European Journal of Nutrition

, Volume 52, Issue 3, pp 949–961 | Cite as

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors

  • Patrizia Riso
  • Dorothy Klimis-Zacas
  • Cristian Del Bo’
  • Daniela Martini
  • Jonica Campolo
  • Stefano Vendrame
  • Peter Møller
  • Steffen Loft
  • Renata De Maria
  • Marisa Porrini
Original Contribution

Abstract

Purpose

Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease.

Methods

Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m2) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed.

Results

Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p ≤ 0.01) and the levels of H2O2-induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p ≤ 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study.

Conclusions

In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function. This study was registered at www.isrctn.org as ISRCTN47732406.

Keywords

Wild blueberry Endothelial function DNA damage Blood lipids Cardiovascular risk 

Abbreviations

AACC

American Association for Clinical Chemistry

ACNs

Anthocyanins

AI

Augmentation index

AI@75

Augmentation index standardized for heart rate of 75 bpm

ANOVA

Analysis of variance

AOAC

Association of Official Analytical Chemists

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

BMI

Body mass index

CI

Confidence interval

CRP

C-reactive protein

CVD

Cardiovascular disease

FMD

Flow-mediated dilation

FPG

Formamidopyrimidine DNA glycosylase

FRHI

Framingham reactive hyperemia index

GGT

Gamma-glutamyltransferase

GSH

Reduced glutathione

GSH-Px

Glutathione peroxidase

GSSG

Oxidized glutathione

GST

Glutathione S-transferase

HDL-C

High-density lipoprotein cholesterol

HPLC

High-performance liquid chromatography

IL-6

Interleukin-6

LC-DAD-MS/MS

Liquid chromatography/diode array detector/mass spectrometry

LDL-C

Low-density lipoprotein cholesterol

LSD

Least significant difference

BMCs

Blood mononuclear cells

NO

Nitric oxide

PAT

Peripheral arterial tone

PBS

Phosphate-buffered saline

PL

Placebo

RH

Reactive hyperemia

RHI

Reactive hyperemia index

SD

Standard deviation

SOD

Superoxide dismutase

SPE

Solid-phase extraction

sVCAM-1

Soluble vascular adhesion molecule-1

TNF-α

Tumor necrosis factor alpha

TFA

Trifluoroacetic acid

TG

Triglycerides

TSC

Total serum cholesterol

UHPLC-MS/MS

Ultra-high-pressure liquid chromatography/mass spectrometry

WB

Wild blueberry

References

  1. 1.
    Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S, Schiffrin EL, Eisenberg MJ (2010) The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 56:1113–1132CrossRefGoogle Scholar
  2. 2.
    Peredes-Lόpez O, Cervantes-Ceja ML, Vigna-Pérez M, Hernández-Pérez T (2010) Berries: improving human health and healthy aging, and promoting quality life-a review. Plant Foods Hum Nutr 65:299–308CrossRefGoogle Scholar
  3. 3.
    Szajdek A, Borowska JE (2008) Bioactive compounds and health-promoting properties of berry fruits: a review. Plant Foods Hum Nutr 63:147–156CrossRefGoogle Scholar
  4. 4.
    Yang YM, Noh K, Han CY, Kim SG (2010) Transactivation of genes encoding for phase II enzymes and phase III transporters by phytochemical antioxidants. Molecules 15:6332–6348CrossRefGoogle Scholar
  5. 5.
    Del Rio D, Borges G, Crozier A (2010) Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br J Nutr 104:S67–S90CrossRefGoogle Scholar
  6. 6.
    Nicoué EE, Savard S, Belkacemi K (2007) Anthocyanins in wild blueberry of Quebec: extraction and identification. J Agric Food Chem 55:5626–5635CrossRefGoogle Scholar
  7. 7.
    Bushway RB, McGann DF, Cook WP, Bushway AA (1983) Mineral and vitamin content of lowbush blueberries (Vaccinium angustifolium). J Food Sci 48:1878–1880CrossRefGoogle Scholar
  8. 8.
    Kong JM, Chia LS, Goh NK, Chia TF, Brouillard R (2003) Analysis and biological activities of anthocyanins. Phytochemistry 64:923–933CrossRefGoogle Scholar
  9. 9.
    Galvano F, La Fauci L, Lazzarino G, Fogliano V, Ritieni A, Ciappellano S, Battistini NC, Tavazzi B, Galvano G (2004) Cyanidins: metabolism and biological properties. J Nutr Biochem 15:2–11CrossRefGoogle Scholar
