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ORDER ELLAGIC ACID

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

**Statements contained herein have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat and cure or prevent disease. Always consult with your professional health care provider before changing any medication.**

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