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Cited by 0Vitamin D Research StudiesHormonal and reproductive studiesSperm and Testicular Function

Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Open access
Paez-Allendes, Loreto, Valenzuela-Fuenzalida, Juan José, Moya, María P., Oyanedel, Gustavo, Cifuentes-Suazo, Gloria, Figueroa-Puig, Julio, Orellana-Donoso, Mathias, Mateluna-Valls, Eduardo +3 more·2026·Nutrients
DOI 10.3390/nu18132090PMC PMC13363579
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Abstract

Background: Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested associations between vitamin D status and androgen-related markers; however, whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain. Objective: This systematic review and meta-analysis evaluated the effects of vitamin D supplementation on total testosterone (TT) and androgen bioavailability markers in adult men, including sex hormone-binding globulin (SHBG), free androgen index (FAI), calculated free testosterone (calculated FT), and bioactive testosterone (BAT) where methodologically compatible. Methods: The review was registered in PROSPERO (CRD420261365005) and conducted according to PRISMA 2020 and Cochrane methodological guidance. Searches were conducted from database inception to April 2026 in PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the WHO ICTRP. Embase was initially planned but was not searched because institutional access was unavailable; this amendment was made before screening, extraction, risk-of-bias assessment, and synthesis. Records were deduplicated in Zotero, screened in a structured matrix, and converted from report-level records into independent comparison-level datasets where appropriate. Meta-analyses used random-effects REML models with Hartung–Knapp adjustment. Results: The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening. The full-text screening file was reconciled to 162 PRISMA-countable reports/records: 135 reports were assessed, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review, and 27 reports/studies were retained for qualitative synthesis. Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 comparison-level records. The primary TT model included 11 comparisons and showed no clear effect of vitamin D supplementation on final TT (MD 0.47 nmol/L, 95% CI −0.50 to 1.44; I2 = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol/L, 95% CI −2.14 to 2.68), FAI (MD −0.37, 95% CI −4.28 to 3.55), calculated FT sensitivity evidence (MD −0.0096 nmol/L, 95% CI −0.0525 to 0.0332), or BAT exploratory evidence (MD −0.47 nmol/L, 95% CI −1.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT. Conclusions: Current randomized evidence does not demonstrate a statistically clear or reproducible effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone. Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of randomized controlled trials found no statistically clear effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and free androgen index, and very low for calculated free testosterone and bioactive testosterone.

Key findings

  • The primary total testosterone model included 11 comparisons and showed no clear effect of vitamin D supplementation on final total testosterone (MD 0.47 nmol/L, 95% CI −0.50 to 1.44; p = 0.306; I² = 24.1%).
  • No clear effects were observed for SHBG (5 comparisons; MD 0.27 nmol/L, 95% CI −2.14 to 2.68; I² = 0.0%), FAI (3 comparisons; MD −0.37, 95% CI −4.28 to 3.55; I² = 0.0%), calculated free testosterone (3 comparisons; MD −0.0096 nmol/L, 95% CI −0.0525 to 0.0332), or bioactive testosterone (2 studies; MD −0.47 nmol/L, 95% CI −1.77 to 0.83).
  • GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone.
  • A sensitivity analysis excluding clinically extreme populations produced a larger statistically significant total testosterone estimate, but the authors describe this as sensitivity-dependent and hypothesis-generating.

Methods

  • The review was registered in PROSPERO (CRD420261365005), conducted according to PRISMA 2020 and Cochrane guidance, and searched PubMed, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP from database inception to April 2026; Embase was not searched because institutional access was unavailable, with the amendment made before screening, extraction, risk-of-bias assessment, and synthesis.
  • The search identified 2854 records; after removing 703 duplicates, 2151 unique records were screened, 162 PRISMA-countable reports/records were reconciled, 27 reports/studies were retained for qualitative synthesis, and 18 reports were operationalized into 21 comparison-level records.
  • Meta-analyses used random-effects REML models with Hartung–Knapp adjustment; risk of bias was assessed with RoB 2 at the outcome level, certainty with GRADE, and outcomes were handled as primary total testosterone, conservative SHBG and FAI models, sensitivity-only calculated free testosterone, and exploratory bioactive testosterone.

Limitations

  • Stated in the paper: Embase was not searched; 27 reports could not be assessed because full text was unavailable or not obtained; several studies could not be included in quantitative synthesis because final values, dispersion measures, units, or scale definitions were unavailable, internally inconsistent, or not comparable; the broad adult male framework introduced clinical heterogeneity; and most androgen outcomes were secondary or exploratory endpoints, limiting confidence in effect-modification analyses and formal publication-bias assessment.
  • Evident from the text: several pooled outcomes relied on very few comparisons (FAI 3, calculated free testosterone 3, bioactive testosterone 2), and formal funnel-plot asymmetry tests were not performed because the number of studies per outcome was below the conventional threshold.
  • Evident from the text: the total testosterone sensitivity analysis excluding clinically extreme populations became statistically significant while other sensitivity analyses attenuated toward the null, indicating that pooled inferences are context-dependent and vulnerable to study-selection decisions.

