Published online Jan 15, 2022. doi: 10.4239/wjd.v13.i1.54
Peer-review started: May 8, 2021
First decision: June 16, 2021
Revised: June 29, 2021
Accepted: January 5, 2022
Article in press: January 5, 2022
Published online: January 15, 2022
Ketone bodies (KB) derived from free fatty acid (FFA) metabolism serve as energy substrates in conditions of reduced glucose availability, but also as metabolic regulators and signalling molecules. Bariatric metabolic surgery (BMS) involves a marked energy deficit that results in massive mobilization of FFAs from adipose tissue, resulting in the activation of ketogenesis. It is not known whether all subjects undergoing BMS become ketotic, and whether there is a relationship between ketogenic capacity and weight loss (WL) following BMS.
We hypothesized that subjects with reduced ketogenic capacity are poorer responders to BMS in terms of WL. Characterization of the relationship between ketogenic capacity and WL following BMS will help understand the metabolic actions of KB and find out whether KB could be used as a predictor of BMS-induced WL.
We assessed the relationship between KB production in the first weeks after BMS and WL at 6 mo. We also assessed the relationship of KB with metabolic parameters and WL at 12 mo.
For this retrospective study, we analyzed data from 39 patients who underwent laparoscopic sleeve gastrectomy, had urinary KB measured within two months of surgery and a follow-up of at least 6 mo. KB production was assessed by the presence of acetoacetic acid in urine using an automated dipstick urinalysis. We compared patients who developed post-operative ketosis with those who did not. The relationship of WL at 6 mo with pre-operative anthropometrics, body composition and metabolic parameters, and with post-operative urinary KBs was studied using bivariate correlation analyses. Variables that were significantly correlated were included in a hierarchical multiple-regression analysis, while controlling for sex, age and BMI.
This was the first study to specifically assess the relationship of ketogenic capacity with weight and metabolic outcomes. Most, but not all patients (69.2%), developed ketosis after a mean of 46.0 ± 13.6 d from surgery. Patients with ketosis were significantly younger [42.9 (37.6; 50.7) years vs 51.9 (48.3; 59.9) years, P = 0.018] and had significantly lower pre-operative fasting plasma glucose [89.5 (82.5; 96.3) mg/dL vs 96.0 (91.0; 105.3) mg/dL, P = 0.025] and triglyceride levels [108.0 (84.5; 152.5) mg/dL vs 152.0 (124.0; 186.0) mg/dL, P = 0.020], but greater LDL cholesterol (121.0 ± 23.5 mg/dL vs 100.2 ± 33.9 mg/dL, P = 0.045). WL at 6 mo was significantly greater in patients who had developed post-operative ketosis (27.5% ± 5.1% vs 23.8% ± 4.3% in the groups with and without ketosis, respectively; P = 0.035). At hierarchical multiple regression, urinary KBs and male sex emerged as significant predictors of WL at 6 mo.
In keeping with the growing body of evidence indicating that nutritional ketosis has several health benefits, our findings suggest that patients who develop nutritional ketosis following BMS might have greater WL and better metabolic responses to BMS.
Our findings should be considered hypothesis-generating. Further research is needed to confirm these data in larger populations, and to assess the relationship between ketogenic capacity and metabolic responses to BMS with more sophisticated techniques.