Does Gluten Affect MTHFR? How and Why?

Gluten has gained a reputation as one of the most problematic components of the modern diet. It is present in both processed and whole foods, which makes it difficult to avoid.

In the past few decades, the number of people with wheat and gluten sensitivities or allergies has risen sharply.  An estimated 0.5-1 percent of the adult population is affected by celiac disease or wheat allergies. Non-celiac gluten sensitivity (NCGS) is also becoming increasingly common. 

Research suggests that gluten may be particularly harmful to another common health concern: the MTHFR genotype. 

Alone, the MTHFR mutation can have a detrimental effect on numerous bodily functions. It impairs the conversion of folate, which contributes to elevated homocysteine levels, inflammation, nutritional deficiencies, and other health concerns. When coupled with gluten sensitivity, these effects are amplified. 

This article will discuss the possible connection between MTHFR and gluten intolerance as well as how gluten may affect an MTHFR mutation. We will also explain the dietary and supplementary protocol for gluten intolerant people with an MTHFR genotype.

The main connection between MTHFR and gluten intolerance is the effect on the gastrointestinal system. 

One of the hallmarks of gluten intolerance is an inflammatory response in the gut. 

While gluten allergies (such as celiac disease) are mediated through immunoglobulin E (IgE) antibodies, gluten intolerances most often affect metabolic pathways. An intolerance is most often triggered by the digestive system, which means symptoms tend to be gastrointestinal in nature. These can include bloating, gas/flatulence, diarrhea, and irritable bowel syndrome (IBS). Reactions can appear immediately or up to 20 hours after a food is eaten.

An intolerance won’t cause a severe reaction such as anaphylaxis, but it can increase levels of inflammation in the body. This inflammation and damage to the digestive tract can also lead to nutritional malabsorption and deficiencies. 

Proper methylation is also a key factor in developing and maintaining the gastrointestinal tract and its microbiome. The intestinal tract is in constant contact with the external environment as it is the entry point for nutrients and other organisms. DNA methylation is central to the functionality of the gut and how it is shaped by external factors, diet, and nutritional status.

Those with the methylenetetrahydrofolate reductase (MTHFR) genotype tend to have higher levels of inflammatory markers in the body due to elevated homocysteine levels. This inflammation can contribute to the damage of sensitive tissues in the gut lining. 

Gluten exposure increases this inflammation further, increasing the risk of intestinal permeability (Leaky Gut) and a pro-inflammatory immune response.

There is also an increased prevalence of the C677T variant in patients with inflammatory bowel disease, largely due to hyperhomocysteinemia. 

A study involving patients with MTHFR variants showed that many had high homocysteine levels and that these were more common when their MTHFR variant was compounded with gluten sensitivity. The researchers concluded that hyperhomocysteinemia is frequent in newly diagnosed gluten intolerance and that hyperhomocysteinemia might contribute to the occurrence of common complications caused by gluten intolerance.

People with a confirmed diagnosis of gluten intolerance are advised to adhere to a life-long gluten-free diet or at least minimize gluten as much as possible. Gluten is a pro-inflammatory wheat protein, and removing it from the diet can help reduce inflammatory markers in the body. 

Foods that should be avoided include gluten-containing grains such as wheat, barley, rye, spelt, couscous, and oats (that have been processed with glutinous grains). 

Reducing dairy intake is also advised. Those with gluten intolerance tend to have secondary lactose intolerance due to damaged intestinal villi, which in turn reduces enzyme production. One study showed that casein caused an inflammatory response in about 50% of the patients with celiac disease. This is due to the structural similarities of casein protein and gliadin, causing the body to react to dairy in the same way. 

Processed foods should also be avoided as they are often fortified with folic acid, which can accumulate in toxic levels in those with impaired methylation and/or MTHFR genetic variants. Processed foods also contain refined sugars, artificial additives, and many other inflammatory ingredients. 

Adopting an anti-inflammatory diet rich in whole foods, healthy fats, and low grains is advisable. The Mediterranean Diet has been clinically proven to reduce homocysteine and systemic inflammation. It emphasizes brightly colored fruits, olives, healthy fats (avocado, olive oil), and low sugar.

