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Vitamin B9 for COVID-19
12 studies with >50,000 patients
Serious outcome risk
Vitamin B9
Control
Results are contradictory. Several studies show higher mortality, however counfounding by indication may be significant — patients prescribed folic acid may have higher risk on average. Folic acid may not be the best form for treatment.
COVID-19 Vitamin B9 studies · October 2026
Results to date are contradictory. Several studies show higher mortality, however counfounding by indication may be significant — patients prescribed folic acid may have significantly higher risk on average. Studies independent of prescriptions based on patient condition show positive results1,2, as do sufficiency studies. Folic acid may not be the most effective or safest form for supplementation3. Studies show that a significant fraction of people have genetic variations limiting the ability to convert folic acid to the active form. Recent:
Tyson
Adetunji.
Covid Analysis Vitamin B9 for COVID-19: real-time meta-analysis of 18 studies (12 treatment studies and 6 sufficiency studies) (Version 9)
Meta-analysis using the most serious outcome reported shows 8% [-18‑41%] higher risk, without reaching statistical significance. 6 sufficiency studies analyze outcomes based on serum levels, showing 22% [7‑34%] lower..
Feb 28
 Adetunji et al., BMC Infectious Diseases, doi:10.1186/s12879-026-12959-7 Association between serum vitamins and COVID-19 infection: a cross-sectional study of healthcare workers in a Nigerian tertiary hospital
Cross-sectional study of 181 healthcare workers showing significantly lower serum levels of most vitamins (A, C, D, E, and B-complex vitamins except B12) in those with COVID-19 infection compared to uninfected controls. Authors hypothesiz..
Jul 15
2025
 Al-Khrasani et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2025.118346 Do vitamins halt the COVID-19-evoked pro-inflammatory cytokines involved in the development of neuropathic pain?
Review of vitamin supplementation for COVID-19-evoked pro-inflammatory cytokines involved in neuropathic pain development. Authors examine how certain vitamins may help prevent post-COVID neuropathic pain by modulating pro-inflammatory cy..
Apr 16
2025
 Morello et al., Italian Journal of Pediatrics, doi:10.1186/s13052-025-01961-5 Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review
Retrospective 1,243 children with COVID-19 showing lower risk of long COVID at 6 months when treated with a Multi-Element Product (MEP) containing antioxidants and anti-inflammatory compounds (magnesium 200 mg, quercetin 150 mg, curcumin ..
Dec 31
2024
 Mohamed et al., The Medical Journal of Cairo University, doi:10.21608/mjcu.2024.411836 Nutritional Assessment of Critically Ill Children with COVID-19 Admitted to PICU
43% lower mortality (p=0.16). Retrospective 60 hospitalized pediatric COVID-19 patients showing deficiencies in vitamin D, folic acid (B9), zinc, and selenium associated with higher mortality.
Dec 20
2024
 Zhang et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2024.1476603 Longitudinal ozone exposure and SARS-CoV-2 infection in late pregnancy: a retrospective cohort study
40% fewer cases (p=0.23). Retrospective 600 pregnant women in an urban area of China showing a significantly lower risk of SARS-CoV-2 infection in late pregnancy with higher gestational ozone exposure levels. Ozone exposure, driven by photochemical reactions, is s..
Jul 31
2024
 Pavlyshyn et al., La Rivista Italiana della Medicina di Laboratorio, doi:10.23736/S1825-859X.24.00247-0 Potential role of vitamins B (B6, B9, B12) in the severity of COVID-19 in children
Retrospective 112 pediatric COVID-19 patients in Ukraine showing lower levels of vitamins B6, B9, and B12 associated with COVID-19 severity.
Jul 18
2024
 Wu et al., Elsevier BV, doi:10.2139/ssrn.4897774 Biomarkers Prediction and Immune Landscape in Covid-19 and “Brain Fog”
In silico study identifying key genes and potential therapeutic agents related to brain fog in COVID-19 patients. Authors analyzed frontal cortex transcriptome data and found upregulated genes involved in immune-related pathways and downr..
