Skip to main content
×
Home
    • Aa
    • Aa

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)...
Abstract

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.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Dr K. D. Ballard, fax +1 860 486 3674, E-mail: kevin.ballard@uconn.edu
References
Hide All
1Lloyd-Jones D, Adams RJ, Brown TM, et al. (2010) Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation 121, e46e215.
2Lakatta EG & Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a “set up” for vascular disease. Circulation 107, 139146.
3Furchgott RF & Vanhoutte PM (1989) Endothelium-derived relaxing and contracting factors. FASEB J 3, 20072018.
4Glasser SP, Selwyn AP & Ganz P (1996) Atherosclerosis: risk factors and the vascular endothelium. Am Heart J 131, 379384.
5Celermajer DS, Sorensen KE, Gooch VM, et al. (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340, 11111115.
6Green D (2005) Point: flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol 99, 12331234, (discussion 1237–1238).
7Parker BA, Tschakovsky ME, Augeri AL, et al. (2011) Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women. Am J Physiol Heart Circ Physiol 301, H1118H1126.
8Anderson TJ, Uehata A, Gerhard MD, et al. (1995) Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26, 12351241.
9Celermajer DS, Sorensen KE, Bull C, 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.
10Widlansky ME, Gokce N, Keaney JF, et al. (2003) The clinical implications of endothelial dysfunction. J Am Coll Cardiol 42, 11491160.
11Celermajer DS, Sorensen KE, Spiegelhalter DJ, 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.
12Donato AJ, Gano LB, Eskurza I, et al. (2009) Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 297, H425H432.
13Taddei S, Virdis A, Ghiadoni L, et al. (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38, 274279.
14Erdmann K, Cheung BW & Schroder H (2008) The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem 19, 643654.
15FitzGerald RJ, Murray BA & Walsh DJ (2004) Hypotensive peptides from milk proteins. J Nutr 134, 980S988S.
16Hirota T, Ohki K, Kawagishi R, 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.
17FitzGerald RJ & Meisel H (1999) Lactokinins: whey protein-derived ACE inhibitory peptides. Nahrung 43, 165167.
18Kawase M, Hashimoto H, Hosoda M, 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.
19Pal S & Ellis V (2010) The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals. Obesity (Silver Spring) 18, 13541359.
20Ballard KD, Bruno RS, Seip RL, 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.
21Harris RA, Nishiyama SK, Wray DW, et al. (2010) Ultrasound assessment of flow-mediated dilation. Hypertension 55, 10751085.
22Shimbo D, Grahame-Clarke C, Miyake Y, et al. (2007) The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis 192, 197203.
23Corretti MC, Anderson TJ, Benjamin EJ, 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.
24Parker BA, Trehearn TL & Meendering JR (2009) Pick your Poiseuille: normalizing the shear stimulus in studies of flow-mediated dilation. J Appl Physiol 107, 13571359.
25Pyke KE & Tschakovsky ME (2007) Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol 102, 15101519.
26Giustarini D, Rossi R, Milzani A, et al. (2008) Nitrite and nitrate measurement by Griess reagent in human plasma: evaluation of interferences and standardization. Methods Enzymol 440, 361380.
27Piraud M, Vianey-Saban C, Bourdin C, et al. (2005) A new reversed-phase liquid chromatographic/tandem mass spectrometric method for analysis of underivatised amino acids: evaluation for the diagnosis and the management of inherited disorders of amino acid metabolism. Rapid Commun Mass Spectrom 19, 32873297.
28Piraud M, Vianey-Saban C, Petritis K, 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.
29Piraud M, Vianey-Saban C, Petritis K, 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.
30Bland JM & Altman DG (1995) Calculating correlation coefficients with repeated observations: Part 1 – Correlation within subjects. BMJ 310, 446.
31De Roos NM, Bots ML, Schouten EG, 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.
32Donald AE, Halcox JP, Charakida M, et al. (2008) Methodological approaches to optimize reproducibility and power in clinical studies of flow-mediated dilation. J Am Coll Cardiol 51, 19591964.
33Pyke KE & Jazuli F (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.
34Csiszar A, Wang M, Lakatta EG, et al. (2008) Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol 105, 13331341.
35Rodriguez-Manas L, El-Assar M, Vallejo S, et al. (2009) Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell 8, 226238.
36Harris RA, Padilla J, Rink LD, et al. (2006) Variability of flow-mediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11, 16.
37Devan AE, Umpierre D, Harrison ML, et al. (2011) Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise. Am J Physiol Heart Circ Physiol 300, H813H819.
38Nerla R, Di Monaco A, Sestito A, et al. (2011) Transient endothelial dysfunction following flow-mediated dilation assessment. Heart Vessels 26, 524529.
39Thijssen DH, Black MA, Pyke KE, et al. (2011) Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 300, H212.
40Thijssen DH, Bullens LM, van Bemmel MM, 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.
41Giugliano D, Marfella R, Verrazzo G, et al. (1997) The vascular effects of l-arginine in humans. The role of endogenous insulin. J Clin Invest 99, 433438.
42Kurz S & Harrison DG (1997) Insulin and the arginine paradox. J Clin Invest 99, 369370.
43Gates PE, Boucher ML, Silver AE, 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.
44Ishibashi T, Yoshida J & Nishio M (1999) Evaluation of NOx in the cardiovascular system: relationship to NO-related compounds in vivo. Jpn J Pharmacol 81, 317323.
45Deanfield JE, Halcox JP & Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115, 12851295.
46Wu J, Aluko RE & Nakai S (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.
47Foltz M, Meynen EE, Bianco V, et al. (2007) Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J Nutr 137, 953958.
48Tousoulis D, Antoniades C, Koumallos N, et al. (2006) Novel therapies targeting vascular endothelium. Endothelium 13, 411421.
49Faggiotto A & Paoletti R (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.
50Nowak J & Wennmalm A (1979) Human forearm and kidney conversion of arachidonic acid to prostaglandins. Acta Physiol Scand 106, 307312.
51Frolich JC (1984) Measurement of icosanoids. Report of the Group for Standardization of Methods in Icosanoid Research. Prostaglandins 27, 349368.
52Catella F, Nowak J & Fitzgerald GA (1986) Measurement of renal and non-renal eicosanoid synthesis. Am J Med 81, 2329.
53Potenza MA, Marasciulo FL, Chieppa DM, 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.
54Metsarinne K, Saijonmaa O, Yki-Jarvinen H, et al. (1994) Insulin increases the release of endothelin in endothelial cell cultures in vitro but not in vivo. Metabolism 43, 878882.
55Serneri GG, Modesti PA, Cecioni I, et al. (1995) Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis. Am J Physiol 268, H1829H1837.
56Agewall S, Doughty RN, Bagg W, 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.
57Bots ML, Westerink J, Rabelink TJ, 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.
58Sipola M, Finckenberg P, Vapaatalo H, et al. (2002) Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats. Life Sci 71, 12451253.
59Wang J, Brown MA, Tam SH, et al. (1997) Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol 24, 418420.
60Power O, Hallihan A & Jakeman P (2009) Human insulinotropic response to oral ingestion of native and hydrolysed whey protein. Amino Acids 37, 333339.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 4
Total number of PDF views: 91 *
Loading metrics...

Abstract views

Total abstract views: 238 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th October 2017. This data will be updated every 24 hours.