The Connection Between MTHFR, Gluten Intolerance and Celiac Disease

Gluten has gained a reputation as one of the most problematic components of the modern diet, particularly for individuals with specific sensitivities. Gluten is present in both wholegrains (i.e., wheat, barley, rye, etc.) and in processed foods such as breads, sauces and snacks, which makes it difficult to avoid.

In the past few decades, the number of people with wheat and gluten sensitivities or allergies has risen significantly. It’s now thought that around 1% of the global population is affected by celiac disease.¹ Non-celiac gluten sensitivity (NCGS) is also becoming increasingly common.

Celiac disease (CD) is defined as “a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals”.²

While not a direct cause of celiac disease, one of the connections between MTHFR and gluten intolerance is elevated homocysteine levels.

The MTHFR mutation impairs methylation, which then affects the conversion of folate. This can lead to increased homocysteine levels due to low folate, which may then trigger inflammation, a major hallmark of celiac disease.³

A “small but noteworthy” study found a high prevalence of the MTHFR mutation in patients with celiac disease. The researchers found that celiac disease may be associated with elevated homocysteine levels, especially in those with homocysteine of around 15–30 µmol/L.⁴ They also explained that elevated homocysteine is likely caused by malabsorption of folate, B12 and B6, which are also common deficiencies in untreated celiac disease.

A more recent study found that patients with untreated celiac disease had higher rates of hyperhomocysteinemia (20-46%) than those who were undergoing treatment.⁵

However, the study also found that the prevalence of MTHFR and MTRR gene mutations in celiac patients was similar to (or lower) than that of the general population, indicating that while MTHFR may influence homocysteine levels, it likely does not increase the overall risk of developing celiac disease.

DNA methylation drives cell growth and normal immune response. Impairments to this process may affect the development and function of gastrointestinal cells, as well as the ability of the gut lining to repair itself. Altered DNA methylation patterns have been linked to various gastrointestinal disorders, including inflammatory bowel disease.⁷

Epigenetic studies suggest altered methylation patterns could play a secondary role in gastrointestinal diseases, but more research is needed to link this directly to celiac disease.

Strict adherence to a gluten-free diet is currently the only effective treatment for managing celiac disease, and will often help to reverse intestinal damage and reduce symptoms over time.⁸

One study found that the severity of the villous atrophy in patients with celiac disease was linked to low vitamin B12 and folate.⁹ This was improved over a year on a gluten-free diet, but some patients may require additional vitamin supplementation if deficiencies persist due to ongoing malabsorption or limited dietary intake.

Folate deficiency - which is common among those with MTHFR - is also common in celiac patients, even after more than a year on a gluten-free diet. This could be partly due to villous atrophy in those with celiac disease, which impairs the absorption of many nutrients, including B vitamins.¹⁰ Folate is primarily absorbed in the jejunum of the small intestine, the main site impacted by celiac disease. Vitamin B12 is mostly absorbed in the ileum (the last section of the small intestine), which is also impacted in celiac patients.

Studies show that around 20–38% of celiac patients have at least one nutritional deficiency, either due to malabsorption or deficiencies within a gluten-free diet. Vitamin B12 deficiency in people with celiac disease may be up to 41%.¹¹

For these reasons, people with MTHFR and/or gluten intolerance are recommended to supplement with methylfolate, the active form of folate that requires no conversion in the body. Active B12 is also recommended as it works alongside folate to reduce homocysteine and support many other aspects of wellbeing.

If you have both celiac disease and MTHFR, your main priority should be a gluten-free diet. However, it’s important to note that the gluten-free diet is also associated with decreased intake of dietary fiber, iron and most B vitamins including B12 and folate, along with increased consumption of unhealthy fats.¹² This makes targeted nutrition even more important in people with both celiac and MTHFR.

People with celiac disease are often low in folate due to low consumption of folate-rich foods. Wheat is a major source of B vitamins, and gluten-free products contain wheat alternatives. 

Many foods rich in both folate and B12 are also gluten-free, for example:

• Lean proteins: Beef, lamb, pork, turkey, chicken and liver are good sources of both vitamins. 
• Eggs: A good source of B12 and also contains folate. 
• Leafy greens: Spinach, kale and other dark green vegetables provide natural folate.
• Seafood: Oysters, mussels and oily fish (salmon, mackerel, trout) are good sources of B12 and some folate.