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. 2023 Jan 31;12(1):77–89. doi: 10.7762/cnr.2023.12.1.77

The Role of Some Vitamins in Respiratory-related Viral Infections: A Narrative Review

Jae-Hee Park 1, Yunjung Lee 1, Mijoo Choi 1, Eunju Park 1,✉
PMCID: PMC9900078  PMID: 36793782

Abstract

This study aimed to find out the effect of vitamins on respiratory-related viral infections, including coronavirus disease 2019 (COVID-19), through the literature reviews. From January 2000 to June 2021, the studies (cohort studies, cross-sectional studies, case-control studies, randomized control trials) related to vitamins (vitamin A, D, E, C, B6, folate, and B12) and COVID-19/severe acute respiratory syndrome/Middle East respiratory syndrome/cold/influenza were selected from the PubMed, Embase, and Cochrane libraries and analyzed. The relationship between vitamins and virus-related respiratory diseases was identified. Through the review, 39 studies were selected on vitamin D, one study on vitamin E, 11 studies on vitamin C, and 3 studies on folate. Regarding COVID-19, 18 studies on vitamin D, 4 studies on vitamin C, and 2 studies on folate showed significant effects of the intake of these nutrients in preventing COVID-19. Regarding colds and influenza, 3 studies on vitamin D, 1 study on vitamin E, 3 studies on vitamin C, and 1 study on folate demonstrated that the intake of these nutrients significantly prevents these diseases. Therefore, this review suggested the intake of vitamins D, E, C, and folate is important for preventing respiratory diseases related to viruses, such as COVID-19, colds, and influenza. The relationship between these nutrients and virus-related respiratory diseases should be continuously monitored in the future.

Keywords: COVID-19, Vitamins, Respiratory tract infection, Virus

INTRODUCTION

Since the coronavirus disease 2019 (COVID-19) outbreak in 2019, the global death toll has approached 6 million, and the pandemic, now in its third year, is not over [1]. The new coronavirus, the causative agent of COVID-19, is a family of RNA viruses [2]. RNA viruses are considered to have high mutation rates and frequent mutations [3]. Therefore, it is not easy to manufacture COVID-19-related vaccines or therapeutics. Among the top 10 infectious diseases that have caused the most deaths in the world (Spanish flu, Asian flu, Hong Kong flu, 7th cholera epidemic, swine influenza, Ebola, Congo measles, West African meningitis, and severe acute respiratory syndrome [SARS]), excluding cholera and meningitis, the remaining diseases are infectious diseases caused by RNA viruses. Currently, there is no specific treatment for coronavirus infection. In early 2020, the World Health Organization (WHO) declared that SARS-coronavirus 2 had established a pandemic infection and was added to the WHO list of blueprint priority diseases [4].

In 2020, the COVID-19 guidelines published by the WHO, the United Nations Food and Agriculture Organization, the European Food Information Commission, the Centers for Disease Control and Prevention, and the American Nutrition Society identified 4 common nutritional issues. 1) Eat foods that improve immune function, such as vitamins, minerals, dietary fiber, and antioxidants, from fresh, not processed foods. 2) Maintain an adequate intake of minerals (copper, iron, zinc) and vitamins (A, B6, B12, C, D, and folate) directly involved in immune function. 3) Eat whole grains and healthy fats, such as omega-3 fatty acids and nuts. 4) Avoid the intake of high-carbohydrate, high-fat, high-salt foods, alcohol, and frozen foods.

Some nutrients were reported to be actively involved in the proper functioning and strengthening of the immune system, including dietary protein, omega-3 fatty acids, vitamins A, D, E, B1, B6, B12, and C. Supplementation with some of these dietary components was also reported to be effective in improving the health status of patients with viral infections [5]. Viral infections are characterized by compromised immune function and deficient micronutrient stores, particularly vitamins, including vitamins A, B6, B12, C, D, and E [6].

Therefore, based on the studies showing that vitamins are effective in preventing COVID-19, this study attempted to investigate the effects of vitamins on respiratory-related viral infections, including COVID-19, through a review.

