Ketogenic diet (but not free-sugar restriction) alters glucose tolerance, lipid metabolism, peripheral tissue phenotype and gut microbiome: RCT

Aaron Hengist, Russell Davies, Jean-Philippe Walhin, Jariya Buniam, Lucy Merrell, Lucy Rogers, Louise Bradshaw, Alfonso Moreno-Cabañas, Peter J Rogers, Jeff M. Brunstrom, Leanne Hodson, L J C van Loon, Wiley Barton, Ciara O'Donovan, Fiona Crispie, Orla O'Sullivan, Paul Cotter, Kathryn Proctor, James Betts, Francoise KoumanovDylan Thompson, Javier Gonzalez

Research output: Contribution to journalArticlepeer-review


Restricted sugar and ketogenic diets can alter energy balance/metabolism, but decreased energy intake may be compensated by reduced expenditure. In healthy adults, randomization to restricting free-sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduces fat mass without changing energy expenditure versus control. Free-sugar restriction minimally affects metabolism or gut microbiome but decreases LDL-C. In contrast, ketogenic diet decreases glucose tolerance, increased skeletal muscle PDK4 and reduced AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose, increases apolipoprotein-B, C-reactive protein, and postprandial glycerol concentrations. However, despite sustained ketosis, these effects are no longer apparent by week 12, when gut microbial beta diversity is altered, possibly reflective of longer-term adjustments to the ketogenic diet and/or energy balance. These data demonstrate that restricting free-sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles and gut microbiome.
Original languageEnglish
JournalCell Reports Medicine
Publication statusAcceptance date - 9 Jul 2024

Data Availability Statement

De-identified data will be publicly available as of the date of publication at and (data accession ID: PRJEB72300). This paper does not report original code. Accession numbers are listed in the key resources table. Any additional information required to reanalyze the data reported in this work paper is available from the Lead Contact upon request.


  • Energy balance
  • Metabolism
  • Ketogenic
  • Sugar
  • Diet
  • Physical activity
  • Body fat
  • Energy intake
  • Lipoprotein

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