Pomegranate

Purported Benefits, Side Effects & More

Pomegranate

Purported Benefits, Side Effects & More
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Pomegranate

Common Names

  • Chinese apple

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

Pomegranate is a reddish-brown fruit that comes from the pomegranate tree. Pomegranate seeds have many nutrients. They are also used in traditional medicine to help with many issues.

Juice made from pomegranate seeds comes in supplements as capsules, tablets, and as powders.

What are the potential uses and benefits?

Pomegranate supplements/juice are used:

  • To prevent and treat heart disease.
  • To lower high cholesterol levels.
  • To reduce high blood pressure.
  • To prevent cancer.

Pomegranate also has other uses that haven’t been studied by doctors to see if they work.

It’s generally safe to eat pomegranate seeds or drink pomegranate juice. Talk with your healthcare provider before taking pomegranate supplements. Herbal supplements are stronger than the herbs you would use in cooking.

Supplements can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of pomegranate juice may include:

  • Diarrhea (loose or watery bowel movements).
What else do I need to know?
  • Talk with your healthcare provider if you’re on blood thinners such as warfarin (Coumadin®, Jantoven®). Pomegranate juice can increase your risk of bleeding.
  • Avoid eating the root, stem, or peel of pomegranate. They contain chemicals that can be harmful.

For Healthcare Professionals

Scientific Name
Punica granatum
Clinical Summary

Pomegranate is a small fruit-bearing tree native to Asia, but it 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 suggest antioxidant and antiatherosclerotic properties, which are attributed to the presence of multiple polyphenols such as tannins, flavonols, anthocyanins, and ellagic acid (1) (2). Preclinical studies also suggest pomegranate juice may suppress inflammatory cell signaling and prostate tumor growth, and lower serum PSA levels (1) (3) (4). In other experiments, it inhibited aromatase activity, endogenous estrogen biosynthesis, and breast cancer cell proliferation (5), and a pomegranate seed extract alleviated ciplatin-induced hepatotoxicity in animal studies (23).

Preliminary studies in humans suggest pomegranate may have some benefit on cognition (43), cardiovascular disease (6) (8), hyperlipidemia (21), or erectile dysfunction (19), but not COPD (9). Data for its use in hypertension is limited (7) (34), and meta-analyses did not find pomegranate helpful to improve oxidative stress (44), although it may help improve some biomarkers of inflammation and vascular dysfunction (45).

A few studies have been conducted in cancer patients. In men with favorable-risk prostate cancer on active surveillance, preliminary data suggest pomegranate fruit extract may alter biomarkers related to androgen signaling and oxidative stress (46). Pomegranate extract before surgery resulted in pomegranate metabolite accumulation in prostate tissue, but did not significantly lower 8-OHdG levels, a measure of oxidative damage (35). Data are conflicting on whether pomegranate juice can slow the rate of prostate-specific antigen increase in men with high PSA levels (2) (24). A planned subset analysis suggests that those with the manganese superoxide dismutase (MnSOD) AA genotype might benefit (36). Supplementation with a blend of green tea, pomegranate, broccoli, and curcumin resulted in lower rates of PSA increase following PSA relapse post-radical treatment (25). However, an adjunctive intervention with pomegranate juice in men with advanced prostate cancer did not produce significant PSA reductions versus placebo (37).

Other investigations suggest pomegranate in combination with other plant extracts may modulate gene expression for osteoclastic and osteogenic processes (26), but intake of pomegranate seed oil did not reduce hot flashes (22), and there was no overall association between pomegranate juice intake and hormonal biomarkers for breast cancer risk (38). Pomegranate extract influenced changes in gene expression in colon tissues from colorectal patients (27). In newly-diagnosed CRC patients, pomegranate consumption may lower plasma LPS-binding protein levels, a marker for endotoxemia (33). More studies are needed to determine the implications of such changes.

Although animal studies suggested pomegranate may inhibit CYP3A and 2C9 (10) (11) (18), humans studies have not shown clinically relevant interactions (12) (39) (40) (41).