MATERIALS AND METHODS

Data extraction

Research searches were performed by 4 independent reviewers, focusing on literature published from January 2000 to June 2021 in the PubMed, Embase, and Cochrane libraries. To identify the publications, individual nutrients and COVID-19/SARS/Middle East respiratory syndrome (MERS)/cold/influenza descriptors were adopted. The articles only written in English, Korean, and Japanese were reviewed. The target nutrients were vitamins A, D, E, C, B6, folate, and B12.

Data selection

The selection criteria for literature in this review were cross-sectional studies, cohort studies, case-controlled studies, and randomized clinical trials (RCTs). The exclusion criteria were: in vitro laboratory research, cell experiments, animal experiments, reviews, systematic literature reviews, meta-analysis studies, and conference proceedings. The lists of bibliographical references of the relevant studies were examined to identify potentially eligible studies. The publications were managed in Rayyan to remove duplicates and apply the inclusion criteria. Whether publications met the selection criteria or not was determined by reviewing the titles and abstracts of the searched papers. When it was difficult to judge a paper based on the title and abstract alone, the text was reviewed to decide whether to select the paper. Through this process, the selected articles were re-examined, and the finally selected papers were included in the review.

RESULTS

A search for individual nutrients and respiratory-related viral infections in the PubMed, Embase, and Cochrane libraries found 168 papers on vitamin A, 982 papers on vitamin D, 431 papers on vitamin E, 901 papers on vitamin C, 151 papers on vitamin B6, 220 papers on folate, and 167 papers on vitamin B12 (Figure 1). Among these publications, only studies related to cohort studies, cross-sectional studies, case-controlled studies, and RCTs were selected.

Figure 1. Flow diagram of study selection for systematic review of each nutrient.

Figure 1

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Vitamin A

Of the total 168 studies on vitamin A, 156 were not related to COVID-19/SARS/MERS/cold/influenza, and 2 animal studies, 3 systematic reviews, and 7 reviews were excluded. Therefore, no cohort studies, cross-sectional studies, case-control studies, or RCTs of vitamin A were found, so a review of vitamin A could not be performed (Figure 1A).

Vitamin D

A total of 982 articles related to vitamin D were found. Among them, 877 articles were excluded by reviewing the title and abstract, and 2 in vitro research studies, 3 meta-analyses, 21 systemic reviews, and 40 reviews were also excluded (Figure 1B). Finally, an article review was conducted on 39 studies, which were classified into 13 cohort studies [7,8,9,10,11,12,13,14,15,16,17,18,19], 11 cross-sectional studies [20,21,22,23,24,25,26,27,28,29,30], 6 case-control studies [31,32,33,34,35,36], and 9 RCTs [37,38,39,40,41,42,43,44,45] (Table 1). The cohort study included 10 COVID-19-related studies and 3 respiratory disease-related studies. The subjects of the study were people infected with COVID-19 in the COVID-19 study and normal people in the study related to respiratory diseases. The cross-sectional study was classified into 9 studies on COVID-19, one study each on influenza, legionella, and pneumonia, and one study each on lung function, respiratory tract infections, and colds. The case-control study consisted of 5 COVID-19-related studies and one influenza-related study. The RCT consisted of 3 studies related to COVID-19 topics, 4 studies related to respiratory diseases, and 2 studies related to influenza. The subjects were divided into a placebo group and an experimental group and took different doses of various forms of vitamin D.

Table 1. Main characteristics of the articles evaluating the association between vitamin D and respiratory-related viral infection.

