MTHFR, Candida Infections, and the Gut-Brain Connection

MTHFR, Candida Infections, and the Gut-Brain Connection

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 25, 2025

Table of Contents

    MTHFR, Candida Infections, and the Gut-Brain Connection

    Candidiasis is an increasingly common condition, with around 25,000 cases1 recorded nationwide each year. It is an opportunistic infection caused by Candida, a type of fungi, and typically colonizes the oropharyngeal, esophageal, and gastrointestinal mucosa.


    Candida infections are particularly common in immunocompromised individuals2. However, research suggests that poor methylation associated with MTHFR mutations may also play an important role in susceptibility due to reduced methionine synthase.


    The gut-brain connection is also impacted by Candida infection, which can exacerbate symptoms of MTHFR.


    This article will explain what a Candida infection is and its symptoms, how it can interfere with methylation, and how you can treat a Candida infection if you have an MTHFR SNP(s).

    What is a Candida Infection?

    Candida albicans remains the leading cause of invasive Candidiasis3 in the United States, affecting an estimated 9 per 100,000 people4.


    Candida albicans is an opportunistic yeast, the most prevalent fungal species of the human microbiota. It lives naturally in the body and is usually kept under control by other gut microbiota.


    Candida overgrowth can occur5 when the immune system is altered, usually due to antibiotics. Stress can also affect the gut microbiome that controls Candida, as well as infection by another microbe, immunosuppressant therapy, poor nutritional intake, or changes to the local environment.


    These circumstances can enable C. albicans to overgrow and result in a wide range of infections affecting the skin, digestive function, brain function, mouth, and more.


    Candida albicans depends upon glycolysis6 to progress, and glucose and other sugars7 influence the ability of Candida cells to form a biofilm.


    The Candida biofilm is largely resistant to current antifungal drugs such as fluconazole. No biofilm-specific drugs exist today for C. albicans (or any microbe), making treatment of biofilm-based infections particularly problematic.


    However, treatment with probiotics and natural antifungal agents8 has proved successful in some cases.


    If left untreated, Candida-related infections can become painful and irritating and may severely affect digestion and skin health.

    Symptoms of a Candida Infection

    Candida overgrowth can affect the mouth, genitals, skin, and digestive system. Recent research in mice suggests it may also affect cognitive function.


    • Gastrointestinal issues9 (bloating, constipation)
    • White patches10 on the tongue, throat, and other mouth areas (oral thrush)
    • Itching, soreness, abnormal discharge11 in the genital area (vaginal thrush)
    • Fungal infection of the skin and/or nails12
    • Cravings for sugar13 and/or simple carbohydrates
    • Possible impaired memory14 or reduced cognitive function

    How Candida Can Interfere with Methylation

    Candida may also interfere with the methylation cycle by producing acetaldehyde15, along with the associated yeast infection. Acetaldehyde is a highly reactive and toxic chemical that inhibits both methionine synthase16 and glutathione.


    Methionine synthase is a crucial component of the methylation process. It is required for donating a methyl group to homocysteine17 from 5-methyltetrahydrofolate, which allows the conversion of homocysteine back to methionine.


    This process is already compromised in those with MTHFR mutations due to the inactive or malfunctioning MTHFR enzyme, which can mean that a Candida infection may increase their risk of elevated homocysteine.


    Researchers have suggested that methionine plays an essential role in preventing the toxic accumulation of homocysteine18 when Candida is present.


    Candida overgrowth in the gut can also affect brain chemistry via the gut-brain axis. One study found that mice colonized with Candida albicans demonstrated anxiety and increased stress hormone levels19 due to changes in the endocannabinoidome.


    Other research has found possible links between mental illness and the gut microbiome. The gut is closely connected with the central nervous system (CNS), as shown by the high incidence of neurological symptoms20 in IBS (Irritable Bowel Syndrome) sufferers.


    Patients with schizophrenia have a higher incidence of Candida infection, along with gastrointestinal dysfunctions and poorer cognitive ability21. Children with autism spectrum behaviors22 are also found to have increased levels of Candida.


    The microbiome is responsible for synthesizing important mediators that influence the central nervous system and can therefore play a specific part in the microbiota-gut-brain axis23 disturbance.


    It is also known that Candida albicans can produce histamine24, which is a crucial neuromodulator in regulating sleep rhythm, appetite, and cognitive actions.

    How to Deal with Candida if You Have an MTHFR Mutation

    Treating a Candida infection requires a multi-pronged approach.

    Diet

    Limit sugars, simple carbohydrates, and alcohol. Candida albicans uses glucose and other sugars to proliferate. Focus on whole foods, fresh fruits and vegetables, and plenty of filtered water.

    Immune support

    Around 70 percent of the body’s immune cells live in the gut, which means the gut microbiome plays a significant role in systemic immunity.


    Supporting immune function with a comprehensive multivitamin can help fill in any diet gaps, especially if you are at risk of nutritional deficiencies due to an MTHFR mutation. Methyl-Life’s range of methylated multivitamins is designed to support vegans, vegetarians, and individuals with MTHFR.

