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:Chen Abdulrahman Scaglione Serseg Kumar Eskandari Ugurel.
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Jun 3 |
(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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
, 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 |
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 |
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 |
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 |
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 |
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 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 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 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 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. | ||
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 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 2014 |
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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