The New Hidden Health Hazard: The MTHFR Mutation (+ 5 Serious Health Problems It Can Cause)

January 20, 2020

When I was in medical school, we learned about a genetic mutation that affects an enzyme involved with many of our everyday metabolic activities from detoxification to mood and to energy production. This enzyme is called “methylenetetrahydrofolate reductase,” or MTHFR. In many people, there is a genetic mutation in this enzyme, which has been termed the MTHFR gene mutation. At that time, I had fun twisting its names into inappropriate words so that I could remember it for my board exams. I didn’t really give it much more thought outside of a general understanding of methylation and that it had something to do with folate levels in the body.

Fast forward to years later, when genetic testing was becoming all the rage, I sent in my kit to analyze my genetics. The results surprised me. I had both variants of the MTHFR mutation present. (There are twovariants of the MTHFR mutation called C677T and A1298C, each one having its own particular impact on methylation pathways.)

As I looked at my results, I was in shock. How could I have both variants of this mutation? I had no major symptoms. So back to my medical books I went, reminding myself of the very intricate details of this mutation and what it meant. As I poured over the details, I came to realize that this mutation likely also affected my father, who had a heart attack at age 40 and death by a stroke at age 58. Now, I can’t help but think that if our modern technology was readily available back then, we may have learned he had the mutation, which might have saved his life.

As I reviewed my health history, I recognized that I had likely avoided major symptoms of the MTHFR mutation likely because I had been a vegetarian for so long. By focusing my diet on plant-based foods, I was frequently eating naturally methylated foods, which likely helped me avoid massive symptoms. But I had always experienced issues with my menstrual cycles, likely due to the impact of poor methylation, which results in storing estrogen hormones excessively. My dad’s side of the family also has a strong history of suicide and depression, which are indicators of this mutation as well. Getting this report was a huge wakeup call for me, and it has changed the way I look at my children’s health as well.


MTHFR - Dr. Pingel


Since that time, so much has been written about the MTHFR mutation and its impact on health, especially in terms of mood, hormones, and toxin removal from the body. Now, I’m seeing patients who are simply looking for more education and understanding as to what this mutation means for future health and how to avoid developing further problems. This is a very complicated process filled with tiny details of vitamins, amino acids, chemistry terms, and complex biochemical pathways—many of which are still being investigated. While the topic is rather complex, I wanted to discuss this concept with you, considering the large number of people who are finding the same surprising result that I did on general genetic screenings—that they have MTHFR mutations.

Today, approximately 40 percent of Americans know they have the MTHFR mutation, and current estimates are that this number may actually be greater. With the increasing likelihood that this condition is growing, it’s important for you to know the signs, understand exactly what it means to have problems with methylation, what symptoms you may experience, what questions to ask if you suspect this could be a concern for you, and some simple treatment options to discuss with your doctor. So, let’s dive in and learn all about methylation and how the MTHFR mutation impacts your health.


What Is Methylation?

As I mentioned, this subject is very chemistry-heavy. So, lets approach this simply. Methylenetetrahydrofolate reductase is an enzyme that is involved in the methylation of dietary folic acid. Simply put, methylation is the biochemical process involving the addition of a methyl group, which is made up of one carbon and three hydrogen atoms, to another substance in your body. This process occurs in order to prompt a reaction—either to create or breakdown something else. This is almost exactly like a chain reaction machine (also known as a Rube Goldberg machine), where one action triggers a reaction, leading to a final outcome.

Your body is full of these types of mechanisms, from the production and breakdown of hormones to toxin removal to regulating bodily processes such as blood pressure and mood. Without efficient methylation, these reactions can’t occur at their normal rates, and this causes a “back up” in your system. Some of the major areas of impact include your nervous and cardiovascular systems, energy production, ability to fight infections, hormone balance, stress response, ability for your body to detoxify metals and chemicals, DNA production and modification, and so much more.

Here’s a very cool fact about your biochemistry: Your body self-donates methyl groups to these reactions by creating what is called a methyl donor. There are a few methyl donors in your body, but the primary one is called SAMe (S-adenosylmethionine), and it is made by an amino acid found in foods. Now, here is the kicker in regards to this genetic mutation: In order for SAMe to donate a methyl group to important bodily processes, such as the production of serotonin or glutathione, it has to be activated. This activation is done by a critical nutrient: activated folate (5-MTHF or methyl-folate). As you may recall from a previous article, folate is a B vitamin that is essential for growth and development.

Now, methyl-folate begins this entire process by providing the first methyl group to SAMe. Without methyl-folate, your body can’t effectively hand out these methyl groups to SAMe. As a result, critical reactions stall, leaving you with problematic symptoms.

