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Life sciences · Journal article
eBioMedicine · October 24, 2026
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Background Obesity involves complex changes in energy metabolism and increased cardiovascular disease (CVD) risk independently of low-density lipoprotein cholesterol (LDL-C). Diets high or low in carbohydrates or fats can be effective for reversing obesity, but their distinct effects on metabolic health and detailed lipid profiles may differentially impact overall CVD risk, particularly with large differences in saturated fatty acid (SFA) intake. Methods In a 2-year randomised controlled trial, 193 males and females with obesity were assigned to 1) an acellular carbohydrate-based diet (A-HCLF, comparator arm), 2) a cellular carbohydrate-based diet (C-HCLF), or 3) a low-carbohydrate high-fat (LCHF) diet (75 energy percent fat, thereof 30 SFAs). As secondary outcomes of the trial, plasma lipids and lipoprotein particle subfractions were quantified by nuclear magnetic resonance spectroscopy assay, and coronary artery calcium score by CT imaging. Data were analysed by constrained linear mixed-effects modelling. Findings Attrition was 74 (39%), 114 (59%), 128 (67%), 135 (70%), and 162 (84%) at 3, 6, 9, 12 and 24 months, respectively. Self-reported adherence ranged from 63 to 85% up to 12 months and 40–60% for the last 12 months. During the first 9–12 months, the LCHF group showed significantly greater reductions than the A-HCLF comparator and C-HCLF diets in very low-density lipoprotein particles (VLDLs), triacylglycerols (TAGs), remnant cholesterol, and the TAG/high-density lipoprotein cholesterol (HDL-C) ratio, alongside increases in HDL-C, total apolipoprotein A1 (apoA1), apoA1 in large HDL particles, LDL-C (attributed to large LDL particles), and the LDL-C/apolipoprotein B ratio. At 24 months, there were still greater reductions on the LCHF compared to the A-HCLF diet for TAGs, VLDL particles, remnant cholesterol, and the TAG/HDL-C ratio, as well as a greater increase in large LDL particles. Interpretation In adults with obesity, an LCHF diet rich in SFA markedly lowered TAG-rich remnants and raised HDL-C and apoA1 compared to higher-carbohydrate diets, while shifting LDL toward larger particles without significantly increasing apoB or small LDLs—a pattern that may indicate greater lipid turnover. Funding This work was supported by the Trond Mohn Research Foundation, Bergen (Norway), the University of Bergen (Norway), Kostfonden, Stockholm (Sweden), and the Norwegian Health Association.