Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial

Nutrients

Volumn 7, Issue 6, 2015, Pages 4107-4123

  Stull, April J ^a   Cash, Katherine C ^a   Champagne, Catherine M ^a   Gupta, Alok K ^b   Boston, Raymond ^c   Beyl, Robbie A ^a   Johnson, William D ^a   Cefalu, William T ^a  

^a PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^b Southeast Louisiana Veterans Health Care System   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Blueberries; Cardiovascular risk factors; Endothelial dysfunction; Endothelial function; Hypertension; Prediabetes

Indexed keywords

CHOLESTEROL; GLUCOSE; HIGH DENSITY LIPOPROTEIN; INSULIN; PLACEBO; GLUCOSE BLOOD LEVEL; TRIACYLGLYCEROL;

ADULT; ARTICLE; BLOOD PRESSURE; BLUEBERRY; BODY FAT; BODY WEIGHT; CELL FUNCTION; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; ECHOGRAPHY; ENDOTHELIUM CELL; FEMALE; GENDER; IMMUNOASSAY; INSULIN SENSITIVITY; MALE; MEDICAL PARAMETERS; METABOLIC SYNDROME X; NUTRITIONAL VALUE; RANDOMIZED CONTROLLED TRIAL; REACTIVE HYPEREMIA INDEX; BLOOD; BLOOD PRESSURE MONITORING; BODY COMPOSITION; BODY MASS; CHEMISTRY; FRUIT; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN RESISTANCE; METABOLISM; MIDDLE AGED; OBESITY; PHYSIOLOGY; TREATMENT OUTCOME; VACCINIUM; VASCULAR ENDOTHELIUM;

VACCINIUM;

ADIPOSITY; BLOOD GLUCOSE; BLOOD PRESSURE; BLOOD PRESSURE MONITORING, AMBULATORY; BLUEBERRY PLANTS; BODY COMPOSITION; BODY MASS INDEX; BODY WEIGHT; CHOLESTEROL; DOUBLE-BLIND METHOD; ENDOTHELIUM, VASCULAR; FEMALE; FRUIT; HUMANS; INSULIN; INSULIN RESISTANCE; MALE; METABOLIC SYNDROME X; MIDDLE AGED; TREATMENT OUTCOME; TRIGLYCERIDES;

EID: 84930960604     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu7064107     Document Type: Article

References (63)

