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Does vitamin D supplementation reduce COVID-19 severity? - a systematic review

Shah et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac040

Feb 2022

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

Meta-analysis of seven systematic reviews showing that vitamin D supplementation reduces the risk of COVID-19 mortality, ventilation, and ICU admission. Authors note that oral and IV supplements were well tolerated, safe, and effective.

12 meta analyses show significant improvements with vitamin D treatment for mortality Argano, Begum, D’Ecclesiis, Hariyanto, Hosseini, Nikniaz, Shah, Xie, mechanical ventilation Hariyanto, Meng, Shah, Xie, ICU admission Hariyanto, Hosseini, Meng, Sartini, Shah, Tentolouris, Xie, hospitalization Argano, severity D’Ecclesiis, Nikniaz, Varikasuvu, Xie, and cases Begum, Sartini, Varikasuvu.

Currently there are 120 vitamin D treatment for COVID-19 studies, showing 36% lower mortality [28‑43%], 16% lower ventilation [-7‑34%], 46% lower ICU admission [28‑60%], 19% lower hospitalization [9‑29%], and 17% fewer cases [9‑24%].

1. Argano et al., Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis, Pharmaceuticals, doi:10.3390/ph16010130.mdpi.com, doi.org.

2. Begum et al., The Role of Vitamin D in COVID-19 Survival and Prevention: A Meta-analysis, Sudan Journal of Medical Sciences, doi:10.18502/sjms.v19i1.15776.knepublishing.com, doi.org.

3. D’Ecclesiis et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis, PLOS ONE, doi:10.1371/journal.pone.0268396.plos.org, doi.org.

4. Hariyanto et al., Vitamin D supplementation and Covid‐19 outcomes: A systematic review, meta‐analysis and meta‐regression, Reviews in Medical Virology, doi:10.1002/rmv.2269.wiley.com, doi.org.

5. Hosseini et al., Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis, Nutrients, doi:10.3390/nu14102134.mdpi.com, doi.org.

6. Meng et al., The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials, Clinical Nutrition, doi:10.1016/j.clnu.2023.09.008.sciencedirect.com, doi.org.

7. Nikniaz et al., The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis, Pharmaceutical Sciences, doi:10.34172/PS.2021.13.ac.ir, doi.org.

8. Sartini et al., Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis, Nutrients, doi:10.3390/nu16050679.mdpi.com, doi.org.

9. Shah et al., Does vitamin D supplementation reduce COVID-19 severity? - a systematic review, QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcac040.oup.com, doi.org.

10. Tentolouris et al., The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression, Diabetes/Metabolism Research and Reviews, doi:10.1002/dmrr.3517.wiley.com, doi.org.

11. Varikasuvu et al., COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials, Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2035217.tandfonline.com, doi.org.

12. Xie et al., Micronutrient perspective on COVID-19: Umbrella review and reanalysis of meta-analyses, Critical Reviews in Food Science and Nutrition, doi:10.1080/10408398.2023.2174948.tandfonline.com, doi.org.

Important missing comments or errors? Let us know.

risk of death, 52.1% lower, OR 0.48, p < 0.001, RR approximated with OR.

risk of mechanical ventilation, 46.1% lower, OR 0.54, p < 0.001, RR approximated with OR.

risk of ICU admission, 63.8% lower, OR 0.36, p < 0.001, RR approximated with OR.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Shah et al., 15 Feb 2022, peer-reviewed, 4 authors.

This Paper Vitamin D All

Does vitamin D supplementation reduce COVID-19 severity? -a systematic review

Komal Shah, Varna Vp, Ujeeta Sharma, Dileep Mavalankar, Jolliffe Martineau Ar, Hooper Da, Greenberg L Rl, Aloia Jf, Al Vitamin, Entrenas Castillo, Costa Lm, Vaquero Barrios, Alcalá Díaz, J F López

doi:10.1093/qjmed/hcac040/6528876

Background and Aim: The evidence regarding the efficacy of vitamin D supplementation in 10 reducing severity of COVID-19 is still insufficient. This is partially due to the lack of primary 11 robust trial-based data and heterogenous study designs. This evidence summary, aims to study the 12 effect of vitamin D supplementation on morbidity and mortality in hospitalized COVID-19 13 patients.

