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:Mohamed Zhang.
May 4 |
Vitamin B9 for COVID-19: real-time meta analysis of 18 studies (12 treatment studies and 6 sufficiency studies) | |
| 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.. | ||
Apr 16 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
, 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 |
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 |
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 |
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 |
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 |
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 8 2022 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 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. | ||
References
Deschasaux-Tanguy et al., Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort, BMC Medicine, doi:10.1186/s12916-021-02168-1.
Farag et al., The Use of Folic acid as a Prophylaxis against COVID-19 among Healthcare Workers, Microbes and Infectious Diseases, doi:10.21608/mid.2022.170328.1405.
Scaglione et al., Folate, folic acid and 5-methyltetrahydrofolate are not the same thing, Xenobiotica, doi:10.3109/00498254.2013.845705.
Please send us corrections, updates, or comments.
c19early involves the extraction of 100,000+ datapoints from
thousands of papers. Community updates
help ensure high accuracy.
Treatments and other interventions are complementary.
All practical, effective, and safe
means should be used based on risk/benefit analysis.
No treatment or intervention is 100% available and effective for all current
and future variants.
We do not provide medical advice. Before taking any medication,
consult a qualified physician who can provide personalized advice and details
of risks and benefits based on your medical history and situation. IMA and WCH
provide treatment protocols.
Thanks for your feedback! Please search before submitting papers and note
that studies are listed under the date they were first available, which may be
the date of an earlier preprint.