What causes folic acid deficiency?

Causes of folate deficiency.

Inadequate intake due to:

• food preferences, low economic level;
• cooking methods (prolonged boiling results in a loss of 40% of folates);
• feeding with goat's milk (1 l contains 6 mcg of folate);
• eating disorders (kwashiorkor, marasmus);
• special diets (for phenylketonuria, maple syrup urine disease);
• prematurity;
• conditions after bone marrow transplantation (special food processing).

Absorption disorders:

• congenital isolated folate malabsorption;
• acquired:
  • idiopathic steatorrhea;
  • tropical spruce;
  • total or partial gastrectomy;
  • multiple diverticula of the small intestine;
  • jejunal resection;
  • inflammation of the ileum;
  • Whipple's disease;
  • intestinal lymphoma;
  • medications: broad-spectrum antibiotics, diphenylhydantoin (Dilantin), primidone, barbiturates, oral contraceptives, cycloserine, metformin, ethanol, dietary amino acids (glycine, methionine);
  • condition after bone marrow transplantation (total irradiation, drugs, intestinal damage).

Increased need:

• accelerated growth (prematurity, pregnancy);
• chronic hemolysis, especially in combination with ineffective erythropoiesis;
• dyserythropoietic anemia;
• malignant diseases (lymphoma, leukemia);
• hypermetabolic states (eg, infections, hyperthyroidism);
• extensive skin lesions (lichen-like dermatitis, exfoliative dermatitis);
• cirrhosis;
• condition after bone marrow transplantation (regeneration of bone marrow and epithelial cells).

Disorders of folate metabolism:

• congenital:
  • methylenetetrahydrofolate reductase deficiency;
  • glutamate formiminotransferase deficiency;
  • functional deficiency of 5-methyltetrahydrofolate-homocysteine methyltransferase due to CblE and CblG pathology;
  • dihydrofolate reductase deficiency;
  • methyltetrahydrofolate cyclohydrolase deficiency;
  • primary deficiency of 5-methyltetrahydrofolate-homocysteine methyltransferase;
• acquired:
  • drugs: folate antagonists (dihydrofolate reductase inhibitors): methotrexate, pyrimethamine, trimethoprim, pentamidine;
  • vitamin B ₁₂ deficiency;
  • alcoholism;
  • liver pathology.

Increased excretion:

• regular dialysis;
• vitamin B ₁₂ deficiency;
• liver disease;
• heart disease.

Folate deficiency is the second most common deficiency disorder in the world (after iron deficiency) and is caused by malnutrition and starvation. The incidence of folate deficiency is higher in women than in men. Folate reserves are depleted within 3 months when there is an increased need for them (during pregnancy and lactation). If the folate content in the fetus is insufficient, its nervous system does not develop properly. This is why women are prescribed folic acid as a preventive measure before conception and during pregnancy. Insufficient intake of folic acid during pregnancy leads to premature birth and low birth weight babies. Clinical manifestations of folate deficiency are rare at birth. Rapid growth in the first few weeks of a child's life is accompanied by an increased need for folic acid, so during this period, the drug is recommended to be prescribed at 0.05-0.2 mg per day for preventive purposes.

When discussing the causes of folate deficiency anemia, it is especially necessary to dwell on the increased need for folates in premature infants and children in the first year of life. The concentration of folates in the blood serum and erythrocytes in newborns is 2-3 times higher than in adults. However, during the first weeks of life, it decreases to the level observed in older children and adults. Average daily losses of folates per unit of body surface are greatest in children in the first days of life, so it is not possible to cover the folate needs through diet. Folic acid deficiency and megaloblastic anemia develop especially easily in premature infants aged 6-10 weeks, who are born with a small folate depot. This is due to the rapid depletion of the folic acid depot due to intensive growth, nutritional characteristics and intercurrent diseases.

During pregnancy, the increase in the need for folic acid is due to the needs of the fetus, which is 100-300 mcg/day.

In hemolytic anemias, the resulting deficiency of folic acid is associated with increased utilization of folates by young cells of the erythroid germ. Particularly low levels of folic acid are observed in patients with sickle cell anemia and thalassemia major.