Mar 24
2024
 Mosadegh et al., AMB Express, doi:10.1186/s13568-024-01690-8 NBS superfood: a promising adjunctive therapy in critically ill ICU patients with omicron variant of COVID-19
RCT 400 critically ill ICU patients with omicron-related ARDS showing significantly reduced mortality and inflammatory markers with a nutritional supplement containing vitamins A, B1-B3, B5, B6, B9, C, D, K, and zinc, potassium, manganese..
Jan 31
2024
 Ulloque-Badaracco et al., SAGE Open Medicine, doi:10.1177/20503121241253957 Association of vitamin B12, folate, and homocysteine with COVID-19 severity and mortality: A systematic review and meta-analysis
Systematic review and meta-analysis of 13 studies with 2,134 patients for the association of vitamin B12, folate, and homocysteine with COVID-19 severity and mortality.
Dec 28
2023
 Pennisi et al., Biomolecules, doi:10.3390/biom14010043 An Integrated In Silico and In Vitro Approach for the Identification of Natural Products Active against SARS-CoV-2
In vitro and in silico study showing SARS-CoV-2 inhibition with folic acid and luteolin-7-O-glucuronide. Enzymatic assays showed that both compounds have micromolar range inhibition of SARS-CoV-2 proteases 3CLpro and PLpro. However, pseud..
Nov 15
2023
 Moatasim et al., Microorganisms, doi:10.3390/microorganisms11112777 Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E
In vitro and in silico analysis finding that methylcobalamin, hydroxocobalamin, and cyanocobalamin forms of vitamin B12 showed broad-spectrum inhibition against SARS-CoV-2, MERS-CoV, and HCoV-229E. Methylcobalamin had the highest activity..
Nov 7
2023
 Akbar et al., Nutrients, doi:10.3390/nu16071037 The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
18% more cases (p=0.29). Retrospective 10,000 adults in Qatar, showing higher risk of COVID-19 cases with vitamin B9 supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Jun 20
2023
 Mahjoub et al., Explore, doi:10.1016/j.explore.2023.06.009 Melatonin, vitamins and minerals supplements for the treatment of Covid-19 and Covid-like illness: a prospective, randomized, double-blind multicenter study.
67% improved recovery (p=0.32). RCT 164 low-risk (no hospitalizations) patients in Tunisia, showing improved recovery with zinc, melatonin, and vitamins A-E. This study includes COVID-19 and COVID-like illness, with 49% of 128 patients receiving a PCR test being COVID-1..
May 21
2023
 Chen et al., Nutrition, doi:10.1016/j.nut.2023.112087 Early oral nutritional supplement improves COVID-19 outcomes among hospitalized older patients during the omicron wave
PSM retrospective 1,181 COVID-19 patients ≥60 years old in China, showing significantly lower mortality with a nutritional supplement. Hospitalization time and viral clearance time was improved with earlier initiation of treatment. The su..
Apr 17
2023
 Abdulrahman et al., The International Journal of Psychiatry in Medicine, doi:10.1177/00912174231171220 Correlates of poor clinical outcomes related to COVID-19 among older people with psychiatric illness - a mixed methods study
75% higher mortality (p=0.63) and 45% lower progression (p=0.42). Retrospective 81 pyschiatric inpatients in the UK, mean age 76, showing no significant difference in COVID-19 mortality with folate deficiency.
Mar 21
2023
 Karakousis et al., Journal of Personalized Medicine, doi:10.3390/jpm13030561 The Role of Folic Acid in SARS-CoV-2 Infection: An Intriguing Linkage under Investigation
Review of the potential benefit of vitamin B9 for COVID-19 and results of 3 clinical studies (currently there are studies).
