Effect of Exogenous Ketones as an Adjunct to Low-Calorie Diet on Metabolic Markers

Nutrients. 2025 Nov 16;17(22):3582. doi: 10.3390/nu17223582.

Abstract

Background/objectives: Overweight and obesity affect a majority of adults, contributing to metabolic disorders. Caloric restriction often leads to undesirable lean mass loss alongside fat reduction. This study investigated whether exogenous β-hydroxybutyrate (BHB) supplementation, as an adjunct to a hypocaloric diet, improves body composition and metabolic markers in overweight and obese adults by preferentially reducing fat mass while preserving lean mass.

Methods: In this 8-week randomized, double-blind, placebo-controlled trial, 51 adults were assigned to receive either racemic BHB mineral salts or placebo (maltodextrin) twice daily, alongside modest caloric restriction. Assessments at baseline and week 8 included dual-energy X-ray absorptiometry for body composition, indirect calorimetry for resting metabolic rate (RMR), and venous blood analyses for cardiometabolic biomarkers (e.g., lipids, HOMA-IR, uric acid, liver enzymes).

Results: Body mass decreased in both groups over the intervention (p < 0.01 within placebo and p < 0.001 within BHB). Within the BHB group, fat mass decreased significantly (-2 kg; p < 0.05 vs. baseline), body fat percentage improved (p < 0.01 vs. baseline), and lean-to-fat mass ratio increased (p < 0.05 vs. baseline); no such significant changes were observed within the placebo group. Group × time interactions were not significant for these body composition variables (p > 0.05). Furthermore, lean mass was largely preserved, with no declines in RMR. Within the BHB group, LDL cholesterol was reduced (p < 0.05 vs. baseline), while other lipids, HOMA-IR, and uric acid remained stable, with liver enzymes showing a positive change.

Conclusions: Exogenous BHB supplementation may enhance the quality of diet-induced weight loss through within-group improvements in fat mass reduction and lean mass preservation, with no adverse metabolic impacts.

Keywords: beta-hydroxybutyrate; body composition; ketones; weight loss.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 3-Hydroxybutyric Acid* / administration & dosage
  • 3-Hydroxybutyric Acid* / pharmacology
  • Absorptiometry, Photon
  • Adult
  • Basal Metabolism / drug effects
  • Biomarkers / blood
  • Body Composition / drug effects
  • Caloric Restriction*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obesity* / diet therapy
  • Overweight* / diet therapy
  • Weight Loss / drug effects

Substances

  • Biomarkers
  • 3-Hydroxybutyric Acid