Exotic Antioxidant Superfruits - Pomegranate: Review of current research

Review of current research

Below are 13 reports from late 2005 to present (PubMed; Ref. 3) on pomegranate as an antioxidant food source. Original abstracts from PubMed are provided followed by a synopsis for general consumers.

1. Mertens-Talcott SU, Jilma-Stohlawetz P, Rios J, Hingorani L, Derendorf H.

Pharmaceutics Department, University of Florida, Gainesville, Florida 32610, USA.

Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers.

J. Agric. Food Chem. 2006 Nov 15;54(23):8956-61.

Abstract. The intake of polyphenols has been demonstrated to have health-promoting and disease-preventive effects. The pomegranate (Punica granatum L.), which is rich in several polyphenols, has been used for centuries in ancient cultures for its medicinal purposes. The potential health benefits of pomegranate polyphenols have been demonstrated in numerous in vitro studies and in vivo experiments. This study investigated the absorption and antioxidant effects of a standardized extract from pomegranate in healthy human volunteers after the acute consumption of 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h. The plasma metabolites urolithin A, urolithin B, hydroxyl-urolithin A, urolithin A-glucuronide, and dimethyl ellagic acid-glucuronide were identified by HPLC-MS. The antioxidant capacity measured with the oxygen radical absorbance capacity (ORAC) assay was increased with a maximum effect of 32% after 0.5 h, whereas the generation of reactive oxygen species (ROS) was not affected. The inflammation marker interleukin-6 (IL-6) was not significantly affected after 4 h after the consumption of the extract. Overall, this study demonstrated the absorbability of EA from a pomegranate extract high in ellagitannin content and its ex vivo antioxidant effects.

Synopsis. These authors examined the rate of absorption into human blood of ellagic acid extracted from pomegranate juice. Maximum blood levels of ellagic acid were reached in one hour after consumption and maximum antioxidant effect assessed by ORAC was reached in 30 minutes.

2. 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.

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

Clin Cancer Res. 2006 Jul 1;12(13):4018-26.

Abstract. 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.

Synopsis. In the first report of the human clinical trials underway at UCLA as mentioned above, these authors state that daily pomegranate juice (8 oz.) decreases an index of prostate cell proliferation and so appears to have potential for inhibiting prostate cancer, although further research is needed to verify this preliminary conclusion.

3. 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 Italy; Excellence Research Center of Cardiovascular Diseases, II University of Naples, Italy.

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

Cardiovasc Res. 2007 Jan 15;73(2):414-23.

Abstract. 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.

Synopsis. There were 4 main findings of this study: punicalagin and pomegranate juice both 1) reduced the activities of oxidation-sensitive genes (meaning they inhibited activation of these genes); 2) increased activity of the enzyme that makes nitric oxide (nitric oxide synthase) which helps to relax arteries and increase blood flow; 3) reduced progression of high blood cholesterol and development of atherosclerosis; and 4) improved response of isolated blood vessels to dilator stimuli. Overall, the study indicates a role for pomegranate juice or punicalagin as a mediator of reduced oxidation and vascular relaxation in atherosclerosis.

4. Kasai K, Yoshimura M, Koga T, Arii M, Kawasaki S.

Research and Development Division, Kikkoman Corporation, 399 Noda, Noda, Chiba 278-0037, Japan.

Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin.

J Nutr Sci Vitaminol (Tokyo). 2006 Oct;52(5):383-8.

