Pomegranate supplement, juice, fruit benefit and extract information by Ray Sahelian, M.D. (index of hundreds of nutritional topics)
January 1 2017

Pomegranate is a delicious fruit (one of my favorites - except for the hassle of peeling) with many beneficial compounds. The fruit has substances, such as polyphenols, that have antioxidant, anti-viral, and anti-tumor activity. Pomegranate may also be helpful in maintaining healthy cholesterol and triglyceride levels, and a recent study indicates it has compounds that play a role in osteoarthritis and prostate health.

Pomegranate is available, of course, as a fruit; as fruit juice, in extract form as a supplement, jam, jelly, juice concentrate, molasses, and even wine and martini. Pomegranate pills are available and are a good option in order to avoid the calories. You can also find ellagic acid supplement by itself.
   Many herb and vitamins ingredient suppliers sell pomegranate at various extract potencies. Some of these include extract at 20 percent ellagic acid, extract at 40 percent ellagic acid, and at 60, 70, 80 and even 90 percent ellagic acid. I have also seen powdered extract sold as 40 percent polyphenol brown, 35% punicalagin A and B, along with pomegranate skin, leaves, and flower. With so many options available it is difficult to know which is the best extract to use. One option is to try different ones over time.

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Pomegranate, 500 mg, 60 Capsules, Ellagic Acid
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Recommendation: Take 1 to 4 pomegranate capsules daily with food or water
You may also consider other healthy herbs and supplements with high antioxidant potential, including Acai berry extract, Cacao extract, Curcumin extract from turmeric, Goji berry extract, Graviola herb, Mangosteen fruit and Noni.

Pomegranate Juice Benefit
Even though it has substances, such as polyphenols, that have antioxidant, anti-viral, and anti-tumor activity, it will take many years to find out how the health benefit of pomegranate juice in humans and how many ounces are required. One drawback with any type of juice is the excess calories and fructose. Hence, a pomegranate extract supplement could be useful by reducing the caloric intake from the pomegranate juice. This is particularly appropriate for those who are overweight.

Pomegranate and cancer
Oxid Med Cell Longev. 2015. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. Pomegranate evokes antiproliferative, anti-invasive, and antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins, upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate blocks the activation of inflammatory pathways including, but not limited to, the NF-κB pathway. The strongest evidence for its anticancer activity comes from studies on prostate cancer.

Q. I would be most grateful if you would be kind enough to let me know whether there is any literature on the efficacy (clinical trials or otherwise) of pomegranate seed extract in shrinking cancer tumors - specifically a liver tumor. I have read your information on the possible benefits in prostate cancer, and just wondered if it was area-specific, or whether it could be applicable to any cancer tumors?
   A. I am not aware of any specific human studies that have looked into the role of pomegranate juice, extract or pomegranate supplements as a treatment for liver cancer or other cancers, but there are laboratory studies that show compounds in pomegranate to have anti-tumor potential.

Breast Cancer Res Treat. 2012. Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer.

Breast Cancer Res Treat. 2012. Cytotoxicity of pomegranate polyphenolics in breast cancer cells in vitro and vivo: potential role of miRNA-27a and miRNA-155 in cell survival and inflammation.

BMC Complement Altern Med. 2013. Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis.

Effect on estrogen
An acid found in pomegranates appears to block aromatase, an enzyme that converts androgen to estrogen, a hormone that plays a role in the development of breast cancer. Many women who have had breast cancer take medicines called aromatase inhibitors -- such as Pfizer's Aromasin, Novartis' Femara and AstraZeneca Plc's Arimidex -- to keep estrogen from stimulating tumors. Chen and colleagues studied whether compounds, or phytochemicals, in pomegranates can suppress aromatase and ultimately block cancer growth. They found that 10 natural compounds in the fruit may potentially prevent estrogen-related breast cancer. Shiuan Chen, of the City of Hope cancer research and treatment center in Duarte, California, believes the compounds would not be a replacement for aromatase inhibitors since they are not as potent as the real drugs. But, these compounds may be helpful for prevention rather than for treatment once the cancer has started.

Heart or cardiovascular disease, metabolic syndrome
Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans.
Drugs Exp Clin Res. 2002.
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 are 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.

Food Funct. 2013. Pomegranate: a fruit that ameliorates metabolic syndrome.

Kidney disease
Investigators gave dialysis patients pomegranate juice and others a placebo drink at the start of each dialysis session, three times a week for a year. The patients who drank the pomegranate juice showed a reduction in both inflammation and damage caused by free radicals. Batya Kristal, MD, FASN, of Western Galilee Hospital in Nahariya, Israel, reports patients with kidney disease who drank pomegranate juice had lower blood pressure and fewer heart problems. American Society of Nephrology Renal Week, Denver, 2010.

Pomegranate, prostate cancer and urological conditions
Diet, nutrition, and life style play a role in the development and the course of urological diseases. Numerous micronutrients and polyphenols found in soy, green tea, and many fruits and vegetables have been described to impact diseases including erectile dysfunction, benign prostatic hyperplasia, and cancer. The efficacy of pomegranate in the modulation of central biological processes like inflammation and oxidative stress that are important in the cause of urological maladies has been demonstrated in preclinical in vitro and in vivo studies.

Pomegranate extract may prevent prostate cancer or slow its growth. These fruits 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.

J Steroid Biochem Mol Biol. 2014 Feb 22. Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo.

