Skip to main content

Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk

  • Jordi Merino (a1), Richard Kones (a2), Raimon Ferré (a1), Núria Plana (a1), Josefa Girona (a1), Gemma Aragonés (a1), Daiana Ibarretxe (a1), Mercedes Heras (a1) and Luis Masana (a1)...

Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1·66 (sd 0·41) v. 1·52 (sd 0·22), P= 0·037). These results were particularly strong in patients with the MS (Q1 = 1·82 (sd 0·32) v. Q4 = 1·61 (sd 027); P= 0·021) and T2D (Q1 = 1·78 (sd 0·31) v. Q4 = 1·62 (sd 0·35); P= 0·011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR − 0·85; 95 % CI 0·19, 0·92; P= 0·031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure 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 or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ 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.

      Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk
      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.

      Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk
      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.

      Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk
      Available formats
Corresponding author
*Corresponding author: J. Merino, fax +34 977319984, E-mail:
Hide All
1Krauss RM, Eckel RH, Howard B, et al. (2000) AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Stroke 31, 27512766.
2Cummings S, Parham ES & Strain GW (2002) Position of the American Dietetic Association: weight management. J Am Diet Assoc 102, 11451155.
3Flock MR & Kris-Etherton PM (2011) Dietary Guidelines for Americans 2010: implications for cardiovascular disease. Curr Atheroscler Rep 13, 499507.
4Halton TL, Willett WC, Liu S, et al. (2006) Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 355, 19912002.
5de Koning L, Fung TT, Liao X, et al. (2011) Low-carbohydrate diet scores and risk of type 2 diabetes in men. Am J Clin Nutr 93, 844850.
6Kuvin JT, Patel AR, Sliney KA, et al. (2003) Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 146, 168174.
7Nohria A, Gerhard-Herman M, Creager MA, et al. (2006) Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol 101, 545548.
8Celermajer DS (2008) Reliable endothelial function testing at our fingertips? Circulation 117, 24282430.
9Dhindsa M, Sommerlad SM, DeVan AE, et al. (2008) Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity. J Appl Physiol 105, 427432.
10Ferre R, Plana N, Merino J, et al. (2012) Effects of therapeutic lifestyle changes on peripheral artery tonometry in patients with abdominal obesity. Nutr Metab Cardiovasc Dis 22, 95102.
11Grundy SM, Cleeman JI, Daniels SR, et al. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol 4, 198203.
12Elosua R, Garcia M, Aguilar A, et al. (2000) Validation of the Minnesota leisure time physical activity questionnaire in Spanish women. Investigators of the MARATDON Group. Med Sci Sports Exerc 32, 14311437.
13DiClemente CC, Prochaska JO, Fairhurst SK, et al. (1991) The process of smoking cessation: an analysis of precontemplation, contemplation, and preparation stages of change. J Consult Clin Psychol 59, 295304.
14Bonetti PO, Pumper GM, Higano ST, et al. (2004) Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 44, 21372141.
15Hamburg NM, Keyes MJ, Larson MG, et al. (2008) Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study. Circulation 117, 24672474.
16Dod HS, Bhardwaj R, Sajja V, et al. (2010) Effect of intensive lifestyle changes on endothelial function and on inflammatory markers of atherosclerosis. Am J Cardiol 105, 362367.
17Miller M, Beach V, Sorkin JD, et al. (2009) Comparative effects of three popular diets on lipids, endothelial function, and C-reactive protein during weight maintenance. J Am Diet Assoc 109, 713717.
18Wycherley TP, Brinkworth GD, Keogh JB, et al. (2010) Long-term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients. J Intern Med 267, 452461.
19Phillips SA, Jurva JW, Syed AQ, et al. (2008) Benefit of low-fat over low-carbohydrate diet on endothelial health in obesity. Hypertension 51, 376382.
20Foster GD, Wyatt HR, Hill JO, et al. (2003) A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 348, 20822090.
21Gardner CD, Kiazand A, Alhassan S, et al. (2007) Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A to Z Weight Loss Study: a randomized trial. JAMA 297, 969977.
22Johnstone AM, Lobley GE, Horgan GW, et al. (2011) Effects of a high-protein, low-carbohydrate v. high-protein, moderate-carbohydrate weight-loss diet on antioxidant status, endothelial markers and plasma indices of the cardiometabolic profile. Br J Nutr 106, 282291.
23Clifton PM, Keogh JB, Foster PR, et al. (2005) Effect of weight loss on inflammatory and endothelial markers and FMD using two low-fat diets. Int J Obes (Lond) 29, 14451451.
24Keogh JB, Brinkworth GD, Noakes M, et al. (2008) Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr 87, 567576.
25Ferrara LA, Innelli P, Palmieri V, et al. (2006) Effects of different dietary protein intakes on body composition and vascular reactivity. Eur J Clin Nutr 60, 643649.
26Pierce GL, Beske SD, Lawson BR, et al. (2008) Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight/obese adults. Hypertension 52, 7279.
27Brook RD (2006) Obesity, weight loss, and vascular function. Endocrine 29, 2125.
28Foo SY, Heller ER, Wykrzykowska J, et al. (2009) Vascular effects of a low-carbohydrate high-protein diet. Proc Natl Acad Sci U S A 106, 1541815423.
29Phillips SA (2007) Effects of low-carbohydrate diet on vascular health: more than just weight loss. Am J Physiol Heart Circ Physiol 292, H2037H2039.
30Volek JS, Ballard KD, Silvestre R, et al. (2009) Effects of dietary carbohydrate restriction versus low-fat diet on flow-mediated dilation. Metabolism 58, 17691777.
31Hamburg NM, Palmisano J, Larson MG, et al. (2011) Relation of brachial and digital measures of vascular function in the community: The Framingham Heart Study. Hypertension 57, 390396.
32Bacon SL, Lavoie KL, Arsenault A, et al. (2011) The research on endothelial function in women and men at risk for cardiovascular disease (REWARD) study: methodology. BMC Cardiovasc Disord 11, 50.
33Lekakis J, Abraham P, Balbarini A, et al. (2011) Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil 18, 775789.
34Schnabel RB, Schulz A, Wild PS, et al. (2011) Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods. Circ Cardiovasc Imaging 4, 371380.
35Chouraqui P, Schnall RP, Dvir I, et al. (2002) Assessment of peripheral artery tonometry in the detection of treadmill exercise-induced myocardial ischemia. J Am Coll Cardiol 40, 21952200.
36Rubinshtein R, Kuvin JT, Soffler M, et al. (2010) Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J 31, 11421148.
37Plana N, Ferre R, Merino J, et al. (2011) Heterozygous familial hypercholesterolaemic patients have increased arterial stiffness, as determined using the augmentation index. J Atheroscler Thromb 18, 11101116.
38Versari D, Daghini E, Virdis A, et al. (2009) Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 32, Suppl. 2, S314S321.
39Aragones G, Ferre R, Girona J, et al. (2012) Small artery dilation and endothelial markers in cardiovascular risk patients. Eur J Clin Invest 42, 3441.
40Ferre R, Aragones G, Plana N, et al. (2011) High-density lipoprotein cholesterol and apolipoprotein A1 levels strongly influence the reactivity of small peripheral arteries. Atherosclerosis 216, 115119.
41Yeboah J, Crouse JR, Hsu FC, et al. (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115, 23902397.
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? *



Altmetric attention score

Full text views

Total number of HTML views: 96
Total number of PDF views: 360 *
Loading metrics...

Abstract views

Total abstract views: 893 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 19th November 2017. This data will be updated every 24 hours.