Abstract. We performed a double-blind, placebo-controlled trial to clinically evaluate the protective and ameliorative effects of ellagic acid-rich pomegranate extract on pigmentation in the skin after ultraviolet ray (UV) irradiation, using female subjects in their 20s to 40s. Thirteen healthy volunteers per group were randomly assigned to three groups; namely, high dose (200 mg/d ellagic acid), low dose (100 mg/d ellagic acid) and control (0 mg/d ellagic acid: placebo). Each group received the respective test foods for 4 wk. Each subject received a 1.5 MED (minimum erythema dose) of UV irradiation on an inside region of the right upper arm, based on the MED value measured on the previous day. Luminance (L), melanin and erythema values were measured before the start of the test food intake, and after 1, 2, 3 and 4 wk following the start of the test food intake. Further, questionnaires were conducted regarding the condition of the skin before the start of the test food intake and at the termination of the test food intake. As a result, decreasing rates of L values from the baseline in the low- and high-dose groups were inhibited by 1.35% and 1.73% respectively, as compared to the control group. Further, a stratified analysis using subjects with a slight sunburn revealed an inhibited decrease of L values compared with the control group at 1, 2 (p<0.01, respectively) and 4 wk (p<0.05) after the start of the test food intake in the low-dose group, and at 2 and 3 wk (p<0.05) in the high-dose group. Furthermore, the results of questionnaires showed ameliorating tendencies due to the test food, in some items such as "brightness of the face" and "stains and freckles." Based on the above-mentioned results, it is suggested that ellagic acid-rich pomegranate extract, ingested orally, has an inhibitory effect on a slight pigmentation in the human skin caused by UV irradiation.

Synopsis. This small clinical study demonstrated that dietary ellagic acid from pomegranate inhibited sunburn in young women and created subjective improvement assessed by the subjects in their own complexions.

5. Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM.

Department of Psychology, Loma Linda University, Loma Linda, CA 92354, USA.

Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease.

Neurobiol Dis. 2006 Dec;24(3):506-15.

Abstract. Although there are no proven ways to delay onset or slow progression of Alzheimer's disease (AD), studies suggest that diet can affect risk. Pomegranates contain very high levels of antioxidant polyphenolic substances as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in different model systems. We asked whether dietary supplementation with pomegranate juice (PJ) would influence behavior and AD-like pathology in a transgenic mouse model. Transgenic mice (APP(sw)/Tg2576) received either PJ or sugar water control from 6 to 12.5 months of age. PJ-treated mice learned water maze tasks more quickly and swam faster than controls. Mice treated with PJ had significantly less (approximately 50%) accumulation of soluble Abeta42 and amyloid deposition in the hippocampus as compared to control mice. These results suggest that further studies to validate and determine the mechanism of these effects, as well as whether substances in PJ may be useful in AD, should be considered.

Synopsis. In this mouse study where pomegranate juice was fed to the animals for 6 months, the juice in the diet appeared to improve performance in a memory task and reduced amyloid deposition in the brain's hippocampus where memory is processed. The authors propose the results are evidence that pomegranate juice and its antioxidant phenolics modify mechanisms of Alzheimer's disease.

6. Ignarro LJ, Byrns RE, Sumi D, de Nigris F, Napoli C.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.

Nitric Oxide. 2006 Apr 18; [Epub ahead of print]

Abstract. Pomegranate juice (PJ), which is a rich source of potent flavonoid antioxidants, was tested for its capacity to protect nitric oxide (NO) against oxidative destruction and enhance the biological actions of NO. Employing chemiluminescence headspace analysis, PJ was found to be a potent inhibitor of superoxide anion-mediated disappearance of NO. PJ was much more potent than Concord grape juice, blueberry juice, red wine, ascorbic acid, and dl-alpha-tocopherol. As little as 3mul of a 6-fold dilution of PJ, in a reaction volume of 5000mul, produced a marked antioxidant effect, whereas 300mul of undiluted blueberry juice or nearly 1000mul of undiluted Concord grape juice were required to produce similar effects. PJ and other antioxidant-containing products were found to augment the anti-proliferative action of NO (DETA/NO) on vascular smooth muscle cell (rat aorta) proliferation. PJ was much more effective than the other products tested and elicited no effects when tested alone in the absence of added NO. Similarly, neither PJ nor the other products enhanced the anti-proliferative action of alpha-difluoromethylornithine, a stable substance that inhibits cell growth by NO-independent mechanisms. In order to determine whether PJ is capable of increasing the production of NO by vascular endothelial cells, PJ was tested for its capacity to upregulate and/or activate endothelial NO synthase (eNOS) in bovine pulmonary artery endothelial cells. PJ elicited no effects on eNOS protein expression or catalytic activity. Moreover, PJ did not enhance promoter activity in the eNOS gene (COS-7 cells transfected with eNOS). These observations indicate that PJ possesses potent antioxidant activity that results in marked protection of NO against oxidative destruction, thereby resulting in augmentation of the biological actions of NO.

