Folate deficiency

Folate deficiency is a lack of folic acid in the diet and the signs are often subtle. Folate deficiency anemia is the medical name given for the condition.

Symptoms
Loss of appetite, and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders.

Women with folate deficiency who become pregnant are more likely to give birth to low birth weight and premature infants, and infants with neural tube defects. In adults, anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate.

Late studies suggested an involvement in tumorogenesis (especially in colon) through demethylation/hypomethylation of fast replicating tissues.

Some of the symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

Depression
Studies suggest that folate and vitamin B12 status may play a role in depression. The role of vitamin B12 and folate in depression is due to their role in transmethylation reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin, epinephrine, nicotinamides, purines, phospholipids).

Low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine (hyperhomocisteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine and serotonin from tyrosine and tryptophan), phospholipids, myelin, and receptors. Hyperhomocysteinemia could also lead to vascular injuries by oxidative mechanisms which can contribute to cerebral dysfunction. All of these can lead to the development of various disorders, including depression.

Low plasma B12 and low plasma folate has been found in studies of depressive patients. Furthermore, some studies have shown that low folate levels are linked to a poor response of antidepressant treatment, and other studies also suggest that a high vitamin B12 status may be associated with better treatment outcomes. Therefore, not only does adequate consumption of these two vitamins help decrease the risks of developing depression, but they can also help in the treatment of depression when antidepressant drugs are used.

Causes
A deficiency of folate can occur when the body's need for folate is increased, when dietary intake of folate is inadequate, or when the body excretes (or loses) more folate than usual. Medications that interfere with the body's ability to use folate may also increase the need for this vitamin. Some research indicates that exposure to ultraviolet light, including the use of tanning beds, can lead to a folic acid deficiency. 

Situational
Some situations that increase the need for folate include:
 * certain anemias
 * kidney dialysis
 * liver disease
 * malabsorption, including celiac disease
 * pregnancy and lactation (breastfeeding)
 * tobacco smoking

Pharmacological
Medications can interfere with folate utilization, including:


 * anticonvulsant medications (such as phenytoin, and primidone)
 * metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
 * methotrexate, an anti-cancer drug also used to control inflammation associated with Crohn's disease, ulcerative colitis and rheumatoid arthritis.
 * sulfasalazine (used to control inflammation associated with Crohn's disease, ulcerative colitis and rheumatoid arthritis)
 * triamterene (a diuretic)

When sulfasalazine is prescribed, folic acid supplements are normally given with the sulfasalazine. The purpose of methotrexate is to inhibit dihydrofolate reductase and thereby reduce the rate de novo purine and pyrimidine synthesis and cell division. It may therefore be counter-productive to take a folic acid supplement with methotrexate. Although the folic acid inhibition of sulfasalazine is normally seen as a side effect, it is possible that it is a part of the therapeutic effect of the drug, given that methotrexate, a frank folic acid inhibitor, is often given if sulfasalazine fails. It would therefore be wise to consult with a physician before taking a folic acid supplement along with sulfasalazine or methotrexate.

Prevention and treatment
When cooking, use of steaming or of a food steamer can help keep more folate content in the cooked foods, thus helping to prevent folate deficiency (see USDA reference in the steaming article).

Folate deficiency during human pregnancy has been associated with an increased risk of infant neural tube defects. Such deficiency during the first four weeks of gestation can result in structural and developmental problems. NIH guidelines recommend oral B vitamin supplements to decrease these risks near the time of conception and during the first month of pregnancy.