MTHFR, Genetics, Homocysteine, & Your Mental Health

In addition to your gut bacteria affecting your mental health, a look at statistics makes it clear that genetics have a lot to do with whether or not a person is diagnosed with a mental health condition. We’ve all seen cases where anxiety runs rampant in one family while it seems like the members of another family are more likely to be depressed. Most of us don’t stop to think, though, that understanding the specifics of these genetic predispositions could help us to better understand the underlying causes of mental illness and, ultimately, help us find out what we can do in order to address these causes and potentially restore mental wellness. There are a few genes that are pretty important determining factors of mental wellness, one of the major ones being the MTHFR gene. We’ll discuss the MTHFR gene and (briefly) its effects on mental health conditions like anxiety, depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder in this blog post.

Methyltetrahydrofolate Reductase. Huh?

First, let’s talk MTHFR. MTHFR is an acronym that actually stands for methylenetetrahydrofolate reductase. I’m sure you see why most people just call it MTHFR! Anyway, MTHFR is an enzyme in the body that helps convert folic acid (vitamin B9) into the active form, methylfolate, which is the form that your body can actually use. The portion of your DNA that controls the production of the MTHFR enzyme is (appropriately) known as the MTHFR gene.

Some people have a variant of the MTHFR gene that makes the enzyme less active. We call this a genetic SNP (which is pronounced “snip,” and stands for single nucleotide polymorphism). All things equal, these people are likely at greater risk for anxiety, depression, various types of cancer, miscarriages, birth defects, and quite a few other physical and mental health conditions.

Folate vs. Folic Acid

Having adequate amounts of the active form of folate in your body can help antidepressant medication, specifically, SSRIs like Zoloft, Prozac, and Paxil, work better. The active form of folate has also been demonstrated in the scientific literature to have antidepressant effects in and of itself, meaning that people who are battling depression would benefit from having adequate folate levels whether they are on medication or not.

Folate and folic acid are both terms that we use to describe vitamin B9, and we tend to use them interchangeably, but they aren’t exactly the same. Folate is naturally found in food, and we typically get it from consuming green, leafy vegetables. On the other hand, folic acid is a synthetic (man-made) form of vitamin B9 and we find it in fortified grains and in some multivitamins and in other (usually lower quality) supplements.

Side note: not all supplements are created equal. If you’re looking for professional-grade supplements, check out the “Dr. Janelle’s Faves” category in my online dispensary. You’ll see my favorite and most frequently recommended B vitamin and multivitamin supplements, as well as a host of additional professional-grade supplements.

If you are a person who has an MTHFR SNP or deficiency, your body may not be able to process the folic acid that you consume from fortified grains and supplements in order to convert it to the active form of folate. You may need to avoid sources of synthetic folic acid. The active form of folate helps a compound called homocysteine to be transformed into SAMe (S-adenosyl-l-methionine), which then plays an important role in neurotransmitter production and mental wellbeing. Homocysteine is the main problem with having an MTHFR SNP because elevated levels increase your risk for physical health conditions like coronary artery disease, stroke, and dementia. Elevated levels also increase your risk and/or worsen your prognosis for mental health conditions such as anxiety, depression, and obsessive-compulsive disorder (OCD), bipolar disorder, and schizophrenia. Your doctor can test your homocysteine levels using a simple blood test which your insurance should cover but, if you don’t have insurance, you can have your homocysteine levels tested at a lab at a cash price by clicking here.

If you have elevated homocysteine levels or if you have an MTHFR SNP which leads to elevated homocysteine, you may need to supplement with the active form of folate (methylfolate, e.g. L-5-methyltetrahydrofolate) to help your body function normally. If you have a genetic polymorphism and you don’t supplement with the active form of folate, your homocysteine may not be transformed into SAMe as effectively and research shows that you may experience increased risk for and/or increased severity of mental health conditions like anxiety, depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder.

MTHFR Genetic Testing

Because of the increased homocysteine levels that often come about as a result, it can be useful to have that genetic test done to determine your MTHFR status. Having your MTHFR gene checked is particularly useful if you’ve tried lots of different medication and nothing has worked for you. If this is your case, I’d definitely look into an MTHFR gene defect. It is far more common than people think. In fact, it’s reported that approximately 10% of Caucasian and Asian populations have 70% less activity at their MTHFR enzyme than the general population and that about 40% of the population has some problem with their MTHFR enzyme leading to decreased ability to convert folic acid into 5-methyltetrahydrofolate.

Your doctor can check for an MTHFR gene polymorphism via a simple blood or saliva sample. It’s a test that I frequently run on my patients, especially the ones who come to me reporting that the medication that their primary care physicians or psychiatrists have put them on has not been as effective as they had hoped. Having your doctor check you for an MTHFR genetic polymorphism is my preferred method of testing because your insurance can cover the testing if your doctor does it and he or she would hopefully be able to provide you with an interpretation of your results as well.

If your doctor is unable or unwilling to test you for an MTHFR SNP, there are a few other options:

  1. True Health provides on-demand laboratory testing that you can request at a cash price without a doctor’s permission or requisition. You can purchase an MTHFR genetic test here. They even have an option for you to add on a homocysteine test.
  2. 23 and Me provides genetic testing that includes testing for the MTHFR gene through their Health and Ancestry kit. I haven’t personally used their testing, but many of my colleagues have and they’ve only reported positive experiences to me.

Keep in mind that the main reason we are interested in the MTHFR gene status is the elevated homocysteine levels that can come about as a result. If you aren’t able to have the genetic testing done, you can always have your doctor check your homocysteine levels or have them drawn at a lab by clicking here.

Final Tips for Optimizing Folate Status and Mental Health

  1. Unless you are on medication that prohibits it (e.g. Coumadin/warfarin), make sure you are consuming sufficient dietary folate (e.g. from leafy greens). The presence of folate and other B vitamins is crucial to the process of making SAMe, which plays a crucial role in neurotransmitter function.
  2. If you’ve been diagnosed with a mental health condition, consider getting tested for an MTHFR genetic polymorphism if you haven’t already.
  3. Get your test results interpreted by a doctor (if you have a doctor run your test) or by using a free or premium online service (if you do something like 23 and Me, here are some interpretation options:
    1. Genetic Genie (free)
    2. Know Your Genetics (free)
    3. Livewello (premium)
  4. Supplement with L-5-methyltetrahydrofolate (L-5-MTHF) if you do have elevated homocysteine or an MTHFR genetic polymorphism.

Comments (4)

  1. Kay says:

    this post was so informational, I had no idea about any of these processes before i read this! They don’t always go into this much detail in my psychology classes. Thanks for educating the mental health community!

    1. mhaspot says:

      No problem, Kay! Glad to share!

  2. Amber says:

    This is so interesting! Im definitely going to look into 23 and me because i dont think i’d be aBle to get the testing done by a doCtor and i couldn’t afford it privately. Great post! X

    1. mhaspot says:

      Thanks for the feedback, Amber! I appreciate it!

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