The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers

Summary

Background

Consumption of fruit and vegetables is associated with a decreased risk of heart disease and cancer.This has been ascribed in part to antioxidants in these foods inactivating reactive oxygen species involved in initiation or progression of these diseases. Non–nutritive anthocyanins are present in significant amounts in the human diet. However, it is unclear whether they have health benefits in humans. AimTo determine whether daily consumption of anthocyanin–rich cranberry juice could alter plasma antioxidant activity and biomarkers of oxidative stress.

Methods

20 healthy female volunteers aged 18–40 y were recruited. Subjects consumed 750 ml/day of either cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine samples were obtained over 4 weeks.The total phenol, anthocyanin and catechin content of the supplements and plasma were measured. Anthocyanin glycosides were identified by tandem mass spectrometry (MS–MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were measured by HPLC. Total antioxidant ability was determined using electron spin resonance (ESR) spectrometry and by the FRAP assay. Plasma total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were measured. Glutathione peroxidase (GSH–Px), catalase (CAT) and superoxide dismutase (SOD) activities were measured in erythrocytes. Urine was collected for analysis of malondialdehyde (MDA) by HPLC and 8–oxo–deoxyguanosine (8–oxo–dG) by ELISA.Endogenous and induced DNA damage were measured by single cell gel electrophoresis (SCGE) in lymphocytes.

Results

Vitamin C, total phenol, anthocyanin and catechin concentrations and FRAP and ESR values were significantly higher in the cranberry juice compared with the placebo. Cyanidin and peonidin glycosides comprised the major anthocyanin metabolites [peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) > cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin glucoside (4.1%) > cyanidin glucoside (1.4 %)]. Plasma vitamin C increased significantly (P<0.01) in volunteers consuming cranberry juice. No anthocyanins (plasma) or catechins (plasma or urine) were detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were unchanged. The antioxidant potential of the plasma, GSH–Px, CAT and SOD activities, and MDA were similar for both groups. Supplementation with cranberry juice did not affect 8–oxo–deoxyguanosine in urine or endogenous or H2O2–induced DNA damage in lymphocytes.

Conclusions

Cranberry juice consumption did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Similarly, cranberry juice had no effect on basal or induced oxidative DNA damage.These results show the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health.

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References

  1. 1.

    Diplock AT (1994) Antioxidants in disease prevention. Mol Aspect Med 15:293–376

    CAS  Google Scholar 

  2. 2.

    Halliwell B (2002) Effect of diet on cancer development: is oxidative DNA damage a biomarker? Free Rad Biol Med 32:968–974

    CAS  Article  Google Scholar 

  3. 3.

    Duthie GG, Duthie SJ, Kyle JAM (2000) Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants. Nutr Res Rev 13:79–106

    CAS  Article  Google Scholar 

  4. 4.

    Clifford MN (2000) Anthocyanins nature, occurrence and dietary burden. J Sci Food Agric 80:1063–1072

    CAS  Google Scholar 

  5. 5.

    Gasiorowski K, Szyba K, Brokos B, Kolaczynska B, Jankowiak–Wlodarczyk M, Oszmianski J (1997) Antimutagenic activity of anthocyanins isolated from aronia melanocarpa fruits. Cancer Letts 119:37–46

    CAS  Google Scholar 

  6. 6.

    Youdim KA, Martin A, Joseph JA (2000) Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Rad Biol Med 29:51–60

    CAS  Article  Google Scholar 

  7. 7.

    Youdim KA, McDonald J, Kalt W, Joseph JA (2002) Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. J Nutr Biochem 13:282–288

    CAS  Google Scholar 

  8. 8.

    Duthie SJ, Gardner PT, Morrice PC, Wood SG, Pirie L, Bestwick C, Milne L, Duthie G (2005) DNA stability and lipid peroxidation in vitamin E–deficient rats in vivo and colon cells in vitro:modulation by the dietary anthocyanin, cyanidin– 3–glycoside. Eur J Nutr (in press)

  9. 9.

    Kamei H, Koide T, Kojimam T, Hasegawa M, Terabe K, Umeda T, Yukawa T, Hashimoto Y (1996) Flavonoid–mediated tumour growth suppression demonstrated by in vivo study. Cancer Biother Radiopharm 11:193–196

    CAS  Google Scholar 

  10. 10.

    Hakimuddin F, Paliyath G, Meckling K (2004) Selective cytotoxicity of a red grape wine flavonoid fraction against MCF–7 cells. Breast Cancer Res Treat 85:65–79

    CAS  Article  Google Scholar 

  11. 11.

