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Cited by 42Hormonal and reproductive studiesVitamin D Research StudiesSexual Differentiation and Disorders

Effects of vitamin D supplementation on androgens in men with low testosterone levels: a randomized controlled trial

Open access
Lerchbaum, Elisabeth, Trummer, Christian, Theiler-Schwetz, Verena, Kollmann, Martina, Wölfler, Monika, Heijboer, Annemieke C., Pilz, Stefan, Obermayer-Pietsch, Barbara·2019·European Journal of Nutrition
DOI 10.1007/s00394-018-1858-zPMC PMC6842386
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Abstract

PURPOSE: It has been hypothesized that vitamin D is associated with androgen levels in men. We, therefore, aimed to evaluate whether vitamin D supplementation increases serum total testosterone (TT) levels in men with low TT levels at baseline. METHODS: The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between March 2013 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. One-hundred healthy men with serum TT levels < 10.4 nmol/l and 25-hydroxyvitamin D [25(OH)D] levels < 75 nmol/l participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 50) or placebo (n = 50) for 12 weeks. Primary outcome was TT measured using mass spectrometry. Secondary outcomes were free testosterone, free androgen index, sex hormone-binding globulin, estradiol, follicle-stimulating hormone, luteinizing hormone, metabolic characteristics, and body composition. RESULTS: Ninety-four men [mean age and 25(OH)D: 47 (± 12) years and 56.3 (± 18.3) nmol/l, respectively] completed the study. We found no significant treatment effect on serum TT or on the remaining secondary outcome variables. CONCLUSION: Vitamin D treatment had no effect on serum TT levels in middle-aged healthy men with low TT levels.

AI snapshot

Written from the paper’s full text.

TL;DR

In the Graz Vitamin D&TT-RCT, 12 weeks of high-dose vitamin D3 did not improve serum total testosterone or other androgen/metabolic outcomes in men with low baseline testosterone. The only notable endocrine finding was a significant between-group difference in SHBG in the subgroup with baseline 25(OH)D < 50 nmol/l, driven by an increase in the placebo group.

Key findings

  • Among 94 men who completed the trial, vitamin D supplementation had no significant treatment effect on serum total testosterone: between-group difference −0.188 nmol/l (95% CI −1.50 to 1.12), p = 0.776.
  • No significant treatment effects were found for free testosterone, free androgen index, SHBG, estradiol, FSH, LH, metabolic parameters, or body composition in the main analyses.
  • In the subgroup with baseline 25(OH)D < 50 nmol/l (n = 39), SHBG increased significantly in the placebo group while remaining unchanged in the vitamin D group (between-group difference −1.7 nmol/l, 95% CI −8.8 to −1.7, p = 0.005); total testosterone and remaining secondary outcomes still showed no significant treatment effect.
  • Vitamin D treatment significantly raised 25(OH)D levels: median increased from 56 to 89 nmol/l in the vitamin D group versus 52 to 62 nmol/l in placebo, between-group difference 32 nmol/l (95% CI 23–41), p < 0.001; no participant developed hypercalcemia.

Methods

  • Single-center, double-blind, randomized placebo-controlled trial conducted March 2013–November 2017 at the Medical University of Graz, Austria; 100 men with serum total testosterone < 10.4 nmol/l and 25(OH)D < 75 nmol/l were randomized 1:1 to 20,000 IU vitamin D3 weekly (n = 50) or placebo (n = 50) for 12 weeks.
  • Primary outcome was change in serum total testosterone measured by ID-LC–MS/MS; secondary outcomes included free testosterone, free androgen index, SHBG, estradiol, FSH, LH, metabolic parameters, and body composition.
  • Analyses used intention-to-treat with available baseline and follow-up values; ANCOVA adjusted for baseline values, with a pre-specified subgroup analysis in participants with baseline 25(OH)D < 50 nmol/l (not pre-specified).

Limitations

  • The authors state that inclusion used total testosterone measured by immunoassay; because ID-LC–MS/MS values were higher than expected (baseline median 12.7 vs 8.2 nmol/l), they cannot exclude vitamin D effects in men with lower testosterone levels.
  • The authors note the cohort had relatively high baseline 25(OH)D levels, so effects in severe vitamin D deficiency cannot be excluded; they also cite the relatively short 12-week treatment period, weekly rather than daily dosing, and single-center design in healthy middle-aged men as limits to generalizability.
  • The paper states that pre-specified sexual, psychological, and physical symptoms were assessed only at baseline due to organizational problems; the text also makes evident that the significant SHBG finding comes from a small, non-pre-specified subgroup (n = 39) and may be due to chance.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s00394-018-1858-z

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 32 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Randomized controlled trials on vitamin D supplementation and testosterone status have consistently shown no statistically significant effect of vitamin D versus placebo on testosterone levels.

