Ellagic acid is usually stored as ellagitannin (a tannin) in raspberries,
strawberries, cranberries, walnuts, pecans, pomegranates, and other plant
foods. Hydrolysis of ellagitannin yields ellagic acid and the dilactone of
hexahydroxydiphenic acid.
RESEARCH FINDINGS
CANCER
The highest levels of ellagic acid are found in raspberries, strawberries, and
pomegranates, especially when they are freeze-dried. Studies have shown
that ellagic acid is able to cause apoptosis (cell death) in cancer cells. Some
also claim that it can prevent the binding of carcinogens to DNA, and
strengthens connective tissue, which may keep cancer cells from spreading
[1-9].
Some studies demonstrate that ellagic acid is able to reduce heart disease,
birth defects, liver fibrosis, and to promote wound healing.
Antiangiogenic properties
The vascular endothelial growth factor (VEGF) and platelet-derived growth
factor (PDGF) receptors play essential roles in angiogenesis and inhibition of
these receptors has been shown to result in potent anti-tumor activity in vivo.
Labrecque L et al reported that ellagic acid inhibits VEGF-induced
phosphorylation of VEGFR-2 in endothelial cell as well as PDGF-induced
phosphorylation of PDGFR in smooth muscle cells. [10]
Bladder Cancer
Researchers, China Medical University, Taiwan, induced cell cycle arrest and
apoptosis in T24 human bladder cancer cells in vitro using ellagic acid. [11]
Breast Cancer
Researchers at Louisiana State University demonstrated that ellagic acid
expressed a selective cytotoxicity and anti-proliferative activity, and induced
apoptosis in Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145
human prostate cancer cells. It was also observed that the mechanism of
apoptosis induction in ellagic acid-treated cancer cells was associated with
decreased ATP production, which is crucial for the viability of cancer cells.
[12]
Esophagus
de Boer JG et al, University of Victoria, Canada, showed the mutation
preventive properties of ellagic acid against the mutagenicity of the
nitrosamine N-nitrosomethylbenzylamine (NMBA) in the esophagus of the rat.
[13]
strawberries, cranberries, walnuts, pecans, pomegranates, and other plant
foods. Hydrolysis of ellagitannin yields ellagic acid and the dilactone of
hexahydroxydiphenic acid.
RESEARCH FINDINGS
CANCER
The highest levels of ellagic acid are found in raspberries, strawberries, and
pomegranates, especially when they are freeze-dried. Studies have shown
that ellagic acid is able to cause apoptosis (cell death) in cancer cells. Some
also claim that it can prevent the binding of carcinogens to DNA, and
strengthens connective tissue, which may keep cancer cells from spreading
[1-9].
Some studies demonstrate that ellagic acid is able to reduce heart disease,
birth defects, liver fibrosis, and to promote wound healing.
Antiangiogenic properties
The vascular endothelial growth factor (VEGF) and platelet-derived growth
factor (PDGF) receptors play essential roles in angiogenesis and inhibition of
these receptors has been shown to result in potent anti-tumor activity in vivo.
Labrecque L et al reported that ellagic acid inhibits VEGF-induced
phosphorylation of VEGFR-2 in endothelial cell as well as PDGF-induced
phosphorylation of PDGFR in smooth muscle cells. [10]
Bladder Cancer
Researchers, China Medical University, Taiwan, induced cell cycle arrest and
apoptosis in T24 human bladder cancer cells in vitro using ellagic acid. [11]
Breast Cancer
Researchers at Louisiana State University demonstrated that ellagic acid
expressed a selective cytotoxicity and anti-proliferative activity, and induced
apoptosis in Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145
human prostate cancer cells. It was also observed that the mechanism of
apoptosis induction in ellagic acid-treated cancer cells was associated with
decreased ATP production, which is crucial for the viability of cancer cells.
[12]
Esophagus
de Boer JG et al, University of Victoria, Canada, showed the mutation
preventive properties of ellagic acid against the mutagenicity of the
nitrosamine N-nitrosomethylbenzylamine (NMBA) in the esophagus of the rat.