Synopsis. A theory of antioxidant protection in human biology is that antioxidants protect other chemicals from being neutralized or destroyed by oxidants. For example, vitamin C, a universal antioxidant, protects other vitamins (like vitamin E) from being oxidized by free radicals. In this study, the authors showed that pomegranate juice antioxidants (punicalagin and other tannins) were highly protective of nitric oxide in vitro in a way more powerful than the antioxidants in grape or blueberry juice, red wine, vitamin C or vitamin E. Pomegranate juice did not exert these effects through activity on the enzyme that synthesizes nitric oxide.

7. Malik A, Mukhtar H.

Department of Dermatology, University of Wisconsin, Madison 53706, USA.

Prostate cancer prevention through pomegranate fruit.

Cell Cycle. 2006 Feb;5(4):371-3.

Abstract. Prostate cancer (CaP) is the second leading cause of cancer-related deaths among U.S. males with a similar trend in many Western countries. CaP is an ideal candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age, and thus even a modest delay in disease progression achieved through pharmacological or nutritional intervention could significantly impact the quality of life of these patients. In this regard we and others have proposed the use of dietary antioxidants as candidate CaP chemopreventive agents. The fruit pomegranate derived from the tree Punica granatum has been shown to possess strong antioxidant and anti-inflammatory properties. In a recent study, we showed that pomegranate fruit extract (PFE), through modulations in the cyclin kinase inhibitor-cyclin-dependent kinase machinery, resulted in inhibition of cell growth followed by apoptosis of highly aggressive human prostate carcinoma PC3 cells. These events were associated with alterations in the levels of Bax and Bcl-2 shifting the Bax:Bcl-2 ratio in favor of apoptosis. Further, we showed that oral administration of a human acceptable dose of PFE to athymic nude mice implanted with CWR22Rnu1 cells resulted in significant inhibition of tumor growth with concomitant reduction in secretion of prostate-specific antigen (PSA) in the serum. The outcome of this study could have a direct practical implication and translational relevance to CaP patients, because it suggests that pomegranate consumption may retard CaP progression, which may prolong the survival and quality of life of the patients.

Synopsis. In preliminary studies, these authors had examined molecular mechanisms of how pomegranate juice antioxidants interfere with the cancer development process. In this report, they show in a mouse cancer model that pomegranate juice inhibits tumor progression and reduces prostate tumor antigen in the blood, indicating that pomegranate juice consumption may be effective for inhibiting development of prostate cancer.

8. Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D.

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

Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells.

J Agric Food Chem. 2006 Feb 8;54(3):980-5.

Abstract. Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.

Synopsis. In this biochemical study allowing precise identification of molecular mechanisms of pomegranate juice antioxidants, it was shown that inflammatory enzymes in colon cancer cells were inhibited by the complete juice. Ellagic acid, a phenolic antioxidant that may be released by punicalagin during metabolism, was not effective by itself, indicating that the whole ellagitannin (punicalagin or other yet unidentified phytochemicals) is the more effective antioxidant in this model.

9. Larrosa M, Tomas-Barberan FA, Espin JC.

Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, Campus de Espinardo, 30100 Espinardo, Murcia, Spain.

The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway.

J Nutr Biochem. 2005 Oct 11; [Epub ahead of print]

Abstract. Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to the so-called hydrolysable tannins found in strawberries, raspberries, walnuts, pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product, ellagic acid (EA), have been reported to induce apoptosis in tumour cells. Ellagitannins are not absorbed in vivo but reach the colon and release EA that is metabolised by the human microflora. Our aim was to investigate the effect of a dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2 and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on Caco-2 cells: down-regulation of cyclins A and B1 and upregulation of cyclin E, cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS-independent, caspase 8-independent) through bcl-XL down-regulation with mitochondrial release of cytochrome c into the cytosol, activation of initiator caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3 and 9 were detected). In the case of Caco-2 cells, no specific effect can be attributed to PUNI since it was hydrolysed in the medium to yield EA, which entered into the cells and was metabolised to produce dimethyl-EA derivatives. Our study suggests that the anticarcinogenic effect of dietary ETs could be mainly due to their hydrolysis product, EA, which induced apoptosis via mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells.

