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Cardio Flow Vegetarian Capsules

Safe, easy, convenient to use
Luscious red pomegranate full of phytochemicals - polyphenols, ellagic acid and anthocyanins – powerful antioxidants. It even looks like a heart!  Pomegranate research has
proven that it provides
powerful cardiovascular
   Contains three times the antioxidant ability of
red wine, green tea, orange and cranberry juice!

Fountainhead CardioFlow
Pomegranate Dietary Supplement

Nappi Code: 706848-001

Get the powerful nutritional health benefits of Pomegranate through Fountainhead CardioFlow Pomegranate Dietary Supplement. When the super fruit is not in season or easily available you can still get the boost of vitality in capsule form.  While pomegranates are very healthy, they can also be expensive and difficult to find. CardioFlow Pomegranate dietary supplement provides all the health benefits of the fruit in an inexpensive and convenient way.  

Benefits Associated with Pomegranates: 

  • Lowers Cholesterol & Prevents Heart Disease*

  • Reduces fatty deposits on artery walls*

  • Reduces blood pressure*

  • Lowers Blood sugar*

  • Reduces cell damage

  • Slows cartilage deterioration and osteoarthritis

  • May prevent the return of prostate cancer after surgery

  • Contains three times the antioxidant ability of red wine, green tea, cranberry juice and orange juice

  • Great source of potassium, vitamin C and polyphenols

  • Promotes a healthy heart 

 *see research studies

CardioFlow contains the active components of the whole Pomegranate through Pomegranate extracts. 2 capsules of CardioFlow is a serving of the concentrated antioxidants of Pomegranate Extracts, Ellagins and Polyphenols.

Recent research has indicated that pomegranate juice may help keep fatty deposits from collecting on artery walls. In one study, mice who were given pomegranate juice were able to reduce this buildup by over 30%. While these results do not directly translate to humans, it does show that pomegranate may be a valuable tool for preventing hardening of the arteries and related diseases such as heart attacks and strokes.  

Pomegranate may also be helpful in maintaining healthy cholesterol and triglyceride levels. The inside of the pomegranate fruit consist of seeds surrounded by juicy pulp. It is a great source of potassium, vitamin C, and many antioxidants.
In fact pomegranates have three times the antioxidant ability than that of red wine and green tea.  

Throughout it history in Greece, Persia, China, and other countries, the pomegranate fruit has enjoyed elevated stature among foods; and its consumption has been associated with longevity and strength.  

Pomegranate antioxidant

Health professionals in the west are discovering through research more and more the benefits of pomegranate.

Pomegranate is the most antioxidant rich fruit available.  

With our bodies being exposed to more free radicals than ever, it is important our diets include foods that can help combat illness such as premature aging, stroke, heart disease, osteoporosis, and cancer. Studies show that Pomegranate can aid in warding off molecules that can cause all these bad effects.  

Antioxidants found in abundance in pomegranate inhibit oxidation in the body. Oxidation is the chemical process that deteriorates living organisms, replacing normal cells with bad ones. Think about apples when they turn brown. Your body goes through a similar process when it ages.  

Of all the health benefits of pomegranate juice antioxidants are tops. They may protect against cardiovascular disease by defending against LDL oxidation and artery-clogging plaque formation. Many studies have correlated antioxidants with low rates of cancer, particularly cancers of the mouth, larynx and oesophagus, but also prostate, breast and skin cancer.  

There are many types of antioxidants including vitamins and minerals. The most powerful antioxidants are called polyphenols. They are phytochemicals or plant chemicals that mop up free radicals and help prevent oxidation or aging in the body.  

