Depression, Genetics, and Nutrition – MTHFR

This is this weeks Topic of the Week.

Depression, Genetics, and Nutrition

The American Journal of Epidemiology recently published a review of literature that that indicated that a common genetic defect may play a role common psychiatric disorders including depression, anxiety, bipolar disorder and schizophrenia. The genetic defect is in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, keeping the person from adequately converting folate (folic acid) into its final usable form. Folate is needed for neurological development, DNA/cell repair, and detoxification.

The review encompasses 26 studies with 1,280 people with depression, 2,762 cases of schizophrenia, and 550 cases of bipolar disorder. They found that people with these disorders were significantly more likely to have this genetic defect, and suggest that supplementation with folate would help.

Other studies have already shown that low blood folate levels are found in 1/3 to ½ of all people suffering from depression. One study showed that low blood plasma levels doubled the chance of depression. Another found that seniors are more likely to have depression with low folate and B-12 levels. Finally, for those with depression, lower folate levels increased the length and severity of there depression.

5-methyltetrahydrofolate (5MTHF) is the fully converted form of folate. People with the genetic defect can utilize this form directly. One study showed that supplementation with 5MTHF caused 81% of patients to see improvement with depression in six weeks. Another study showed that patients with normal blood folate levels that were given 5MTHF, improved the same amount as those on antidepressive drugs.

Other causes for folate deficiencies are excessive alcohol consumption, smoking, celiac disease, kidney dialysis, diabetes, MS, age, other nutritional deficiencies. Drugs such as aspirin/ibuprofin/NAIDs, antacids, antibiotics, barbiturates, birth control pills, anticonvulsive/epileptic/bipolar medications, diuretics, H2 blockers (Tagamet, Pepsid, Zantak), and proton pump inhibitors (Nexium, Prevacid, Prilosec).


Folic acid deficiencies also play a role in headaches, certain forms of cancer (including breast and colon), Alzheimer’s, strokes, heart attacks, anemia, schizophrenia, bipolar disorder, and cell growth.

Other nutrients that I’ve seen help depression include Vitamin C, Iron, Niacinamide, B-6, Manganese, Zinc, and Copper.


Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Gilbody S, Lewis S, Lightfoot T.Am J Epidemiol. 2007 Jan 1;165(1):1-13. Epub 2006 Oct 30.

The methylation, neurotransmitter, and antioxidant connections between folate and depression. Miller, AL. Altern Med Rev. 2008 Sep;13(3):216-26.

5-methyltetrahydrofolate. Monograph. Altern Med Rev. 2006 Dec;11(4):330-7.

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About Dr. Michael Polsinelli, DC

I really enjoy my work. It is a combination of listening, analyzing, and the skill of performing my craft. I love the expression on my patients faces when I puzzle out a long standing problem of theirs, or when their pain leaves after gently adjusting them. Read more about me

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