7 replies to this topic

[maxwatt]

I've heard a few reports of joint pain or tendonitis associated with drinking pomegranate juice, where symptoms resolved on ceasing to drink the juice or supplement. Coincidence? Probably, but I'm asking if anyone has experienced this, and if you have, what other supplements were you taking at the time?

[suspire]

I've heard a few reports of joint pain or tendonitis associated with drinking pomegranate juice, where symptoms resolved on ceasing to drink the juice or supplement. Coincidence? Probably, but I'm asking if anyone has experienced this, and if you have, what other supplements were you taking at the time?

I used to drink at least 8 oz of pomegranate juice per day, plus take various pomegranate supplements daily. No joint pain. I only recently stopped the pomegranate juice to cut down on the daily sugars, but still take the supplements.

Not what you were asking, I know, but I wanted to give a counter that despite a good amount of pomegranate substances per day, every day, for quite awhile, I've never had any associated joint pains. Then again, I haven't had with resv either--but I've never gone over 2 grams per day, and that was only for a short time (down to under 1 gram now).

[funkmasterflex]

I've been extra sore lately, and got back into my pom juice. Hmmm...I shall stop and see. I do work out like a madman sometimes though. Also, adrenal fatigue catches up with me. A lot of factors, but I could do an anecdotal accounts and see what happens. (N=1) hehe...

[balance]

I probably hold the record in terms of amount of pomegranate consumed per day (1200mg punicalagins, 5000mg total pomegranate). Never the juice though. I never got any joint pain of any kind from it, having used it long term (2 years). The only thing I ever noticed is that it greatly improved my skin, especially on the back of both my hands! I have reported this here:

http://www.imminst.o...;hl=pomegranate

[nameless]

Do you happen to take any medications? A pomegranate-drug interaction is a possibility. I'm not sure if such an interaction, even if it existed, would cause joint pain, but some drugs could potentially have lots of side effects, so you never know.

The best way to know for sure is to handle it like an elimination diet/allergy thing. Stop it, see if the symptoms go away. Then start again, see if they come back. Then stop it again.

[niner]

Regarding pomegranate drug interactions: 3A4 and 2C9 are inhibited by pomegranate. If it behaves like other fruits, it's a mechanism based inhibition, so it may take at least a week off, maybe more, for things to get back to normal, if this is what's happening. Consider what drugs you are taking and how they are metabolized.

Am J Cardiol. 2006 Sep 1;98(5):705-6. Epub 2006 Jul 14.
Rhabdomyolysis associated with pomegranate juice consumption.
Sorokin AV, Duncan B, Panetta R, Thompson PD.

Section of Preventive Cardiology, Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, Connecticut, USA.

This 48-year-old man with possible underlying myopathy was successfully treated with ezetimibe 10 mg/day and rosuvastatin 5 mg every other day for 17 months. Three weeks before presentation, he began drinking pomegranate juice (200 ml twice weekly). He presented urgently with thigh pain and an elevated serum creatine kinase level (138,030 U/L, normal < 200 U/L). In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4.

PMID: 16923466

Rosuvastatin is metabolized by 2C9, and lo and behold...

Drug Metab Dispos. 2007 Feb;35(2):302-5. Epub 2006 Nov 28. Free Full Text.
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 CYP2C9) 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

[maxwatt]

Regarding pomegranate drug interactions: 3A4 and 2C9 are inhibited by pomegranate. If it behaves like other fruits, it's a mechanism based inhibition, so it may take at least a week off, maybe more, for things to get back to normal, if this is what's happening. Consider what drugs you are taking and how they are metabolized.

Am J Cardiol. 2006 Sep 1;98(5):705-6. Epub 2006 Jul 14.
Rhabdomyolysis associated with pomegranate juice consumption.
Sorokin AV, Duncan B, Panetta R, Thompson PD.

Section of Preventive Cardiology, Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, Connecticut, USA.

This 48-year-old man with possible underlying myopathy was successfully treated with ezetimibe 10 mg/day and rosuvastatin 5 mg every other day for 17 months. Three weeks before presentation, he began drinking pomegranate juice (200 ml twice weekly). He presented urgently with thigh pain and an elevated serum creatine kinase level (138,030 U/L, normal < 200 U/L). In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4.

PMID: 16923466

Rosuvastatin is metabolized by 2C9, and lo and behold...

Drug Metab Dispos. 2007 Feb;35(2):302-5. Epub 2006 Nov 28. Free Full Text.
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 CYP2C9) 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

That helps; there is a great deal of variability in Cytochrome CYP450-mediated metabolism as with CYP2C9, which is involved with resveratrol, hydrocodone, Provigil et al. It's likely a combination could induce myopathy manifested as tendinitis and joint pain. The wash-out period is about three days.

[niner]

That helps; there is a great deal of variability in Cytochrome CYP450-mediated metabolism as with CYP2C9, which is involved with resveratrol, hydrocodone, Provigil et al. It's likely a combination could induce myopathy manifested as tendinitis and joint pain. The wash-out period is about three days.

Do you mean that the wash-out period that people are observing, i.e., the time it takes for the pain to subside after the last dose of pomegranate, is three days? That would be consistent with a mechanism-based inhibition of a P450, assuming there's something around that should be getting metabolized by 3A4 or 2C9, and could cause the symptoms if it builds up, as certain statins are known to do.