AbstractObjectiveThe aim of this study was to investigate the effectiveness of an intermittent low‐carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms.MethodsThirty‐four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self‐administered 2‐week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500–600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared.ResultsThe ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein‐1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low‐density lipoprotein cholesterol and total cholesterol (−0.36 mmol/L, 95% CI: −0.68 to −0.04; −0.40 mmol/L, 95% CI: −0.73 to −0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low‐density lipoprotein cholesterol (r = −0.81 and −0.72).ConclusionsThis study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.