Synopsis. This study examined the hydrolysis of punicalagin into ellagic acid and concluded that ellagic acid was essential for the anti-cancer effect of dietary pomegranate ellagitannins like punicalagin. Induction of apoptosis (stimulated natural cell death) in human colon cancer cells in vitro was the experimental determinant of an ellagic acid effect.

10. Neurath AR, Strick N, Li YY, Debnath AK.

Biochemical Virology Laboratory, Lindsley F. Kimball Research Institute, 310 East 67 Street, New York, NY 10021, USA

Punica granatum (pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide.

Ann N Y Acad Sci. 2005 Nov;1056:311-27.

Abstract. For approximately 24 years the AIDS pandemic has claimed approximately 30 million lives, causing approximately 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be acceptable, accessible, affordable, and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients (inactive materials of drug dosage forms) or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Therefore, fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor, and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. The results indicate that HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Therefore, these results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.

Synopsis. This study applied in vitro methods to show that pomegranate juice had antiviral effects that may be transferable to widespread use of the juice as an anti-HIV preventative. The mechanism of inhibition by pomegranate juice appears to be inhibition of binding by the virus and reduction of its ability to spread in the experimental environment of these experiments. Such results are promising but need further evaluation to demonstrate the in vitro mechanisms and in vivo efficacy of using pomegranate juice for such a complex, diversified application.

11. Jeune MA, Kumi-Diaka J, Brown J.

Department of Biological Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Davie, FL 33314-7714, USA.

Anticancer activities of pomegranate extracts and genistein in human breast cancer cells.


J Med Food. 2005 Winter;8(4):469-75.

Abstract. Previous studies have demonstrated the anticarcinogenic activity of pomegranate extracts and genistein in a series of human cancer cells. In the present study, the potential anticancer effects of pomegranate extracts and genistein on inhibition of cell proliferation and induction of apoptosis in human breast cancer cells was investigated. Human breast cancer cells (MCF-7) were cultured as monolayers in complete RPMI 1640 medium. The cells were cultured for 48 hours to allow growth and achieve about 80% confluence in 48-well culture plates, and then exposed to the agents for 24 hours in single and combination treatments. Post-treatment growth rate and apoptosis induction were assessed by the use of a series of bioassays-lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (inner salt) for viability and cytotoxicity; acridine orange-ethidium bromide and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays for induction of apoptosis. Both pomegranate extracts and genistein had significant (dose- and time-dependent) cytotoxic and growth inhibition effects on MCF-7 cancer cells. Both growth inhibition and cytotoxicity were significantly higher (P < .01) in the combination treatments than in the single treatments with either agent. The data revealed that both drugs in single and in combination treatments induced apoptosis in MCF-7 cells. Apoptotic induction in the combination treatments was significantly higher (P < .01) than in single treatments. Both pomegranate extracts and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis, with combination treatment being more efficacious than single treatments.

Synopsis. Similar to a 2005 biochemical study on apoptosis (natural cell death) of human breast cancer cells in vitro reported before the one above, these investigators demonstrate that pomegranate extracts -- whether alone or in combination with genistein, an antioxidant from soy beans -- stimulated apoptosis and inhibited the growth of the breast cancer cells. Combining pomegranate with soy appears to be even more effective than either phytochemical source alone.

12. Rosenblat M, Hayek T, Aviram M.

The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, 31096 Haifa, Israel.

Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages.

Atherosclerosis. 2005 Oct 11; [Epub ahead of print]

Abstract. Diabetes is associated with increased oxidative stress and atherosclerosis development. In the present study, we investigated the effects of pomegranate juice (PJ; which contains sugars and potent antioxidants) consumption by diabetic patients on blood diabetic parameters, and on oxidative stress in their serum and macrophages. Ten healthy subjects (controls) and 10 non-insulin dependent diabetes mellitus (NIDDM) patients who consumed PJ (50ml per day for 3 months) participated in the study. In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances (TBARS) were both increased, by 350% and 51%, respectively, whereas serum SH groups content and paraoxonase 1 (PON1) activity, were both decreased (by 23%). PJ consumption did not affect serum glucose, cholesterol and triglyceride levels, but it resulted in a significant reduction in serum lipid peroxides and TBARS levels by 56% and 28%, whereas serum SH groups and PON1 activity significantly increased by 12% and 24%, respectively. In the patients versus controls monocytes-derived macrophages (HMDM), we observed increased level of cellular peroxides (by 36%), and decreased glutathione content (by 64%). PJ consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%) in the patients' HMDM. The patients' versus control HMDM took up oxidized LDL (Ox-LDL) at enhanced rate (by 37%) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake (by 39%). We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in antioxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.