1. Go, A.S.; Mozaffarian, D.; Roger, V.L.; Benjamin, E.J.; Berry, J.D.; Blaha, M.J.; Dai, S.; Ford, E.S.; Fox, C.S.; Franco, S.; et al. Heart disease and stroke statistics—2014 update: A report from the american heart association. Circulation 2014, 129, e28–e292.
2. Alberti, K.G.; Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a who consultation. Diabet. Med. 1998, 15, 539–553.
3. Yeboah, J.; Crouse, J.R.; Hsu, F.C.; Burke, G.L.; Herrington, D.M. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The cardiovascular health study. Circulation 2007, 115, 2390–2397.
4. Vita, J.A.; Treasure, C.B.; Nabel, E.G.; McLenachan, J.M.; Fish, R.D.; Yeung, A.C.; Vekshtein, V.I.; Selwyn, A.P.; Ganz, P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990, 81, 491–497.
5. Celermajer, D.S.; Sorensen, K.E.; Bull, C.; Robinson, J.; Deanfield, J.E. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J. Am. Coll. Cardiol. 1994, 24, 1468–1474.
6. Rimm, E.B.; Ascherio, A.; Giovannucci, E.; Spiegelman, D.; Stampfer, M.J.; Willett, W.C. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996, 275, 447–451.
7. Joshipura, K.J.; Ascherio, A.; Manson, J.E.; Stampfer, M.J.; Rimm, E.B.; Speizer, F.E.; Hennekens, C.H.; Spiegelman, D.; Willett, W.C. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999, 282, 1233–1239.
8. Cassidy, A.; Mukamal, K.J.; Liu, L.; Franz, M.; Eliassen, A.H.; Rimm, E.B. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 2013, 127, 188–196.
9. Stull, A.J.; Cash, K.C.; Johnson, W.D.; Champagne, C.M.; Cefalu, W.T. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J. Nutr. 2010, 140, 1764–1768.
10. DeFuria, J.; Bennett, G.; Strissel, K.J.; Perfield, J.W., 2nd; Milbury, P.E.; Greenberg, A.S.; Obin, M.S. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J. Nutr. 2009, 139, 1510–1516.
11. Vendrame, S.; Kristo, A.S.; Schuschke, D.A.; Klimis-Zacas, D. Wild blueberry consumption affects aortic vascular function in the obese Zucker rat. Appl. Physiol. Nutr. Metab. 2014, 39, 255–261.
12. Norton, C.; Kalea, A.Z.; Harris, P.D.; Klimis-Zacas, D.J. Wild blueberry-rich diets affect the contractile machinery of the vascular smooth muscle in the Sprague-Dawley rat. J. Med. Food 2005, 8, 8–13.
13. Kristo, A.S.; Kalea, A.Z.; Schuschke, D.A.; Klimis-Zacas, D.J. A wild blueberry-enriched diet (Vaccinium angustifolium) improves vascular tone in the adult spontaneously hypertensive rat. J. Agric. Food Chem. 2010, 58, 11600–11605.
14. Kalea, A.Z.; Clark, K.; Schuschke, D.A.; Kristo, A.S.; Klimis-Zacas, D.J. Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the vascular reactivity in the aorta of young spontaneously hypertensive rats. J. Nutr. Biochem. 2010, 21, 14–22.
15. Kalea, A.Z.; Clark, K.; Schuschke, D.A.; Klimis-Zacas, D.J. Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat. J. Med. Food 2009, 12, 21–28.
16. Shaughnessy, K.S.; Boswall, I.A.; Scanlan, A.P.; Gottschall-Pass, K.T.; Sweeney, M.I. Diets containing blueberry extract lower blood pressure in spontaneously hypertensive stroke-prone rats. Nutr. Res. 2009, 29, 130–138.
17. Elks, C.M.; Reed, S.D.; Mariappan, N.; Shukitt-Hale, B.; Joseph, J.A.; Ingram, D.K.; Francis, J. A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress. PLoS ONE 2011, 6, e24028.
18. Vita, J.A.; Treasure, C.B.; Nabel, E.G.; McLenachan, J.M.; Fish, R.D.; Yeung, A.C.; Vekshtein, V.I.; Selwyn, A.P.; Ganz, P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990, 81, 491–497.
19. Celermajer, D.S.; Sorensen, K.E.; Bull, C.; Robinson, J.; Deanfield, J.E. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J. Am. Coll. Cardiol. 1994, 24, 1468–1474.
20. Rimm, E.B.; Ascherio, A.; Giovannucci, E.; Spiegelman, D.; Stampfer, M.J.; Willett, W.C. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996, 275, 447–451.
21. Joshipura, K.J.; Ascherio, A.; Manson, J.E.; Stampfer, M.J.; Rimm, E.B.; Speizer, F.E.; Hennekens, C.H.; Spiegelman, D.; Willett, W.C. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999, 282, 1233–1239.