Tannins are polyphenols that add colour and tartness to many fruits and vegetables. Pomegranates have an abundance of tannins, thus the fruit contains large amounts of beneficial antioxidants. 2 vegetarian capsules of CardioFlow a day will keep oxidation away!  
Cardiovascular Health

Pomegranate Juice May Clear Clogged Arteries 
Antioxidants in Pomegranate Juice May Fight Hardening of the Arteries 
By Jennnifer Warner WebMD Medical News
March 21, 2005 -- A new study shows that pomegranate juice may help fight hardening of the arteries. 
Researchers found that pomegranate juice not only appears to prevent hardening of the arteries by reducing blood vessel damage, but the antioxidant-rich juice may also reverse the progression of this disease. 
Hardening of the arteries, known medically as atherosclerosis, refers to the build up of plaque in the walls of arteries. This causes decreased blood flow that can lead to heart attacks and strokes. 
Pomegranate Juice Soothes Stressed Arteries 
In the study, researchers tested the effects of pomegranate juice on samples of human cells that line blood vessels. The cells were exposed to excessive physical stressstress, such as might occur with high blood pressurehigh blood pressure. 
Cells that were treated with pomegranate juice had less evidence of damage from the stress. In addition, tests on mice showed that pomegranate juice significantly slowed hardening of the arteries that developed from high cholesterol.
If further studies show those results in humans, researchers say pomegranate juice may be useful in both prevention and treatment of heart disease.
Pomegranate Tops Other Juices
The tests showed that pomegranate juice reduced the effects of stress on human blood vessel cells by stimulating the production of nitric oxide. This chemical is thought to help keep arteries open and keep blood flowing. 
Researchers say the beneficial effects of pomegranate juice on hardening of the arteries are likely largely due to its high antioxidant content. The study showed that the antioxidant level in pomegranate juice was higher than that found in other fruit juices, including blueberry, cranberry, orange, and even red wine.

Previous studies on red wine, black tea, and purple grape juice have already indicated these antioxidant-rich beverages can protect arteries from damage by improving blood flow. However, large clinical trials using different antioxidants have yet to show that antioxidants can prevent heart attacks and other major heart-related events.  

The results of this study appear in the current issue of the Proceedings of the National Academy of Sciences.

SOURCES: Nigris, F. Proceedings of the National Academy of Sciences, March 21, 2005 early online edition; vol 102: pp 4896-4901. 

Pomegranate Juice Fights Heart Disease, Study Says
by Stefan Lovgren
for National Geographic News, March 22, 2005

In the mythology of ancient Babylonia, pomegranate was considered an agent of resurrection. Now there is scientific evidence for the fruit's restorative powers. 
According to a new study, antioxidants contained in pomegranate juice may help reduce the formation of fatty deposits on artery walls. Antioxidants are compounds that limit cell damage.

Scientists have tested the juice in mice and found that it combats hardening of the arteries (atherogenesis) and related diseases, such as heart attacks and strokes. "In this experimental study, we have established that polyphenols [antioxidant chemicals] and other natural compounds contained in the pomegranate juice may retard atherogenesis," said Claudio Napoli, a professor of medicine and clinical pathology at the University of Naples, Italy. 
The research is published this week in the Proceedings of the National Academy of Sciences.

Legendary Powers 
Pomegranate (Punica granatum) is native to a region ranging from Iran to the Himalaya. It later spread to the Mediterranean area and now grows in most of the United States. 
The apple-size fruit, which grows on rounded plants 15 to 20 feet (4.6 to 6 meters) tall, contains a sack of seeds and a juicy pulp. 
In ancient Greece pomegranate was known as the fruit of the dead. In Hebrew tradition pomegranates adorned the vestments of the high priest. Ancient Persians believed that pomegranate seeds made their warriors invincible. In China the fruit symbolized longevity. Scientists have long known about health benefits of pomegranates. The latest study, in particular, shows that the juice limits the genetic tendency toward hardening of the arteries. 
"The protective effects of pomegranate juice were higher than previously assumed," Napoli said.

The study was done at the University of Naples, Italy, and the University of California, Los Angeles.

The researchers used mice to test the health effects of pomegranate juice. The fruit juice is rich in natural polyphenols, including tannins and anthocyanins, which have protective effects on the arterial wall. 

"Although it is difficult to extrapolate human indications from experimental data, it is conceivable that 500 milliliters [1 pint] of pomegranate juice may exert some beneficial effects in patients with early stages of atherosclerotic diseases," Napoli said. 
Other Juices 
The antioxidant level in pomegranate juice was found to be higher than that in other natural juices, such as blueberry, cranberry, and orange juices, as well as red wine. 
Scientists have found that polyphenols from red wine can reduce LDL ("bad" cholesterol). Black tea consumption also reverses endothelial dysfunction (damage to the linings of the arteries) in patients with chronic heart disease. 
Similarly, the polyphenols contained in purple grape juice have also been found to have beneficial effects on patients with coronary heart disease.  

