About Herbs, Botanicals & Other Products

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). One 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).
The anticancer properties of ellagic acid have not been established in humans. Ellagic acid was also shown to induce apoptosis and potentiate all trans retinoic acid myeloid differentiation therapy in human leukemia HL-60 cells (9). Another study found that six pomegranate-derived ellagitannins demonstrated anti-aromatase activity and suppressed testosterone-induced breast cancer cell proliferation, but ellagic acid did not have these effects (10). Ellagic acid obtained from dietary sources appears to be safe, but its long-term toxicity effects have not been evaluated.

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Food Sources

Red raspberries, strawberries, pomegranates, walnuts.

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Purported Uses
  • Cancer prevention
  • Hypercholesterolemia
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Constituents

Ellagic acid.

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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).

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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 (16). Metabolites are excreted and detected in urine and feces (17).

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Adverse Reactions
  • None known
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Herb-Drug Interactions

There is evidence that ellagic acid inhibits cytochrome P450 (14) (15). In theory, this may increase the blood level of drugs that are metabolized through the same pathways.

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Literature Summary and Critique

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

This study investigated the effect of freeze-dried strawberry powder on plasma lipid levels and biomarkers of oxidative stress and inflammation in women with metabolic syndrome. Sixteen women with at least 3 features of metabolic syndrome (waist circumfernece > 35 inches, triglycerides > 150 mg/dl, fasting blood glucose between 100 mg/dl and 126 mg/dl, HDL < 50 mg/dl or blood pressure > 130/85 mm/Hg) were enrolled. Subjects consumed one cup of strawberry drink (25 g freeze-dried strawberry powder in water) twice daily for four weeks. Fasting blood analyses, anthropometrics, dietary intake, blood pressure, biomarkers of oxidative stress and inflammation, and plasma ellagic acid levels were all evaluated at baseline and again at four weeks. Study results indicated that mean serum total cholesterol and LDL-cholesterol levels were significantly lower at 4 weeks compared to baseline (-5% and -6%, respectively [p<0.05]). Lipid peroxidation, as indicated by malondialdehyde and hydroxynonenal, was also reduced (-14%, p < 0.01). Markers of inflammation, such as C-reactive protein and adiponectin, were not affected. Increased plasma ellagic acid levels were detected in 81% of subjects at four weeks without any change in dietary intake compared to baseline. The authors concluded that short-term supplementation with freeze-dried strawberries appears to have a hypocholesterolemic effect and decrease lipid peroxidation in women with metabolic syndrome.

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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.
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How It Works

Bottom Line: There is no proof that ellagic acid can treat cancer. Ellagic acid is found in many foods that are part of a healthy diet, but it is too soon to say whether it can help prevent cancer in humans.

Ellagic acid is a naturally occuring compound called a tannin. It can be isolated from foods such as red raspberries, strawberries, and walnuts, and has been studied in the laboratory, but not in humans. In laboratory animals, ellagic acid has been found to have cancer-preventing activity. For example, rats fed ellagic acid before and during exposure to carcinogens (cancer-causing substances) develop fewer liver tumors than rats fed a normal diet. Similar results have been 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. Unfortunately, neither of these promising effects have been shown to occur in the human body.

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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. No studies have been performed in humans to test whether ellagic acid is safe and effective.
  • 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. However, further research is needed to confirm this effect.
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Research Evidence

The safety and efficacy of ellagic acid needs to be further studied in large, well-controlled .

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Patient Warnings
  • Ellagic acid is known to disrupt the activity of certain liver enzymes (cytochrome P450 enzymes) that are important in the metabolism and clearance of many medications from the body. Ask your doctor if you are taking any medications that are metabolized by cytochrome P450 enzymes, because ellagic acid might interfere with their metabolism and cause higher than normal levels of these medications in the blood.
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Dosage (Inside MSKCC Only)
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Last updated: March 4, 2011