Nutrition, deficiency & diseases: Vitamin B9 ( folate or folic acid) deficiency diseases

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What is vitamin B9?

Vitamin B9, also known as folic acid or folate, is an essential micronutrient. Vitamin B9 is one of the water-soluble B-complex group of vitamins.

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Folic acid is a cofactor in certain biochemical reactions. Folic acid is essential for cell division, cell proliferation and growth. The human body requires folic acid for carrying out basic cellular functions like synthesis of DNA, repair of DNA, and methylation of DNA.

Vitamin B9 deficiency is a rare nutritional disease which can become serious when not properly treated. Folic acid is available from several food sources of both plant and animal origins. Intestinal bacteria can synthesize small amounts of vitamin B9. Low blood serum levels of the folic acid occurs in certain specific situations such as severe malnutrition, alcoholism, certain medications, malabsorption diseases and pregnancy and lactation.

Low serum levels of folic acid, especially during pregnancy and infancy, limits cell division and affects normal growth.

Folic acid food sources

Vitamin B9 naturally occurs in a wide variety of plant foods including dark green leafy vegetables, asparagus, brussels sprouts, nuts, beans, peas, spinach, fruits and fruit juices, avocado and yeast. Most of the animal sources including dairy products, meat, liver, kidney, brain, fish, shellfish, poultry and eggs have considerable amounts of folic acid. In several countries it is mandatory to fortify wheat-flour and other ready-to-eat cereals with folic acid. The Recommended Dietary Allowance (RDA) for folic acid is 300 μg/day for adults and 400-500 μg/day for pregnant women and women of childbearing age.

Absorption and excretion of folic acid

In the diet, vitamin B9 exist as polyglutamates. For its absorption, vitamin B9 has to be converted into monoglutamates by reductase enzyme in the jejunal mucosa. Vitamin B9 is absorbed two-fold better in folic acid form than other forms. Naturally occurring vitamin B9 forms are rather unstable, losing their vitamin activity, at high temperatures and on exposure UV light. The absorbed folic acid is converted into biologically active form in the liver. Being water-soluble, excess of folic acid is excreted in the urine.

Functions of folic acid

Folic acid is essential for numerous metabolic functions. It is a cofactor in many vital biological processes. In the liver, the absorbed monoglutamate form of vitamin B9 is converted into dihydrofolate by the enzyme dihydrofolate synthetase. It is further converted into tetrahydrofolate by dihydrofolate reductase enzyme. The enzyme serine hydroxymethyltransferase converts tetrahydrofolate into 5,10-methylenetetrahydrofolate. Tetrahydrofolate as well as its methylated forms function as methyl donors.

Folic acid is required for the biosynthesis of RNA and DNA, repair of DNA and methylation of DNA.
Folic acid is a cofactor in methylation of homocysteine and coupling with vitamin B12 metabolism.
Vitamin B9 is very essential for cell division, especially in life stages with amplified cell division such fetus and neonate.
The conversion of homocysteine to methionine is a vitamin B9 dependent reaction.

Folic acid deficiency causes

The primary inadequacy occurs due very low dietary intake of vitamin B9.
Prolonged cooking and baking can cause loss of folic acid from the diet by degradation.
Malabsorption diseases including, short bowel syndrome, coeliac disease, Crohn's disease, chronic diarrhea and ulcerative colitis can cause deficiency of vitamin B9 in the body.
Genetic defects in the absorption mechanisms can impair absorption of folic acid.
Roux-en-Y gastric bypass surgery, by the elimination of high vitamin B9 absorptive duodenum and proximal jejunum, causes inadequacy of folic acid in the body.
During pregnancy fetal demands cause insufficiency of the vitamin in the mother's blood. Severe morning sickness may compound the problem.
Alcoholism and the related undernourishment may cause deficiency of folic acid.
Medications like trimethoprim, pyrimethamine, and methotrexate interfere with the synthesis of bioactive dihydrofolate form of vitamin B9, by inhibiting dihydrofolate reductase enzyme, which leads to deficiency of functional folic acid form in the body.
Valproic acid, the most commonly prescribed anticonvulsants, inhibits folic acid functions.
Exposure to UV light including tanning beds can deplete folic acid from the body.

Folic acid status and its deficiency is diagnosed by analysis of the plasma/serum concentration which is closely correlated to the red blood cell folic acid concentration.

Folic acid deficiency symptoms

The common symptoms of inadequate blood levels of vitamin B9 are:

diarrhea,
glossitis,
peptic ulcers,
megaloblastic, macrocytic anemia,
weakness,
breathlessness,
polyneuropathy,
mental depression,
irritability,
mental confusion,
cognitive deficits,
behavioral disorders,
headaches,
heart palpitations and
hyperhomocisteinemia (homocysteine accumulation).

Vitamin B9 deficiency diseases

Congenital malformations and neural tube defects, increased homocysteine level in the blood and associated cardiovascular ramifications, infertility, risk of preterm delivery, infant low birth weight and fetal growth retardation, spontaneous abortion, pregnancy complications, placental abruption, pre-eclampsia and eclampsia are associated with vitamin B9 deficiency.

Congenital malformations and neural tube defects

Neural tube defects are severe abnormalities of the central nervous system that develop in embryos during the first few weeks of pregnancy due to folic acid deficiency. Malformations like spina bifida and anencephaly occur due to vitamin B9 inadequacy. Low serum levels of folic acid may increase the risk of congenital heart defects, cleft lips, defective limbs and urogenital anomalies.

Megaloblastic, macrocytic anaemia

Folic acid insufficiency results in ineffective erythropoiesis (production of red blood cells). The erythroblasts proliferation during their differentiation get inhibited due to folic acid deficiency. The inhibition of DNA synthesis during red blood cell production leads to continuing cell growth without division, which presents as macrocytosis. The red blood cells grow larger but the number of cells decreases and the hemoglobin content per cell becomes insufficient. The total blood hemoglobin concentration becomes less than normal.

Hyperhomocysteinemia

Hyperhomocysteinemia is a disease wherein an abnormally high level of homocysteine is present in the blood. The deficiency of B-complex vitamins involved in the biochemical reactions of homocysteine causes this disorder. High levels of homocysteine is a risk factor for cardiovascular disease, thrombosis, renal dysfunction, Alzheimer's disease, schizophrenia and increased fractures. Supplementation with pyridoxine, folic acid or vitamin B12 reduces the concentration of homocysteine in the bloodstream.