Life Extension Magazine May 2010
Is Conventional Pomegranate Extract Enough?
By Julius Goepp, MD
Pomegranate Seed Oil: A Potent Cancer Fighter
Cutting-edge research has uncovered numerous life-saving modes of action for pomegranate seed oil, most notably in the area of chemoprevention.2 Other roles for pomegranate seed oil include facilitating repair of aging skin, immune function modulation, and inflammation reduction.2,31-33
The data on pomegranate seed oil’s cancer fighting potential is most compelling in tissues of the male and female reproductive systems. Pomegranate seed oil is a potent inhibitor of aromatase, the enzyme that produces estrogen from testosterone, and 17-beta-hydroxysteroid dehydrogenase type 1, which is responsible for the conversion of estrone to potent estradiol. This enzymatic blockade contributes to pomegranate seed oil’s ability to inhibit growth of estrogen-dependent breast cancer cells in culture. It also reduces the cancer cells’ invasiveness (ability to cross barriers). A separate mechanism is also clearly at work here, because the oil also increases cellular suicide (apoptosis) even in cancer cells that lack estrogen receptors.34
Cancer cells need to grow new blood vessels to support their rapid growth and tissue invasion (angiogenesis). They typically do this by ramping up production of a variety of growth factors, including vascular endothelial growth factor (VEGF) and inflammatory interleukins.
Pomegranate seed oil powerfully inhibits production of VEGF while upregulating production of migratory inhibitory factor (MIF) in breast cancer cells. In a laboratory model of vessel growth, these modulations translated into a significant decrease in new blood vessel formation.35 Pomegranate seed oil’s capacity to block breast cancer development was also demonstrated in an organ culture model of mouse breast cancer.36 Treating the glands with the oil prior to exposure to a powerful carcinogen resulted in an astonishing 87% reduction in the number of cancerous lesions compared with controls—substantially greater protection than has been previously reported for derivatives of pomegranate juice.
As with flower extracts, pomegranate seed oil contains a number of unique chemical constituents with potent biological effects. Punicic acid is an omega-5 polyunsaturated fatty acid that inhibits both estrogen-dependent and estrogen-independent breast cancer cell proliferation in lab cultures.37 Punicic acid also induced apoptosis at rates up to 91% higher than those in untreated cell cultures—effects which appear to be related to fundamental regulation of cancer cell signaling pathways.37
Another common malignancy that often depends on sex hormones for its growth is prostate cancer, a leading cause of cancer-related mortality in American men, accounting for more than 29,000 deaths each year.38 Because of its slow rate of growth and appearance later in life, prostate cancer has been identified as an ideal target for nutritional chemoprevention.10
Pomegranate seed oil sharply inhibits proliferation of a number of human prostate cancer lines through changes in the cell growth cycle and also by inducing apoptosis (cell death). At the same time, it has been shown to powerfully suppress cancer cell invasion.39 Pomegranate oil also acts in synergy with other pomegranate components, suppressing prostate cancer proliferation and metastatic potential more effectively than each component individually.40
An abundance of data supports the power of pomegranate extract as a broad-spectrum, multi-modal defense against multiple diseases of aging. It has been shown to inhibit pro-inflammatory nuclear factor-kappaB (NF-kB), downregulate production of certain cancer-stimulating androgens, and upregulate expression for the paraoxonase molecular complex associated with artery-cleansing HDL.
The most recent research suggests that the various botanical components of the fruit tree may be required to obtain pomegranate’s full protective benefit, in particular its flowers and seeds.
Extracts from pomegranate flower have been shown to suppress signaling of endothelin-1, a blood vessel-narrowing peptide implicated in cardiac fibrosis (abnormal thickening of the heart valves) and to help arrest the onset of metabolic syndrome as well as its associated pathologies of obesity, type 2 diabetes, and heart disease.
Pomegranate seed oil offers further promise as a powerful anti-cancer agent, with particular potential in combating breast and prostate cancers.
There is now solid published data to support the value of supplementing with pomegranate fruit extract, along with pomegranate flower and seed oil extracts.
1. Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern Med Rev. 2008 Jun;13(2):128-44.
2. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007 Jan 19;109(2):177-206.
3. Aviram M, Volkova N, Coleman R, et al. Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein e-deficient (E 0) mice and in vitro in cultured macrophages and lipoproteins. J Agric Food Chem. 2008 Feb 13;56(3):1148-57.
4. Heber D. Multitargeted therapy of cancer by ellagitannins. Cancer Lett. 2008 Oct 8;269(2):262-8.
5. Hong MY, Seeram NP, Heber D. Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. J Nutr Biochem. 2008 Dec;19(12):848-55.
6. Rosenblat M, Aviram M. Paraoxonases role in the prevention of cardiovascular diseases. Biofactors. 2009 Jan-Feb;35(1):98-104.
7. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33.
8. Basu A, Penugonda K. Pomegranate juice: a heart-healthy fruit juice. Nutr Rev. 2009 Jan;67(1):49-56.
9. Aviram M, Dornfeld L, Kaplan M, et al. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp Clin Res. 2002;28(2-3):49-62.
10. Syed DN, Afaq F, Mukhtar H. Pomegranate derived products for cancer chemoprevention. Semin Cancer Biol. 2007 Oct;17(5):377-85.