Along with avoiding gluten, those with a dual diagnosis should focus on optimizing their body’s methylation - especially those who have a double MTHFR mutation. The diet’s main goal should be to increase active folate and vitamin B levels and support the homocysteine-methionine pathway. This will help to protect your cells from harmful homocysteine and improve the function of your immune system, brain, nervous system, and digestion.

Vitamins B6 and B12 work alongside folate in the methylation cycle, reducing homocysteine levels and supporting detoxification. Increasing active dietary folate, vitamin B6, vitamin B12, and betaine has been shown to help control or alleviate the risk of elevated homocysteine.  

Many whole foods are naturally rich in folate and B vitamins, and some studies suggest that eating a diet rich in folate can help to lower homocysteine as effectively as taking a 5-MTHF supplement. 

However, those who are deficient in folate due to a MTHFR mutation are unlikely to replenish their folate levels by diet alone. 

Folate-rich foods include:

• Leafy greens (spinach, kale, romaine lettuce))
• Broccoli
• Clams
• Avocado
• Sprouted legumes (mung beans, chickpeas)
• Asparagus
• Cabbage
• Fermented foods (sauerkraut, miso, yogurt)
• Berries (blueberries, strawberries)
• Citrus fruits (oranges, grapefruit)

Many of these foods are already high in B vitamins, but other B-vitamin foods include red meat (especially liver), nuts, seeds, and dairy products.  

Gut health is particularly important, as the gut microbiome plays an important role in the body’s ability to obtain nutrients from food. This, in turn, will support overall health and wellbeing. Gut-healing foods are those rich in protein and probiotic bacteria, which help restore the integrity of the digestive tract. Fermented foods such as kimchi, kefir, and miso are good options, along with bone broth, flaxseeds, chia seeds, and turmeric.

Essential fatty acids such as omega-3 can help reduce inflammation and the risk of heart disease. All foods should be in their whole, natural state. Choose hormone-free, grass-fed meats, grass-fed butter or ghee, and organic free-range eggs.

Vitamin deficiencies caused by malabsorption are also important determinants of both gluten intolerance and MTHFR. Deficiency in folate and B12 is common in MTHFR and also occurs in a significant proportion of celiac patients. 

When first diagnosed, an individual's nutritional status may be low, requiring repletion doses of vitamins and minerals in higher amounts.

Folate and B12 are two of the most essential nutritional factors for methylation, and their efficient absorption is essential for normal epigenetic regulation and numerous enzymatic functions. Those with MTHFR and gluten sensitivity are advised to focus on restoring levels of both nutrients, especially methylfolate. 

Methylfolate is the bioactive form of folate which is readily available for use in the body. It bypasses the MTHFR polymorphism and is well absorbed even when digestive function is poor. Most importantly, its bioavailability is not affected by metabolic defects.

It can be difficult to replenish poor nutrient status through food alone. Supplementation is often the most efficient way to restore a nutrient deficiency, particularly when nutritional uptake is compromised by a dual diagnosis. 

Reducing homocysteine levels is also crucial, and scientists recommend treatment with B-complex vitamins to reduce homocysteine levels. This is best done with a methylfolate supplement.

Taking folate as 5-MTHF directly has been shown to significantly increase blood serum folate levels and reduce homocysteine levels. It’s also much more effective than taking folic acid in lowering homocysteine. 

Some of the best methylfolate supplements for those with MTHFR and gluten sensitivity are in the Methyl-Life® range. These include Methylfolate,  B-Methylated II, and Methylated Multivitamin. These products have been created by a team of natural health experts and contain the purest, most stable, and most potent of the world’s four industry-leading patented methylfolates. This form of methylfolate is also suitable for vegans and those with cardiovascular risks. 

For those who are unable to properly absorb B12, Methy-Life’s® B12 Complete is ideal. B12 Complete contains a combination of the 3 most bioactive forms of B12 (hydroxocobalamin, methylcobalamin, and adenosylcobalamin) for maximum delivery and uptake.