MTHFR, Lithium, Dopamine and You: Who is in the driver’s seat around here?

Keep Methylation Central

A mutation in the MTHFR C677T gene is linked to heart disease, stroke, macular degeneration, certain cancers and leukemia, among other health issues.

Methylene tetrahydrofolate reductase, the enzyme for which the MTHFR gene encodes, is an important determinant of whether your body converts folic acid into 5 methyl tetrahydrofolate, a form of folic acid that your body needs to function well.

If you have a mutation in the MTHFR C677T gene, you are also more likely to have anxiety and mood fluctuations. Lithium has been known for years to be useful for mood disorders. Despite all that is known about lithium’s impact on biochemical pathways,
no one has described why lithium has its impact on mood. It is likely to be an effect on multiple pathways, since there are a number of enzymes in the body that are impacted by lithium.

Lithium comes together with the MTHFR enzyme and methylation at COMT, the enzyme catechol-o-methyl-transferase. COMT uses methyl groups to do its job, and MTHFR is important in the production of methyl groups. COMT’s job is deactivating the catecholamine neurotransmitters, dopamine and nor epinephrine. Dopamine is a critical neurotransmitter for pleasure-seeking, motivation, focus, and attention.
Norepinephrine is involved with modulating the impact of stress.

Lithium increases the transport of B12 and folate into the cell. B12 and folate are pivotal substances in the production of methyl groups, which happens inside the cell. Lithium increases B-12 and folic acid transport into the cell which supports the production of methyl groups. Lithium may also increase the production of COMT, which then uses these methyl groups to deactivate dopamine. All anti-psychotics currently on the market are dopamine antagonists, acting to reduce dopamine in one way or another. So, one of the modes of action of lithium may be to reduce the level of dopamine in the body by enhancing the production of methyl groups and increasing the level of COMT.

Dr. Amy Yasko noted that a number of adults and children using her protocol have low lithium levels, which may act to unbalance dopamine. She started looking carefully at lithium levels and noticed correlations between low lithium, symptom formation and particular mutations in the methyl group producing pathway. Certain SNPs are associated with excess lithium excretion. These mutations are MTHFR C677T +, MTR+, SHMT+, and CBS+. You may have low lithium levels if you have one of these mutations.

Lithium is an essential trace element. You must get it from your diet. The average intake of lithium from the diet should be up to 3100 mcg, or 3.1 mg, per day. What it takes to increase your serum lithium levels into the normal range can be significantly more.

There is more information on methyl groups and methylation on my website at


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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