Food Sources

Whole fruit, juice

Purported Uses and Benefits
  • Cardiovascular disease
  • High cholesterol
  • Hypertension
  • Cancer prevention
Mechanism of Action

Pomegranate juice has antioxidant and antiatherosclerotic properties due to the presence of polyphenols such as tannins, flavonols, anthocyanins, and ellagic acid. Punicalagin, an ellagitannin, is the most abundant polyphenol that accounts for >50% of antioxidant activity (1) (2).

In animal models, constituents such as ellagic acid and luteolin inhibit ovarian cancer metastasis by downregulating MMP2 and MMP9 (28). In prostate cancer cells, a pomegranate extract induced apoptosis and impaired metastasis also by downregulating MMP2/9 along with TIMP2 upregulation (29). Prevention of chemically-induced mammary carcinogenesis by another extract likely involved anti-inflammatory mechanisms such as differential regulation of NF-κB and NF-erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) signaling (30). Pomegranate extract suppressed breast cancer stem cell characteristics by inhibiting the epithelial to mesenchymal transition (31). It can also inhibit aromatase activity and decrease endogenous estrogen synthesis (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). Recent interest in the link between gut microbiota and cancer explores possible mechanisms. In one RCT, consumption of pomegranate decreased plasma lipopolysaccharide binding protein levels, a known marker associated with onset and development of colorectal cancer (33).

Warnings
  • Pomegranate juice may increase the risk of rhabdomyolysis for patients on statin therapy (17).
  • Diabetic patients should be careful because of the sugar content of pomegranate.
Adverse Reactions

Generally well tolerated (25) (42).

No significant adverse effects were observed in men following daily consumption of 8 ounces of pomegranate juice for over 2 years (2). In a study of prostate cancer patients, few related adverse events occurred, including mild to moderate nausea, constipation, and decreased appetite (36). Diarrhea occurred with higher doses in some patients (24).

Case report

Transient elevated alkaline phosphatase: In a 20-month-old boy, caused by daily consumption of pomegranate juice due to feeding and appetite problems over a 2-month period (47).

