MTHFR Mutation 101: What it is and 6 Things To Do In Response

MTHFR Mutation

One of the biggest challenges of nutritional requirements is the genetic individuality. Genetic differences — just like all the ones that make you unique enough to be reading this — also affect how you process nutrients.

One of the most common ones that has gotten substantial interest recently is a mutation in the MTHFR enzyme.

No…it doesn’t stand for Mother-effer…

It’s an enzyme critical to methylation which touches almost every reaction in your body. 

Read on to learn about methylation and some things you may be able to do if you have a mutation.

What is Methylation and MTHFR?

MTHFR is an abbreviation for methylenetetrahydrofolate reductase, an enzyme that converts vitamin B9 (folate) into its active form, methyl-folate. Methyl folate is essential for a process called methylation.

Methylation is a metabolic process occurring in every cell of the body and involves one molecule passing a methyl group to another molecule. Ok, ok that might not mean very much to you non-science geeks out there. But, in layman’s terms, it’s essential for a healthy, well-functioning body and mind.

Some important reactions that involve methylation include:

  • Metabolizing B vitamins
  • Repairing cellular damage
  • Detoxification
  • Hormone metabolism
  • Regulating neurotransmitters that are responsible for mood, sleep, and behavior
  • Regulation of gene expression (turning genes on and off)
  • Producing energy within cells

One of the ways methylation completes these vital physiologic tasks is playing a pivotal role in the methionine homocysteine cycle.

If you have a mutation in MTHFR, you cannot properly methylate folate. Methylfolate is necessary to convert homocysteine back into methionine. Thus, inadequate MTHFR activity tends to lead to elevated homcysteine levels. This is associated with a number of diseases described below.

Additionally, deficient methionine leads to deficient SAM-e production. Recent studies implicate SAM-e in depression .

We each have a pool of amino acids circulating through our bodies at all times. These amino acids come from eating protein foods as well as the break down and rebuilding of muscle and other physiologic processes.

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So the mthfr enzyme helps recycle excess homocysteine into methionine through methylation. This process is critical for two main reasons:

  1. Methionine is essential to the above dynamic reactions such as detox, production of glutathione to protect and repair cells, inflammation response, etc..
  2. Elevated levels of homocysteine increase inflammation in the body and can be harmful. High homocysteine is associated with a number of health conditions, especially blood clots, stroke, embolism and heart attacks (*).

A Bit More on Homocysteine

Homocysteine is an amino acid (a building block of protein) found in the blood and is a byproduct of methionine metabolism – that is breaking down methionine to be excreted in urine. 

The risks that come with elevated homocysteine include (*):

  • Cardiovascular disease
  • Blood clots in veins
  • Pregnancy complications
  • Deep vein thrombosis (DVT)
  • Neural tube defects
  • Vascular dementia and Alzheimer’s disease
  • Additional conditions that are being investigated: Downs Syndrome, MS, migraines, autism, PCOS and cognitive impairment 

Homocysteine’s role in cardiovascular disease is not fully understood but seem to include impacting several factors involved with blood clotting and endothelial damage (*). More clinical studies are needed to define its exact role. 

In addition to the cardiovascular risks, elevated homocysteine is a modifiable risk factor for vascular dementia and Alzheimer’s disease (the most common form of dementia). 

Research shows that hyperhomocysteinemia is associated with changes in the white matter of the brain, cognitive decline, brain atrophy, and neurofibrillary tangles (*). Studies have shown that in high risk populations these changes can be slowed when vitamin B status is corrected (*).

Homocysteine can be tested in the blood. Classifications for what is considered normal have not been entirely standardized but typical ranges are below (*):

  • Normal: < 15 µmol/L 
  • Mildly Elevated: 15 – 30 µmol/L 
  • Moderately Elevated: 30 – 60 µmol/L 
  • Severely Elevated: >60 µmol/L 

However, remember that these reference ranges are set based on the average population. And you sure as hell don’t want to be average. I like to see homocysteine < 7. 

Some people with elevated homocysteine need more B vitamins. One of the best sources on the carnivore diet is beef liver. Yes, it’s hard to swallow…but I can help. Sign up below for some great liver recipes and a FAQ. 

