Vitamin D in the era of the COVID-19 pandemic – reducing the risk and shortening the duration of the disease new clinical trials

Since the onset of the COVID-19 pandemic, a number of population-based and cross-sectional studies have shown an association between low serum levels of the active vitamin D metabolite (25-hydroxyvitamin D; 25(OH)D) and the risk of illness, severity and death in patients with COVID-19 [1]. In a study by Mercola et al. patients with serum 25(OH)D levels > 30 ng/ml experienced mild illness, while patients with serum 25(OH)D levels below 30 ng/ml COVID-19 had significantly higher mortality rates [2]. Other studies have shown that the majority of hospitalised COVID-19 patients were vitamin D deficient, which was associated with a 3.79-fold increased risk of severe COVID-19 and a 4.07-fold increased risk of death [3-5]. This has been linked to, among other things, the effect of vitamin D in modulating both innate and acquired immune responses, including a reduction in neutrophil activity, suppression of excessive Th1 lymphocyte activity, which prevents the development of a cytokine storm [1], and the direct positive effect of 25(OH)D on the expression of ACE2, the host cell surface receptor for SARS-CoV-2 [6-8].

Lowering the risk of SARS-COV-2 infection

A recent randomised clinical study evaluated the efficacy of vitamin D in preventing SARS-CoV-2 infection in highly exposed individuals and its effect on disease severity. The study was conducted on frontline health care workers (nurses, doctors) who were caring for COVID-19 patients, even before the introduction of the vaccine. Participants were randomly allocated to a group receiving 4 000 IU of vitamin D (VDG; n = 94) or placebo (PG; n = 98) every day for 30 days. During the study, RT-PCR tests for COVID-19 infection were performed, IgG antibodies against SARS-Cov-2 were measured, and plasma 25(OH)D levels were determined [9]. The study showed that vitamin D supplementation resulted in a significant increase in 25(OH)D levels, the rate of SARS-CoV-2 infection was significantly lower in the VDG group than in the PG group (6.4 vs 24.5%, p <0.001), and the risk of infection in the intervention group was 77% lower (RR: 0.23; 95% CI: (+0.09) 0.55 The therapy used was very safe, and no significant adverse events were identified [9]. The results of this study clearly indicate that vitamin D protects against SARS- CoV-2 infection, even in highly exposed individuals [9].

Lower recovery time

Another study evaluated the effect of daily oral vitamin D3 supplementation on the improvement of symptoms and other clinical parameters in patients with COVID-19 infection. The study included 69 adult patients with positive RT-PCR for SARS-CoV-2, hospitalised for mild to moderate COVID-19. Patients were randomly assigned to a group receiving oral vitamin D 5000 IU (n = 36) or 1000 IU (n = 33) for 2 weeks. During the study, 25(OH)D levels, blood morphological parameters, renal and hepatic profiles, inflammatory markers and time to resolution of disease symptoms including fever, headache, dyspnoea, cough, sore throat, fatigue, loss of smell and taste were assessed. The study showed that patients in the 5000 IU intake group had significantly faster resolution of disease symptoms than in the 1000 IU group (6.2±0.8 versus 9.1±0.8 days), and faster return of taste (11.4±1.0 versus 16.9±1.7; p = 0.035) and smell (11.2±1.1 versus 16.3±1.7; p = 0.14) [10]. This study demonstrates that daily vitamin D3 supplementation at the dose of 5000 IU during COVID-19 infection reduces recovery time and can be recommended as complementary therapy.

