Since heart disease has become rampant among parrots, I am constantly researching good natural options for these birds. Pomegranate ranks high on the list. I have been impressed by the large number of good scientific studies that have been run on pomegranate juice as well as the extract. Since many bird species love pomegranate, I feel that this fruit should be liberally included in natural cardiac and arthritis protocols. Since we can't send our parrots on the daily fifty mile flights that they take in the wild, and even our smaller birds are in deplorable physical condition when compared to their wild counterparts, pomegranate extract and juice can be extremely beneficial for birds who are in pain due to debility. The juice and extract can lower cholesterol and even help to dissolve arterial plaque. I have seen a large number of testimonials from people with cardiovascular disease who were able to avert bypass surgery and/or who were able to come off of medications for blood pressure and cholesterol after drinking approximately 8 ounces of pomegranate juice daily for a few weeks or months. Pomegranate juice and extract also appear to reverse arthritic conditions: I read some exciting testimonials about people with crippling cases of osteoarthritis who responded beautifully to pomegranate juice and were soon able to move freely without pain. For older birds, I feel that a half ounce of juice daily or a half capsule of extract would be an extremely healthful addition to the daily diet. Or, lots of fresh pomegranate would work too!

Below is some of the research, loads more online via google.

Lainey Alexander

Disclaimer: These statements have not been evaluated by the Food and Drug Administration, or by any veterinarian. All information, including any product or technique mentioned, is for educational purposes only. None of the information is intended to diagnose or treat any disease.

Pomegranate Research Update

Pomegranate fruit extracts can block enzymes that contribute to osteoarthritis according to a Case Western Reserve University School of Medicine study published in the September 2005 issue of the Journal of Nutrition. The study looked at the ability of an extract of pomegranate fruit against Interleukin-1b (IL-1b), a pro-inflammatory protein molecule that plays a key role in cartilage degradation in osteoarthritis. Plant-based flavonoids found in fruits, leaves and vegetables have attracted a lot of attention for their beneficial health effects in various diseases. Pomegranate, in particular, has been found to possess antioxidant and anti-inflammatory properties that have potential therapeutic benefits in a variety of diseases. The Case study demonstrated for the first time the ability of pomegranate fruit extracts to slow the deterioration of human cartilage.

Pomegranate extract may prevent prostate cancer or slow its growth, if results of lab experiments conducted at the University of Wisconsin in Madison translate to real-world benefits. Pomegranates are high in polyphenolic compounds, making its juice higher in antioxidant activity than red wine and green tea. When they incubated prostate cancer cells with low concentrations of pomegranate extract, they observed a dose-related inhibition of cell growth. In prostate cancer cells driven by male hormones (androgens) and expressing prostate specific antigen (PSA), treatment with pomegranate extract decreased androgen receptors and PSA expression. When human prostate cancer cells were injected into mice, feeding the animals pomegranate extract delayed the appearance of tumors. Tumor growth was significantly inhibited and survival was prolonged.

In men with recurrent prostate cancer, drinking 8 ounces per day of pomegranate juice significantly increases the time it takes for an increase in levels of prostate specific antigen (PSA), an indicator of prostate cancer. Before the men in the study began consuming pomegranate juice, the average PSA doubling time, a measure of tumor activity, was 15 months. The average time after treatment was 37 months. So, there was almost a 2-year increase in the doubling time. Pomegranate juice contains a number of antioxidants thought to have anti-cancer effects, Pomegranate juice contains estrogen-like plant substances called phytoestrogens that could be useful in combating prostate cancer. Pomegranate juice therapy was well tolerated and no serious adverse effects were reported. In addition to the beneficial increase in PSA doubling time, in vitro testing showed decreased cancer cell division and proliferation and increased cancer cell death. Urine testing confirmed the presence of pomegranate antioxidants in all men. The study was funded by the Stewart and Lynda Resnick Trust, which own the POM Wonderful pomegranate juice company.

Drinking pomegranate juice during pregnancy may help reduce the risk of brain injuries in babies.

Decreased blood flow and oxygen to an infant's developing brain during pregnancy, birth and early development is linked to premature birth and can lead to brain tissue loss, seizures and mobility impairments such as cerebral palsy. The phenomenon, called hypoxia ischemia, causes brain injury in approximately two of every 1,000 full-term human births and in a very high percentage of babies born before 34 weeks of gestation. Researchers at the Washington University School of Medicine in St. Louis found that newborn mice whose mothers drank water mixed with pomegranate concentrate lost 60 percent less brain tissue than mice whose mothers drank sugar water or other fluids. Pomegranates contain very high concentrations of polyphenols, a substance also found in berries and grapes, which has been shown to potentially have anti-aging and neuroprotective effects.

