MTHFR, More Than An Acronym For A Curse Word

MTHFR is no longer just shorthand for a curse word. This gene and its gene family are gaining attention both from the medical world (clinical and research alike), but from many patients and bloggers. Why would a gene with such a bad name be getting so much press? Because its medical reputation matches its acronym. MTHFR and the methylation cycle in which it sits has been found in research to be related to blood clots, miscarriages, autism, cancer, heart disease, fibromyalgia, chronic fatigue, heavy metal toxicity, thyroid disease, hormonal imbalances, and more. Not only that, but estimates place this one gene affecting possibly 20 to 40 % of the population. Significance and preponderance combine to pack quite a punch.

So what if someone has it? What about you? Does it matter for you as you read this? Maybe, maybe not? If you are healthy, feeling well, and have none of these issues, it may not be the top health concern for you right now. If you eat fast food daily, don’t ever exercise, smoke, and aren’t concerned with how you feel or how long you live, you have other issues to think about before MTHFR genetics. However, if you have any of the health problems mentioned above, have family members with these problems, are considering having children, or don’t feel well despite trying to follow a healthy lifestyle, this topic deserves at least a few minutes of your time.

This explanation cannot squeeze hours of study into a page so that the intricacies of these topic are perfectly clear, but I will attempt to point readers towards a basic recognition of how this might be affecting their current or future health. An overview of the methylation cycle will be provided. How the MTHFR gene and methylation cycle can be evaluated will be discussed. Further information on who should consider their MTHFR and methylation status will be added. The question of who should take supplements or adjust their diet to improve their methylation will round out the article as I address sources for methylation nutrition. Hopefully, by the end of this you will have enough knowledge to decide whether or not to go further down the rabbit hole of MTHFR and methylation.

MTHFR is just one gene interwoven with other genes which direct the production of protein enzymes which then control the methylation of other substances in the body. Genes are our DNA blueprints which determine which amino acid building block goes into which position in protein production. Proteins act in numerous ways to build and operate our body. Their role in body operations are mainly through actions as enzymes which serve to change one substance into another. Enzymes allow our body to convert food into energy and into all the structures of the body (muscle, bone, nerves, etc.). MTHFR itself converts one form of folate, a vitamin, into another form which is more functional in our cells.

That seems too simple of a function to be so important, just changing one folate into another. Well, the new folate allows vitamin B12 to continue changing homocysteine into methionine. Again, you ask, “So what?” Well, ultimately this process leads to the production of SAMe, a little chemical that is necessary for over 200 enzyme guided chemical reactions in your body. You will understand when you see the list of body functions affected by SAMe and thus by MTHFR’s simple reaction. Neurotransmitters like serotonin, dopamine, melatonin, and epinephrine are metabolized by enzymes using SAMe. Your hormones like estrogen are metablized differently depending on how much SAMe you have. Other genes in your DNA make-up are turned on and off by using SAMe (pronounced “sam – ee” ands stands for S-adenosyl methionine) to “methylate” your DNA. This can affect not only your health, but the new study of epigenetics is discovering that this process can affect your children’s genetic outworkings as well. This turning on or off of genes also plays a part in cancer development and growth. Ongoing research is looking at the impact of this cycle on developmental disorder like autism as well as psychiatric problems like depression and anxiety. Clinically, this cycle has been used in the treatment of fibromyalgia and chronic fatigue syndrome through its effect on neurotransmitters and energy production.

Although I am unable to sketch a detailed portrait of the cycle in this article, here is a short explanation (look at Seeking Health Institute or MTHFR Support for a visual picture and further details, or schedule a consult with a provider knowledgeable in this area). The methylation cycle is like a collection of interlocking, rotating cogs which intersect at various points. These intersections mean that for one cogwheel to continue rotating, the other is required to continue turning or else it locks up. The MTHFR gene’s enzyme produces methyl folate which is required to put a “methyl group” back on vitamin B12 after it gives a methyl group to homocysteine. The de-methylated folate goes back into a circle in order to produce more methylfolate. The re-methylated B12 makes more methionine (an amino acid). The methionine continues in its cogwheel circle to produce SAMe which is transported throughout cells, tissues, and organs of the body for other enzyme circles making all kinds of necessary substances for healthy body function. Methyl-folate and methyl B12 are critical as they are part of the center cogwheel which allows many, many other cogwheels in the body to turn around their functions. Stopping these critical cogwheels slows downs or stops other cogwheels.

Rare, complete absences in the enzymes of this cogwheel cycle can halt the wheels turning entirely, but this is not what occurs with the changes we are discussing here. More commonly,these minor defects slow it down, simply producing the symptoms and diseases that we see clinically. These “slowing down” changes are called SNP’s (pronounced “snips”) which stands for Single Nucleotide Polymorphisms. This is scientific language for a single change in the DNA string which may produce a change in the amino acid sequence of the protein enzyme. Polymorphisms means that not everybody in the world has the exact same DNA sequence, but a few different ones are compatible with life function (although some function better than others). These SNPs are different than genetic diseases like cystic fibrosis or sickle cell disease in which the disease is either all or nothing based on whether a gene is present or absent. SNP’s produce just a small change in the enzyme kind of like cutting one or two cables on a suspension bridge. The enzyme still functions relatively normal as long as not too much stress is placed on it. If an infection, a toxic exposure, a nutritional deficiency, or some other disease process puts too much pressure on the enzyme, it falters under the pressure and causes the cogwheels of the cycle to either slow down, speed up in a bad direction, or overstress other enzymes which leads to a domino effect. Think of it this way. The enzyme cable bridge can handle a car or mini-van driving over it, but with the broken cables it can’t handle the semi with a full load going over it (not my original idea, but a common explanation by many in the field).