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

Integrity signals

Registry

Crossref · 10.3390/nu18132090

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

32 of 73 cited sources checked · 14 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Supplementation effects depend strongly on baseline vitamin D status, assay standardization, dose, formulation, adherence, and population context.

    “supplementation effects depend strongly on baseline status, assay standardization, dose, formulation, adherence, and population context [1,2,3,4,5,6].”
    Quote in the paperSubstantial claim4 of 6 sources checked
    • cites [1] Holick, 2007, Vitamin D deficiency, N. Engl. J. Med. source
    • cites [2] Bikle, 2014, Vitamin D metabolism, mechanism of action, and clinical applications, Chem. Biol. source

      In Vitamin D Production (page unavailable), Bikle reports that D2 and D3 supplementation produce different 25OHD levels unless D2 is given daily. Clinical Applications > The Skeleton (page unavailable) reports a dose-response relationship for fracture prevention. The paper also discusses differences in vitamin D measurement and clinical contexts, but these passages do not establish that supplementation effects depend strongly on baseline status, assay standardization, or adherence. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [3] Giustina, 2024, Consensus statement on vitamin D status assessment and supplementation: Whys, whens, and hows, Endocr. Rev. source
    • cites [4] Demay, 2024, Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab. source
    • cites [5] Bouillon, 2022, The health effects of vitamin D supplementation: Evidence from human studies, Nat. Rev. Endocrinol. source

      The safety-outcomes section reports different results by baseline vitamin D status and dose, while the T2DM section describes findings by adherence and participant characteristics. The review therefore supports much of the claim, but our copy does not establish that supplementation effects depend on assay standardization or formulation; assay standardization appears only in a cited reference title. No page numbers were available in the indexed passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Bendotti, G., Biamonte, E., Leporati, P., Goglia, U., Ruggeri, R.M., and Gallo, M. (2025). Vitamin D supplementation: Practical advice in different clinical settings. Nutrients, 17. source

      The Conclusions (section 7) say supplementation efficacy varies across clinical settings and should account for baseline 25(OH)D levels and formulation; the Obesity section (section 2) also discusses baseline levels and dose. The Pregnancy/Breastfeeding section (section 6) identifies adherence as an issue in supplementation strategies. Our copy does not address assay standardization as a factor in supplementation effects, so the full list is not supported by this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Leydig-cell steroidogenesis is sensitive to aging, metabolic dysfunction, inflammatory stress, and changes in the testicular niche.

    “Experimental and translational evidence also indicates that Leydig-cell steroidogenesis is sensitive to aging, metabolic dysfunction, inflammatory stress, and changes in the testicular niche [13,14].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [13] Kaltsas, A., Dimitriadis, F., Zachariou, A., and Sofikitis, N. (2026). When testosterone fades: Leydig cell aging shaped by environmental toxicants, metabolic dysfunction, and testicular niche crosstalk. Cells, 15. source
    • cites [14] Luo, D., Qi, X., Xu, X., Yang, L., Yu, C., and Guan, Q. (2023). Involvement of p38 MAPK in Leydig cell aging and age-related decline in testosterone. Front. Endocrinol., 14. source

      The Results report reduced Leydig-cell steroidogenic proteins in aged and high-fat-diet mice, while the Discussion links obesity-associated oxidative stress and inflammation to Leydig-cell aging. The paper also observes changes in testicular tissue, including interstitial lipid deposition, but does not establish changes in the testicular niche as a distinct influence on steroidogenesis. Page numbers are unavailable in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    The present results are consistent with the broader vitamin D trial literature, where extra-skeletal effects often appear weaker in randomized evidence than in observational studies.

    “The present results are consistent with the broader vitamin D trial literature, where extra-skeletal effects often appear weaker in randomized evidence than in observational studies [3,4,5,6].”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [3] Giustina, 2024, Consensus statement on vitamin D status assessment and supplementation: Whys, whens, and hows, Endocr. Rev. source
    • cites [4] Demay, 2024, Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab. source
    • cites [5] Bouillon, 2022, The health effects of vitamin D supplementation: Evidence from human studies, Nat. Rev. Endocrinol. source
    • cites [6] Bendotti, G., Biamonte, E., Leporati, P., Goglia, U., Ruggeri, R.M., and Gallo, M. (2025). Vitamin D supplementation: Practical advice in different clinical settings. Nutrients, 17. source

      Section 2, “Vitamin D and Obesity” (page unavailable), reports an association between low vitamin D levels and obesity, while a meta-analysis of trials found no significant effect of supplementation on weight or fat mass. This illustrates weaker trial findings for one extra-skeletal outcome, but the review does not establish that pattern across extra-skeletal effects generally or explicitly compare randomized with observational evidence across the broader literature. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingown data

    The low-risk comparison was Maghsoumi-Norouzabad 2021.