The Difference Between Methyl Folate and Folic Acid

I remember when I was pregnant and everyone kept telling me to take a supplemented folic acid so my baby could develop. What they didn’t know was that due to my MTHFR mutation, I am unable to use folic acid in my body. Why? Well, folic acid is NOT methyl-folate. [1] And methyl-folate is what’s needed to trigger methylation by SAMe.

Folic acid must be converted into methyl folate by an enzyme called methylenetetrahydrofolate reductase, and this is the enzyme that is impacted by the MTHFR mutation. This means folic acid will not convert, and you will become deficient in methyl-folate, resulting in poor methylation. Your Rube Goldberg will not move forward to the next element. And taking folic acid when you have this mutation actually will make your symptoms worse, not better!

So what does this mean in regards to your health? Let’s take a look at the problems that come when your body cannot efficiently convert folic acid into methyl-folate, resulting in decreased methylation.


5 Health Problems Poor Methylation and MTHFR Can Cause

As I mentioned above, today approximately 40 percent of Americans have the genetic mutation MTHFR, which makes it challenging for their bodies to convert folic acid into active folate. Without methyl folate, SAMe cannot donate methyl groups to some very important areas of our body.

If your body isn’t methylating properly, it will impact your production of important antioxidants, such as glutathione and coenzyme Q10 (CoQ10). Glutathione is essential for making DNA, which builds your cells. It supports your immune function, keeping you free of invading colds and flus and protecting you against cancerous cells. It’s also involved in recycling vitamins C and E, helping enzymes do their jobs in your body, and protecting and repairing your brain cells. And guess what? It requires methylation!

Methylation is also key in managing important neurotransmitters and hormones, such as epinephrine, serotonin, and melatonin. But its role doesn’t stop there. It also involved in everything from your eye health to your fat metabolism to your detoxification process and so much more. If your body isn’t methylating properly, you will ultimately develop some serious health complications. It’s simply inevitable.

In addition to a predisposition to the MTHFR mutation, other factors can also impact proper methylation. These include: unhealthy genetic factors, toxin exposure (such as pollution, heavy metals, and nicotine), inflammation, poor nutrition, and even just the simple process of aging. When you combine these items with the MTHFR mutation, even more damage can occur. What kind of damage? Take a look at some of the most common health concerns caused by the MTHFR mutation.

1. Type 2 diabetes

It turns out that having the MTHFR mutation could not only put you at greater risk of developing type 2 diabetes, but it may also actually increase your risk of developing diabetes-related complications. In a study of more than 200 people with type 2 diabetes and more than 300 people without diabetes, researchers found that those with the MTHFR mutation were more than twice as likely to have type 2 diabetes. [2]

Meanwhile, another study revealed that type 2 diabetes patients with the MTHFR mutation are at increased risk of experiencing diabetic retinopathy, due it the effects on homocysteine levels. [3] Fortunately, the researchers noted that consuming a high-methylated folate diet could decrease homocysteine levels, helping to prevent the onset of diabetic retinopathy.

2. Anxiety and/or depression

This one may shock you, but researchers have discovered that depression is more common in those with the MTHFR mutation than it is in people without the mutation. [4] In fact, depression and anxiety are the most common symptoms that I see in my patients who possess this mutation. And a 2013 study on people suffering from depression revealed that those with the MTHFR mutation tend to experience more severe symptoms. [5] If you extend this further, because of poor methylation, these people will also have a more difficult time metabolizing pharmaceutical medications that impact these pathways because they require methylation to process. Unfortunately, this often results in more serious depressive symptoms.

Amazingly, a 2013 study revealed that taking a methylated B vitamin complex supplement has a positive effect on symptoms associated with depression and anxiety. The researchers believed that attaining appropriate levels of B vitamins and SAMe supports mental health by regulating the MTHFR activity found in the mutations. [6]

3. Cardiovascular disease

Cardiovascular disease is one of the leading causes of death in the world. And now studies have shown that it’s linked to the MTHFR mutation. A 2006 study showed that having the MTHFR mutation puts you at greater risk of having an arterial stroke. [7] And another study revealed that having the MTHFR mutation actually increases your risk of hypertension by up to 87 percent and your risk of cardiovascular disease by up to 40 percent! [8]

4. Chronic pain and fatigue

One of the other common complaints I see from my patients with this genetic mutation is chronic pain. And studies are backing up these claims. In a study with more than 400 participants, researchers found that those with the MTHFR mutation were more than twice as likely to suffer from migraines with auras. [9]

Furthermore, a 2018 study on 200 participants revealed that the MTHFR mutation as well as another genetic mutation were linked to the development of fibromyalgia, a syndrome known to include chronic fatigue syndrome. The researcher also revealed that having the MTHFR mutation was associated with increased symptoms of stiffness and dry eyes. [10]

5. Certain cancers

By now, you’ve likely heard about genetic predispositions to certain types of cancers, including the BRCA gene, also known as the breast cancer gene. But did you know that having the MTHFR mutation could also increase your risk of certain cancers?

