Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Jan 4;25(1):11.
doi: 10.1186/s12931-023-02642-9.

High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections

Gustav Wall-Gremstrup  1   2 , Rune Holt  1   2 , Sam Kafai Yahyavi  1   2 , Mads Joon Jorsal  2 , Anders Juul  3   4   5 , Niels Jørgensen  3   4 , Martin Blomberg Jensen  6   7
Affiliations
Randomized Controlled Trial

High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections

Gustav Wall-Gremstrup et al. Respir Res. .

Abstract

Background: Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs.

Methods: A double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients.

Results: At baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25-50; 50-75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005).

Conclusions: High-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs.

Trial registration: NCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.

Keywords: Immune system; Respiratory tract infections; Vitamin D; White blood cell count.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Scatterplots of inflammatory markers at baseline with 95% confidence intervals for the regression lines, as a function of serum vitamin D of all men irrespective of randomization in a pooled linear regression model. a Leucocytes. b Neutrophils. c Eosinophils. d Lymphocytes. e Monocytes. f Orosomucoid. r-values: Pearson’s correlation coefficient. P-values: Pearson’s correlation with a two-tailed test of significance. * p < 0.05, ** p < 0.01, and *** p < 0.001. Abbreviations: S-25OHD3, serum 25-hydroxyvitamin D3
Fig. 2
Fig. 2
Scatterplots of inflammatory markers in the vitamin D3 group and placebo group after 150 days of treatment. Vitamin D3 group presented as red dots with red trend line and 95% confidence intervals for the regression lines. Placebo group presented as blue dots with a blue trend line and 95% confidence intervals for the regression lines, both as a function of serum 25(OH)D3 in a pooled linear regression model. (a) Leucocytes. (b) Neutrophils. (c) Eosinophils. (d) Lymphocytes. (e) Monocytes. (f) Orosomucoid. r-values: Pearson’s correlation coefficient. P-values: Pearson’s correlation with a two-tailed test of significance. * p < 0.05, ** p < 0.01, and *** p < 0.001. Regression p-values for leucocytes and monocytes were 0.016 and 0.013, respectively. Neutrophils and lymphocytes were borderline significant, 0.059 and 0.077, respectively. Regression p-values were calculated with Student’s t-test. Abbreviations: S-25(OH)D3, serum 25-hydroxyvitamin D3
Fig. 3
Fig. 3
Respiratory infections after 150 days of treatment between the vitamin D3 group and placebo group. The data are presented as numbers of cases of RTI. The Vitamin D3 group had 83 cases (55%) of RTI, while 68 cases (45%) had no RTI. The placebo group had 61 cases (39%) of RTI, while 95 cases (61%) had no RTI, during the trial. Cases of common cold infections vitamin D3 group 61%, placebo group 45%. Influenza cases (28% and 20%, respectively). Tonsilitis cases (6% and 6%, respectively). Pneumonia (5% and 0%, respectively). **P-value: <0.01, conducted with Pearson’s Chi-squared test. Abbreviation: RTI, Respiratory tract infections
See this image and copyright information in PMC

References

    1. Prosser D, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci [Internet]. 2004;29(12):664–73. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0968000404002701. - PubMed
    1. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev [Internet]. 2019 Aug 1 [cited 2023 May 10];40(4):1109–51. Available from: https://academic.oup.com/edrv/article/40/4/1109/5126915. - PMC - PubMed
    1. Blomberg Jensen M, Nielsen JE, Jørgensen A, Rajpert-De Meyts E, Kristensen DM, Jørgensen N et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod [Internet]. 2010;25(5):1303–11. Available from: https://pubmed.ncbi.nlm.nih.gov/20172873/. - PubMed
    1. Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab [Internet]. 2011 [cited 2023 May 10];25(4):543–59. Available from: https://pubmed.ncbi.nlm.nih.gov/21872797/. - PubMed
    1. Jensen MB. Vitamin D and male reproduction. Nat Rev Endocrinol [Internet]. 2014;10(3):175–86. Available from: http://www.nature.com/articles/nrendo.2013.262. - PubMed

Publication types

Associated data