Authors Study design Sample size Biomarker Dose Result* Mean or range of age (yr) Target
Baktash et al. (2020) [7] Cohort 70 (66.7%), COVID-19-positive group 25(OH)D - + 81 (79.46–81.16) COVID-19
35 (33.3%), COVID-19-negative group
D’Avolio et al. (2020) [8] Cohort 107, patients who underwent a nasopharyngeal swab PCR analysis for SARS-CoV-2 and a 25(OH)D measurement 25(OH)D - + 73 COVID-19
Meltzer et al. (2020) [9] Cohort 489, patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020 25(OH)D or 1,25(OH)2D - + 49.2 COVID-19
Cereda et al. (2021) [10] Cohort 129, consecutive adult COVID-19 patients hospitalized 25(OH)D - + 73.6 ± 13.9 COVID-19
Gavioli et al. (2021) [11] Cohort 437, COVID-19 patients 25(OH)D - − 67 (56–79) COVID-19
Hastie et al. (2021) [12] Cohort 341,184, UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection 25(OH)D - − 37–73 COVID-19
Infante et al. (2021) [13] Cohort 137, consecutive patients with SARS-CoV-2 infection 25(OH)D - + 34–89 COVID-19
Lohia et al. (2021) [14] Cohort 270, patients with confirmed COVID-19 Vitamin D - − 63.81 ± 14.69 COVID-19
Orchard et al. (2021) [15] Cohort 50, SARS-CoV-2 PCR positive hospitalizations Vitamin D - +/− 60 (51.2–67.0) COVID-19
Osman et al. (2021) [16] Cohort 445, hospitalized patients Vitamin D - + 50.8 (15–94) COVID-19
Sabetta et al. (2010) [17] Cohort 198, healthy adults 25(OH)D - + 20–88 Acute viral respiratory tract infections
Berry et al. (2011) [18] Cohort 6,789, participants in the nationwide 1958 British birth cohort 25(OH)D - + 45 Respiratory infections and lung function
Brenner et al. (2020) [19] Cohort 9,940, recruited by their general practitioners during a routine health check-up between 2000 and 2002 25(OH)D - + 50–75, 62.1 Respiratory disease
Ling et al. (2020) [20] Cross-sectional 444, patients had symptoms and signs suggestive of SARS-CoV-2 infection Cholecalciferol Approximately ≥ 280,000 IU in a time period of up to 7 wk) + 63–83 COVID-19
Serum 25(OH)D −
Abdollahi et al. (2021) [21] Cross-sectional 118, patients with COVID-19 who were hospitalized in ICU 25(OH)D - + 65.05 ± 15.75 COVID-19
De Smet et al. (2021) [22] Cross-sectional 186, severe acute respiratory syndrome coronavirus 2 infected individuals hospitalized 25(OH)D - Male, + 52–80 COVID-19
Female, −
Katz et al. (2021) [23] Cross-sectional 884, patients positively diagnosed with COVID-19 Vitamin D - + All ages COVID-19
31,950, patients had vitamin D deficiency
87, patients had both vitamin D deficiency and COVID-19
Luo et al. (2021) [24] Cross-sectional 560, individuals who underwent the physical examination program 25(OH)D - + Control, 49–60 COVID-19
335, COVID-19 patients COVID-19, 43–64
Nasiri et al. (2021) [25] Cross-sectional 329, confirmed cases of COVID-19 Vitamin D - +/− 64.7 ± 18.5 (15–99) COVID-19
Meoli et al. (2021) [26] Cross-sectional 735, adolescents enrolled during the compulsory military fitness-for-duty evaluation 25(OH)D - − 18–19 COVID-19
Pugach and Pugach (2021) [27] Cross-sectional 10 countries 25(OH)D - + 37.8–47.8 COVID-19
Yadav et al. (2021) [28] Cross-sectional 37 countries Vitamin D - + - COVID-19
Pletz et al. (2014) [29] Cross-sectional 101, control 25(OH)D, 1,25(OH)2D - − Control, 59.43 Influenza
50, influenza + Influenza, 60.13 Legionella
49, legionella Legionella, 62.65 Streptococcus pneumoniae
100, Streptococcus pneumoniae Streptococcus pneumoniae, 57.41
