Original Research2 September 2014
A Randomized Trial
    Author, Article, and Disclosure Information



    Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.


    To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.


    A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271)


    A large academic medical center.


    148 men and women without clinical cardiovascular disease and diabetes.


    A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.


    Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.


    Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, −3.5 kg [95% CI, −5.6 to −1.4 kg]; P = 0.002), fat mass (mean difference in change, −1.5% [CI, −2.6% to −0.4%]; P = 0.011), ratio of total–high-density lipoprotein (HDL) cholesterol (mean difference in change, −0.44 [CI, −0.71 to −0.16]; P = 0.002), and triglyceride level (mean difference in change, −0.16 mmol/L [−14.1 mg/dL] [CI, −0.31 to −0.01 mmol/L {−27.4 to −0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet.


    Lack of clinical cardiovascular disease end points.


    The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.

    Primary Funding Source:

    National Institutes of Health.


    • 1. Go ASMozaffarian DRoger VLBenjamin EJBerry JDBorden WBet alAmerican Heart Association Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation2013;127:e6-e245. [PMID: 23239837] doi:10.1161/CIR.0b013e31828124ad CrossrefMedlineGoogle Scholar
    • 2. Halton TLWillett WCLiu SManson JEAlbert CMRexrode Ket alLow-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med2006;355:1991-2002. [PMID: 17093250] CrossrefMedlineGoogle Scholar
    • 3. Lagiou PSandin SLof MTrichopoulos DAdami HOWeiderpass ELow carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. BMJ2012;344:e4026. [PMID: 22735105] doi:10.1136/bmj.e4026 CrossrefMedlineGoogle Scholar
    • 4. Stern LIqbal NSeshadri PChicano KLDaily DAMcGrory Jet alThe effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med2004;140:778-85. [PMID: 15148064] LinkGoogle Scholar
    • 5. Davis NJTomuta NSchechter CIsasi CRSegal-Isaacson CJStein Det alComparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes. Diabetes Care2009;32:1147-52. [PMID: 19366978] doi:10.2337/dc08-2108 CrossrefMedlineGoogle Scholar
    • 6. Sacks FMBray GACarey VJSmith SRRyan DHAnton SDet alComparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med2009;360:859-73. [PMID: 19246357] doi:10.1056/NEJMoa0804748 CrossrefMedlineGoogle Scholar
    • 7. Krauss RMEckel RHHoward BAppel LJDaniels SRDeckelbaum RJet alAHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation2000;102:2284-99. [PMID: 11056107] CrossrefMedlineGoogle Scholar
    • 8. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation2002;106:3143-421. [PMID: 12485966] CrossrefMedlineGoogle Scholar
    • 9. Stone NJVanHorn LTherapeutic lifestyle change and Adult Treatment Panel III: evidence then and now. Curr Atheroscler Rep2002;4:433-43. [PMID: 12361490] CrossrefMedlineGoogle Scholar
    • 10. Nutrition Data System for ResearchThe Minnesota Nutrition Data System. Minneapolis, MN: Univ of Minnesota; 2005. Google Scholar
    • 11. Pickering TGHall JEAppel LJFalkner BEGraves JHill MNet alSubcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure ResearchRecommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension2005;45:142-61. [PMID: 15611362] MedlineGoogle Scholar
    • 12. Allain CCPoon LSChan CSRichmond WFu PCEnzymatic determination of total serum cholesterol. Clin Chem1974;20:470-5. [PMID: 4818200] CrossrefMedlineGoogle Scholar
    • 13. Friedewald WTLevy RIFredrickson DSEstimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem1972;18:499-502. [PMID: 4337382] CrossrefMedlineGoogle Scholar
