-memory-impaired remnants of an article i read ... will find link for another time am sorry am not up to it.

such a good researcher i am these days. bad waves.

Quote:

Originally Posted by waves (Post 173927)

pomegranate interactions before. it is used in the case of urinary tract infections, which makes me think kidneys but this is all imagination so far...

ooooops. :rolleyes: cranberry is used for urinary tract infections (UTI). pomegranate i could not comment on.

any Mod: can you pls modify original post by deleting in it the text indicated in red above. THANKS. this post itself should remain for any who may have read the previous, to specify the change in content.

~ waves ~ from half a brain and not even half a migraine.

Quote:

Originally Posted by waves (Post 174650)

Dear Waves,
Thanks for answering the citrus question again.
I forget it because I like limes much better than lemons. :D

That's ok. I can learn to like lemon juice.

I imagine that one day I will not need the meds and will not need to take food and other various precautions. I will be all better. I keep telling myself that.

Mari

Here is a list of the meds that I took that were affected. Buspar, depakote and dalmane. All my stabilizers. I was a nervous, aggitated wreck for days and still my body isn't back to where it should. I'm not eating right. Lunch is a toss up lately...don't feel like eating.

Depakote is hard on some people...

Just by itself.
Here is a monograph:
http://www.drugdigest.org/DD/DVH/Use...psules,00.html

Does your doctor test your liver regularly?
Depakote can screw up liver functions in some people.

Also with time Depakote can lower carnitine levels in the body. So you can
ask for a carnitine test. In some people this can become extreme, and deaths have occurred.
http://findarticles.com/p/articles/m...0/ai_n15855244

http://professionals.epilepsy.com/me...eriouside.html

Thank you Mrs. D. I am tested regularly. Actually I think I am due for my check in a month or so.