Association between ss-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition

Background: Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), whereas preserving fat-free mass (FFM). Additionally, animal data support the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge, a potential association between B-hydroxybutyrate (BHB) plasma concentrations and changes in body composition has never been explored.Objectives: The main aim of this analysis was to determine if BHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity.Methods: Data from 199 individuals (BMI = 36.6 & PLUSMN; 4.3 kg/m2; age = 43.6 & PLUSMN; 9.8 y; 82 men) were collated from 3 weight loss studies employing common measures of body composition (air displacement plethysmography) and BHB plasma concentration (ELISA). The association between BHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multi variable linear regression was used to determine if BHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors.Results: BHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r = 0.182, P = 0.01, n = 199) and a trend with weight loss (r = 0.128, P = 0.072, n = 199). BHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study.Conclusions: The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved. This trial was registered at clinicaltrials.gov identifier as NCT01834859, NCT04051190, NCT02944253.