Pomegranate Juice Each Day Makes PSA Levels Stay

LOS ANGELES, July 7 ? Men with rising PSA levels after definitive prostate cancer therapy had significant slowing of their PSA doubling time when they drank eight ounces of pomegranate juice daily, researchers here reported.

The men took nearly four times as long for their PSA levels to double as they did before they started drinking the juice, reported urologist Allan J. Pantuck, M.D., of the University of California at Los Angeles here, and colleagues.

In a study of 50 men with rising PSA after definitive therapy for adenocarcinoma of the prostate (prostatectomy or radiotherapy), they found that drinking an eight-ounce glass of pomegranate juice each day resulted in increases in PSA doubling time from 15 months to 54 months, the researchers reported in the July 1 issue of Clinical Cancer Research.

" I was surprised when I saw such an improvement in PSA numbers," Dr. Pantuck said. "In older men 65 to 70 who have been treated for prostate cancer, we can give them pomegranate juice and it may be possible for them to outlive their risk of dying from their cancer. We're hoping we may be able to prevent or delay the need for other therapies usually used in this population such as hormone treatment or chemotherapy, both of which bring with them harmful side effects."

Dr. Pantuck and colleagues reported interim results of the study at the 2005 meeting of the American Urological Association in San Antonio. At that time, they had seen PSA doubling times increase from 15 to 37 months in 48 men followed for two years.

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Pomegranate juice is rich in polyphenols, antioxidants compounds that help to slow the growth of cancerous cells.

"Commercial pomegranate juice shows potent antioxidant and antiatherosclerotic properties attributed to its high content of polyphenols, including ellagic acid in its free and bound forms (as ellagitannins and ellagic acid glycosides), gallotannins, and anthocyanins (cyanidin, delphinidin, and pelargonidin glycosides) and other flavonoids (quercetin, kaempferol, and luteolin glycosides)," the investigators wrote.

In the current study, they reported longer follow-up data on the men in the original cohort.

A total of 50 men with rising PSA after either radical prostatectomy or radiotherapy were enrolled in the phase II study. To be eligible, they had to have PSAs of more than 0.2 and less than 5 ng/mL and Gleason scores of 7 or less.

The patients drank eight ounces of pomegranate juice daily (Wonderful variety, containing 570 mg total polyphenol gallic acid equivalents) until disease progression was noted.

Clinical end points included safety, effect on serum PSA, serum-induced proliferation and apoptosis in prostate cancer cell lines, serum-lipid peroxidation, and serum nitric oxide levels.

The authors found that the mean PSA doubling time significantly increased from a mean of 15 months at baseline to 54 months post-treatment (P

When they compared the effects of patients' serum in vitro using samples collected both before and after a course of daily pomegranate juice consumption, they found that the post-treatment serum caused a 12% decrease over baseline in cell proliferation (P=0.0048), and a 17% increase in apoptosis (P=0.0004).

In addition, they saw a 23% increase in serum nitric oxide (P = 0.0085), and significant reductions in oxidative state and sensitivity to oxidation of serum lipids in the patient samples taken after pomegranate juice consumption compared with baseline (P

"This is not a cure, but we may be able to change the way prostate cancer grows," Dr. Pantuck said. "We don't know yet the specific factors behind this response - that's our next step in this research. We want to find out what cell signaling pathways might be affected, what is happening to keep PSA levels stable."

He and his colleagues are planning a phase III trial slated for 10 centers across the country. The trial will compare commercial pomegranate juice and a pomegranate juice extract with higher polyphenol content than commercially available juices with placebo in a randomized, double-blind design to address some of the limitations of this study, Dr. Pantuck said in an interview.

The authors pointed out that it remains controversial whether modulation of PSA levels represents an equally valid clinical endpoint. The FDA has not yet accepted a PSA endpoint to support drug approval,

The study was underwritten by the makers of the pomegranate juice product used. Dr. Pantuck said that he has no financial interests in the company and is not a paid consultant.