Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans

J Clin Endocrinol Metab. 2015 Jun;100(6):2291-302. doi: 10.1210/jc.2014-3868. Epub 2015 Mar 30.


Context: The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms.

Objective: We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans.

Design: Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data.

Results: The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes.

Conclusions: Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.

Trial registration: NCT01631123.

Publication types

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

MeSH terms

  • Brain / drug effects
  • Brain / physiology
  • CLOCK Proteins / genetics
  • Carbohydrate Metabolism / drug effects
  • Circadian Clocks / drug effects*
  • Circadian Clocks / genetics
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics
  • Diet, Carbohydrate-Restricted
  • Diet, Fat-Restricted
  • Diet, High-Fat
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrocortisone / metabolism
  • Lipid Metabolism / drug effects
  • Monocytes / drug effects
  • Monocytes / metabolism


  • Dietary Carbohydrates
  • Dietary Fats
  • CLOCK Proteins
  • Hydrocortisone

Associated data