Synopsis. In this analysis of diabetic patients, the investigators showed that pomegranate juice improved ability of macrophages (immune-response cells) to absorb low-density lipids, indicating this effect may inhibit atherosclerosis development. The authors concluded that pomegranate juice consumption over 3 months may help diabetic patients by lowering oxidative stress that often leads to vascular disease during diabetes.

13. Sumner MD, Elliott-Eller M, Weidner G, Daubenmier JJ, Chew MH, Marlin R, Raisin CJ, Ornish D.

The Preventive Medicine Research Institute, Sausalito, California, USA.

Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.

Am J Cardiol. 2005 Sep 15;96(6):810-4.

Abstract. Pomegranate juice contains antioxidants such as soluble polyphenols, tannins, and anthocyanins and may have antiatherosclerotic properties. However, no study has investigated the effects of pomegranate juice on patients who have ischemic coronary heart disease (CHD). We investigated whether daily consumption of pomegranate juice for 3 months would affect myocardial perfusion in 45 patients who had CHD and myocardial ischemia in a randomized, placebo-controlled, double-blind study. Patients were randomly assigned into 1 of 2 groups: a pomegranate juice group (240 ml/day) or a placebo group that drank a beverage of similar caloric content, amount, flavor, and color. Participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months. Visual scoring of images using standardized segmentation and nomenclature (17 segments, scale 0 to 4) was performed by a blinded independent nuclear cardiologist. To assess the amount of inducible ischemia, the summed difference score (SDS) was calculated by subtracting the summed score at rest from the summed stress score. The experimental and control groups showed similar levels of stress-induced ischemia (SDS) at baseline (p >0.05). After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group (SDS -0.8 +/- 2.7) but increased in the control group (SDS 1.2 +/- 3.1, p <0.05). This benefit was observed without changes in cardiac medications, blood sugar, hemoglobin A1c, weight, or blood pressure in either group. In conclusion, daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have CHD.

Synopsis. This study examined the effect of 3 months of daily consumption of pomegranate juice on parameters of heart function in patients with heart disease. During an exercise stress test, the patients who consumed pomegranate juice had better heart performance scores and so may have improved heart function resulting from phytochemicals in pomegranate juice.

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General References

  1. Gross PM, Crown I. Is mangosteen a superfruit? Nutrient and antioxidant properties, Natural Products Information Center, in press, 2007. Update by NPICenter, http://www.npicenter.com/anm/anmviewer.asp?a=17613&z=201
  2. Nutrition data for pomegranate, http://www.nutritiondata.com/facts-C00001-01c20Ws.html
  3. PubMed, http://pubmed.gov
  4. Wikipedia on pomegranate, http://en.wikipedia.org/wiki/Pomegranate

About the Author
Paul M. Gross, Ph.D., received his doctorate in physiology from the University of Glasgow, Scotland and was a post-doctoral fellow in neuroscience at the Laboratory of Cerebral Metabolism, National Institutes of Health, Bethesda, MD. A former Research Scholar for the Heart and Stroke Foundation of Ontario, he published 85 peer-reviewed journal reports and book chapters over a 25 year career in medical science, and was recipient of the Karger Memorial Award, Switzerland, for publications on brain capillaries. Dr. Gross is on the Steering Committee of the International Berry Health Association. He is senior author of a 2006 book on the goji berry entitled Wolfberry: Nature’s Bounty of Nutrition and Health (Booksurge Publishing, Amazon.com, http://wolfberry.org/) and is publisher of The Berry Doctor's Journal, http://berrydoctor.com where the public can obtain free information on berry science and nutrition.

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