MTHFR Gene Mutations: What You Need to Know

All humans have the same set of genes.

Our differences come from the tiny variations in those genes.

Those variations influence not only how you look or behave different to others, but how your body reacts differently to external factors.

Especially how it reacts to the foods you eat.

For example, some have great difficulty metabolizing caffeine. For others, it could be alcohol (1, 2).

Then there are the people who have zero issues with either.

This is because we all have certain genetic variations or “defects” that can influence how we metabolize certain nutrients.

One of the more common and potentially dangerous variations is known as an MTHFR mutation.

This gene variation can severely impact how well your body metabolizes folate and folic acid. Both are forms of vitamin B9, required for numerous critical bodily functions.

Unfortunately, a fault in this metabolic cycle is linked to many serious health problems (3).

This article describes the MTHFR mutation and explores what implications it may have for your health and diet.

What You’ll Learn:

  • What MTHFR is and its role in folate metabolism.
  • What an MTHFR mutation actually means and the risks for disease and disability.
  • MTHFR symptoms to look out for (should you get tested?).
  • The basic problem with folic acid and the basic solution.
  • Implications for MTHFR and pregnancy.
  • Recommendations for your diet.
  • Where to get tested.

What is MTHFR, the MTHFR gene, and MTHFR mutation?

MTHFR, short for Methylenetetrahydrofolate Reductase, is a very important enzyme in the body.

It’s necessary for Methylation to occur, a metabolic process that switches genes on and off, repairs DNA and many other important things.

Methylation is also essential to convert both folate and folic acid – each a form of Vitamin B9 – into its active, usable form.

This is a diagram of how complex it is, but you only need to see the final step.

folic-acid-metabolism from DietvsDisease.org

All the steps required to convert folate and folic acid into their active form, 5-MTHF

(Source: Image adapted from MTHFR Support Aus.)

You can see that the final (bottom) step requires MTHFR in order to create the active form.

So without the enzyme activity of MTHFR, methylation of folate and folic acid cannot occur properly.

For a more detailed yet easy to follow explanation of this process, see Methylation for Dummies.

MTHFR gene
Put simply, the MTHFR gene triggers the production of MTHFR enzymes.

Think of the gene as the flower, the enzyme as the honey-bee and active folic acid as honey.

Without flowers, there will be no honeybees. Without honeybees, no honey is created.

MTHFR mutation
test tube dna genetics colourfulRoughly 30-50 percent of us carry a mutation in the MTHFR gene, passed down from our parents.

The two main functional mutations (also known as polymorphisms) of the gene are MTHFR C677T and MTHFR A1298C (3).

Specifics aside, these genetic mutations are collectively known as MTHFR mutations. They can be like a “defect” which limits production of your MTHFR enzymes.

Most people with a mutation remain unaffected and do not experience symptoms.

However, for some, enzyme efficiency can drop down to between 30-70 percent depending on the variant of mutation (4).

Note that there are numerous genetic mutations that can potentially hinder methylation. An MTHFR mutation is just one of many, but it’s the most well-researched and likely most important.

Summary: MTHFR is an enzyme necessary for an important metabolic process called methylation. It is this process that converts folate and folic acid into an active form the body can use. The MTHFR gene produces this enzyme, but a genetic mutation can inhibit its function.

MTHFR mutation may increase the risk of cardiovascular disease and vitamin B deficiencies
AA043368Those with an MTHFR mutation are at risk for poor MTHFR enzyme efficiency.

Consequently, folate and folic acid cannot be efficiently converted into their active form, known as 5-MTHF. Therefore those nutrients can’t perform one of their key functions: breaking down (recycling) Homocysteine.

Homocysteine is an amino acid thought to damage the lining of your arteries and other cells of the body. It is naturally formed in the body, but gets broken down (recycled) by 5-MTHF.

Elevated homocysteine levels in the blood is an independent risk factor for heart disease, stroke and other forms of cardiovascular disease (5, 6, 7).

It has also been linked with a wide range of other health problems including macular degeneration, Alzheimer’s disease, hearing loss and cancer.

A lack of active folic acid (alongside a low folate diet) can also lead to a Folate Deficiency, which has major health implications on its own.

