Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Nutr Diabetes. 2018 Mar 7;8(1):11. doi: 10.1038/s41387-018-0020-6.


Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic-hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport.

Publication types

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

MeSH terms

  • Bile Acids and Salts / blood*
  • Body Mass Index*
  • Diet*
  • Dietary Fiber / administration & dosage
  • Dietary Fiber / pharmacology*
  • Dietary Proteins / administration & dosage
  • Dietary Proteins / pharmacology*
  • Edible Grain
  • Energy Intake
  • Fasting
  • Female
  • Fibroblast Growth Factors / blood
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Milk Proteins / administration & dosage
  • Milk Proteins / pharmacology
  • Obesity / blood*
  • Obesity / complications
  • Overweight


  • Bile Acids and Salts
  • Dietary Fiber
  • Dietary Proteins
  • FGF19 protein, human
  • Insulin
  • Milk Proteins
  • Fibroblast Growth Factors