Ebbeling · BMJ (Clinical research ed.) 2018 · randomized controlled trial · n=164

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

Cited 278 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 30429127 · doi:10.1136/bmj.k4583 · record verified 2026-08-29

What was done

Following a run-in phase achieving approximately 12% weight loss, 164 adults with a BMI of 25 or higher (aged 18–65) across two US sites were randomized to one of three protein-controlled diets for 20 weeks: high-carbohydrate (60%, n=54), moderate-carbohydrate (40%, n=53), or low-carbohydrate (20%, n=57). Diets were energy-adjusted to maintain body weight within 2 kg of target. The primary outcome was total energy expenditure measured by doubly labeled water using intention-to-treat (ITT) and per-protocol analyses. Secondary outcomes included resting energy expenditure, physical activity, leptin, and ghrelin, with subgroup analyses based on pre-weight loss insulin secretion.

What was found

Total energy expenditure differed significantly across diets (ITT n=162, P=0.002), increasing by 52 kcal/d (95% CI 23 to 82) for every 10% reduction in carbohydrate intake. Compared with the high-carbohydrate group, total energy expenditure was 91 kcal/d greater (-29 to 210) in the moderate-carbohydrate group and 209 kcal/d greater (91 to 326) in the low-carbohydrate group in the ITT analysis. In the per-protocol analysis (n=120, P<0.001), the differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411), respectively. Among participants in the highest tertile of baseline insulin secretion, the difference between low- and high-carbohydrate diets reached 308 kcal/d (ITT) and 478 kcal/d (per protocol, P<0.004). Ghrelin was significantly lower in the low-carbohydrate group in both analyses, while leptin was significantly lower in the per-protocol analysis.

Why it matters

This study provides evidence that dietary macronutrient composition can alter total energy expenditure independently of body weight, suggesting that carbohydrate restriction may attenuate the metabolic slowdown typical of weight loss maintenance.

Limits

The findings are restricted to weight-loss maintenance rather than active weight loss. The per-protocol analysis had substantial attrition (n=120 remaining of 164 randomized). Long-term adherence, clinical outcomes beyond 20 weeks, and effects in normal-weight individuals were not evaluated.

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