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Pomegranate

Pomegranate

Common Names

  • Chinese apple

For Patients & Caregivers

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Pomegranate was shown effective in lowering blood pressure and high cholesterol. More research is needed to know if it can help prevent or treat cancer.

Pomegranate is a small fruit-bearing tree native to Asia. Juice from the seed pulp contains compounds known as polyphenols that may contribute to its activity. A few studies suggest pomegranate juice can benefit patients with heart disease and can lower cholesterol and blood pressure. It was shown in laboratory studies to prevent growth of cancer cells. In a human study, intake of pomegranate juice was found to have some benefit in patients with prostate cancer, but more clinical trials are needed to confirm such effects.

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  • Cancer prevention
    Data from laboratory studies showed that pomegranate is effective against tumor cells. A single study in humans showed some indirect benefit of pomegranate juice for patients with prostate cancer, but more studies are needed.
  • Cardiovascular Disease
    A small, short-term study suggests that
    pomegranate juice may benefit patients with coronary heart disease, but more studies are needed.
  • Hypercholesterolemia
    There is evidence from a few studies that pomegranate lowers cholesterol level.
  • Hypertension
    A few small scale studies suggest that drinking pomegranate juice may reduce hypertension. More studies are needed to verify this effect.
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  • Pomegranate juice may increase the risk of rhabdomyolysis (breakdown of muscle fibers and release of muscle fiber contents into circulation) for patients on statin therapy.
  • Diabetic patients should be careful because of the sugar content of pomegranate.
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  • You are taking medications that interact with grapefruit juice: Pomegranate may have effects similar to grapefruit juice.
  • You are taking warfarin: Pomegranate juice may interact with warfarin.
  • You are taking metformin: Pre-administration of pomegranate juice reduced the efficacy of metformin, in a rat model. Whether similar effect occurs in humans is not yet known.
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No significant side effects were reported with use of pomegranate juice.

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Patients should be aware that pomegranate is not an approved cancer treatment.

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For Healthcare Professionals

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Punica granatum L.
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Pomegranate is a small fruit-bearing tree native to Asia, but is also cultivated in many parts of the world including the United States. The fruit juice extracted from the arils of the seeds is used in drinks and as a dietary supplement. Several studies have shown that pomegranate has antioxidant and antiatherosclerotic properties attributed to the presence of multiple polyphenols such as tannins, flavonols, anthocyanins and ellagic acid (1) (2).

Consumption of pomegranate juice was found to benefit patients with carotid artery stenosis (6), those with hypertension (7), hyperlipidemia (21), mild to moderate erectile dysfunction (19), and in patients with coronary heart disease (CHD) (8), but had no effect in patients with chronic obstructive pulmonary disease (COPD) (9). In a study of postmenopausal women, intake of pomegranate seed oil did not reduce hot flashes (22)

Pomegranate juice has been shown to suppress inflammatory cell signaling (1), inhibit prostate tumor growth and lower serum PSA levels (3) (4), and also inhibit aromatase activity, endogenous estrogen biosynthesis and breast cancer cell proliferation (5) in vitro. A pomegranate seed extract alleviated ciplatin-induced hepatotoxicity in animal studies (23). Pomegranate juice was also reported to slow the rate of increase of PSA in men with high PSA levels, but data are conflicting (2) (24). However, supplementation with a blend of green tea, pomegranate, broccoli and curcumin resulted in a reduction in the rate of prostate-specific antigen (PSA) increase among men with prostate cancer following a PSA relapse post-radical treatment (25).

Recent investigations have shown that oral intake of pomegranate extracts modulates gene expression for both osteoclastic and osteogenic processes in postmenopausal women, suggesting a possible role in bone health (26); and influences changes in gene expression in colon tissues from colorectal patients (27). Future studies are needed to determine the implications of such changes.

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Whole fruit, juice

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  • Cancer treatment and prevention
  • Atherosclerosis
  • Coronary heart Disease
  • Hypercholesterolemia
  • Hyperlipidemia
  • Hypertension
  • HIV
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Several studies have indicated that pomegranate juice has antioxidant and antiatherosclerotic properties due to the presence of multiple polyphenols such as tannins, flavonols, anthocyanins and ellagic acid. Punicalagin, an ellagitannin, is the most abundant polyphenol that accounts for >50% of the antioxidant activity (1) (2).