Rafiq et al. (2018) [30] Cross-sectional 6,138, participants in the NEO study 25(OH)D - BMI > 30, + 45–65 Lung function, airway inflammation, common colds
Abdollahi et al. (2021) [31] Case-control 201, patients with coronavirus infection 25(OH)D - + Case, 48 COVID-19
201, controls Control, 46.34
Al-Daghri et al. (2021) [32] Case-control 138, RT-PCR-confirmed SARS-CoV-2 positive 25(OH)D - + 43 ± 15 COVID-19
82, negative controls
Alguwaihes et al. (2021) [33] Case-control 150, SARS-CoV-2 (+) 25(OH)D - + 56.6 ± 16.2 COVID-19
72, SARS-CoV-2 (−)
Hernández et al. (2021) [34] Case-control 197, COVID-19 with confirmed COVID-19, COVID-19 patients on oral vitamin D supplements for more than 3 mon, 197 control 25(OH)D Cholecalciferol, 25,000 IU/monthly in 10 cases, 5,600 IU/weekly in 1, and calcifediol 0.266 mg/monthly in 8 patients were on + COVID-19 patients, 61 (47.5–70.0) COVID-19
COVID-19 patients + vitamin D supplementation, 60 (59.0–75.0)
Controls, 61 (56.0–66.0)
Ye et al. (2021) [35] Case-control 80, healthy controls and 62 patients diagnosed with COVID-19 25(OH)D - + Control, 42 (31–52) COVID-19
Case 43, (32–59)
Nanri et al. (2017) [36] Case-control 179, cases who reported influenza diagnosis 25(OH)D - − 37.6 ± 11.6 Influenza
353, participants who did not reported influenza diagnosis
Rastogi et al. (2020) [37] RCT 16, vitamin D supplementation group 25 (OH)D 60,000 IU/day, 7 day + Intervention group, 50 COVID-19
24, control group for asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals Control group, 47.5
Ohaegbulam et al. (2020) [38] RCT 2, vitamin D-high dose Vitamin D 1,000 IU cholecalciferol, 50,000 IU ergocalciferol, 1 mon + Vitamin D-high dose, 41, 57 COVID-19
2, vitamin D-standard dose Vitamin D-standard dose, 74, 53
Murai et al. (2021) [39] RCT 119, vitamin D3 group Mortality rate 200,000 IU, 4 mon − 200,000 IU of vitamin D3 56.5 or placebo 56 COVID-19
118, placebo group
Rees et al. (2013) [40] RCT 399, vitamin D3 group Cold, influenza prevalence Vitamin D3 (1,000 IU/day) + Ca (1,200 mg/day) − Vitamin D3 group, 57.9 Upper respiratory tract
360, placebo group Placebo group, 57.8
Aglipay et al. (2017) [41] RCT 354, vitamin D dose 400 IU/d No. of subjects Vitamin D 400 IU/d or 2,000 IU/d, 4 mon − Vitamin D dose 400 IU/d, 2.76 Viral upper respiratory tract infections
349, vitamin D dose 2,000 IU/d Vitamin D dose 2,000 IU/d, 2.70
Shimizu et al. (2018) [42] RCT 105, placebo group 25(OH)D 10 μg/, 16 wk Prevalence, − Placebo, 52.6 ± 6.7 Upper respiratory tract infection
110, 25(OH)D group Duration, + 25(OH)D group, 52.8 ± 6.2
Loeb et al. (2019) [43] RCT 650, vitamin D group 25(OH)D 14,000 U/wk, 8 mon − Vitamin D, 8.6 Respiratory infections
650, placebo group Placebo, 8.4
Urashima et al. (2014) [44] RCT 148, vitamin D3 group Influenza A prevalence 2,000 IU/day, 2 mon − - Influenza A
99, placebo group
Zhou et al. (2018) [45] RCT 168, low dose vitamin D Person infected with influenza A 400 IU or 1,200 IU, 4 mon + Low dose vitamin D, 7.7 ± 2.5 Seasonal influenza A
164, high dose vitamin D High dose vitamin D, 8.0 ± 2.7
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COVID-19, coronavirus disease 2019; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; 25(OH)D, 25-hydroxyvitamin D; ICU, intensive care unit; NEO, Netherlands Epidemiology of Obesity; BMI, body mass index; RT-PCR, reverse transcription polymerase chain reaction; RCT, randomized control trial.

