University of Oulu

Gürdeniz, G., Uusitupa, M., Hermansen, K., Savolainen, M. J., Schwab, U., Kolehmainen, M., Brader, L., Cloetens, L., Herzig, K.-H., Hukkanen, J., Rosqvist, F., Ulven, S. M., Gunnarsdóttir, I., Thorsdottir, I., Oresic, M., Poutanen, K. S., Risérus, U., Åkesson, B., & Dragsted, L. O. (2022). Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids. Clinical Nutrition, 41(2), 441–451.

Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids

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Author: Gürdeniz, Gözde1,2; Uusitupa, Matti3; Hermansen, Kjeld4;
Organizations: 1Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
2Department of Food Science, University of Copenhagen, Frederiksberg, Denmark
3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
5Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland
6Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
7Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden
8Institute of Biomedicine and Biocenter of Oulu, University of Oulu, Finland
9Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
10Department of Public Health and Caring Sciences, Uppsala University, Sweden
11Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
12Unit for Nutrition Research, Faculty of Food Science and Nutrition, University of Iceland, Reykjavík, Iceland
13Unit for Nutrition Research, Landspitali National University Hospital, Reykjavik, Iceland
14Turku Center for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
15VTT Technical Research Centre of Finland, Espoo, Finland
16Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Elsevier, 2022
Publish Date: 2022-08-18


Background & aims: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers.

Methods: During 18–24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g.whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers.

Results: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = −0.06; 95% CI: −0.09, −0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol.

Conclusions: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials.

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Series: Clinical nutrition
ISSN: 0261-5614
ISSN-E: 1532-1983
ISSN-L: 0261-5614
Volume: 41
Issue: 2
Pages: 441 - 451
DOI: 10.1016/j.clnu.2021.12.031
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
Funding: Systems biology in controlled dietary interventions and cohort studies (SYSDIET) is one of the three projects in the Nordic Centre of Excellence Programme on Food, Nutrition and Health nominated and funded by NordForsk for years 2007–2012 (SYSDIET; 070014). The SYSDIET intervention was also funded by the Academy of Finland, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, The Sigfrid Juselius Foundation, and EVO funding from Kuopio University Hospital (Finland); the Druvan Foundation, ESPEN, Skåne County Council Research and Development Foundation, The Heart-Lung Foundation, Diabetesfonden, and Foundation Cerealia (Sweden), The Danish Obesity Research Centre (DanORC,, The Danish Council for Strategic Research (DairyHealth, BioFunCarb, FoodBAll) (Denmark), The Agricultural Productivity Fund, The Research Fund of the University of Iceland (Iceland). The metabolomics analysis was supported by a Semper Ardens grant on biomarkers from the Carlsberg Foundation to LOD.
Copyright information: © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (