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Pomegranate Update Fall 2008

Jacob Schor, ND, FABNO

September 1, 2008

Costco now sells PomWonderful pomegranate juice in a 60 oz bottle.  It is huge. The bottle no longer evokes the sexy Venus d’Milo look of the original bottle with its thin waist and curved hip look.   It looks like a cross between Mrs. Butterworth and Aunt Jemima on steroids.

I haven’t written about pomegranates since the UCLA prostate cancer study published in the summer of 2006.  That’s the one by Pantuck et al, in which men with advanced prostate cancer drank a glass of PomWonderful a day.  The cancer in the juice drinkers took more than 3 years to grow to the same extent as the cancers in non-juice drinkers did in eleven months.  

http://denvernaturopathic.com/news/PomandPC.html

My silence doesn’t mean interest in pomegranates has waned.  Far from it.  Studying this unshapely giant bottle has inspired me to see what new data has been published on pomegranates over the last year or so.  There’s quite a bit.

Pantuck’s paper triggered the need for explanations.  Why would pomegranate be so effective against prostate cancer? 

His team of researchers has published several more papers.  In September 2007 they detailed  various laboratory studies they had undertaken to understand the mechanism by which the juice had acted.  They consider the ellagitannins (ETs) to be the active constituent in the juice. Once eaten these ETs are broken down releasing ellagic acid (EA) that is then fermented by bacteria in the intestine into the chemical,  3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one.  A rather long name; it’s usually referred to as urolithin A, or UA for short. 

In February Pantuck’s group published another paper detailing how pomegranate prevented angiogenesis in prostate cancer cells.

In May, Hong et al from UCLA reported that pomegranate juice prevents prostate cancer cells from generating their own testosterone to stimulate their own growth.   Heber also from Pantuck’s original group at UCLA had an article published in Cancer Letters in May, again on ellagic acid and prostate cancer.

Though pomegranate appears excellent at hindering prostate cancer growth, it appears to stimulate beneficial changes in the same vicinity.  In April an article was published detailing how pomegranate increases sperm count. 

The research has also touched on cardiovascular health.  Extracts from pomegranate prevent development of arthrosclerosis.   Speaking of circulation, several papers have been published suggesting that pomegranate as a treatment for erectile dysfunction. It seems pomegranate juice increases nitric oxide (NO) which in today’s biology is a big thing.

Topical application of pomegranate extracts has again been shown to protect the skin from UV exposure.   This idea has been kicking around for years.  We first mentioned this in a newsletter several years ago:

http://denvernaturopathic.com/news/pomupdate.html

Aviram the cardiologist from Haifa has published again.  Recall that he is the guy who first started all the interest in pomegranates and cardiovascular disease by showing that drinking pomegranate juice removed artherosclerotic plaque from occluded carotid arteries.  Back in February he and his colleagues had an article published detailing their experiments feeding pomegranate juice and other pomegranate stuff to mice bred to develop atherosclerosis.

They tried out various parts of the pomegranate fruit separately: peels, arils, seeds, and flowers, in comparison to whole fruit juice. They fed this stuff to the atherosclerotic mice for 3 months. All these things had antioxidative properties when measured in the lab.   After 3 months, almost all the mice showed improvement and reduction of atherosclerosis. The amount of reduction varied widely with the part of the plant the mice were fed.

Part of Fruit                     Reduction in atherosclerosis

Pomegranate Juice                  44%

peels                                       38%,                                 

Arils                                          6%

Seeds                                       no effect

Flowers                                  70%

Consumption of the flowers also reduced serum lipids and glucose levels by 18-25%.   At this point we don’t have the option of consuming pomegranate flowers.

In the last few years a good number of manufacturers have introduced pomegranate extracts in pill form hoping to pass on the benefit of pomegranate juice to eager consumers.  It’s not clear that these concentrates will be as effective as the juice.  Some of them may actually be too strong.  Ephraim Lansky, MD, PhD, who has long been my guru in all things to do with pomegranate, wrote an article suggesting that these concentrates that contain as much as 40% may have less effect than the less concentrated extracts.

