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The metabolic signature of salt intake : a cross-sectional analysis from the SCAPIS-study

Wuopio, Jonas ; Yi-Ting, Lin ; Dekkers, Koen F. ; Fall, Tove ; Smith, J. Gustav LU orcid ; Larsson, Anders ; Engström, Gunnar LU ; Orho-Melander, Marju LU ; Johnson, Linda S. LU and Ärnlöv, Johan (2025) In Nutrition and Metabolism 22(1).
Abstract

Background: Untargeted metabolomic analysis provides novel insights into the relationship between sodium intake and cardiometabolic risk. This study examined cross-sectional associations between estimated sodium intake and plasma metabolite profiles in a large Swedish cohort. Methods: This cross-sectional analysis was conducted in the in the SCAPIS cohort (mean age 50–64 years, n = 8,957). Sodium intake was estimated using the Kawasaki formula (est24hNa) from urine samples. Plasma metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) (Metabolon Inc®), identifying 713 metabolites grouped into eight biochemical classes (CC). Principal component analysis (PCA) was... (More)

Background: Untargeted metabolomic analysis provides novel insights into the relationship between sodium intake and cardiometabolic risk. This study examined cross-sectional associations between estimated sodium intake and plasma metabolite profiles in a large Swedish cohort. Methods: This cross-sectional analysis was conducted in the in the SCAPIS cohort (mean age 50–64 years, n = 8,957). Sodium intake was estimated using the Kawasaki formula (est24hNa) from urine samples. Plasma metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) (Metabolon Inc®), identifying 713 metabolites grouped into eight biochemical classes (CC). Principal component analysis (PCA) was conducted for each CC, and the first principal component (PC1) was used as the response variable, with est24hNa, age, sex, and cardiovascular risk factors as predictors in restricted cubic spline models. ANOVA and pathway enrichment analyses were performed to explore associations. Results: Est24hNa was significantly associated with the lipid and energy CC. Lower est24hNa was linked to higher concentrations of free fatty acids and citric acid cycle intermediates, suggesting enhanced beta-oxidation. Bonferroni-adjusted analyses revealed 231 metabolites significantly associated with est24hNa, with 2 S,3R-dihydroxybutyrate (β = -0.13, p = 2.28 × 10− 37) showing the strongest association. Lipid subgroups including phosphatidylcholines, lysophospholipids, bile acids, and plasmalogens were positively associated with est24hNa. Pathway enrichment suggested links to branched-chain amino acid metabolism and biosynthesis of unsaturated fatty acids. Conclusions: Lower salt intake was associated with a metabolic profile indicative of increased beta-oxidation, while higher salt intake was linked to lipid species previously implicated in atherosclerosis. These findings highlight potential metabolic pathways through which salt intake may influence cardiovascular health and merit further evaluation in longitudinal studies.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular disease, Metabolism, Metabolomics, Prevention, Salt, Sodium
in
Nutrition and Metabolism
volume
22
issue
1
article number
104
publisher
Karger
external identifiers
  • scopus:105015068031
  • pmid:40898250
ISSN
0250-6807
DOI
10.1186/s12986-025-00997-y
language
English
LU publication?
yes
id
f75cf6e5-e134-4d61-b861-59cdb20c8c84
date added to LUP
2025-10-02 14:47:32
date last changed
2025-10-16 16:41:36
@article{f75cf6e5-e134-4d61-b861-59cdb20c8c84,
  abstract     = {{<p>Background: Untargeted metabolomic analysis provides novel insights into the relationship between sodium intake and cardiometabolic risk. This study examined cross-sectional associations between estimated sodium intake and plasma metabolite profiles in a large Swedish cohort. Methods: This cross-sectional analysis was conducted in the in the SCAPIS cohort (mean age 50–64 years, n = 8,957). Sodium intake was estimated using the Kawasaki formula (est24hNa) from urine samples. Plasma metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) (Metabolon Inc<sup>®</sup>), identifying 713 metabolites grouped into eight biochemical classes (CC). Principal component analysis (PCA) was conducted for each CC, and the first principal component (PC1) was used as the response variable, with est24hNa, age, sex, and cardiovascular risk factors as predictors in restricted cubic spline models. ANOVA and pathway enrichment analyses were performed to explore associations. Results: Est24hNa was significantly associated with the lipid and energy CC. Lower est24hNa was linked to higher concentrations of free fatty acids and citric acid cycle intermediates, suggesting enhanced beta-oxidation. Bonferroni-adjusted analyses revealed 231 metabolites significantly associated with est24hNa, with 2 S,3R-dihydroxybutyrate (β = -0.13, p = 2.28 × 10<sup>− 37</sup>) showing the strongest association. Lipid subgroups including phosphatidylcholines, lysophospholipids, bile acids, and plasmalogens were positively associated with est24hNa. Pathway enrichment suggested links to branched-chain amino acid metabolism and biosynthesis of unsaturated fatty acids. Conclusions: Lower salt intake was associated with a metabolic profile indicative of increased beta-oxidation, while higher salt intake was linked to lipid species previously implicated in atherosclerosis. These findings highlight potential metabolic pathways through which salt intake may influence cardiovascular health and merit further evaluation in longitudinal studies.</p>}},
  author       = {{Wuopio, Jonas and Yi-Ting, Lin and Dekkers, Koen F. and Fall, Tove and Smith, J. Gustav and Larsson, Anders and Engström, Gunnar and Orho-Melander, Marju and Johnson, Linda S. and Ärnlöv, Johan}},
  issn         = {{0250-6807}},
  keywords     = {{Cardiovascular disease; Metabolism; Metabolomics; Prevention; Salt; Sodium}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Karger}},
  series       = {{Nutrition and Metabolism}},
  title        = {{The metabolic signature of salt intake : a cross-sectional analysis from the SCAPIS-study}},
  url          = {{http://dx.doi.org/10.1186/s12986-025-00997-y}},
  doi          = {{10.1186/s12986-025-00997-y}},
  volume       = {{22}},
  year         = {{2025}},
}