NIH| The global community is struggling to find clinically effective treatments for COVID-19, causing a shift in focus towards approaches that may boost the immune system.
As SARS-CoV-2 has been known to provoke multiple inflammatory responses that attack the immune system, pharmaceutical companies are developing drugs and dangerous vaccines against it.
However, what the fear mongers don’t tell you is that a balanced diet rich in vitamins A, B, C, D, E and K as well as micronutrients like zinc, sodium, potassium, calcium chloride and phosphorus are incredibly beneficial in preventing and managing infectious diseases.
This review examines recent evidence of how these vitamins and minerals could help reduce morbidity and mortality rates associated with COVID-19 by improving immune response. It also looks at how deficiencies of these substances can lead to lowered immunity which can contribute to illness severity.
Currently, there is no registered treatment for COVID-19 due to the lack of knowledge about the pathogen-host response. Remdesivir is the only FDA-approved treatment for COVID-19 in the US, though this is restricted to hospitalized patients with severe symptoms
To combat infection two important steps are proper nutrition and activation of the immune system. Scientists continue work on finding a suitable cure, while it is our responsibility to stay safe and not put our health at risk by disregarding safety precautions against COVID-19.
Vitamins and trace elements play an essential role in increasing immunity against infection.
Since the beginning of the COVID-19 pandemic, fear and panic have been felt all around the world. The severity of this virus can vary depending on one’s immune system; as our daily activities have a huge effect on how strong our immunity is. Therefore, it is evident that COVID-19 affects people differently, based on their individual immuno-competence.
SARS-CoV-2 virus is able to attach itself to ACE2 expressing cells located in oral tissues, especially alveolar lung cells, bronchial epithelium and vascular endothelial cells. The infection of the lungs leads to a suppression of ACE2 receptors and RAS dysfunctions, resulting in acute lung injury.
People with stronger immune systems are better able to fight off the virus more effectively; however, it has been proposed that inflammation, poor T cell functioning due to dietary imbalances or lack of essential nutrients may be responsible for a weakening of immunity.
Nutritional deficiencies can negatively impact one’s immune system, leading to increased susceptibility to infection.
Recent evidence has suggested that nutritional supplementation in higher than the recommended daily doses may be beneficial in reducing viral load and hospitalization for COVID-19 patients.
Vitamins are essential dietary components due to their antioxidant properties and immunomodulatory effects. These vitamins regulate gene expression in immune cells and aid in the maturation and differentiation of these same cells. Vitamins C and E act as powerful antioxidants, helping to combat free radicals.
Certain lifestyle factors, diseases such as viral infections, diabetes, obesity, or an increased demand for activation energy during an infection can all lead to nutritional deprivation .
Clinical trials testing the effectiveness of vitamin supplements are outlined in the following table from the NIH Website:
|S.no||Study title||No. of subjects||Intervention/ treatment||Recruitment status||Study type||Primary outcome measures||Secondary outcome measures||Clinical trails.gov identifier|
|1||The effect of melatonin and vitamin c on COVID-19||150||Vitamin C and melatonin||Recruiting||Interventional (Clinical Trial)||Symptom severity [ time frame: 14 days]
Symptom severity will be tracked electronically
|Symptom progression [ time frame: 14 days]
Determine symptom course of those with moderate or severe symptoms
|2||Administration of Intravenous vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation (avocado)||20||L-Ascorbic acid||Completed
|Interventional (Clinical Trial)||Incidence of serious adverse reactions [ Time Frame: Days 1–4]
Occurrence of serious adverse events during study drug infusion
Documented days free off mechanical ventilation the first 28 days post-enrollment
Documented days free of ICU admission the first 28 days post-enrollment
[ Time Frame: Days 1–28]
|3||Efficacy and safety of high-dose vitamin C combined with Chinese medicine against coronavirus pneumonia (COVID-19)||60||Chinese medicine formula combined with high-dose vitamin C treatment||Active but not recruiting||Interventional (Clinical Trial)||Recovery time [ Time Frame: From date of randomization until the date of discharge, assessed up to 6 months]||Respiratory rate [ Time Frame: 1–14 days after treatment],
PaO2 and PaCO2 [ Time Frame: 1–14 days after treatment] in kPa with blood gas analysis
|4||N-terminal Pro B-type natriuretic peptide and vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia||100||Vitamin D||Recruiting||Observational||NT-pro-BNP and vitamin D [ Time Frame: 6 month]||Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection [ Time Frame: 6 month]||NCT04487951|