Napoli points out that not every antioxidant study has confirmed that the chemicals can help prevent heart attacks. 

Pomegranate and Health Study
Pomegranate and Health Study on the Effects of Pomegranate Juice Consumption on Myocardial Perfusion in Patients With Coronary Heart Disease 
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 [1] 2.7) but increased in the control group (SDS 1.2 [1] 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. © 2005 Elsevier Inc. All rights reserved. (Am J Cardiol 2005;96:810–814)  
Study by: Michael D. Sumner, PhDa, Melanie Elliott-Eller, RN, MSNa, Gerdi Weidner, PhDa, Jennifer J. Daubenmier, PhDa, Mailine H. Chew, MDb, Ruth Marlin, MDa, Caren J. Raisin, RNa, and Dean Ornish, MD  

The results of this study demonstrate, for the first time, that daily consumption of pomegranate juice for 3 months may decrease myocardial ischemia and improve myocardial perfusion in patients who have ischemic CHD as measured by the SDS. This effect occurred without change in perfusion abnormalities at rest as measured by the summed rest score. 
The clinical significance of this finding is further illustrated by an average improvement of 17% in myocardial perfusion in the experimental group and an average worsening of 18% in the control group (i.e., a 35% relative between-group difference) after only 3 months. Also, there were no negative effects on lipids, blood glucose, hemoglobin A1c, body weight, or blood pressure.  

Dietary supplementation with polyphenolic antioxidants inhibits low-density lipoprotein oxidation and macrophage foam cell formation and attenuates development of atherosclerosis in animals.  

The antioxidative and antiatherogenic characteristics of pomegranate juice also occur in atherosclerotic apolipoprotein E–deficient (E0) mice. 

Pomegranate juice is rich in polyphenols and demonstrates high capability in scavenging free radicals and inhibiting low-density lipoprotein oxidation in vitro and in vivo.

Our findings are consistent with results reported by others who have demonstrated beneficial effects of beverages high in polyphenols. For example, purple grape juice may decrease platelet aggregation, increase platelet- derived nitric oxide release, and decrease superoxide production.  

Red wine may increase endothelial function. However, neither grape juice nor red wine has been shown to improve myocardial ischemia in humans who have CHD. Although the sample in this study was relatively small, the strength of the design and the clinically significant and statistically significant improvements in myocardial perfusion observed in the experimental group over a rather short period suggest that daily consumption of pomegranate juice may have important clinical benefits in this population. In a recent study of 2,686 patients, the best predictor of nonfatal myocardial infarction was the amount of ischemia as indicated by the SDS. 
Further studies appear to be warranted to determine the effects of pomegranate juice on myocardial perfusion in a larger sample of patients over a longer period. In addition, it would be of interest to assess the effects of pomegranate juice on coronary atherosclerosis using methods such as quantitative coronary arteriography and intravascular ultrasound.  

For more details:
Preventive Medicine Research Institute, Sausalito, California; California Pacific Medical Center and the School of Medicine, University of California, San Francisco, San Francisco, California. Manuscript received December 28, 2004; revised manuscript received and accepted May 11, 2005. 
This study was supported by a grant from the Resnick Foundation, Los Angeles, California, to the Preventive Medicine Research Institute, which also provided the pomegranate juice. The foundation did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the report. *Corresponding author: Tel: 415-332-2525, ext 222; fax: 415-332- 2588. E-mail address: dean.ornish@pmri.org (D. Ornish).

Cardiovascular Health Study
Pomegranate juice improves Carotid Artery Health and Lowers Blood Pressure in Patients with Carotid Artery Stenosis

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;23:423–433.

