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 also 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 have also been conducted in humans. In middle-aged and older adults, pomegranate may have some benefit on cognition ⁽⁴³⁾. It may also benefit some patients with carotid artery stenosis ⁽⁶⁾, coronary heart disease ⁽⁸⁾, hyperlipidemia ⁽²¹⁾, or erectile dysfunction ⁽¹⁹⁾, but had no effect in patients with COPD ⁽⁹⁾. In addition, data for its use in hypertension is limited ^(7) (34), and meta-analyses did not find pomegranate helpful to improve oxidative stress parameters ⁽⁴⁴⁾, although it may help improve some biomarkers of inflammation and vascular dysfunction ⁽⁴⁵⁾.

A few studies have also 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⁾. Although pomegranate juice slowed the rate of prostate-specific antigen 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 following 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⁾.

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)}.