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.

Mehta R, Lansky EP. University of Illinois at Chicago, Chicago

We previously reported anticancer effects of pomegranate extracts in human breast cancer cells in vitro and also chemopreventive activity of pomegranate fermented juice polyphenols (W) in a mouse mammary organ culture. In the present study we decided to expand the investigations to also include an evaluation of the potential chemopreventive efficacy of a purified chromatographic peak of W (Peak B), and also of whole pomegranate seed oil. The results highlight enhanced breast cancer preventive potential both for the purified compound peak B and for pomegranate seed oil, both greater than that previously reported for pomegranate fermented juice polyphenols.

Pomegranate fruit extract can block skin tumor formation in mice exposed to a cancer-causing agent, according to a report in the International Journal of Cancer. Dr. Hasan Mukhtar and colleagues from the University of Wisconsin at Madison conducted a variety of experiments to test the anti-cancer effects of pomegranate, a chemical with strong anti-inflammatory and antioxidant properties. In mice, putting pomegranate on the skin before exposure to the cancer-causing substance TPA inhibited the skin swelling and excessive cell growth that typically occurs. Moreover, mice treated with pomegranate developed fewer skin tumors than untreated mice.

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

BMC Infect Dis. 2004 Oct 14;4(1):41.

RESULTS: 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. CONCLUSION: 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.

Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia.

J Med Food. 2004 Fall;7(3):305-8.

This study assessed the effect of concentrated pomegranate juice consumption on lipid profiles of type II diabetic patients with hyperlipidemia. In this quasi-experimental study 22 otherwise healthy diabetic patients, 14 women and eight men were recruited from among patients referred to the Iranian Diabetes Society. The patients were followed for 8 weeks to establish a baseline for normal dietary intake before beginning the concentrated pomegranate juice intervention. During the pre-study period a 24-hour food recall and food records (recording flavonoid-rich foods) were completed every 10 days. At the end of the eighth week, anthropometric and biochemical assessments were done. Thereafter the patients consumed 40 g/day of concentrated pomegranate juice for 8 weeks, during which time dietary assessment was continued. After completing the study, anthropometric and blood indices were again evaluated. After consumption of concentrated pomegranate juice, significant reductions were seen in total cholesterol, low-density lipoprotein (LDL)-cholesterol, LDL-cholesterol / high-density lipoprotein (HDL)-cholesterol, and total cholesterol/HDL-cholesterol. But, there were no significant changes in serum triacylglycerol and HDL-cholesterol concentrations. Anthropometric indices, physical activity, kind and doses of oral hypoglycemic agents, and the intakes of nutrients and flavonoid-rich foods showed no change during the concentrated pomegranate juice consumption period. It is concluded that concentrated pomegranate juice consumption may modify heart disease risk factors in hyperlipidemic patients, and its inclusion therefore in their diets may be beneficial.

Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells.

J Med Food. 2004 Fall;7(3):274-83.

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO(2)-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED(50)) was 70 microg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED(50) = 250 g/mL). Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

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.

Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with pomegranate juice for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during pomegranate juice consumption. In the control group that did not consume pomegranate juice, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, pomegranate juice consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The results of the present study thus suggest that pomegranate juice consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to the potent antioxidant characteristics of pomegranate juice polyphenols.

Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells.

J Med Food. 2004 Spring;7(1):13-8.

Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo. Here we tested flavonoid-rich fractions from fresh (J) and fermented (W) pomegranate juice and from an aqueous extraction of pomegranate pericarps (P) as potential differentiation-promoting agents of human HL-60 promyelocytic leukemia cells. Four assays were used to assess differentiation: nitro blue tetrazolium reducing activity, nonspecific esterase activity, specific esterase activity, and phagocytic activity. In addition, the effect of these extracts on HL-60 proliferation was evaluated. Extracts W and P were strong promoters of differentiation in all settings, with extract J showing only a relatively mild differentiation-promoting effect. The extracts had proportional inhibitory effects on HL-60 cell proliferation. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.

Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice.

J Ethnopharmacol. 2004 May;92(1):93-101.

