Treatment of depression: time to consider folic acid and vitamin B12

Abstract

We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.

Folate: Essential and Beneficial, but is it Safe?

“…Folate is metabolized into S-adenosylmethionine (SAMe) and both are involved in the production of dopamine, norepinephrine and serotonin, all neurotransmitters implicated in depression. These neurotransmitters affect the production of tertrahydrobiopterin, an antioxidant and cofactor in the synthesis of these neurotransmitters [9,10].…”

Folic Acid - The Occurrence and the Role in Human Nutrition

“…Its beneficial effects on the function of this system is associated with its participation in the formation of neuro-stimulating substances in the body such as dopamine, norepinephrine and epinephrine (Paul et al 2004, Coppen & Bolander-Gouaille 2005, Reynolds 2006). Many clinical and epidemiological studies have shown that folate deficiency in the diet leads to a number of neuropsychiatric disorders such as depression, psychosis, dementia and seizures (Quadri et al 2004, Luchsinger et al 2007.…”

The Importance of Nutrition as the Best Medicine for Eating Disorders

“…Low levels of folate have been implicated in poor response rates to standard antidepressant therapy. 26 B vitamins also convert glucose into energy in the brain cells and assists in the manufacture of neurotransmitters. B 12 is essential for nerve cell health.…”