  10. 10.
    Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D (2007) Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res 51:675–683CrossRefGoogle Scholar
  11. 11.
    Tsuda T, Horio F, Uchida K, Aoki H, Osawa T (2003) Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr 133:2125–2130Google Scholar
  12. 12.
    Norton C, Kalea AZ, Harris PD, Klimis-Zacas DJ (2005) Wild blueberry-rich diets affect the contractile machinery of the vascular smooth muscle in the Sprague-Dawley rat. J Med Food 8:8–13CrossRefGoogle Scholar
  13. 13.
    Sasaki R, Nishimura N, Hoshino H, Isa Y, Kadowaki M, Ichi T, Tanaka A, Nishiumi S, Fukuda I, Ashida H, Horio F, Tsuda T (2007) Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol 74:1619–1627CrossRefGoogle Scholar
  14. 14.
    Ataie-Jafari A, Hosseini S, Karimi F, Pajouhi M (2008) Effects of sour cherry juice on blood glucose and some cardiovascular risk factors improvements in diabetic women: a pilot study. Nutr Food Sci 38:355–360CrossRefGoogle Scholar
  15. 15.
    Titta L, Trinei M, Stendardo M, Berniakovich I, Petroni K, Tonelli C, Riso P, Porrini M, Minucci S, Pelicci PG, Rapisarda P, Reforgiato Recupero G, Giorgio M (2010) Blood orange juice inhibits fat accumulation in mice. In. J Obes (Lond) 34:578–588CrossRefGoogle Scholar
  16. 16.
    Basu A, Du M, Leyva MJ, Sanchez K, Betts NM, Wu M, Aston CE, Lyons TJ (2010) Blueberry decrease cardiovascular risk factors in obese men and women with metabolic syndrome. J Nutr 140:1582–1587CrossRefGoogle Scholar
  17. 17.
    Weisel T, Baum M, Eisenbrand G, Dietrich H, Will F, Stockis JP, Kulling S, Rüfer C, Johannes C, Janzowski C (2006) An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands. Biotechnol J 1:388–397CrossRefGoogle Scholar
  18. 18.
    Riso P, Visioli F, Gardana C, Grande S, Brusamolino A, Galvano F, Galvano G, Porrini M (2005) Effects of blood orange juice intake on antioxidant bioavailability and on different markers related to oxidative stress. J Agric Food Chem 53:941–947CrossRefGoogle Scholar
  19. 19.
    Manach C, Williamson G, Morand C, Scalbert A, Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S–242SGoogle Scholar
  20. 20.
    Del Bo’ C, Ciappellano S, Klimis-Zacas D, Martini D, Gardana C, Riso P, Porrini M (2010) Anthocyanin absorption, metabolism and distribution from a wild blueberry-enriched diet (Vaccinium angustifolium) is affected by diet duration in the Sprague-Dawley rat. J Agric Food Chem 58:2491–2497CrossRefGoogle Scholar
  21. 21.
    Del Bo’ C, Kristo AS, Kalea AZ, Ciappellano S, Riso P, Porrini M, Klimis-Zacas D (2012) The temporal effect of a wild blueberry (Vaccinium angustifolium)-enriched diet on vasomotor tone in the Sprague-Dawley rat. Nutr Metab Cardiovasc Dis 22:127–132CrossRefGoogle Scholar
  22. 22.
    Del Bo’ C, Martini D, Vendrame S, Riso P, Ciappellano S, Klimis-Zacas D, Porrini M (2010) Improvement of lymphocyte resistance against H2O2-induced DNA damage in Sprague-Dawley rats after eight weeks of a wild blueberry (Vaccinium angustifolium)-enriched diet. Mutat Res 703:158–162CrossRefGoogle Scholar
  23. 23.
    Kalea AZ, Clark K, Schuschke DA, Klimis-Zacas DJ (2009) Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat. J Med Food 12:21–28CrossRefGoogle Scholar
  24. 24.
    Kalea AZ, Clark K, Schuschke DA, Kristo AS, Klimis-Zacas DJ (2010) Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the vascular reactivity in the aorta of young spontaneously hypertensive rats. J Nutr Biochem 21:14–22CrossRefGoogle Scholar
  25. 25.
    Kristo AS, Kalea AZ, Schuschke DA, Klimis-Zacas DJ (2010) A wild blueberry-enriched diet (Vaccinium angustifolium) improves vascular tone in the adult spontaneously hypertensive rat. J Agric Food Chem 58:11600–11605CrossRefGoogle Scholar
  26. 26.
    Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT (2010) Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr 140:1764–1768CrossRefGoogle Scholar
  27. 27.
