MTHFR and Alcohol

MTHFR and Alcohol

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - Bachelor of Science in Nursing

Medical Reviewer:

Kari Asadorian - Bachelor of Science in Nursing
Jamie Hope - Founder of Methyl-Life

Edited By:

Jamie Hope - Founder of Methyl-Life

Updated On:

January 20, 2025

Table of Contents

    Alcohol and the impact on folate levels in the body

    Studies have shown that drinking alcohol can have immediate effects on folate levels and on the body’s ability to absorb folate in the tissues. This is partly because acetaldehyde (the initial metabolite of alcohol) has an oxidative effect on L-methylfolate, which can destroy it.1

    As well as reducing folate levels, alcohol also inhibits methionine synthesis, which then reduces SAMe levels. The result is impaired methylation, and increased levels of homocysteine.2
    Elevated homocysteine can then lead to various health issues, including cardiovascular disease and neurological conditions.

    Chronic alcohol use has numerous negative effects on health, including cancer, liver disease, cardiovascular diseases, nervous system damage, and abnormal development in children during pregnancy. 

    More recently, researchers have found that the impact of alcohol on the methylation process may also have epigenetic effects. When the body breaks down alcohol, it creates stress on cells that can change how genes work without altering the DNA itself. This happens through a few processes: it shifts the balance of certain cell molecules (NADH and NAD+), produces harmful byproducts called ROS (reactive oxygen species), and generates a substance called acetate. Together, these effects can influence gene activity in ways that may lead to health problems over time.3

    Does MTHFR cause alcohol intolerance?

    There is no evidence to suggest that MTHFR causes alcohol intolerance. 

    However, both alcohol and acetaldehyde (a byproduct of alcohol) can interfere with the breakdown of folate in the body. Chronic alcoholics tend to have higher homocysteine levels and lower B vitamins than non-alcoholics, most likely due to poor diet and the direct effects of heavy alcohol intake.4

    MTHFR is not a risk factor for alcohol dependence. However, having this gene mutation may increase future health risks for people who drink alcohol, especially those with alcohol dependence.5

    Alcoholism and the treatment of withdrawal symptoms with folate

    Alcoholic liver disease (ALD) often leads to folate deficiency due to low folate in the diet, intestinal malabsorption, reduced liver uptake and storage, and increased excretion of folate in the urine.6

    Folate deficiency then promotes the progression of liver disease through mechanisms by affecting methionine metabolism, which impairs DNA synthesis and stability. Low folate also affects epigenetic processes involved in liver damage.7

    One study found that treatment with folate and vitamin B12 improved liver fibrosis and reduced homocysteine levels in rodents with ALD.8

    Folic acid treatment has been shown to prevent and improve non-alcoholic fatty liver disease by exerting antioxidant and anti-inflammatory effects.9

    It is also worth noting that the combination of high folate and low alcohol intake - referred to as the “methyl group diet” - appears to have a strong protective effect against chronic disease. This highlights the important role of folate and methylation.10

    Alcohol, MTHFR and increased cancer risk

    High alcohol consumption may increase the risk of certain cancers due to disruptions in DNA methylation. Various studies have also linked the MTHFR C677T to some cancers, including esophageal, gastric, ovarian, breast, and lung cancer.11

    Alcohol affects DNA methylation by reducing the availability of SAMe, a key compound involved in this process. This occurs because alcohol lowers folate levels and blocks enzymes that support one-carbon metabolism, which is essential for producing SAMe. Alcohol also interferes with DNA methyltransferases, the enzymes directly involved in methylation. Additionally, genetic variations such as MTHFR can further impair one-carbon metabolism and increase the risk of alcohol-related cancers.12

    Liver cancer is commonly associated with impaired methylation caused by alcohol. Some studies into the effects of MTHFR and alcohol on liver cancer have indicated that lower SAMe levels (due to poor folate metabolism) and higher homocysteine can increase the risk of liver cancer, especially if folate is already low.13

    Postmenopausal women with MTHFR C677T and higher lifetime alcohol consumption may have a greater risk of breast cancer than non-drinkers with the same genotype. This may be due to the effects of alcohol on the one-carbon metabolism process.14

    Alcohol drinkers with the MTHFR TT genotype are estimated to have a fivefold increased risk of gastric cancer compared with drinkers with the wild homozygous variant.15

    Another study has found that people with the homozygous MTHFR C677T mutation may have a higher risk for head and neck cancer if they have a heavy drinking history. However, further studies are needed.16

    Alcohol, MTHFR and liver disease

    Some research has shown that MTHFR C677TT may contribute to liver disease by increasing the risk of thrombosis (blood clots) and fibrosis (scarring) in the liver, including patients who aren’t affected by hepatitis. This indicates that MTHFR may increase genetic predisposition to liver disease.17

    Other research has concluded that MTHFR C677T may increase the risk of hyperhomocysteinemia, which is associated with fatty liver disease.18 Increased homocysteine is an independent risk factor for non-alcoholic fatty liver disease as it can lead to vascular damage and the generation of free radicals.19

    MTHFR and Alcohol

    Key Takeaways

    • Icon Chronic alcoholics are often low in folate and many other vitamins, partly due to poor dietary intake. Alcohol also affects the absorption, storage, and activation of folate and other vitamins.
    • Icon Chronic alcohol intake can impair the methylation process, which can lead to other health issues.
    • Icon Folate may be used to treat people recovering from alcoholism.

