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Preventive supplements for COVID-19: What is the recent evidence?

M3 India Newsdesk May 21, 2021

The pandemic has been reaching new heights in our country recently. With new developments being discovered every day, one needs to be updated about the preventive measures of the disease. This article probes the current status of vitamin C and D, and zinc in preventing COVID-19.

For our comprehensive coverage and latest updates on COVID-19 click here.


Recent updates on precautions

The Centre for Disease Control recently advocated the mandatory use of either N95 masks or double masks which includes a disposable mask underneath cloth mask. This is an adjunct to the previous instructions of social distancing and frequent hand sanitation. New and improved developments keep coming up regarding the disease and its virulence.

The innate immune system plays a pivotal role in determining the outcome of the infection. The sensing of foreign nucleic acids is the first step in the pathway to an effective immune response leading to viral clearance. Various supplements have been thought to be useful to boost the immunity of which vitamin C, vitamin D and zinc stand out. They have also shown improvements in patients who are infected and are recovering from the disease.


Vitamin C

Vitamin C is an important co-factor involved in the formation of blood vessels, cartilage, muscle and collagen in bone and is vital for the healing process. As an antioxidant, the vitamin might help protect cells from damage by chemical free radicals. Vitamin C reduces endothelial dysfunction, manages hypertension, reduces cardiovascular disease risk, and prevents stroke, certain types of cancer, diabetes, gout and possibly even Alzheimer's disease.

Overall, regular use of vitamin C supplements shortens the duration of the common cold but does not reduce the risk of contracting a cold except in persons undergoing heavy physical stress (e.g. marathon runners, skiers, or soldiers). Taking vitamin C supplements once cold symptoms have already begun has no proven benefits. It is likely that this antiviral effect is why vitamin C has attracted interest as a possible treatment of COVID-19. The recommended daily allowance for vitamin C intake is 90 mg for adult men and 75 mg for adult women.


Vitamin D

Vitamin D is a steroid hormone that exists in different forms. While 25-hydroxyvitamin D is the primary circulating form, the biologically active form is 1,25-dihydroxy vitamin D. Vitamin D mediates several physiological processes, including bone and extra-skeletal metabolism, cardiovascular and calcium homeostasis, and, most importantly, immune functions. On the other hand, vitamin D deficiency (VDD) is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infection.

Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.

A study found the risk of severe COVID-19 to be 17.3% among patients with severe VDD, whereas it was only 14.6% in patients with normal levels of vitamin D. Interestingly, VDD and COVID-19 severity match similar prevalence patterns such as advanced age, male gender, obesity, diabetes, hypertension, ethnic minorities, and nursing home residents. Ageing can weaken innate immunity, increasing the viral load and chances for severe COVID-19.

COVID-19 increases coagulopathy with elevated D-dimer levels, reduced platelet count, and prolonged prothrombin time (PT). VDD potentially worsens COVID-19 severity by a prothrombotic action and derangement of the immune response. Reports suggest an association between vitamin D status and severe COVID-19 based on the strong connection between VDD and C Reactive Proteins (CRP) which is a marker of inflammation. Both preclinical and clinical evidence showed that VDD is associated with hypertension and diabetes, major risk factors of COVID-19 fatality.

Most of the studies, based on retrospective data suggest a link between VDD and increased susceptibility to SARS-CoV-2 infection while underlining the importance of restoring vitamin D levels to normal. These findings are significant because vitamin D boosts cellular immunity, regulates the adaptive immune response, and enhances antioxidant-related gene expression. Therefore, several researchers suggest vitamin D supplements as a preventive and curative measure for COVID-19. Moreover, lockdown and quarantine can decrease physical activity and the consequent deconditioning of muscles. Therefore, optimising vitamin D levels with supplements will help regain muscle health and strength, a clear advantage in COVID-19. Certain studies imply that vitamin D can attenuate lung injury by modulating the Renin-Angiotensin System.

Since the COVID-19 pandemic has potentially exacerbated VDD (because of mandatory indoor confinement and the associated UVB exposure deficit), vitamin D supplementation, the UK recommends at least 400 international unit (IU) vitamin D daily to the general population while the USA and European Union recommend 600 IU for the general population and 800 IU for those over 70 years.


Zinc

The trace element zinc is important for the development and function of the immune system across all kinds of species. As zinc deficiency results in altered numbers and dysfunction of all immune cells, subjects with suboptimal zinc state have an increased risk for infectious diseases, autoimmune disorders, and cancer.

The entry of infectious agents into the human body is prevented by tissue barriers equipped with cilia and mucus, anti-microbial peptides like lysozymes and interferons. Regarding SARS-CoV2, the angiotensin-converting enzyme 2 (ACE2) and the cellular protease TMPRSS2 are the major mechanisms for entering the cells.

  1. Mucociliary clearance of viruses is affected by zinc:  Infections with coronaviruses damage the ciliated epithelium impairing mucociliary clearance. Studies have shown that physiological concentrations of zinc increase ciliary beat frequency which not only improves the removal of virus particles; it also reduces the risk of secondary bacterial infections.
  2. Zinc is essential for preserving tissue barriers: An ex-vivo model of chronic obstructive pulmonary disease (COPD) showed that decreasing zinc levels raised the leakage of the epithelium of the respiratory tract, while zinc supplementation improved lung integrity.
  3. Zinc-dependent alterations in gene expression by pneumocytes could affect viral entering:  ACE-2, mainly expressed on pneumocytes type 2, is a zinc-metalloenzyme. Zinc binds to its active centre and is thus essential for its enzymatic activity.

How does zinc work?

 

As a virus, SARS-CoV2 is highly dependent on the metabolism of the host cells. Zinc can prevent fusion with the host membrane, decrease the viral polymerase function, impair protein translation and processing, block viral particle release, and destabilise the viral envelope. Low-dose zinc supplementation together with small concentrations of the zinc ionophores, pyrithione or hinokitol decreases RNA synthesis by directly inhibiting the RNA-dependent RNA polymerase of the virus. There is evidence that zinc can enhance the effect of chloroquine.

Zinc deficiency has been associated with elevated levels of pro-inflammatory mediators, increased reactive oxygen species (ROS) levels and pre-disposing for severe progression of inflammatory diseases, especially those affecting the lung, often reversible by zinc supplementation. Zinc is an essential regulator in TLR-4- and TLR-3-induced signalling in innate immune cells. Thus, zinc deficiency disturbs the innate immune response toward SARS-CoV2, enabling the virus to easily spread throughout the host’s body. Clinical improvement of COVID-19 patients was correlated to an increase of CD14+ monocytes and NK cells in the recovery phase which needs sufficient intracellular zinc levels.

A major vascular complication of COVID-19 is coagulopathy. Zinc influences thrombocyte aggregation and coagulation. Recently, a functional association between zinc and ROS production in platelets was described, indicating that zinc could decrease thrombus formation in a clinical context. Complications of SARS-CoV2 infections also include tissue damage affecting the gastrointestinal system, the liver, heart, nervous system, kidneys, blood vessels, and the skin.

In this regard it should be mentioned that balanced zinc homeostasis is essential for wound healing and tissue recovery after mechanical and inflammation-mediated damage, adding more potential benefits of zinc supplementation of COVID-19 patients.


Conclusion

All three nutritional supplements help to build up the body’s immune system and decrease the inflammatory effects of the virus on the tissues. They also help to build up strong immune cells, bone and muscle mass. They act as defence adjuncts for the SARS CoV-2 virus and its effects on the lungs and the body. The use of all three as nutrition supplements and adjunctive during the treatment of COVID-19 cannot be stressed enough.

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