Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: the EVITA trial
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 D 3 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 D 3 supplement of 4000 IU for 3 years did not prevent the decline in testosterone indices.
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Zitterman et al. found no between-group difference regarding androgen levels and SHBG in the EVITA trial.
“At study end, there was no between-group difference regarding androgen levels and SHBG.”
From Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial (2019) · cites this paper as [23]
Zittermann et al. observed no treatment effect on SHBG levels in the EVITA trial.
“Correspondingly, Zittermann et al. [23] observed no treatment effect on SHBG levels in the EVITA trial.”
From Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial (2019) · cites this paper as [23]
High-risk comparisons were Zittermann 2019/EVITA and Pilz 2011.
“High-risk comparisons were Zittermann 2019 [31]/EVITA and Pilz 2011 [17].”
The 11 included total-testosterone comparisons were drawn from Gheflati et al., Maghsoumi-Norouzabad et al., Zittermann et al., Pilz et al., Saha et al., Ulrich et al., Rips et al., Mielgo-Ayuso et al., Michalczyk et al., and Ramezani Ahmadi et al.
“The 11 included total-testosterone comparisons were drawn from Gheflati et al. [27], Maghsoumi-Norouzabad et al. [28], Zittermann et al. [31], Pilz et al. [17], Saha et al. [20], Ulrich et al. [21], Rips et al. [22], Mielgo-Ayuso et al. [23], Michalczyk et al. [24], and Ramezani Ahmadi et al. [25].”
Zittermann et al. reported no between-group differences in total testosterone, SHBG, calculated free testosterone, or bioactive testosterone in men with advanced heart failure.
“Zittermann et al. reported no between-group differences in TT, SHBG, calculated FT, or BAT in men with advanced heart failure [31]”
Cites
Effect of Vitamin D Supplementation on Testosterone Levels in Men
Pilz, S., Frisch, S., Koertke, H., Kuhn, J., Dreier, J., Obermayer-Pietsch, B., Wehr, E., & Zittermann, A. (2011) · Hormone and Metabolic Research · doi:10.1055/s-0030-1269854 · Cited by 325 · see citing works
Self-citationNuesch, E., Trelle, S., Reichenbach, S., Rutjes, A. W. S., Burgi, E., Scherer, M., Altman, D. G., & Juni, P. (2009) · BMJ · doi:10.1136/bmj.b3244 · Cited by 248 · see citing works
Canguven, O., Talib, R. A., El Ansari, W., Yassin, D.-J., & Al Naimi, A. (2017) · The Aging Male · doi:10.1080/13685538.2016.1271783 · Cited by 112 · cited 2× · see citing works
“In line with these findings, a prospective, non-randomized, non-controlled trial in middleaged men showed that vitamin D2 bolus administration was associated with an improvement in T concentrations [8].”
ResultVitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial
Lerchbaum, E., Pilz, S., Trummer, C., Schwetz, V., Pachernegg, O., Heijboer, A. C., & Obermayer-Pietsch, B. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01428 · Cited by 60 · cited 2× · see citing works
“A very recent RCT in 100 healthy eugonadal men with 25OHD below 75 nmol/L also failed to show an effect of vitamin D supplementation (20,000 IU weekly for 12 weeks) on T status [27].”
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Lerchbaum, E., Trummer, C., Theiler-Schwetz, V., Kollmann, M., Wölfler, M., Heijboer, A. C., Pilz, S., & Obermayer-Pietsch, B. (2019) · European Journal of Nutrition · doi:10.1007/s00394-018-1858-z · Cited by 40 · see citing works
Self-citationPaez-Allendes, L., Valenzuela-Fuenzalida, J. J., Moya, M. P., Oyanedel, G., Cifuentes-Suazo, G., Figueroa-Puig, J., Orellana-Donoso, M., Mateluna-Valls, E., Cabezas-Salgado, J. J., Sanchis-Gimeno, J., et al. (2026) · Nutrients · doi:10.3390/nu18132090
- Authors
- Zittermann, A., Ernst, J. B., Prokop, S., Fuchs, U., Dreier, J., Kuhn, J., Knabbe, C., Berthold, H. K., Gouni-Berthold, I., Gummert, J. F., Börgermann, J., & Pilz, S.
- Affiliations
- Heart and Diabetes Center North Rhine-Westphalia (DE)
- Evangelisches Krankenhaus Bielefeld (DE)
- Medical University of Graz (AT)
- Corresponding author
- Zittermann, Armin
- ORCID
- Venue
- European Journal of Nutrition
- Published
- 2018-03-15
- Volume
- 58
- Issue
- 2
- Pages
- 673-680
- ISSN
- 1436-6207 (ISSN-L)
- 1436-6215
- OpenAlex
- W2789697188
- Cited by
- 18
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 2
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Funders
- Merck KGaA (EMR200109-616)
- DiaSorin
- Friede Springer Herzstiftung
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- vitamin D supplementation, testosterone decline, advanced heart failure, 25-hydroxyvitamin D, sex hormone-binding globulin, free testosterone, vitamin D3, male patients
- MeSH terms
- Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Testosterone, Vitamin D, Vitamin D Deficiency, Vitamins, Dietary Supplements
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