COVID-19 and MTHFR

COVID-19 and MTHFR

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder
Last updated:

What is COVID-19?

Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 

COVID rapidly spread worldwide and was declared a pandemic by the World Health Organization in March, 2020. As of 2025, it has resulted in more than 7 million deaths worldwide.1

New variants of the virus continue, and a significant number of individuals experience post‑infection symptoms known as long COVID.2

Link between Covid-19 and MTHFR

The MTHFR gene encodes an enzyme required for converting homocysteine to methionine. Common mutations of the MTHFR gene, particularly C677T and A1298C, reduce the activity of the MTHFR enzyme by up to 70%, leading to higher homocysteine levels.3

Population data has also suggested that regions with a higher prevalence of the MTHFR C677T variant - including parts of Southern Europe and Latin America - had higher COVID‑19 mortality rates. The frequency of the MTHFR C677 T allele in the Latino population (50%) is higher than that reported for most of the other populations in the world, while regions with very low C677T prevalence (such as Finland and sub‑Saharan Africa) had much lower rates of COVID.4

The study authors suggest that measuring both MTHFR genotype and homocysteine levels may help assess COVID‑19 risk and prognosis. They also recommended supplementation with B vitamins (particularly B6, B12, and B9) to help reduce elevated homocysteine levels and potentially reduce infection severity.

Link between Covid-19 and homocysteine levels

Several studies have reported higher homocysteine levels in patients with severe or post‑COVID conditions. A 2022 systematic review (including 694 patients) found a 15-24% increase in homocysteine levels among severe cases compared to mild infections.

One proposed mechanism is that SARS‑CoV‑2 replication depletes S‑adenosylmethionine (SAMe), impairing methylation and allowing homocysteine to accumulate.5

A 2025 PNAS study reported that patients with homzygous MTHFR C677T mutation also had a higher incidence of severe COVID‑19 along with abnormalities in one-carbon cycle metabolites.6

Higher homocysteine is known to increase oxidative stress, inflammation, the risk of thrombosis, and also the risk of cognitive decline.7 COVID-19 patients with high homocysteine levels are more likely to be admitted to ICU, with one study showing that each unit increase in homocysteine levels approximately doubled the risk of death in COVID-19 patients.8

COVID-19 risk when you have MTHFR

Current research has suggested that MTHFR variants may be a factor that potentially increases COVID‑19 severity and the risk of thrombosis. However, most experts agree that these variants are not major independent risk factors. Other factors such as age, obesity, cardiovascular disease, and nutritional status play much more significant roles in overall health.9

Those with MTHFR variants are advised to maintain a balanced diet, regular exercise, and monitor their own nutritional status.

MTHFR and COVID vaccines

Evidence to date does not suggest that MTHFR variants increase the risk of side effects or thromboembolic events following COVID‑19 vaccination. People with MTHFR mutations can safely receive standard COVID vaccines.10

Precautions to take against COVID when you have MTHFR

For those with MTHFR variants, monitoring homocysteine levels is important because elevated levels may worsen COVID‑19 outcomes.

Homocysteine metabolism depends on vitamins B9 (folate), B12, and B6. Supplementation with these nutrients - particularly methylfolate, the active form of folate - can support healthy methylation.11 Supplementing with these nutrients has been shown to reduce elevated homocysteine levels in people with MTHFR.12

COVID-19 and MTHFR

Key takeaways

  • Icon MTHFR mutations impair homocysteine metabolism, leading to higher homocysteine levels that may worsen the severity of a COVID‑19 infection.
  • Icon The COVID-19 virus may lead to increased homocysteine due to its depletion of SAMe. Monitoring homocysteine is strongly advised.
  • Icon Supplementation with vitamins B6, B9, and B12 is recommended for individuals with MTHFR mutations, as it helps maintain normal homocysteine levels and may reduce the risk of severe infection.

