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Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: the EVITA trial

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Abstract

Purpose

Observational studies indicate a positive association between circulating 25-hydroxyvitamin D (25OHD) and testosterone (T) concentrations. Because low 25OHD concentrations and T deficiency are considered to be a generalized phenomenon in patients with advanced heart failure (HF), we aimed to investigate whether vitamin D supplementation has beneficial effects on T indices in these patients.

Methods

In a pre-specified secondary analysis of the EVITA (effect of vitamin D on mortality in heart failure) randomized controlled trial, we analyzed in male subjects with 25OHD concentrations < 75 nmol/L the effect of a daily vitamin D3 supplement of 4000 IU for 3 years (n = 71) vs. placebo (n = 62) on total T (TT), sex hormone-binding globulin (SHBG), free T (fT), and bioactive T (BAT). We assessed changes from baseline until study termination and between-group differences at study termination.

Results

25OHD increased in the placebo group from 36.6 nmol/L by 9.2 nmol/L (95% CI 3.2–15.1 nmol/L; P = 0.003) and in the vitamin D group from 36.5 nmol/L by 63.9 nmol/L (95% CI 52.6–75.3 nmol/L; P < 0.001), with a significant between-group difference at study termination (P < 0.001). TT and SHBG concentrations did not change significantly, neither in the placebo group nor in the vitamin D group (P = 0.845–0.082), but concentrations of fT and BAT declined significantly in both groups (P = 0.025–0.008). At study termination, there were no between-group differences in TT (P = 0.612), SHBG (P = 0.393), fT (P = 0.861), or BAT (P = 0.960).

Conclusions

In male patients with advanced HF and low 25OHD concentrations, a daily vitamin D3 supplement of 4000 IU for 3 years did not prevent the decline in testosterone indices.

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Acknowledgements

The study was sponsored by the Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Germany. The Friede Springer Herz Stiftung (Berlin, Germany) and Merck KGaA (Darmstadt, Germany, EMR200109-616) provided funding for the study. Merck KGaA also provided the study medication and DiaSorin (Dietzenbach, Germany) provided the 25OHD test kits. The funding sources were not involved in the study design, collection, analysis, or interpretation of data, or in preparation or submission of the manuscript for publication. We thank Birgit Drawe and Bärbel Kammel, Institute for Laboratory and Transfusion Medicine, Heart- and Diabetes Center NRW, Ruhr-University of Bochum, Bad Oeynhausen, Germany, for their excellent technical assistance.

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Authors and Affiliations

  1. Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Georgstraße 11, 32545, Bad Oeynhausen, Germany

    Armin Zittermann, Jana B. Ernst, Sylvana Prokop, Uwe Fuchs, Jan F. Gummert & Jochen Börgermann

  2. Institute for Laboratory and Transfusion Medicine, Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Bad Oeynhausen, Germany

    Jens Dreier, Joachim Kuhn & Cornelius Knabbe

  3. Department of Internal Medicine and Geriatrics, Bethel Clinic (EvKB), Bielefeld, Germany

    Heiner K. Berthold

  4. Polyclinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University of Cologne, Cologne, Germany

    Ioanna Gouni-Berthold

  5. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Stefan Pilz

Authors
  1. Armin Zittermann
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  2. Jana B. Ernst
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  3. Sylvana Prokop
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  4. Uwe Fuchs
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  9. Ioanna Gouni-Berthold
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  10. Jan F. Gummert
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  11. Jochen Börgermann
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  12. Stefan Pilz
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Corresponding author

Correspondence to Armin Zittermann.

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Conflict of interest

Armin Zittermann has received speaker honoraria from DiaSorin, Germany. Jana B. Ernst, Sylvana Prokop, Uwe Fuchs, Jens Dreier, Joachim Kuhn, Heiner K Berthold, Ioanna Gouni-Berthold, Jan F. Gummert, Jochen Börgermann, and Stefan Pilz declare that they have no conflict of interest.

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Zittermann, A., Ernst, J.B., Prokop, S. et al. Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: the EVITA trial. Eur J Nutr 58, 673–680 (2019). https://doi.org/10.1007/s00394-018-1666-5

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  • DOI: https://doi.org/10.1007/s00394-018-1666-5

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