Ellagic acid

• How It Works

  Ellagic acid is found in many foods that are part of a healthy diet, but there is no evidence to support its use for cancer treatment.

  Ellagic acid is a naturally occurring compound called a tannin, found in red raspberries, strawberries, and walnuts. It has been studied in the laboratory, but not in humans. In laboratory animals, ellagic acid showed cancer-preventive properties. For example, rats fed ellagic acid before and during exposure to carcinogens (cancer-causing substances) developed fewer liver tumors than rats fed a normal diet. Similar results were shown in mice with lung or esophageal cancer. Scientists think that ellagic acid exerts these effects in two ways. First, ellagic acid enhances the activity of certain detoxification enzymes in the liver, speeding up the removal of dangerous substances from the body, while it also inhibits the cytochrome P450 liver enzymes and may prevent them from metabolizing carcinogens into more dangerous forms. Second, ellagic acid causes changes in the cell cycle of cancer cells in the test tube, leading to cell death.

• Purported Uses
  • To prevent cancer
    Although experiments in the laboratory and in animals suggest that ellagic acid may have anti-cancer properties, these results are not always transferable to the human body. There are no data on the safety and efficacy of ellagic acid in humans.
  • To lower cholesterol
    One study found that consumption of a drink made with freeze-dried strawberry powder for 4 weeks lowered total cholesterol and LDL levels in obese women with metabolic syndrome. Further research is needed to confirm this effect.
• Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450: (Ellagic acid may increase the risk of side effects of these drugs).
• 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). A small clinical study found that ellagic acid may lower cholesterol and decrease lipid peroxidation in patients with metabolic syndrome ⁽⁷⁾. Other studies have reported that ellagic acid is a potent antioxidant ^(1) (8).

  Pre-clinical studies indicate anticarcinogenic effects of ellagic acid against liver, esophageal, prostate, and colorectal cancer cell lines ^{(3) (4) (5) (6)}. It was also shown to induce apoptosis and potentiate all-trans retinoic acid myeloid differentiation therapy in human leukemia HL-60 cells ⁽⁹⁾. Human studies have yet to be conducted.

  In another study, pomegranate-derived ellagitannins exhibited anti-aromatase activity and suppressed testosterone-induced breast cancer cell proliferation, but ellagic acid did not have such effects  ⁽¹⁰⁾.

• Food Sources

  Red raspberries, strawberries, pomegranates, walnuts.

• Purported Uses
  • Cancer prevention
  • Hypercholesterolemia
• Mechanism of Action

  Ellagic acid appears to inhibit chemical-induced esophageal carcinogenesis in animals ⁽¹¹⁾. 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 ⁽¹²⁾. In vitro studies report that ellagic acid protects cells from oxidative DNA damage caused by hydrogen peroxide and bleomycin ⁽⁸⁾. Ellagic acid’s ability to induce detoxification enzymes NADPH and quinone reductase contribute to some of its chemopreventive activities ⁽¹³⁾. Conversely, certain cytochrome P450 enzymes are inhibited by ellagic acid, preventing other carcinogens from being metabolized into more mutagenic forms ^(14) (15).

• Herb-Drug Interactions

  Cytochrome P450 substrates: Ellagic acid inhibits cytochrome P450 and can affect the intracellular concentration of drugs metabolized by this enzyme ^(14) (15).

• 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. Basu A, Wilkinson M, Penugonda K, et al. Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic sndrome: baseline and post intervention effects. Nutr Journal. 2009 Sept;8:43.

  8. 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.

  9. Hagiwara Y, Kasukabe T, Kaneko Y, Niitsu N, Okabe-Kado J. Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells. Int J Hematol. 2010 Jul;92(1):136-43.

  10. Adams LS, Zhang Y, Seeram NP, Heber D, Chen S. Pomegranate ellagitannin-derived compounds exhibit anti proliferative and anti-aromatase activity in breast cancer cells in vitro. Cancer Prev Res. 2010 Jan;3(1):108-113.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Doyle B, Griffiths LA. The metabolism of ellagic acid in the rat. Xenobiotica 1980;10:247-56.