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Vitamin B9 for COVID-19
9 studies from 172 scientists
35,148 patients in 7 countries
4 sufficiency studies with 481 patients in 4 countries
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. Folic acid may not be the best form for supplementation.
COVID-19 Vitamin B9 studies. Jun 2023.
0 0.5 1 1.5+ All studies -11% Mortality -62% Hospitalization 28% Cases 9% RCTs 88% Sufficiency 12% Prophylaxis -11% Favorsvitamin B9 Favorscontrol
Vitamin B9 COVID-19 studies. 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 results [Deschasaux-Tanguy, Farag], as do sufficiency studies. Folic acid may not be the most effective or safest form for supplementation [Scaglione]. Studies show that a significant fraction of people have genetic variations limiting the ability to convert folic acid to the active form. Recent:
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Jun 3
Covid Analysis (Preprint) (meta analysis) Vitamin B9 for COVID-19: real-time meta analysis of 13 studies (9 treatment studies and 4 sufficiency studies)
Meta analysis using the most serious outcome reported shows 11% [-19‑52%] higher risk, without reaching statistical significance. • Sufficiency studies, analyzing outcomes based on serum levels, show 12% [2‑21%] im..
May 21
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
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
Karakousis et al., Journal of Personalized Medicine, doi:10.3390/jpm13030561 (Review) 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
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
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
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.
Aug 24
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
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
Loucera et al., medRxiv, doi:10.1101/2022.08.14.22278751 (Preprint) Real-world evidence with a retrospective cohort of 15,968 Andalusian COVID-19 hospitalized patients suggests 21 new effective treatments and one drug that increases death risk
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.
May 27
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
Chen et al., Pharmaceutical Biology, doi:10.1080/13880209.2022.2063341 (In Vitro) 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
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
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
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.
Mar 29
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
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 8
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
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
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
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
Leal-Martínez et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph19031172 (date from earlier 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..
Jul 15
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 2
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 8
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
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
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.
May 31
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
Kumar et al., VirusDisease, doi:10.1007/s13337-020-00643-6 (date from earlier 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
Scaglione et al., Xenobiotica, doi:10.3109/00498254.2013.845705 (Review) 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 ..
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