POMEGRANATE SIDE EFFECTS, supplements, juice, fruit benefits and
extracts
June 2013
POMEGRANATE HEALTH BENEFITS
Pomegranates [Punica granatum], which are native to the Middle East, are packed with healthy anti-oxidants
and anti-inflammatory agents. The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to
its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid. It is also a good source of
ascorbic acid. [11]

ANTIOXIDANT ACTIVITES
Oxidative damage is related to the development of several chronic diseases, such as age-related
neurodegeneration, carcinogenesis and atherosclerosis. Pomegranate packed with multiple potent
antioxidants may have benefits against these chronic diseases. [2]
The health benefits attributed to the consumption of Pomegranate and its extracts are related to their
antioxidant activity. Studies have shown the inverse relationship between the intake of Pomegranate extracts
(or its juice) and cardiovascular diseases. And, this could be related to pomegranate polyphenols' ability to
inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. [3,6]

Two possible pathways may be involved in the LDL oxidation inhibition: (1) a direct interaction of the
polyphenols with the lipoprotein or/and (2) an indirect effect through accumulation of polyphenols in arterial
macrophages.

Pomegranate juice was shown to mediate suppression of oxidized LDL degradation and of cholesterol
biosynthesis in macrophages can lead to reduce cellular cholesterol accumulation and foam cell formation. [6]
Consequently, 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. [3]

A recent research study has also shown that long-term oral administration of pomegranate flower extract (500
mg kg(-1)) reduces cardiac triglyceride content and decreases plasma levels of triglyceride and total
cholesterol in Zucker diabetic fatty (ZDF) rats. Pomegranate flower extract exerts this effect probably via
inhibition of increased cardiac FA uptake and oxidation in the diabetic condition. [8]

CORONARY HEART DISEASES AND BLOOD PRESSURE
As discussed in previous sections, pomegranate juice or its extracts contain antioxidants such as soluble
polyphenols, tannins, and anthocyanins and may have benefits on atherosclerosis.  Pomegranate juice is rich
in tannins, possesses anti-atherosclerotic properties, has anti-aging effects, and potent anti-oxidative
characteristics. As some antioxidants have been shown to reduce blood pressure. Pomegranate juice
consumption may reduce systolic blood pressure, inhibits serum ACE activity, and is convincingly a heart-
healthy fruit. [Stowe CB., Complement Ther Clin Pract. 2011 May;17(2):113-5.] Daily consumption of
pomegranate juice may have benefits in patients who have coronary heart diseases.

In a double-blind study, researchers supplied pomegranate juice daily to 45 patients suffered from coronary
heart disease and myocardial ishemia for 3 months. Based on the data of tomographic scintigraphy, blood
sugar, hemoglobin A1c, weight, or blood pressure, the researchers concluded that pomegranate juice
decreased the extent of stress-induced ischemia. [5]

As discussed, pomegranate juice can offer benefits against cardiovascular diseases via its anti-oxidant
activities. Researchers further found that pomegranate juice consumption could also reduce the systolic blood
pressure of hypertensive patients. This effect is in a dose-dependent fashion and related to a change of
angiotensin converting enzyme activity. [12]

ANTI-CANCER ACTIVITIES
Researchers have previously reported anticancer effects of pomegranate extracts in human breast cancer
cells in vitro and also anti-cancer activity of pomegranate fermented juice polyphenols in a mouse mammary
organ culture. [13]

Colon Cancer
In a recent study, at 100 microg/ml, pomegranate juice, ellagic acid, punicalagin and total pomegranate tannin
were found to be able to induce apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, ellagic
acid, punicalagin and total pomegranate tannin but not pomegranate juice induced apoptosis. [7]

Breast Cancer
Roughly, 70% of breast cancer will be estrogen receptor-alpha (ER-α) positive. The presence of ER-α is
associated with better prognosis and is able to determine if tumors will respond to the estrogen-blocking/ER-
antagonist drug Tamoxifen. However, a significant fraction of ER-positive tumors respond with minimal or no
response to Tamoxifen. Researchers found Pomegranate fruit extracts  enhance the Tamoxifen action in both
sensitive and Tamoxifen-resistant MCF-7 cells through the inhibition of cell viability (regular or estrogen-
induced) by inducing cell-death machinery. [Banerjee S, et al, J Cell Commun Signal. 2011 Jun 27.]