Pomegranate is known to contain estrogens (estradiol, estrone, and estriol) and show estrogenic activities in mice. In this study, we investigated whether pomegranate extract is effective on experimental menopausal syndrome in ovariectomized mice. Prolongation of the immobility time in forced swimming test, an index of depression, was measured 14 days after ovariectomy. The bone mineral density (BMD) of the tibia was measured by X-ray absorptiometry and the structure and metabolism of bone were also analyzed by bone histomorphometry. Administration of pomegranate extract (juice and seed extract) for 2 weeks to ovariectomized mice prevented the loss of uterus weight and shortened the immobility time compared with 5% glucose-dosed mice (control). In addition, ovariectomy-induced decrease of BMD was normalized by administration of the pomegranate extract. The bone volume and the trabecular number were significantly increased and the trabecular separation was decreased in the pomegranate-dosed group compared with the control group. Some histological bone formation/resorption parameters were significantly increased by ovariectomy but were normalized by administration of the pomegranate extract. These changes suggest that the pomegranate extract inhibits ovariectomy-stimulated bone turnover. It is thus conceivable that pomegranate is clinically effective on a depressive state and bone loss in menopausal syndrome in women.

Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo.

Angiogenesis. 2003;6(2):121-8.

We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W). VEGF was strongly downregulated in MCF-10A and MCF-7, and MIF upregulated in MDA-MB-231, overall showing significant potential for downregulation of angiogenesis by pomegranate fractions. An anti-proliferative effect on angiogenic cells was shown in human umbilical vein endothelial cell (HUVEC) and in myometrial and amniotic fluid fibroblasts, and inhibition of HUVEC tubule formation demonstrated in an in vitro model employing glass carrier beads. Finally, we showed a significant decrease in new blood vessel formation using the chicken chorioallantoic membrane (CAM) model in vivo. 'In sum, these varied studies employing different models in different laboratories overall demonstrate for the first time an anti-angiogenic potential of pomegranate fractions, suggesting further in vivo and clinical investigations

Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice.

J Med Food. 2003 Fall;6(3):157-61.

Hora JJ, Maydew ER, Lansky EP, Dwivedi C.

Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD

Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5-week-old, female CD(1) mice were used. Both groups had skin cancer initiated with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA application. Conclusions: Pomegrante seed oil (5%) significantly decreased tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlight the potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.

Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic.

J Agric Food Chem. 2003 May 21;51(11):3493-501.

The water-soluble ellagitanin punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (> or =2 g/L), the present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found in treated rats in any blood parameter analyzed (including the antioxidant enzymes gluthatione peroxidase and superoxide dismutase) with the exception of urea and triglycerides, which remained at low values throughout the experiment. Although the reason for the decrease is unclear, it could be due to the lower nutritional value of the punicalagin-enriched diet with respect to the standard rat food. Histopathological analysis of liver and kidney corroborated the absence of toxicity. In principle, the results reported here, together with the large safety margin considered, indicate the lack of toxic effect of punicalagin in rats during the 37 day period investigated. However, taking into account the high punicalagin content of pomegranate-derived foodstuffs, safety evaluation should be also carried out in humans with a lower dose and during a longer period of intake.

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.

The beneficial health effects attributed to the consumption of fruit and vegetables are related, at least in part, to their antioxidant activity. Of special interest is the inverse relationship between the intake of dietary nutrients rich in polyphenols and cardiovascular diseases. This effect is attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate polyphenols can protect LDL against cell-mediated oxidation via two pathways, including either direct interaction of the polyphenols with the lipoprotein and/or an indirect effect through accumulation of polyphenols in arterial macrophages. Pomegranate polyphenols were shown to reduce the capacity of macrophages to oxidatively modify LDL, due to their interaction with LDL to inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen species and also due to accumulation of polyphenols in arterial macrophages; hence, the inhibition of macrophage lipid peroxidation and the formation of lipid peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. These antioxidative and antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice. Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atherosclerotic lesions and this may be attributed to the protection of LDL against oxidation.

Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models.

J Agric Food Chem. 2002 Aug 14;50(17):4791-5.