Studies using animal models indicate that ellagic acid and luteolin, components of pomegranate juice, inhibit metastasis of ovarian cancer by down-regulating matrix metalloproteinases MMP2 and MMP9 (28); a pomegranate extract induced apoptosis and impaired metastatis in prostate cancer cells also by down-regulating MMP2/MMP9 along with up-regulating tissue inhibitor of metalloproteinase TIMP2 (29); and another extract mediated prevention of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis likely involving anti-inflammatory mechanisms via differential regulation of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) signaling (30). In addition, a pomegranate extract was shown to suppress breast cancer stem cell characteristics by inhibiting the epithelial to mesenchymal transition (EMT) (31). But pomegranate extract can also inhibit aromatase activity and decrease the endogenous synthesis of estrogen (5).

Some commercial pomegranate juices are marketed with claims of higher antioxidant activity than green tea and red wine (13). However such effects could be due to colonic microflora metabolites and not the polyphenols present in the juice (14).

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  • Pomegranate juice may increase the risk of rhabdomyolysis for patients on statin therapy, possibly due to the inhibition of CYP 450 enzymes (17).
  • Diabetic patients should be careful because of the sugar content of pomegranate.
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No significant adverse effects were observed in men following daily consumption of 8 ounces of pomegranate juice for over two years (2).

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  • Cytochrome P4503A substrates: Studies in rats indicate that pomegranate juice may inhibit cytochrome P450 3A (CYP3A) activity similar to grapefruit juice (10) (11), but a study in humans demonstrated that pomegranate juice did not alter clearance of intravenous or oral midazolam, whereas grapefruit juice is known to have this effect (12).
  • CYP 2C9 substrates: A study done in rats showed that pomegranate juice inhibited CYP2C9 activity and increased tolbutamide bioavailability (18).
  • Warfarin: According to a case report, pomegranate juice may interact with warfarin (20).
  • Metformin: Pre-administration of pomegranate juice reduced the efficacy of metformin, in a rat model (32). The clinical relevance in humans has yet to be determined.
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  1. Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem. Feb 8 2006;54(3):980-985.

  2. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. Jul 1 2006;12(13):4018-4026.

  3. Lansky EP, Jiang W, Mo H, et al. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest New Drugs. Jan 2005;23(1):11-20.

  4. Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. Oct 11 2005;102(41):14813-14818.

  5. Kim ND, Mehta R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat. Feb 2002;71(3):203-217.

  6. Sumner MD, Elliott-Eller M, Weidner G, et al. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol. Sep 15 2005;96(6):810-814.

  7. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother. Jul-Aug 2006;40(7-8):1472-1473.

  8. Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos. May 2005;33(5):644-648.

  9. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem. Oct 2000;48(10):4581-4589.

  10. Cerda B, Llorach R, Ceron JJ, Espin JC, Tomas-Barberan FA. Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eur J Nutr. Jan 2003;42(1):18-28.

  11. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol. Sep 1 2006;98(5):705-706.

  12. Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos. Feb 2007;35(2):302-305.

  13. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy. 2009 Aug;29(8):1002-6.

  14. Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F. Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr. 2010 Aug;104(3):402-6.

  15. Yildirim NC, Kandemir FM, Ceribasi S, Ozkaraca M, Benzer F. Pomegranate seed extract attenuates chemotherapy-induced liver damage in an experimental model of rabbits.Cell Mol Biol (Noisy-le-grand). 2013 Feb 2;59 Suppl:OL1842-7.

  16. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer.Prostate Cancer Prostatic Dis. 2013 Mar;16(1):50-5.

  17. Lin Y, Kazlova V, Ramakrishnan S, Murray MA, Fast D, Chandra A, Gellenbeck KW. Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study. Phytomedicine. 2016 Jan 15;23(1):18-26.

  18. Awad R, Mallah E, Khawaja BA, et al. Pomegranate and licorice juices modulate metformin pharmacokinetics in rats. Neuro Endocrinol Lett. 2016 Jul;37(3):202-206.

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