Folate deficiency
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body.[1] This may result in a type of anemia in which red blood cells become abnormally large and is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition.[3] Signs of folate deficiency are often subtle.[4] Symptoms may include feeling tired, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes.[1][5] Temporary reversible infertility may occur.[6] Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.[6]
Folate deficiency
Feeling tired, shortness of breath, changes in the color of the skin or hair, irritability[1]
Folic acid supplementation[1]
Very rare (countries with fortification programs)[2]
Not consuming enough folate can lead to folate deficiency within a few months.[1] Otherwise, causes may include increased needs as with pregnancy, and in those with shortened red blood cell lifespan.[1] Folate deficiency can be secondary to vitamin B12 deficiency or a defect in homocysteine methyl transferase that leads to a "folate trap" in which is an inactive metabolite that cannot be recovered.[1] Diagnosis is typically confirmed by blood tests, including a complete blood count, and serum folate levels.[1] Increased homocysteine levels may suggest deficiency state, but it is also affected by other factors.[1] Vitamin B12 deficiency must be ruled out, if left untreated, may cause irreversible neurological damage.[1]
Treatment may include dietary changes and folic acid supplements.[1] Dietary changes including eating high foods in folate such as, fruits and green leafy vegetables can help.[1] Prevention is recommended for pregnant women or those who are planning a pregnancy.[1]
Folate deficiency is very rare in countries with folic acid fortification programs.[2] Worldwide prevalence of anemia due to folic acid deficiency generally is very low.[2]
Signs and symptoms[edit]
Signs of folate deficiency anemia most of the time are subtle.[4] Anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency in adults.[1] Folate deficiency anemia may result in feeling tired, weakness, changes to the color of the skin or hair, open sores on the mouth, shortness of breath, palpitations, lightheadedness, cold hands and feet, headaches, easy bleeding or bruising, low-grade fevers, loss of appetite, weight loss, diarrhea, decreased taste, irritability, and behavioral disorders.[1][5]
Women with folate deficiency who become pregnant are more likely to give birth to low birth weight premature infants, and infants with neural tube defects and even spina bifida. In infants and children, folate deficiency can lead to failure to thrive or slow growth rate, diarrhea, oral ulcers, megaloblastic anemia, neurological deterioration. An abnormally small head, irritability, developmental delay, seizures, blindness and cerebellar ataxia can also be observed.[7]
Folate deficiency is diagnosed with a blood test to measure the serum level of folate, measured as methyltetrahydrofolate (in practice, "folate" refers to all derivatives of folic acid, but methylhydrofolate is the quasi unique form of "folate" in the blood[29]).
Homocysteine is elevated (5-MTHF is used to convert homocysteine to methionine) as in vitamin B12 deficiency, whereas methylmalonic acid is normal (elevated in vitamin B12 deficiency).
More specifically, according to a 2014 UK guideline,[30]
Prevention and treatment[edit]
Diet[edit]
Folate is acquired in the diet by the consumption of leafy green vegetables, legumes and organ meats.[31] When cooking, use of steaming, a food steamer, or a microwave oven can help keep more folate content in the cooked foods.[32][33][34]
Supplementation[edit]
Folic acid is a synthetic derivative of folate and is acquired by dietary supplementation.[25] Multi-vitamin dietary supplements contain folic acid as well as other B vitamins. Non-prescription folic acid is available as a dietary supplement in some countries, and some countries require the fortification of wheat flour, corn meal or rice with folic acid with the intention of promoting public health through increasing blood folate levels in the population.
Fortification[edit]
After the discovery of the link between insufficient folic acid and neural tube defects,[35] governments and health organizations worldwide made recommendations concerning folic acid supplementation for women intending to become pregnant. Because the neural tube closes in the first four weeks of gestation, often before many women even know they are pregnant, many countries in time decided to implement mandatory food fortification programs.[36] A meta-analysis of global birth prevalence of spina bifida showed that when mandatory fortification was compared to countries with healthcare professionals advising women but no mandatory fortification program, there was a 30% reduction in live births with spina bifida,[37] with some countries reported a greater than 50% reduction.[26]
Over 80 countries require folic acid fortification in some foods.[31] Fortification of rice is common.[27] The USDA has required the fortification of flour since 1998.[26] Since then, Hispanics in the United States have seen the greatest reduction of neural tube defects.[26] Canada has mandated folic acid fortification of flour since 1998 which has resulted in a 42% decrease in neural tube defects.[28] Fortification of wheat and corn flour, milk and rice is required in Costa Rica which has led to a reduction of neural tube defects of as much as 60%.[26]
Research[edit]
Folate deficiency during gestation or infancy due to development by the fetus or infant of autoantibodies to the folate receptor might result in various developmental disorders.[38]
Studies suggest that insufficient folate and vitamin B12 status may contribute to major depressive disorder and that supplementation might be useful in this condition.[39]
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).[39][40] The proposed mechanism, is that low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine (hyperhomocysteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine and serotonin from tyrosine and tryptophan), phospholipids, myelin, and receptors. High homocysteine levels in the blood can 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.[39][40]