    Probiotics

    Support a healthy gut microbiome by taking probiotic supplements. Probiotic bacteria from the Lactobacillus and Bifidobacterium25 species and probiotic yeasts such as Saccharomyces boulardii26 have been found effective in reducing Candida albicans infection.


    Spore-based probiotics have advantages over other probiotics as they can survive the harsh gastric conditions of the stomach27 and intestines and eventually germinate in the digestive tract. The probiotic supplement Mega SporeBiotic™ is a 100% probiotic blend of 5 Bacillus spores that have been shown to maintain healthy gut barrier and immune function28.


    RestorFlora™ is also highly recommended for those with Candida overgrowth. RestoreFlora™ is a blend of the probiotic yeast Saccharomyces boulardii, Bacillus subtilis HU58, and Bacillus clausii SC109. These well-researched strains support digestive flora and help to maintain a healthy intestinal environment.


    Both Mega SporeBiotic™ and RestorFlora™ contain ​​Bacillus subtilis, which has been shown to help fight Candida albicans29.


    Starting a probiotic regimen may have some unpleasant symptoms as the gut microbiome is altered, but these eventually pass. Please seek the advice of a medical professional before commencing any new supplement regimen.

    References

    1. Centers for Disease Control and Prevention

      https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html

    2. Arya N. R, Naureen B. Rafiq; "Candidiasis"; StatPearls [Internet]; 2023 May

      https://www.ncbi.nlm.nih.gov/books/NBK560624/

    3. Emily E Ricotta, Yi Ling Lai, Ahmed Babiker, Jeffrey R Strich, Sameer S Kadri, Michail S Lionakis, D Rebecca Prevots, Jennifer Adjemian; "Invasive Candidiasis Species Distribution and Trends, United States, 2009-2017"; The Journal of infectious diseases; 2021 Apr

      https://pubmed.ncbi.nlm.nih.gov/32798221/

    4. Sharon Tsay, Sabrina Williams, Yi Mu, Erin Epson, Helen Johnston, Monica M Farley, Lee H Harrison, Brittany Vonbank, Sarah Shrum, Ghinwa Dumyati, Alexia Zhang, William Schaffner, Shelley Magill, Snigdha Vallabhaneni; "363. National Burden of Candidemia, United States, 2017"; Open Forum Infectious Diseases; 2018 Nov

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255127/

    5. Clarissa J Nobile, Alexander D Johnson; "Candida albicans Biofilms and Human Disease"; Annual review of microbiology; 2016 Jul

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930275/

    6. Christopher Askew, Adnane Sellam, Elias Epp, Hervé Hogues, Alaka Mullick, André Nantel, Malcolm Whiteway; "Transcriptional Regulation of Carbohydrate Metabolism in the Human Pathogen Candida albicans"; PLoS Pathogens; 2009 Oct

      https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000612

    7. Tzu Shan Ng, Mohd Nasir Mohd Desa, Doblin Sandai, Pei Pei Chong, Leslie Thian, Lung Than; "Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations"; Infection, Genetics and Evolution, Vol. 40 Pg. 331-338; 2016 Jun

      https://www.sciencedirect.com/science/article/abs/pii/S1567134815003718?via%3Dihub

    8. A Zida, S Bamba, A Yacouba, R Ouedraogo-Traore, R T Guiguemdé; "Anti-Candida albicans natural products, sources of new antifungal drugs: A review"; Journal de mycologie médicale; 2017 Mar

      https://pubmed.ncbi.nlm.nih.gov/27842800/

    9. Askin Erdogan, Satish S C Rao; "Small intestinal fungal overgrowth"; Current gastroenterology reports; 2015 Apr

      https://pubmed.ncbi.nlm.nih.gov/25786900/

    10. Michael Taylor, Melina Brizuela, Avais Raja; "Oral Candidiasis"; StatPearls [Internet]; 2023 Jul

      https://www.ncbi.nlm.nih.gov/books/NBK545282/

    11. Rebecca Jeanmonod, Venu Chippa, Donald Jeanmonod; "Vaginal Candidiasis"; StatPearls [Internet]; 2024 Feb

      https://www.ncbi.nlm.nih.gov/books/NBK459317/

    12. Andreas Kühbacher, Anke Burger-Kentischer, Steffen Rupp; "Interaction of Candida Species with the Skin"; Microorganisms; 2017 Jun

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488103/

    13. Joe Alcock, Carlo C Maley, C Athena Aktipis; "Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms"; BioEssays : news and reviews in molecular, cellular and developmental biology; 2014 Aug

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270213/

    14. Yifan Wu, Shuqi Du, Jennifer L Johnson, Hui-Ying Tung, Cameron T Landers, Yuwei Liu, Brittany G Seman, Robert T Wheeler, Mauro Costa-Mattioli, Farrah Kheradmand, Hui Zheng, David B Corry; "Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits"; Nature Communications; 2019 Jan