    “The low-risk comparison was Maghsoumi-Norouzabad 2021 [28].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] Mansoori, 2021, The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: A randomized, triple blind, placebo-controlled clinical trial, Reprod. Biol. Endocrinol. source

      The Materials and methods section (Randomization and blinding and interventions; page unavailable) identifies this as a vitamin D3-versus-placebo comparison and describes computer-generated randomization and masking intended to reduce bias. The paper does not itself classify the comparison as “low-risk,” so that assessment is not established by this source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingown data

    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).”
    • Also stated in: § 3.12. GRADE Certainty of Evidence and Summary of Findings · plain
      “Although the FAI sensitivity analysis including a median/IQR-derived comparison shifted the estimate upward, the confidence interval remained wide.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [18] Lerchbaum, 2019, Effects of vitamin D supplementation on androgens in men with low testosterone levels: A randomized controlled trial, Eur. J. Nutr. source
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 64

  • May combine two claims.

    Premisecitation

    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].”
    Quote in the paperSubstantial claim5 of 10 sources checked
    • cites [17] Pilz, 2011, Effect of vitamin D supplementation on testosterone levels in men, Horm. Metab. Res. source
    • cites [18] Lerchbaum, 2019, Effects of vitamin D supplementation on androgens in men with low testosterone levels: A randomized controlled trial, Eur. J. Nutr. source

      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
    • cites [19] Heijboer, 2015, Vitamin D supplementation and testosterone concentrations in male human subjects, Clin. Endocrinol. source
    • cites [20] Saha, 2018, Vitamin D and calcium supplementation, skeletal muscle strength and serum testosterone in young healthy adult males: Randomized control trial, Clin. Endocrinol. source
    • cites [21] Ulrich, 2021, Serum testosterone levels are not modified by vitamin D supplementation in dialysis patients and healthy subjects, Nephron source
    • cites [22] Rips, 2022, Seven-month wintertime supplementation of 1200 IU vitamin D has no effect on hand grip strength in young, physically active males: A randomized, controlled study, J. Int. Soc. Sports Nutr. source

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

      Experimental — accuracy not yet measured
    • cites [23] Mielgo-Ayuso, J., Calleja-González, J., Urdampilleta, A., León-Guereño, P., Córdova, A., Caballero-García, A., and Fernandez-Lázaro, D. (2018). Effects of vitamin D supplementation on haematological values and muscle recovery in elite male traditional rowers. Nutrients, 10. source

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

      Experimental — accuracy not yet measured
    • cites [24] Michalczyk, M.M., Gołaś, A., Maszczyk, A., Kaczka, P., and Zając, A. (2020). Influence of sunlight and oral D3 supplementation on serum 25(OH)D concentration and exercise performance in elite soccer players. Nutrients, 12. source

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

      Experimental — accuracy not yet measured
    • cites [25] Mohammadshahi, 2020, Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial, Eur. J. Sport Sci. source
    • cites [26] Jain, 2024, Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: A placebo-controlled double-blind clinical trial, BMJ Nutr. Prev. Health source

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

      Experimental — accuracy not yet measured

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

    Study design and conductcitation

    Risk of bias was assessed independently by J.F.-P. and J.J.C.-S. using the RoB 2 tool at the outcome level, with disagreements resolved by consensus.

    “Risk of bias was assessed independently by J.F.-P. and J.J.C.-S. using the RoB 2 tool at the outcome level [39], with disagreements resolved by consensus.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [39] Sterne, 2019, RoB 2: A revised tool for assessing risk of bias in randomised trials, BMJ source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Risk of bias in randomized controlled trials was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) at the outcome level.

    “Risk of bias in randomized controlled trials was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) at the outcome level [39].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [39] Sterne, 2019, RoB 2: A revised tool for assessing risk of bias in randomised trials, BMJ source

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

    Study design and conductcitation

    The review was conducted and reported in accordance with PRISMA 2020 and Cochrane methodological guidance.

    “The review was conducted and reported in accordance with the PRISMA 2020 statement [37] and with contemporary methodological guidance for reviews of interventions, including the Cochrane Handbook where applicable [38].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [37] Page, 2021, The PRISMA 2020 statement: An updated guideline for reporting systematic reviews, BMJ source
    • cites [38] Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2024). Cochrane Handbook for Systematic Reviews of Interventions, Version 6.5 (Updated August 2024), Cochrane. Available online: https://training.cochrane.org/handbook.

      Not checked in the free run.

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

    Study design and conductown data

    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.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [30] Lerchbaum, 2017, Vitamin D and testosterone in healthy men: A randomized controlled trial, J. Clin. Endocrinol. Metab. source
    • cites [18] Lerchbaum, 2019, Effects of vitamin D supplementation on androgens in men with low testosterone levels: A randomized controlled trial, Eur. J. Nutr. source

  • May combine two claims.

