Effect of vitamin D supplementation regimens on clinical outcomes in asthma: A systematic review
Abstract
Background: Vitamin D has immunomodulatory properties that may improve asthma outcomes; however, randomized controlled trials (RCTs) have reported inconsistent findings. Variations in supplementation regimens, particularly bolus versus non-bolus dosing, may contribute to these discrepancies. Objective: To systematically evaluate the effects of vitamin D supplementation on clinical outcomes in patients with asthma, with particular emphasis on dosing regimens. Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261378116). PubMed, Scopus, and the Cochrane Library were searched for RCTs investigating vitamin D supplementation in asthma. Studies were categorized into non-bolus (daily or weekly) and bolus (high-dose intermittent) regimens. Primary outcomes included asthma exacerbations, lung function, and asthma control. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Six RCTs met the inclusion criteria. Non-bolus supplementation was more consistently associated with improved asthma control and modest improvements in lung function, whereas bolus regimens generally showed no significant clinical benefit. Limited benefits of bolus dosing were observed only among participants with severe vitamin D deficiency. Overall, the included studies demonstrated low risk of bias to some concerns. Conclusions: Vitamin D supplementation may improve asthma outcomes, but its effectiveness appears to depend on the dosing regimen. Regular non-bolus supplementation may provide greater clinical benefits than intermittent bolus dosing, particularly in individuals with vitamin D deficiency. Further high-quality RCTs are needed to confirm regimen-specific effects.Downloads
References
Reddel, Helen K, Bacharier, Leonard B, Bateman, Eric D, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. American journal of respiratory and critical care medicine. 2022;205:17-35.
Hammad, Hamida, Lambrecht, Bart N. The basic immunology of asthma. Cell. 2021;184:1469-85. https://doi.org/https://doi.org/10.1016/j.cell.2021.02.016
Jayasooriya, Shamanthi M, Devereux, Graham, Soriano, Joan B, et al. Asthma: epidemiology, risk factors, and opportunities for prevention and treatment. The Lancet Respiratory Medicine. 2025;13:725-38. https://doi.org/10.1016/S2213-2600(24)00383-7 External Link
Zhu, Yiqun, Jing, Danrong, Liang, Huaying, et al. Vitamin D status and asthma, lung function, and hospitalization among British adults. Frontiers in Nutrition. 2022;Volume 9 - 2022:https://doi.org/10.3389/fnut.2022.954768
Jolliffe, David A, Camargo, Carlos A, Sluyter, John D, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. The lancet Diabetes & endocrinology. 2021;9:276-92. https://doi.org/10.1016/S2213-8587(21)00051-6 External Link
Busse, William W, Castro, Mario, Casale, Thomas B. Asthma management in adults. The Journal of Allergy and Clinical Immunology: In Practice. 2023;11:21-33. https://doi.org/https://doi.org/10.1016/j.jaip.2022.10.015
Pratiwi, Donna, Harimawan, Agustinus I Wayan, Weta, I Wayan, Sumartini, Ni Ketut, Awan, Syuma Adhy, Sutadarma, I Wayan Gede. Effect of astaxanthin supplementation on oxidative stress in adult women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Universa Medicina. 2026;45:125-34. https://doi.org/https://doi.org/10.18051/UnivMed.2026.v45.125-134
Mosnaim, Giselle. Asthma in adults. New England Journal of Medicine. 2023;389:1023-31. https://doi.org/DOI: 10.1056/NEJMcp2304871
Scott, Hayley A, Ng, Shawn HM, McLoughlin, Rebecca F, et al. Effect of obesity on airway and systemic inflammation in adults with asthma: a systematic review and meta-analysis. Thorax. 2023;78:957-65. https://doi.org/https://doi.org/10.1136/thorax-2022-219268