    “data from randomized controlled trials (RCTs) on vitamin D supplementation and testosterone status have consistently shown no statistically significant effect of vitamin D vs. placebo regarding testosterone levels [16].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch BR, Lerchbaum E (2018) Vitamin D, PCOS and androgens in men: a systematic review. Endocr Connect 7:R95–R113 (Epub ahead of print) source

      The Intervention studies section reports no significant vitamin D effect in several RCTs, including the Graz Vitamin D&TT-RCT. But it also reports an RCT with increased testosterone after supplementation, notes that this study did not test between-group differences, and concludes that RCT results are conflicting. The claim that trials have consistently shown no significant effect versus placebo therefore overstates the review. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Observational studies have mostly shown that vitamin D deficiency is associated with low testosterone concentrations.

    “Observational studies have, by the majority, shown that vitamin D deficiency is associated with low testosterone concentrations [16].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch BR, Lerchbaum E (2018) Vitamin D, PCOS and androgens in men: a systematic review. Endocr Connect 7:R95–R113 (Epub ahead of print) source
  • Findingown data

    There was no significant treatment effect on serum calcium levels.

    “We observed no significant treatment effect on PTH, serum calcium or urine calcium levels in both groups.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the subgroup of men with 25(OH)D < 50 nmol/l, there was no significant effect of vitamin D treatment on serum total testosterone levels.

    “There was no significant effect on serum TT levels or the remaining secondary outcome parameters in this subgroup.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the subgroup of men with 25(OH)D < 50 nmol/l, there was no significant effect of vitamin D treatment on the remaining secondary outcome parameters.

    “There was no significant effect on serum TT levels or the remaining secondary outcome parameters in this subgroup.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 25
  • May combine two claims. 16
  • The quote only partly states this claim. 1

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Serum 25(OH)D and total testosterone were measured by isotope-dilution liquid chromatography-tandem mass spectrometry and used for statistical analyses.

    “Serum levels of 25(OH)D and TT were additionally measured by well-adjusted isotope-dilution liquid chromatography–tandem mass spectrometry (ID-LC–MS/MS) methods in 2018 [18, 19]. 25(OH)D and TT measured by ID-LC–MS/MS were used for statistical analyses.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [18] Dirks NF, Vesper HW, van Herwaarden AE, van den Ouweland JM, Kema IP, Krabbe JG, Heijboer AC (2016) Various calibration procedures result in optimal standardization of routinely used 25(OH)D ID-LC–MS/MS methods. Clin Chim Acta 462:49–54 source
    • cites [19] Büttler RM, Martens F, Fanelli F, Pham HT, Kushnir MM, Janssen MJ, Owen L, Taylor AE, Soeborg T, Blankenstein MA, Heijboer AC (2015) Comparison of 7 published LC–MS/MS methods for the simultaneous measurement of testosterone, androstenedione, and dehydroepiandrosterone in serum. Clin Chem 61:1475–1483 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous observational studies found an inverse association of 25(OH)D and SHBG levels.

    “In this context, it should also be noted that previous observational studies found an inverse association of 25(OH)D and SHBG levels [16, 24].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [16] Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch BR, Lerchbaum E (2018) Vitamin D, PCOS and androgens in men: a systematic review. Endocr Connect 7:R95–R113 (Epub ahead of print) source
    • cites [24] Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch B (2010) Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf) 73:243–248 source

  • May combine two claims.

    Findingown data

    In the subgroup of men with 25(OH)D < 50 nmol/l, there was a significant increase in SHBG levels after 12 weeks in the placebo group, whereas SHBG levels remained unchanged in the vitamin D group.

    “When analyses were restricted to men with 25(OH)D levels < 50 nmol/l, we found a significant increase of SHBG levels after 12 weeks in the placebo group, whereas SHBG levels remained unchanged in the vitamin D group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Vitamin D treatment significantly increased 25(OH)D levels at study end in the whole cohort and in the subgroup with baseline 25(OH)D < 50 nmol/l.

    “We found a significant treatment effect on 25(OH)D levels at study end in both groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There was no significant treatment effect on urine calcium levels.

    “We observed no significant treatment effect on PTH, serum calcium or urine calcium levels in both groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the subgroup with baseline 25(OH)D < 50 nmol/l, there was a significant increase in SHBG levels after 12 weeks in the placebo group, whereas SHBG levels remained unchanged in the vitamin D group.