Q. My husband had a recent prostatecomy and came back with undetectable PSA. We want to keep it that way as long as we can - by drinking pomagranate juice - and want to use organics and natural products (i.e. tomatoes, etc). He is consuming 8 ounces pom juice per day - however it's getting expensive. I read over the information on extract vs. juice and it's a little confusing. Does a person get the same benefit regarding prostate cancer whether it's a juice or extract? (given a standardized high quality product)? or is there something in the juice that the extract / pill won't contain. Pomegranate juice is high in sugar (husband in thin so it's really not a problem) - but capsules and extract is a lot more economical IF the benefits are the same.
     A. This is a good question and scientists don't know at this time which form of pomegranate is better for prostate health since human studies have not been done comparing the two ways to ingest pomegranate. As a rule we prefer pomegranate extract over pomegranate juice since it avoids the fructose, but we cannot say at this time whether the pomegranate juice is more effective than pomegranate extract capsules or vice versa.

Medication interaction
Pomegranate juice inhibits human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.
May decrease warfarin or Coumadin metabolism and thus lead to an increase in INR.
A component of pomegranate inhibits the human CYP3A-mediated metabolism of carbamazepine. The juice alters carbamazepine pharmacokinetics in rats.

I have heard that pomegranate has the potential to cause a longer life span of certain medications such as anti-depressants and anti-seizure drugs. Some of these would be lamotrigine, Xanax and busprione. Do you know anything about this?
    Some rodent studies and case histories in human have show interactions with medications, but the full story is not yet clear since few well controlled studies have been done in humans.

Interaction with warfarin, Coumadin
Potential interaction between pomegranate juice and warfarin.
Pharmacotherapy. 2009.
Investigators from previous animal and in vitro studies have reported a potential for pomegranate juice to inhibit metabolism involving the cytochrome P450 system, an effect that could translate into a clinical drug-diet interaction with warfarin. This case report describes a 64-year-old Caucasian woman who was treated with warfarin for recurrent deep vein thrombosis. She had been receiving a relatively stable dosage of warfarin 4 mg/day for several months, with stable international normalized ratios (INRs). During that time, the patient was consuming pomegranate juice 2-3 times/week. She stopped drinking the juice, and her INRs became subtherapeutic. Her dosage of warfarin was increased to maintain therapeutic anticoagulation. No rechallenge with pomegranate juice was performed. Use of the Drug Interaction Probability Scale indicated a possible relationship between the patient's subtherapeutic INR and the pomegranate juice. Although this potential interaction needs to be explored further, clinicians should be aware of the interaction and thoroughly interview and closely monitor their patients who are receiving warfarin.

Protection from medication harm
J Laryngol Otol. January 2014. Pomegranate extract: a potential protector against aminoglycoside ototoxicity.

Safety, adverse effects
No toxicity is known thus far but do note the medication interactions as mentioned above.

Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic.
J Agric Food Chem. 2003.
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, 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. Histopathological analysis of liver and kidney corroborated the absence of toxicity.

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. The Case study demonstrated for the first time the ability of pomegranate fruit extracts to slow the deterioration of human cartilage.

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

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.

Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia.
J Med Food. 2004.
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 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.
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.
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.

Some people misspell it as pomegranite

Q. How does 500 mg of pomegranate extract compare to 8oz of the juice? I would like to substitute the pomegranate extract capsules for for the juice that I've been drinking.
     A. It is very difficult to compare since no studies have been done to find out which form is better and what the equivalency of pomegranate juice is to the extract. The juice has a lot of calories and fructose. On average, most people take 1 to 3 pomegranate capsules a day. Studies in the future could perhaps shed some light.

Q. Can you tell me how much ellagic acid is found in pomegranate juice? Also what are punicalagins?
     A. There are variations in ellagic acid content in various pomegranate juice products depending on where the pomegranate is grown. We found one study where a person was given 180 ml (about 6 ounces) of pomegranate juice, and there apparently was ellagic acid 25 mg and hydrolyzable ellagitannins 318 mg, as punicalagins, the major fruit ellagitannin.

Q. I read an article where it said drinking 1 ounce of pomegranate juice a day reduces plaque buildup in the arteries. Is pomegranate juice effective for arteriosclerosis (calcium deposits) or atherosclerosis (fatty deposits)? Or is pomegranate juice effective in reducing both types of buildup? Is 1 ounce daily enough to be effective?
   A. We see two studies related to pomegranate juice and benefits. Pomegranate juice appears to be beneficial in reducing oxidation of lipids and may reduce the risk for atherosclerosis. How much pomegranate juice is required is not well known, and perhaps alternating the use with pomegranate supplements is one option in order to reduce the calories from fructose present in pomegranate juice.

Anti-oxidative effects of pomegranate juice consumption by diabetic patients on serum and on macrophages.
Atherosclerosis. 2006 The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel.
In the present study, we investigated the effects of pomegranate juice; which contains sugars and potent anti-oxidants) 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 pomegranate juice (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. Pomegranate juice 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%. Pomegranate juice  consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%).  We thus conclude that pomegranate juice consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in anti-oxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.

Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.
Am J Cardiol. 2005. 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.
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. After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group but increased in the control group. 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 coronary heart disease.

Q. I'm taking ortho tri cyclen. If I take a pomegranate supplement will it flush the hormone pill out of my system?
   A. I doubt this will happen but I have not seen any studies with the combination of Ortho Tri Cyclen and pomegranate supplements or the combination of pomegranate juice and hormone pills.

Other products available to purchase
Nature's Way, Pomegranate, Standardized, 60 Veggie Caps
Pomegranate Extract (Punica granatum) from a pure, whole-fruit source to maximize its antioxidant benefits. Get the benefits of the juice and avoid all the calories and sugar (fructose).

Buy Pomegranate supplement or Ellagic acid

Supplement Facts
Serving Size: 1 Capsule
  Amount Per Serving % DV
Pomegranate Extract (whole-fruit), 85% Polyphenols (170 mg) 200 mg **
Pomegranate (seed) 150 mg **
**Daily Value (DV) not established.

Other products to buy online
Source Naturals, Ellagic Active, 300 mg, 60 Tablets