MTHFR and Gout: Is There a Link? | Methyl-Life®

MTHFR and Gout: Is There a Link? | Methyl-Life®

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Conor Sheehy - PharmD, BCPS

Medical Reviewer:

Dr. Conor Sheehy - PharmD, BCPS
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 28, 2025

MTHFR and Gout

Gout is a painful form of arthritis and a condition that is steadily increasing worldwide. It is now the most common type of inflammatory joint condition in adults, affecting around 8.3 million adults1 in the U.S. alone.


Cases of hyperuricemia have also increased dramatically over the last 50 years, with an estimated 43.3 million Americans now affected2.


Gout causes severe joint pain and swelling, especially in the toes, knees, elbows, wrists, and fingers. If left untreated, it can cause severe damage to joints, kidneys, and overall quality of life. It has also been described as one of the most understood and manageable arthritic diseases.


While gout is often associated with poor diet and obesity, recent research has suggested that the risk of gout may be linked to the MTHFR polymorphism. This common genetic mutation affects some 30-40 percent 3 of the American population.


There is also evidence that elevated homocysteine may be linked to uric acid4 levels.


This article will explain gout and its etiology. We will also discuss the link between MTHFR and gout and how the risk of developing gout can be minimized with the right nutrients.

What is Gout?

Gout is one of the most common causes of chronic inflammatory arthritis in the United States. This painful condition is characterized by the deposition of uric acid crystals (monosodium urate monohydrate) in the tissues.


The leading cause of gout is hyperuricemia5, a metabolic disorder resulting from excess uric acid levels in the blood.


The exact cause of hyperuricemia is often linked to dietary factors. Uric acid is a waste product formed in the body following the breakdown of purines (adenine, guanine, and xanthine), which are naturally present within the body's cells and in certain foods.


Consumption of foods and beverages high in purines will increase uric acid levels. Purine compounds are either produced in the body or accumulate from eating high-purine foods. If the body is unable to break down these purines, uric acid levels will increase.


The excess uric acid can then produce uric acid crystals, which build up in soft tissues and joints, causing the painful symptoms of gout.


High-purine sources include:

  • Alcoholic beverages (all types)
  • Seafood, especially fish such as anchovies, sardines, herring, trout; and shellfish such as mussels and scallops
  • Dark or cured meats such as salami, bacon, veal, venison, turkey
  • Organ meats such as liver


Other causes of gout include hereditary disorders that affect uric acid excretion and purine metabolism.


In males, the risk of developing hyperuricemia has also been linked to low intake of folate and B126.


The common MTHFR mutation C677T has been shown to lead to elevated homocysteine levels, contributing to higher uric acid levels. Researchers have noted that an MTHFR mutation is a risk factor for hyperuricemia7 in older men.


A 2018 study published in the Journal of Clinical Medicine investigated the role of folate, B6, and B12 on hyperuricemia8. Men with hyperuricemia were found to have lower intakes of folate, folic acid and vitamin B12. Women with higher intakes of total folate high a lower risk of hyperuricemia; not there was no relationship associated with vitamin B6 or vitamin B12. Folate appears to be particularly crucial as it helps to inactivate xanthine oxidoreductase (XOR)9, the enzyme responsible for the oxidation of hypoxanthine to xanthine and xanthine to uric acid.

What is the Relationship Between Uric Acid Buildup and Homocysteine?

Hyperuricemia and hyperhomocysteinemia are both believed to be risk factors for cardiovascular disease. However, the exact relationship has not yet been determined. Some studies have reported a direct correlation between uric acid and homocysteine, while others have claimed no significant correlations between homocysteine levels in patients with gout and control groups.


One study found that homocysteine levels were elevated in male patients with gout10. Hyperhomocysteinemia was not correlated with uric acid levels, but it appeared to be higher in patients who had impaired renal function.


In a large cohort study, hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, suggesting a significant association between hyperhomocysteinemia and hyperuricemia11. The researchers concluded that accelerated atherosclerosis might be a consequence of the combined effect of these two factors.


A 2011 study found that elevated homocysteine levels and uric acid12 were associated with albuminuria (a sign of kidney disease) independently of one another and of renal function.


