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

1 Citation (SciVal)

Abstract

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 low-density lipoprotein cholesterol (LDL-C). In contrast, a ketogenic diet decreases glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose and 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
Article number101667
JournalCell Reports Medicine
Volume5
Issue number8
Early online date5 Aug 2024
DOIs
Publication statusPublished - 20 Aug 2024

Data Availability Statement

De-identified data will be publicly available as of the date of publication at https://researchdata.bath.ac.uk/id/eprint/1366 and https://www.ebi.ac.uk/ena/browser/ (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.

Funding

This work was supported by an initial grant from The Rank Prize Funds with subsequent funding from Cosun Nutrition Center, The University of Bath, and Ian Tarr. NMR was funded by BHF Senior fellowships (FS/15/56/31645 and FS/SBSRF/21/31013) to LH. FK is funded by the MRC (MR/P0002927/1). PDC is a co-founder and CTO of SeqBiome Ltd. JTG has received research funding from BBSRC, MRC, British Heart Foundation, Clasado Biosciences, Lucozade Ribena Suntory, ARLA Foods Ingredients, Cosun Nutrition Center, and the Fruit Juice Science Centre; is a scientific advisory board member to ZOE; and has completed paid consultancy for 6d Sports Nutrition. JAB is an investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, ARLA foods, Cosun Nutrition Center, American Academy of Sleep Medicine Foundation and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg’s, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in Chief of International Journal of Sport Nutrition & Exercise Metabolism, The Dairy Council, PepsiCo, Violicom Medical, Tour Racing Ltd., and SVGC.

Keywords

  • body fat
  • diet
  • energy balance
  • energy intake
  • ketogenic
  • lipoprotein
  • low carbohydrate
  • metabolism
  • physical activity
  • sugar

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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