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Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials

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Abstract

Background

In addition to regulating calcium homoeostasis and bone health, vitamin D influences vascular and metabolic processes including endothelial function (EF) and insulin signalling. This systematic review and meta-analysis of randomised clinical trials (RCTs) were conducted to investigate the effect of vitamin D supplementation on EF and to examine whether the effect size was modified by health status, study duration, dose, route of vitamin D administration, vitamin D status (baseline and post-intervention), body mass index (BMI), age and type of vitamin D.

Methods

We searched the Medline, Embase, Cochrane Library and Scopus databases from inception until March 2015 for studies meeting the following criteria: (1) RCT with adult participants, (2) vitamin D administration alone, (3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography, applanation tonometry and laser Doppler.

Results

Sixteen articles reporting data for 1177 participants were included. Study duration ranged from 4 to 52 weeks. The effect of vitamin D on EF was not significant (SMD: 0.08, 95 % CI −0.06, 0.22, p = 0.28). Subgroup analysis showed a significant improvement of EF in diabetic subjects (SMD: 0.31, 95 % CI 0.05, 0.57, p = 0.02). A non-significant trend was found for diastolic blood pressure (β = 0.02; p = 0.07) and BMI (β = 0.05; p = 0.06).

Conclusions

Vitamin D supplementation did not improve EF. The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function. This remains to be tested in future studies.

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Acknowledgments

The systematic review was conceived by JCM, TH and MS. AM, AA and MS searched, collected and analysed the data, and all authors contributed to data interpretation. AM, AA, IS and MS drafted the manuscript. All authors contributed to the final version of the manuscript. The corresponding author (AM) is the guarantor for the manuscript and had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final version of the paper.

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    Authors and Affiliations

    1. Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK

      Azizah Mat Hussin, Ammar W. Ashor, John C. Mathers & Mario Siervo

    2. Institute of Medical Science Technology, Universiti Kuala Lumpur, Kuala Lumpur, Malaysia

      Azizah Mat Hussin

    3. College of Medicine, University of Al-Mustansiriyah, Baghdad, Iraq

      Ammar W. Ashor

    4. Elsie Widdowson Laboratory, MRC Human Nutrition Research, 120 Fulbourn Road, Cambridge, CB1 9NL, UK

      Inez Schoenmakers & Mario Siervo

    5. School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, UK

      Tom Hill

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    Correspondence to Mario Siervo.

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    PROSPERO Database registration: CRD42014009668 http://www.crd.york.ac.uk/prospero/.

    Azizah Mat Hussin and Ammar W. Ashor have equally contributed to this work.

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    Hussin, A.M., Ashor, A.W., Schoenmakers, I. et al. Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials. Eur J Nutr 56, 1095–1104 (2017). https://doi.org/10.1007/s00394-016-1159-3

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