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