Nov 20
2022
 Farag et al., Microbes and Infectious Diseases, doi:10.21608/mid.2022.170328.1405 The Use of Folic acid as a Prophylaxis against COVID-19 among Healthcare Workers
88% fewer cases (p<0.0001). Cluster RCT 526 healthcare workers in Egypt, showing lower COVID-19 cases with folic acid supplementation, and a dose-response relationship. Each wave of health care workers was randomized within 14 day isolation periods, introducing pote..
Nov 9
2022
 Darand et al., British Journal of Nutrition, doi:10.1017/S0007114522003075 The association between B vitamins and the risk of COVID-19
Retrospective 9,189 adults showing no significant relationship between vitamin B9 intake and COVID-19 cases.
Oct 10
2022
 Yas et al., HIV Nursing, 22:2 Impact of Folic acid status or its metabolites and hypoxia on COVID-19
Retrospective 75 COVID-19 patients and 45 healthy controls in Iraq, showing lower folic acid levels in COVID-19 patients, and lower levels for severe vs. moderate cases.
Sep 27
2022
 Keskin et al., Progress in Nutrition, doi:10.23751/pn.v24i3.13462 Association between low serum folic acid and vitamin B12 levels with COVID-19 prognosis
32% shorter hospitalization (p<0.0001). Retrospective 529 hospitalized COVID-19 patients in Turkey showing lower serum folic acid levels associated with longer hospitalization and higher mortality. Folic acid deficiency and insufficiency were common. There was no significant as..
Aug 24
2022
 Topless et al., BMJ Open, doi:10.1136/bmjopen-2022-062945 Folic acid and methotrexate use and their association with COVID-19 diagnosis and mortality: a case–control analysis from the UK Biobank
164% higher mortality (p<0.0001) and 51% more cases (p<0.0001). UK Biobank retrospective showing higher cases and mortality with folic acid supplementation.
Aug 17
2022
 Zhang et al., Frontiers in Microbiology, doi:10.3389/fmicb.2022.980903 Folic acid restricts SARS-CoV-2 invasion by methylating ACE2
In vitro and mouse study showing that folic acid decreased ACE2 expression and inhibited SARS-CoV-2.
Aug 16
2022
 Loucera et al., Virology Journal, doi:10.1186/s12985-023-02195-9 (date from preprint) Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
1% lower mortality (p=0.88). Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing no significant difference in mortality with existing use of folic acid. Since only hospitalized patients are included, results do not reflect different probabilities of..
May 27
2022
 Galmés et al., Nutrients, doi:10.3390/nu14112254 Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations
Ecological study in Spain, showing lower intake of vitamin D, A, B9, and zinc in regions with the highest COVID-19 incidence and mortality. Vitamin D intake was associated with lower prevalence, incidence, and a combined incidence+mortali..
May 20
2022
 Chen et al., Pharmaceutical Biology, doi:10.1080/13880209.2022.2063341 Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein
In silico and in vitro study identifying folic acid as a potential inhibitor of the SARS-CoV-2 nucleocapsid protein.
May 16
2022
 Eskandari, V., Journal of Molecular Modeling, doi:10.1007/s00894-022-05138-3 Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein
In silico study identifying folic acid, among other compounds, as a potential inhibitor of the SARS-CoV-2 Mpro and spike proteins.
Apr 30
2022
 Voelkle et al., Nutrients, doi:10.3390/nu14091862 Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study
12% lower combined mortality/ICU admission (p=0.02). Prospective study of 57 consecutive hospitalized COVID-19 patients in Switzerland, showing lower risk of mortality/ICU admission with vitamin B9. Adjustments only considered age.
Apr 21
2022
 Doğan et al., Sağlık Akademisi Kastamonu, doi:10.25279/sak.1102076 Folate, B12 and Iron Levels in COVID 19 Patients Observational Case-Control Study
56% lower mortality (p=0.46) and 11% higher ICU admission (p=1). Retrospective 70 COVID-19 cases and 70 non-COVID-19 controls in Turkey, showing no significant differences based on folic acid levels.