    Prior RL, Lazarus S, Cao G, Muccitelli H, Hammerstone JF (2001) Identification of procyanidins and anthocyanins in blueberries and cranberries (Vaccinium Spp. ) using high–performance liquid chromatography–mass spectrometry. J Agric Food Chem 49:1270–1276

    CAS  Article  Google Scholar 

  12. 12.

    Vvedenskaya IO, Rosen RT, Guido JE, Russell DJ, Mills KA, Vorsa N (2004) Characterization of flavonols in cranberry (Vaccinium macropon) powder. J Agric Food Chem 52:188–195

    CAS  Article  Google Scholar 

  13. 13.

    Leahy M, Speroni J, Starr M (2002) Latest developments in cranberry health research. Pharm Biol 40:50–54

    CAS  Google Scholar 

  14. 14.

    Sun J, Chu YF, Wu XZ, Liu RH (2002) Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem 50:7449–7454

    CAS  Google Scholar 

  15. 15.

    Porter ML, Krueger CG, Wiebe DA, Cunningham DG, Reed JD (2001) Cranberry proanthocyanins associate with low–density lipoprotein and inhibit in vitro Cu2+–induced oxidation. J Sci Food and Agric 81:1306–1313

    CAS  Google Scholar 

  16. 16.

    Cunningham DG, Vannozzi SA, Turk R, Roderick R, O’Shea E, Brilliant K (2004) Cranberry phytochemicals and their health benefits. Nutraceutical Beverages. Chem Nutr and Health 871:35–51

    CAS  Google Scholar 

  17. 17.

    Reed J (2002) Cranberry flavonoids, atherosclerosis and cardiovascular health. Clinical Reviews in Food Sci and Nutr 42:301–316

    CAS  Google Scholar 

  18. 18.

    Boushey CJ, Beresford SAA, Omenn GS (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274:1049–1057

    CAS  Article  Google Scholar 

  19. 19.

    Jenkinson A McE, Collins AR, Duthie SJ, Wahle KWJ, Duthie GG, (1999) The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes. FASEB J 13:2138–2142

    CAS  Google Scholar 

  20. 20.

    Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic– phosphotungstic acid reagents. Am J Enology Viticult 16:144–158

    CAS  Google Scholar 

  21. 21.

    Kivits GAA, VanderSman FJP, Tijburg LBM (1997) Analysis of catechins from green and black tea in humans: a specific and sensitive colorimetric assay of total catechins in biological fluids. Int J Food Sci Nutr 48:387–392

    CAS  Google Scholar 

  22. 22.

    Ribéreau–Gayon P, Stonestreet E (1965) Le dosage des anthocyanes dans le vin rouge. Bull Soc Chim 9:2649–2652

    Google Scholar 

  23. 23.

    Mullen W, McGinn J, Lean MEJ, MacLean MR, Gardner P, Duthie, GG, Crozier A (2002) Ellagitannins, flavonoids and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties. J Agric Food Chem 50:5191–5196

    CAS  Google Scholar 

  24. 24.

    Ross MA (1994) Determination of ascorbic acid and uric acid in plasma by high–performance liquid chromatography. J Chromatogr B Biomed Appl 657:197–200

    CAS  Google Scholar 

  25. 25.

    Serafini M, Maiani G, Ferro–Luzzi A (1998) Alcohol–free red wine enhances plasma antioxidant capacity in humans. J Nutr 128:1003–1007

    CAS  Google Scholar 

  26. 26.

    Gardner PT, McPhail DB, Duthie GG (1997) Electron spin resonance spectroscopic assessment of the antioxidant potential of teas in aqueous and organic media. J Sci Food Agric 76:257–262

    Google Scholar 

  27. 27.

    Gardner PT, White AC, McPhail DB, Duthie GG (2000) The relative contributions of vitamin C, carotenoids and phenolics to the antioxidant potential of fruit juices. Food Chem 68:471–474

    CAS  Article  Google Scholar 

  28. 28.

    Pedersen CB, Kyle J, Jenkinson A McE, Gardner PT, McPhail DB, Duthie GG (2000) Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers. Eur J Clin Nutr 54:405–408

    CAS  Google Scholar 

  29. 29.

    Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": The FRAP assay. Anal Biochem 239:70–76

    CAS  Article  Google Scholar 

  30. 30.

    Duthie SJ, Grant G, Narayanan S (2000) Increased uracil misincorporation in lymphocytes from folate–deficient rats. Br J Cancer 83:1532–1537

    CAS  Article  Google Scholar 

  31. 31.

    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characteristics of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  Google Scholar 

  32. 32.

    Aebi H (1984) Catalase in vitro. Methods in Enzymol 105:121–126

    CAS  Google Scholar 

  33. 33.

    Arthur JR, Boyne R (1985) Superoxide dismutase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle. Life Sci 36:1569–1575

    CAS  Article  Google Scholar 

  34. 34.

    Wong S, Knight JA, Hopfer SM, Zaharia O, Leach CN Jr, Sunderman FW Jr (1987) Lipid peroxides in plasma as measured by liquid chromatographic separation of malondialdehyde–thiobarbituric acid adducts. Clin Chem 33:214–220

    CAS  Google Scholar 

  35. 35.

    Erhola M, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Uchida K, Osawa T, Nieminen MM, Alho H, Kellokumpu– Lehtinen P (1997) Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8–hydroxy– 2’–deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment. FEBS Lett 409:287–291

    CAS  Article  Google Scholar 

  36. 36.

    Duthie SJ, Ma AG, Ross MA, Collins AR (1996) Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res 56:1291–1295

    CAS  Google Scholar 

  37. 37.

    Kenward MG (1987) A method of comparing profiles of repeated measurements. Appl Stat 36:296–308

    Google Scholar 

  38. 38.

    World Cancer Research Fund and American Institute for Cancer Research (1997) In: Food, Nutrition and Prevention of Cancer; a global perspective. World Cancer Research Fund and American Institute for Cancer Research (1997)

  39. 39.

    Williams C (1995) Healthy eating: clarifying advice about fruit and vegetables. Brit Med J 310:1453–1455

    CAS  Google Scholar 

  40. 40.

    Duthie SJ, Dobson V (1999) Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Eur J Nutr 38:28–34

    CAS  Article  Google Scholar 

  41. 41.

    Lazze MC, Pizzalo R, Savio M, Stivala LA, Prosperi E, Bianchi L (2003) Anthocyanins protect against DNA damage induced by tert–butyl–hydroperoxide in rat smooth muscle and hepatoma cells. Mutat Res Genet Toxicol Environ Mutagen 535:103–115

    CAS  Google Scholar 

  42. 42.

    Serraino V, Dugo L, Dugo P, Mondello L, Mazzon E, Dugo G, Caputi AP, Cuzzocrea S (2003) Protective effects of cyanidin–3–O–glucoside from blackberry extract against peroxynitrite–induced endothelial dysfunction and vascular failure. Life Sci 73:1097–1114

    CAS  Article  Google Scholar 

  43. 43.

    Kang SY, Seeram NP, Nair MG, Bourquin LD (2003) Tart cherry anthocyanins inhibit tumour development in Apc(Min) mice and reduce proliferation of human colon cancer cells. Cancer Letts 194:13–19

    CAS  Google Scholar 

  44. 44.

    Singletary KW, Stansbury MJ, Giusti M, Van Breemen RB, Wallig M, Rimando A (2003) Inhibition of rat mammary tumorigenesis by Concord grape juice constituents. J Agric Food Chem 51:7280–7286

    CAS  Article  Google Scholar 

  45. 45.

    Kamei H, Koide T, Kojimam T, Hasegawa M, Terabe K, Umeda T, Hashimoto Y (1996) Flavonoid–mediated tumour growth suppression demonstrated by in vivo study. Cancer Biother Radiopharm 11:193–196

    CAS  Google Scholar 

  46. 46.

    Giovanelli L, Testa G, De Filippo C, Cheynier V, Clifford MN, Dolara P (2000) Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo. Eur J Nutr 39:207–212

    Google Scholar 

  47. 47.

    Tsuda T, Horio F, Kitoh J, Osawa T (1999) Protective effects of dietary cyanidin 3–O–β–D–glucoside on liver ischemia– reperfusion injury in rats. Arch Biochem Biophys 368:361–366

    CAS  Article  Google Scholar 

  48. 48.

    Ramirez–Tortosa C, Anderson O, Gardner PT, Morrice PC, Wood S, Duthie SJ, Collins AR, Duthie GG (2001) Anthocyanin– rich extract decreases indices of lipid peroxidation and DNA damage in vitamin E–depleted rats. Free Rad Biol Med 31:1033–1037

    CAS  Google Scholar 

  49. 49.

    Wang C–J, Wang J–M, Lin W–L, Chu C–Y, Chou F–P, Tseng T–H (2000) Protective effects of hibiscus anthocyanins against tert–butyl hydroperoxide–induced hepatic toxicity in rats. Food and Chem Toxicol 38:411–416

    CAS  Google Scholar 

  50. 50.