Methylation and Gene Expression

We used to think nurture (our environment) and nature (our inherited genes) were completely separate influences over health and disease that do not interact with each other. We now know that our environment can, in fact, influence our genetic material.

Methylation of DNA is how this physiologic phenomenon plays out in our bodies. Methylation impacts how our genetic material is expressed – effectively turning on or turning off genes and influencing our likelihood for health and disease in the process (*).

Improper methylation can lead to inappropriate gene silencing, such as the tumor suppressor genes in cancer cells (*). This is not something to mess around with. 

Your genes are not fixed…and methylation is the control center for this process. If your MTHFR mutation is suppressed it’s like the control tower at an airport falling asleep. 

What is the MTHFR Gene Mutation?

Let’s take a trip back to high school biology for a minute, shall we? 

We each have a unique genetic makeup comprised of genes from our parents. The MTHFR gene is the genetic material responsible for the production of the MTHFR enzyme. You have two copies of this gene – one from your mom and one from your dad.

When part of a DNA sequence varies from the normal healthy population it is called a variant or mutation. It’s important to note that everyone has some variation in their genes. If the MTHFR gene is mutated it can interfere with the production of the MTHFR enzyme and therefore impact all the important reactions that involve methylation.

If you have elevated homocysteine, these mutations are likely culprits. 

What are the Signs and Symptoms of the MTHFR Gene Mutation?

Some people have the MTHFR mutation and have no symptoms. However, others may experience an array of symptoms including:

  • Elevated homocysteine
  • Migraines
  • Nerve pain
  • Anxiety
  • Chronic fatigue and pain
  • Digestive issues
  • Sleep disruption
  • Increased sensitivity to medications
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How Does the Mutation Impact MTHFR & Methylation?

Mutations can be in one or both copies of the MTHFR gene. If both copies are mutated, there is a larger impact on the MTHFR enzyme and therefore a higher likelihood of an impact on your health.

There are two common variations of this gene and depending on the combination of mutations you carry, MTHFR enzyme activity can be decreased anywhere from approximately 30-75% (*). 

The two most common variants of the MTHFR gene are C677T and A1298C. You can be heterozygous for each variant or for both (meaning you’ve got one copy of each variant) or you can be homozygous for one (meaning you’ve got two copies of one variant).

The C677T variant impacts 20-40% of white and Hispanics within the US and is less common among African Americans, where only 1-2% have the variant (*). In those that are heterozygous for this variant, enzyme function is reduced by 35%. In those that are homozygous enzyme function is reduced by 70% (*).

Health Conditions and MTHFR Mutation

Several conditions have been connected to the MTHFR mutation. Because of the vital role of methylation, a mutation in the MTHFR gene leaves the body vulnerable to disease processes fueled by oxidative stress and the inability to detoxify.

While more research is needed to better understand the connection. In the meantime, I’m sure you’ll agree you’d like to avoid a higher than normal risk of these conditions.

Some of the health conditions associated with MTHFR mutation include (*,*):

  • Mental health disorders: anxiety, depression, bipolar disorder, schizophrenia
  • Cancers: colon cancer, leukemia
  •  Infertility and pregnancy complications: recurrent miscarriages, neural tube defects
  •  Cardiovascular diseases: blood clots, stroke, embolism, and heart attacks
  •  Disordered gallbladder and bile functioning: thick, sticky bile (think molasses consistency when optimal functioning requires thin, dish soap consistency).

Nutrient Impact of MTHFR Mutation

There are some shifts in metabolism with this mutation. Probably the most obvious given that the MTHFR enzyme converts B9 into active folate is that active folate is not present to do its job effectively. 

Other B vitamins like Riboflavin and B12 are critical to this process. This is why homocysteine levels tend to be negatively correlated with B vitamin intake . (The best food in the world for b vitamins is beef liver).

As a result of not having enough folate, choline steps in as a methyl donor and takes on some of the work of folate. Consequently, more choline is needed to meet the increased demand.

In addition to choline, lack of folate contributes to wasting of glycine. Glycine is yet another amino acid in this scientific soap opera! Glycine is important because it is one of the amino acids used to produce glutathione – that master antioxidant I mentioned before that helps your body to minimize damage from oxidative stress like cigarette smoke, pollution, UV rays etc.. 

Methylfolate preserves glycine, so in its absence you are vulnerable to glycine losses that must be made up with dietary sources.

