Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

Abstract

Objective: To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.

Design: Randomized trial.

Setting: Multicenter collaboration at US two sites, August 2014 to May 2017.

Participants: 164 adults aged 18-65 years with a body mass index of 25 or more.

Interventions: After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).

Main outcome measures: The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.

Results: Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval -29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).

Conclusions: Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.

Trial registration: ClinicalTrials.gov NCT02068885.

Fig 1

Study design

Fig 2

Participant flow (see supplementary figure for details of exclusions)

Fig 3

Change in total energy expenditure, the primary outcome, in intention-to-treat (top) and per protocol (bottom) analyses. Data are shown as mean change from start of test phase, with whiskers representing 1 standard error above and below the mean. P tests uniformity across diet groups for average of changes at midpoint and end of test phase

Fig 4

Effect modification by pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose) in intention-to-treat and per protocol analyses. Pre-weight loss body weight differed by third (first third, 83.8 kg; second third, 92.8 kg; third third 98.4 kg, P<0.001 in the intention-to-treat analysis). Change in body weight during the test phase did not differ by third (P=0.08) or across diet groups (P=0.43)

Fig 5

Biomeasures of compliance in intention-to-treat and per protocol analyses. Measures include 1,5-anhydroglucitol (upper), mean pre-weight loss value 17 μg/mL; triglycerides (middle), mean pre-weight loss value 78 mg/dL (retransformed); and high density lipoprotein cholesterol (lower), mean pre-weight loss value 48 mg/dL. Data are shown as mean change from start of test phase, with whiskers representing 1 standard error above and below the mean. P tests uniformity across diet groups for average of changes at midpoint and end of test phase. Left, intention-to-treat analysis; right, per-protocol analysis