|5||Impact of vitamin D level and supplement on SLE patients during COVID-19 pandemic||38||Vitamin D||Completed||Observational||Level of serum vitamin D in SLE infected with COVID-19 [ Time Frame: 6 months]||Vitamin D level with COVID-19 severity [ Time Frame: 6 months]||NCT04709744|
|6||Vitamin D and COVID-19 Trial (VIVID)||2700||Vitamin D||Recruiting||Interventional (Clinical Trial)||Rate of seeking healthcare visits for symptoms or concerns related to COVID-19 or deaths in participants newly diagnosed with COVID-19 (index cases) [ Time Frame: 4 weeks]||Self-reported disease severity in index cases [ Time Frame: 4 weeks]
Severity: 1 = no COVID-19 illness; 2 = COVID-19 illness with no hospitalization; 3 = COVID-19 illness with hospitalization; or 4 = death
|7||Vitamin D supplementation in patients with COVID-19||240||Vitamin D||Completed||Interventional (Clinical Trial)||Length of hospitalization [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month]
total number of days that patient remained hospitalized
|Mortality [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month]
number of patients that died
|8||Low vs. moderate to high-dose vitamin D for prevention of COVID-19||2000||Vitamin D3||Recruiting||Interventional (Clinical Trial)||SARS-CoV-2 infection as measured by patient report of clinically confirmed COVID-19 (or viral PCR when available) [ Time Frame: 9-months]||SARS-CoV-2 antibody seroconversion confirmed by a COVID-19 antibody test [ Time Frame: 9 months]||NCT04868903|
|9||Vitamin D3 levels in COVID-19 outpatients from Western Mexico||42||Vitamin D3||Completed||Interventional (Clinical Trial)||Correlation between D-dimer and vitamin D serum levels in COVID-19 patients [ Time Frame: At baseline]||–||NCT04793243|
|10||A Phase 2, double blind, randomized, placebo-controlled clinical trial to investigate the safety and effects of oral vitamin K2 supplementation in COVID-19||40||Vitamin K2 in the form of Menaquinone-7 (MK-7)||Recruiting
|Interventional (Clinical Trial)||Plasma desmosine levels and dp-ucMGP levels before and during vitamin K supplementation in intervention versus control patients.[ Time Frame: Day 1 until day 28 or until discharge if this is earlier.]||Serum PIVKA-II levels before and during vitamin K supplementation in intervention versus control patients.[ Time Frame: Day 1 until day 28 or until discharge if this is earlier.]||NCT04770740|
Role of vitamin A in COVID-19
Vitamin A, also known as retinoic acid (RA), is a part of the family of retinyl-esters and has been found to control various genes that are involved in innate and adaptive immune responses.
Furthermore, Vitamin A serves as a T-cell effector, helping with both innate and adaptive immunity (Raverdeau and Mills 2014).
Several studies have indicated the protective effect of both natural and synthetic retinoids against various viruses, such as hepatitis B virus (HBV), influenza, norovirus, MeV, and cytomegalovirus (Angulo et al. 1998; Trottier et al. 2008; Lee and Han 2016; Li et al. 2018).
Role of vitamin B in COVID-19
Vitamin B is a naturally occurring component that has been found to be involved in the production of Red Blood Cells (RBCs). All the vitamins under the B complex category are essential for normal physiological functioning of body cells, as per Zhang et al. (2018).
Vitamin B helps your body make use of energy-yielding nutrients like carbohydrates, fat and protein, which helps maintain healthy skin, brain cells and other tissues.
The B complex comprises 8 vitamins namely thiamine [B1], riboflavin [B2], niacin [B3], pantothenic acid [B5], pyridoxine [B6], biotin [B7], folate or folic acid [B9] and cyanocobalamin [B12].
It also plays a vital role in colonic immune regulation and aids in maintaining intestinal barrier function (Lindschinger et al., 2019).
Vitamin B1 (thiamine)
Thiamine, a coenzyme essential for energy production in the body, helps regulate temperature and is involved in fat synthesis (Kraft and Angert 2017). It has also been suggested that vitamin B1 may have an anti-inflammatory effect when acting on macrophages, as well as reduce oxidative stress caused by NF-kappa B activation (Spinas et al. 2015).
When thiamine levels are depleted, the immune system can be affected due to inflammation, oxidative stress, and metabolic disruptions which lead to abnormal antibody production (Mikkelsen and Apostolopoulos 2019). Additionally, research has shown that thiamine can help combat SARS-CoV-2 by bolstering humoral immunity and cell-mediated immunity, making it a key element in building immunity against this virus.
Vitamin B2 (riboflavin)
Research has shown that Vitamin B2 (riboflavin) can act as a prophylactic agent against liver damage induced by CCL4, mediated by TNF, in animal models (Yoshii et al. 2019). Additionally, the combination of riboflavin and UV light is known to cause permanent damage to nucleic acids, which effectively inhibits replication of pathogens.
