Could Vitamin D reduce obesity-Associated inflammation? Observational and Mendelian randomization study

Saranya Palaniswamy, Dipender Gill, N. Maneka De Silva, Estelle Lowry, Jari Jokelainen, Toni Karhu, Shivaprakash J. Mutt, Abbas Dehghan, Eeva Sliz, Daniel I. Chasman, Markku Timonen, Heimo Viinamäki, Sirkka Keinänen-Kiukaanniemi, Elina Hyppönen, Karl Heinz Herzig, Sylvain Sebert, Marjo Riitta Järvelin

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5 Citations (Scopus)


Background: Obesity is associated with inflammation but the role of vitamin D in this process is not clear. Objectives: We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. Methods: Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-Acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. Results: In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. Conclusions: The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

Original languageEnglish
Pages (from-to)1036-1047
Number of pages12
JournalAmerican Journal of Clinical Nutrition
Issue number5
Publication statusPublished or Issued - 1 May 2020


  • 25(OH)D
  • BMI
  • Mendelian randomization
  • Vitamin D
  • inflammation
  • mediation
  • obesity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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