    Kawano H, Motoyama T, Kugiyama K, Hirashima O, Ohgushi M, Yoshimura M, Ogawa H, Okumura K, Yasue H (1996) Menstrual cyclic variation of endothelium-dependent vasodilation of the brachial artery: possible role of estrogen and nitric oxide. Proc Assoc Am Physicians 108:473–480Google Scholar
  28. 28.
    American Heart Association. http://www.heart.org/HEARTORG/. Accessed 25 June 2011
  29. 29.
    Porrini M, Gentile MG, Fidanza F (1995) Biochemical validation of a self-administered semi-quantitative food-frequency questionnaire. Br J Nutr 74:323–333CrossRefGoogle Scholar
  30. 30.
    AOAC Method 991.43 (1995) Total, insoluble and soluble dietary fiber in food-enzymatic-gravimetric method, MES-TRIS buffer. Official methods of analysis, 16th edn. AOAC International, GaithersburgGoogle Scholar
  31. 31.
    Campolo J, De Chiara B, Caruso R, De Maria R, Sedda V, Dellanoce C, Parolini M, Cighetti G, Penco S, Baudo F, Parodi O (2006) Methionine challenge paradoxically induces a greater activation of the antioxidant defence in subjects with hyper- vs. normohomocysteinemia. Free Radic Res 40:929–935CrossRefGoogle Scholar
  32. 32.
    Riso P, Brusamolino A, Moro M, Porrini M (2009) Absorption of bioactive compounds from steamed broccoli and their effect on plasma glutathione S-transferase activity. Int J Food Sci Nutr 60:56–71CrossRefGoogle Scholar
  33. 33.
    Bonetti PO (2005) Attenuation of digital reactive hyperemia in patients with early and advanced coronary artery disease. JACC 45(3 Suppl):407AGoogle Scholar
  34. 34.
    Schnabel RB, Schulz A, Wild PS, Sinning CR, Wilde S, Eleftheriadis M, Herkenhoff S, Zeller T, Lubos E, Lackner KJ, Warnholtz A, Gori T, Blankenberg S, Münzel T (2011) Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods. Circ Cardiovasc Imaging 4:371–380CrossRefGoogle Scholar
  35. 35.
    Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A (2010) Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J 31:1142–1148CrossRefGoogle Scholar
  36. 36.
    Hamburg NM, Keyes MJ, Larson MG, Schnabel R, Pryde MM, Mitchell GF, Sheffy J, Vita JA, Benjamin EJ (2008) Cross-sectional relations of digital vascular function to cardiovascular risk factors in The Framingham Heart Study. Circulation 117:2467–2474CrossRefGoogle Scholar
  37. 37.
    Hamburg NM, Benjamin EJ (2009) Assessment of endothelial function using digital pulse amplitude tonometry. Trends Cardiovasc Med 19:6–11CrossRefGoogle Scholar
  38. 38.
    Wilkinson IW, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ (2000) The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 525:263–270CrossRefGoogle Scholar
  39. 39.
    Collins AR, Dušinská M, Gedik CM, Stetina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469Google Scholar
  40. 40.
    Forchhammer L, Johansson C, Loft S, Möller L, Godschalk RW, Langie SA, Jones GD, Kwok RW, Collins AR, Azqueta A, Phillips DH, Sozeri O, Stepnik M, Palus J, Vogel U, Wallin H, Routledge MN, Handforth C, Allione A, Matullo G, Teixeira JP, Costa S, Riso P, Porrini M, Møller P (2010) Variation in the measurement of DNA damage by comet assay measured by the ECVAG inter-laboratory validation trial. Mutagenesis 25:113–123CrossRefGoogle Scholar
  41. 41.
    Johansson C, Møller P, Forchhammer L, Loft S, Godschalk RW, Langie SA, Lumeij S, Jones GD, Kwok RW, Azqueta A, Phillips DH, Sozeri O, Routledge MN, Charlton AJ, Riso P, Porrini M, Allione A, Matullo G, Palus J, Stepnik M, Collins AR, Möller L (2010) An ECVAG trial on assessment of oxidative damage to DNA measured by the comet assay. Mutagenesis 25:125–132CrossRefGoogle Scholar
  42. 42.
    Guarnieri S, Loft S, Riso P, Porrini M, Risom L, Poulsen HE, Dragsted LO, Møller P (2008) DNA repair phenotype and dietary antioxidant supplementation. Br J Nutr 99:1018–1024CrossRefGoogle Scholar
  43. 43.
    Riso P, Pinder A, Santangelo A, Porrini P (1999) Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr 69:712–718Google Scholar
  44. 44.
    Chalopin M, Tesse A, Martínez MC, Rognan D, Arnal JF, Andriantsitohaina R (2010) Estrogen receptor alpha as a key target of red wine polyphenols action on the endothelium. PLoS One 5:e8554CrossRefGoogle Scholar
