Rising PSA levels can be a sign of a growing tumor. But the hyped-up pilot study had no placebo group, so there was no way to tell if drinking pomegranate juice actually made any difference. Beginning in , the researchers randomly assigned men treated for prostate cancer to take a liquid extract of pomegranate juice or a placebo liquid every day.
POM says the juice extract has the same ingredients as the juice. Over the next three years, PSA levels rose at the same rate in both groups. No word on why it took so long for these results to become public. So was the POM Wonderful company. Additional studies indicate that pomegranate may protect against breast and colon cancer as well. In prostate-cancer patients, serum PSA levels are the most commonly used marker to assess disease status. One standard for evaluating cancer progression is to measure the time it takes for PSA levels to double from a baseline value.
The longer it takes for PSA to double, the slower the cancer is progressing. In one study, men received 8 ounces of pomegranate juice daily following surgery or radiotherapy for prostate cancer. But after treatment with pomegranate juice, PSA took an average of 54 months to double its value, which is a clinically and statistically significant difference.
In this study, taking pomegranate extract daily for up to 18 months increased the time it took for PSA to double from One of the first questions about any natural compound or drug, for that matter is how well it is absorbed after oral intake. It is also important to determine how much of the compound ultimately reaches its target tissues glands, organs, etc. When the patients supplemented with mg of pomegranate extracts for 15 days prior to surgery, it resulted in significant accumulation of the extracts and their active breakdown products in colon tissue, indicating a targeted effect.
This has been demonstrated in animal studies of xenografts, which are implants of human cancer cells that are surgically engrafted into host animals.
Xenograft studies now demonstrate that not only can pomegranate extracts delay the development of a tumor after it has been implanted, but they can also decrease the size and blood supply of those tumors that do develop. As a result, none of the implanted tumors metastasized.
This is a tremendously important finding, especially considering the terrible prognosis in humans when metastasis occurs. Pomegranate extracts, long known for their contributions to heart health, are now emerging as potentially major players in the field of cancer chemoprevention. Lab studies reveal at least seven major targets by which pomegranate extracts work to fight malignant transformation of cells.
Animal studies demonstrate that pomegranate supplementation leads to reductions in tumor incidence, size, and number. Human studies show that pomegranate extracts can slow the progression of prostate cancer.
Pomegranate extracts have positive effects in breast and colon cancer as well. This is a technique that is commonly used in studying cancers of the colon and digestive tract.
Such cancer-inducing treatment leads to the development of early precancerous lesions known as aberrant crypt foci in colon tissue, which represent areas of abnormal cell replication and growth in the folds of tissue that line the intestine. But that story changes when animals are given pomegranate extracts prior to exposure to the toxic cancer-causing compound. In these scenarios, aberrant crypt foci occurred significantly less frequently in the animals supplemented with pomegranate extracts, compared to the unsupplemented animals.
When pomegranate extracts were given to rats before and after they were exposed to a chemical that caused breast cancer, the extract was found to reduce the incidence, number, and size of breast tumors. The good news is that in studies of animals with experimentally-induced colitis, the pomegranate constituent ellagic acid has been found to inhibit the progression of colitis, and to downregulate many of the molecular signaling pathways that get switched on and promote cancer in colitis patients.
Cancer is a complicated, multifactorial disease, with no single cause and no likely single cure. Because of that, cancer prevention strategies are most effective when they simultaneously address the many underlying causes of cancer in a multitargeted fashion.
This is what makes natural compounds such as pomegranate so appealing for cancer prevention. Studies show that pomegranate extracts and polyphenols exert seven different mechanisms of action on developing cancer cells. Mutations in DNA genes can arise from exposure to radiation including ultraviolet light , to toxins, and even to byproducts of normal metabolism, such as oxidative stress.
Laboratory studies demonstrate that pomegranate extracts, including punicalagin and ellagic acid, can prevent DNA damage from many different sources.
Such proliferation occurs as a result of changes in specific genes that normally maintain regulation over the cell proliferation. When DNA regulatory genes are suppressed, endless cellular replication contributes to more rapid cancer progression. Pomegranate extracts are capable of interfering with abnormal cell-proliferation cycles, thereby impeding aberrant replication.
Normally dividing cells receive many signals to stop replicating, and in many cases, to take themselves out of the picture so that normal tissue can form. The problem is that malignant cells suppress genes that trigger apoptosis. Findings from these two large trials contrasted sharply with findings from earlier single-arm or uncontrolled trials. However, preplanned subset analyses in the two more recent placebo-controlled trials did show that patients with a specific genotype of manganese superoxide dismutase MnSOD seemed to benefit from the supplements.
In , our group completed a dose-finding study of 18 months of pomegranate extract treatment in the PSA-recurrent patient population. PSA doubling time increased from 12 months at baseline to 18 to 19 months on treatment. No significant difference was seen between the low- and high-dose arms. That concern increased when we noted that patients on placebo arms of two randomized controlled trials experienced a significant increase in PSA doubling time that was not induced by any active therapy.
In response, we launched a retrospective analysis of the natural history of two cohorts of patients with PSA-recurrent prostate cancer: Johns Hopkins Hospital patients who chose to defer treatment and patients on the placebo arm of a randomized clinical trial.
IN , Pantuck et al completed the first large randomized placebo-controlled trial of pomegranate extract treatment in PSA-recurrent men. We are currently validating a Clinical Laboratory Improvement Amendments—certified test for the MnSOD genotype and, through the Department of Defense Prostate Cancer Clinical Trials Consortium, planning a much larger multisite study to answer that question and to determine whether baseline antioxidant status modulates the outcome. The second unanswered question concerns Pomi-T, a supplement composed of a blend of green tea, pomegranate, broccoli, and curcumin, which was reported in to lower the rate of PSA increase 8.
Since one of the Pomi-T four components, pomegranate, has already been shown to have no effect on PSA doubling time in the PSA-recurrent patient population, a multiarm trial of the other three components in parallel with a replication of the original study would help determine which component s are effective or whether only the combination should be recommended.
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