    Premisecitation

    Vitamin D supplementation effects depend on baseline 25(OH)D status, dose, formulation, adherence, duration, body composition, and whether participants are deficient or already replete at baseline.

    “Vitamin D supplementation effects depend on baseline 25(OH)D status, dose, formulation, adherence, duration, body composition, and whether participants are deficient or already replete at baseline [3,4,5,6].”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [3] Giustina, 2024, Consensus statement on vitamin D status assessment and supplementation: Whys, whens, and hows, Endocr. Rev. source
    • cites [4] Demay, 2024, Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab. source
    • cites [5] Bouillon, 2022, The health effects of vitamin D supplementation: Evidence from human studies, Nat. Rev. Endocrinol. source

      The T2DM section reports post hoc differences by baseline deficiency, BMI and adherence, while the safety-outcomes section reports different effects at high doses and with intermittent boluses. The Conclusions distinguish deficient from vitamin D-replete people. The review lists trial durations but does not establish that effects depend on duration, and the passages found do not establish an effect of formulation; the T2DM subgroup findings are also more tentative than the claim suggests. No page numbers are available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Bendotti, G., Biamonte, E., Leporati, P., Goglia, U., Ruggeri, R.M., and Gallo, M. (2025). Vitamin D supplementation: Practical advice in different clinical settings. Nutrients, 17. source

  • Classified as probably not a substantial claim.

    Premisecitation

    A recent meta-analytic review evaluated vitamin D and androgen/anabolic outcomes in adult males.

    “A recent meta-analytic review evaluated vitamin D and androgen/anabolic outcomes in adult males [34].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] Abu-Zaid, A., Saleh, S.A.K., Adly, H.M., Baradwan, S., Alharran, A.H., Alkhaldi, M.G., Alzayed, M.M., Alotaibi, M.N., Saad, A.R., and Alfayadh, H.M. (2024). The impact of vitamin D on androgens and anabolic steroids among adult males: A meta-analytic review. Diseases, 12. source

  • May combine two claims.

    Premisecitation

    Modern mechanistic literature on Leydig-cell aging and metabolic dysfunction supports the biological plausibility of endocrine vulnerability, but it also indicates that testosterone decline is multifactorial and unlikely to be reversed by a single micronutrient intervention in unselected populations.

    “Modern mechanistic literature on Leydig-cell aging and metabolic dysfunction supports the biological plausibility of endocrine vulnerability, but it also indicates that testosterone decline is multifactorial and unlikely to be reversed by a single micronutrient intervention in unselected populations [13,14].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [13] Kaltsas, A., Dimitriadis, F., Zachariou, A., and Sofikitis, N. (2026). When testosterone fades: Leydig cell aging shaped by environmental toxicants, metabolic dysfunction, and testicular niche crosstalk. Cells, 15. source

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

      Experimental — accuracy not yet measured
    • cites [14] Luo, D., Qi, X., Xu, X., Yang, L., Yu, C., and Guan, Q. (2023). Involvement of p38 MAPK in Leydig cell aging and age-related decline in testosterone. Front. Endocrinol., 14. source

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

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Lerchbaum et al. found no significant effect on total testosterone or secondary androgen outcomes in men with low baseline testosterone.

    “Lerchbaum et al. found no significant effect on TT or secondary androgen outcomes in men with low baseline testosterone [18]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [18] Lerchbaum, 2019, Effects of vitamin D supplementation on androgens in men with low testosterone levels: A randomized controlled trial, Eur. J. Nutr. source

  • May combine two claims.

    Findingown data

    Across the 11 independent comparisons included in the primary total testosterone analysis, one comparison was judged as low risk of bias, eight as having some concerns, and two as high risk of bias.

    “Across the 11 independent comparisons included in the primary total testosterone analysis, one comparison was judged as low risk of bias, eight as having some concerns, and two as high risk of bias.”
    • Also stated in: § 3.3. Risk-of-Bias Results · plain
      “Across the 11 total testosterone comparisons, one was judged at low risk of bias, eight as having some concerns, and two as high risk.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Of the 162 reports, 135 reports were assessed at full text or with sufficient available material.

    “Of these, 135 reports were assessed at full text or with sufficient available material,”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Three FAI comparisons were retained for the primary conservative model because they reported FAI in a comparable scale with final mean and SD data.

    “Three comparisons were retained for the primary conservative model because they reported FAI in a comparable scale with final mean and SD data.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The total testosterone estimate remained directionally similar and not statistically clear after excluding high-risk-of-bias studies.

    “The estimate remained directionally similar and not statistically clear after excluding high-risk-of-bias studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    GRADE certainty was low for total testosterone, SHBG, and free androgen index, and very low for calculated free testosterone and bioactive testosterone.

    “GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT.”
    • Also stated in: § Abstract · plain
      “GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The certainty of evidence was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone.

