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A Balanced Approach to the ‘MTHFR Diet’

Written by Dr. Ruscio on March 24, 2021

Written by Dr. Ruscio on March 24, 2021 — Reviewed by Aimee Gallo

How to Eat for Optimal Health With MTHFR Gene Variants

• What Is MTHFR|
• MTHFR Gene Variants|
• MTHFR Diet|
• The Best Diet for Methylation and Overall Health|
• Supplements for MTHFR Support|
• Diet, Lifestyle, and Gut Health|
• Recommended Products|

A specialized “MTHFR diet” and supplement regimen has been promoted online for people who have common MTHFR gene variations. However, research has not been able to confirm that a specific diet is beneficial for people with these genetic profiles. 

That said, if you’re interested in modifying your diet and lifestyle to improve your health, and resolve symptoms like fatigue, brain fog, or digestive issues, you’re on the right track. 

In this article, we’ll dig deeper into recommendations for MTHFR diets and supplements, including dietary principles to follow for overall health, and how to know whether or not you should be taking supplements like methyl-folate or vitamin B12. 

We’ll also explain how to improve the markers that are sometimes associated with MTHFR gene mutations (including folate and homocysteine levels) through diet and lifestyle support. 

What Is MTHFR? 

MTHFR, short for methylenetetrahydrofolate reductase, is a gene that instructs the body on how to make the enzyme of the same name [1]. 

The MTHFR enzyme converts folic acid from food (or supplements) into methyl-folate (the active form of folate), which is used for an important process in the body called methylation.

The methylation process helps to regulate metabolic function, detoxification, brain function, digestion, hormonal balance, and energy production.

What MTHFR Gene Variants Mean  

Common variants in the MTHFR gene (often referred to as genetic mutations or polymorphisms) may result in a somewhat reduced capacity to produce the MTHFR enzyme and may therefore affect methylation. 

Based on this concept, MTHFR polymorphisms have been tenuously linked to an increased risk of developing several different ​health issues, including Alzheimer’s disease, breast cancer, colon cancer, schizophrenia, thyroid issues, and heart disease. 

Consumer-focused genetic tests, such as those offered by 23andme, can show you whether or not you have an MTHFR gene variation.  

However, a closer look at the research shows that the health risks associated with MTHFR variants are minimal at most, and the utility of genetic testing is limited [1, 2]. 

For example, one of the biggest concerns associated with MTHFR gene variants is the potential effect on homocysteine levels. However, a 2019 analysis found that the actual impact of MTHFR gene variations on homocysteine levels was at most 1% [3]. We’ll dive deeper into this below. 

MTHFR, Folate, and Homocysteine 

Because the MTHFR gene plays a role in folate metabolism, many of the concerns that have been raised about it relate to the risk of low levels of folate (vitamin B9). 

Low levels of folate and other B vitamins may lead to higher levels of homocysteine (an amino acid found in the blood), which have been linked to various health conditions including cardiovascular disease [4, 5, 6]. 

Based on these relationships, online advice about MTHFR gene polymorphisms often involves an entire diet, supplement, and lifestyle regimen centered around increasing folate and vitamin B levels, decreasing homocysteine levels, and enhancing methylation. 

However, research shows that the actual impact of the MTHFR gene on homocysteine levels, folate metabolism, and health outcomes is quite small, so MTHFR-targeted diet and supplement measures are probably not necessary [3, 7]. 

What Is an MTHFR Diet?

Some people suggest that individuals with MTHFR gene variations should follow a specialized “MTHFR diet” and supplement regimen focused on increasing levels of folate and vitamin B12, and on improving methylation. 

While many of the foods that contain folate and B vitamins are healthy and have a place in a well-rounded diet, building your entire diet and lifestyle around the MTHFR gene is not necessary. 

There is no diet that has been shown to be specifically beneficial for those who have MTHFR gene variations. A 2015 American Heart Association review concluded the following [1]: 

“The presence of MTHFR mutations does not require any special treatment, such as supplementation with folic acid, vitamin B6, or vitamin B12.” 

