Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue phenotype, and gut microbiome: RCT.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 39106867 · doi:10.1016/j.xcrm.2024.101667
What was done
Healthy adults were randomized to a 12-week intervention involving free-sugar restriction, overall carbohydrate restriction (ketogenic diet), or a control diet. Investigators measured changes in body fat mass, energy expenditure, glucose tolerance, lipid and inflammatory markers (LDL-C, apolipoprotein B, C-reactive protein, postprandial glycerol), skeletal muscle signaling markers (PDK4, AMPK, GLUT4), and gut microbial beta diversity across 4 and 12 weeks.
What was found
The abstract reports directions of effect without numerical values or confidence intervals. Both dietary interventions reduced fat mass without altering energy expenditure compared with controls. Free-sugar restriction decreased LDL-C with minimal impact on other metabolic markers or the gut microbiome. The ketogenic diet reduced glucose tolerance, increased muscle PDK4, and decreased muscle AMPK and GLUT4. At week 4, the ketogenic diet decreased fasting glucose and increased apolipoprotein B, C-reactive protein, and postprandial glycerol; these specific week-4 changes were no longer evident by week 12 despite sustained ketosis. At week 12, the ketogenic diet significantly altered gut microbial beta diversity.
Why it matters
These findings show that while both sugar restriction and ketogenic diets can achieve fat loss without slowing energy expenditure, they have divergent physiological effects, with the ketogenic diet inducing acute reductions in glucose tolerance and changes in gut microbiome composition not seen with free-sugar restriction alone.
Limits
The abstract does not disclose the sample size, participant demographics, dietary compliance metrics, or numerical effect sizes. The 12-week duration in healthy adults limits conclusions regarding long-term clinical safety, durability, or generalizability to populations with baseline metabolic disorders.
Cited by
- supports A 2024 randomized controlled trial from the University of Bath published in Cell Reports Medicine compared a control diet, a low-sugar diet, and a ketogenic diet over 12 weeks in 53 participants.
- supports In the 2024 University of Bath randomized controlled trial, the ketogenic diet group lost an average of 2.9 kg of fat and the low-sugar group lost approximately 2.1 kg of fat.
- supports In the 2024 University of Bath trial, the ketogenic diet group experienced a significant rise in LDL cholesterol and ApoB, whereas the low-sugar group had no change in ApoB.
- supports In the University of Bath trial, the ketogenic diet reduced dietary fiber intake to around 15 grams per day and caused a significant, sustained reduction in Bifidobacteria.
- supports A randomized controlled trial from the University of Bath showed that a ketogenic diet temporarily reduces glucose tolerance due to a muscular adaptation to low carbohydrate availability.