Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men

Abstract

Background: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat.

Objective: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition.

Design: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW).

Results: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass.

Conclusion: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.

Keywords: body composition; carbohydrate; energy expenditure; fat; insulin; ketogenic diet; macronutrients.

FIGURE 1

Overview of the study design. Seventeen overweight and obese men were confined to metabolic wards where they consumed a BD designed to represent a habitual high-carbohydrate intake for a 28-d run-in period followed by an isocaloric KD for an additional 28 d. Dietary protein was kept constant throughout, and the subjects were prescribed 90 min of low-intensity daily aerobic exercise. Every week, subjects spent 2 consecutive days residing in metabolic chambers to measure total daily energy expenditure, respiratory quotient, and sleeping energy expenditure. Body composition was measured by DXA, and the average energy expenditure during the last 2 wk of each diet period was measured by the DLW method. BD, high-carbohydrate baseline diet; DLW, doubly labeled water; DXA, dual-energy X-ray absorptiometry; KD, low-carbohydrate ketogenic diet.

FIGURE 2

Body composition and overall energy balance. Subjects experienced an unintentional loss of (A) body weight (◆) and (B) fat mass (□) throughout the study, indicating an overall state of negative energy balance. Weight loss was accelerated during the first 2 wk of the KD, but the rate of body fat loss slowed during this period. During the final 2 wk of the KD, both the rates of body weight and fat loss were similar to baseline. (C) The calculated negative energy balance during the last 2 wk of the baseline period (BD −15 to 0 d) and the KD period (15–28 d) was not significantly different whether assessed by the measured body composition changes (DXA; n = 16) or by calculating energy intake minus expenditure as measured by DLW (n = 16). Horizontal solid lines indicate significant weight changes from the final BD day, P < 0.0012 as assessed by a paired, 2-sided t test and Bonferroni adjusted for 43 comparisons. *Significant change in fat mass from final BD day, P < 0.017 as assessed by a paired, 2-sided t test and Bonferroni adjusted for 3 comparisons. Means ± 95% CIs are presented. BD, high-carbohydrate baseline diet; DLW, doubly labeled water; DXA, dual-energy X-ray absorptiometry; KD, low-carbohydrate ketogenic diet.

FIGURE 3

Changes in total daily energy expenditure, SEE, and RQ. (A) EE_chamber significantly increased within the first week of the KD compared with that of the final BD day, but subsequently there was a significant decreasing linear trend (P = 0.002). (B) SEE rapidly increased during the KD, but subsequently there was a significant decreasing linear trend (P < 0.0001). (C) Daily RQ (24-h RQ; n = 17) decreased within the first week of the KD and stayed significantly below that of BD throughout the remainder of the study and was close to the calculated mean change in food quotient (thick dashed black line) and within its 95% CI (thin dashed black lines). Means ± 95% CIs are presented, n = 17. *Significant change from the final BD day, P < 0.0045 as assessed by a paired, 2-sided t test and Bonferroni adjusted for 11 comparisons. Note that the statistical analyses presented in the main text and Table 2 used a repeated-measures mixed model rather than pairwise Bonferroni-adjusted comparisons with the final BD day. BD, high-carbohydrate baseline diet; EE_chamber, total daily energy expenditure measured during repeated stays in metabolic chambers; KD, low-carbohydrate ketogenic diet; RQ, respiratory quotient; SEE, sleeping energy expenditure.

FIGURE 4

Changes in circulating plasma fuel sources in the overnight fasted state. Plasma ketones (calculated as the sum of acetoacetate and beta hydroxybutyrate) (A) and FFAs (B) both significantly increased during the KD compared with those in the final BD day, whereas glucose (C) and glycerol (D) were unchanged from baseline. Plasma triglycerides (E) tended to decrease during the KD, and the overall circulating energy (F) was unchanged. Means ± 95% CIs are presented, n = 17. *Significant change from the final BD day, P < 0.0125 as assessed by a paired, 2-sided t test and Bonferroni adjusted for 4 comparisons. Note that the statistical analyses presented in the main text and Table 4 used a repeated-measures mixed-model rather than pairwise Bonferroni-adjusted comparisons with the final BD day. BD, high-carbohydrate baseline diet; FFA, free fatty acid; KD, low-carbohydrate ketogenic diet.