    “The certainty of evidence was low for TT, SHBG, and FAI, and very low for calculated FT and BAT.”
    • Also stated in: § 3.12. GRADE Certainty of Evidence and Summary of Findings · plain
      “The certainty of evidence was low for TT, SHBG, and FAI and very low for calculated FT and BAT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most frequent sources of concern were incomplete or per-protocol outcome data, testosterone being assessed as a secondary or exploratory biomarker, subgroup-based male analyses, and potential cointerventions such as structured weight loss, athletic training, calcium co-supplementation, or prior sunlight exposure.

    “The most frequent sources of concern were incomplete or per-protocol outcome data, testosterone being assessed as a secondary or exploratory biomarker, subgroup-based male analyses, and potential cointerventions such as structured weight loss, athletic training, calcium co-supplementation, or prior sunlight exposure.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The sensitivity analysis excluding clinically extreme populations produced a larger statistically significant estimate.

    “The sensitivity analysis excluding clinically extreme populations produced a larger statistically significant estimate”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The primary random-effects model included 11 comparisons.

    “The primary random-effects model included 11 comparisons.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Six FAI comparisons were identified as potentially extractable.

    “Six comparisons were identified as potentially extractable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The remaining comparisons were judged as having some concerns, mainly because testosterone was a secondary or exploratory outcome, because analyses were restricted to male subgroups, or because per-protocol/incomplete outcome data and cointerventions could influence the estimate.

    “The remaining comparisons were judged as having some concerns, mainly because testosterone was a secondary or exploratory outcome, because analyses were restricted to male subgroups, or because per-protocol/incomplete outcome data and cointerventions could influence the estimate.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Excluding athlete, military, or active sport populations and excluding strong cointerventions attenuated the estimate toward the null.

    “Excluding athlete, military, or active sport populations and excluding strong cointerventions attenuated the estimate toward the null.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In the FAI sensitivity model including Lerchbaum 2019, heterogeneity increased to a moderate level (tau2 = 10.96; I2 = 45.1%; Q = 5.23, p = 0.156).

    “In this model, heterogeneity increased to a moderate level (tau2 = 10.96; I2 = 45.1%; Q = 5.23, p = 0.156)”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Of the 162 reports, 27 reports/studies were retained for qualitative synthesis.

    “27 reports/studies were retained for qualitative synthesis.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The official search set identified 2854 records; after removal of 703 duplicates, 2151 unique records were screened.

    “The official search set identified 2854 records. After removal of 703 duplicates, 2151 unique records were screened.”
    • Also stated in: § Abstract · plain
      “The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The two high-risk comparisons were driven by substantial missing outcome data in a secondary analysis of advanced heart failure patients and by non-prespecified testosterone analysis in a male subgroup of a broader weight-loss trial.

    “The two high-risk comparisons were driven by substantial missing outcome data in a secondary analysis of advanced heart failure patients and by non-prespecified testosterone analysis in a male subgroup of a broader weight-loss trial.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Five SHBG comparisons were eligible for the primary conservative model because they provided mean/SD data directly or allowed straightforward conversion from SE or 95% CI.

    “Five comparisons were eligible for the primary conservative model because they provided mean/SD data directly or allowed straightforward conversion from SE or 95% CI.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Of the 162 reports, 108 were excluded after full-text assessment with standardized reasons.

    “108 were excluded after full-text assessment with standardized reasons,”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingreasoning

    Total testosterone was treated as the most reproducible quantitative anchor because it was the most consistently reported androgen outcome.

    “TT was treated as the most reproducible quantitative anchor because it was the most consistently reported androgen outcome”
    • Also stated in: § 2.2. Eligibility Criteria · plain
      “TT was treated as a secondary biochemical anchor because it was the most consistently reported androgen outcome across candidate trials”
    Quote in the paperSubstantial claim

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

    Findingown data

    Seven SHBG comparisons were extractable.

    “Seven comparisons were extractable.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The final PRISMA-countable full-text universe was set at 162 reports/records after excluding two operational duplicates/overlapping records.

    “The final PRISMA-countable full-text universe was set at 162 reports/records after excluding two operational duplicates/overlapping records from the count while retaining their traceability in the audit file.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 independent comparison-level records.

    “Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 independent comparison-level records.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The prediction interval for the FAI sensitivity model was wide (−10.26 to 14.95).

    “the prediction interval was wide (−10.26 to 14.95).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The full-text screening matrix was reconciled to 162 PRISMA-countable reports/records.

    “The full-text screening matrix was reconciled to 162 PRISMA-countable reports/records.”
    • Also stated in: § Abstract · plain
      “The full-text screening file was reconciled to 162 PRISMA-countable reports/records:”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Of the 162 reports, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review.

    “27 reports could not be assessed because the full text was unavailable or had not been obtained for review,”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 27 reports that could not be assessed because the full text was unavailable or had not been obtained for review would not materially change the review's conclusions.

  • May combine two claims.