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    Frequently Asked Questions about Alcohol and MTHFR

    How does alcohol affect folate levels?

    Studies have shown that acetaldehyde, one of the byproducts of alcohol, can destroy folate through oxidation. Alcohol can also hinder the body’s ability to absorb folate in the tissues.20
    Many people with chronic alcoholism are low in folate, although this can also be due to poor diet and gastrointestinal malabsorption.
    Alcohol also inhibits methionine synthesis, which then reduces SAMe levels and impairs the methylation process.21

    Do alcoholics have folate or B12 deficiency?

    Alcoholics are often found to have folate deficiency due to low dietary folate intake and poor absorption of folate in the gut. Alcohol also reduces the body’s ability to store folate in the liver while increasing the loss of folate through urine.
    Low folate worsens liver disease by disrupting methionine, an important nutrient for DNA production and stability, and also by affecting gene activity in ways that contribute to liver damage.22
    A 2022 study showed that while the majority of alcoholics had normal vitamin B12 levels, about a fifth had suboptimal levels.23

    Does alcohol affect MTHFR?

    Drinking alcohol can interfere with how the body absorbs, activates, and stores folate and other nutrients needed for healthy cell function. This disruption can lead to low folate levels, which may harm DNA by reducing methylation (a process that controls gene activity), especially in important areas of genes. It also affects the creation and repair of DNA, potentially leading to further health issues.24

    What vitamin deficiency is caused by alcohol?

    Chronic alcoholics are often deficient in several vitamins, including folate, vitamin B6, thiamine (B1) and vitamin A. Although poor dietary intake is the most common cause of deficiencies, alcohol also affects the absorption, storage, metabolism, and activation of many of these vitamins.25

    References

    1. S Shaw, E Jayatilleke, V Herbert, N Colman; "Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide"; The Biochemical Journal; 1989 Jan

      https://pubmed.ncbi.nlm.nih.gov/2537625/

    2. Samir Zakhari; "Alcohol Metabolism and Epigenetics Changes"; Alcohol Research Current Reviews; 2013

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3860421

    3. Samir Zakhari; "Alcohol Metabolism and Epigenetics Changes"; Alcohol Research Current Reviews; 2013

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3860421

    4. Chiuve Stephanie E, Giovannucci Edward L, Hankinson Susan E, Hunter David J, Stampfer Meir J, Willett Walter C, Rimm Eric B; "Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine"; The American Journal of Clinical Nutrition Vol. 82 Iss. 1; 2005 Jul

      https://www.sciencedirect.com/science/article/pii/S0002916523295234

    5. Huidrom Suraj Singh, Kabita Salam, Kallur Nava Saraswathy; "A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India"; Journal Of Biomarkers; 2014 Oct

      https://pmc.ncbi.nlm.nih.gov/articles/PMC4437350

    6. Valentina Medici, Charles H Halsted; "Folate, Alcohol, and Liver Disease"; Molecular Nutrition & Food Research; 2014 Apr

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3736728/

    7. Valentina Medici, Charles H Halsted; "Folate, Alcohol, and Liver Disease"; Molecular Nutrition & Food Research; 2014 Apr

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3736728/

    8. Ya-Ling Chen, Sien-Sing Yang, Hsiang-Chi Peng, Yi-Ching Hsieh, Jiun-Rong Chen, Suh-Ching Yang; "Folate and vitamin B12 improved alcohol-induced hyperhomocysteinemia in rats"; Nutrition; 2011 Oct

      https://pubmed.ncbi.nlm.nih.gov/21353475/

    9. Maria Jesus Delgado-Villa, Maria Luisa Ojeda, Jose Maria Rubio, Maria Luisa Murillo, Olimpia Carreras Sánchez; "Beneficial role of dietary folic acid on cholesterol and bile acid metabolism in ethanol-fed rats"; Journal Of Studies On Alcohol And Drugs; 2009 Jul

      https://pubmed.ncbi.nlm.nih.gov/19515303/

    10. Dong-Hyun Kim; "The interactive effect of methyl-group diet and polymorphism of methylenetetrahydrofolate reductase on the risk of colorectal cancer"; Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Vol. 622 Iss. 1–2 Pg. 14-18; 2007 Sep

      https://www.sciencedirect.com/science/article/abs/pii/S0027510707002102

    11. Carlo Fabris, Pierluigi Toniutto, Edmondo Falleti, Elisabetta Fontanini, Annarosa Cussigh, Davide Bitetto, Ezio Fornasiere, Elisa Fumolo, Claudio Avellini, Rosalba Minisini, Mario Pirisi; "MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption"; Alcoholism: Clinical and Experimental Research Vol. 33 Iss. 1 p. 102-107; 2008 Dec

      https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2008.00816.x

    12. Marta Varela-Rey, Ashwin Woodhoo, Maria-Luz Martinez-Chantar, José M Mato, Shelly C Lu; "Alcohol, DNA Methylation, and Cancer"; Alcohol Research Current Reviews; 2013