References

Bouillon, Manousaki, Rosen, Trajanoska, Rivadeneira et al., The 281 health effects of vitamin D supplementation: evidence from human studies, Nat Rev 282 Endocrinol

Chen, Mei, Xie, Yuan, Ma et al., Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in 285 hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort 286 studies and RCTs, BMJ Open, doi:10.1186/s12937-021-00744-y28815

Chung, Silwal, Kim, Modlin, Jo, Vitamin D-cathelicidin axis: At the 330 crossroads between protective immunity and pathological inflammation during infection. 331, Immune Netw

Grønborg, Tetens, Christensen, Andersen, Jakobsen et al., Vitamin 333 D-fortified foods improve wintertime vitamin D status in women of Danish and Pakistani 334 origin living in Denmark: a randomized controlled trial, Eur J Nutr

Han, Jones, Tangpricha, Brown, Hao et al., High dose Vitamin 264 D administration in ventilated intensive care unit patients: A pilot double blind 265 randomized controlled trial, J Clin Transl Endocrinol, doi:10.1016/j.jcte.2016.04.004

Hariyanto, Intan, Hananto, Harapan, Kurniawan, Vitamin D supplementation 293 and Covid-19 outcomes: A systematic review, meta-analysis and meta-regression, Rev 294 Med Virol

Karahan, Katkat, Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients 276 with COVID-19 in Turkey, J Nutr Heal Aging

Kulie, Groff, Redmer, Hounshell, Schrager, Vitamin D: An evidence-based 328 review, J Am Board Fam Med

Mercola, Grant, Wagner, Radujkovic, Hippchen et al., Vitamin D 273 and COVID-19 severity and related mortality: a prospective study in Italy, BMC Infect

Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a 260 Single High Dose of Vitamin D3on Hospital Length of Stay in Patients with Moderate to 261 Severe COVID-19: A Randomized Clinical Trial, JAMA -J Am Med Assoc

Nikniaz, Akbarzadeh, Hosseinifard, Hosseini, The impact of vitamin D 296 supplementation on mortality rate and clinical outcomes of COVID-19 patients: A 297 systematic review and meta-analysis, Pharm Sci

Pal, Banerjee, Bhadada, Shetty, Singh et al., Vitamin D supplementation 299 and clinical outcomes in COVID-19: a systematic review and meta-analysis, Diabetes Metab Syndr Clin Res Rev, doi:10.1007/s40618-021-30101614-4302

Rizzoli, Griffin ; G, Hewison, Hopkin, Kenny, Quinton et al., Vitamin D and 322 COVID-19: Evidence and recommendations for supplementation, R Soc Open Sci, doi:10.1007/s40520-020-32001678-x321

Shah, Saxena, Mavalankar, Vitamin D supplementation, COVID-19 and disease 306 severity: A meta-analysis, Qjm

Shen, Mei, Zhang, Xu, The Effect of Vitamin D Supplementation on Clinical 278 Outcomes for Critically Ill Patients: A Systemic Review and Meta-Analysis of 279 Randomized Clinical Trials, Front Nutr

Stroehlein, Wallqvist, Iannizzi, Mikolajewska, Metzendorf et al., Vitamin D supplementation for the treatment of COVID-19: a living systematic review

Vaughan, Trott, Sapkota, Premi, Roberts et al., Changes in 25-315 hydroxyvitamin D levels post-vitamin D supplementation in people of Black and Asian 316 ethnicities and its implications during COVID-19 pandemic: A systematic review, Nutr Diet

Wang, Wang, Li, Chen, Han et al., Human Cathelicidin Inhibits 325 SARS-CoV-2 Infection: Killing Two Birds with One Stone, ACS Infect Dis

Webb, Kazantzidis, Kift, Farrar, Wilkinson et al., Colour Counts: 338 Sunlight and Skin Type as Drivers of Vitamin D Deficiency at UK Latitudes, Nutrients

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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

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