ELLAGIC ACID IS A POWERFUL ANTI-CANCER SUPPLEMENT
SLOAN-KETTERING CLINICAL SUMMARY
A phenolic compound derived from ellagitannins commonly found
in red raspberries, strawberries and walnuts. Ellagic acid has
antiviral and antibacterial properties (1) (2). Recent studies
have indicated that ellagic acid may have anticarcinogenic effects
against liver, esophageal, prostate, and colorectal cancer cell
lines (3) (4) (5) (6). Other studies have reported that ellagic
acid is a potent antioxidant (1) (7). The anticancer properties of
ellagic acid have not been established in humans. Ellagic acid
obtained from dietary sources appears to be safe, but its
long-term toxicity effects have not been evaluated.
FOOD SOURCES
Red raspberries, strawberries, terminalia chebula, pomegranates,
walnuts.
USES
Cancer prevention
CONSTITUENTS
Ellagic acid.
MECHANISM OF ACTION
Ellagic acid appears to inhibit chemical-induced esophageal
carcinogenesis in animals (8). It down-regulates insulin-like
growth factor IGF-II (6) and activates p53/p21 expression, leading
to cell cycle arrest at the G1/S phase and apoptosis (9). In vitro
studies report that ellagic acid protects cells from oxidative DNA
damage caused by hydrogen peroxide and bleomycin (7). Ellagic
acid’s ability to induce detoxification enzymes NADPH and
quinone reductase contribute to some of its chemopreventive
activities (10). Conversely, certain cytochrome P450 enzymes are
inhibited by ellagic acid, preventing other carcinogens from being
metabolized into more mutagenic forms (11) (12).
PHARMACOKINETICS
Ellagitannins from berries and nuts are hydrolyzed in the
intestine into ellagic acid. Animal models show that some of the
ellagic acid is further metabolized by microflora in the
intestine. After absorption, ellagic acid and its metabolites are
localized preferentially in the lung tissues and, to a lesser
extent, in the liver tissues (13). Metabolites are excreted and
detected in urine and feces (14).
ADVERSE REACTIONS
None known
DRUG INTERACTIONS
There is evidence that ellagic acid inhibits cytochrome P450
(11) (12). In theory, this may increase the blood level of drugs
that are metabolized through the same pathways.
LITERATURE SUMMARY AND CRITIQUE
No clinical trials evaluate ellagic acid use in humans.
REFERENCES
(1) Atta UR, et al. New antioxidant and antimicrobial ellagic acid
derivatives from Pteleopsis hylodendron. Planta Medica
2001;67:335-9.
(2) Akiyama H, et al. Antibacterial action of several tannins
against Staphylococcus aureus. J Antimicrob Chemother
2001;48:487-91.
(3) Tanaka T, et al. Inhibitory effect of ellagic acid on
N-2-fluorenylacetamide-induced liver carcinogenesis in male ACI/N
rats. Jpn J Cancer Res 1988;79:1297-303.
(4) Stoner GD, et al. Isothiocyanates and freeze-dried
strawberries as inhibitors of esophageal cancer. Toxicol Sci
1999;52(2 Suppl):95-100.
(5) Narayanan BA, et al. Interactive gene expression pattern in
prostate cancer cells exposed to phenolic antioxidants. Life Sci
2002;70:1821-39.
(6) Narayanan BA, Re GG. IGF-II down regulation associated cell
cycle arrest in colon cancer cells exposed to phenolic antioxidant
ellagic acid. Anticancer Res 2001;21:359-64.
(7) Festa F, et al. Strong antioxidant activity of ellagic acid
in mammalian cells in vitro revealed by the comet assay.
Anticancer Res 2001;21:3903-8.
(8) Siglin JC, et al. Effects of dietary phenethyl
isothiocyanate, ellagic acid, sulindac and calcium on the
induction and progression of N-nitrosomethylbenzylamine-induced
esophageal carcinogenesis in rats. Carcinogenesis 1995;16:1101-6.
(9) Narayanan BA, et al. p53/p21(WAF1/CIP1) expression and its
possible role in G1 arrest and apoptosis in ellagic acid treated
cancer cells. Cancer Lett 1999;136:215-21.
(10) Barch DH, Rundhaugen LM. Ellagic acid induces
NAD(P)H:quinone reductase through activation of the antioxidant
responsive element of the rat NAD(P)H:quinone reductase gene.
Carcinogenesis 1994;15:2065-8.
(11) Zhang Z, et al. Inhibition of liver microsomal cytochrome
P450 activity and metabolism of the tobacco-specific nitrosamine
NNK by capsaicin and ellagic acid. Anticancer Res 1993;13:2341-6.
(12) Barch DH, et al. Dietary ellagic acid inhibits the
enzymatic activity of CYP1A1 without altering hepatic
concentrations of CYP1A1 or CYP1A1 mRNA. Biochem Biophys Res
Commun 1994;201:1477-82.
(13) Boukharta M, Jalbert G, Castonguay A. Biodistribution of
ellagic acid and dose-related inhibition of lung tumorigenesis in
A/J mice. Nutr Cancer 1992;18:181-9.
(14) Doyle B, Griffiths LA. The metabolism of ellagic acid in
the rat. Xenobiotica 1980;10:247-56.
Written: 05/03/2003 Updated: 06/24/2004
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have not been evaluated by the Food and Drug Administration. These
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