The Best Diet To Support Methylation and Overall Health 

While a diet based on your MTHFR gene is not necessary, a healthy diet is essential for your overall wellness. 

Regardless of your genetic profile, the right diet can improve methylation, detoxification, immune system health, brain function, and gut health, helping to resolve common concerns like fatigue, brain fog, and digestive issues [8, 9, 10]  

A well-rounded diet rich in whole foods can also help to naturally balance your levels of folate, vitamin B12, and homocysteine [11]. 

The Paleo Diet

Key principles of a healthy diet include reducing inflammation, balancing blood sugar, and eliminating foods you may have sensitivities to. 

A diet that fits these criteria and helps many people feel better is the Paleo diet [8, 12, 13]. 

The Paleo diet eliminates processed foods, refined sugar, and artificial sweeteners, which are known to contribute to inflammation, gut health imbalances, and other health problems.

The Paleo diet also eliminates commonly inflammatory foods like grains (including gluten), dairy products, and legumes (such as beans and lentils).  

Foods to enjoy on a Paleo diet include: 

• Fresh vegetables 
• Fresh fruit 
• Nuts and seeds
• Grass-fed meats and fresh fish 
• Eggs 
• Healthy fats, including olive oil and avocados 

Foods High in Folate

If you are concerned about methylation, folate, or homocysteine levels, you may want to include more foods that are high in folate in your diet. 

If you are following a Paleo or similar diet, it’s likely that you will naturally be eating many of these foods, which have several additional health benefits. 

Paleo-friendly dietary sources of folate include: 

• Leafy green vegetables (including spinach and kale) 
• Asparagus 
• Broccoli 
• Avocado 
• Oranges and mangoes 

Supplements for MTHFR and Methylation Support 

A common misconception is that everyone who has an MTHFR gene variant should take supplemental B vitamins and methyl-folate in order to enhance methylation. 

Supplements may be helpful in some cases, but they shouldn’t be taken based on genetic testing for MTHFR. 

There are a few important things to consider when it comes to supplementation for methylation:

• Too much methylation can be harmful. While proper methylation is important, research shows that more is not always better. Too much methylation (known as hypermethylation) can be dangerous, just like too little methylation (hypomethylation) [14]. Taking unnecessary supplements including high-dose B vitamins, folic acid, or methyl-folate can lead to hypermethylation [15].
  
• The MTHFR gene doesn’t determine your folate or homocysteine levels. While taking folic acid and B12 supplements can help to reduce homocysteine levels, research shows that the impact of the MTHFR gene on homocysteine levels is extremely low [1, 3]. Blood tests can determine your actual levels of homocysteine, folate, and B12, in order to discern whether or not supplementation may be warranted.
  
• Diet and lifestyle factors should come first. There are a number of ways to support the body’s production of B vitamins and to reduce homocysteine levels, eliminating or reducing the need for long-term vitamin supplementation. For example, one study found that increasing healthy bacteria in the gut with probiotics increased the production of B vitamins and decreased homocysteine levels [16].

With this in mind, folic acid or vitamin B supplements may be recommended in moderate doses if: 

• Blood test results show low folate, low vitamin B12, and/or high homocysteine levels, and; 
• Diet, lifestyle, and gut health factors are already in place. 

Folic Acid vs. Methyl-Folate 

Proponents of the MTHFR diet and lifestyle have suggested that those with MTHFR gene polymorphisms and low folate status should avoid folic acid supplements (the more common and synthetic form of folate). Mechanistically, people with MTHFR polymorphisms should require methylfolate, which means to some functional medicine professionals that MTHFR folks should only take methylfolate supplements (also known as 5-methyltetrahydrofolate or 5-MTHF) to raise low folate levels.

But a few studies show that this isn’t typically the case, and people with a MTHFR mutation can safely increase their folate levels with regular folic acid. In fact, most people in the U.S. have one of the MTHFR variants, and there is no evidence to support that folic acid supplements are more harmful or less effective than methylfolate supplements [17, 18, 19]. Perhaps this is possible because we don’t yet know about some side pathways that allow people with MTHFR variants to metabolize synthetic folate.