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  • High-Dose L Methylfolate 15 Mg for Natural Mood Support²
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Vegan, Non-GMO, Chewable Mint Tablets

Frequently Asked Questions about Covid-19 and MTHFR

Does COVID raise homocysteine levels?

Some research has suggested that the COVID-19 virus increases homocysteine by depleting S-adenosylmethionine (SAMe) during its viral replication, allowing homocysteine to accumulate.13
However, people with elevated homocysteine are also at greater risk of more severe COVID illness, so it’s important to monitor homocysteine levels.

Can you get the Covid vaccine if you have MTHFR?

Yes, current evidence shows no risk of adverse reactions for individuals with MTHFR variants.

What blood disorders are linked to the COVID vaccine?

Although extremely rare, some autoimmune blood conditions (e.g., thrombocytopenia or hemolytic anemia) have been reported after various vaccines, including COVID‑19 vaccines, but no direct link with MTHFR has been established.14

What causes high levels of homocysteine?

High homocysteine is most often due to deficiencies of specific enzymes and nutrients. The pathway in which homocysteine is remethylated to methionine requires folate and B12. The transsulfuration pathway requires vitamin B6 to convert homocysteine into cysteine and subsequently into sulfate.15
Genetic causes include MTHFR mutations (which results in MTHFR enzyme deficiency), defects in methionine, impaired vitamin B12 absorption/uptake, and/or nutritional deficiency of folate.

Acquired hyperhomocysteine may result from alcohol consumption, untreated celiac disease, prolonged use of proton pump inhibitors, and other lifestyle factors, clinical conditions, and medications. These factors affect the nutrients that have a key role in homocysteine metabolism.

References

  1. World Health Organisation; "Coronavirus disease (COVID-19)"; 2025 Nov

    https://www.who.int/news-room/fact-sheets/detail/coronavirus-disease-(covid-19)

  2. Destin Groff, Ashley Sun, Anna E Ssentongo, Djibril M Ba, Nicholas Parsons, Govinda R Poudel, Alain Lekoubou, John S Oh, Jessica E Ericson, Paddy Ssentongo, Vernon M Chinchilli; "Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review"; JAMA network open; 2021 Oct

    https://pubmed.ncbi.nlm.nih.gov/34643720/

  3. Boryana Petrova, Caitlin Syphurs, Andrew J Culhane, Jing Chen, Ernie Chen, Chris Cotsapas, Denise Esserman, Ruth R Montgomery, Steven H Kleinstein, Kinga K Smolen, Kevin Mendez, IMPACC Network, Jessica Lasky-Su, Hanno Steen, Ofer Levy, Joann Diray-Arce, Naama Kanarek; "MTHFR allele and one-carbon metabolic profile predict severity of COVID-19"; Proceedings of the National Academy of Sciences of the United States of America; 2025 Dec

    https://pubmed.ncbi.nlm.nih.gov/41410771/

  4. Giovanni Ponti, Lorenza Pastorino, Marco Manfredini, Tomris Ozben, Gabriella Oliva, Shaniko Kaleci, Raffaele Iannella, Aldo Tomasi; "COVID‐19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence"; Journal of clinical laboratory analysis; 2021 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8209953/

  5. Valter Bergant, Shintaro Yamada, Vincent Grass, Yuta Tsukamoto, Teresa Lavacca, Karsten Krey, Maria‐Teresa Mühlhofer, Sabine Wittmann, Armin Ensser, Alexandra Herrmann, Anja vom Hemdt, Yuriko Tomita, Shutoku Matsuyama, Takatsugu Hirokawa, Yiqi Huang, Antonio Piras, Constanze A Jakwerth, Madlen Oelsner, Susanne Thieme, Alexander Graf, Stefan Krebs, Helmut Blum, Beate M Kümmerer, Alexey Stukalov, Carsten B Schmidt‐Weber, Manabu Igarashi, Thomas Gramberg, Andreas Pichlmair, Hiroki Kato; "Attenuation of SARS‐CoV‐2 replication and associated inflammation by concomitant targeting of viral and host cap 2'‐O‐ribose methyltransferases"; The EMBO journal; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9350232/