Finally, creatine synthesis declines due to a reduction in methylation activity. Therefore more creatine is needed through diet or supplemental sources. Increasing dietary creatine sources (ie. meat) beyond what you need for protein and other nutrients may offset the benefits due to a subsequent increase in methionine. Therefore supplemental creatine may be the best option. 

MTHFR Diet: 6 Ways You May Be Able to Do in Response to the MTHFR Mutation

The MTHFR mutation is a common variation in metabolism. If you have it, studies show these are some things you may be able to do in response. 

Experts in the field suggest an entire lifestyle approach to managing this common mutation. Studies show that these 6 ways are the best approach to giving your MTHFR enzyme additional support. 

1.  Additional Riboflavin May Be Necessary 

An additional 1.6 mg of riboflavin per day (above the standard Recommended Dietary Allowance or RDA) may increase MTHFR enzyme activity among those with an MTHFR mutation and poor riboflavin status. The impact of this is a reduction of homocysteine by as much as 40% (*). While deficiency of riboflavin is reported to be rare, a recent study found that poor riboflavin status based on biochemical markers was quite common (*).

Nutrition expert Dr. Chris Masterjohn recommends 3 mg of riboflavin to meet the RDA plus the additional 1.6 mg. One of the best ways to get this is through 6-8oz of of liver per week (ex. Beef, bison, lamb)

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2.  Eat food sources of folate

It may go without saying but with the MTHFR mutation, converting folate into its active form is limited. Incorporating more dietary sources of folate, can supply the body with more of this essential nutrient. Some particularly good food sources are listed below. On the carnivore diet, beef liver is the best source of folate.

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3.  Incorporate glycine

Low levels of folate may cause you to waste or lose glycine more frequently. This is because folate is required for amino acid homeostasis. Therefore more dietary glycine is required.

Glycine is found in the skin and bones of animals – and other parts you won’t typically find in your average meal. However, you can obtain these nutrients through making your own bone broth, consuming foods like sardines that contain bones, or adding collagen powder to your regimen.

4.  Increase Choline intake 

As more choline is used to do the job of folate, you’ll need to eat more choline. Some experts recommend 900-1200 mg of choline per day. This amounts to 4-5 egg yolks per day or a serving of liver + 2-3 egg yolks. Some vegetables are also sources of choline however, if you want a food that multi-tasks stick with liver and eggs as they address more than one nutrient recommendation on this list (all the best foods do!)

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5.  Support Gut Health

If your gut’s a mess, you won’t be able to use all this nutrient-dense food. The first step toward good gut health is paying attention to how and when you eat.

Incorporating protein and glycine-rich foods as noted in #3 and #4 above may help maintain a strong gut lining (which happens to be a muscle) to make sure what you’re eating stays in the gut until its ready to be delivered elsewhere. 

Consider this snippet a primer on gut health, more information can be found in my leaky gut article.

6.  Reduce Oxidative Stress and Toxic Exposures

With impaired methylation, your body is less equipped to deal with environmental stressors and toxins. Why? With the MTHFR mutation, production of the body’s master antioxidant, glutathione may decrease. Antioxidants protect cells against damage from free radicals.

Some general rules of thumb you may want to follow:

  • Don’t smoke
  • Reduce exposure to pesticides, herbicides, common household chemicals, etc.
  • Manage stress
  • Get enough sleep

Conclusion

Each and every individual is unique. While this article provides a wealth of information – let’s be honest, I don’t know you, man! The best way for you to manage your own health is to learn more about your genes and then get to work.

I recommend everybody gets a genetic test to determine their enzyme activity. From all the information above, it should be clear that Liver and egg yolks are the kryptonite of decrease MTHFR activity. 

Yes…beef liver definitely doesn’t taste like a ribeye dripped in butter. Sign up below if you’re interested in 5 ways to cook beef liver and answers to the most frequently asked questions. 

Get 5 Delicious Beef Liver Recipes & Answers to FAQ

 DISCLAIMER: The goal of Carnivore Aurelius is to educate and motivate others to take charge of their health. I am not a medical doctor, registered dietitian, or qualified to give individualized recommendations regarding health, nutrition or fitness. All views expressed are based on my own personal research and experiences. For specific health-related questions, please consult your doctor.

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