*+: significant effect on the prevention of respiratory-related viral infection; −: no significant effect on the prevention of respiratory-related viral infection.

Vitamin E

We identified 431 studies related to vitamin E in our database. Of these, 415 papers were excluded by reviewing the study titles and abstracts. Only one case was eligible for a literature review, with exclusion of 6 animal experiments, 2 systematic reviews, and 7 reviews (Figure 1C, Table 2). The eligible study was an RCT study to confirm the efficacy of vitamin E in respiratory infections [46].

Table 2. Main characteristics of included article evaluated the association between vitamin E and respiratory-related viral infection.

Authors Study design Sample size Biomarker Dose Result* Mean or range of age (yr) Target
Meydani et al. (2004) [46] RCT 70 (66.7%), COVID-19-positive group Incidence, No. of subjects and No. of days with respiratory infections (upper and lower), and No. of new antibiotic prescriptions Vitamin E 200 IU + Vitamin E, 84.7 or placebo, 84.3 Respiratory infection
35 (33.3%), COVID-19-negative group
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COVID-19, coronavirus disease 2019.

*+: significant effect on the prevention of respiratory-related viral infection; −: no significant effect on the prevention of respiratory-related viral infection.

Vitamin C

In vitamin C, 901 papers were searched (Figure 1D), and 855 papers were excluded based on the titles and abstracts. A total of 11 documents were used in the study after excluding 2 in vitro studies, 3 animal experiments, 5 meta-analyses, 5 systematic reviews, one mixed meta-analysis and systematic review, and 19 literature reviews (Table 3). Of these, 3 cross-sectional studies were COVID-19-related studies [47,48,49], and 8 RCTs included 3 studies related to COVID-19 [50,51,52] and 5 studies related to the common cold [53,54,55,56,57].

Table 3. Main characteristics of included article evaluated the association between VC and respiratory-related viral infection.

Authors Study design Sample size Biomarker Dose Result* Mean or range of age (yr) Target
Xing et al. (2021) [47] Cross-sectional 25, COVID-19 patients treated with VC VC Patients with COVID-19: IV VC at a dose of 100 mg/kg/day + Patients treated with VC (n = 39) COVID-19
6, COVID-19 patients Patients treated without VC (n = 35.63), Healthy (n = 31.42)
51, healthy volunteers
Zhao et al. (2021) [48] Cross-sectional 6, severe Inflammatory response, immune Severe, 162.7 mg/kg/days + Severe, 56 Critical, 63 COVID-19
6, critical Critical, 178.6 mg/kg/days
Zhao et al. (2021) [49] Cross-sectional 55, HDIVC group No. of patients, duration of systemic inflammatory response syndrome 100 mg/kg/day − HDIVC, 36 COVID-19
55, control group Control, 36
Zhang et al. (2021) [50] RCT 27, severe SARS-CoV-2-related pneumonia. HDIVC group Mortality, P/F ratio, IL-6 IV VC 24 g + HDIVC, 66.7 COVID-19
29, placebo group Control, 66.3
Thomas et al. (2021) [51] RCT 50, usual care 50% reduction in symptoms Ascorbic acid 8,000 mg, Zinc gluconate 50 mg, Ascorbic acid 8,000 mg + Zinc gluconate 50 mg − 45.2 COVID-19
48, ascorbic acid Standard of care, 42.0
58, zinc gluconate Ascorbic acid only, 45.6
58, ascorbic acid + zinc gluconate Zinc only, 44.1
Ascorbic acid with zinc, 48.7
Kumari et al. (2020) [52] RCT 75, intervention (standard of care + IV VC) No. of days required for treatment, hospital stay VC 50 mg/kg/day + Intervention, 52 COVID-19
75, placebo (standard of care) Placebo, 53
Audera et al. (2001) [53] RCT 42, VC 0.03 g Daily symptoms, severity VC 0.03 g − VC 0.03 g, 38.6 Common cold
47, VC 1 g VC 1 g VC 1 g, 40.1
50, VC3 g VC 3 g VC 3 g, 39.9
45, VC 3 g + additives VC 3 g + bioflavenoids 75 mg, rutin 150 mg, hisperidin 150 mg, rose hip extract 750 mg acerola 150 mg VC 3 g + additives, 45.1
Van Straten and Josling (2002) [54] RCT 84, active treatment Recorded any common cold infections and symptoms in a daily diary VC 500 mg + Active treatment, 47.7 Common cold
84, placebo Placebo, 48.5
Sasazuki et al. (2006) [55] RCT 120, 50 mg of VC Symptom, cold duration VC 50/500 mg − Low dose, 58.7 Common cold
144, 500 mg of VC High dose, 56.3
Johnston et al. (2014) [56] RCT 15, VC Plasma vitamin, cold episodes, duration, cold duration and severity VC 1,000 mg + VC, 23.0 Cold incidence
13, placebo Placebo, 23.2
Kim et al. (2020) [57] RCT 695, VC group Diagnosis of common colds VC 6,000 mg + < 19, 491 Common cold
749, placebo group 20–22, 878
> 23, 75
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IV, intravenous; VC, vitamin C; COVID-19, coronavirus disease 2019; HDIVC, high-dose intravenous vitamin C; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; P/F, PaO2/FiO2; IL, interleukin; RCT, randomized control trial.

