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Symptoms associated with MTHFR

Irritability, Anxiety and/or stress

Having a MTHFR mutation can be related to or the cause of some anxiety. Sometimes, methylfolate can aggravate or cause anxiety, also. When treating MTHFR the focus is to rectify a deficiency of methylfolate; however, there is the chance that more problems occur when there are other enzymatic deficiencies that methylfolate feeds in subsequent pathways. Methyl folate is a crucial nutrient required to manufacture neurotransmitters and when methyl folate is increased this will likely lead to an increase in neurotransmitter production. When you have a genetic defect in the enzymes that break down those neurotransmitters this results in a surplus of neurotransmitters. This leads to feelings of anxiousness, irritability, stress and an overall uncomfortable experience. When this happens the answer is to reduce the dose of methyl folate.

Consider the following before taking methyl folate: 1) Do you tend to experience anxiety? 2) Do you have problems with not sleeping well? 3) Do your struggle with chronic allergies? If you answer yes to these questions, then you are likely to be more vulnerable to side effects when taking methyl folate. Also, answering yes to the above questions likely indicates a decline in the breakdown of amines (including histamine). Consider adding a Magnesium supplement to assist in the breakdown of those neurotransmitters to correct this problem.

Achy Joints

Methyl folate aids in the creation of cell membranes by supporting in the production of SAMe. Cell membranes are made up of phospholipids, such as phosphatidylcholine, and other fatty acids. These are under-going constant damage and repair; and therefore, they are constantly being manufactured. Methyl folate supports this action; however, if you take too much it can have a negative impact on this process.

If you find that taking methyl folate does cause your joints to ache, but in the beginning of using the supplement it was actually helping then try taking phosphatidylcholine instead of methyl folate.

Digestive Issues

As discussed previously, poor digestion is often the cause of limited absorption of micronutrients (including folates, B vitamins, minerals, etc.). Often there is a microbial imbalance that needs to be corrected before starting supplementation with methyl folate. While working to resolve digestive issues, you may consider taking a liposomal form of methyl folate or other methyl donors (betaine, methionine, choline) instead of methyl folate.


Alterations within the MTHFR gene may cause headaches; however, you could experience headaches while being treated for a MTHFR defect, too. The headaches may be occurring as the body increases detoxification. Of course, headaches can occur for many different reasons and may have nothing to do with MTHFR or methyl folate. If you have determined there is a connection between taking methyl folate and your headache then reduce the amount of methyl folate you are taking. If you continue to feel unwell, add magnesium and trace minerals to support methylation.

Supporting the methylation cycle in its entirety is important. While you likely need methyl folate, you likely also need other nutrients; as you probably do not have a complete understanding of your genetics. Now, there is more methylation happening when you are consuming methyl folate and this leads to a need for support of other enzymes that impact methylation and those enzymes that occur downstream in this process. Enzyme co-factors include B1, B2, B3, B6, B12, magnesium and trace minerals. A great rule of thumb is the more methyl folate you take the more reinforcements, in the form of co-factor support, is required for the whole process to maintain equilibrium.

Vitamin B12 and methyl folate have an interdependent type of relationship and should be taken in combination. A standard recommendation for B12 is 1000 mcg; sublingually (under the tongue) for best absorption.

Betaine, or Trimethylglycine (TMG), and Vitamin B6 are additional supplements that are available to strengthen methylation. Consider adding a B-complex (without folic acid) 1 to 2 times a week and consider increasing your dosage based on how you are feeling.

MTHFR mutations call for concern and should be managed with the assistance of your qualified healthcare practitioner. A defective MTHFR enzyme generates many health concerns that impact different parts of the body. If you have a MTHFR defect, please consider partnering with a qualified healthcare practitioner that will help you understand how genes impact your health, physical disease, mental disease, etc. Determine your MTHFR status and educate yourself on the impact these genetic alterations are likely to play in your health. Be aware that your environment plays a role, too. A MTHFR defect often requires a personalized approach so that you can achieve health and wellness.

Return tomorrow to read about the nutritional approach for a MTHFR mutation.


  1. Terranella, Robin. MTHFR Gene Therapy Demystified: Crack Your Genetic Code to Better Health. 2017.

  2. Murray, Michael T., et al. “Vitamins.” The Encyclopedia of Healing Foods, Time Warner International, 2006.

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