Folate Deficiency

Signs and Symptoms

Folate deficiency, or vitamin B9 deficiency, primarily manifests with subtle symptoms. These can include feeling tired, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the colour of the skin or hair, irritability, and behavioural changes. In severe cases, it can lead to megaloblastic anaemia, where red blood cells become abnormally large. During pregnancy, folate deficiency can result in low birth weight, premature infants, and neural tube defects. In children, it can lead to failure to thrive, diarrhoea, neurological deterioration, and developmental delays.

Causes

Folate deficiency arises when the body's need for folate increases, dietary intake or absorption is inadequate, or the body excretes more folate than usual. It is more common in pregnant women, infants, children, and adolescents, and can also be due to poor diet or alcoholism. Additionally, medications such as anticonvulsants, metformin, methotrexate, and sulfasalazine can interfere with folate metabolism. Certain conditions like Crohn's disease, celiac disease, and chronic enteritis can reduce folate absorption. A defect in homocysteine methyltransferase or vitamin B12 deficiency can also cause a “methyl-trap” of tetrahydrofolate, mimicking folate deficiency.

Diagnosis

Diagnosis of folate deficiency is confirmed through blood tests measuring serum folate levels. A serum folate level of less than 7 nmol/L is indicative of deficiency. In cases where there is a strong suspicion of folate deficiency despite normal serum folate levels, a red cell folate test may be performed. Elevated homocysteine levels can also suggest folate deficiency, but this can be influenced by other factors. Vitamin B12 deficiency must be ruled out to prevent irreversible neurological damage.

Treatment and Prevention

Treatment of folate deficiency includes dietary changes and folic acid supplements. Consuming foods high in folate, such as fruits and green leafy vegetables, can help. Folic acid, a synthetic derivative of folate, is available through dietary supplements. In some countries, wheat flour, corn meal, or rice are fortified with folic acid to increase blood folate levels in the population. This fortification has led to a significant reduction in neural tube defects.

Diet

Folate is primarily acquired through leafy green vegetables, legumes, and organ meats. Cooking methods such as steaming or using a microwave oven can help retain more folate content in foods.

Supplementation

Folic acid supplements are recommended, especially for pregnant women or those planning pregnancy to prevent neural tube defects. A daily intake of 400-450 micrograms of folic acid is advised.

Fortification

Mandatory food fortification programmes have been implemented worldwide to reduce the incidence of folate deficiency. Over 80 countries require some form of folic acid fortification in foods. In the UK, fortification of wheat flour with folic acid is being considered to improve public health outcomes.

Epidemiology

Folate deficiency is very rare in countries with folic acid fortification programmes. The worldwide prevalence of anaemia due to folic acid deficiency is generally low, though data on specific high-risk groups is limited.

Research

Recent studies suggest a link between insufficient folate and vitamin B12 status and major depressive disorder. Supplementation may be useful due to folate and vitamin B12's roles in neurotransmitter formation. High homocysteine levels resulting from low folate can lead to vascular injuries and cerebral dysfunction, potentially contributing to depression.

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Self-assessment MCQs (single best answer)

Which specialty is primarily concerned with folate deficiency?

Which symptom is NOT typically associated with folate deficiency?

Which of the following is a severe consequence of folate deficiency during pregnancy?

Which of the following medications can interfere with folate metabolism?

What is the threshold serum folate level for diagnosing folate deficiency?

Which food is NOT a good source of folate?

What is the recommended daily intake of folic acid for pregnant women?

Which condition can mimic folate deficiency due to a "methyl-trap" mechanism?

In which type of countries is folate deficiency very rare?

Recent studies suggest a link between folate deficiency and which mental health disorder?