A 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


      To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects.


      We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months.


      Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = −0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = −30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = −2.0 mg/dL, P = 0.005), independent of weight loss.


      In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Festa A.
        • D'Agostino R.
        • Mykkanen L
        • et al.
        LDL particle size in relation to insulin, proinsulin, and insulin sensitivity.
        Diabetes Care. 1999; 10: 1688-1693
        • Kang H.S.
        • Gutin B.
        • Barbeau P.
        • Litaker M.S.
        • Allison J.
        • Le N.A.
        Low-density lipoprotein particle size, central obesity, cardiovascular fitness, and insulin resistance syndrome markers in obese youths.
        Int J Obes Relat Metab Disord. 2002; 26: 1030-1035
        • Samaha F.F.
        • Iqbal N.
        • Seshadri P
        • et al.
        Low carbohydrate as compared to low fat diet in severe obesity.
        N Engl J Med. 2003; 348: 2074-2081
        • Foster G.D.
        • Wyatt H.R.
        • Hill J.O
        • et al.
        A multi-center, randomized, controlled trial of a low-carbohydrate diet for obesity.
        N Engl J Med. 2003; 348: 2082-2090
      1. Executive Summary of the 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). JAMA. 2001;285:2486–2497.

        • Otvos J.D.
        • Jeyarajah E.J.
        • Cromwell W.C.
        Measurement issues related to lipoprotein heterogeneity.
        Am J Cardiol. 2002; 90: 22i-29i
        • Blake G.J.
        • Otvos J.D.
        • Rifai N.
        • Ridker P.M.
        Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women.
        Circulation. 2002; 106: 1930-1937
        • Williams P.T.
        • Krauss R.M.
        • Vranizan K.M.
        • Wood P.D.
        Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men.
        Circulation. 1990; 81: 1293-1304
        • Festa A.
        • D'Agostino R.
        • Howard G.
        • Mykkanen L.
        • Tracy R.P.
        • Haffner S.M.
        Chronic subclinical inflammation as part of the insulin resistance syndrome.
        Circulation. 2000; 102: 42-47
      2. ATP III Final Report. II. Rationale for intervention. Circulation. 2002;106:3163–3223.

        • Laimer M.
        • Ebenbichler C.F.
        • Kaser S
        • et al.
        Markers of chronic inflammation and obesity.
        Int J Obes Relat Metab Disord. 2002; 26: 659-662
        • Tchernof A.
        • Nolan A.
        • Sites C.K.
        • Ades P.A.
        • Poehlman E.T.
        Weight loss reduces C-reactive protein levels in obese postmenopausal women.
        Circulation. 2002; 105: 564-569
        • McLaughlin T.
        • Abbasi F.
        • Lamendola C
        • et al.
        Differentiation between obesity and insulin resistance in the association with C-reactive protein.
        Circulation. 2002; 106: 2908-2912
      3. National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases. Obesity education initiative. In: Clinical Guidelines on the Identification, Education, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, Maryland: National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases; 1998. NIH Publication No. 98-4083.

        • Karvetti R.L.
        • Knuts L.R.
        Validity of the 24-hour dietary recall.
        Contin Educ. 1985; 85: 1437-1442
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein in plasma, without the use of preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Katz A.
        • Sridhar S.
        • Nambi S.S
        • et al.
        Quantitative insulin sensitivity check index.
        J Clin Endocrinol Metab. 2000; 85: 2402-2410
        • Otvos J.D.
        • Jeyarajah E.J.
        • Bennett D.
        • Krauss R.M.
        Development of a proton magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement.
        Clin Chem. 1992; 38: 1632-1638
        • Freedman D.S.
        • Otvos J.D.
        • Jeyarajah E.J.
        • Barboriak J.J.
        • Anderson A.J.
        • Walker J.A.
        Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease.
        Arterioscler Thromb Vasc Biol. 1998; 18: 1046-1053
        • Grundy S.M.
        • Vega G.L.
        • Otvos J.D.
        • Rainwater D.L.
        • Cohen J.C.
        Hepatic lipase influences high density lipoprotein subclass distribution in normotriglyceridemic men.
        J Lipid Res. 1999; 40: 229-234
        • Otvos J.D.
        Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy.
        Clin Lab. 2002; 48: 171-180
        • Bonow R.O.
        • Eckel R.H.
        Diet, obesity, and cardiovascular risk.
        N Engl J Med. 2003; 348: 2057-2058
        • Blankenhorn D.H.
        • Alaupovic P.
        • Wickham E.
        • Chin H.P.
        • Azen S.P.
        Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts.
        Circulation. 1990; 81: 470-476
        • Mack W.J.
        • Krauss R.M.
        • Hodis H.N.
        Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS).
        Arterioscler Thromb Vasc Biol. 1996; 16: 697-704
      4. Karpe F, Steiner G, Olivecrona T, Carlson LA, Hamsten A. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. J Clin Invest. 1993;91:3:748–758.

        • Ai M.
        • Tanaka A.
        • Ogita K
        • et al.
        Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes.
        J Am Coll Cardiol. 2001; 38: 1628-1632
        • Ginsberg H.N.
        Is hypertriglyceridemia a risk factor for atherosclerotic cardiovascular disease? A simple question with a complicated answer.
        Ann Intern Med. 1997; 126: 912-914
        • Gotto A.M.
        Lipid Disorders.
        Handbooks in Healthcare Co., Newtown, Pennsylvania2001
        • Lamarche B.
        • Tchernof A.
        • Moorjani S
        • et al.
        Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men.
        Circulation. 1997; 95: 69-75
        • Kuller L.
        • Arnold A.
        • Tracy R
        • et al.
        Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1175-1180
        • Miller N.E.
        Associations of high density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis.
        Am Heart J. 1987; 113: 589-597
        • Johansson J.
        • Carlson L.A.
        • Landou C.
        • Hamsten A.
        High density lipoproteins and coronary atherosclerosis.
        Arterioscler Thromb. 1991; 11: 174-182