    Findingown data

    The primary total testosterone model showed a small pooled mean difference with a confidence interval crossing the null and a prediction interval compatible with small effects in either direction.

    “The primary model showed a small pooled mean difference with a confidence interval crossing the null and a prediction interval compatible with small effects in either direction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Most androgen outcomes were secondary or exploratory endpoints, limiting confidence in effect-modification analyses and formal publication-bias assessment.

    “Most androgen outcomes were secondary or exploratory endpoints, limiting confidence in effect-modification analyses and formal publication-bias assessment.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingreasoning

    The total testosterone model provides the broadest quantitative anchor because total testosterone was the most consistently extractable androgen outcome.

    “The TT model provides the broadest quantitative anchor because TT was the most consistently extractable androgen outcome.”
    Quote in the paperSubstantial claim

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

    Findingnone given

    27 reports could not be assessed because the full text was unavailable or had not been obtained for review.

    “27 reports could not be assessed because the full text was unavailable or had not been obtained for review.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain.

    “whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The primary inference is based on the full prespecified total testosterone model rather than on any single sensitivity analysis.

    “Therefore, the primary inference is based on the full prespecified TT model rather than on any single sensitivity analysis.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Free testosterone extraction was completed with method-specific classification.

    “Free testosterone extraction was completed with method-specific classification.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Studies with internally inconsistent dispersion data were excluded from the primary quantitative synthesis and retained in the qualitative synthesis.

    “Studies with internally inconsistent dispersion data were excluded from the primary quantitative synthesis and retained in the qualitative synthesis.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Absence of Embase may have reduced search sensitivity, particularly for intervention studies variably indexed across biomedical databases.

    “We acknowledge that absence of Embase may have reduced search sensitivity, particularly for intervention studies variably indexed across biomedical databases.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Studies with ambiguous units, internally inconsistent dispersion, or non-comparable outcome scales were excluded from primary pooling to protect scale validity.

    “Studies with ambiguous units, internally inconsistent dispersion, or non-comparable outcome scales were retained in the audit trail but excluded from primary pooling to protect scale validity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The exclusion of studies with ambiguous units, internally inconsistent dispersion, or non-comparable outcome scales did not introduce bias into the primary total testosterone estimate.

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

    Study design and conductnone given

    Studies with extractable testosterone data were retained in the primary synthesis even when judged as high risk of bias, but prespecified sensitivity analyses were performed excluding high-risk studies.

    “Studies with extractable testosterone data were retained in the primary synthesis even when judged as high risk of bias, but prespecified sensitivity analyses were per-formed excluding high-risk studies.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    An amendment to the original search plan not to search Embase was made before title and abstract screening, data extraction, risk-of-bias assessment, and synthesis.

    “An amendment to the original search plan was made before title and abstract screening, data extraction, risk-of-bias assessment, and synthesis.”
    • Also stated in: § 2.1. Protocol and Registration · plain
      “This deviation was documented prospectively as a protocol amendment before eligibility or synthesis decisions were made.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The review was registered in PROSPERO under registration number CRD420261365005.

    “This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) in 2026 under the registration number CRD420261365005.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Directly measured free testosterone and calculated free testosterone were not pooled together.

    “Directly measured FT and calculated FT were not pooled together.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Directly measured free testosterone and calculated free testosterone were not pooled together because they reflect analytically distinct constructs and may differ in assay performance, calibration, and biological interpretation.

    “Directly measured FT and calculated FT were not pooled together because they reflect analytically distinct constructs and may differ in assay performance, calibration, and biological interpretation.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    The final search strategy combined three major bibliographic databases, two trial registries, broad and targeted search strings, deduplication in Zotero 9.0.4, full-text audit trails, and citation checking of relevant reviews and included reports.

    “To mitigate this limitation, the final strategy combined three major bibliographic databases (PubMed, Web of Science, and Scopus), two trial registries (ClinicalTrials.gov and WHO ICTRP), broad and targeted search strings, deduplication in Zotero 9.0.4, full-text audit trails, and citation checking of relevant reviews and included reports.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Sensitivity analyses were prespecified to evaluate robustness after excluding high-risk-of-bias comparisons, clinically extreme populations, athlete/military/active sport populations, and studies with strong cointerventions.

    “Sensitivity analyses were prespecified to evaluate robustness after excluding high-risk-of-bias comparisons, clinically extreme populations, athlete/military/active sport populations, and studies with strong cointerventions.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    To avoid unit-of-analysis errors, reports were converted into unique studies and, where appropriate, independent analytic comparisons before quantitative extraction.

    “To avoid unit-of-analysis errors, reports were converted into unique studies and, where appropriate, independent analytic comparisons before quantitative extraction.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated free testosterone was handled as sensitivity evidence and bioactive testosterone as exploratory evidence.

    “Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The certainty of evidence for each outcome was assessed using the GRADE approach.

