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 Trusted SourcePubMedGo to source].
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.
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% . 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).
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 Trusted SourcePubMedGo to source]:
“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 Trusted SourcePubMedGo to source, 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, 12].
The Paleo Diet
Key principles of a healthy diet include reducing inflammation, balancing blood sugar, and eliminating foods you may have sensitivities to.
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:
Nuts and seeds
Grass-fed meats and fresh fish
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)
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) [15, 16]. Taking unnecessary supplements including high-dose B vitamins, folic acid, or methyl-folate can lead to hypermethylation .
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 Trusted SourcePubMedGo to source, 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 [18 Trusted SourcePubMedGo to source].
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 should avoid folic acid supplements (the more common and synthetic form of folate).
Instead, they suggest opting for more expensive methyl-folate supplements (also known as 5-methyltetrahydrofolate or 5-mthf).
However, there is no evidence to support that folic acid supplements are more harmful or less effective than methyl-folate supplements [19 Trusted SourcePubMedGo to source, 20]. Therefore, if you are going to take folate supplements, either form should be fine, regardless of your MTHFR genotype.
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:
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].
Support detoxification. Sweating with the help of Epsom salt baths, saunas, and/or exercise can help to support healthy detoxification . Eating an anti-inflammatory diet and staying hydrated are also helpful detox strategies.
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.
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