[4] Symptoms may include fatigue, 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] 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.
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.
The therapeutic effects of methotrexate are due to its inhibition of dihydrofolate reductase and thereby reduce the rate de novo purine and pyrimidine synthesis and cell division.
[22][24] Folate deficiency can occur during pregnancy as a result of the increasing number of cells of the growing fetus, decreased absorption and intake of folate, maternal hormones that mediate its metabolism, vascular circulation of maternal and fetal blood and an increasing amount of blood resulting in dilution.
[25] Sickle cell anemia and living in areas of malaria result in even higher folate needs for women who are pregnant.
[26][27] Utilization of folic acid supplementation before conception has shown to result in a decrease in neural tube defects by 70%.
[citation needed] More specifically, according to a 2014 UK guideline,[30] Folate is acquired in the diet by the consumption of leafy green vegetables, legumes and organ meats.
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.
[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%.
[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][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.