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

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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. Am J Clin Nutr 2011;93:1062-72.

Original languageEnglish
Pages (from-to)1062-1072
Number of pages11
JournalThe American Journal of Clinical Nutrition
Issue number5
Early online date9 Mar 2011
Publication statusPublished - May 2011

Bibliographical note

DA - 20110310 IS - 1938-3207 (Electronic) IS - 0002-9165 (Linking) LA - ENG PT - JOURNAL ARTICLE


  • in-situ hybridization
  • chain fatty-acids
  • targeted oligonucleotide probes
  • butyrate-producing bacteria
  • N-nitroso compounds
  • large-bowel cancer
  • colorectal-cancer
  • red meat
  • endogenous formation
  • phenolic compounds


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