References

1. Dudek-Makuch M. Suplementacja witaminy D w prewencji zakażeniem SARS-COV-2 i łagodzenia przebiegu COVID-19. https://chc.com.pl/suplementacja-witaminy-d-w-prewencji-zakazeniem-sars-cov-2-i-lagodzenia-przebiegu-covid-19/
2. Mercola J, Grant WB, Wagner CL. Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients. 2020 Oct 31;12(11):3361. doi: 10.3390/nu12113361. PMID: 33142828; PMCID: PMC7692080.4 ].
3. Karonova TL, Andreeva AT, Golovatuk KA, Bykova ES, Simanenkova AV, Vashukova MA, Grant WB, Shlyakhto EV. Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19. Nutrients. 2021 Aug 29;13(9):3021. doi: 10.3390/nu13093021. PMID: 34578898; PMCID: PMC8468115.
4. Karonova TL, Kudryavtsev IV, Golovatyuk KA, Aquino AD, Kalinina OV, Chernikova AT, Zaikova EK, Lebedev DA, Bykova ES, Golovkin AS, Shlyakhto EV. Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19. Pharmaceuticals (Basel). 2022 Mar 2;15(3):305. doi: 10.3390/ph15030305. PMID: 35337103; PMCID: PMC8955127.
5. Carpagnano GE, Di Lecce V, Quaranta VN, Zito A, Buonamico E, Capozza E, Palumbo A, Di Gioia G, Valerio VN, Resta O. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest. 2021 Apr;44(4):765-771. doi: 10.1007/s40618-020-01370-x. Epub 2020 Aug 9. PMID: 32772324; PMCID: PMC7415009.
6. Agraz-Cibrian JM, Giraldo DM, Urcuqui-Inchima S. 1,25-Dihydroxyvitamin D3 induces formation of neutrophil extracellular trap-likestructures and modulates the transcription of genes whose products are neutrophil extracellular trap-associated proteins: A pilot study. 2019 Jan;141:14-22. doi: 10.1016/j.steroids.2018.11.001. Epub 2018 Nov 7. PMID: 30414422.
7. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019 Aug 1;40(4):1109-1151. doi: 10.1210/er.2018-00126. PMID: 30321335; PMCID: PMC6626501.
8. Xu J, Yang J, Chen J, Luo Q, Zhang Q, Zhang H. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017 Nov;16(5):7432-7438. doi: 10.3892/mmr.2017.7546. Epub 2017 Sep 20. PMID: 28944831; PMCID: PMC5865875.
9. Villasis-Keever MA, López-Alarcón MG, Miranda-Novales G, Zurita-Cruz JN, Barrada-Vázquez AS, González-Ibarra J, Martínez-Reyes M, Grajales-Muñiz C, Santacruz-Tinoco CE, Martínez-Miguel B, Maldonado-Hernández J, Cifuentes-González Y, Klünder-Klünder M, Garduño-Espinosa J, López-Martínez B, Parra-Ortega I. Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial. Arch Med Res. 2022 Jun;53(4):423-430. doi: 10.1016/j.arcmed.2022.04.003. Epub 2022 Apr 18. PMID: 35487792; PMCID: PMC9013626.
10. Sabico S, Enani MA, Sheshah E, Aljohani NJ, Aldisi DA, Alotaibi NH, Alshingetti N, Alomar SY, Alnaami AM, Amer OE, Hussain SD, Al-Daghri NM. Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial. Nutrients. 2021 Jun 24;13(7):2170. doi: 10.3390/nu13072170. PMID: 34202578; PMCID: PMC8308273.

Biographical note

Marlena Dudek-Makuch has 20 years of experience in phytochemical and biological research and scientific information (assistant professor at the Department of Pharmacognosy, Poznań University of Medical Sciences). She authored experimental and review papers on isolation and identification of compounds of plant origin and evaluation of their biological activity. Since 2015 she has been teaching postgraduate courses “Herbs in Practice and Therapy”. She currently works at CHC in the Regulatory Affairs Department of the R&D Division. She is responsible, among others, for preparing Expert Reports (clinical report, non-clinical report) for medicinal products, clinical report for changes in the availability category of a medicinal product (switch OTC), clinical assessment for medical devices and conducting activities in the area of safety supervision of medical devices, as well as safety assessment of plant raw materials used in medicinal products, medical devices and dietary supplements. She is a member of the Polish Herbal Committee.