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The effect of vitamin D3 supplementation on markers of cardiovascular health in hyperparathyroid, vitamin D insufficient women: a randomized placebo-controlled trial

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Abstract

Purpose

Emerging data supports an association between parathyroid hormone (PTH) and aldosterone. It has been speculated, that potential adverse cardiovascular effects of vitamin D insufficiency may partly be caused by the development of secondary hyperparathyroidism with increased activity of the renin-angiotensin-aldosterone system (RAAS).

We aimed to investigate the effect of normalizing vitamin D status and/or reducing PTH levels on RAAS activity and other markers of cardiovascular health.

Methods

In a double-blinded study during wintertime, we randomized 81 healthy postmenopausal women with secondary hyperparathyroidism (PTH > 6.9 pmol/l) and 25-hydroxy-vitamin D (25(OH)D) levels < 50 nmol/l to 12 weeks of treatment with vitamin D3 70 µg/day (2800 IU/day) or identical placebo.

Markers of cardiovascular health were defined as changes in the plasma RAAS, glycated hemoglobin, lipids, and lipoproteins, blood pressure, vascular stiffness, heart rate, and cardiac conductivity.

Results

Compared to placebo, vitamin D3 treatment significantly increased plasma levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI: 189–272%) and 58% (190–271%), respectively. Vitamin D3 treatment reduced PTH by 17% (11–23%), but did not reduce RAAS activity. Compared to placebo, vitamin D3 treatment increased plasma levels of high-density lipoproteins (HDL) by 4.6% (0.12–9.12%), but did not affect other measured indices.

Conclusions

Vitamin D3 supplementation normalized vitamin D levels and reduced PTH. The supplement increased levels of HDL, but had no effects on RAAS activity or other indices of cardiovascular health.

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Acknowledgements

We acknowledge the laboratory technicians at Aarhus University Hospital and Department of Medical Research Holstebro for invaluable help. Additionally, we acknowledge support from our Hospital Pharmacy, Danish Health Data Authority and Orkla Health A/S. Most importantly we thank all participants for their exceptional commitment and goodwill.

Funding

Aarhus University, The Research Foundation of Central Denmark Region, The Augustinus Foundation, The Foundation of Endocrinology Aarhus University Hospital, Toyota Foundation, A.P. Møller & wife Chastine MC-Kinney Møllers Foundation and P. A. Messerschmidt & wife foundation funded the study. Orkla Health donated vitamin D and vitamin D placebo tablets free of charge, but had no influence on analyses and interpretation of data.

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

    Lise Sofie Bislev, Lene Langagergaard Rødbro, Tanja Sikjaer & Lars Rejnmark

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Lise Sofie Bislev & Lars Rejnmark

  3. University Clinic in Nephrology and Hypertension, Hospital Unit West: Holstebro Hospital, Aarhus University, Holstebro, Denmark

    Jesper Nørgaard Bech & Erling Bjerregaard Pedersen

  4. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

    Alisa D. Kjaergaard & Søren Andreas Ladefoged

  5. Department of Surgery, Aarhus University Hospital, Aarhus, Denmark

    Lars Rolighed

  6. Department of Otolaryngology, Aarhus University Hospital, 8000, Aarhus C, Denmark

    Lars Rolighed

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  1. Lise Sofie Bislev
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  4. Erling Bjerregaard Pedersen
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Corresponding author

Correspondence to Lise Sofie Bislev.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

We conducted the study in accordance to the Helsinki II declaration considering biomedical research regarding humans. The Danish Data Protection Agency (1-16-02-492-14), the Regional Committee on Biomedical Research Ethics (1-10-72-326-14), The Danish Health Authority (2014-003645-10) and Danish Health Data Authority (FSEID-00001274) approved the project. The local unit for Good Clinical Practice at Aarhus University Hospital monitored the study. Clinicaltrials.gov: #NCT02572960.

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Informed consent was obtained from all individual participants included in the study.

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Bislev, L.S., Langagergaard Rødbro, L., Bech, J.N. et al. The effect of vitamin D3 supplementation on markers of cardiovascular health in hyperparathyroid, vitamin D insufficient women: a randomized placebo-controlled trial. Endocrine 62, 182–194 (2018). https://doi.org/10.1007/s12020-018-1659-4

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  • DOI: https://doi.org/10.1007/s12020-018-1659-4

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