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

• Published in: The American Journal of Clinical Nutrition
• Main Authors: Palaniswamy, Saranya, Gill, Dipender, De Silva, N Maneka, Lowry, Estelle, Jokelainen, Jari, Karhu, Toni, Mutt, Shivaprakash J, Dehghan, Abbas, Sliz, Eeva, Chasman, Daniel I, Timonen, Markku, Viinamäki, Heimo, Keinänen-Kiukaanniemi, Sirkka, Hyppönen, Elina, Herzig, Karl-Heinz, Sebert, Sylvain, Järvelin, Marjo-Riitta
• Other Authors: Academy of Finland, EGEA, Medical Research Council, The Joint Programming Initiative a Healthy Diet for a Healthy Life, National Health and Medical Research Council, Orion Research Foundation, Emil Aaltonen Foundation, Finnish Cultural Foundation, Yrjö Jahnsson Foundation, Päivikki and Sakari Sohlberg Foundation, European Union's Horizon 2020 programmes
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2020
• Subjects: Nutrition and Dietetics; Medicine (miscellaneous); Northern Finland
• Online Access: http://dx.doi.org/10.1093/ajcn/nqaa056; http://academic.oup.com/ajcn/article-pdf/111/5/1036/38693901/nqaa056.pdf

ABSTRACT 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 ...