    Cao G, Prior RL (1999) Anthocyanins are detected in human plasma after oral administration of an elderberry extract. Clin Chem 45:574–576

    CAS  Google Scholar 

  51. 51.

    Murkovic M, Mulleder U, Adam U, Pfannhauser W (2001) Detection of anthocyanins from elderberry juice in human urine. J Sci Food and Agric 81:934–937

    CAS  Google Scholar 

  52. 52.

    Wu X, Cao G, Prior RL (2002) Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 132:1865–1871

    CAS  Google Scholar 

  53. 53.

    Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747

    CAS  Google Scholar 

  54. 54.

    Aura A–M, Martin–Lopez P, O’Leary KA, Williamson G, Oksman–Caldentey KM, Poutanen K, Santos–Buelga C (2004) In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr (in press)

  55. 55.

    Kay CD, Holub BJ (2002) The effects of wild blueberry (Vaccinium angustifolium) consumption on postprandial serum antioxidant status in human subjects. Br J Nutr 88:389–397

    CAS  Google Scholar 

  56. 56.

    Choy CKM, Benzie IFF, Cho P (2003) Antioxidants in tears and plasma: interrelationships and effect of vitamin C supplementation. Current Eye Res 27:55–60

    Google Scholar 

  57. 57.

    Cao G, Russell RM, Lischner N, Prior RL (1998) Serum antioxidant capacity is increased by consumption of strawberries, spinach, red wine or vitamin C in elderly women. J Nutr 128:2383–2390

    CAS  Google Scholar 

  58. 58.

    Cadenas S, Rojas C, Mendez J, Herrero A, Barja G (1996) Vitamin C decreases urine lipid peroxidation products in young healthy human volunteers under normal conditions. Pharmacol Toxicol 79:247–253

    CAS  Google Scholar 

  59. 59.

    Wen Y, Cooke T, Feely J (1997) The effect of pharmacological supplementation with vitamin C on low–density lipoprotein oxidation. Br J Clin Pharmacol 44:94–97

    CAS  Article  Google Scholar 

  60. 60.

    Anderson D, Phillips BJ, Yu T, Edwards AJ, Ayesh R, Butterworth KR (1997) The effects of vitamin C supplementation on biomarkers of oxygen radical generated damage in human volunteers with “low” or “high” cholesterol levels. Environ Mol Mutagen 30:161–174

    CAS  Google Scholar 

  61. 61.

    Nyysson K, Poulsen HE, Hayn M, Agerbo P, Porkkala–Sarataho E, Kaikkonen J, Salonen R, Salonen JT (1997) Effect of supplementation on smoking men with plain or slow release ascorbic acid on lipoprotein oxidation. Eur J Clin Nutr 51:154–163

    Google Scholar 

  62. 62.

    Green MHL, Lowe JE, Waugh APW, Aldrich KE, Cole J, Arlett CF (1994) Effect of diet and vitamin C on DNA strand breakage in freshly–isolated human white blood cells. Mutat Res 316:91–102

    CAS  Google Scholar 

  63. 63.

    Fraga CG, Motchnik PA, Shigenaga MK, Helbeck HJ, Jacob RA, Ames BN (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 88:11003–11006

    CAS  Google Scholar 

  64. 64.

    Porkkala–Sarataho E, Salonen JT, Nyyssonen K, Kaikkonen J, Salonen R, Ristonmaa U, Diczfalusy U, Brigelius–Flohe R, Loft S, Poulsen HE (2000) Long–term effects of vitamin E, vitamin C and combined supplementation on urinary 7–hydroxy–8–oxo–2–deoxyguanosine, serum cholesterol oxidation products and oxidation resistance of lipids in non–depleted men. Arterioscler Thromb Vasc Biol 20:2087–2093

    CAS  Google Scholar 

  65. 65.

    Boyle SP, Dobson VL, Duthie SJ, Kyle JAM, Collins AR (2000) Absorption and DNA protective effects of flavonoid glycosides from an onion meal. Eur J Nutr 39:213–223

    CAS  Article  Google Scholar 

  66. 66.

    Boyle SP, Dobson VL, Duthie SJ, Hinselwood DC, Kyle JAM, Collins AR (2000) Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study. Eur J Clin Nutr 54:774–782

    CAS  Article  Google Scholar 

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Correspondence to Dr. S. J. Duthie.

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Duthie, .J., Jenkinson, A.M., Crozier, A. et al. The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers. Eur J Nutr 45, 113–122 (2006). https://doi.org/10.1007/s00394-005-0572-9

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Key words

  • cranberry
  • human study
  • vitamin C
  • antioxidant capacity
  • oxidative DNA damage
  • anthocyanin