22. Cassidy, A.; Mukamal, K.J.; Liu, L.; Franz, M.; Eliassen, A.H.; Rimm, E.B. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 2013, 127, 188–196.
23. Stull, A.J.; Cash, K.C.; Johnson, W.D.; Champagne, C.M.; Cefalu, W.T. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J. Nutr. 2010, 140, 1764–1768.
24. DeFuria, J.; Bennett, G.; Strissel, K.J.; Perfield, J.W., 2nd; Milbury, P.E.; Greenberg, A.S.; Obin, M.S. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J. Nutr. 2009, 139, 1510–1516.
25. Vendrame, S.; Kristo, A.S.; Schuschke, D.A.; Klimis-Zacas, D. Wild blueberry consumption affects aortic vascular function in the obese Zucker rat. Appl. Physiol. Nutr. Metab. 2014, 39, 255–261.
26. Norton, C.; Kalea, A.Z.; Harris, P.D.; Klimis-Zacas, D.J. Wild blueberry-rich diets affect the contractile machinery of the vascular smooth muscle in the Sprague-Dawley rat. J. Med. Food 2005, 8, 8–13.
27. Kristo, A.S.; Kalea, A.Z.; Schuschke, D.A.; Klimis-Zacas, D.J. A wild blueberry-enriched diet (Vaccinium angustifolium) improves vascular tone in the adult spontaneously hypertensive rat. J. Agric. Food Chem. 2010, 58, 11600–11605.
28. Kalea, A.Z.; Clark, K.; Schuschke, D.A.; Kristo, A.S.; Klimis-Zacas, D.J. Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the vascular reactivity in the aorta of young spontaneously hypertensive rats. J. Nutr. Biochem. 2010, 21, 14–22.
29. Kalea, A.Z.; Clark, K.; Schuschke, D.A.; Klimis-Zacas, D.J. Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat. J. Med. Food 2009, 12, 21–28.
30. Shaughnessy, K.S.; Boswall, I.A.; Scanlan, A.P.; Gottschall-Pass, K.T.; Sweeney, M.I. Diets containing blueberry extract lower blood pressure in spontaneously hypertensive stroke-prone rats. Nutr. Res. 2009, 29, 130–138.
31. Elks, C.M.; Reed, S.D.; Mariappan, N.; Shukitt-Hale, B.; Joseph, J.A.; Ingram, D.K.; Francis, J. A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress. PLoS ONE 2011, 6, e24028.
32. Mykkanen, O.T.; Huotari, A.; Herzig, K.H.; Dunlop, T.W.; Mykkanen, H.; Kirjavainen, P.V. Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet. PLoS ONE 2014, 9, e114790.
33. Zhu, Y.; Xia, M.; Yang, Y.; Liu, F.; Li, Z.; Hao, Y.; Mi, M.; Jin, T.; Ling, W. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin. Chem. 2011, 57, 1524–1533.
34. Rodriguez-Mateos, A.; Rendeiro, C.; Bergillos-Meca, T.; Tabatabaee, S.; George, T.W.; Heiss, C.; Spencer, J.P. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: A randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. Am. J. Clin. Nutr. 2013, 98, 1179–1191.
35. Riso, P.; Klimis-Zacas, D.; Del Bo, C.; Martini, D.; Campolo, J.; Vendrame, S.; Moller, P.; Loft, S.; De Maria, R.; Porrini, M. Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors. Eur. J. Nutr. 2013, 52, 949–961.
36. McAnulty, S.R.; McAnulty, L.S.; Morrow, J.D.; Khardouni, D.; Shooter, L.; Monk, J.; Gross, S.; Brown, V. Effect of daily fruit ingestion on angiotensin converting enzyme activity, blood pressure, and oxidative stress in chronic smokers. Free Radic. Res. 2005, 39, 1241–1248.
37. Johnson, S.A.; Figueroa, A.; Navaei, N.; Wong, A.; Kalfon, R.; Ormsbee, L.T.; Feresin, R.G.; Elam, M.L.; Hooshmand, S.; Payton, M.E.; et.al. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: A randomized, double-blind, placebo-controlled clinical trial. J. Acad. Nutr. Diet 2015, 115, 369–377.
38. Del Bo, C.; Riso, P.; Campolo, J.; Moller, P.; Loft, S.; Klimis-Zacas, D.; Brambilla, A.; Rizzolo, A.; Porrini, M. A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers. Nutr. Res. 2013, 33, 220–227.
39. Basu, A.; Du, M.; Leyva, M.J.; Sanchez, K.; Betts, N.M.; Wu, M.; Aston, C.E.; Lyons, T.J. Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome. J. Nutr. 2010, 140, 1582–1587.
40. Gupta, A.K.; Greenway, F.L.; Cornelissen, G.; Pan, W.; Halberg, F. Prediabetes is associated with abnormal circadian blood pressure variability. J. Hum. Hypertens 2008, 22, 627–633.
41. Slinkard, K.; Singleton, V.L. Total phenol analysis—Automation and comparison with manual methods. Am. J. Enol. Viticult. 1977, 28, 49–55.