Therefore, those with a “bad” MTHFR mutation are at an increased risk for health problems if the issue is not addressed and their diet is not rich in folate.

Summary: Those with an MTHFR mutation may be predisposed to increased levels of homocysteine, a strong risk factor for cardiovascular disease. They are also more likely to develop a folate deficiency if their diet is not rich in folate.

What about other disease states and disabilities, like anxiety?
HeadacheConsidering that genes are influenced by our diet and environment, many studies are also able to find a link between MTHFR and a particular disease process or disability.

This ranges from cancer risk to hypothyroidism to autoimmune diseases and more; however it’s difficult to pinpoint an MTHFR mutation alone as a direct risk factor.

There is a dubious compilation of the research here, but the studies are not very convincing and not all the research is listed.

The reality is that overall evidence for these health claims are very weak, and MTHFR mutations are unlikely to be a direct causal factor.

Summary: MTHFR could very well contribute to or exacerbate heart disease and folate deficiency, but this is due to excessive homocysteine. The mutation itself does not appear to directly cause certain disease states or disabilities.

MTHFR symptoms of a problem
Avoid food products high in added sugar pregnantIf you believe you may have an MTHFR issue, there is no way to know for sure without getting tested.

In saying that, there are some trending “MTHFR symptoms” among those with a defect that warrant an MTHFR test:

  • High homocysteine levels: Caused by poor methylation.
  • Folate deficiency: A deficiency in folic acid (folate) could be linked to MTHFR and is worth checking out. Common symptoms include extreme fatigue, light-headedness, and forgetfulness.
  • Had a miscarriage: Many practitioners recommend testing for MTHFR mutations if you have had one or more miscarriages.
  • Longstanding gastrointestinal issues: Such as irritable bowel syndrome.
  • An autoimmune disease: Based more on anecdotes than solid science.
  • Long history of anxiety or depression: Based more on anecdotes than solid science.

It’s important to note that an MTHFR mutation itself is not inherently dangerous… but any form of genetic variance has the possibility to affect your health.

Knowing what the gene is and how it could affect you is seen by many as beneficial.

Summary: There are some common trends among those who have an MTHFR mutation. If you experience any “MTHFR symptoms” it could be worthwhile getting tested.

Folic acid is a problem, 5-MTHF is a solution
Business Advertising. Stand Out. Business concept.Folic acid is the conventional supplement for treating B-vitamin deficiency, lowering homocysteine levels and reducing the incidence of Neural Tube Defects (8, 9).

It is so effective that the addition (fortification) of folic acid to wheat flour is now mandatory in Australia, USA, Canada and several other countries (10).

This is a big problem for people who don’t metabolize folic acid well, whether from low MTHFR activity or another enzyme issue (11).

It becomes an even bigger problem when you consider the recommended daily intake for folic acid is 400 μg, yet unmetabolized folic acid already appears in the blood when we consume just 200 μg per day (12).

Folic acid accumulating in the blood can potentially mask dangerous vitamin B deficiencies such as megaloblastic anaemia.

Fortunately there is a somewhat simple solution
Aside from limiting your intake of fortified wheat flour, folic acid supplements should be replaced with the active form: 5-MTHF.

It bypasses any MTHFR defects and is shown to be equally (if not more) effective at increasing plasma folate levels and reducing homocysteine concentrations (13, 14).

5-MTHF is also better absorbed and interacts with fewer medications than folic acid (15).

So far the FDA and European Food Standard Agency have approved several products containing 5-MTHF. Many speculate it will soon replace folic acid as the protocol treatment.

There are some important factors to consider before taking 5-MTHF though, namely your vitamin B12 levels (and a particular variation of vitamin B12). This is why guidance from a Dietitian or GP that specializes in this area is so important.

Summary: Folic acid can be very problematic for some, particularly those with an MTHFR mutation. Those people should avoid fortified wheat flour and look to swapping regular folic acid supplements for 5-MTHF.

Folic acid, MTHFR and pregnancy
Avoid alcohol and caffeine when pregnantActive folic acid is highly protective against Neural Tube Defects.

However, a conventional folic acid supplement is likely not protective of your child if it remains inactivated in your blood stream.

That’s why testing for and flagging an MTHFR mutation could be especially useful for women of childbearing age.