Asghari, Golaleh, Yuzbashian, Emad, Nikparast, Ali, et al. Impact of daily vitamin D3 supplementation on the risk of vitamin D deficiency with the interaction of rs2282679 in vitamin D binding protein gene (GC) among overweight and obese children and adolescents: A one-year randomized controlled trial. Frontiers in Nutrition. 2022;Volume 9 - 2022:https://doi.org/10.3389/fnut.2022.1061496
Pratiwi, Donna, Sidartha, Miko, Wiyarta, Elvan, et al. Comparison of the risk of obesity in the FTO rs9939609 genotype in a multiethnic group in Asia systematic review and meta-analysis. Frontiers in Medicine. 2025;Volume 12 - 2025:https://doi.org/10.3389/fmed.2025.1522318
Peng, Biao, Xiong, Yi, Ouyang, Ting, et al. High ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 increases the risk of asthma attack in American asthma adults: a population study. BMC Public Health. 2024;24:2670. https://doi.org/https://doi.org/10.1186/s12889-024-20185-6
Maison, Nicole, Omony, Jimmy, Illi, Sabina, et al. T2-high asthma phenotypes across lifespan. European respiratory journal. 2022;60:https://doi.org/https://doi.org/10.1183/13993003.02288-2021
Chen, Yuxiong, Kong, Dehui, Fu, Jia, et al. Associations between ambient temperature and adult asthma hospitalizations in Beijing, China: a time-stratified case-crossover study. Respiratory research. 2022;23:38. https://doi.org/https://doi.org/10.1186/s12931-022-01960-8
Sluyter, John D., Camargo, Carlos A., Waayer, Debbie, et al. Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial. Nutrients. 2017;9:1353. https://doi.org/https://doi.org/10.3390/nu9121353
Watkins, Stephanie, Harrison, Tanja, Mushtaq, Sohail. A 12-week double-blind randomised controlled trial investigating the effect of dietary supplementation with 125 μg/d vitamin D in adults with asthma. British Journal of Nutrition. 2024;132:738-49. https://doi.org/10.1017/S0007114524000953
Yu, Hang, Huang, Xi, Zhu, Hua-He, et al. Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway. Phytomedicine. 2023;111:154646. https://doi.org/10.1016/j.phymed.2023.154646
Page, Matthew J, McKenzie, Joanne E, Bossuyt, Patrick M, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. bmj. 2021;372:https://doi.org/https://doi.org/10.1136/bmj.n71
Denlinger, Loren C., King, Tonya S., Cardet, Juan Carlos, et al. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. American Journal of Respiratory and Critical Care Medicine. 2016;193:634-41. https://doi.org/10.1164/rccm.201506-1169OC
Andújar-Espinosa, Rubén, Salinero-González, Lourdes, Illán-Gómez, Fátima, Castilla-Martínez, Manuel, Hu-Yang, Chunshao, Ruiz-López, Francisco José. Effect of vitamin D supplementation on asthma control in patients with vitamin D deficiency: the ACVID randomised clinical trial. Thorax. 2021;76:126-33. https://doi.org/https://doi.org/10.1136/thoraxjnl-2019-213936
Chiewchalermsri, Chirawat, Sangkanjanavanich, Sasipa, Pradubpongsa, Panitan, et al. Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in the build-up phase of house dust mite-specific immunotherapy. Allergy, Asthma & Immunology Research. 2023;15:336. https://doi.org/10.4168/aair.2023.15.3.336
Camargo, Carlos A., Toop, Les, Sluyter, John, et al. Effect of Monthly Vitamin D Supplementation on Preventing Exacerbations of Asthma or Chronic Obstructive Pulmonary Disease in Older Adults: Post Hoc Analysis of a Randomized Controlled Trial. Nutrients. 2021;13:521. https://doi.org/https://doi.org/10.3390/nu13020521
Crocker, Thomas Frederick, Lam, Natalie, Jordao, Magda, et al. Risk-of-bias assessment using Cochrane's revised tool for randomized trials (RoB 2) was useful but challenging and resource-intensive: observations from a systematic review. Journal of clinical epidemiology. 2023;161:39-45. https://doi.org/https://doi.org/10.1016/j.jclinepi.2023.06.015
