Supplementary folic acid related to increased threat of COVID-19 prognosis and mortality

In a latest examine printed within the journal BMJ Open, researchers investigated the impression of folic acid dietary supplements and methotrexate, together or individually, on illness severity and mortality in coronavirus illness 2019 (COVID-19) circumstances.

Supplementary folic acid related to increased threat of COVID-19 prognosis and mortalityExamine: Folic acid and methotrexate use and their affiliation with COVID-19 prognosis and mortality: a case–management evaluation from the UK Biobank. Picture Credit score: Pixel-Shot / Shutterstock


Folate, or vitamin B9, performs an important function in varied mobile features, together with amino acid synthesis in protein metabolism and nucleic acid metabolism for the synthesis of deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). Nevertheless, research have proven that extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the host cell’s folate and glucose reserves to copy the viral genome. This viral replication is reported to be delicate to folate inhibitors comparable to methotrexate, which is broadly prescribed as a chemotherapy agent and a first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA).

Folic acid — the oxidized type of folate — is prescribed as a complement to pregnant ladies and as a remedy for circumstances comparable to sickle cell anemia and epileptic seizures. In the USA and 80 different nations, folic acid is used to fortify meals, and the UK intends to comply with swimsuit. Contemplating the present and future widespread use of folic acid dietary supplements, it is very important perceive the function of folic acid in aiding SARS-CoV-2 replication and exacerbating COVID-19 severity.

Concerning the examine

The current examine carried out a case-control evaluation to find out the differential COVID-19 prognosis and mortality threat related to the usage of folic acid dietary supplements and methotrexate medicines. The dataset obtained from the UK Biobank (UKBB) consisted of knowledge from 380,380 contributors who had been prescribed folic acid, methotrexate, anticonvulsants, iron dietary supplements, and different medicines comparable to statins. The provision of physique mass index (BMI) measure, Townsend deprivation index, and smoking standing knowledge additionally decided the number of contributors.

Individuals had been thought-about COVID-19 optimistic primarily based on a optimistic PCR take a look at for SARS-CoV-2 and an Worldwide Classification of Illnesses (ICD)-10 code for confirmed or possible COVID-19. Of the 380,380 contributors chosen from UKBB, 26,033 had been COVID-19 optimistic circumstances, of whom 820 had succumbed to the illness.

The info had been additionally grouped in line with ethnicity, intercourse, age (under 60 and above 74 years), and extra comorbidity elements comparable to RA and sickle cell anemia. The affiliation of the prescription knowledge with COVID-19 prognosis and mortality was analyzed. Statistical fashions had been adjusted for demographic elements, comorbidities, and different medicines.


The examine outcomes point out a 1.5-fold improve in COVID-19 prognosis threat and a 2.5-fold improve in COVID-19-related mortality threat related to folic acid complement prescriptions. Sufferers on prescribed methotrexate and folic acid dietary supplements weren’t at elevated threat of COVID-19 prognosis or demise, indicating that methotrexate might play an antagonistic function in opposition to the deleterious impact of folic acid in COVID-19 sufferers.

Methotrexate was not related to an elevated threat of COVID-19 prognosis. Nevertheless, given the small pattern measurement of mortality circumstances who had been prescribed methotrexate within the absence of folic acid dietary supplements, the researchers couldn’t decide the mortality threat related to a prescription of solely methotrexate.

Rheumatoid arthritis sufferers who weren’t on DMARD remedy had been at an elevated threat of COVID-19-related mortality, which might point out the absence of the protecting impact of methotrexate, confounded by indications on account of different medicines or poor illness administration. In comparison with medicines like sulfasalazine, rituximab, and different immunosuppressants, methotrexate confirmed decrease odds of COVID-19-related mortality.

The examine additionally presents info highlighting the significance of optimum folate ranges. Folate deficiency has been linked to suppression of immune operate and poor outcomes in some COVID-19 sufferers. Low vitamin B12 ranges linked to folate deficiency have additionally been related to COVID-19 severity. The authors imagine that host resistance to COVID-19 would possibly rely upon an optimum vary of folate within the physique, with each deficiency and extra being detrimental to the resistance in opposition to SARS-CoV-2.

A number of the limitations to the evaluation embody (1) the shortcoming to account for different remedy strategies comparable to antivirals and monoclonal antibodies affecting the end result in COVID-19 sufferers and (2) the issue in generalizing the findings of the examine to the bigger inhabitants because the pattern set was dominated by middle-aged (older than 45 years) white European contributors.


To summarize, with caveats on the inference of causality, the examine helps the speculation that prime folate ranges ensuing from folic acid dietary supplements might improve the chance of COVID-19 prognosis and demise. Methotrexate, a folate antagonist, gives some protecting impact in opposition to the detrimental results of folic acid in COVID-19 sufferers. Nonetheless, the widespread, use of folic acid dietary supplements highlights the necessity for extra thorough research on the function of folic acid in COVID-19 development.

Journal reference:

  • Topless, R., Inexperienced, R., Morgan, S. L., Robinson, P., Merriman, T., & Gaffo, A. L. (2022). Folic acid and methotrexate use and their affiliation with COVID-19 prognosis and mortality: a case–management evaluation from the UK Biobank. BMJ Open, 12(8), e062945., material/12/8/e062945.information

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