Vitamin D, Immunity, COVID-19
Vitamin D was traditionally prescribed in the form of codliver oil for the treatment of rickets. We still think of vitamin D and calcium supplements for maintaining bone strength, but vitamin D (also considered a hormone) is now increasingly studied as an important substance associated with immune system regulation. Currently it is considered a potentially valuable nutrient to assist in the fight against COVID-19.
While many countries have not yet established an effective nationwide vaccination program, others are now starting to rollback their COVID-related mandates. Despite these measures, the data shows that even vaccinated people are getting re-infected. The rapid waning of boosters is part of the problem, with many people balking at the prospect of getting an additional shot every three months.
Forced retrenchments, city-wide lockdowns, curfews, internet censorship and other radical measures have all been used to support high vaccination take-up. However, the health of the economy now takes precedence over non-vaccination measures which have been rapidly rolled back to allow consumption to return to healthy levels. Masks, hand washing, social distancing and home quarantine are inconvenient for travel, tourism and business but, unfortunately, effective preventative measures.
We should therefore look to what we can do to help ourselves given that the virus continues to evolve and circulate. In fact, according to the latest scientific evidence, superfoods, phytonutrients, mineral supplements and other remedies have a critical role to play in maintaining immune barriers regardless of public health measures.
A cornerstone of this approach is the identification of nutrient deficiencies which may suppress immunity. On this point, we should ask if there is any evidence for a connection between vitamin D deficiency and COVID-19 infection, a link that has already been established with zinc deficiency. In fact, using data from the University Of Florida Health Centre, a recent 2021 study found that patients with vitamin D deficiency were 4.6 times more likely to be positive for COVID-19.1
An earlier 2020 research paper identified fourteen studies which showed an inverse correlation between serum vitamin D and severity of COVID-19 symptoms and/or death. A variety of mechanisms were offered for the role of vitamin D in reducing disease severity including ‘maintaining intact epithelial layers, reducing the survival and replication of viruses, reducing the production of pro-inflammatory cytokines, and increasing ACE2 concentrations.2
Vitamin D is actually a group of related substances called steroids. Two of the most important are vitamin D3 (cholecalciferol), which is synthesised in the skin with exposure to UVB, and vitamin D2 (ergocalciferol) obtained from the diet or supplements. These two substances are transformed in the liver and kidneys into active vitamin D (calcitriol). Calcitriol binds to the vitamin D receptor (VDR), which is expressed in many types of tissues including immune cells.
Interestingly, an inverse association has been found between exposure to UVB and case fatality rates due to pneumonia during the 1918-1919 influenza pandemic, pointing to a key role for vitamin D in immune regulation. To be precise, recent research shows that regulation occurs in both the innate and adaptive (specific) branches of the immune system. The Innate immune response occurs mostly on mucosal barriers of the skin where dendritic cells, neutrophils, macrophages, antigen-presenting cells, antimicrobial molecules and inflammatory cytokines are all regulated through the VDR. The adaptive response is also regulated through vitamin D’s influence on Th1,2,17 and T-reg cells, as well as cytokine production in this branch of the immune system. Furthermore, direct antiviral effects of vitamin D include the induction of specific CD8+ T cells, antimicrobial cathelicidin, autophagy and the blocking of viral entry into cells and viral replication.3
It is clear from this that a vitamin D deficiency will cause dysregulation in the immune system, something that is blamed on the risk of an infected patient developing a catastrophic cytokine storm. What remains to be seen is whether or not supplementation or high-dose therapy in patients with low, or even normal levels of vitamin D, will prevent disease severity and even aid recovery.
To this end there are many clinical trials underway and a 2022 meta-analysis of just 11 out of some 1376 trials found, ‘Vitamin D supplements were shown to be useful in significantly reducing ICU admissions and/or mortality in four of the studies, but not in diminishing the duration of hospitalization of COVID-19 patients.’4
Nevertheless, a recent study involving 69 patients from four Saudi Arabian hospitals demonstrated a useful clinical effect from supplementation with vitamin D. They compared a daily dose of 1000IU to daily dose of 4000IU over two weeks, and found a significant increase of serum vitamin D as well as a reduction in hospital stays with the higher dose.5 This reduction in hospital stays was not, however, reproduced in Brazil where a single high dose of 200000IU was given to 240 patients with the same mild to moderate COVID symptoms.6
Furthermore, a trial conducted in Mexico City set out to see if vitamin D supplementation was protective for health care workers in hospital settings, by administrating 4000IU daily. They discovered that this dosage reduced the risk of infection to 6.4% compared to 24.5% in the placebo group. This effect held regardless of vitamin D status in the 320 enrolled workers.7
It is apparent from this research that a vitamin D deficiency is a significant risk factor for infection with COVID-19 as well as disease severity. Vitamin D is available from oily fish, fortified dairy and supplements readily available in the supermarket. My favourite source of vitamin D apart from moderate sunbathing is codliver oil, which also includes anti-inflammatory omega 3 and vitamin A. A tin of sardines also provides you with plenty of vitamin D along with many other minerals, healthy fats, proteins and nutrients that are essential cofactors for healthy immune function.
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Disclaimer:
This article is intended for the purpose of general education only, and is not a substitute for a diagnosis, treatment advice, or a prescription given in a consultation with a qualified physician.
References:
1. Katz J, Yue S, Xue W. Increased risk for COVID-19 in patients with vitamin D deficiency. Nutrition 2021;84:111106.
2. Mercola J, Grant WB, Wagner CL. Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients 2020;12:E3361.
3. Xu Y, Baylink DJ, Chen C-S, et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J Transl Med 2020;18:322.
4. Bania A, Pitsikakis K, Mavrovounis G, et al. Therapeutic Vitamin D Supplementation Following COVID-19 Diagnosis: Where Do We Stand?-A Systematic Review. J Pers Med 2022;12:419.
5. Sabico S, Enani MA, Sheshah E, et al. 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;13:2170.
6. Murai IH, Fernandes AL, Sales LP, et al. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA 2021;325:1053–60.
7. Villasis-Keever MA, López-Alarcón MG, Miranda-Novales G, et al. Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial. Arch Med Res 2022;S0188-4409(22)00045-5.
8. Aldén M, Olofsson Falla F, Yang D, et al. Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line. Current Issues in Molecular Biology 2022;44:1115–26.