Strong associations have been noted between homocysteine levels and MTHFR13 polymorphisms due to the way MTHFR deficiency disrupts homocysteine metabolism. Previous research has demonstrated that the C677T polymorphism increases homocysteine concentration and decreases folate14.


People with hyperhomocysteinemia were also found to have lower levels of folic acid and vitamin B12 and higher uric acid levels15 than those with normal homocysteine levels. Uric acid was positively associated with higher homocysteine.


Folate, vitamin B6, and vitamin B12 all play major roles in lowering homocysteine by converting it to methionine.  However, a lack of these nutrients can impair the conversion process, resulting in higher accumulating homocysteine levels16.

What Should People with Gout and MTHFR Know?

People with gout should be aware that their condition may not be preventable through lifestyle changes alone, especially if they have an MTHFR mutation. In the case of an MTHFR mutation, mediation and/or supplements may help to get their condition under control.


Uric acid is a significant factor in gout, and many epidemiological studies17 have shown the relationship between uric acid and obesity, metabolic syndrome, hypertension, and coronary artery disease. These disorders are also linked to elevated homocysteine.


Several studies have shown a link between uric acid concentrations and homocysteine levels. However, this exact relationship is uncertain18.


It is vital to note that deficiencies in folic acid, vitamin B12, and vitamin B6 levels have also been linked to both elevated homocysteine and uric acid19 levels. 


Folate, vitamin B6, and vitamin B12 all play crucial roles in lowering homocysteine20. Folate also helps to inactivate xanthine oxidoreductase (XOR)21, the enzyme responsible for the oxidation of hypoxanthine to xanthine and xanthine to uric acid.


However, both of these processes require the active form of folate, methylfolate. An MTHFR mutation impairs the conversion of dietary folate and synthetic folic acid into L-Methylfolate.


The most effective way to overcome this impairment and optimize folate levels is to take a bioactive form of folate. L-Methylfolate is the only form of folate that crosses the blood-brain barrier22 and can be used instantly in the body.


Studies have shown that methylated folate can help to reduce both homocysteine and uric acid levels. Supplementation with folate and vitamin B12 could help to prevent excess uric acid levels in both men and women and ultimately prevent the incidence and recurrence of gout23.


Some of the best methylfolate supplements for those with MTHFR mutations or cardiovascular risks include Methyl-Life® products (B-Methylated II, Methylated Multivitamin, Methylfolate 7.5+ or Methylfolate 15+.) This product range has been created by a team of natural health experts and used successfully by those with cardiovascular conditions or nutritional deficiencies.  The form of L-Methylfolate used in Methyl-Life® products is the purest, most stable, and most is the purest, most stable, and most potent of the world’s four industry-leading patented L-Methylfolates.

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References

  1. "Gout"; National Kidney Foundation

    https://www.kidney.org/atoz/content/gout/patient-facts

  2. Wiley-Blackwell; "Gout prevalence swells in U.S. over last two decades; Increase in obesity and hypertension are likely contributors"; ScienceDaily; 2011 Jul

    https://www.sciencedaily.com/releases/2011/07/110728082551.htm

  3. The Genetic and Rare Diseases Information Center (GARD) provides an overview of the MTHFR gene mutation, discussing its genetic implications and associated health conditions.

    https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation

  4. Franziska Marti, Peter Vollenweider, Pedro-Manuel Marques-Vidal, Vincent Mooser, Gérard Waeber, Fred Paccaud, Murielle Bochud; "Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study"; BMC Public Health; 2011 Sep

    https://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-11-733

  5. Christina George, Stephen W. Leslie, David A. Minter; "Hyperuricemia"; StatPearls [Internet].; 2023 Oct

    https://www.ncbi.nlm.nih.gov/books/NBK459218/

  6. Yiying Zhang, Hongbin Qiu; "Folate, Vitamin B6 and Vitamin B12 Intake in Relation to Hyperuricemia"; Journal of Clinical Medicine; 2018 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111262/

