Protein leverage affects energy intake of high-protein diets in humans

Am J Clin Nutr. 2013 Jan;97(1):86-93. doi: 10.3945/ajcn.112.046540. Epub 2012 Dec 5.


Background: The protein leverage hypothesis requires specific evidence that protein intake is regulated more strongly than energy intake.

Objective: The objective was to determine ad libitum energy intake, body weight changes, and appetite profile in response to protein-to-carbohydrate + fat ratio over 12 consecutive days and in relation to age, sex, BMI, and type of protein.

Design: A 12-d randomized crossover study was performed in 40 men and 39 women [mean ± SD age: 34.0 ± 17.6 y; BMI (in kg/m(2)): 23.7 ± 3.4] with the use of diets containing 5%, 15%, and 30% of energy from protein from a milk or plant source.

Results: Protein-content effects did not differ by age, sex, BMI, or type of protein. Total energy intake was significantly lower in the high-protein (7.21 ± 3.08 MJ/d) condition than in the low-protein (9.33 ± 3.52 MJ/d) and normal-protein (9.62 ± 3.51 MJ/d) conditions (P = 0.001), which was predominantly the result of a lower energy intake from meals (P = 0.001). Protein intake varied directly according to the amount of protein in the diet (P = 0.001). The AUC of visual analog scale appetite ratings did not differ significantly, yet fluctuations in hunger (P = 0.019) and desire to eat (P = 0.026) over the day were attenuated in the high-protein condition compared with the normal-protein condition.

Conclusions: We found evidence to support the protein leverage hypothesis in that individuals underate relative to energy balance from diets containing a higher protein-to-carbohydrate + fat ratio. No evidence for protein leverage effects from diets containing a lower ratio of protein to carbohydrate + fat was obtained. It remains to be shown whether a relatively low protein intake would cause overeating or would be the effect of overeating of carbohydrate and fat. The study was registered at as NCT01320189.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Appetite / drug effects
  • Biomarkers / urine
  • Body Weight
  • Cross-Over Studies
  • Diet*
  • Dietary Carbohydrates / administration & dosage
  • Dietary Fats / administration & dosage
  • Dietary Proteins / administration & dosage*
  • Energy Intake / physiology*
  • Energy Metabolism
  • Female
  • Humans
  • Hunger / physiology
  • Linear Models
  • Male
  • Meals
  • Middle Aged
  • Single-Blind Method
  • Young Adult


  • Biomarkers
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins

Associated data