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320369/

    15. M. L. Gainza-Cirauqui, M. T. Nieminen, L. Novak Frazer, J. M. Aguirre-Urizar, M. D. Moragues, R. Rautemaa; "Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders"; Journal of Oral Pathology & Medicine, Vol. 42, Iss. 3 p. 243-249; 2012 Aug

      https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0714.2012.01203.x

    16. Susan H Kenyon, Anna Nicolaou, William A Gibbons; "The Effect of Ethanol and Its Metabolites Upon Methionine Synthase Activity In Vitro"; Alcohol, Vol. 15, Iss. 4, Pg. 305-309; 1998 May

      https://linkinghub.elsevier.com/retrieve/pii/S0741832997001341

    17. ScienceDirect; "Methionine Synthase"; Agricultural and Biological Sciences; 2017

      https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/methionine-synthase

    18. Jennifer Scott, Monica Sueiro-Olivares, Benjamin P. Thornton, Rebecca A. Owens, Howbeer Muhamadali, Rachael Fortune-Grant, Darren Thomson, Riba Thomas, Katherine Hollywood, Sean Doyle, Royston Goodacre, Lydia Tabernero, Elaine Bignell, Jorge Amich; "Targeting Methionine Synthase in a Fungal Pathogen Causes a Metabolic Imbalance That Impacts Cell Energetics, Growth, and Virulence"; American Society for Microbiology; 2020 Oct

      https://journals.asm.org/doi/10.1128/mBio.01985-20

    19. Laura Markey, Andrew Hooper, Laverne C Melon, Samantha Baglot, Matthew N Hill, Jamie Maguire, Carol A Kumamoto; "Colonization with the commensal fungus Candida albicans perturbs the gut-brain axis through dysregulation of endocannabinoid signaling"; Psychoneuroendocrinology; 2020 Nov

      https://pubmed.ncbi.nlm.nih.gov/32739746/

    20. Mihaela Fadgyas-Stanculete, Ana-Maria Buga, Aurel Popa-Wagner, Dan L Dumitrascu; "The relationship between irritable bowel syndrome and psychiatric disorders: from molecular changes to clinical manifestations"; Journal of Molecular Psychiatry; 2014 Jun

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223878/

    21. Emily G Severance, Kristin L Gressitt, Catherine R Stallings, Emily Katsafanas, Lucy A Schweinfurth, Christina L Savage, Maria B Adamos, Kevin M Sweeney, Andrea E Origoni, Sunil Khushalani, F Markus Leweke, Faith B Dickerson, Robert H Yolken; "Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder"; Open Access; 2016 May

      https://www.nature.com/articles/npjschz201618

    22. Anna Herman, Andrzej Przemysław Herman; "Could Candida Overgrowth Be Involved in the Pathophysiology of Autism?"; Journal of Clinical Medicine; 2022 Jan

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778531/

    23. Yu Gu, Guoqiong Zhou, Xiali Qin, Shumin Huang, Bangmao Wang, Hailong Cao; "The Potential Role of Gut Mycobiome in Irritable Bowel Syndrome"; Frontiers in Microbiology; 2019 Aug

      https://www.frontiersin.org/articles/10.3389/fmicb.2019.01894/full

    24. Voropaeva EA; "[Resistance to antibiotics and histamine production at the bacteria, isolated from the stomatopharynx of the children with bronchial asthma]."; Antibiotics and Chemoterapy; 2002 Jan

      https://europepmc.org/article/med/16127900

    25. José Carlos Andrade, Sunil Kumar, Awanish Kumar, Lucia Černáková, Célia F Rodrigues; "Application of probiotics in candidiasis management"; Critical reviews in food science and nutrition; 2022

      https://pubmed.ncbi.nlm.nih.gov/34024191/

    26. Lohith Kunyeit, Anu-Appaiah K A, Reeta P Rao; "Application of Probiotic Yeasts on Candida Species Associated Infection"; Journal of Fungi; 2020 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711718/

    27. Joan Colom, Daniela Freitas, Annie Simon, Andre Brodkorb, Martin Buckley, John Deaton, Alison M. Winger; "Presence and Germination of the Probiotic Bacillus subtilis DE111® in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study"; Frontiers in Microbiology; 2021 Aug

      https://www.frontiersin.org/articles/10.3389/fmicb.2021.715863/full

    28. Joan Colom, Daniela Freitas, Annie Simon, Andre Brodkorb, Martin Buckley, John Deaton, Alison M. Winger; "Presence and Germination of the Probiotic Bacillus subtilis DE111® in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study"; Frontiers in Microbiology; 2021 Aug

      https://www.frontiersin.org/articles/10.3389/fmicb.2021.715863/full

    29. Olfa Tabbene, Leila Kalai, Imen Ben Slimene, Ines Karkouch, Salem Elkahoui, Abdelhamid Gharbi, Pascal Cosette, Maria-Luisa Mangoni, Thierry Jouenne, Ferid Limam; "Anti-Candida effect of bacillomycin D-like lipopeptides from Bacillus subtilis B38"; FEMS Microbiology Letters, Vol. 316, Iss. 2; 2011 Mar

      https://academic.oup.com/femsle/article/316/2/108/563789?login=false

    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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