In an open label, parallel group clinical trial, 19 patients (5 women and 14 men, aged 65-75 years) with severe carotid artery stenosis (CAS) were selected to receive 50 ml concentrated pomegranate juice (PJ) containing 1.5 mmoles of polyphenols per day, the equivalent of 8.3 oz (250 ml) of 100% juice (treatment group; n = 10) or no PJ (control group; n = 9). The CAS was measured at 70-90% occlusion of the internal carotid arteries as confirmed by Doppler ultrasound. The PJ was prepared from the crushed fruit of hand-picked pomegranates and was filtered, pasteurized, concentrated, and stored at –18 C. The concentrated PJ was diluted with water to obtain a single strength juice. 
The antioxidant composition of the juice was measured as follows: 1978 mg/l tannins (1561 mg/l punicalagins and 417 mg/l hydrolysable tannins), 384 mg/l anthocyanins (delphinidin 3,5-diglucoside, cyanidin 3,5-diglucoside, delphinidin-3-glucoside, cyanidin 3-glucoside, pelargonidine 3-glucoside), and 121 mg/l ellagic acid derivatives. The juice also contained 3 mg vitamin C per 100 ml juice. The study period lasted for 1 year, and 5 patients consuming PJ continued for another 2 years. 
The primary outcome was the change in intima-media thickness (IMT) over time measured at the distal common carotid artery by Doppler ultrasound. IMT refers to the intima plus media layers of the carotid artery. IMT measures the distance between the lumen intima boundary (the space in which blood flows) and the media adventitia boundary (the outermost region of the artery). Additional outcomes included a range of cardiovascular parameters: 
• peak systolic velocity (PSV); 
• end diastolic velocity (EDV); 
• total cholesterol; 
• high density lipoprotein (HDL) cholesterol; 
• triglycerides; 
• apolipoproteins A-1 and B-100; 
• serum paraoxonase 1 (PON 1) arylesterase activity, an HDL-associated enzyme that can reduce lipid peroxides, thereby decreasing oxidative stress; 
• total antioxidant status; 
• serum anti Oxidized low density lipoprotein (Ox-LDL) antibodies; 
• LDL oxidation; 
• total antioxidant status (TAS); and 
• chemical analyses of atherosclerotic plaques obtained by endartherectomy for cholesterol, lipid peroxides, and reduced glutathione (GSH) concentrations. 
Compared to pretreatment values, mean IMT decreased significantly in the treatment group after 3, 6, 9, and 12 months (–13%, –22%, –26%, and –35%, respectively; p < 0.01). After 12 months of treatment the mean IMT had decreased from 1.5 ± 0.2 mm at baseline to 1.1 ± 0.1 mm (p < 0.01) and remained at that approximate mean thickness for the duration of the study. In contrast, from baseline to 12 months, the mean IMT in the placebo group significantly increased from 1.52 ± 0.03 to 1.65 ± 0.04 mm, (p < 0.01). Significant decreases after 1 year of treatment were noted for mean PSV (cm/s), which decreased from 135 ± 6 to 103 ± 10 (p < 0.01), and for mean EDV, which decreased from 38 ±1 to 30 ± 12 (p < 0.01), with no additional significant reductions for the remainder of the trial. 

