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Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women

  • Kevin D. Ballard (a1) (a2), Brian R. Kupchak (a1), Brittanie M. Volk (a1), Eunice Mah (a2), Aida Shkreta (a3), Cary Liptak (a3), Adam S. Ptolemy (a3), Mark S. Kellogg (a3), Richard S. Bruno (a2), Richard L. Seip (a4), Carl M. Maresh (a1), William J. Kraemer (a1) and Jeff S. Volek (a1)
  • DOI:
  • Published online: 13 June 2012

Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.

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2EG Lakatta & D Levy (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease. Circulation 107, 139146.

4SP Glasser , AP Selwyn & P Ganz (1996) Atherosclerosis: risk factors and the vascular endothelium. Am Heart J 131, 379384.

5DS Celermajer , KE Sorensen , VM Gooch , et al. (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340, 11111115.

6D Green (2005) Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol 99, 12331234, (discussion 1237–1238).

7BA Parker , ME Tschakovsky , AL Augeri , et al. (2011) Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women. Am J Physiol Heart Circ Physiol 301, H1118H1126.

8TJ Anderson , A Uehata , MD Gerhard , et al. (1995) Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26, 12351241.

9DS Celermajer , KE Sorensen , C Bull , et al. (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 24, 14681474.

10ME Widlansky , N Gokce , JF Keaney , et al. (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42, 11491160.

11DS Celermajer , KE Sorensen , DJ Spiegelhalter , et al. (1994) Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 24, 471476.

12AJ Donato , LB Gano , I Eskurza , et al. (2009) Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 297, H425H432.

13S Taddei , A Virdis , L Ghiadoni , et al. (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38, 274279.

14K Erdmann , BW Cheung & H Schroder (2008) The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem 19, 643654.

16T Hirota , K Ohki , R Kawagishi , et al. (2007) Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: contribution of the inhibitory action of angiotensin-converting enzyme. Hypertens Res 30, 489496.

17RJ FitzGerald & H Meisel (1999) Lactokinins: whey protein-derived ACE inhibitory peptides. Nahrung 43, 165167.

18M Kawase , H Hashimoto , M Hosoda , et al. (2000) Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure. J Dairy Sci 83, 255263.

19S Pal & V Ellis (2010) The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals. Obesity (Silver Spring) 18, 13541359.

20KD Ballard , RS Bruno , RL Seip , et al. (2009) Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial. Nutr J 8, 34.

21RA Harris , SK Nishiyama , DW Wray , et al. (2010) Ultrasound assessment of flow-mediated dilation. Hypertension 55, 10751085.

22D Shimbo , C Grahame-Clarke , Y Miyake , et al. (2007) The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis 192, 197203.

23MC Corretti , TJ Anderson , EJ Benjamin , et al. (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39, 257265.

24BA Parker , TL Trehearn & JR Meendering (2009) Pick your Poiseuille: normalizing the shear stimulus in studies of flow-mediated dilation. J Appl Physiol 107, 13571359.

25KE Pyke & ME Tschakovsky (2007) Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102, 15101519.

26D Giustarini , R Rossi , A Milzani , et al. (2008) Nitrite and nitrate measurement by Griess reagent in human plasma: evaluation of interferences and standardization. Methods Enzymol 440, 361380.

28M Piraud , C Vianey-Saban , K Petritis , et al. (2005) Ion-pairing reversed-phase liquid chromatography/electrospray ionization mass spectrometric analysis of 76 underivatized amino acids of biological interest: a new tool for the diagnosis of inherited disorders of amino acid metabolism. Rapid Commun Mass Spectrom 19, 15871602.

29M Piraud , C Vianey-Saban , K Petritis , et al. (2003) ESI-MS/MS analysis of underivatised amino acids: a new tool for the diagnosis of inherited disorders of amino acid metabolism. Fragmentation study of 79 molecules of biological interest in positive and negative ionisation mode. Rapid Commun Mass Spectrom 17, 12971311.

30JM Bland & DG Altman (1995) Calculating correlation coefficients with repeated observations: Part 1 – Correlation within subjects. BMJ 310, 446.

