Ketogenic diet (but not sugar restriction) alters glucose tolerance, lipid metabolism, peripheral tissue phenotype and the gut microbiome: an RCT.
Restricted sugar and ketogenic diets can both alter energy balance and metabolism, but any resultant decrease in energy intake may be counteracted by compensatory reductions in energy expenditure. In healthy adults, randomization to restriction of free-sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduced fat mass without changes in physical activity or resting metabolic rate, compared to a control diet. Free-sugar restriction had minimal effect on metabolism or gut microbiome other than decreased serum low-density lipoprotein cholesterol concentrations. In contrast, ketogenic diet-induced weight loss decreased glucose tolerance, coinciding with increased PDK4 and reduced AMPK and GLUT4 levels in skeletal muscle. In the first 4 weeks, the ketogenic diet reduced fasting glucose, increased apolipoprotein B, C-reactive protein and postprandial glycerol concentrations. However, despite sustained ketosis, these effects were no longer apparent by week 12, when gut microbial beta diversity was altered, possibly reflective of longer-term ketotic adaptation and/or new energy balance status. These data demonstrate that restricting either free-sugars or overall carbohydrates can reduce energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles and gut microbial composition.