Hall · The American journal of clinical nutrition 2016 · Non-randomized sequential inpatient feeding trial · n=17

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

Cited 330 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized sequential within-subject feeding trial (fixed diet order without randomized crossover).

PubMed 27385608 · doi:10.3945/ajcn.116.133561 · record verified 2026-08-29

What was done

Seventeen overweight or obese men were admitted to an inpatient metabolic ward and consumed a high-carbohydrate baseline diet (BD) for 4 weeks followed by an isocaloric low-carbohydrate ketogenic diet (KD) with clamped protein for 4 weeks. Subjects spent 2 consecutive days per week in metabolic chambers to measure chamber energy expenditure (EEchamber), sleeping energy expenditure (SEE), and respiratory quotient (RQ). Doubly labeled water (EEDLW) assessed average energy expenditure during the final 2 weeks of each diet phase, and body composition was tracked using dual-energy X-ray absorptiometry.

What was found

Participants maintained an overall negative energy balance of ~300 kcal/d and lost weight across the entire study. Compared with the baseline diet, the ketogenic diet significantly increased EEchamber (57 ± 13 kcal/d, P = 0.0004), SEE (89 ± 14 kcal/d, P < 0.0001), and EEDLW (151 ± 63 kcal/d, P = 0.03), while reducing RQ (-0.111 ± 0.003, P < 0.0001). Despite these small increases in energy expenditure, body fat loss slowed during the ketogenic diet phase, which coincided with increased protein utilization and loss of fat-free mass.

Why it matters

These tightly controlled metabolic ward findings challenge the carbohydrate-insulin model of obesity by demonstrating that an isocaloric exchange of carbohydrate for fat does not accelerate body fat loss, yielding only minor increases in energy expenditure.

Limits

The sample size was small (n = 17) and included only men. The fixed sequential design (baseline diet always preceding the ketogenic diet without randomization or a washout phase) leaves findings vulnerable to time and cumulative energy-deficit effects. Observations were limited to 4 weeks per diet.

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