Apr 20
2022
 Pandya et al., Informatics in Medicine Unlocked, doi:10.1016/j.imu.2022.100951 Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach
In silico study showing significant interaction with SARS-CoV-2 targets for multiple vitamins.
Mar 29
2022
 MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
no change in cases (p=1). Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of vitamin B9.
Feb 28
2022
 Nimer et al., Bosnian Journal of Basic Medical Sciences, doi:10.17305/bjbms.2021.7009 The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
28% lower hospitalization (p=0.23) and 28% lower severe cases (p=0.16). Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B9 prophylaxis, without statistical significance.
Jan 13
2022
 Tyson et al., Journal of Independent Medicine, doi:10.71189/JIM/2025/V01N02A06 (date from preprint) Low Rates of Hospitalization and Death in 4376 COVID-19 Patients Treated With Early Ambulatory Medical and Supportive Care: A Case Series and Observational Study
98% lower mortality (p<0.0001) and 99% lower hospitalization (p<0.0001). Retrospective 4,376 patients with mild/moderate COVID-19 in the USA treated with multiple medications including HCQ/ivermectin, zinc, azithromycin, budesonide, and dexamethasone (exact treatments specific to each patient), showing signifi..
Jan 8
2022
 Monserrat Villatoro et al., Pharmaceuticals, doi:10.3390/ph15010078 A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
132% higher mortality (p=0.003). PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine..
Dec 31
2021
 Tseimakh et al., Siberian Medical Review, doi:10.20333/25000136-2021-6-60-69 Effect of folic acid in patients with lung damage caused by coronavirus SARS-CoV-2
Prospective study of 117 patients in Serbia, 78 treated with folic acid, pyridoxine hydrochloride, and cyanocobalamin, showing improved resolution of CT findings and faster viral clearance. 5mg folic acid, 4mg pyridoxine hydrochloride, an..
Nov 30
2021
 Deschasaux-Tanguy et al., BMC Medicine, doi:10.1186/s12916-021-02168-1 Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort
16% fewer cases (p=0.02). Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.
Nov 10
2021
 Bliek-Bueno et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph182211786 Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy
87% higher mortality (p<0.0001). Retrospective 8,570 individuals in Spain and Italy, showing higher mortality with combined vitamin B9 and B12 supplementation. Adjustments only considered age.
Oct 25
2021
 Leal-Martínez et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph19031172 (date from preprint) Effect of a Nutritional Support System to Increase Survival and Reduce Mortality in Patients with COVID-19 in Stage III and Comorbidities: A Blinded Randomized Controlled Clinical Trial
86% lower mortality (p=0.03) and 57% lower ventilation (p=0.31). 80 patient RCT with 40 patients treated with a comprehensive regimen of nutritional support, showing significantly lower mortality with treatment. Treatment contained cholecalciferol, vitamin C, zinc, spirulina maxima, folic acid, glutami..
Sep 5
2021
 Al-Alwan et al., Indian Journal of Forensic Medicine & Toxicology, doi:10.37506/ijfmt.v15i4.18454 Assessment of Serum Ferritin, Folate, Vitamin B12, C-reactive Protein, D-dimer and Homocysteine in Patients with Severe and Critical Covid-19 Infection
Analysis of 88 COVID-19 patients showing lower folic acid and vitamin B12 levels in severe vs. non-severe cases.
Jul 15
2021
 Serseg et al., Current Computer-Aided Drug Design, doi:10.2174/1573409916666200422075440 Hispidin and Lepidine E: Two Natural Compounds and Folic Acid as Potential Inhibitors of 2019-novel Coronavirus Main Protease (2019-nCoVMpro), Molecular Docking and SAR Study
In silico study identifying folic acid, hispidin, and lepidine E as potential SARS-CoV-2 Mpro inhibitors.
