MTHFR: A Common Genetic Variant That May Affect Your Emotional And Physical Health

MTHFR: A Common Genetic Variant That May Affect Your Emotional And Physical Health

By: Holly L. Thacker, MD • Posted on July 11, 2016


MTHFR stands for Methyl TetraHydroFolate Reductase and is a gene that produces an essential enzyme in the body. This MTHFR plays a key role with regard to many aspects of physical and mental health.

We each receive an MTHFR gene (allele) from our mother and our father at conception. There are some common changes or mutations in the normal gene. A mutation is a naturally occurring process that causes a specific variation on one or more alleles of a particular gene, slightly changing a sequence in our DNA. Having a mutation on both alleles of a specific location on a gene sequence (being “homozygous”) is generally associated with a greater impact than if only allele is affected (referred to as “heterozygous”). Since these mutations are so common they are also sometimes referred to as “normal variants.”


If you or your loved one has been diagnosed with any of the following, then this column is for you as the cause of your condition could be related to a MTHFR mutation:

  1. Depression
  2. Bipolar disorder
  3. Migraine headaches
  4. Schizophrenia
  5. Attention Deficit Disorder (ADD or ADHD)
  6. Autism
  7. Recurrent miscarriages
  8. Recurrent DVT blood clots (Deep Vein Thrombosis)
  9. Heart disease

It is worth understanding about this common mutation MTHFR if one or more of these medical conditions runs in your family.


Because up to 50% of the population may have a variant of MTHFR, some say it is not worth being tested. I don’t agree. I don’t agree because some MTHFR mutations are more concerning than others, for example a mutation in homozygous form of C677T is much more concerning than then A1298C or a so-called “compound heterozygote” C677T/A1298C variant.

In general, the following below listed 3 (MTHFR) variants are currently considered unlikely to be of serious clinical significance. Your doctor can discuss the differences between these variants and how it affects your personal health. If you have one of the 3 listed variant you may OR may not want to take optimized folate.

  1. C677T heterozygote
  2. A1298C homozygote
  3. Compound heterozygote

HOWEVER, if you have the homozygous C677T variant you should strongly consider taking optimized L-methylfolate and perhaps methylated B12 as well.

MTHFR's Connection to Autism and ADD/ADHD

The preliminary research on MTHFR, autism and ADD/ADHD suggests that adequate prenatal intake of folate both in the period three months before conceiving and during the first month of pregnancy in particularly can reduce these risks in all children.

Many newer birth control pills are now including L-Methylfolate (also called levo-mefolate, methylated folate or optimized folate) to reduce neural tube defects. Beyaz and Safryl are both FDA approved oral hormonal contraceptions to treat severe PMS/PMDD and contain the longer acting L-methylfolate.

Interestingly, the L-methyfolate was not added to treat the mood disorder, rather the March of Dimes encouraged oral contraceptive agents to include long acting optimized folate to reduce neural tube defects. All women regardless of MTHFR status need to take folate prior to conceiving and during pregnancy, as even one bad diet day can lead to lower blood levels and be hurtful to brain and spinal cord development in the early days and weeks of pregnancy.

When To See A Doctor

If you have not responded as expected to conventional medical treatment for the following disorders, then it is worth speaking to your physician about being tested for MTHFR mutation. Those disorders include:

  1. Depression
  2. Migraine headache
  3. Mood disorders
  4. PMS
  5. PMDD
  6. Anxiety
  7. Panic
  8. Peripheral neuropathy

Treatment for Allele Mutation

MTHFR is part of your genetic makeup, so it currently can’t be “cured,” but it is very treatable. If you have a homozygous C677T variant, the compound heterozygous state or even a single heterozygous single allele mutation, it is very easy to treat with L-methylfolate.

In addition, despite increased risks of some conditions, having a specific MTHFR mutation has been associated with a lower risk of acute lymphatic leukemia (ALL) and some forms of colon cancer in those who have adequate levels of folate.

If you have an MTHFR mutation, you do need to know that you'll have a reduced ability to metabolize folic acid, the synthetic form of folate that is found in many processed foods like breads and cereals and many vitamins.

7 Steps to Reduce The Risks Associated with a MTHFR Mutatation

There are some simple and inexpensive steps to reduce the risks associated with an MTHFR mutation. These steps can also possibly improve response to depressant therapies and help you feel better in general!

  1. MTHFR Testing - Speak to your physician about whether MTHFR testing is appropriate for you. Your medical insurance may or may not cover this expense.
  2. Folate Supplements - Swap out folic acid for the more bioavailability form of folate, L-Methylfolate. This is more usable by the body and is easily found in health food stores, many pharmacies and online. (Note: L-methylfolate is sometimes referred to as "optimize folate”) It can also be prescribed in a high dose capsule of 7.5 mg or 15 mg Deplin by your physician, which is commonly done after assuring normal B12 levels to make antidepressants work more effectively.
  3. Avoid Folic Acid - Avoid processed foods and supplements that contain the folic acid form of folate. It's not easily metabolized by persons with an MTHFR mutation and could interfere with the absorption of L-Methylfolate.
  4. Eat Green Vegetables - Strive to eat folate rich foods like leafy greens, broccoli and lentils. Many breads are great sources of folate and other brain friendly nutrients.
  5. B12 Vitamin - MTHFR impacts the process of methylation, which compromises the absorption of B12. It is recommended that you take a form of B12 that is Methylcobalamin rather than the more commonly available Cyanocobalamin to help with B12 absorption. B12 absorption is essential for good mental health and memory. I commonly prescribe CerefolinNAC, a prescription vitamin with methylated B12, L-Methylfolate and N-Acetyl Cysteine. If you have memory concerns see your physician for an evaluation. If you have diabetic neuropathy or other peripheral nerve problems, talk to your physician about a prescription vitamin called Metanx, which includes methylated B12, methylated folate and B6/pyridoxine.
  6. Pregnancy and MTHFR - If you are planning a pregnancy and are positive for the homozygous MTHFR mutation, you may also need to add either a low-dose aspirin or blood thinner to your regimen to reduce the risk of blood clots particularly, if you have had recurrent miscarriages, a DVT or systemic lupus erythematosus (SLE). It is very important to speak to your Obstetrician or Mid-Wife before conceiving to optimize your pregnancy outcome.
  7. Children and MTHFR - If your child or grandchild's parents has an MTHFR mutation particularly, if this child has attention difficulties or mental health issues, please speak to your child's pediatrician about whether you should supplement their diet with L-methyl folate and at what dose.

Be Strong. Be Healthy. Be in Charge!

-Holly L. Thacker, MD

Holly L. Thacker, MD, FACP is nationally known for her leadership in women’s health. She is the founder of the Cleveland Clinic Women’s Health Fellowship and is currently the Professor and Director of the Center for Specialized Women’s Health at Cleveland Clinic and Lerner College of Medicine at Case Western Reserve University. Her special interests are menopause and related medical problems including osteoporosis, hormone therapy, breast cancer risk assessment, menstrual disorders, female sexual dysfunction and interdisciplinary women’s health. Dr. Thacker is the Executive Director of Speaking of Women’s Health and the author of The Cleveland Clinic Guide to Menopause.

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