    • 14. Samaha FFIqbal NSeshadri PChicano KLDaily DAMcGrory Jet alA low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med2003;348:2074-81. [PMID: 12761364] CrossrefMedlineGoogle Scholar
    • 15. Brehm BJSeeley RJDaniels SRD'Alessio DAA randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab2003;88:1617-23. [PMID: 12679447] CrossrefMedlineGoogle Scholar
    • 16. Seshadri PIqbal NStern LWilliams MChicano KLDaily DAet alA randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med2004;117:398-405. [PMID: 15380496] CrossrefMedlineGoogle Scholar
    • 17. Wilson PWD'Agostino RBLevy DBelanger AMSilbershatz HKannel WBPrediction of coronary heart disease using risk factor categories. Circulation1998;97:1837-47. [PMID: 9603539] CrossrefMedlineGoogle Scholar
    • 18. Molenberghs GKenward MMissing Data in Clinical Studies. Hoboken, NJ: J Wiley; 2007. Google Scholar
    • 19. Brinkworth GDNoakes MBuckley JDKeogh JBClifton PMLong-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr2009;90:23-32. [PMID: 19439458] doi:10.3945/ajcn.2008.27326 CrossrefMedlineGoogle Scholar
    • 20. Dansinger MLGleason JAGriffith JLSelker HPSchaefer EJComparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA2005;293:43-53. [PMID: 15632335] CrossrefMedlineGoogle Scholar
    • 21. Foster GDWyatt HRHill JOMakris APRosenbaum DLBrill Cet alWeight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med2010;153:147-57. [PMID: 20679559] doi:10.7326/0003-4819-153-3-201008030-00005 LinkGoogle Scholar
    • 22. Foster GDWyatt HRHill JOMcGuckin BGBrill CMohammed BSet alA randomized trial of a low-carbohydrate diet for obesity. N Engl J Med2003;348:2082-90. [PMID: 12761365] CrossrefMedlineGoogle Scholar
    • 23. Shai ISchwarzfuchs DHenkin YShahar DRWitkow SGreenberg Iet alDietary Intervention Randomized Controlled Trial (DIRECT) GroupWeight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med2008;359:229-41. [PMID: 18635428] doi:10.1056/NEJMoa0708681 CrossrefMedlineGoogle Scholar
    • 24. Gardner CDKiazand AAlhassan SKim SStafford RSBalise RRet alComparison 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. JAMA2007;297:969-77. [PMID: 17341711] CrossrefMedlineGoogle Scholar
    • 25. Hu TMills KTYao LDemanelis KEloustaz MYancy WSet alEffects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol2012;176 Suppl 7:S44-54. [PMID: 23035144] doi:10.1093/aje/kws264 CrossrefMedlineGoogle Scholar
    • 26. Ebbeling CBSwain JFFeldman HAWong WWHachey DLGarcia-Lago Eet alEffects of dietary composition on energy expenditure during weight-loss maintenance. JAMA2012;307:2627-34. [PMID: 22735432] doi:10.1001/jama.2012.6607 CrossrefMedlineGoogle Scholar
    • 27. Gardner CDFortmann SPKrauss RMAssociation of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA1996;276:875-81. [PMID: 8782636] CrossrefMedlineGoogle Scholar
    • 28. Ross RAtherosclerosis—an inflammatory disease. N Engl J Med1999;340:115-26. [PMID: 9887164] CrossrefMedlineGoogle Scholar
    • 29. Cardillo SSeshadri PIqbal NThe effects of a low-carbohydrate versus low-fat diet on adipocytokines in severely obese adults: three-year follow-up of a randomized trial. Eur Rev Med Pharmacol Sci2006;10:99-106. [PMID: 16875041] MedlineGoogle Scholar
    • 30. U.S. Preventive Services Task ForceAspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med2009;150:396-404. [PMID: 19293072] LinkGoogle Scholar
    • 31. Larosa JCFry AGMuesing RRosing DREffects of high-protein, low-carbohydrate dieting on plasma lipoproteins and body weight. J Am Diet Assoc1980;77:264-70. [PMID: 7410754] MedlineGoogle Scholar