If you are like most of my patients, the question you probably want answered is, "what SHOULD my treatment for my MTHFR gene mutation look like?" This is probably a wrong question because it assumes there is one simple way to treat all MTHFR gene mutations.  This is not the case. Each person is a little unique in how they respond to MTHFR treatment. What works best for you may not work for someone else. The reason for such a difference in responses from one person to the next will be the focus of this article. Specifically we will focus on why your treatment approach may not be producing the desired benefits. 

What is MTHFR Gene Mutation

Methylene tetrahydrofolate reductase (MTHFR) is an enzyme that is directly and indirectly essential for many metabolic reactions in the body through its action on folate methylation. MTHFR gene carries the information for the production of this enzyme. Thus, any alteration in the structure of this gene (MTHFR gene mutation) will result in functional or absolute deficiency of MTHFR enzyme and inability to utilize folate.

Symptoms of MTHFR enzyme deficiency can be: fatigue, depression, anxiety, poor exercise tolerance, neuropathy, poor memory, increased risk for blood clots, headaches, slowed healing of tissues, and more.

Common Questions About MTHFR

So when we are referring to MTHFR gene mutation treatment we are expecting improvement in these symptoms.  Some people with MTHFR gene alterations may not feel they have fatigue, depression or any of the above symptoms. However upon being treated for it, they do notice better energy and mood. That's not the case for everyone though.

Poor Response to MTHFR Gene Mutation Treatment

The most common treatment approach for an MTHFR gene mutation is to use some form of methylfolate. This is logical since the body is not making this substance like it naturally should. However unexpected problems can arise when methylfolate is the only consideration. 

For instance, taking methylfolate can cause more fatigue, more depression, body aches, headaches, etc. Yes, these are the same symptoms it is intended to improve. There are several reasons for this as we will discuss below. 

Digestive Problems and MTHFR Gene Treatment

Many people have problems with their digestion and they don't even know it.  If you are considering or started treatment for MTHFR you should start with this question.  How is your digestion?  In the case of MTHFR mutation treatment many people find out their digestion is not doing to well. Upon taking methylfolate or other b vitamins some people start to have abdominal pain or discomfort, headaches, rashes, heart palpitations, or other symptoms.  

Many people wrongly assume these symptoms are from the b vitamins themselves. While this may be, a bigger consideration is to make sure you don't have a problem in your digestive tract. 

Small intestinal bacterial overgrowth, fungal overgrowth and other pathogenic bacteria can and do consume b vitamins triggering these and other symptoms. 

While digestive problems are one big cause for side effects or poor response to MTHFR gene mutation treatment, there are many other health issues that can do this too. That is why I emphasize and focus on bringing the entire person back into balance not just this one gene. 

Folate Transporter and MTHFR Gene Treatment

While some may have clinical improvement following methylfolate supplementation, a significant proportion of patients may fail to respond to this treatment.  Another explanation for this is the concomitant presence of an abnormality in folate transport. Transportation of all folates through your blood and into your cells is mediated by a carrier protein known as “reduced folate carrier protein 1 (RFC1)”, that is encoded by a gene (human solute carrier family 19, member 1 (SLC19A1) gene).1

Although the incidence of folate transport abnormality in patients with MTHFR gene mutation is not known, Cai et al. found that half the Chinese adults study participants had both abnormalities.2

As this carrier protein is also involved in the transportation of antifolates such as methotrexate, Charasson et al, discovered that expression of the SLC19A1 gene was associated with increased sensitivity to several drugs (antifolates, thiopurines, nitrosoureas, and platinum drugs).3

It is also important to note that folic acid uses the same transporter. This is why those with MTHFR should try to limit their consumption of foods and vitamins with folic acid in it. These are foods like rice, bread, cereals, corn and multivitamins (those with folic acid).  

If your MTHFR gene mutation treatment (methylfolate supplement) is not giving the desired effect, a mutation in SLC19A1 gene coexisting with that of MTHFR gene may be part of the problem.  

Methylation Metabolites Considerations

The MTHFR gene is a critical enzyme right at the heart of methylation. Because of this it can have affects on neurotransmitters, energy production and utilization, detoxification, and more.  If your body starts to make more neurotransmitters it also will need to break them down too.  If it's not efficient at this you may feel worse, have more allergies, anxiety, palpitations, or other symptoms.  The post below goes into this in a little more detail.

3 more problems you may encounter with MTHFR Gene.

Optimal MTHFR Gene MutationTreatment

Getting optimal methylation and MTHFR gene treatment requires a broad understanding of the different methylation genes and health in general.  The tips listed above are key to optimal methylation but do not detail all the possible scenarios that may come up.  To discuss your specific situation consult with an mthfr doctor by clicking the link below. 

Reference list
Yee SW, Gong L, Badagnani I, Giacomini KM, Klein TE, Altman RB. SLC19A1 Pharmacogenomics Summary. Pharmacogenetics and genomics. 2010;20(11):708-715. doi:10.1097/FPC.0b013e32833eca92

Cai C, Xiao R, Van Halm-Lutterodt N, et al. Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults. Nutrients. 2016;8(10):665. doi:10.3390/nu8100665.

Charasson V, Hillaire-Buys D, Solassol I et al. Involvement of gene polymorphisms of the folate pathway enzymes in gene expression and anticancer drug sensitivity using the NCI-60 panel as a model. European Journal of Cancer. 2009;45(13):2391-2401. doi:10.1016/j.ejca.2009.05.013.