*+: significant effect on the prevention of respiratory-related viral infection; −: no significant effect on the prevention of respiratory-related viral infection.

Vitamin B6

For vitamin B6, 151 articles were searched, and 147 articles were excluded by reviewing the titles and abstracts. One systematic review and 3 reviews were also excluded (Figure 1E). Thus, no articles were eligible for a literature review.

Folate

A total of 220 articles on folic acid were searched (Figure 1F). As a result of reviewing the titles and abstracts, 217 were excluded. Three papers were classified into 2 cross-sectional studies and one cohort study and underwent literature reviews (Table 4).

Table 4. Main characteristics of included article evaluated the association between folate and respiratory-related viral infection.

Authors Study design Sample size Biomarker Dose Result* Mean or range of age (yr) Target
Acosta-Elias and Espinosa-Tanguma (2020) [58] Cross-sectional 94, pregnant women The likelihood of requiring hospitalization for SARS-CoV-2 infection - + - COVID-19
137, non-pregnant in 2009 A-H1N1 pandemic A-H1N1 pandemic
908 of those patients were non-pregnant women in reproductive age
55, pregnant women in COVID-19 pandemic
Hamer et al. (2009) [59] Cross-sectional 352 Vitamins and minerals concentration - + Men, 75.8 Respiratory infections
Women, 73.7
Itelman et al. (2020) [60] Cohort 162 Blood folate concentration - + 52 COVID-19
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COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

*+: significant effect on the prevention of respiratory-related viral infection; −: no significant effect on the prevention of respiratory-related viral infection.

The cross-sectional studies consisted of one study on COVID-19 [58] and A-H1N1 and one study on respiratory infections [59]. A cohort study related to COVID-19 was conducted [60].

Vitamin B12

The search yielded 167 studies related to vitamin B12, and among them, 164 papers were excluded by reviewing the titles and abstracts (Figure 1G). No papers underwent a literature review because one systematic review and 2 reviews were excluded.

DISCUSSION

This review was conducted to investigate the effects of vitamins on COVID-19/SARS/MERS/cold/influenza-related viral infections.

