Dietary carbohydrate quality and health : focus on low-grade systemic inflammation and cardiometabolic risk factors

Dietary carbohydrate quality, characterized by content of whole grain (WG), dietary fiber, and sugars, is important for human health. Whole grain consumption and cereal fiber can reduce the risk of chronic disorders such as cardiovascular disease (CVD) and type 2 diabetes, an effect partly mediated by alterations in cardiometabolic risk factors and low-grade systemic inflammation. High-fructose or high-galactose diets may trigger pro-inflammatory and negative metabolic effects, but fermentable dietary fiber, e.g., fructooligosaccharides (FOS), may mitigate these effects. This thesis examined the effect of dietary carbohydrate quality, characterized by intake of specific WGs and sugars, on low-grade systemic inflammation and cardiometabolic risk factors. In particular, it evaluated: 1) associations between long-term WG rye or wheat intake and inflammatory, endothelial function, and CVD risk-related biomarkers; 2) alkylresorcinols (AR) in adipose tissue as potential biomarkers of long-term WG intake; 3) effects of WG/bran rye and refined wheat on inflammatory and endothelial function biomarkers in individuals with low-grade prostate cancer; and effects of high fructose and galactose intake, with or without added FOS, on 4) selected metabolic factors and inflammatory and gut permeability biomarkers; and 5) modulation of gut microbiota in rats.

Data and samples from two prospective cohort studies, Swedish Mammography Cohort-Clinical (SMC-C) (n=109) and Cohort of Swedish Men-Clinical (COSM-C) (n=149), were used to analyze associations between long-term WG intake and selected biomarkers of inflammation, endothelial function, and metabolic factors. WG intake was assessed by food frequency questionnaires and using alkylresorcinols (AR) in plasma and adipose tissue as biomarkers. Combined WG rye and WG wheat intake was positively associated with cathepsin S, while total AR in plasma was inversely associated with endostatin (adjusted for age, sex, and BMI). Long-term WG rye intake was modestly correlated (r=0.31-0.41) with AR in adipose tissue, whereas WG wheat was poorly correlated (r=0.17-0.33) over 14 years for men and 17 years for women. The effect of WG/bran rye on selected inflammatory biomarkers was explored in a dietary intervention cross-over study of 17 men with low-grade prostate cancer. TNF-R2, e-selectin, and endostatin were significantly lower in these men after consumption of WG/bran rye products than consumption of refined wheat with added cellulose. In an animal study with rats (n=6/group and time point) fed a high-fructose or high-galactose diet, with/without added FOS, or three control diets for six or 12 weeks, the intervention diets affected several metabolic factors and gut integrity markers, but not inflammation biomarkers. High-fructose and high-galactose diets did not cause substantial changes in gut microbiota composition, but addition of FOS favored the genus Bifidobacterium. Gut microbiota was associated with several metabolic and inflammation biomarkers.

These results suggest that WG wheat and rye may have positive impacts on some inflammation biomarkers. Fructose and particularly galactose had adverse metabolic effects in rats, but no obvious effect on inflammation markers. Sugars did not markedly affect gut microbiota composition in rats.

List of scientific papers

I. Nor Adila Mhd Omar, Huaxing Wu, Anders Larsson, Alicja Wolk, Rikard Landberg. Long term whole grain rye and wheat consumption and their associations with selected biomarkers of inflammation, endothelial function and cardiovascular disease. European Journal of Clinical Nutrition. 2020.
https://doi.org/10.1038/s41430-020-00714-3

II. Huaxing Wu, Nor Adila Mhd Omar, Niclas Håkansson, Alicja Wolk, Karl Michaëlsson and Rikard Landberg. Evaluation of alkylresorcinols in adipose tissue biopsies as a long-term biomarker of whole-grain wheat and rye intake in free-living Swedish men and women. Public Health Nutrition. 2018; 21(10), 1933-1942.
https://doi.org/10.1017/S1368980018000484

III. Galia Zamaratskaia, Nor Adila Mhd Omar, Carl Brunius, Göran Hallmans, Jan-Erik Johansson, Sven-Olof Andersson, Anders Larsson, Per Åman, Rikard Landberg. Consumption of whole grain/bran rye instead of refined wheat decrease concentrations of TNF-R2, e-selectin, and endostatin in an exploratory study in men with prostate cancer. Clinical Nutrition. 2019.
https://doi.org/10.1016/j.clnu.2019.01.007

IV. Nor Adila Mhd Omar, Jan Frank, Johanita Kruger, Federica Dal Bello, Claudio Medana, Massimo Collino, Galia Zamaratskaia, Karl Michaëlsson, Alicja Wolk, Rikard Landberg. Effects of high intake of fructose and galactose with or without added fructooligosaccharides on metabolic factors, inflammation and gut integrity in a rat model. [Submitted]

V. Nor Adila Mhd Omar, Johan Dicksved, Johanita Kruger, Galia Zamaratskaia, Karl Michaëlsson, Alicja Wolk, Jan Frank, Rikard Landberg. Effect of a diet rich in galactose or fructose with or without fructooligosaccharides on gut microbiota consumption in rats. [Submitted]