[13]
Ellagic Acid benefits and side effects
updated on March 7, 2009
updated on March 7, 2009
Leukemia
It has been demonstrated that quercetin and ellagic acid interacted
synergistically in the induction of apoptosis in the human leukemia cell line,
MOLT-4.[14-15]
Prostate Cancer
Lansky EP et al, Rimonest Ltd, Israel showed the anti-tumor activities of ellagic
acid against human PC-3 prostate cancer cells in vitro.[16]
Researchers at Louisiana State University demonstrated that ellagic acid
expressed a selective cytotoxicity and anti-proliferative activity, and induced
apoptosis in Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145
human prostate cancer cells. It was also observed that the mechanism of
apoptosis induction in ellagic acid-treated cancer cells was associated with
decreased ATP production, which is crucial for the viability of cancer cells.[17]
Anti-microbial Activity
Lu HF, Cheng Hsin Rehabilitation Medical Center, Taiwan, demonstrated that
ellagic acid was able to elicit dose-dependent bacteriostatic activity and
inhibition of N-acetylation of 2-aminofluorene (AF). [18]
Absorption
Ellagic acid was detected in human plasma at a maximum concentration (31.9
ng/ml) after 1 h post-ingestion of pomegranate juice but was rapidly eliminated
by 4 h. [19]
Degradation
Industrial processing reduces ohenolic content and antioxidant activity of
strawberry. However, the levels are still high. [20].
Side Effects
Up to the day that this article was prepared, no serious side effect is known.
Ellagic Acid Products or Supplements
Most manufacturers derive ellagic acid from pomegranate to a standardized
extract containing 40% of ellagic acid. It is believed that pomegranate is also
able to relieve bacterial and viral infections, intestinal parasites, chronic
mucous discharges and hemorrhages. [21]
Some manufacturers combine pomegranate extract (whole-fruit) and
pomegranate (seed) together in the product.
Citrus bioflavonoids are commonly combined with ellagic acid in a product.
Manufacturers believe that citrus bioflavonoids may maximize the absorption
and effects.
__________________________________________________
SELECTED, RECENT STUDIES ON ELLAGIC ACID
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. Seeram NP et, UCLA, J. Nutr Biochem. 2005 Jun;
16(6):360-7.
Pomegranate fruits are widely consumed as juice, and its antioxidant and
anti-atherosclerotic activities are attributed to ellagitannin and ellagic acid.
Ellagic acid, totol pomegranate tannin and punicalagin but not pomegranate
juice could induce apoptosis in colon cancer cells HCT116. However,
pomegranate juice had a better antioxidant activity than ellagic acid.
Enhancement of radiation-induced oxidative stress and cytotoxicity in
tumor cells by ellagic acid. Bhosle SM et al. Clin Chim Acta. 2005 May 26.
Combined treatment of tumor with ellagic acid and radiation enhances
oxidative stress and cytotoxicity in tumor cells in a study of mice. Ellagic acid
generated ROS in tumor cells, which increased, by an order of magnitude
when cells were treated with ellagic acid in combination with gamma radiation.
Ellagic acid protects normal cells against radiation damage.
It has been demonstrated that quercetin and ellagic acid interacted
synergistically in the induction of apoptosis in the human leukemia cell line,
MOLT-4.[14-15]
Prostate Cancer
Lansky EP et al, Rimonest Ltd, Israel showed the anti-tumor activities of ellagic
acid against human PC-3 prostate cancer cells in vitro.[16]
Researchers at Louisiana State University demonstrated that ellagic acid
expressed a selective cytotoxicity and anti-proliferative activity, and induced
apoptosis in Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145
human prostate cancer cells. It was also observed that the mechanism of
apoptosis induction in ellagic acid-treated cancer cells was associated with
decreased ATP production, which is crucial for the viability of cancer cells.[17]
Anti-microbial Activity
Lu HF, Cheng Hsin Rehabilitation Medical Center, Taiwan, demonstrated that
ellagic acid was able to elicit dose-dependent bacteriostatic activity and
inhibition of N-acetylation of 2-aminofluorene (AF). [18]
Absorption
Ellagic acid was detected in human plasma at a maximum concentration (31.9
ng/ml) after 1 h post-ingestion of pomegranate juice but was rapidly eliminated
by 4 h. [19]
Degradation
Industrial processing reduces ohenolic content and antioxidant activity of
strawberry. However, the levels are still high. [20].
Side Effects
Up to the day that this article was prepared, no serious side effect is known.
Ellagic Acid Products or Supplements
Most manufacturers derive ellagic acid from pomegranate to a standardized
extract containing 40% of ellagic acid. It is believed that pomegranate is also
able to relieve bacterial and viral infections, intestinal parasites, chronic
mucous discharges and hemorrhages. [21]
Some manufacturers combine pomegranate extract (whole-fruit) and
pomegranate (seed) together in the product.