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3860423/

    13. Carlo Fabris, Pierluigi Toniutto, Edmondo Falleti, Elisabetta Fontanini, Annarosa Cussigh, Davide Bitetto, Ezio Fornasiere, Elisa Fumolo, Claudio Avellini, Rosalba Minisini, Mario Pirisi; "MTHFR C677T polymorphism and risk of HCC in patients with liver cirrhosis: role of male gender and alcohol consumption"; Alcoholism, Clinical And Experimental Research; 2009 Jan

      https://pubmed.ncbi.nlm.nih.gov/18945219/

    14. Mary E Platek, Peter G Shields, Catalin Marian, Susan E McCann, Matthew R Bonner, Jing Nie, Christine B Ambrosone, Amy E Millen, Heather M Ochs-Balcom, Sylvia K Quick, Maurizio Trevisan, Marcia Russell, Thomas H Nochajski, Stephen B Edge, Jo L Freudenheim; "Alcohol consumption and genetic variation in MTHFR and MTR in relation to breast cancer risk"; Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology; 2010 Sep

      https://pmc.ncbi.nlm.nih.gov/articles/PMC2941988

    15. Francesco Graziano, Kazuyuki Kawakami, Annamaria Ruzzo, Go Watanabe, Daniele Santini, Francesca Pizzagalli, Renato Bisonni, Davide Mari, Irene Floriani, Vincenzo Catalano, Rosarita Silva, Giuseppe Tonini, Valter Torri, Lucio Giustini, Mauro Magnani; "Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population"; International Journal Of Cancer; 2006 Feb

      https://pubmed.ncbi.nlm.nih.gov/16094648/

    16. Xianlu Zhuo, Jue Song, Dairong Li, Yongzhong Wu, Qi Zhou; "MTHFR C677T polymorphism interaction with heavy alcohol consumption increases head and neck carcinoma risk"; Scientific Reports Vol. 5; 2015 Jun

      https://www.nature.com/articles/srep10671

    17. Mario D'Amico, Francesca Pasta, Linda Pasta; "Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population"; Gene; 2015 Aug

      https://pubmed.ncbi.nlm.nih.gov/25987440/

    18. Carlo Fabris, Pierluigi Toniutto, Edmondo Falleti, Elisabetta Fontanini, Annarosa Cussigh, Davide Bitetto, Ezio Fornasiere, Elisa Fumolo, Claudio Avellini, Rosalba Minisini, Mario Pirisi; "MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol Consumption"; Alcoholism: Clinical and Experimental Research Vol. 33 Iss. 1 Pg. 102-107; 2008 Dec

      https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2008.00816.x#b11

    19. Benan Kasapoglu, Cansel Turkay, Kadir Serkan Yalcin, Ali Kosar, Alper Bozkurt; "MTHFR 677C/T and 1298A/C mutations and non-alcoholic fatty liver disease"; Clinical Medicine (London); 2015 Jun

      https://pmc.ncbi.nlm.nih.gov/articles/PMC4953108/

    20. S Shaw, E Jayatilleke, V Herbert, N Colman; "Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide"; The Biochemical Journal; 1989 Jan

      https://pubmed.ncbi.nlm.nih.gov/2537625/

    21. Samir Zakhari; "Alcohol Metabolism and Epigenetics Changes"; Alcohol Research Current Reviews; 2013

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3860421

    22. Valentina Medici, Charles H Halsted; "Folate, Alcohol, and Liver Disease"; Molecular Nutrition & Food Research; 2014 Apr

      https://pmc.ncbi.nlm.nih.gov/articles/PMC3736728

    23. Tesfaye Madebo, Mitra Bemanian, Jørn Henrik Vold, Ranadip Chowdhury, Christer Frode Aas, Karl Trygve Druckrey-Fiskaaen, Kjell Arne Johansson, Lars Thore Fadnes; "Vitamin B12 Levels, Substance Use Patterns and Clinical Characteristics among People with Severe Substance Use Disorders: A Cohort Study from Western Norway"; Nutrients; 2022 May

      https://pmc.ncbi.nlm.nih.gov/articles/PMC9105230/

    24. Mary E Platek, Peter G Shields, Catalin Marian, Susan E McCann, Matthew R Bonner, Jing Nie, Christine B Ambrosone, Amy E Millen, Heather M Ochs-Balcom, Sylvia K Quick, Maurizio Trevisan, Marcia Russell, Thomas H Nochajski, Stephen B Edge, Jo L Freudenheim; "Alcohol consumption and genetic variation in MTHFR and MTR in relation to breast cancer risk"; Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology; 2010 Sep

      https://pmc.ncbi.nlm.nih.gov/articles/PMC2941988

    25. A M Hoyumpa; "Mechanisms of vitamin deficiencies in alcoholism"; Alcoholism, Clinical And Experimental Research; 1986 Dec

      https://pubmed.ncbi.nlm.nih.gov/3544907

    26. Banner Image Designed by Freepik

      https://www.freepik.com/

    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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