In any case, even if you have an MTHFR mutation, you probably want to avoid taking long-term, high-dose supplemental folate if your levels are normal on a blood test. There is some concern that unmetabolized folic acid can build up in the body over time, but the existing evidence for this is inconclusive and weak [20]. In other words, the evidence isn’t strong enough to outweigh the many benefits of folic acid on our health, so you don’t need to completely avoid it in fortified foods or supplements. And if you are going to take folate supplements, either form should be fine, regardless of your MTHFR genotype. It really depends on how much you want to spend: synthetic folate is a lot cheaper than 5-MTHF.

How to Find the Best Folate Supplement for You

If you have a known MTHFR mutation and folate deficiency, and you’re still not convinced that folic acid is the way to go, you’ve come by that notion honestly. There’s a lot of anti-folic acid rhetoric out there, and there is really no harm in going with a methylated form (aside from its higher price point). But because it’s likely safe [18], effective [17, 19], and inexpensive, you might consider trying folic acid first and see if it helps raise your levels.

If your serum folate levels quickly increase after starting folic acid, it likely means your body is metabolizing it well. If your numbers don’t budge or you have to take very high doses of folic acid to see a difference, try a methylated form to see if your body utilizes it better. Making the switch to methylfolate or folinic (not folic) acid can help safely increase your levels and prevent unused folic acid from building up in your body if you are a true folic acid non-responder. 

We don’t know everything about how folate metabolism works—hidden routes may exist, and each body may use them differently. It’s always important to remember to do what works for you, and not get stuck in the MTHFR mutation rabbit hole.

Diet, Lifestyle, and Gut Health Foundations 

The best way to support methylation, detoxification, and overall health is to focus on creating a healthy environment within your body, including your gut. 

Eating an anti-inflammatory diet, which we covered above, is one of the most important things you can do to create this healthy environment. There are also a few other foundational pieces that work together with your diet for the best outcomes.

The foundations of a healthy internal environment include: 

• Eat an anti-inflammatory diet. A diet that emphasizes whole foods and reduces inflammation is one of the most important factors when it comes to overall health. Anti-inflammatory diets, including the Paleo diet and the Mediterranean diet, have been shown to improve cognitive function, gut health, metabolic health, and heart health [8, 21, 22, 23, 24].
• Make sure to get enough sleep. Lack of sleep is one of the biggest risk factors for chronic illness and inflammatory disease, and getting 7-9 hours of restful sleep per night can significantly improve your health [25, 26]. 
• Get regular exercise. Regular exercise is essential when it comes to reducing the risk of disease and improving overall health [27, 28]. 
• Support detoxification. Sweating with the help of Epsom salt baths, saunas, and/or exercise can help to support healthy detoxification [29]. Eating an anti-inflammatory diet and staying hydrated are also helpful detox strategies.
• Take probiotics. Probiotic supplements help to improve the balance of bacteria in your gut, which can influence everything from nutrient levels to inflammation and disease risk [16, 30, 31, 32, 33, 34]. 

A Big Picture Approach To Your Diet and Health

The best diet for your health should be based on a combination of your individual needs and fundamental health principles, not your genetic profile. 

MTHFR gene variations are common and have not been proven to have a significant impact on health outcomes. However, if you have concerns about methylation, folate levels, or homocysteine levels (which have been associated with the MTHFR gene), you can support them with your diet and lifestyle. 

The best general approach is to follow an anti-inflammatory diet (like the Paleo diet) that includes whole foods that are naturally high in folate. Supporting gut health with high-quality probiotics, regular exercise, and quality sleep is also important. 

By taking a well-rounded, big-picture approach to your diet and your health, you can likely improve or resolve many of the symptoms that have been mistakenly associated with the MTHFR gene and feel better.

To learn more about healing your gut and improving your overall health, check out my book, Healthy Gut, Healthy You.

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