In a 2017 study, researchers found that the MTHFR mutation was associated with an increased risk of both breast and ovarian cancer. [11]

Other studies have also linked this mutation to an increased likelihood of developing cancers of the skin, lung, thyroid, and more, including leukemia. [12, 13, 14, 15]

Stress, Methylation, and MTHFR

While stress wasn’t included in the list above, it’s important to understand chronic stress impacts methylation. When your body responds to stress, it utilizes many nutrients, including the B vitamins as well as vitamin C. During this process, your body diverts from “repair mode” to “run mode,” slowing the regular detoxification and regenerative aspects of your metabolism. This process also impacts your body’s ability to absorb and use the nutrients you’ve consumed. (Remember, you don’t digest your food when you’re “running from a bear.”)

As a result, the vitamins your body uses to respond to stress become depleted, especially vitamins B6, B12, and C. This process of methylation requires these nutrients to be available in conjunction with methyl-folate. Stress will impact methylation in everyone, but particularly in those with the MTHFR mutation. Your body will continue the cycle of B vitamin depletion, resulting in even more symptoms. Also, because it impacts the production of antioxidants, such as glutathione, this chronically stressed state takes a major toll on your immune system, predisposing you to more stress-induced illnesses.

Signs You May Have a Methylation Problem

By now you’re likely wondering how you can tell if you may have a problem with methylation— and maybe even the MTHFR mutation. Take a look at these top signs this could be a problem for you. If these sound familiar, speak with your doctor about your desire to take a genetic test and how you can get started on methylated folate to help supplement the folate in your body to support proper methylation.

  • Fatigue
  • Family or personal history of anxiety, depression (including bipolar disorder), and/or cardiovascular disease ( including hypertension or stroke)
  • Irritability and mood swings
  • Cognitive issues, such as trouble focusing
  • History of inflammation-related conditions
  • Hormone concerns such as PCOS, estrogen dominance, endometriosis, or a history of painful and troublesome menstrual periods, infertility, and/or miscarriages. You may also experience poor response to hormone replacement therapies.
  • Elevated homocysteine in lab work
  • Systemic illness that develops post breast implants or other implantable devices [16]
  • Headaches and/or migraines
  • Signs of B vitamin deficiencies, such as pale skin, lightheadedness, numbness and tingling of body parts, muscle weakness, red blood cell changes, anemia, and/or mouth sores


Moving Forward: Testing and Treating MTHFR

OK, so here’s the good news: MTHFR mutations are easy to test for, and the treatment is even easier! So, what does this mean? It’s means you don’t have to deal with all of the potential ramifications of this mutation. You can live a productive, healthy life simply by making yourself aware of it and by modifying your lifestyle accordingly. And, even if you don’t possess this mutation, assisting the methylation pathways in your body will only enhance and help them. It’s truly a win-win.

So, how do you test for MTHFR? A simple swab of spit will identify the two variants of this mutation. Personally, I did mine as part of an overall health and ancestry screening. Not only did I find out about my ancestry, but I also identified my genetic weaknesses, such as MTHFR.

If you discover that you do, in fact, have the MTHFR mutation or if you just want to ensure you have proper methylation support, this requires sufficiency in a variety of nutrients. And all of these nutrients should be discussed with your doctor before starting to determine appropriate dosing for your unique body and collection of symptoms. First and foremost, if you are found to have the MTHFR mutation, you must supplement with methylated folate, not folic acid. You can also get methylated folate from most green plants, making plant-based diets incredibly beneficial. Some of the top folate-rich foods include broccoli, avocado, Brussels sprouts, kale, beets, mushrooms, spinach, and lentils.

Other nutrients that are also key players in methylation include: vitamin B12 (methylcobalamin), vitamin B6 (pyridoxial 5’ phosphate), vitamin B2 (riboflavin), magnesium, betaine, and vitamin D.

As you’re discussing your dietary and supplementation needs with your doctor, keep in mind that lifestyle factors such as regular daily exercise and stress management are also critical for those with methylation issues. So, make sure to discuss those important factors as well. And, remember, when it comes to proper methylation and the MTHFR mutation, knowledge is power. Knowing how your body is methylating is crucial for your overall health and well-being. Once you have that knowledge, you can confidently take the next steps on your wellness journey.


Key Takeaways

  • Approximately 40 percent of Americans know they have the MTHFR mutation, which makes it hard for your body to create active folate.
  • MTHFR and poor methylation are linked to type 2 diabetes, anxiety and/or depression, cardiovascular disease, chronic pain and fatigue, and certain cancers.
  • Signs you may have a methylation problem include fatigue, family history of mental health concerns, irritability, trouble focusing, history of headaches or migraines, and more.
  • You can (and should) test for the MTHFR mutation with a simple swab of spit. Based on your results, treatment is fairly simple, involving proper nutrient support.
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