Citrus bioflavonoids are commonly combined with ellagic acid in a product.
Manufacturers believe that citrus bioflavonoids may maximize the absorption
and effects.
__________________________________________________
SELECTED, RECENT STUDIES ON ELLAGIC ACID
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. Seeram NP et, UCLA, J. Nutr Biochem. 2005 Jun;
16(6):360-7.
Pomegranate fruits are widely consumed as juice, and its antioxidant and
anti-atherosclerotic activities are attributed to ellagitannin and ellagic acid.
Ellagic acid, totol pomegranate tannin and punicalagin but not pomegranate
juice could induce apoptosis in colon cancer cells HCT116. However,
pomegranate juice had a better antioxidant activity than ellagic acid.
Enhancement of radiation-induced oxidative stress and cytotoxicity in
tumor cells by ellagic acid. Bhosle SM et al. Clin Chim Acta. 2005 May 26.
Combined treatment of tumor with ellagic acid and radiation enhances
oxidative stress and cytotoxicity in tumor cells in a study of mice. Ellagic acid
generated ROS in tumor cells, which increased, by an order of magnitude
when cells were treated with ellagic acid in combination with gamma radiation.
Ellagic acid protects normal cells against radiation damage.
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Fish Oil
Flaxseed
Garlic
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Supplements
Acetyl-L Carnitine
Acidophilus
Bladderwrack
Bilberry
Chromium
CLA
Cod Liver Oil
Coenzyme Q
Colostrum
Dandelion
EGCG
Echinacea
Eleuthero
Ellagic Acid
Eve. Primrose Oil
Fish Oil
Flaxseed
Garlic
Ginger
Ginseng
Ginkgo Biloba
Glucosamine
Gotu Kola
Guar Gum
Hyaluronic acid
Lecithin
Lycopene
Milk Thistle
Nattokinase
Passion Flower
Probiotics
Policosanol /
Polycosanol
Pycnogenol
Reishi / Lingzhi
Resveratrol
Rhodiola
Royal Jelly
Stevia
Whey
Xylitol
Recent Article 2008 Dec Girish C and Pradhan SC. from Jawaharlal Institute of Postgraduate Medical Education and Research
proposed four phytochemicals for liver diseases - ellagic acid for antifibrotic treatment, phyllanthin for treating chronic hepatitis B,
glycyrrhizin to treat chronic viral hepatitis and picroliv for liver regeneration. [B1]
proposed four phytochemicals for liver diseases - ellagic acid for antifibrotic treatment, phyllanthin for treating chronic hepatitis B,
glycyrrhizin to treat chronic viral hepatitis and picroliv for liver regeneration. [B1]
References
1. Agricultural Research Services. Boosting ellagic acid in strawberries. United States Department of Agriculture Web site. October 8, 1999. 2. Ahn D, Putt D, Kresty L, Stoner GD, Fromm D, Hollenberg
PF. The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes. Carcinogenesis. 1996;17:821-828. 3. Fetrow CW, Avila JR. Professional's Handbook of
Complimentary and Alternative Medicines. Springhouse, PA: Springhouse Corp; 1999. 4. Harttig U, Hendricks JD, Stoner GD, Bailey GS. Organ specific, protocol dependent modulation of
7,12-dimethylbenz-[a]anthracene carcinogenesis in rainbow trout (Oncorhyncus mykiss) by dietary ellagic acid. Carcinogenesis. 1996;17:2403-2409. 5. Medical Economics. PDR for Herbal Medicines.
Montvale, NJ: Medical Economics Company; 1998. . Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW. P53/p21 (WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in
ellagic acid treated cancer cells. Cancer Lett. 1999;136:215-221. 7. Stoner GD, Morse MA. Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer. Cancer Lett. 1997;114:113-119.
8. Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity. J Exp Clin Cancer Res. 1998;17:431-434. [10] Combined inhibition of PDGF
and VEGF receptors by ellagic acid, a dietary-derived phenolic compound. Carcinogenesis. 2005 Apr;26(4):821-6. Epub 2005 Jan 20.[11] Li TM et al, Ellagic acid induced p53/p21 expression, G1 arrest and
apoptosis in human bladder cancer T24 cells, Anticancer Res. 2005 Mar-Apr;25(2A):971-9.[12] In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004 Nov;15(11):672-8. [13]
Chemoprotection against N-nitrosomethylbenzylamine-induced mutation in the rat esophagus., Nutr Cancer. 2004;50(2):168-73.[14] Mertens Talcott SU et al. Ellagic acid potentiates the effect of quercetin on
p21waf1/cip1, p53, and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitro. J Nutr. 2005 Mar;135(3):609-14.] [15] Mertens Talcott SU et al. Ellagic acid and quercetin
interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells., Cancer Lett. 2005 Feb 10;218(2):141-51.][16] Pomegranate (Punica
granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel., Invest New Drugs. 2005 Mar;23(2):121-2. [17] In vitro anti-proliferative activities
of ellagic acid. J Nutr Biochem. 2004 Nov;15(11):672-8.] [18]Ellagic acid inhibits growth and arylamine N-acetyltransferase activity and gene expression in Staphylococcus aureus. In Vivo. 2005
Jan-Feb;19(1):195-9.] [19] Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta. 2004 Oct;348(1-2):63-8.] [20]
Phenolic composition and antioxidant activities in flesh and achenes of strawberries (Fragaria ananassa). J Agric Food Chem. 2005 May 18;53(10):4032-40.][21] Nature's Benefit Ellagic Acid Plus 90 capsules,
online publication, smartbomb.com June 6, 2005] [B1] Girish C, Pradhan SC. Drug development for liver diseases: focus on picroliv, ellagic acid and curcumin. Fundam Clin Pharmacol. 2008
Dec;22(6):623-32.Click here to read
1. Agricultural Research Services. Boosting ellagic acid in strawberries. United States Department of Agriculture Web site. October 8, 1999. 2. Ahn D, Putt D, Kresty L, Stoner GD, Fromm D, Hollenberg
PF. The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes. Carcinogenesis. 1996;17:821-828. 3. Fetrow CW, Avila JR. Professional's Handbook of
Complimentary and Alternative Medicines. Springhouse, PA: Springhouse Corp; 1999. 4. Harttig U, Hendricks JD, Stoner GD, Bailey GS. Organ specific, protocol dependent modulation of
7,12-dimethylbenz-[a]anthracene carcinogenesis in rainbow trout (Oncorhyncus mykiss) by dietary ellagic acid. Carcinogenesis. 1996;17:2403-2409. 5. Medical Economics. PDR for Herbal Medicines.
Montvale, NJ: Medical Economics Company; 1998. . Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW. P53/p21 (WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in
ellagic acid treated cancer cells. Cancer Lett. 1999;136:215-221. 7. Stoner GD, Morse MA. Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer. Cancer Lett. 1997;114:113-119.
8. Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity. J Exp Clin Cancer Res. 1998;17:431-434. [10] Combined inhibition of PDGF
and VEGF receptors by ellagic acid, a dietary-derived phenolic compound. Carcinogenesis. 2005 Apr;26(4):821-6. Epub 2005 Jan 20.[11] Li TM et al, Ellagic acid induced p53/p21 expression, G1 arrest and
apoptosis in human bladder cancer T24 cells, Anticancer Res. 2005 Mar-Apr;25(2A):971-9.[12] In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004 Nov;15(11):672-8. [13]
Chemoprotection against N-nitrosomethylbenzylamine-induced mutation in the rat esophagus., Nutr Cancer. 2004;50(2):168-73.[14] Mertens Talcott SU et al. Ellagic acid potentiates the effect of quercetin on
p21waf1/cip1, p53, and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitro. J Nutr. 2005 Mar;135(3):609-14.] [15] Mertens Talcott SU et al. Ellagic acid and quercetin
interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells., Cancer Lett. 2005 Feb 10;218(2):141-51.][16] Pomegranate (Punica
granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel., Invest New Drugs. 2005 Mar;23(2):121-2. [17] In vitro anti-proliferative activities
of ellagic acid. J Nutr Biochem. 2004 Nov;15(11):672-8.] [18]Ellagic acid inhibits growth and arylamine N-acetyltransferase activity and gene expression in Staphylococcus aureus. In Vivo. 2005
Jan-Feb;19(1):195-9.] [19] Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta. 2004 Oct;348(1-2):63-8.] [20]
Phenolic composition and antioxidant activities in flesh and achenes of strawberries (Fragaria ananassa). J Agric Food Chem. 2005 May 18;53(10):4032-40.][21] Nature's Benefit Ellagic Acid Plus 90 capsules,
online publication, smartbomb.com June 6, 2005] [B1] Girish C, Pradhan SC. Drug development for liver diseases: focus on picroliv, ellagic acid and curcumin. Fundam Clin Pharmacol. 2008
Dec;22(6):623-32.Click here to read