How does one find out if they have a weak cable in one of these MTHFR enzymes? There are a few different means of testing, the two main groups being direct testing for the DNA change and testing for poor functioning of the genes. The first, testing for the DNA changes directly, can look at a single gene at a time. Many labs now test for MTHFR C677T, probably the most studied and impactful SNP so far. The results tells a person whether they have one or two copies of this SNP (we receive one copy each from our mother and father, either of which can be normal or changed). In some cases, such as testing why someone had a blood clot in their leg or lungs, this may be sufficient. In other cases, broader testing is needed. Then panels of SNP’s may be evaluated, meaning that a number of genes involved in this methylation pathway are tested and reported. Since these enzymes interact intricately in our bodies, this broader testing is often needed in more complex diseases like depression, fibromyalgia, chronic fatigue syndrome, and others.

The second means of testing involves looking at whether the enzymes are doing the job God designed them for. Basically, the lab measures the substances used by the enzyme and the substances produced by the enzyme to see if the levels are too high or too low. Measuring homocysteine and methylmalonic acid, for example, evaluate whether this cycle is working correctly. These can be done by nearly all conventional laboratories. Some functional tests require testing by specialty labs however. These include tests for SAMe levels, tests for various forms of folate, and tests for other substances processed by the methylation cycle. In some patients, functional tests are sufficient. In some patients, genetic tests are sufficient. In many, both types of testing are needed to develop a treatment plan.

Again, there are numerous areas of health where methylation may play a role in causing disease and may play a role in restoring health. A full list of patient situations who need testing is not possible, but an overview of these areas is in order. Certain diseases have already been mentioned. Other diseases include congenital heart disease, bipolar disease, autoimmune disease (lupus, rheumatoid arthritis, Crohn’s disease). Some conventional medications may affect vitamin levels as well, interfering with proper functioning of the methylation cycle. These include metformin for diabetes (lowers B12 levels), methotrexate (interferes with folate), birth control pills (changes the cycle), anti-seizure medications (affect vitamin levels), and high dose niacin (which depletes SAMe). The mentioned diseases might warrant genetic testing whereas the medication related problems probably deserve some form of monitoring for vitamin deficiencies with functional testing.

With all this on your plate, you might ask if everyone should just start taking methyl-folate or methyl vitamin B12 as a supplement. Not so fast. First, everyone should focus on a healthy and balanced diet which includes adequate green, leafy vegetables, colorful veggies (for vitamins and antioxidants), fruits, proteins (wisely chosen), and vitamins. Second, not everyone has a SNP which is affecting their health. Some SNPs are just sitting there as cars drive over their cable bridge without causing any problem. A healthy diet and lifestyle may be all that is necessary if no symptoms are present and no pregnancy is planned. Some people don’t have an important SNP. For those planning pregnancy, taking methyl-folate rather than folic acid is the best approach, but nothing extraordinary.

For others, such as those with before mentioned diseases, healthy diet or simple supplementation will be insufficient. If your oxidative stress is high (many causes), you have other vitamin or mineral deficiencies (B6, Zinc, Iron, Selenium, Riboflavin), or you have hormonal problems, you should investigate deeper for guidance. You still must start with diet and lifestyle, but some supplementation may be necessary to heal or to prevent disease. Even then the goal is to minimize long term need for supplements if not stop them altogether.

This article will never make you an expert in what is currently known about MTHFR and the methylation cycle. Even if it could now, this field is quickly developing as new research uncovers more and more about it. Hopefully, it has provided enough knowledge and practical wisdom that you can decide if you need to dig further into your own methylation well-being. Not all of you who read this need to go beyond healthy diet and lifestyle, but those that need more should make a decision to seek help from someone who can guide them to better health. I pray that you are able to discern where you are in this spectrum and make the right decision.

PS: One final question: Will insurance pay for testing and treatment? There is no easy answer for this. In certain situations, insurance companies will pay for laboratory testing, but in others, no. If prescription medications are necessary (not common in this field), insurance might pay. For supplements, insurance is highly unlikely to pay for vitamins or herbal remedies. But what is the cost of poor health? At some point, the cost will become worth the benefits reaped from feeling better and possibly longer life (God-willing).

Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.

About the Author :


  1. Avatar

    First, let me again thank you for being knowledgeable about this issue. You are an answered prayer. I am compound heterozygous for MTHFR, and am considering (if I can work up the courage after four miscarriages)trying one more time to have a baby. After researching this issue online I am confused as to whether or not I need additional testing of certain markers…..CBS being one of them. I read that if you start taking methylfolate without knowing your CBS results or without taking additional B12, then it can be harmful. I have been told I have low egg reserve so I feel pressured to figure out what I need to do quickly. Due to my prior miscarriages my RE wants me to take daily lovenox injections, baby aspirin, and crinone while pregnant. Since I have MTHFR, from what I understand, my body may not easily get rid of toxins. Taking all those medicines while pregnant makes me feel like my body will get overwhelmed with toxins if I can not detoxify normally. Just wanted to say we are conceiving naturally, not with IVF.
    We plan on seeing you in January. Any advice and wisdom on this matter is greatly appreciated!

    1. Avatar
      Eric Potter

      I look forward to meeting you and will be praying. These recommendations by the other physicians are not off base, but let’s work through this a step at a time in person. I will be ready with a plan with this in mind.

      Prayer: Father, guide us in participating in your work of creating new life. There is both great joy and opportunities for great fear. You tell us to “Be courageous” but it is so hard in this area of life. Be with Elizabeth and her husband in this and guide me as I walk through it with them. Amen.

Leave a Comment