- Chinese apple
For Patients & Caregivers
How It Works
There is limited evidence that pomegranate may help conditions related to heart disease. Research on protective effects in prostate cancer patients are mixed. More definitive research is needed.
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, but the evidence is limited. Pomegranate juice had some benefit in patients with prostate cancer, but more clinical trials are needed to confirm such effects.
Data on whether pomegranate can exert protective effects in prostate cancer patients are mixed, although there may be some indirect benefit. More studies are needed.
A small short-term study suggests that pomegranate juice may benefit patients with coronary heart disease, but more studies are needed.
There is evidence from a few studies that pomegranate lowers cholesterol levels.
A few small-scale studies suggest that drinking pomegranate juice may reduce hypertension. More studies are needed to verify this effect.
Do Not Take If
- 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: In an animal study, pomegranate juice reduced the effectiveness of metformin. Whether similar effects occur in humans is not yet known.
For Healthcare Professionals
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 have shown that pomegranate has antioxidant and antiatherosclerotic properties which are 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), hypertension (7), hyperlipidemia (21), or mild to moderate erectile dysfunction (19), as well as patients with coronary heart disease (8), but had no effect in patients with chronic obstructive pulmonary disease (COPD) (9). A systematic review determined the evidence on pomegranate supplementation for blood pressure management is limited (34). In a study of postmenopausal women, intake of pomegranate seed oil did not reduce hot flashes (22).
In preclinical studies, pomegranate juice suppressed inflammatory cell signaling (1), inhibited prostate tumor growth, and lowered serum PSA levels (3) (4). It also inhibited aromatase activity, endogenous estrogen biosynthesis, and breast cancer cell proliferation (5). A pomegranate seed extract alleviated ciplatin-induced hepatotoxicity in animal studies (23).
In prostate cancer patients, the safety and utility of pomegranate has been studied neoadjuvantly, during active surveillance or with biochemical recurrence, and in those with advanced cancer. 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). Although pomegranate juice slowed the rate of prostate-specific antigen (PSA) increase in men with high PSA levels, data are conflicting (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 among men with prostate cancer following a PSA relapse post-radical treatment (25). An adjunctive intervention with pomegranate juice in men with advanced prostate cancer did not produce significant PSA reductions versus placebo (37).
Recent investigations suggest pomegranate extract can modulate gene expression for both osteoclastic and osteogenic processes in postmenopausal women, suggesting a possible role in bone health (26), but 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.
Mechanism of Action
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 antioxidant activity (1) (2).
Animal models indicate that constituents such as ellagic acid and luteolin inhibit metastasis of ovarian cancer by downregulating matrix metalloproteinases MMP2 and MMP9 (28). In prostate cancer cells, a pomegranate extract induced apoptosis and impaired metastasis, also by downregulating MMP2/MMP9 along with upregulating tissue inhibitor of metalloproteinase TIMP2 (29). Prevention of chemically-induced mammary carcinogenesis by another extract likely involved anti-inflammatory mechanisms such as differential regulation of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) signaling (30). A pomegranate extract suppressed breast cancer stem cell characteristics by inhibiting the epithelial to mesenchymal transition (EMT) (31). However, 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). Recent interest in the link between gut microbiota and cancer explores possible mechanisms. In one RCT, consumption of pomegranate was found to decrease plasma lipopolysaccharide binding protein (LBP) levels, which is a known marker that is associated with the onset and development of colorectal cancer (33).
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).
- Cytochrome P4503A substrates: Although studies in rats suggest that pomegranate juice may inhibit cytochrome P450 3A (CYP3A) activity similar to grapefruit juice (10) (11), studies in humans did not show clinically relevant inhibition (12) (39) (40).
- CYP 2C9 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.