Prostate Cancer
Pomegranate juice  was also shown in a clinical trial to inhibit progression of prostate cancer. In addition to
causing cell death of hormone-refractory prostate cancer cells, Pomegranate juice also increases cell
adhesion and decreases cell migration of the cells that do not die. [Wang L, et al, Integr Biol (Camb). 2011 Jul
1;3(7):742-54]


Skin Cancer
Pomegranate fruit extract and diallyl sulfide alone delayed onset and tumor incidence by 55% and 45%,
respectively, while their combination at low doses synergistically decreased tumor incidence more potentially
(84%, p<0.01). Mechanistic studies revealed that this inhibition was associated with decreased expression of
phosphorylated ERK1/2, JNK1 and activated NF-κB/p65, IKKα, IκBα phosphorylation and degradation in skin
tissue/tumor. [George J, et al, Food Chem Toxicol. 2011 Jul;49(7):1511-20]

Combinational Use of Pomegranate Extract and An Anti-cancer Drug
Cisplatin, one of the most active cytotoxic agents against cancer, has adverse side effects, such as
nephrotoxicity and hepatotoxicity. Pomegranate seed extract significantly attenuated these side effects of
cisplatin by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. [Cayır K etl, J Med Food.
2011 May 6.]

ANTI-BACTERIA ACTIVITIES
Pomegranate extracts may have benefits on prevention of certain diseases induced by bbacterial diseases.  
Low dose of pomegranate extract concentration was found to delay Staphylococcus aureus growth, while high
doses even eliminated Staphylococcus aureus growth. [9]

In addition, methanolic pomegranate extracts has been shown to dramatically enhance the activity of certain
antibiotics tested.  Researchers evaluated the synergic activity between pomegranate extracts and antibiotics
against 30 clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive
Staphylococcus aureus.They detected the synergic activities between pomegranate extracts and the 5
antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to
73%. Pomegranate extracts increased the post-antibiotic effect of ampicillin from 3 to 7 h. [4]

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REFERENCE
[1] Proceedings of the National Academy of Sciences, Early Edition September 26, 2005. [2] Blomhoff R
Antioxidants and oxidative stress Tidsskr Nor Laegeforen. 2004 Jun 17;124(12):1643-5. [3] Aviram M et al,
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. [4] Braga LC et al, Synergic
interaction between pomegranate extract and antibiotics against Staphylococcus aureus. Can J Microbiol.
2005 Jul;51(7):541-7. [5] Sumner MD et al, Effects of pomegranate juice consumption on myocardial perfusion
in patients with coronary heart disease. Am J Cardiol. 2005 Sep 15;96(6):810-4. [6] Fuhrman B et al,
Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages. J Nutr Biochem.
2005 Sep;16(9):570-6. [7] Seeram NP et al, In vitro antiproliferative, apoptotic and antioxidant activities of
punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other
polyphenols as found in pomegranate juice. J Nutr Biochem. 2005 Jun;16(6):360-7.  [8] Huang TH et al,
Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating
lipids. Br J Pharmacol. 2005 Jul;145(6):767-74. [9] raga LC et al, Pomegranate extract inhibits Staphylococcus
aureus growth and subsequent enterotoxin production. J Ethnopharmacol. 2005 Jan 4;96(1-2):335-9. [10]
Igea JM et al, Adverse reaction to pomegranate ingestion. Allergy. 1991 Aug;46(6):472-4. [11] Perez-Vicente
A et al, In vitro gastrointestinal digestion study of pomegranate juice phenolic compounds, anthocyanins, and
vitamin C. J Agric Food Chem. 2002 Apr 10;50(8):2308-12. [12] Aviram M et al, Pomegranate juice
consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure.
Atherosclerosis. 2001 Sep;158(1):195-8. [13] Mehta R et al, 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.
Pomegranate is a delicious fruit and it may provide us many health benefits. Pomegranate may have
anti-viral, anti-tumor activities and it may also benefit people at risk of high cholesterol, osteoarthritis and
prostate issues. Many people are interested by its potential anti-cancer activities. Scientists at the University
of Wisconsin found pomegranate juice might ward off prostate cancer in a cell-culture study. Pomegranate
extracts killed the cancer cells in a dose-dependent way. The higher the dose of pomegranate juice, the
more cancer cells died. In another study, cancer progression was significantly slowed in animals receiving the
higher pomegranate dose. Their blood also contained decreased levels of prostate-specific antigen, a
marker commonly used to monitor prostate cancer. [1]

In general, pomegranate may be safe. However, side effect or adverse event of pomegranate did happen in
the past. For instance, Spanish care-providers presented a non-atopic 85-year-old woman, with a late-onset
recidivant tongue angio-edema due to pomegranate intake. [10]

Pomegranate is available as a fruit; as fruit juice, extracts, jams, wine and some other forms. Most fruit juice
contains high calories, some users prefer supplement extracts. Most pomegranate extracts contain 40% of
ellagic acid or higher.
THIS WEBSITE TALKS ABOUT THE SIDE EFFECTS AND THE POTENTIAL HEALTH BENEFITS OF HERBS, SUPPLEMENTS,
PHYTONUTRIENTS AND DRUG PRODUCTS. THIS WEBSITE ALSO TALKS ABOUT SOME POPULAR HEALTH ISSUES AND DISEASES.
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