Herb-Drug Interactions
  • CYP3A substrates: Although studies in rats suggest that pomegranate juice may inhibit CYP3A activity similar to grapefruit juice (10) (11), studies in humans did not show clinically relevant inhibition (12) (39) (40).
  • CYP2C9 substrates: A study in rats showed that pomegranate juice inhibited CYP2C9 activity and increased tolbutamide bioavailability (18), but pomegranate juice and extract had no effect on CYP2C9 activity in humans (41).
  • Warfarin: According to a case report, pomegranate juice may interact with warfarin (20).
  • Metformin: In a rat model, pre-administration of pomegranate juice reduced metformin efficacy (32). The clinical relevance in humans has yet to be determined.
Dosage (OneMSK Only)
References
  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. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. Jun 2004;23(3):423-433.
  7. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.Atherosclerosis. Sep 2001;158(1):195-198.
  8. 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.
  9. Cerda B, Soto C, Albaladejo MD, et al. Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5-week randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. Feb 2006;60(2):245-253.
  10. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother. Jul-Aug 2006;40(7-8):1472-1473.
  11. 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.
  12. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol. Mar 2007;47(3):286-294.
  13. 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.
  14. Cerda B, Espin JC, Parra S, Martinez P, Tomas-Barberan FA. The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur J Nutr. Aug 2004;43(4):205-220.
  15. 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.
  16. Seeram NP, Lee R, Heber D. Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta. Oct 2004;348(1-2):63-68.
  17. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol. Sep 1 2006;98(5):705-706.
  18. 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.
  19. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. Int J Impot Res. 2007 Nov-Dec;19(6):564-7.
  20. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy. 2009 Aug;29(8):1002-6.
  21. 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.
  22. Auerbach L, Rakus J, Bauer C, et al.Pomegranate seed oil in women with menopausal symptoms: a prospective randomized, placebo-controlled, double-blinded trial. Menopause. 2012 Apr;19(4):426-32.
  23. 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.
  24. 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.
  25. Thomas R, Williams M, Sharma H, Chaudry A, Bellamy P. A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the U.K. NCRN Pomi-T study. Prostate Cancer Prostatic Dis. 2014 Jun;17(2):180-6.
  26. 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.
  27. Nuñez-Sánchez MA, González-Sarrías A, García-Villalba R, et al. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem. 2017 Apr;42:126-133.
  28. Liu H, Zeng Z, Wang S, Li T, et al. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol Ther. 2017 Dec 2;18(12):990-999.
  29. Deng Y, Li Y, Yang F, et al. The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells. Biomed Pharmacother. 2017 Sep;93:976-984.
  30. Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways. Nutrients. 2017 Apr 28;9(5):436.
  31. Nallanthighal S, Elmaliki KM, Reliene R. Pomegranate Extract Alters Breast Cancer Stem Cell Properties in Association with Inhibition of Epithelial-to-Mesenchymal Transition.Nutr Cancer. 2017 Oct;69(7):1088-1098.
  32. 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.
  33. González-Sarrías A, Núñez-Sánchez MA, Ávila-Gálvez MA, et al. Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial. Food Funct. 2018 May 23;9(5):2617-2622.
  34. Gbinigie OA, Onakpoya IJ, Spencer EA. Evidence for the effectiveness of pomegranate supplementation for blood pressure management is weak: A systematic review of randomized clinical trials. Nutr Res. Oct 2017;46:38-48.
  35. Freedland SJ, Carducci M, Kroeger N, et al. A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy. Cancer Prev Res (Phila). Oct 2013;6(10):1120-1127.
  36. Pantuck AJ, Pettaway CA, Dreicer R, et al. A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer. Prostate Cancer Prostatic Dis. Sep 2015;18(3):242-248.
  37. Stenner-Liewen F, Liewen H, Cathomas R, et al. Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer - Results of a Phase IIb Randomized Controlled Trial. J Cancer. 2013;4(7):597-605.
  38. Kapoor R, Ronnenberg A, Puleo E, et al. Effects of Pomegranate Juice on Hormonal Biomarkers of Breast Cancer Risk. Nutr Cancer. 2015;67(7):1113-1119.
  39. Misaka S, Nakamura R, Uchida S, et al. Effect of 2 weeks’ consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther. Feb 2011;33(2):246-252.
  40. Park SJ, Yeo CW, Shim EJ, et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet. Aug 2016;41(4):339-344.
  41. Hanley MJ, Masse G, Harmatz JS, et al. Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther. Nov 2012;92(5):651-657.
  42. Paller CJ, Pantuck A, Carducci MA. A review of pomegranate in prostate cancer. Prostate Cancer Prostatic Dis. Sep 2017;20(3):265-270.
  43. Siddarth P, Li Z, Miller KJ, et al. Randomized placebo-controlled study of the memory effects of pomegranate juice in middle-aged and older adults. Am J Clin Nutr. Jan 1 2020;111(1):170-177.
  44. Morvaridzadeh M, Sepidarkish M, Daneshzad E, et al. The effect of pomegranate on oxidative stress parameters: A systematic review and meta-analysis. Complement Ther Med. Jan 2020;48:102252.
  45. Wang P, Zhang Q, Hou H, et al. The effects of pomegranate supplementation on biomarkers of inflammation and endothelial dysfunction: A meta-analysis and systematic review. Complement Ther Med. Mar 2020;49:102358.
  46. Jarrard D, Filon M, Huang W, et al. A phase II randomized placebo-controlled trial of pomegranate fruit extract in men with localized prostate cancer undergoing active surveillance. Prostate. Jan 2021;81(1):41-49.
  47. Molina Gutiérrez MA, Alcobendas Rueda RM, Martínez Villar M, et al. Transient Hyperphosphatasemia Due to Pomegranate Juice. Cureus. Apr 30 2021;13(4):e14779.
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