Eighteen of the 27 studies related to vitamin D and COVID-19 reported the effect of low levels of vitamin D in the blood on the occurrence of COVID-19. The 25-hydroxyvitamin D (25(OH)D) blood levels of COVID-19-positive patients were reported to be lower than 10–11.1 ng/mL [8,11]. Patients with vitamin D deficiency have seemed more than 5 times higher to be infected with COVID-19 than patients without vitamin D deficiency [23]. In addition, it was reported that for every 1% increase in the prevalence of vitamin D deficiency, the number of deaths from COVID-19 increases by 55 per million [27]. Serum 25(OH)D concentrations in COVID-19-positive patients were 25.95 ± 14.56 ng/mL [20]. Ye et al. [35] identified a potential threshold of serum 25(OH)D of 41.19 nmol/L for COVID-19 prevention. COVID-19-positive patients were hospitalized for a prolonged period if they had low vitamin D levels at the time of admission [25]. It has been reported that the normalization of serum 25(OH)D levels shortened hospital stays and reduced inflammatory biomarkers [37]. Of the 16 subjects who consumed 60,000 IU/d of vitamin D for 7 days, 10 tested negative for COVID-19, and only 5 of the 24 subjects who did not take vitamin D tested negative for COVID-19 [37]. However, 9 studies reported that vitamin D had no significant effect on COVID-19 prevention. Among the 12 studies related to respiratory diseases, 5 studies reported that vitamin D had a significant effect on the prevention of respiratory diseases. Serum 25(OH)D concentrations above 38 ng/mL lowered the risk of developing acute viral respiratory infections by about half [17], and mortality from respiratory diseases increased significantly as 25(OH)D levels fell below 50 nmol/L [19]. The group that consumed 1,200 IU of vitamin D for 4 months (8.0 ± 2.7 years) had a significantly lower number of influenza A infections than the group that consumed 400 IU (7.7 ± 2.5 years) [45].

Vitamin E has not been studied for its effect on COVID-19, and only one study was related to respiratory infections. The number of respiratory infections was significantly lower in the vitamin E intake group (200 IU, 84.7 years) than in the vitamin E non-intake group (84.3 years) [46].

Vitamin C reduced COVID-19-positive diagnoses in 4 out of 6 studies involving COVID-19. The vitamin C concentration in the plasma of COVID-19 patients was 5 times lower than that of healthy people (p < 0.001) [47], and C-reactive protein levels were significantly reduced when 162.7–178.6 mg/kg/day of vitamin C was consumed (p < 0.05), and lymphocyte counts, CD4+ T-cells, and respiratory function were significantly increased (p < 0.05) [48]. The intravenous administration of 24 g of vitamin C reduced COVID-19-induced mortality and interleukin-6 (p = 0.04) levels [50], an inflammatory index. The duration of symptoms and duration of hospitalization were significantly reduced when 50 mg/kg/day of vitamin C was supplied in the same way (p <0.001) [52]. In the studies on vitamin C and colds, 3 out of 5 studies showed the effect of reducing the cold diagnosis rate and the duration of cold symptoms by a vitamin C intake of 500–6,000 mg [54,56,57].

Two studies related to folate and COVID-19 found that folate had a positive effect on COVID-19 prevention. Folate supplementation was a factor in protecting patients from COVID-19 infection [58]. The reason is that folate inhibits furin protease, which is necessary for viruses to enter host cells, and folate inactivates protease 3C-like protease, a protein that the virus needs to replicate [58]. Indeed, it has been reported that blood folate levels were low in patients with severe COVID-19 (p = 0.014) [60]. A study related to folate and respiratory infections also reported that a deficiency in micronutrients, such as folate, was closely related to the occurrence of pneumonia or cold (p < 0.001) [59]. In this study, no publications on the relationship between vitamins and SARS/MERS were found during the study period.

Thus, the results of this study found that maintaining normal blood levels of vitamin D, vitamin E, vitamin C, and folate had a positive effect on the prevention of COVID-19/cold/influenza. This effect is thought to be possible by maintaining normal blood levels through the daily intake of these nutrients. However, due to the limited period of this study, additional research publications related to these vitamins and COVID-19/SARS/MERS/cold/influenza will need to be collected, analyzed and evaluated periodically in the future.

Footnotes

Funding: This work was supported by the Amway corporation.

Conflict of Interest: The authors declare that they have no competing interests.

Author Contributions:
  • Conceptualization: Park E.
  • Funding acquisition: Park E.
  • Investigation: Park JH, Lee Y, Choi M.
  • Methodology: Lee Y.
  • Project administration: Lee Y.
  • Supervision: Park EJ.
  • Writing - original draft: Park JH, Lee Y, Choi M.
  • Writing - review & editing: Park JH.

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