31NM De Roos , ML Bots , EG Schouten , et al. (2003) Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies. Ultrasound Med Biol 29, 401406.

32AE Donald , JP Halcox , M Charakida , et al. (2008) Methodological approaches to optimize reproducibility and power in clinical studies of flow-mediated dilation. J Am Coll Cardiol 51, 19591964.

33KE Pyke & F Jazuli (2011) Impact of repeated increases in shear stress via reactive hyperaemia and handgrip exercise: no evidence of systematic changes in brachial artery FMD. Am J Physiol Heart Circ Physiol 300, H1078H1089.

34A Csiszar , M Wang , EG Lakatta , et al. (2008) Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol 105, 13331341.

35L Rodriguez-Manas , M El-Assar , S Vallejo , et al. (2009) Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell 8, 226238.

36RA Harris , J Padilla , LD Rink , et al. (2006) Variability of flow-mediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11, 16.

37AE Devan , D Umpierre , ML Harrison , et al. (2011) Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise. Am J Physiol Heart Circ Physiol 300, H813H819.

38R Nerla , A Di Monaco , A Sestito , et al. (2011) Transient endothelial dysfunction following flow-mediated dilation assessment. Heart Vessels 26, 524529.

39DH Thijssen , MA Black , KE Pyke , et al. (2011) Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 300, H212.

40DH Thijssen , LM Bullens , MM van Bemmel , et al. (2009) Does arterial shear explain the magnitude of flow-mediated dilation? A comparison between young and older humans. Am J Physiol Heart Circ Physiol 296, H57H64.

41D Giugliano , R Marfella , G Verrazzo , et al. (1997) The vascular effects of l-arginine in humans. The role of endogenous insulin. J Clin Invest 99, 433438.

42S Kurz & DG Harrison (1997) Insulin and the arginine paradox. J Clin Invest 99, 369370.

43PE Gates , ML Boucher , AE Silver , et al. (2007) Impaired flow-mediated dilation with age is not explained by l-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression. J Appl Physiol 102, 6371.

44T Ishibashi , J Yoshida & M Nishio (1999) Evaluation of NOx in the cardiovascular system: relationship to NO-related compounds in vivo. Jpn J Pharmacol 81, 317323.

46J Wu , RE Aluko & S Nakai (2006) Structural requirements of Angiotensin I-converting enzyme inhibitory peptides: quantitative structure–activity relationship study of di- and tripeptides. J Agric Food Chem 54, 732738.

48D Tousoulis , C Antoniades , N Koumallos , et al. (2006) Novel therapies targeting vascular endothelium. Endothelium 13, 411421.

49A Faggiotto & R Paoletti (1999) State-of-the-Art lecture. Statins and blockers of the renin-angiotensin system: vascular protection beyond their primary mode of action. Hypertension 34, 987996.

50J Nowak & A Wennmalm (1979) Human forearm and kidney conversion of arachidonic acid to prostaglandins. Acta Physiol Scand 106, 307312.

52F Catella , J Nowak & GA Fitzgerald (1986) Measurement of renal and non-renal eicosanoid synthesis. Am J Med 81, 2329.

53MA Potenza , FL Marasciulo , DM Chieppa , et al. (2005) Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 289, H813H822.

54K Metsarinne , O Saijonmaa , H Yki-Jarvinen , et al. (1994) Insulin increases the release of endothelin in endothelial cell cultures in vitro but not in vivo. Metabolism 43, 878882.

56S Agewall , RN Doughty , W Bagg , et al. (2001) Comparison of ultrasound assessment of flow-mediated dilatation in the radial and brachial artery with upper and forearm cuff positions. Clin Physiol 21, 914.

57ML Bots , J Westerink , TJ Rabelink , et al. (2005) Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J 26, 363368.

58M Sipola , P Finckenberg , H Vapaatalo , et al. (2002) Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats. Life Sci 71, 12451253.

59J Wang , MA Brown , SH Tam , et al. (1997) Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol 24, 418420.

60O Power , A Hallihan & P Jakeman (2009) Human insulinotropic response to oral ingestion of native and hydrolysed whey protein. Amino Acids 37, 333339.

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