Pomegranate (Punica granatum) peel extracts from the pomegranate tree fruit have been shown to possess significant antioxidant activity in various in vitro models. Dried pomegranate peels were powdered and extracted with methanol for 4 h. The dried methanolic extract was fed to albino rats of the Wistar strain, followed by carbon tetrachloride (CCl4), and the levels of various enzymes, such as catalase, peroxidase, and superoxide dismutase (SOD), and lipid peroxidation were studied. Treatment of rats with a single dose of CCl4 at 2.0 g/kg of body weight decreases the levels of catalase, SOD, and peroxidase by 81, 49, and 89% respectively, whereas the lipid peroxidation value increased nearly 3-fold. Pretreatment of the rats with a methanolic extract of pomegranate peel at 50 mg/kg (in terms of catechin equivalents) followed by CCl4 treatment causes preservation of catalase, peroxidase, and SOD to values comparable with control values, wheres lipid peroxidation was brought back by 54% as compared to control. Histopathological studies of the liver were also carried out to determine the hepatoprotection effect exhibited by the pomegranate peel extract against the toxic effects of CCl4. Histopathological studies of the liver of different groups also support the protective effects exhibited by the MeOH extract of pomegranate peel by restoring the normal hepatic architecture. 

ScienceDaily (Sep. 1, 2005) — Pomegranate fruit extracts can block enzymes that contribute to osteoarthritis according to a Case Western Reserve University School of Medicine study published in the September 2005 issue of the Journal of Nutrition.

The study looked at the ability of an extract of pomegranate fruit against Interleukin-1b (IL-1b), a pro-inflammatory protein molecule that plays a key role in cartilage degradation in osteoarthritis. Current treatments for osteoarthritis -- which affects 20 million people nationwide, according to the National Institutes of Health -- offer limited effectiveness and do little to slow joint destruction and disease progression.

"This has generated considerable interest in the identification and development of new approaches and reagents to treat and inhibit, if not abolish, the progress of the disease," said Tariq M. Haqqi, Ph.D., professor of medicine at Case.

"Arthritis is one of the foremost diseases for which patients seek herbal or traditional medicine treatments. However, all the extracts and herbs have not yet been scientifically evaluated for their efficacy and safety. Indeed, some of them may even interfere with the current treatments," Haqqi said. "Therefore, careful use of supplements and herbal medicines during early stages of disease or treatment may be made to limit the disease progression."

Plant-based flavonoids found in fruits, leaves and vegetables have attracted a lot of attention for their beneficial health effects in various diseases. Pomegranate, in particular, has been found to possess antioxidant and anti-inflammatory properties that have potential therapeutic benefits in a variety of diseases. The Case study demonstrated for the first time the ability of pomegranate fruit extracts to slow the deterioration of human cartilage.

"It has been revered through the ages for its medicinal properties," said Haqqi. "Studies in animal models of cancer suggest that pomegranate fruit extract consumption may be anticarcinogenic, whereas studies in mice and humans indicate that it may also have a potential therapeutic and chemopreventive adjuvant effect in cardiovascular disorders."

A bonus with the native Persian fruit is that its antioxidant constituents are rapidly absorbed by the body and are non-toxic.

Using tissue samples of human cartilage affected by osteoarthritis, researchers added a water extract of pomegranate fruit to the culture using a well-established in vitro model. The findings showed a new activity for pomegranate fruit extract -- namely cartilage protection -- in addition to its previously discovered antioxidant and anti-inflammatory properties.

The IL-1b protein molecules create an overproduction of inflammatory molecules including matrix metalloproteases (MMP), which are tightly regulated enzymes necessary for tissue remodeling. When overproduced in a disease state, such as osteoarthritis, they degrade the cartilage resulting in joint damage and destruction.

The Case study results indicate that pomegranate fruit extracts inhibit the overproduction of MMP enzymes in human cartilage cells.

"This suggests that consumption of pomegranate fruit extract may help in protecting cartilage from the effects of IL-1b by suppressing cartilage degradation in OA," Haqqi said.

More studies are needed to determine the absorption rate of pomegranate fruit extracts in the joints. Future plans include animal model studies in osteoarthritis to determine whether the fruit extract promotes cartilage repair, and whether it can also be effective in treating rheumatoid arthritis.


This research was supported in part by grants from the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases and from the National Center for Complementary and Alternative Medicine.

Adapted from materials provided by Case Western Reserve University, via EurekAlert!, a service of AAAS.

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Case Western Reserve University (2005, September 1). Pomegranate Fruit Shown To Slow Cartilage Deterioration In Osteoarthritis. ScienceDaily. Retrieved March 18, 2008, from http://www.sciencedaily.com /releases/2005/09/050901072114.htm