Twelve Weeks Of Ketogenic Diet Increases Atherogenic Lipoprotein Profiles Despite Meaningful Fat Loss

PURPOSE: Restricting energy availability by skipping breakfast or alternate-day fasting causes reductions in physical activity. Carbohydrate availability may contribute to these effects, but this has not been directly investigated. Free-sugar restriction is a public health strategy to influence energy balance and metabolic health, and ketogenic carbohydrate restriction is an alternative approach. We investigated the effects of sugar and overall carbohydrate restriction on physical activity, energy balance, and metabolism throughout a 12-week lifestyle intervention. METHODS: In a randomized parallel group design, 53 healthy women (n = 30) and men (mean ± SD, age 35 ± 16 y, body mass index 24 ± 3 kg/m2) were allocated for 12 weeks to groups consuming either: a moderate sugar, moderate carbohydrate diet (MODSUG); low sugar, moderate carbohydrate diet (LOWSUG); or low carbohydrate, ketogenic diet (LOWCHO). At baseline, week 4, and week 12, physical activity was assessed using combined accelerometry and heart rate, energy balance was characterized by assessing body composition (DEXA), RMR (indirect calorimetry), and energy intake (food diaries), and metabolic health was characterized with fasting and postprandial blood samples following a mixed meal. Data were analyzed by ANCOVA with baseline values as co-variate for between group comparisons, and one-way ANOVA for within-group comparisons. RESULTS: Physical activity energy expenditure was not different between conditions at week 4 (p = 0.30) or week 12 (p = 0.83). Mean (95% CI) fat mass decreased by 1.6 ± 1.6 kg and 2.7 ± 2.1 kg in LOWSUG and LOWCHO respectively at week 12 (both p < 0.01 vs MODSUG). Fasting LDL-cholesterol and Apolipoprotein B concentrations were higher in LOWCHO at week 4 and week 12 (both p < 0.05). Postprandial serum glucose, βOHB, and NEFA responses were greater, and lactate responses lower, in LOWCHO at week 4 and week 12 compared to other conditions (both p < 0.05). CONCLUSIONS: Dietary sugar and carbohydrate restriction in a free-living setting cause reductions in body fat without changing physical activity across 12 weeks in healthy humans. Ketogenic carbohydrate restriction increases LDL-cholesterol and Apolipoprotein B concentrations, whereas sugar restriction alone does not, supporting dietary guidance to restrict free sugar intake.