University of Oulu

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, Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study, The American Journal of Clinical Nutrition, Volume 111, Issue 5, May 2020, Pages 1036–1047,

Could vitamin D reduce obesity-associated inflammation? : observational and Mendelian randomization study

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Author: Palaniswamy, Saranya1,2,3; Gill, Dipender3; De Silva, N. Maneka3;
Organizations: 1Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Department of Epidemiology and Biostatistics, School of Public Health, MRC Centre for Environment and Health, Imperial College London, London, United Kingdom
4Unit of Primary Care, Oulu University Hospital, Oulu, Finland
5Institute of Biomedicine, Medical Research Center, University of Oulu, and Oulu University Hospital, Oulu, Finland
6Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
7Preventive Medicine Division, Brighamand Women’s Hospital, Harvard Medical School, Boston, MA, USA
8Institute of Clinical Medicine/Psychiatry, University of Eastern Finland, Kuopio, Finland; and Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
9Australian Centre for Precision Health, South Australian Cancer Researc hInstitute, University of South Australia, Adelaide, Australia
10South Australian Health and Medical Research Institute, Adelaide, Australia
11Departmentof Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
12Department of Genomics of Complex Diseases, School of Public Health, Imperial College London, London, United Kingdom
13Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, United Kingdom
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
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Language: English
Published: Oxford University Press, 2020
Publish Date: 2020-07-06


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.

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Series: American journal of clinical nutrition
ISSN: 0002-9165
ISSN-E: 1938-3207
ISSN-L: 0002-9165
Volume: 111
Issue: 5
Pages: 1036 - 1047
DOI: 10.1093/ajcn/nqaa056
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3141 Health care science
Funding: This research was supported by the Academy of Finland grant numbers 24300796, 24302031, 285547 (EGEA); the Medical Research Council (MRC) UK (grant number G0601653); Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE (Nutrition & Epigenome, The Joint Programming Initiative a Healthy Diet for a Healthy Life (JPI HDHL/EU-H2020)); the National Health and Medical Research Council, Australia (grant number APP1123603); Biocenter Oulu Doctoral Program, Juho Vainio Foundation, Orion Research Foundation sr, Emil Aaltonen Foundation, Finnish Cultural Foundation, Yrjö Jahnsson Foundation, Päivikki and Sakari Sohlberg Foundation sr; the European Union's Horizon 2020 programmes, DynaHEALTH (grant number 633595), LifeCycle (grant number 733206), and iHealth-T2D (grant number 643774); and the Wellcome 4i Clinical PhD Program at Imperial College London. No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors do not have the authority to make data public.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
(643774) iHealth-T2D - Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact