MTHFR Mutations, Depression, and Other Chronic Illness

What would happen if all the traffic lights in your county started to malfunction at the same time? Say they all came on and stayed on. Or they all went dark. Even lesser degrees of malfunction, delays in lights’ changing for example, or one light out here or there at important intersections, would cause major SNAFU’s in traffic flow. The orderly, clockwork traffic performance that we all expect would be interrupted. You wouldn’t be able to get anywhere without major delays.

Methyl groups are like the traffic lights of your biochemical pathways. They turn on certain reactions and turn off others. They are involved in both the formation and deactivation of neurotransmitters. They are necessary for the fluidity of your cell membranes that need to pass substances into and out of the cell. The receptor sites embedded in the cell membrane also do not work well unless the membrane is methylated.


Methyl groups are primary epigenetic regulators, a regulation of genetic function that comes from outside of the gene, ‘epi-‘ meaning around. The methyl groups in the cellular fluid surrounding a chromosome impact the function of the gene. When a methyl group attaches to a gene, it silences the expression of that gene. It turns the gene off. This is important for genes that cause inflammation or immune activation. You don’t want those genes expressing when they should not be active, thereby causing an inflammatory disorder or autoimmunity.

Your MTHFR gene encodes for the MTHFR enzyme. The MTHFR enzyme catalyzes the production of methylfolate, a B vitamin that is critically necessary to methyl group generation. When there is a mutation in the MTHFR C677T gene or the MTHFR 03 gene, there is a slowdown in methyl group production. Other genes in the methyl group-forming pathway may be mutated also, which further compromises methyl group production.

In order to get free from depression, you need appropriate methyl group formation because methyl groups are pivotal to neurotransmitter function. They play a role in both neurotransmitter production and breakdown. In addition, methyl groups function in the activation of your immune system. If your immune system does not have an appropriate supply of methyl groups, you can’t mount a defense against gastrointestinal infection or yeast infestation. You may be aware of the depression caused by dysbiosis, non-optimal organisms in your GI tract.

Your gastrointestinal lining breaks down on an ongoing basis. Methyl groups are necessary for cellular regeneration. If you do not have sufficient methyl groups to rebuild your gastrointestinal lining, you cannot absorb the nutrition in your food into your body properly. This is a major cause of depression.

There are myriad impacts from the production of too few methyl groups. MTHFR C677T and MTHFR 03 are major actors in the production of methyl groups. Supplementing to bypass mutations in these genes is essential to health, and to a feeling of well-being and being free from depression.

If you would like to get my input on your health issue, I would like to offer you an Exploratory Conversation. It does not involve filling out lengthy history forms or becoming my patient. I will answer your questions, look at whatever data you want to send, and discuss whatever you like for 30 minutes. The fee for this service is $119. This fee can be applied to the cost of a new patient appointment if the appointment occurs within 30 days of the conversation. You will not be invoiced, sent a superbill, or sent written information on whatever it is I may tell you to do. 

Exploratory Conversations are meant for folks who are not my patients who would like to talk to me to get my input about their condition or treatment. They are phone calls. They are not office visits. The idea is to streamline the communication of information so that effective work can happen in one half hour.

Email me at Let me know that you want an Exploratory Conversation, and I will send you the information about how to schedule one.

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About Nancy Mullan, MD

Some people call Dr. Nancy Mullan the MTHFR genetic medicine expert. Dr. Mullan works with people who are struggling with chronic disease or other significant illness, who are willing to use diet and genetics-based nutritional supplementation, and who want to increase wellbeing and energy, enhance immunity, lift mood, fine-tune genetic function, and get their lives back. Dr. Mullan has studied at a number of exceptional institutions: the University of Pennsylvania, Tufts University School of Medicine, and the University of Chicago Hospitals and Clinics. She excels at integrating the results of biochemical and genetic testing into sustained clinical improvement for you. She has succeeded with patients who confounded the specialists at Massachusetts General Hospital, the Mayo Clinic, the Cleveland Clinic, Stanford, and many well-known integrative medical doctors. When recommending her, her patients say, “This is the woman you need to talk to. She really knows how to handle tough clinical problems.” Dr. Mullan's specialty areas are MTHFR+, methylation genetics, and genetics-based nutritional supplementation. Within this context, she most often works with Chronic Fatigue Syndrome, Lyme Disease, Psychiatric Disorders, Autism Spectrum Disorders, Women’s Health Issues, Thyroid Disorder, Gastrointestinal Disorder, and Heavy Metal Toxicity.
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