Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET)

Marjo Tuomainen*, Olli Kärkkäinen, Jukka Leppänen, Seppo Auriola, Marko Lehtonen, Markku J. Savolainen, Kjeld Hermansen, Ulf Risérus, Björn Åkesson, Inga Thorsdottir, Marjukka Kolehmainen, Matti Uusitupa, Kaisa Poutanen, Ursula Schwab, Kati Hanhineva

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Background: Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet. Objectives: The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study. Methods: The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health. Results: Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P = 0.00032) at the end of the intervention and correlated directly (P < 0.0001) with intakes of dietary fiber (r = 0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r = 0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P < 0.001, r = -0.300; P < 0.01, r = -0.250, respectively), as well as IL-1 receptor antagonist (P < 0.01, r = -0.232 at the beginning; P < 0.01, r = -0.236 at the end) and serum LDL/HDL cholesterol (P < 0.01, r = -0.239 at the beginning; P < 0.01, r = -0.241 at the end). Conclusions: Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds. This trial was registered at clinicaltrials.gov as NCT00992641.

Original languageEnglish
Pages (from-to)1108-1118
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Issue number5
Publication statusPublished - 1 Nov 2019

Bibliographical note

Supported by the Academy of Finland (to K Hanhineva), Biocenter Finland (to K Hanhineva), Biocenter Kuopio (to SA and ML), and the Lantmännen Research Foundation (to K Hanhineva). Systems biology in controlled dietary interventions and cohort studies (SYSDIET) was 1 of the 3 projects in the Nordic Centre of Excellence Programme on Food, Nutrition and Health nominated and funded by NordForsk for the years 2007-2012 (SYSDIET; 070014). The intervention study 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, www.danorc.dk), The Danish Council for Strategic Research (Dairy-Health, BioFunCarb) (Denmark); The Agricultural Productivity Fund, The Research Fund of the University of Iceland (Iceland). The food products for the study participants were provided by the following companies: Kesko Food Ltd, Raisio Group (Finland); Belico Food AB, Fazer Bageri Sverige, Lantmännen, Oatly AB, Olle Svensson AB, Procordia Food AB, Pågen AB, Unilever, Wasabröd AB (Sweden); Lantmännen Food R&D, Jan Import A/S, Ardo A/S, Scandic Food A/S, WASA, Glyngøre Limfjord A/S, Royal Greenland A/S, Arla Foods (Denmark); The Mother Earth Farm at Vallanes (Iceland); and Unilever Nordic (Sweden, Denmark, Iceland).

Publisher Copyright:
Copyright © American Society for Nutrition 2019.

Other keywords

  • betainized compounds
  • fiber
  • healthy Nordic diet
  • pipecolic acid betaine
  • quantitative
  • rye
  • whole grain


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