Hall · Nature medicine 2021 · Randomized crossover trial · n=20

Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake.

Cited 246 times in the scientific literature.

Level 2 - randomized trial

Randomized crossover clinical trial

PubMed 33479499 · doi:10.1038/s41591-020-01209-1 · record verified 2026-08-29

What was done

Twenty adults (mean age 29.9 ± 1.4 years, BMI 27.8 ± 1.3 kg m⁻²) were admitted as inpatients to a clinical research center and randomized to consume ad libitum either a minimally processed plant-based low-fat diet (10.3% fat, 75.2% carbohydrate) or an animal-based ketogenic diet (75.8% fat, 10.0% carbohydrate) for 2 weeks, followed immediately by the alternate diet for 2 weeks. The primary outcome was mean daily ad libitum energy intake across the 2-week period and during the final week of each diet.

What was found

The low-fat diet resulted in 689 ± 73 kcal d⁻¹ less energy intake than the ketogenic diet over the full 2 weeks (P < 0.0001) and 544 ± 68 kcal d⁻¹ less over the final week (P < 0.0001).

Why it matters

These findings contradict the carbohydrate-insulin model of obesity, demonstrating that a high-carbohydrate, low-fat diet did not stimulate higher ad libitum energy intake compared to a ketogenic diet in tightly controlled conditions.

Limits

The sample size was small (n = 20) with a brief intervention period of 2 weeks per diet phase. Inpatient feeding restricts generalizability to free-living populations, long-term outcomes were not evaluated, and one participant withdrew due to hypoglycemia during the ketogenic diet.

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