  7. M Zuo, H Nishio, M J Lee, K Maejima, S Mimura, K Sumino; "The C677T mutation in the methylene tetrahydrofolate reductase gene increases serum uric acid in elderly men"; Journal of human genetics; 2000

    https://pubmed.ncbi.nlm.nih.gov/10944859/

  8. Yiying Zhang, Hongbin Qiu; "Folate, Vitamin B6 and Vitamin B12 Intake in Relation to Hyperuricemia"; Journal of Clinical Medicine; 2018 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111262/

  9. Brassard D, Tessier-Grenier M, Allaire J, et al.; "Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial"; The American Journal of Clinical Nutrition; 2017 Apr

    https://academic.oup.com/ajcn/article/105/4/775/4569746

  10. Sang Tae Choi, Jin Su Kim, Jung-Soo Song; "Elevated Serum Homocysteine Levels Were Not Correlated with Serum Uric Acid Levels, but with Decreased Renal Function in Gouty Patients"; Journal of Korean Medical Science

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055811/

  11. Eytan Cohen, Amos Levi, Susan E Vecht-Lifshitz, Elad Goldberg, Moshe Garty, Ilan Krause; "Assessment of a possible link between hyperhomocysteinemia and hyperuricemia"; Journal of investigative medicine : the official publication of the American Federation for Clinical Research; 2015 Mar

    https://pubmed.ncbi.nlm.nih.gov/25646870/

  12. Franziska Marti, Peter Vollenweider, Pedro-Manuel Marques-Vidal, Vincent Mooser, Gérard Waeber, Fred Paccaud, Murielle Bochud; "Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study"; BMC Public Health; 2011 Sep

    https://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-11-733

  13. David S Wald; "Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis"; The BMJ; 2002 Aug

    https://www.bmj.com/content/325/7374/1202

  14. Qiang Zeng, Fan Li, Tianyuan Xiang, Weimin Wang, Cong Ma, Chao Yang, Haixu Chen, Hang Xiang; "Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in Chinese population"; Molecular nutrition & food research; 2017 Feb

    https://pubmed.ncbi.nlm.nih.gov/27515258/

  15. Hee-Jin Kim, Il Woong Sohn, Young Seo Kim, Jae-Bum Jun 2; "The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment"; Nutrients; 2020 Apr

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230180/

  16. Elizabeth A. Varga, Amy C. Sturm, Caron P. Misita, Stephan Moll; "Homocysteine and MTHFR Mutations: Relation to Thrombosis and Coronary Artery Disease"; Circulation; 2005 May

    https://www.ahajournals.org/doi/10.1161/01.CIR.0000165142.37711.E7

  17. Daria Pasalic, Natalija Marinkovic, Lana Feher-Turkovic; "Uric acid as one of the important factors in multifactorial disorders – facts and controversies"; Biochemia medica; 2012 Feb

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062324/

  18. Sang Tae Choi, Jin Su Kim, Jung-Soo Song; "Elevated Serum Homocysteine Levels Were Not Correlated with Serum Uric Acid Levels, but with Decreased Renal Function in Gouty Patients"; Journal of Korean Medical Science

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055811/

  19. Yiying Zhang, Hongbin Qiu; "Folate, Vitamin B6 and Vitamin B12 Intake in Relation to Hyperuricemia"; Journal of Clinical Medicine; 2018 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111262/

  20. K Pietrzik, A Brönstrup; "Vitamins B12, B6 and folate as determinants of homocysteine concentration in the healthy population"; European journal of pediatrics; 1998 Apr

    https://pubmed.ncbi.nlm.nih.gov/9587042/

  21. The American Journal of Clinical Nutrition | A Journal of the American Society for Nutrition

    https://academic.oup.com/ajcn/article/105/4/775/4569746

  22. Richard C Shelton, J Sloan Manning, Lori W Barrentine, Eleanor V Tipa; "Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial"; The primary care companion for CNS disorders; 2013 Aug

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869616/

  23. Li-Ching Lyu, Chi-Yin Hsu, Ching-Ying Yeh, Meei-Shyuan Lee, Su-Hua Huang, Ching-Lan Chen; "A case-control study of the association of diet and obesity with gout in Taiwan";

    https://pubmed.ncbi.nlm.nih.gov/14522726/

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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