This being the case, it makes best to stick with the juice rather than swallowing pills.  Almost all of the research on pomegranate published has used the PomWonderful brand juice at 8 ounces a day.  Costco’s new jumbo bottle provides a week’s worth of juice.  What could be simpler?  Cost was just under ten bucks.

Last years article “In praise of Costco” is posted at:

http://denvernaturopathic.com/Costco.htm

References:

Clin Cancer Res. 2006 Jul 1;12(13):4018-26.Click here to read Links

    Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

    Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L, Belldegrun A.

    Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1738, USA. apantuck@mednet.ucla.edu

    PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.

J Agric Food Chem. 2007 Sep 19;55(19):7732-7. Epub 2007 Aug 28.Click here to read Links

    Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland.

    Seeram NP, Aronson WJ, Zhang Y, Henning SM, Moro A, Lee RP, Sartippour M, Harris DM, Rettig M, Suchard MA, Pantuck AJ, Belldegrun A, Heber D.

    Center for Human Nutrition, Greater Los Angeles VA Medical Center, Los Angeles, California, USA. nseeram@mednet.ucla.edu

    Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP.

Int J Oncol. 2008 Feb;32(2):475-80.Click here to read Links

    Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo.

    Sartippour MR, Seeram NP, Rao JY, Moro A, Harris DM, Henning SM, Firouzi A, Rettig MB, Aronson WJ, Pantuck AJ, Heber D.

    Center for Human Nutrition, Los Angeles, CA 90095-1742, USA.

    Angiogenesis is critical to tumor growth and is stimulated by tissue hypoxia due to poor oxygen delivery. In turn, cellular hypoxia leads to angiogenesis via the induction of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at a cellular level. Pomegranate juice and extracts, which are rich sources of ellagitannins, have been shown to have chemopreventive potential against prostate cancer, but there have been no studies on the effects of an ellagitannin-rich pomegranate extract on angiogenesis. Human prostate cancer cells (LNCaP) and human umbilical vein endothelial cells (HUVEC) were incubated with a pomegranate extract standardized to ellagitannin content (POMx), under normoxic and hypoxic conditions in vitro. Human prostate cancer cells (LAPC4) were injected subcutaneously into severe combined immunodeficient (SCID) mice and the effects of oral administration of POMx on tumor growth, microvessel density, and HIF-1alpha and VEGF expression were determined after 4 weeks of treatment. POMx inhibited the proliferation of LNCaP and HUVEC cells significantly under both normoxic and hypoxic conditions. HIF-1alpha and VEGF protein levels were also reduced by POMx under hypoxic conditions. POMx decreased prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-1alpha expression after 4 weeks of treatment in SCID mice. These results demonstrate that an ellagitannin-rich pomegranate extract can inhibit tumor-associated angiogenesis as one of several potential mechanisms for slowing the growth of prostate cancer in chemopreventive applications. Further studies in humans are needed to confirm that angiogenesis can be inhibited by an ellagitannin-rich pomegranate extract administered orally as a dietary supplement.

J Nutr Biochem. 2008 May 12. [Epub ahead of print]Click here to read Links

    Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor.

    Hong MY, Seeram NP, Heber D.

    Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

    Prostate cancer is dependent on circulating testosterone in its early stages and is treatable with radiation and surgery. However, recurrent prostate tumors advance to an androgen-independent state in which they progress in the absence of circulating testosterone, leading to metastasis and death. During the development of androgen independence, prostate cancer cells are known to increase intracellular testosterone synthesis, which maintains cancer cell growth in the absence of significant amounts of circulating testosterone. Overexpression of the androgen receptor (AR) occurs in androgen-independent prostate cancer and has been proposed as another mechanism promoting the development of androgen independence. The LNCaP-AR cell line is engineered to overexpress AR but is otherwise similar to the widely studied LNCaP cell line. We have previously shown that pomegranate extracts inhibit both androgen-dependent and androgen-independent prostate cancer cell growth. In this study, we examined the effects of pomegranate polyphenols, ellagitannin-rich extract and whole juice extract on the expression of genes for key androgen-synthesizing enzymes and the AR. We measured expression of the HSD3B2 (3beta-hydroxysteroid dehydrogenase type 2), AKR1C3 (aldo-keto reductase family 1 member C3) and SRD5A1 (steroid 5alpha reductase type 1) genes for the respective androgen-synthesizing enzymes in LNCaP, LNCaP-AR and DU-145 human prostate cancer cells. A twofold suppression of gene expression was considered statistically significant. Pomegranate polyphenols inhibited gene expression and AR most consistently in the LNCaP-AR cell line (P=.05). Therefore, inhibition by pomegranate polyphenols of gene expression involved in androgen-synthesizing enzymes and the AR may be of particular importance in androgen-independent prostate cancer cells and the subset of human prostate cancers where AR is up-regulated.

J Agric Food Chem. 2008 Feb 13;56(3):1148-57. Epub 2008 Jan 4.Click here to read Links

    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.

    Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M.

    The Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel. aviram@tx.technion.ac.il

    We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E 0 mice consumed POM extracts [200 microg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E (0) mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18-25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E (0)-MPM were significantly reduced by approximately 15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.

Int J Impot Res. 2007 Nov-Dec;19(6):564-7. Epub 2007 Jun 14.Click here to read Links

    Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study.

    Forest CP, Padma-Nathan H, Liker HR.

    The Male Clinic, Beverly Hills, CA, USA. cforest@usc.edu

    This randomized-controlled trial examined the efficacy of wonderful variety pomegranate juice versus placebo in improving erections in 53 completed subjects with mild to moderate erectile dysfunction. The crossover design consisted of two 4-week treatment periods separated by a 2-week washout. Efficacy was assessed using International Index of Erectile Function (IIEF) and Global Assessment Questionnaires (GAQ). Of the 42 subjects who demonstrated improvement in GAQ scores after beverage consumption, 25 reported improvement after drinking pomegranate juice. Further, 17 subjects showed preference of one beverage to the other. Subjects were more likely to have improved scores when pomegranate juice was consumed (P=0.058). Although overall statistical significance was not achieved, this pilot study suggests the possibility that larger cohorts and longer treatment periods may achieve statistical significance.

Nitric Oxide. 2007 Aug;17(1):50-4. Epub 2007 May 5.Click here to read Links

    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.

    de Nigris F, Balestrieri ML, Williams-Ignarro S, D'Armiento FP, Fiorito C, Ignarro LJ, Napoli C.

    Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, Complesso S. Andrea delle Dame, Via de Crecchio 7, 1st School of Medicine, II University of Naples, Naples 80138, Italy.

    Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P<0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression (P <0.05). Plasma nitrate and nitrite (NO(x)) levels were significantly increased by PFE and PJ (P<0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome.

Cardiovasc Res. 2007 Jan 15;73(2):414-23. Epub 2006 Sep 1.Click here to read Links

    Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis.

    de Nigris F, Williams-Ignarro S, Sica V, Lerman LO, D'Armiento FP, Byrns RE, Casamassimi A, Carpentiero D, Schiano C, Sumi D, Fiorito C, Ignarro LJ, Napoli C.

    Department of General Pathology, School of Medicine, University of Naples, 80134 Naples, Italy.

    BACKGROUND: Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. AIM OF THE STUDY: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. RESULTS: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of L-arginine to L-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC(25) values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. CONCLUSION: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.

Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4896-901. Epub 2005 Mar 21.Click here to read Click here to read Links

    Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress.

    de Nigris F, Williams-Ignarro S, Lerman LO, Crimi E, Botti C, Mansueto G, D'Armiento FP, De Rosa G, Sica V, Ignarro LJ, Napoli C.

    Department of General Pathology, School of Medicine, University of Naples, 80131 Naples, Italy.

    Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. The aim of the present study was to evaluate the effects of intervention with pomegranate juice (PJ) on oxidation-sensitive genes and endothelial NO synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Cultured human coronary artery endothelial cells (EC) exposed to high shear stress in vitro and hypercholesterolemic mice were used in this study. PJ concentrate reduced the activation of redox-sensitive genes (ELK-1 and p-JUN) and increased eNOS expression (which was decreased by perturbed shear stress) in cultured EC and in atherosclerosis-prone areas of hypercholesterolemic mice. Moreover, oral administration of PJ to hypercholesterolemic mice at various stages of disease reduced significantly the progression of atherosclerosis. This experimental study indicates that the proatherogenic effects induced by perturbed shear stress can be reversed by chronic administration of PJ. This approach may have implications for the prevention or treatment of atherosclerosis and its clinical manifestations.

    PMID: 15781875 [PubMed - indexed for MEDLINE]

J Agric Food Chem. 2008 Aug 22. [Epub ahead of print]Click here to read Links

    Protective Effects of Standardized Pomegranate (Punica granatum L.) Polyphenolic Extract in Ultraviolet-Irradiated Human Skin Fibroblasts.

    Pacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU.

    Departments of Nutrition and Food Science and Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843, and Pharmanza Herbals Pvt. Ltd., 31 Park West, West Premises Co-operative Society, Union Park, Pali Hill Road, Khar, Mumbai 400052, India smtalcott@tamu.edu.

    Exposure to ultraviolet (UV) radiation has been associated with several acute and chronic conditions, including sunburn, edema, hyperplasia, immunosuppression, photoaging, and skin cancer. The role of naturally occurring phytochemicals in the prevention of such UV-related conditions has captured increased interest. Pomegranate ( Punica granatum L.) is a rich source of polyphenolics, which have been shown to exert anti-inflammatory, antioxidant, and anticarcinogenic activity in numerous in vivo and in vitro studies. This work investigated potential protective effects of a pomegranate fruit extract standardized to punicalagins against UVA- and UVB-induced damage in SKU-1064 human skin fibroblast cells. Pomegranate extract (PE), in a range from 5 to 60 mg/L, was effective at protecting human skin fibroblasts from cell death following UV exposure, likely related to a reduced activation of the pro-inflammatory transcription factor NF-kappaB, a downregulation of proapoptotic caspase-3, and an increased G0/G1 phase, associated with DNA repair. Higher polyphenolic concentrations (500-10000 mg/L) were needed to achieve a significant reduction in UV-induced reactive oxygen species levels and increased intracellular antioxidant capacity (from 1.9 to 8.6 muM Trolox equivalents/mL). Results from this study demonstrate the protective effects of PE against UVA- and UVB-induced cell damage and the potential use of pomegranate polyphenolics in topical applications.

J Agric Food Chem. 2008 Feb 13;56(3):1148-57. Epub 2008 Jan 4.Click here to read Links

    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.

    Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M.

    The Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel. aviram@tx.technion.ac.il

    We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E 0 mice consumed POM extracts [200 microg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E (0) mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18-25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E (0)-MPM were significantly reduced by approximately 15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.

J Med Food. 2006 Spring;9(1):119-22.Click here to read Links

    Beware of pomegranates bearing 40% ellagic Acid.

    Lansky EP.

    Rimonest Ltd., Haifa, Israel. info@rimonest.com

    A recent profusion of pomegranate nutraceutical products, "standardized to 40% ellagic acid," has appeared in the marketplace. This Perspective reviews the chemical and functional studies of pomegranate as well as the virtues and dangers of ellagic acid, and concludes that synergy among the various pomegranate fractions and phytochemicals is the most important factor for assessing strength of pomegranate nutraceutical preparations, and not simply the concentration of ellagic acid. Ellagic acid concentration in final products is likely to have an optimal therapeutic range, which very likely is less than 40%. The wisdom of designing and engineering pomegranate nutraceutical products to maximize therapeutic or chemopreventive synergy is suggested, as opposed to preparations that are designed and engineered simply to maximize the concentration of a single phytochemical. The implications of this strategy may be generalized for the optimization of nutraceutical preparations from other medicinal plants as well.


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