    “We observed a significant increase in SHBG levels after 12 weeks in the placebo group, whereas SHBG levels remained unchanged in the vitamin D group (Table 4).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Participants complied with the study medication regimen.

  • The quote only partly states this claim.

    Findingown data

    Vitamin D supplementation had no significant treatment effect on the remaining secondary outcome variables (free testosterone, free androgen index, SHBG, estradiol, FSH, LH, metabolic characteristics, and body composition) compared to placebo.

    “We found no significant treatment effect on serum TT or on the remaining secondary outcome variables.”
    • Also stated in: § Primary and secondary outcome variables · plain
      “We found no significant treatment effect on primary and secondary outcome variables.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Participants complied with the study medication regimen.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Analyses of primary and secondary outcome variables were performed according to the intention-to-treat principle and included all participants with baseline and follow-up values.

    “Analyses of primary and secondary outcome variables were performed according to the intention-to-treat principle and inclusion of all participants with baseline and follow-up values.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Study medication was placed into numbered bottles according to the computer-generated randomization list.

    “Study medication was placed into numbered bottles according to this computer-generated randomization list.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Subgroup analyses of primary and secondary endpoints in participants with serum 25-hydroxyvitamin D levels < 50 nmol/l at baseline were performed and were not pre-specified.

    “Further, we performed subgroup analyses of primary and secondary endpoints in study participants with serum 25-hydroxyvitamin D levels < 50 nmol/l at baseline (not pre-specified).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All investigators who enrolled participants, collected data, and assigned intervention were masked to participant allocation.

    “All investigators who enrolled participants, collected data, and assigned intervention were masked to participant allocation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Analysis of covariance with adjustments for baseline values was applied to test for differences in the primary and secondary outcome variables between the treatment and the placebo group at study end.

    “Analysis of covariance with adjustments for baseline values was applied to test for differences in the primary and secondary outcome variables between the treatment and the placebo group at study end.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Randomization was performed using a computer-generated randomization list with 1:1 allocation via web-based software.

    “Subjects were allocated to the vitamin D or placebo group according to a computer-generated randomization list using a ratio of 1:1.”
    • Also stated in: § Intervention · plain
      “Randomization procedures were conducted using a web-based software (http://www.randomizer.at/) with GCP compliance as confirmed by the Austrian Agency for Health and Food Safety (AGES).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Details on sample size calculation have been published previously.

    “Details on sample size calculation have been published previously [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Lerchbaum E, Pilz S, Trummer C, Schwetz V, Pachernegg O, Heijboer AC, Obermayer-Pietsch B (2017) Vitamin D and testosterone in healthy men: a randomized controlled trial. J Clin Endocrinol Metab 102:4292–4302 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    There was no change in study outcomes after the trial had commenced.

    “There was no change in study outcomes after the trial had commenced.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Sexual, psychological, and physical symptoms were pre-specified as secondary outcomes but were assessed only at baseline due to organizational problems.

    “Although pre-specified as secondary outcome, sexual, psychological, and physical symptoms were assessed only at baseline, as we were not able to document these data at study end due to organizational problems.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The Graz Vitamin D&TT-RCT was a single-center, double-blind, randomized placebo-controlled trial conducted at the Medical University of Graz, Austria.

    “The Graz Vitamin D&TT-RCT is a single-center, double-blind, randomized placebo-controlled trial conducted between March 2013 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study protocol was approved by the ethics committee of the Medical University of Graz and written informed consent was obtained from each participant before entering the study.

    “The study protocol was approved by the ethics committee of the Medical University of Graz (EK 23-513 ex 10/11) and written informed consent was obtained from each participant before entering the study.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The trial was registered at clinicaltrialsregister.eu and clinicaltrials.gov.

    “The trial was registered at http://www.clinicaltrialsregister.eu (EudraCT number, 2011-003575-11) and at clinicaltrials.gov (ClinicalTrials.gov Identifier NCT01748370).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The design, conduction and publication of this study adhere to the recommendations of the CONSORT Statement.

    “The design, conduction and publication of this study adhere to the recommendations of the CONSORT Statement (http://www.consort-statement.org/).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Free testosterone values were calculated from total testosterone, SHBG, and albumin according to Vermeulen.

    “FT values were calculated from TT (measured by ID-LC–MS/MS), SHBG, and albumin according to Vermeulen [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study included a relatively large number of participants.

    “Further, we included a relatively large number of participants”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The dropout rate was low.

    “and the dropout rate was low.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Observational studies point towards a positive association of vitamin D and insulin sensitivity.

    “Observational studies point towards a positive association of vitamin D and insulin sensitivity [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M (2013) Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev 12:976–989 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The SHBG finding in the subgroup may be due to chance.

