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| Date: 11-30-2015 | HC# 041541-533 |
Vlachojannis C, Zimmermann BF, Chrubasik-Hausmann S. Efficacy and safety of pomegranate medicinal products for cancer. Evid Based Complement Alternat Med. March 1, 2015;2015:258598. doi: 10.1155/2015/258598.
Polyphenol fractions of pomegranate (Punica granatum, Lythraceae) fruit, rind, juice, seed, and seed oil have promising anticancer effects, inhibiting cancer cell lines and cancer indicators in vitro and in vivo. Research has suggested that fermentation with Lactobacillus plantarum may enrich pomegranate's coactive compounds, enhancing its antimicrobial and anticancer effects. Pomegranate fruit extracts increase the action of tamoxifen, used in breast cancer, in tamoxifen-resistant and tamoxifen-sensitive breast cancer cells. In in vitro studies, its polyphenols, mainly oligomeric punicalagin and monomeric ellagic acid, inhibited expression of genes for androgen-synthesizing enzymes and receptors in androgen-independent prostate cancer cells. In vivo, oral infusion of pomegranate fruit extract dose-dependently inhibited tumor growth and decreased prostate-specific antigen (PSA) levels.
All pomegranate-derived materials contribute to its anticancer effects; however, research suggests that many of the pomegranate-derived compounds may contribute to its anticancer effects creating a synergistic effect. Indeed, 100% pomegranate juice may be more effective than its components alone. Homogenates from whole fruits had about 20 times the antioxidant activity of juices from the arils alone. Of pomegranate's polyphenols, the ellagitannins punicalagin and punicalin are metabolized during absorption. One metabolite, ellagic acid, is further metabolized by colonic microflora to urolithin A, also with anticancer effects. Taken together, the clinical effectiveness of pomegranate products in treating prostate and other cancers needs further study.
In this report, the authors conducted an electronic literature search, identified, and summarized data on the efficacy and safety of pomegranate in cancer treatment to assemble a detailed and wide-ranging report. To assist in their critique of the literature, the authors conducted their own chemical analysis on commercial products which they obtained. Their chemical analysis did not always match with other peer-reviewed scientific articles. Nevertheless, the authors reviewed and analyzed the literature with the goal of discerning a clinically effective dose with respect to prostate cancer. The search was not limited by language or methodology. References were hand-searched for other publications. Study data were extracted and evaluated for quality and strength of evidence on the basis of having or not having 13 quality markers. Evidence of efficacy was characterized as strong, moderate, or weak depending on the number and quality of studies showing benefit. Searches for "pomegranate cancer" and "pomegranate prostate" initially yielded 162 and 65 reports, respectively; each group included the same four clinical trials (CTs) investigating pomegranate products in prostate cancer, the only CTs meeting inclusion criteria. Searches for "pomegranate safety" and "pomegranate toxicity" found 65 and 57 studies, respectively; of these, 26 experimental and five clinical studies met criteria, as well as 17 experimental and 15 clinical studies found in hand searches, for a total of 63.
Regarding the safety of pomegranate products, there were no observed adverse effects, even at large doses. They were found to be embryoprotective against a range of toxins, reduce the RNA-damaging effects of others, and boost antioxidant defense mechanisms against carbon tetrachloride-induced reproductive toxicity. The products were also protective against methotrexate-induced and heavy metal toxicities, as well as kidney tissue from nephrotoxins. Pomegranate protects against damage from certain chemotherapeutic medicines. One study reported that a 50% ethanol extract of whole pomegranate fruit caused DNA damage; its use should probably be based on a risk-benefit analysis, although the damage occurred at doses higher than normally used in vivo or in the Cuban folk medicine on which this extract is based. In human studies, pomegranate is well tolerated, with increased diarrhea reported at high doses in some studies and very rare allergic reactions. Mannitol, found in pomegranate, can cause immunoglobulin E (IgE)-mediated hypersensitivity.
Dosage of pomegranate preparations was also assessed. CTs evaluating pomegranate products in patients with prostate cancer used different products at different dosages over different time periods. In two observational studies, positive effects included increased PSA doubling time. In two placebo-controlled trials, no differences were seen after four weeks in active or placebo groups; study duration was perhaps too short. One of these, a phase IIb, double-blinded, randomized, placebo-controlled trial in patients with confirmed prostate cancer, used a product with only 5% the amount of pomegranate's active principle as that of products investigated in other trials.
In their analysis of 19 pomegranate products, the quantity and spectrum of phenolic ingredients varied widely, partly depending on relative ripeness of fruit used. Commercial processing causes losses in phenolic compounds, with heat and light being the main culprits. Enzymes, co-pigments, sugars, and pH affect anthocyanin stability in juices. The authors critique the use of photometry alone to assess coactive ingredients, as photometry "overestimate[s] the true polyphenol content by detecting all polyphenolic or antioxidative compounds regardless of their clinical activity." In a similar situation involving cranberry (Vaccinium macrocarpon, Ericaceae) products, high-performance liquid chromatography (HPLC) assessment has provided benchmark doses to prevent urinary tract infections; the authors suggest that this method be used as well to determine and list punicalagin, ellagic acid, and anthocyanin content on pomegranate product labels along with photometric estimates of total polyphenols, and that a benchmark be established for prostate cancer treatment. Of products tested, "only a limited number … were believably authentic." Lacking more definitive research on pomegranate compounds that exert an anticancer effect and better regulatory guidance, consumers have little chance of choosing an effective anticancer pomegranate product. The article would have benefited from more information on adulteration and nutraceutical fraud.
—Mariann Garner-Wizard
