A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects

Am J Clin Nutr. 2011 Apr;93(4):748-55. doi: 10.3945/ajcn.110.002758. Epub 2011 Jan 26.


Background: High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations.

Objective: We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects.

Design: Men (n = 16) aged 22 ± 1 y (mean ± SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 ± 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 ± 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac (31)P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively.

Results: Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P < 0.05), 9% lower cardiac PCr/ATP (P < 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P < 0.01), speed (P < 0.001), and mood (P < 0.01) after the high-fat, low-carbohydrate diet.

Conclusion: Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Affect / drug effects
  • Attention / drug effects
  • Cognition / drug effects*
  • Cross-Over Studies
  • Diet, Carbohydrate-Restricted / psychology
  • Dietary Carbohydrates / pharmacology
  • Dietary Fats / adverse effects*
  • Echocardiography
  • Energy Intake
  • Energy Metabolism / drug effects*
  • Fatty Acids, Nonesterified / blood*
  • Heart / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Phosphocreatine / metabolism*
  • Reference Values
  • Young Adult


  • Dietary Carbohydrates
  • Dietary Fats
  • Fatty Acids, Nonesterified
  • Phosphocreatine
  • Adenosine Triphosphate