    “The certainty of evidence for each outcome was assessed using the GRADE approach [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Schünemann, H., Brożek, J., Guyatt, G., and Oxman, A. (2013). GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations Using the GRADE Approach, GRADE Working Group.

      Not checked in the free run.

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

    Study design and conductnone given

    Full-text eligibility was assessed using a standardized decision matrix, with disagreements resolved through discussion and senior methodological adjudication when required.

    “Full-text eligibility was subsequently assessed using a standardized decision matrix, with disagreements resolved through discussion and senior methodological adjudication when required.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Bioactive testosterone was assessed as exploratory because compatible data were available from only two studies.

    “Bioactive testosterone was assessed as exploratory because compatible data were available from only two studies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    When testosterone units were ambiguous or physiologically implausible, the study was excluded from the primary analysis unless unit verification was available.

    “When testosterone units were ambiguous or physiologically implausible, the study was excluded from the primary analysis unless unit verification was available; sensitivity analyses were considered only when a biologically plausible unit correction could be transparently justified.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Factorial trials were handled using a single prespecified vitamin D main-effect contrast to avoid double counting.

    “Factorial trials were handled using a single prespecified vitamin D main-effect contrast to avoid double counting.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Primary total testosterone extraction used final post-intervention values when mean and SD were available, or when SD could be defensibly derived from internally consistent 95% confidence intervals and sample size.

    “Primary total testosterone extraction used final post-intervention values when mean and SD were available, or when SD could be defensibly derived from internally consistent 95% confidence intervals and sample size.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Title and abstract screening was performed independently by A.B.-M., J.J.V.-F., and G.O.

    “Title and abstract screening was performed independently by A.B.-M., J.J.V.-F., and G.O.”
    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

    Gheflati 2021 was retained with a unit-label flag because the table label was physiologically implausible, but the values were consistent with nmol/L.

    “Gheflati 2021 [27] was retained with a unit-label flag because the table label was physiologically implausible, but the values were consistent with nmol/L.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Gheflati, 2021, Effects of vitamin D supplementation on semen quality and reproductive hormones in patients with asthenozoospermia: A randomized double-blind placebo-controlled clinical trial, J. Nutr. Food Secur. source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Values reported as median/IQR, figure-only estimates, p values only, or narrative statements without extractable dispersion were not used in the primary final-value model.

    “Values reported as median/IQR, figure-only estimates, p values only, or narrative statements without extractable dispersion were not used in the primary final-value model.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Small-study effects and publication bias were considered qualitatively.

    “Small-study effects and publication bias were considered qualitatively.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    SHBG final-value extraction was completed after source-level verification of the eligible full texts and tables.

    “SHBG final-value extraction was completed after source-level verification of the eligible full texts and tables.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    FAI final-value extraction was completed after source-level verification of the eligible full texts and tables.

    “FAI final-value extraction was completed after source-level verification of the eligible full texts and tables.”
    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 conductreasoning

    Formal funnel-plot asymmetry tests were not performed because the number of studies contributing to each outcome-specific meta-analysis was below the conventional threshold required for reliable interpretation, and because several outcomes included clinically and methodologically heterogeneous comparisons.

    “Formal funnel-plot asymmetry tests were not performed because the number of studies contributing to each outcome-specific meta-analysis was below the conventional threshold required for reliable interpretation, and because several outcomes included clinically and methodologically heterogeneous comparisons.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The broad adult male framework improved feasibility but introduced clinical heterogeneity.

    “The broad adult male framework improved feasibility but introduced clinical heterogeneity.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    This review was prospectively registered.

    “It was prospectively registered”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    This review assessed risk of bias at the outcome level.

    “assessed risk of bias at the outcome level”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The positive signal from early work should be regarded as hypothesis-generating rather than confirmatory.

    “The positive signal from early work should therefore be regarded as hypothesis-generating rather than confirmatory.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The quantitative free testosterone analysis was restricted to method-compatible calculated free testosterone studies.

    “The quantitative FT analysis was therefore restricted to method-compatible calculated FT studies”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The total testosterone findings suggest that apparent signals are context-dependent and vulnerable to study-selection decisions.

    “Overall, the TT findings suggest that apparent signals are context-dependent and vulnerable to study-selection decisions.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    This review followed PRISMA 2020 and Cochrane methodological guidance.

    “followed PRISMA 2020 and Cochrane methodological guidance”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Embase was not searched because institutional access was unavailable.

    “Embase was not searched because institutional access was unavailable.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The review avoided combining analytically non-equivalent constructs, which is particularly important for free testosterone and bioactive testosterone.

    “The review also avoided combining analytically non-equivalent constructs, which is particularly important for FT and BAT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Directly measured free testosterone and calculated free testosterone are analytically non-equivalent and may differ in calibration, assay performance, assumptions, and dependence on total testosterone, SHBG, and albumin.

