Folate and Mental Health

Of all the micronutrients, B vitamins may be the most important to the cause and progression of late-life depression. They are certainly the most studied, especially folate and vitamin B12.

Both vitamins affect brain health through their roles in neurotransmitter synthesis (e.g. folate deficiency has been demonstrated to cause decreased serotonin synthesis in humans and rats), myelin formation and energy metabolism.
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Low folate levels have been linked with depression and dementia, although it is difficult to establish whether this relationship is causal. Some studies need to be reviewed and updated to take account of the widespread use of fortified grain products (required in the U.S. since 1998) and B vitamin supplements (B6 and B12 in addition to B9).

The evidence of folate being a causal factor in depression is strengthened by an emerging association between the common polymorphism of a gene involved in the metabolism of folate – MTHFR and depression.

A folate-depression relationship was reported as early as the 1960s when a study of psychiatric inpatients found that half had low folate levels. Causality is unclear, not only because the study was cross-sectional but because many of the low-folate subjects were alcoholics or had used folate-diminishing medications.

Another hospital study found that depressed subjects had lower folate levels than either non-depressed psychiatric patients or non-psychiatric patients.

High intakes of folic acid and vitamins may reduce the risk for depressive disorders and increase medication response in depressed patients.

MTHFR

• The specific polymorphism MTHFR C677T (the most common variant in the MTHFR gene) has been found to be associated with depression in several studies.
• MTHFR C677T has been associated with greater depressed mood during pregnancy, increased risk of general depressive episodes and an increase in homocysteine*.
• Patients with the MTHFR C677T mutation have a reduced ability to convert folic acid into its active form, L-methylfolate. Both L-methylfolate and folic acid are possible treatment options for these patients.
• When consuming the same amount of folic acid, people with the MTHFR 677 TT genotype have an average amount of folate in their blood that is only slightly lower (about 16% lower) than people with the MTHFR 677 CC genotype.

Homocysteine

• Vitamin B12 deficiency prevents the 5-MTHF form of folate from being converted into THF due to the “methyl trap”. This disrupts the folate pathway and leads to an increase in homocysteine which damages cells (for example, damage to endothelial cells can result in increased risk of thrombosis)
• Chronic consumption of alcohol may also result in increased plasma levels of homocysteine.
• Vitamin B12 deficiency, when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well.

To summarise

Not getting enough B group vitamins (especially folate and B12) could cause depression. To avoid deficiency, have regular blood check-ups or take B group vitamins.

*Homocysteine is an amino acid produced when proteins are broken down (you get it mostly from eating meat). High homocysteine levels in the blood can damage the lining of the arteries. High homocysteine levels are associated with low levels of vitamins B6, B12 or folate.