Mar 31
2021
 Dalbeni et al., Nutrition, Metabolism and Cardiovascular Diseases, doi:10.1016/j.numecd.2020.12.005 Excessive vitamin B12 and poor outcome in COVID-19 pneumonia
Prospective study of 49 hospitalized COVID-19 patients in Italy showing higher vitamin B12 levels associated with worse outcomes. In multivariate analysis, only age was independently associated with worse outcomes.
Mar 2
2021
 Meisel et al., Nutrients, doi:10.3390/nu13030812 Folate Levels in Patients Hospitalized with Coronavirus Disease 2019
27% lower mortality (p=0.54) and 6% lower combined mortality/intubation (p=0.88). Retrospective 333 hospitalized patients in Israel, showing no significant difference in outcomes with low folate levels or with folic acid supplementation.
Feb 28
2021
 Bejan et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2376 (date from preprint) DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9% lower mortality (p=0.87), 1% lower ventilation (p=0.99), and 17% lower ICU admission (p=0.7). Retrospective 9,748 COVID-19 patients in the USA showing no significant differences with vitamin B9 use, without statistical significance.
Feb 8
2021
 Ersöz et al., International Journal of Clinical Practice, doi:10.1111/ijcp.14078 The association between micronutrient and hemogram values and prognostic factors in COVID-19 patients: A single-center experience from Turkey
Retrospective 310 hospitalized COVID-19 patients in Turkey, showing patients that were admitted to the ICU, intubated, or died had lower vitamin B9 levels compared to those that were not (statistically significant for ICU admission and in..
Jan 18
2021
 Hosseini et al., Precision Clinical Medicine, doi:10.1093/pcmedi/pbab001 Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs
In silico study identifying novel ligands as potential inhibitors for SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp.
Nov 30
2020
 Ugurel et al., International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.138 Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13)
In silico study reporting that folic acid, cangrelor, fludarabine, and polydatin are potential inhibitors of SARS-CoV-2 Nsp13.
Sep 8
2020
 Galmés et al., Nutrients, doi:10.3390/nu12092738 Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework
Ecological study of European countries analyzing 10 vitamins and minerals endorsed by the European Food Safety Authority as having sufficient evidence for a causal relationship between intake and optimal immune system function: vitamins D..
Jul 26
2020
 Wiltshire et al., Medical Hypotheses, doi:10.1016/j.mehy.2020.110142 High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia
Hypothesis that high-dose folic acid (5-10mg daily) may be beneficial for COVID-19 related pulmonary hypertension and hypoxemia, based on systemic vascular effects showing improved endothelial function and prevention of nitrate tolerance ..
May 31
2020
 Itelman et al., Israel Medical Association Journal, 22:5 Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center
Retrospective 162 COVID-19 patients in Israel, showing lower vitamin B9 levels associated with increased COVID-19 severity.
May 27
2020
 Kumar et al., VirusDisease, doi:10.1007/s13337-020-00643-6 (date from preprint) In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19
In silico analysis identifying folic acid and derivates like tetrahydrofolic acid and 5-methyl tetrahydrofolic acid as potentially beneficial for SARS- COV-2.
Feb 4
2014
 Scaglione et al., Xenobiotica, doi:10.3109/00498254.2013.845705 Folate, folic acid and 5-methyltetrahydrofolate are not the same thing
Review of folate as an essential micronutrient and possible forms for supplementation in case of deficiency - folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF). Authors note that 5-MTHF has important advantages over synthetic ..
Oct 1
2009
 EFSA, EFSA Journal, doi:10.2903/j.efsa.2009.1213 Scientific Opinion on the substantiation of health claims related to folate and blood formation (ID 79), homocysteine metabolism (ID 80), energy-yielding metabolism (ID 90), function of the immune system (ID 91), function of blood vessels (ID 94, 175, 192), cell division (ID 193), and maternal tissue growth during pregnancy (ID 2882) pursuant to Article 13(1) of Regulation (EC) No 1924/2006
European Food Safety Administration review concluding that there is a causal relationship between the intake of vitamin B9 and immune system function.
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