Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers

Jennifer Miao, Katherine N Bachmann, Shi Huang, Yan Ru Su, Jeffery Dusek, Christopher Newton-Cheh, Pankaj Arora, Thomas J Wang, Jennifer Miao, Katherine N Bachmann, Shi Huang, Yan Ru Su, Jeffery Dusek, Christopher Newton-Cheh, Pankaj Arora, Thomas J Wang

Abstract

Background Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids. Methods and Results This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs-CRP (high-sensitivity C-reactive protein), N-terminal pro-B-type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25-hydroxyvitamin-D [25-OH-D] ≤25 ng/mL) receiving low-dose (400 IU/d) versus high-dose (4000 IU/d) vitamin D3 for 6 months. A meta-analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25-OH-D increased in the high-dose relative to the low-dose vitamin D group (+15.5 versus +4.6 ng/mL, P<0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high-dose compared with the low-dose group (+11.3 versus -6.2 mg/dL, P<0.001). The meta-analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs-CRP, but no changes in low-density lipoprotein, after vitamin D supplementation compared with control groups. Conclusions In the DAYLIGHT randomized controlled trial, high-dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01240512.

Keywords: high‐sensitivity C‐reactive protein; insulin resistance; lipids; meta‐analysis; vitamin D.

Conflict of interest statement

Dr Wang reports consultant fees from DiaSorin before 2014. Dr Bachmann owns stock in Medtronic, unrelated to the current project. The remaining authors have no disclosures to report.

Figures

Figure 1. Circulating biomarkers in groups receiving…
Figure 1. Circulating biomarkers in groups receiving low‐dose (400 IU/d) or high‐dose (4000 IU/d) vitamin D supplementation over 6 months.
Mean change ±1 standard error in 25‐hydroxyvitamin D (25‐OH‐D; A), high‐sensitivity C‐reactive protein (hs‐CRP; B), homeostatic model assessment of insulin resistance (HOMA‐IR; C), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; D), total cholesterol (E), low‐density lipoprotein (LDL; F), and triglycerides (G) in the high‐dose and low‐dose vitamin D supplementation groups are reported.
Figure 2. Forest plots comparing effect size…
Figure 2. Forest plots comparing effect size for vitamin D supplementation on changes in biomarkers for studies included in the meta‐analysis.
Changes in low‐density lipoprotein (LDL; A), homeostatic model assessment of insulin resistance (HOMA‐IR; B), and high‐sensitivity C‐reactive protein (hs‐CRP; C) are reported. The gray boxes correspond with study precision, and the lines denote 95% CIs. Studies are ordered by the cumulative vitamin D dose delivered during the course of the study (vitamin D dose×duration), from lowest to highest. The asterisks and plus sign denote combinations of vitamin D with or without calcium supplementation for two different treatment arms enrolled in the same RCT. Asemi* indicates vitamin D 50 000 IU weekly+calcium 1000 mg daily whilst Asemi+ group received vitamin D 50 000 IU weekly; Foroozanfard*, vitamin D 4000 IU daily; Foroozanfard+, vitamin D 1000 IU daily; and MD, mean difference. References: Foroozanfard+ 2017, 11 Yousefi Rad 2014, 12 Ghaderi 2017, 13 Maktabi 2017, 14 Tabassi 2017, 15 Foroozanfard* 2017, 11 Ryu 2014, 16 Sepehrmanesh 2016, 17 Asemi+ 2015, 18 Asemi * 2015, 18 Dastorani 2018, 19 Ponda 2012, 20 Dalan 2016, 21 Rajpathak 2010, 10 Raja‐Khan 2014, 22 Sollid 2014, 23 Jorde 2009, 24 Zittermann 2009, 25 Angelloti 2019, 26 Jamilian 2017, 27 Osati 2016, 28 Seyyed 2018, 29 Maktabi 2018, 30 Mousa 2017, 31 and Zheng 2018. 32

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Source: PubMed

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