Systolic, but not diastolic, blood pressure (mmHg) was significantly reduced after 1 month of treatment from 174 ± 8 to 162 ± 9 (p < 0.05); compared to baseline, blood pressure was significantly reduced even further after 12 months to 153 ± 7 (p < 0.01). Blood pressure was not significantly changed in the placebo group at any time period compared to baseline. Compared to baseline, anti-Ox-LDL antibodies (EU/ml) significantly decreased by 24% after 1 month of treatment and by 19% after 3 months (p < 0.01). Mean TAS (nmol/L) increased after 12 months of PJ consumption. However, one month after stopping PJ, mean TAS was found to decrease. Mean serum lipid oxidation (nmol lipid peroxides/ml) significantly decreased in the PJ group after 12 months of treatment (p < 0.01) and was found to further decrease after 28 months and 36 months compared to baseline (p < 0.01). PON 1 (U/ml) significantly increased in the treatment group after 1 year (p < 0.01) and continued to significantly increase at 3 years in those patients taking PJ for an additional 2 years (p < 0.01); however, one month after stopping PJ, PON 1 activity was found to decrease. LDL cholesterol isolated from patients showed that LDL-associated lipid peroxides were reduced by 90% after 6 months, and the susceptibility of LDL to copper ion induced oxidation was gradually and significantly decreased over the course of 1 year. Carotid endarterectomy (surgery that removes harmful plaque from major arteries that carry blood to the head) was performed in two patients, one after 3 months and one after 12 months of consuming PJ, due to clinical deterioration during the trial. Compared to 7 controls, their carotid lesions had significantly lower mean concentrations of cholesterol (58% and 20% lower, respectively; p < 0.01), lipid peroxides (61% and 44%, respectively; p < 0.01), and lesion-induced LDL oxidation (43% and 32%, respectively; p < 0.01), and significantly higher reduced glutathione (2.5 times higher in both samples; p < 0.01). No adverse events were reported. 
Comments/Opinions: The results of this very small study suggest that regular consumption of PJ is beneficial to persons with CAS. In addition to anti-atherosclerotic properties (as seen with the reduced common carotid IMT), the juice also appears to have significant antioxidant activity as noted by the decrease in LDL-oxidation and the significant increase in PON 1 activity. The increase in PON 1 activity was not only seen in the 10 patients consuming PJ at 1 year but was also found to continually increase over an additional 2 years in 5 patients. PON 1 is an interesting measure of lipid oxidation activity and has been found to decrease in persons with hypercholesterolemia, diabetes, and cardiovascular disease.1,2 PON 1 is inactivated by oxidized lipids, and PJ appears to act like red wine flavonoids and licorice-derived glabridin to preserve PON 1 activity during lipid peroxidation.3 Another remarkable finding in this trial is the significant reduction in systolic blood pressure after 1 year of juice consumption.  
Most of the chemical analysis of pomegranate has focused on the juice, peel/pericarp, and seed oil. The juice/fruit contains high amounts of hydrolyzable tannins, in particular ellagitannins (gallic acid and ellagic acid), anthocyanins (cyanidin, delphinidin, pelargonidin), as well as the phenolic acids: ellagic acid, caffeic acid, and chlorogenic acid.6,7 The pericarp is also high in hydrolyzable tannins.8 (Note: The pericarp is the skin surrounding the seed, really the “aril.” The seed is only the hard, white internal seed; the red juicy edible sacs, including the seed, are called arils.) Pressing the whole fruit results in juice that is much higher in the pericarp polyphenols. Luteolin, quercetin, kaempferol, and narigenin are also found in the peels. The seed oil consists of about 63.5% punicic acid—a rare trans 18-carbon fatty acid (structurally related to conjugated linolenic acid).4 According to one source, the seed also contains the highest concentration of estrone in the plant kingdom—approximately 17 mg/kg of dried seed.9 Interest has been growing in the past few years about the potential of pomegranate oil as a potent phytoestrogen and its potential cancer preventive properties, especially with regard to breast cancer.10 For the past several years, Israeli researchers, lead by Dr. Michael Aviram (Lipid Research Laboratory, Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel) have been focusing on the antioxidant properties of PJ as well as the potential cardiovascular benefits. In one study, pomegranate juice was found to reduce atherosclerotic lesion size in apolipoprotein E-deficient mice.11 An ex vivo study with healthy male volunteers found that consumption of 50 ml of concentrated pomegranate juice per day (equal to 8 oz./day of 100% juice) reduced LDL susceptibility to oxidation and increased activity of serum paraoxonase (PON1).12 Finally, a clinical trial found that consumption of 50 ml of concentrated pomegranate juice per day (equal to 8 oz./d of 100% juice) for 2 weeks resulted in a 36% decrease in serum angiotensin converting enzyme (ACE) activity and a 5% reduction in systolic blood pressure in 10 patients (age 62-77 years) with hypertension.13 The reviewed study with PJ is a continuation of their work and hopefully the beginning of new, exciting findings into the cardiovascular health benefits of pomegranate. 

