High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health

Am J Clin Nutr. 2011 May;93(5):1062-72. doi: 10.3945/ajcn.110.002188. Epub 2011 Mar 9.


Background: Diets that are high in protein but reduced in carbohydrate contents provide a common approach for achieving weight loss in obese humans. However, the effect of such diets on microbiota-derived metabolites that influence colonic health has not been established.

Objective: We designed this study to assess the effect of diets with reduced carbohydrate and increased protein contents on metabolites considered to influence long-term colonic health, in particular the risk of colorectal disease.

Design: We provided 17 obese men with a defined weight-maintenance diet (85 g protein, 116 g fat, and 360 g carbohydrate/d) for 7 d followed by 4 wk each of a high-protein and moderate-carbohydrate (HPMC; 139 g protein, 82 g fat, and 181 g carbohydrate/d) diet and a high-protein and low-carbohydrate (HPLC; 137 g protein, 143 g fat, and 22 g carbohydrate/d) diet in a crossover design. Fecal samples were analyzed to determine concentrations of phenolic metabolites, short-chain fatty acids, and nitrogenous compounds of dietary and microbial origin.

Results: Compared with the maintenance diet, the HPMC and HPLC diets resulted in increased proportions of branched-chain fatty acids and concentrations of phenylacetic acid and N-nitroso compounds. The HPLC diet also decreased the proportion of butyrate in fecal short-chain fatty acid concentrations, which was concomitant with a reduction in the Roseburia/Eubacterium rectale group of bacteria, and greatly reduced concentrations of fiber-derived, antioxidant phenolic acids such as ferulate and its derivatives.

Conclusions: After 4 wk, weight-loss diets that were high in protein but reduced in total carbohydrates and fiber resulted in a significant decrease in fecal cancer-protective metabolites and increased concentrations of hazardous metabolites. Long-term adherence to such diets may increase risk of colonic disease.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antioxidants / analysis
  • Carcinogens / analysis
  • Colonic Diseases / epidemiology
  • Cross-Over Studies
  • Diet, Carbohydrate-Restricted / adverse effects*
  • Diet, Reducing / adverse effects*
  • Dietary Fiber / administration & dosage
  • Dietary Fiber / metabolism
  • Dietary Proteins / adverse effects*
  • Dietary Proteins / metabolism
  • Eubacterium / growth & development
  • Eubacterium / isolation & purification
  • Fatty Acids, Volatile / analysis
  • Fatty Acids, Volatile / chemistry
  • Feces / chemistry
  • Feces / microbiology
  • Humans
  • Male
  • Middle Aged
  • Nitroso Compounds / analysis
  • Obesity / complications
  • Obesity / diet therapy*
  • Phenols / analysis
  • Phenylacetates / analysis
  • Phenylacetates / chemistry
  • Risk
  • Young Adult


  • Antioxidants
  • Carcinogens
  • Dietary Fiber
  • Dietary Proteins
  • Fatty Acids, Volatile
  • Nitroso Compounds
  • Phenols
  • Phenylacetates
  • phenylacetic acid