Therefore, this property could be used to reduce the number of pathogens present in the blood plasma of COVID-19 patients and consequently decrease the risk of transfusion-transmitted infection.
Vitamin B3 [niacin (nicotinic acid, pantothenic acid)]
Niacin has been found to have extensive modulatory effects on the generation of inflammatory mediators and immune cell movement, which suggests that it has an anti-inflammatory impact. Considering its therapeutic features for inflammation reduction, research into its application for COVID-19 patients is ongoing; a recent study indicating that targeting IL-6 could reduce inflammation in these patients (Liu et al. 2020).
Moreover, evidence from Nagai et al. (1994) reveals that niacin can decrease neutrophil infiltration in those with ventilator-induced lung injury. Finally, another study demonstrated that nicotinamide reduces viral infection while stimulating defense mechanisms – suggesting that it could be used as an adjunct therapy for COVID-19 patients (Mehmel et al. 2020).
Vitamin B6 (pyridoxine)
Studies have indicated that Vitamin B6 has a significant influence on innate/adaptive immunity, cellular function and proliferation (Ueland et al. 2017). Those deficient in vitamin B6 were found to have inhibited release of cytokines/chemokines. In addition, a recent study revealed that supplementing with Vitamin B6 can help to alleviate symptoms of COVID-19 by improving immune responses, reducing pro-inflammatory cytokines, protecting endothelial integrity and preventing hypercoagulability.
Vitamin B9 (folic acid, folate)
A recent study determined that folic acid, an essential vitamin for DNA and protein synthesis and a key factor in the adaptive immune response, can inhibit furin, an enzyme responsible for bacterial and viral infections. This suggests that folic acid could be beneficial in controlling COVID-19-associated respiratory disease during its early stages.
Additionally, Kumar and Jena (2020) found that derivatives of folic acid–specifically 5-methyl tetrahydrofolic acid and tetrahydrofolic acid–have a strong affinity against SARS-CoV-2.
Role of vitamin C in COVID-19
Vitamin C is a powerful nutrient with numerous antiviral properties, such as increasing interferon-alpha production, modulating cytokines, reducing inflammation, improving endothelial dysfunction and restoring mitochondrial function (Carr and Maggini 2017; Dey and Bishayi 2018). Nobel Prize winner Linus Pauling first proposed the beneficial effect of vitamin C against common cold in the 1930s and 1970s (Heikkinen and Järvinen 2003), while more recent studies have found evidence that it may also possess viricidal properties (Furuya et al. 2008).
Vitamin C plays an important role in supporting immune system health to fight off bacterial and viral infections by eliminating dead cells and replacing them with new ones. Additionally, its antioxidant properties protect against damage caused by oxidative stress. Studies have demonstrated that taking daily 1–2 g of vitamin C supplementation can reduce the risk associated with upper respiratory tract infections (Carr and Maggini 2017) – this was confirmed by Hemilä et al.’s review on adults’ and children’s symptoms of common cold (Hemilä and Chalker 2013).
Furthermore, intravenous administration of vitamin C has been shown to significantly reduce severe infections such as sepsis or acute respiratory distress syndrome (ARDS) in patients.
Role of vitamin D in COVID-19
Vitamin D is a secosteroid that has anti-inflammatory and antioxidant properties, playing a key role in regulating the calcium–phosphorus metabolism. Studies have suggested that vitamin D suppresses the overproduction of inflammatory cytokines such as IL-1α, IL-1β and tumor necrosis factor-α.
Furthermore, it is involved in modulating both infectious and autoimmune diseases’ immune responses. Sunlight emits ultraviolet B radiation which is absorbed into the skin to convert 7-dehydrocholesterol into cholecalciferol.
As dietary sources are inadequate to provide an adequate amount of vitamin D, oral supplementation through fortification is often necessary. Recent research has revealed that COVID-19 affected areas have similar temperatures and latitudes to those cities most affected by it. This is particularly significant because people living in high latitude countries generally have low levels of vitamin D.
Previous investigations had already reported on cases where individuals from these high alert areas were found to be suffering from vitamin D insufficiency. Additionally, the prevalence of this deficiency varies across geographical regions within each country making it difficult to simplify results obtained from them.
Role of vitamin E in COVID-19
Vitamin E is essential for regulating and supporting the immune system as an effective antioxidant (Jayawardena et al. 2020). It functions as a free radical scavenger, minimizing oxidative stress, and counteracting unshared electrons that create reactive oxygen species (ROS) that quickly interact with oxygen.
In addition to its antioxidant and anti-inflammatory qualities, vitamin E also has a role in immunity. Alpha-tocopherol is thought to inhibit cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes (Vitamin E—Health Professional Fact Sheet). Studies have suggested that elderly individuals benefit more from increased vitamin E intake when it comes to maintaining their immune function than younger individuals.
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