    “Our findings are difficult to interpret and we cannot exclude that they are caused by chance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The mean overall treatment period was 84 ± 4 days in the vitamin D group and 85 ± 7 days in the placebo group, with no significant difference (p = 0.809).

    “The mean overall treatment period was 84 ± 4 days in the vitamin D and 85 ± 7 days in the placebo group (p = 0.809).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Men with combined androgen and vitamin D deficiencies are at high risk for mortality, and a parallel deficiency of both hormones has been suggested to be a marker of poor overall health.

    “As men with combined androgen and vitamin D deficiencies are at high risk for mortality, a parallel deficiency of both hormones has been suggested to be a marker of poor overall health [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Lerchbaum E, Pilz S, Boehm BO, Grammer TB, Obermayer-Pietsch B, März W (2012) Combination of low free testosterone and low vitamin D predicts mortality in older men referred for coronary angiography. Clin Endocrinol (Oxf) 77:475–483 source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study used an RCT design.

    “Strengths of our study include the study design of an RCT”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A total of 94 men completed the study and were analyzed for primary and secondary outcomes.

    “A total of 94 men completed the study (Fig. 1) and were analyzed for primary and secondary outcomes.”
    • Also stated in: § Results · plain
      “Ninety-four men [mean age and 25(OH)D: 47 (± 12) years and 56.3 (± 18.3) nmol/l, respectively] completed the study.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Data from men with normal serum TT levels participating in the Graz Vitamin D&TT-RCT suggest a significant decrease of SHBG levels after 3 months in the vitamin D group but not in the placebo group.

    “Data from men with normal serum TT levels participating the Graz Vitamin D&TT-RCT suggest a significant decrease of SHBG levels after 3 months in the vitamin D group but not in the placebo group [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Lerchbaum E, Pilz S, Trummer C, Schwetz V, Pachernegg O, Heijboer AC, Obermayer-Pietsch B (2017) Vitamin D and testosterone in healthy men: a randomized controlled trial. J Clin Endocrinol Metab 102:4292–4302 source

  • May combine two claims.

    Interpretationown data

    The clinical relevance of the SHBG finding remains to be determined because the change in SHBG was not accompanied by a change in serum TT or FT levels.

    “As the change in SHBG levels was not accompanied by a change in serum TT or FT levels, the clinical relevance of our finding remains to be determined.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The results regarding varying serum TT levels assessed via immunoassay and ID-LC-MS/MS support previous statements on the unreliable results of currently used immunoassays and the need for at least two measurements of low TT levels to confirm hypogonadism.

    “Our results regarding varying serum TT levels assessed via immunoassay and ID-LC–MS/MS supports previous statements on the unreliable results of the currently used immunoassays [25] as well as the need for at least two measurements of low TT levels to confirm the diagnosis of hypogonadism [26].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Handelsman DJ, Wartofsky L (2013) Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metab 98:3971–3973 source
    • cites [26] Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA (2018) Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 103:1715–1744 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The study used state-of-the-art and standardized methods to measure 25(OH)D and TT concentrations.

    “as well as the use of state-of-the-art and standardized methods to measure 25(OH)D as well as TT concentrations in our samples [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA (2018) Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 103:1715–1744 source
33 of 33

  • The paper relies on this without support.

    This study is the first randomized controlled trial specifically designed to analyze vitamin D effects on androgen levels in men with low baseline serum total testosterone levels.

    “To our knowledge, this is the first RCT specifically designed to analyze vitamin D effects on androgen levels in men with low baseline serum TT levels.”

  • The paper relies on this without support.

    Participants complied with the study medication regimen.

    “To improve and verify compliance, patients were asked to return the study medication bottles (full as well as empty bottles) at study end (visit 3).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Existing trials have yielded mixed findings: some reported increases in total testosterone, calculated free testosterone, bioactive testosterone, or free androgen index after supplementation, whereas others showed no meaningful change in total testosterone, SHBG, or free testosterone-related outcomes.

    “Existing trials have yielded mixed findings: some reported increases in TT, calculated FT, BAT, or FAI after supplementation, whereas others showed no meaningful change in TT, SHBG, or FT-related outcomes [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33].”

    From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [18]

    Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Vitamin D deficiency is associated with low testosterone concentrations.

    “Experimental studies have shown that vitamin D deficiency is associated with low testosterone concentrations [3,23].”

