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

Cell reports. Medicine. 2024;5(8):101667

Plain language summary

A low sugar and a ketogenic diet can both reduce total energy intake but this may be compensated by reduced energy expenditure. 60 healthy adults were randomised to a diet low in free sugars (LOWSUG, 50% carbohydrates of which 5% sugars, 15% protein, 35% fat), a ketogenic diet (KETO, 77% fat, 15% protein, 8% carbohydrates of which 2% sugars) and control diet (MODSUG, 50% carbohydrates of which 20% sugars, 35% fat, 15% protein) for 12 weeks. 45 participants completed the 12 weeks. Both intervention groups significantly reduced energy intake, body mass and fat mass compared to the control group, the reduction was greater in the KETO than the LOWSUG group although it is not reported whether this difference is statistically significant. Energy expenditure was not affected. Compared to the LOWSUG diet, the KETO diet decreased glucose tolerance, increased fat oxidation and altered beta-diversity of the microbiome. The LOWSUG diet had no significant effect on glucose metabolism or microbiome composition but lowered low lipoprotein (LDL) cholesterol. The authors conclude that the LOWSUG diet may be more appropriate than the KETO diet for most people, as the reduction in glucose tolerance and alteration in gut microbiome may have negative effects on cardiometabolic health despite the weight loss achieved with the KETO diet.

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.

Lifestyle medicine

Fundamental Clinical Imbalances : Hormonal ; Structural
Patient Centred Factors : Mediators/Carbohydrates
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood ; Stool
Bioactive Substances : Sugar

Methodological quality

Jadad score : 3
Allocation concealment : Not applicable

Metadata