Practice Implications: 
Although the patient population is small in this new clinical trial, the results are impressive when considering the length of the study. Focusing on patients with CAS, the study supports previous findings that PJ possesses anti-atherosclerotic properties and also decreases systolic blood pressure. Hopefully, this study will result in larger trials focusing on the long-term cardiovascular benefits of PJ and will do a more thorough comparison statistically with a placebo group. The availability of encapsulated extracts of pomegranate also offers health care professionals alternatives to the juice for diabetic patients and those wishing to use a more concentrated form of pomegranate for prevention of cardiovascular disease. Hopefully, companies will develop standardized extracts that reflect the tannin and total polyphenol content critical to the cardiovascular benefits of PJ. 
From The Journal of the American Botanical Council Issue: 65 Page: 28-30 Reviewed: Aviram M, Rosenblat M, Gaitini D, et al. 
1. Aviram M. Does serum paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today. 1999;5:381–386. 
2. Mackness MJ, Harty D, Bhantnagar D, et al. Serum paroxonase activity in familial hypercholesterolemia and insulin dependent diabetes mellitus. Atherosclerosis. 1991;86:193–199. 
3. Aviram M, Rosenblat M, Billecke S, et al. Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radical Biol. 1999;26:892–904. 
4. Schubert SY, Lansky EP, Neeman I. Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. J Ethnopharmacol. 1999;66:11–17. 
5. Langley P. Why a pomegranate? BMJ. 2000;321:1153–1154. 
6. Artik N, Ceremroglu B, Murakami H, Mori T. Determination of phenolic compounds in pomegranate juice by HPLC. Fruit Process. 1998;8:492–499. 
7. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agri Food Chem. 2000;48:4581-4589. 
8. Ben Nasar N, Ayed M. Quantitative determination of polyphenolic content of pomegranate peel. Z Lebensm Unters Frosch. 1996;203:374–378. 
9. Heftmann E, Ko ST, Bennett RD. Identification of estrone in pomegranate seeds. Phytochem. 1966;5:1337–1340. 
10. Kim ND, Metha R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treatment. 2002;71:203–217. 
11. Kaplan M, Hayek T, Raz A, et al. Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr. 2001;131:2082–2089. 
12. Aviram M, Dronfeld L, Rosenblat M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000;71:1062–1076. 
13. Aviram M, Dronfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001;158:195–198. Dr. Brown would like to acknowledge John Neustadt, ND4, for his assistance in preparing the clinical summaries in this column. 
American Botanical Council, 6200 Manor Rd, Austin, TX 78723 Phone: (512) 926-4900 | Fax: (512) 926-2345 Email: abc@herbalgram.org | URL: http://www.herbalgram.org The information on this site is intended for educational purposes only and is not a substitution for the advice of a qualified healthcare professional. ABC is a nonprofit, tax-exempt research and education organization under IRS section 501(c)(3). All text, images and content Copyright © 2002 American Botanical Council.

Pomegranate Juice protects nitric oxide
Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.
Nitric Oxide. 2006 Apr 18; 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.
Pomegranate juice, a rich source of potent flavonoid antioxidants, was tested for its capacity to protect nitric oxide against oxidative destruction. Pomegranate juice was found to be a potent inhibitor of superoxide anion-mediated disappearance of NO. Pomegranate juice was much more potent than Concord grape juice, blueberry juice, red wine, ascorbic acid, and dl-alpha-tocopherol. These observations indicate that pomegranate juice possesses potent antioxidant activity that results in marked protection of nitric oxide against oxidative destruction, thereby resulting in augmentation of the biological actions of NO.
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

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.
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. 
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.
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.
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 (CPJ) consumption on lipid profiles of type II diabetic patients with hyperlipidemia (cholesterol >/= 5.2 mmol/L or triacylglycerol >/= 2.3 mmol/L). In this quasi-experimental study 22 otherwise healthy diabetic patients, 14 women (63.6%) and eight men (36.4%), 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 CPJ 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 CPJ for 8 weeks, during which time dietary assessment was continued. After completing the study, anthropometric and blood indices were again evaluated. The Wilcoxon signed test was used for statistical analysis. A value of P <.05 was considered significant. Mean (+/-SD) age, weight, and duration of diabetes were 52.5 +/- 5.2 years, 71.5 +/- 10.3 kg, and 7.9 +/- 6.6 years, respectively. After consumption of CPJ, significant reductions were seen in total cholesterol (P <.006), low-density lipoprotein (LDL)-cholesterol (P <.006), LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (P <.001), and total cholesterol/HDL-cholesterol (P <.001). 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 CPJ 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 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.

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.
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, whereas 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. 

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