11. Bell C, Hawthorne S. Ellagic acid, pomegranate and prostate cancer—a mini review. J Pharm Pharmacol. 2008 Feb;60(2):139-44.
12. Rasheed Z, Akhtar N, Anbazhagan AN, Ramamurthy S, Shukla M, Haqqi TM. Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells. J Inflamm (Lond). 2009;6:1.
13. Rettig MB, Heber D, An J, et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008 Sep;7(9):2662-71.
14. Romier-Crouzet B, Van De Walle J, During A, et al. Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells. Food Chem Toxicol. 2009 Jun;47(6):1221-30.
15. Lucas DL, Were LM. Anti-Listeria monocytogenes activity of heat-treated lyophilized pomegranate juice in media and in ground top round beef. J Food Prot. 2009 Dec;72(12):2508-16.
16. Reddy MK, Gupta SK, Jacob MR, Khan SI, Ferreira D. Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L. Planta Med. 2007 May;73(5):461-7.
17. Perez C, Anesini C. In vitro antibacterial activity of Argentine folk medicinal plants against Salmonella typhi. J Ethnopharmacol. 1994 Aug;44(1):41-6.
18. Katz SR, Newman RA, Lansky EP. Punica granatum: heuristic treatment for diabetes mellitus. J Med Food. 2007 Jun;10(2):213-7.
19. Wang R, Wei W, Wang L, Liu R, Yi D, Du L. Constituents of the flowers of Punica granatum. Fitoterapia. 2006 Dec;77(7-8):534-7.
20. Jafri MA, Aslam M, Javed K, Singh S. Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats. J Ethnopharmacol. 2000 Jun;70(3):309-14.
21. Huang TH, Peng G, Kota BP, et al. Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component. Toxicol Appl Pharmacol. 2005 Sep 1;207(2):160-9.
22. Huang TH, Peng G, Kota BP, et al. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. Br J Pharmacol. 2005 Jul;145(6):767-74.
23. Li Y, Qi Y, Huang TH, Yamahara J, Roufogalis BD. Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties. Diabetes Obes Metab. 2008 Jan;10(1):10-7.
24. Huang TH, Yang Q, Harada M, et al. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. J Cardiovasc Pharmacol. 2005 Dec;46(6):856-62.
25. Zoico E, Garbin U, Olioso D, et al. The effects of adiponectin on interleukin-6 and MCP-1 secretion in lipopolysaccharide-treated 3T3-L1 adipocytes: role of the NF-kappaB pathway. Int J Mol Med. 2009 Dec;24(6):847-51.
26. Xie Y, Morikawa T, Ninomiya K, et al. Medicinal flowers. XXIII. New taraxastane-type triterpene, punicanolic acid, with tumor necrosis factor-alpha inhibitory activity from the flowers of Punica granatum. Chem Pharm Bull (Tokyo). 2008 Nov;56(11):1628-31.
27. Ursini F. TNF-alpha and insulin-resistance: metabolic effects of in vivo therapeutic blockade. Reumatismo. 2009 Oct-Dec;61(4):254-9.
28. Bagri P, Ali M, Aeri V, Bhowmik M, Sultana S. Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Food Chem Toxicol. 2009 Jan;47(1):50-4.
29. Xu KZ, Zhu C, Kim MS, Yamahara J, Li Y. Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. J Ethnopharmacol. 2009 Jun 22;123(2):280-7.
30. Li Y, Wen S, Kota BP, et al. Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats. J Ethnopharmacol. 2005 Jun 3;99(2):239-44.
31. Aslam MN, Lansky EP, Varani J. Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells. J Ethnopharmacol. 2006 Feb 20;103(3):311-8.
32. Yamasaki M, Kitagawa T, Koyanagi N, et al. Dietary effect of pomegranate seed oil on immune function and lipid metabolism in mice. Nutrition. 2006 Jan;22(1):54-9.
33. de Nigris F, Balestrieri ML, Williams-Ignarro S, et al. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide. 2007 Aug;17(1):50-4.
34. Kim ND, Mehta R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat. 2002 Feb;71(3):203-17.
35. Toi M, Bando H, Ramachandran C, et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis. 2003;6(2):121-8.
36. Mehta R, Lansky EP. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev. 2004 Aug;13(4):345-8.
37. Grossmann ME, Mizuno NK, Schuster T, Cleary MP. Punicic acid is an omega-5 fatty acid capable of inhibiting breast cancer proliferation. Int J Oncol. 2010 Feb;36(2):421-6.
38. Syed DN, Suh Y, Afaq F, Mukhtar H. Dietary agents for chemoprevention of prostate cancer. Cancer Lett. 2008 Jul 8;265(2):167-76.
39. Albrecht M, Jiang W, Kumi-Diaka J, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004 Fall;7(3):274-83.
40. Lansky EP, Jiang W, Mo H, et al. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest New Drugs. 2005 Jan;23(1):11-20.
41. Berrougui H, Khalil A. Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity. Rejuvenation Res. 2009 Apr;12(2):117-26.
42. Shiner M, Fuhrman B, Aviram M. Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPAR gamma and AP-1 pathway activation. Atherosclerosis. 2007 Dec;195(2):313-21.
43. Staels B, Maes M, Zambon A. Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2008 Sep;5(9):542-53.
44. Cho N, Momose Y. Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem. 2008;8(17):1483-507.