    “Directly measured FT and calculated FT were not pooled because they are analytically non-equivalent and may differ in calibration, assay performance, assumptions, and dependence on TT, SHBG, and albumin [8,9,10].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [8] Vermeulen, 1999, A critical evaluation of simple methods for the estimation of free testosterone in serum, J. Clin. Endocrinol. Metab. source
    • cites [9] Jayasena, 2022, Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism, Clin. Endocrinol. source
    • cites [10] Fiers, 2018, Reassessing free-testosterone calculation by liquid chromatography-tandem mass spectrometry direct equilibrium dialysis, J. Clin. Endocrinol. Metab. source

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

    Study design and conductnone given

    This review used structured extraction and audit trails.

    “used structured extraction and audit trails”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The deviation from the original plan not to search Embase was documented before screening, extraction, risk-of-bias assessment, and synthesis.

    “This deviation from the original plan was documented before screening, extraction, risk-of-bias assessment, and synthesis”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These findings should not be interpreted as definitive proof of absence of biological activity in all male subgroups; rather, they indicate that current randomized trials do not provide reproducible evidence of an androgen-related benefit.

    “These findings should not be interpreted as definitive proof of absence of biological activity in all male subgroups; rather, they indicate that current randomized trials do not provide reproducible evidence of an androgen-related benefit.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    This review documented scale-compatibility and extractability decisions in the Supplementary Materials.

    “documented scale-compatibility and extractability decisions in the Supplementary Materials.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Bioactive testosterone was treated as exploratory because compatible data were available from only two studies.

    “BAT was even more limited, with compatible data available from only two studies; it was therefore treated as exploratory.”
    Quote in the paperSubstantial claim
81 of 81

  • The paper relies on this without support.

    The 27 reports that could not be assessed because the full text was unavailable or had not been obtained for review would not materially change the review's conclusions.

    “27 reports could not be assessed because the full text was unavailable or had not been obtained for review,”

  • The paper relies on this without support.

    The 11 comparisons included in the primary total testosterone model are sufficiently independent and clinically comparable to pool.

    “The clean final-value total testosterone dataset contains 11 independent comparisons suitable for the primary model.”

  • The paper relies on this without support.

    The exclusion of studies with ambiguous units, internally inconsistent dispersion, or non-comparable outcome scales did not introduce bias into the primary total testosterone estimate.

    “Studies with ambiguous units, internally inconsistent dispersion, or non-comparable outcome scales were retained in the audit trail but excluded from primary pooling to protect scale validity.”

  • The paper relies on this without support.

    SHBG influences the interpretation of total testosterone by determining the proportion of hormone that is free or weakly albumin-bound.

    “SHBG influences the interpretation of TT by determining the proportion of hormone that is free or weakly albumin-bound.”

  • The paper relies on this without support.

    Adiposity, insulin resistance, inflammation, physical activity, sunlight exposure, chronic disease, and general health status can influence both vitamin D status and androgen physiology.

    “Adiposity, insulin resistance, inflammation, physical activity, sunlight exposure, chronic disease, and general health status can influence both vitamin D status and androgen physiology.”

  • The paper relies on this without support.

    Eligible intervention studies may be variably indexed when Embase is not searched.

    “eligible intervention studies may be variably indexed.”
6 of 6

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Authors
Paez-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., & Bruna-Mejias, A.
Affiliations
  • Departamento de Ciencias y Geografía, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Valparaíso 2360072, Chile
  • Escuela de Medicina, Facultad de Medicina, Universidad Andrés Bello, Viña del Mar 2520000, Chile
  • Universidad Autónoma de Chile (CL)
  • Faculty of Health and Social Sciences, University of the Americas, Santiago 8370040, Chile
  • Universidad Católica de la Santísima Concepción (CL)
  • Universidad Mayor (CL)
  • Escuela de Medicina, Universidad Finis Terrae, Santiago 7501015, Chile
  • Académico Carrera de Kinesiología, Departamento de Salud, Comunidad y Gestión, Facultad de Ciencia de la Salud, Universidad de Playa Ancha, Valparaíso 2340000, Chile
  • Facultad de Medicina, Universidad Católica del Maule, Talca 3460000, Chile
  • GIAVAL Research Group, Department of Anatomy and Human Embryology, Faculty of Medicine, University of Valencia, 46001 Valencia, Spain
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2026-06-26
Volume
18
Issue
13
Pages
2090
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu18132090
PMC
PMC13363579
OpenAlex
W7166022930
Cited by
0
References
37
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
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 › Reproductive Medicine › Sperm and Testicular Function
Keywords
vitamin D supplementation, total testosterone, sex hormone-binding globulin, free androgen index, adult male, male reproductive health, vitamin D receptor, androgen metabolism, hypogonadism, vitamin D status
MeSH terms
Adult, Androgens, Biological Availability, Humans, Male, Sex Hormone-Binding Globulin, Testosterone, Vitamin D, Biomarkers, Randomized Controlled Trials as Topic, 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.

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