Therefore, a more conservative and thoughtful approach to folic acid supplementation is warranted for those with MTHFR issues.

If you are planning to have a child, or less than 13 weeks after conception, then supplement with 5-MTHF instead of folic acid.

While you’re at it, you should be avoiding these 6 foods too.

Summary: Women with an MTHFR mutation who are planning to have a child or already less than 13 weeks pregnant should be supplementing with 5-MTHF rather than folic acid.

MTHFR diet and nutrition recommendations
biting appleThe importance of folate cannot be overstated.

That is why MTHFR symptoms warrant such concern in the first place.

While more folic acid (synthetic vitamin B9) is not desirable, more folate (natural vitamin B9) certainly is.

This is especially true for those with an MTHFR defect, as more folate in the diet means more opportunities to create the active form 5-MTHF.

The body easily recycles leftover folate into a harmless compound, whereas it cannot do so with folic acid. Without getting into details, that is why folate does not accumulate in the blood, but folic acid does.

According to NutritionData, the best sources of folate per 100 g serving are:

  • Beans and lentils (~50% RDI)
  • Raw spinach (49% RDI)
  • Asparagus (37% RDI)
  • Romaine (Cos) lettuce (34% RDI)
  • Broccoli (27% RDI)
  • Avocado (20% RDI)
  • Oranges/Mangoes (~10% RDI)

(RDI = Recommended Daily Intake)

Studies have even shown that a folate-rich diet can match the homocysteine-lowering effects of either a regular folic acid or 5-MTHF supplement (16).

As though we needed any additional reasons to eat more vegetables and legumes.

There are several other important nutrients to think about for folate metabolism. Namely vitamin B2 (Riboflavin) and vitamin B6 (Pyridoxine), which assist in the formation of 5-MTHF.

The top food sources for B2 and B6 can be found here and here, respectively. If you are lacking in either of these nutrients, the whole system can break down.

What foods to avoid?
It is commonly thought that antacids, some blood pressure medications, metformin (for type 2 diabetes) and contraceptives may all inhibit dietary absorption of B-vitamins to some extent.

If you regularly take any of these, it is best to seek personalized health advice from your Dietitian or GP.

Summary: Natural folate is a nutrient that we all need to eat more of… MTHFR defect or not. Vitamins B2 and B6 are also important given their role in folate metabolism.

How and where to get an MTHFR test

Chemist researcher working with microscope for forensic evidenceOnly a genetic test can verify if you have a gene mutation and what specific type.

Most service providers can mail the testing kit out to you, so it remains non-invasive and you don’t have to go anywhere. Simply send back a saliva swab and await your results.

One of the most well-known companies that cater worldwide is 23andme.com. They provide the most comprehensive genetic profile as it relates to methylation and the MTHFR gene.

Additionally, instead of trying to interpret your own results, you can run your 23andme methylation analysis through GeneticGenie.org (free) and it explains exactly what you need to know.

If you choose to use your own local lab, ensure they test for the MTHFR C677T and A1298C mutations, which are the main ones. Not all labs do so make sure you ask first.

Remember that genetic testing is only a tool to support you in better health. Having a genetic mutation does not necessarily mean it will affect you.

As they say, “Genes load the gun, environment pulls the trigger.”

Always consult with a Dietitian or GP who can put your results into context.

And eat more folate-rich foods… That goes for everybody.

 

Written by Joe Leech (MSc Nutrition), you can see the original post on Diet vs Disease.

42 comments

Siyus Copetallus
Siyus Copetallus3 years ago

Thank you for sharing.

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Elena Poensgen
Elena Poensgen3 years ago

Thank you

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Jordan G.
Jordan G3 years ago

Joe, your work is excellent. TY for posting.

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Elena Poensgen
Elena Poensgen3 years ago

Thank you

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Jordan G.
Jordan G3 years ago

Brilliant. thanks

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Elena Poensgen
Elena Poensgen3 years ago

Thank you

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Jim Ven
Jim V3 years ago

thanks for the article.

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Erika Acosta
Erika Acosta3 years ago

Thanks

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Caroline B.
Caroline B3 years ago

Very interesting.

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Paulinha Russell
Paulinha Russell3 years ago

Thank you

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