  45. 45.
    Schroter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103:1024–1029CrossRefGoogle Scholar
  46. 46.
    Fisher ND, Hughes M, Gerhard-Herman M, Hollenberg NK (2003) Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens 21:2281–2286CrossRefGoogle Scholar
  47. 47.
    Fisher ND, Hollenberg NK (2006) Aging and vascular responses to flavanol-rich cocoa. J Hypertens 24:1575–1580CrossRefGoogle Scholar
  48. 48.
    Hollenberg NK, Fisher ND (2007) Is it the dark in dark chocolate? Circulation 116:2360–2362CrossRefGoogle Scholar
  49. 49.
    Dohadwala MM, Holbrook M, Hamburg NM, Shenouda SM, Chung WB, Titas M, Kluge MA, Wang N, Palmisano J, Milbury PE, Blumberg JB, Vita JA (2011) Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. Am J Clin Nutr 93:934–940CrossRefGoogle Scholar
  50. 50.
    Wilms LC, Boots AW, de Boer VC, Maas LM, Pachen DM, Gottschalk RW, Ketelslegers HB, Godschalk RW, Haenen GR, van Schooten FJ, Kleinjans JC (2007) Impact of multiple genetic polymorphisms on effects of a 4-week blueberry juice intervention on ex vivo induced lymphocytic DNA damage in human volunteers. Carcinogenesis 28:1800–1806CrossRefGoogle Scholar
  51. 51.
    Frese R (2006) Markers of oxidative DNA damage in human intervention with fruit and berries. Nutr Cancer 54:143–147CrossRefGoogle Scholar
  52. 52.
    Møller P, Loft S, Alfthan G, Freese R (2004) Oxidative DNA damage in circulating mononuclear blood cells after ingestion of blackcurrant juice or anthocyanin-rich drink. Mutat Res 551:119–126CrossRefGoogle Scholar
  53. 53.
    Shih PH, Yeh CT, Yen GC (2007) Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis. J Agric Food Chem 55:9427–9435CrossRefGoogle Scholar
  54. 54.
    Traustadóttir T, Davies SS, Stock AA, Su Y, Heward CB, Roberts LJ 2nd, Harman SM (2009) Tart cherry juice decreases oxidative stress in healthy older men and women. J Nutr 139:1896–1900CrossRefGoogle Scholar
  55. 55.
    Guarrera S, Sacerdote C, Fiorini L, Marsala R, Polidoro S, Gamberini S, Saletta F, Malaveille C, Talaska G, Vineis P, Matullo G (2007) Expression of DNA repair and metabolic genes in response to a flavonoid-rich diet. Br J Nutr 98:525–533CrossRefGoogle Scholar
  56. 56.
    Basu A, Wilkinson M, Penugonda K, Simmons B, Betts NM, Lyons TJ (2009) Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome: baseline and post intervention effects. Nutr J 8:43CrossRefGoogle Scholar
  57. 57.
    Erlund I, Koli R, Alfthan G, Marniemi J, Puukka P, Mustonen P, Mattila P, Jula A (2008) Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87:323–331Google Scholar
  58. 58.
    Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009) Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks. J Nutr 139:2266–2271CrossRefGoogle Scholar
  59. 59.
    Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C (2008) Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men. Br J Nutr 99:352–359CrossRefGoogle Scholar
  60. 60.
    Ellis CL, Edirisinghe I, Kappagoda T, Burton-Freeman B (2011) Attenuation of meal-induced inflammatory and thrombotic responses in overweight men and women after 6-week daily strawberry (Fragaria) intake. A randomized Placebo-controlled trial. J Atheroscler Thromb 18:318–327CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Patrizia Riso
    • 1
  • Dorothy Klimis-Zacas
    • 2
  • Cristian Del Bo’
    • 1
  • Daniela Martini
    • 1
  • Jonica Campolo
    • 3
  • Stefano Vendrame
    • 2
  • Peter Møller
    • 4
  • Steffen Loft
    • 4
  • Renata De Maria
    • 3
  • Marisa Porrini
    • 1
  1. 1.DeFENS, Department of Food, Environmental and Nutritional SciencesUniversità degli Studi di MilanoMilanItaly
  2. 2.Department of Food Science and Human NutritionUniversity of MaineOronoUSA
  3. 3.Dipartimento Cardiovascolare, Istituto di Fisiologia Clinica CNROspedale Niguarda Ca’ GrandaMilanItaly
  4. 4.Department of Public Health, Section of Environmental HealthUniversity of CopenhagenCopenhagenDenmark

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