Manousaki, Despoina, Paternoster, Lavinia, Standl, Marie, et al. Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study. PLOS Medicine. 2017;14:e1002294. https://doi.org/10.1371/journal.pmed.1002294
Thomas, Dennis, McDonald, Vanessa M., Pavord, Ian D., Gibson, Peter G. Asthma remission: what is it and how can it be achieved? European Respiratory Journal. 2022;60:2102583. https://doi.org/10.1183/13993003.02583-2021
Sharma, Sunita, Gerber, Anthony N, Kraft, Monica, Wenzel, Sally E. Asthma pathogenesis: phenotypes, therapies, and gaps: summary of the Aspen Lung Conference 2023. American journal of respiratory cell and molecular biology. 2024;71:154-68. https://doi.org/https://doi.org/10.1165/rcmb.2024-0082WS
Camargo, Carlos A, Jr, Sluyter, John, Stewart, Alistair W, et al. Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial. Clinical Infectious Diseases. 2020;71:311-7. https://doi.org/10.1093/cid/ciz801
Schleich, Florence, Bougard, Nicolas, Moermans, Catherine, Sabbe, Mare, Louis, Renaud. Cytokine-targeted therapies for asthma and COPD. European Respiratory Review. 2023;32:https://doi.org/https://doi.org/10.1183/16000617.0193-2022
Savin, Innokenty A, Zenkova, Marina A, Sen’kova, Aleksandra V. Bronchial asthma, airway remodeling and lung fibrosis as successive steps of one process. International journal of molecular sciences. 2023;24:16042. https://doi.org/https://doi.org/10.3390/ijms242216042
Feng, Kang-ni, Meng, Ping, Zou, Xiao-ling, et al. IL-37 protects against airway remodeling by reversing bronchial epithelial–mesenchymal transition via IL-24 signaling pathway in chronic asthma. Respiratory Research. 2022;23:244. https://doi.org/https://doi.org/10.1186/s12931-022-02167-7
Martineau, Adrian R, MacLaughlin, Beverley D, Hooper, Richard L, et al. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs). Thorax. 2015;70:451-7. https://doi.org/http://doi.org/10.1183/20734735.121116
Stikker, Bernard S, Hendriks, Rudi W, Stadhouders, Ralph. Decoding the genetic and epigenetic basis of asthma. Allergy. 2023;78:940-56. https://doi.org/https://doi.org/10.1111/all.15666
Qian, Ling, Mehrabi Nasab, Entezar, Athari, Seyyede Masoume, Athari, Seyyed Shamsadin. Mitochondria signaling pathways in allergic asthma. Journal of Investigative Medicine. 2022;70:863-82. https://doi.org/https://doi.org/10.1136/jim-2021-002098
Cabrera López, Carlos, Sánchez Santos, Alejandra, Lemes Castellano, Angelina, et al. Eosinophil subtypes in adults with asthma and adults with chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine. 2023;208:155-62. https://doi.org/https://doi.org/10.1164/rccm.202301-0149OC
Legaki, Evangelia, Arsenis, Christos, Taka, Styliani, Papadopoulos, Nikolaos G. DNA methylation biomarkers in asthma and rhinitis: Are we there yet? Clinical and translational allergy. 2022;12:e12131. https://doi.org/https://doi.org/10.1002/clt2.12131
Prietl, Barbara, Treiber, Gerlies, Pieber, Thomas R., Amrein, Karin. Vitamin D and Immune Function. Nutrients [Internet]. 2013; 5(7):[2502-21 pp.].
Liu, Lu, Zhou, Ling, Wang, Lingling, et al. MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway. Respiratory Research. 2023;24:255. https://doi.org/https://doi.org/10.1186/s12931-023-02550-y
Pratiwi, Donna, Harimawan, Agustinus I Wayan. Prognostic performance of GNRI versus PNI for predicting mortality in elderly critically ill patients. World Nutrition Journal. 2026;9:1-12. https://doi.org/10.25220/WNJ.V09.i2.0001
Habib, Nazia, Pasha, Muhammad Asghar, Tang, Dale D. Current understanding of asthma pathogenesis and biomarkers. Cells. 2022;11:2764. https://doi.org/https://doi.org/10.3390/cells11172764
Olsthoorn, Simone EM, van Krimpen, Anneloes, Hendriks, Rudi W, Stadhouders, Ralph. Chronic inflammation in asthma: looking beyond the Th2 cell. Immunological Reviews. 2025;330:e70010. https://doi.org/https://doi.org/10.1111/imr.70010
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