Effects of a 2-y dietary weight-loss intervention on cholesterol metabolism in moderately obese men

Am J Clin Nutr. 2011 Nov;94(5):1189-95. doi: 10.3945/ajcn.111.018119. Epub 2011 Sep 21.


Background: Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear.

Objective: We assessed the effects of 2 y of weight loss achieved with various diet regimens on phytosterols (markers of intestinal cholesterol absorption), lanosterol (marker of de novo cholesterol synthesis), and changes in apolipoprotein concentrations.

Design: We conducted the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low-carbohydrate diets). We assessed circulating phytosterol and lanosterol concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100 in 90 DIRECT participants at 0, 6, and 24 mo.

Results: We observed a significant upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P < 0.001) and a downregulation of the markers of cholesterol synthesis (lanosterol: -16.5%, P = 0.008) during the active weight-loss phase (first 6 mo, weight loss of 5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P < 0.001) during the next 18 mo (weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL cholesterol continuously increased during the study (17.0%, P < 0.001), whereas LDL cholesterol remained constant. At the end of the 24-mo follow-up period, campesterol (P < 0.001) and lanosterol (P = 0.016) amounts were significantly higher than baseline values. The concentration of apolipoprotein B-100 correlated with cholesterol metabolism (ρ = 0.299 and P = 0.020 for lanosterol; ρ = -0.105 and NS for campesterol), and the homeostasis model assessment of insulin resistance correlated with lanosterol (ρ = 0.09, P = 0.001).

Conclusions: Long-term weight loss is related to a characteristic response suggestive of altered cholesterol and apolipoprotein metabolism. Various diets have a similar effect on these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.

Publication types

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

MeSH terms

  • Adult
  • Apolipoprotein A-I / blood
  • Apolipoprotein B-100 / blood
  • Body Weight / physiology
  • Cholesterol / metabolism*
  • Diet, Reducing / methods*
  • Diet, Reducing / standards
  • Humans
  • Lanosterol / blood
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / diet therapy*
  • Obesity / metabolism*
  • Phytosterols / blood
  • Statistics, Nonparametric
  • Weight Loss / physiology*


  • Apolipoprotein A-I
  • Apolipoprotein B-100
  • Phytosterols
  • Lanosterol
  • Cholesterol

Associated data

  • ClinicalTrials.gov/NCT00160108