Short-Term Isocaloric Intake of a Fructose- but not Glucose-Rich Diet Affects Bacterial Endotoxin Concentrations and Markers of Metabolic Health in Normal Weight Healthy Subjects

Mol Nutr Food Res, 2019; //doi: 10.1002/mnfr.201800868

Nier A, Brandt A, Rajcic D, et al.

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  • To determine if an isocaloric exchange of complex carbohydrates with fructose or glucose affects surrogate markers of liver health and vascular endothelial function in healthy normal weight young male and female adults. If so, the goal is to whether these effects are related to changes in markers of intestinal permeability like bacterial endotoxin and lipopolysaccharide binding protein (LBP).


  • Dietary pattern and impairments of intestinal barrier function are thought to be critical in the development of metabolic impairments.
  • Results of animal studies employing pair-feeding models also suggest that consumption of fructose, particularly in combination with saturated fat, may be critical in the development of NAFLD, vascular dysfunction and hypertension.
  • However, results of short-term intervention studies in healthy humans show contradictory results regarding the effects of fructose on liver, which may be due marked differences in study design and duration. Further, data on the effects on vascular endothelium in humans to our knowledge are lacking. 


  • A total of 15 normal weight healthy subjects were enrolled in the study, and after three participants dropped out, only 12 subjects were included in the final analysis.
  • All participants received a standardized diet for 4 days, which was based their individual caloric needs and the recommendations of the German Society of Nutrition. This was followed by a diet in which complex carbohydrates were either exchanged with fructose or glucose (25% of total energy intake) for 3 days.
  • All participants analyzed consumed both sugar-enriched diets after being dietary standardized for 4 days starting with the fructose intervention. Sugar interventions were separated by a washout period of at least 3 weeks during which all participants consumed their usual diet.
  • Nutritional intake was assessed using two independent 24-h recalls conducted by an experienced nutritionist before the study.  Physical activity level was assessed using the World Health Organization’s Global Physical Activity Questionnaire.  Nutritional data and total energy expenditure were analyzed using the computer software EBISpro.
  • Fasting blood samples, anthropometric data and blood pressure were assessed at the beginning of the study, after consuming the standard diets and after the intervention periods.
  • Peripheral blood mononuclear cells (PBMCs), plasma endotoxin, liver transaminase and blood lipid concentrations were analyzed.


  • Following diet standardization, serum triglycerides and insulin levels increased significantly, while alanine aminotransferase (ALT) serum activity and bacterial endotoxin levels decreased.
  • Fasting insulin, glucose and triglyceride levels were not affected by either intervention diet.  Uric acid levels significantly decreased following the high glucose diet.
  • Plasma NOx levels, which are indicative of vascular endothelial dysfunction, were significantly lower after subjects had consumed the fructose-enriched diet for 3 days. This effect was not seen after subjects consumed the glucose-enriched diet.
  • ALT activity significantly increased after subjects consumed the fructose-enriched diet, as compared to the diet standardization phase. This effect was not seen after subjects consumed the glucose-enriched diet, and Aspartate aminotransferase (AST) activity was not altered by any of the dietary interventions.
  • Leptin and adiponection plasma concentrations were not affected by any of the diets, and non-significant increases in PAI-1 were noted following the consumption of the fructose-rich diet compared to the standard diet.
  • Plasma endotoxin concentrations increased significantly when subjects consumed the fructose-enriched diet for 3 days compared to the respective standard diet.  This effect was not seen after subjects consumed the glucose-enriched diet.  Plasma concentrations of LBP, d-lactate and l-citrulline levels were not changed after the consumption of either diet.
  • Expressions of TLR4, TLR2 and MYD88 mRNA in PBMCs were significantly increased after subjects had consumed the fructose-enriched diet but not after subjects received the glucose-enriched diets as compared to standard diet.


  • According to the authors, the results of this study may provide additional support of the  hypothesis that dietary fructose may be critical in the development of NAFLD and vascular endothelial dysfunction in humans and that, similar to the findings in animal studies, impairments of intestinal barrier function and an increased translocation of bacterial endotoxin may be critical.
  • Results of the present study suggest that at short-term glucose may not have these effects on parameters related to liver and vascular endothelial as well as intestinal barrier function.
  • Results of the present study also suggest that changing dietary pattern only for a few days may markedly impact liver, vascular endothelial and intestinal barrier function. However, molecular mechanisms involved and especially those underlying the effects of fructose on intestinal barrier function need to be determined in future studies.

Points to Consider

  • The small study sample and the inclusion of only young, healthy adults limits the generalization of this study’s findings.
  • Direct measurement of intestinal permeability and liver health was not included in the present study, as each was assessed via surrogate markers.
  • All study food and beverages were provided, mostly prepared and consumed in the study center. This does not reflect real-world experience and results would likely differ in a more realistic setting.