  6. Boryana Petrova, Caitlin Syphurs, Andrew J. Culhane, Jing Chen, Ernie Chen, Chris Cotsapas, Denise Esserman, Ruth R. Montgomery, Steven H. Kleinstein, Kinga K. Smolen, Kevin Mendez, IMPACC Network, Jessica Lasky-Su, Hanno Steen, Ofer Levy, Joann Diray-Arce, Naama Kanarek; "MTHFR allele and one-carbon metabolic profile predict severity of COVID-19"; Proc. Natl. Acad. Sci. U.S.A.; 2025 Dec

    https://www.pnas.org/doi/10.1073/pnas.2509118122

  7. Pinar Oner, Seda Yilmaz, Serpil Doğan; "High Homocysteine Levels Are Associated with Cognitive Impairment in Patients Who Recovered from COVID-19 in the Long Term"; Journal of personalized medicine; 2023 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10056581/

  8. Işılay Kalan Sarı, Olgun Keskin, Ayşegül Seremet Keskin, Hamit Yaşar Elli̇dağ, Orbay Harmandar; "Is Homocysteine Associated with the Prognosis of Covid-19 Pneumonia"; International Journal of Clinical Practice; 2023 Mar

    https://onlinelibrary.wiley.com/doi/10.1155/2023/9697871

  9. Sura F Alsaffar, Noor Nihad Baqer; "Association between Methylenetetrahydrofolate Reductase (MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) Polymorphisms in Iraqi Patients with COVID-19"; Iranian journal of medical sciences; 2024 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC11300940/

  10. Melbourne Vaccine Education Centre; "MTHFR Gene"; 2026

    https://mvec.mcri.edu.au/references/mthfr-gene

  11. Alessandra Vezzoli, Cinzia Dellanoce, Teresa Maria Caimi, Daniele Vietti, Michela Montorsi, Simona Mrakic-Sposta, Roberto Accinni; "Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments"; Nutrients; 2020 Jun

    https://pubmed.ncbi.nlm.nih.gov/32630031/

  12. Evgeny Pokushalov, Andrey Ponomarenko, Sevda Bayramova, Claire Garcia, Inessa Pak, Evgenya Shrainer, Marina Ermolaeva, Dmitry Kudlay, Michael Johnson, Richard Miller; "Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial"; Nutrients; 2024

    https://www.mdpi.com/2072-6643/16/11/1550

  13. Giovanni Ponti, Laura Roli, Gabriella Oliva, Marco Manfredini, Tommaso Trenti, Shaniko Kaleci, Raffaele Iannella, Brigida Balzano, Antonietta Coppola, Giuseppe Fiorentino, Tomris Ozben, Venere Delli Paoli, Daria Debbia, Elena De Santis, Valentina Pecoraro, Alessandra Melegari, Monica Rosalia Sansone, Marina Lugara, Aldo Tomasi; "Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: a multicenter study on 313 Covid-19 patients"; Clinical chemistry and laboratory medicine; 2021 Mar

    https://pubmed.ncbi.nlm.nih.gov/33768762/

  14. María Eva Mingot-Castellano, Nora Butta, Mariana Canaro, María del Carmen Gómez del Castillo Solano, Blanca Sánchez-González, Reyes Jiménez-Bárcenas, Cristina Pascual-Izquierdo, Gonzalo Caballero-Navarro, Laura Entrena Ureña, Tomás José González-López on behalf of the GEPTI; "COVID-19 Vaccines and Autoimmune Hematologic Disorders"; Vaccines (Basel); 2022 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9231220/

  15. Domingo González-Lamuño, Francisco Jesús Arrieta-Blanco, Elena Dios Fuentes, María Teresa Forga-Visa, Monstserrat Morales-Conejo, Luis Peña-Quintana, Isidro Vitoria-Miñana; "Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition"; Nutrients; 2023 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10780827/

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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