    From Influence of Sunlight and Oral D3 Supplementation on Serum 25(OH)D Concentration and Exercise Performance in Elite Soccer Players (2020) · cites this paper as [3]

    The Introduction says that most observational studies found an association between vitamin D deficiency and low testosterone. It does not attribute that association to experimental studies; it says randomized trials consistently found no statistically significant effect of vitamin D supplementation on testosterone. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In athletes, a serum 25(OH)D concentration <30 ng/mL may negatively affect aerobic and anaerobic performance, androgen hormone concentration and fat mass.

    “In athletes, a serum 25(OH)D concentration <30 ng/mL may negatively affect aerobic and anaerobic performance, androgen hormone concentration and fat mass [3,7,8].”

    From Influence of Sunlight and Oral D3 Supplementation on Serum 25(OH)D Concentration and Exercise Performance in Elite Soccer Players (2020) · cites this paper as [3]

    The Discussion (page unavailable) says the authors cannot exclude vitamin D effects on androgen levels in men with severe deficiency, which offers limited support for the claim's hedged androgen component. But this trial studied middle-aged men, not athletes, and found no significant effect on androgen levels; it does not establish an effect below 30 ng/mL on athletic performance or fat mass. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • A sensitivity analysis including Lerchbaum 2019, converted from median and interquartile range, yielded a directionally higher but still non-significant pooled FAI estimate (mean difference 2.35, 95% CI −4.57 to 9.27; p = 0.359).

    “A sensitivity analysis including Lerchbaum 2019 [18], converted from median and interquartile range, yielded a directionally higher but still non-significant pooled estimate (mean difference 2.35, 95% CI −4.57 to 9.27; p = 0.359).”

    From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [18]

  • Two additional SHBG comparisons from Lerchbaum 2017 and Lerchbaum 2019 were retained for sensitivity analysis because they required conversion from median and interquartile range.

    “Two additional comparisons from Lerchbaum 2017 [30] and Lerchbaum 2019 [18] were retained for sensitivity analysis because they required conversion from median and interquartile range.”

    From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • SHBG treatment estimate does not match its confidence interval

    Minor

    In Table 4, the reported SHBG estimate is −1.7, exactly the upper confidence limit. The midpoint of the stated 95% CI is −5.25, not −1.7.

    Reported -1.7 · recomputed -5.25

  • Free-testosterone estimate has the opposite sign from its CI midpoint

    Minor

    In Table 4, the free-testosterone estimate is reported as 0.05, but the stated confidence limits have a midpoint of −0.045. The discrepancy is much larger than rounding.

    Reported 0.05 · recomputed -0.045

  • Glucose-AUC estimate has the opposite sign from its CI midpoint

    Minor

    In Table 4, the stated confidence limits are centered on +6.3, whereas the reported treatment estimate is −6.3.

    Reported -6.3 · recomputed 6.3

  • Subgroup serum-calcium estimate is inconsistent with its CI

    Minor

    In Table 6, the reported estimate of −0.1 is at the lower confidence limit, while the stated limits are centered on zero. Rounding to one decimal place cannot account for the difference.

    Reported -0.1 · recomputed 0

  • Fat-mass analysis includes more men than reportedly completed the study

    Minor

    The paper says 94 men completed the study and were analyzed for outcomes, but Table 2 lists 48 vitamin D participants and 49 placebo participants-97 in total-with paired fat-mass measurements.

5 of 5

Cites

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Related

Authors
Lerchbaum, E., Trummer, C., Theiler-Schwetz, V., Kollmann, M., Wölfler, M., Heijboer, A. C., Pilz, S., & Obermayer-Pietsch, B.
Affiliations
  • Medical University of Graz (AT)
  • Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author
Lerchbaum, Elisabeth
ORCID
Venue
European Journal of Nutrition
Publisher
Springer Science and Business Media LLC
Published
2018-11-20
Volume
58
Issue
8
Pages
3135-3146
ISSN
  • 1436-6207 (ISSN-L)
  • 1436-6215
DOI
10.1007/s00394-018-1858-z
PMC
PMC6842386
OpenAlex
W2900764716
Semantic Scholar
250eb9c3b4ed0b2a30bf907c5def2b15dd40ff13
Cited by
40
References
29
Citations by year
2026: 3 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 5
FWCI
2.98
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Nutrition (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • Pure Amsterdam UMC (acceptedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
ÖNB Jubiläumsfonds (14846)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
vitamin D supplementation, vitamin D3, testosterone, androgen deficiency, androgens, free testosterone, free androgen index, sex hormone-binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, 25-hydroxyvitamin D, middle-aged men, body composition
MeSH terms
Adult, Androgens, Austria, Double-Blind Method, Humans, Male, Middle Aged, Testosterone, Vitamin D, Vitamins, Dietary Supplements

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-04.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-04.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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