42. Cheng, G.W.; Breen, P.J. Activity of phenylalanine ammonia-lyase (PAL) and concentrations of anthocyanins and phenolics in developing strawberry fruit. J. Am. Soc. Hortic. Sci. 1991, 116, 865–869.
43. Ou, B.X.; Hampsch-Woodill, M.; Prior, R.L. Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J. Agric. Food Chem. 2001, 49, 4619–4626.
44. Rubinshtein, R.; Kuvin, J.T.; Soffler, M.; Lennon, R.J.; Lavi, S.; Nelson, R.E.; Pumper, G.M.; Lerman, L.O.; Lerman, A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur. Heart J. 2010, 31, 1142–1148.
45. Cefalu, W.T.; Werbel, S.; Bell-Farrow, A.D.; Terry, J.G.; Wang, Z.Q.; Opara, E.C.; Morgan, T.; Hinson, W.H.; Crouse, J.R.. Insulin resistance and fat patterning with aging: Relationship to metabolic risk factors for cardiovascular disease. Metab. Clin. Exp. 1998, 47, 401–408.
46. Boston, R.C.; Stefanovski, D.; Moate, P.J.; Sumner, A.E.; Watanabe, R.M.; Bergman, R.N. Minmod millennium: A computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol. Ther. 2003, 5, 1003–1015.
47. Streppel, M.T.; Arends, L.R.; van’t Veer, P.; Grobbee, D.E.; Geleijnse, J.M. Dietary fiber and blood pressure—A meta-analysis of randomized placebo-controlled trials. Arch. Intern. Med. 2005, 165, 150–156.
48. Reverri, E.J.; LaSalle, C.D.; Franke, A.A.; Steinberg, F.M. Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol. Nutr. Food Res. 2015, 59, 323–333.
49. Nagaya, N.; Yamamoto, H.; Uematsu, M.; Itoh, T.; Nakagawa, K.; Miyazawa, T.; Kangawa, K.; Miyatake, K. Green tea reverses endothelial dysfunction in healthy smokers. Heart 2004, 90, 1485–1486.
50. Hermann, F.; Spieker, L.E.; Ruschitzka, F.; Sudano, I.; Hermann, M.; Binggeli, C.; Luscher, T.F.; Riesen, W.; Noll, G.; Corti, R. Dark chocolate improves endothelial and platelet function. Heart 2006, 92, 119–120.
51. Heiss, C.; Kleinbongard, P.; Dejam, A.; Perre, S.; Schroeter, H.; Sies, H.; Kelm, M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J. Am. Coll. Cardiol. 2005, 46, 1276–1283.
52. Fisher, N.D.; Hughes, M.; Gerhard-Herman, M.; Hollenberg, N.K. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J. Hypertens. 2003, 21, 2281–2286.
53. Duffy, S.J.; Keaney, J.F., Jr.; Holbrook, M.; Gokce, N.; Swerdloff, P.L.; Frei, B.; Vita, J.A. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 2001, 104, 151–156.
54. Hausberg, M.; Lang, D.; Barenbrock, M.; Kosch, M. Large artery wall properties—What is relevant for the management of hypertension? Deut. Med. Wochenschr. 2005, 130, 2657–2661.
55. Rice, B.H. Dairy and cardiovascular disease: A review of recent observational research. Curr. Nutr. Rep. 2014, 3, 130–138.
56. Astrup, A. Yogurt and dairy product consumption to prevent cardiometabolic diseases: Epidemiologic and experimental studies. Am. J. Clin. Nutr. 2014, 99, 1235S–1242S.
57. Serafini, M.; Ghiselli, A.; FerroLuzzi, A. In vivo antioxidant effect of green and black tea in man. Eur. J. Clin. Nutr. 1996, 50, 28–32.
58. Reddy, V.C.; Sagar, G.V.V.; Sreeramulu, D.; Venu, L.; Raghunath, M. Addition of milk does not alter the antioxidant activity of black tea. Ann. Nutr. Metab. 2005, 49, 189–195.
59. Leenen, R.; Roodenburg, A.J.C.; Tijburg, L.B.M.; Wiseman, S.A. A single dose of tea with or without milk increases plasma antioxidant activity in humans. Eur. J. Clin. Nutr. 2000, 54, 87–92.
60. van het Hof, K.H.; Kivits, G.A.A.; Weststrate, J.A.; Tijburg, L.B.M. Bioavailability of catechins from tea: The effect of milk. Eur. J. Clin. Nutr. 1998, 52, 356–359.
61. Cebeci, F.; Sahin-Yesilcubuk, N. The matrix effect of blueberry, oat meal and milk on polyphenols, antioxidant activity and potential bioavailability. Int. J. Food Sci. Nutr. 2014, 65, 69–78.
62. Lerman, A.; Burnett, J.C., Jr. Intact and altered endothelium in regulation of vasomotion. Circulation 1992, 86, 12–19.
63. Forstermann, U.; Munzel, T. Endothelial nitric oxide synthase in vascular disease: From marvel to menace. Circulation 2006, 113, 1708–1714.