What is folate?

Folate has originated from Folium which means leaf and it refers to all types of derivatives of pteroic acid showing vitamin activity within the human body. It is also called vitamin B9 or M. Because this nutrient helps synthesis of amino and nucleic acid, it is very important in the growth, development, and reproduction. It is also involved in the synthesis of erhythrocyte and growth of cells. Therefore, it is heavily required in growth, pregnancy, and nursing period. It is largely found in vegetables, however, only limited amounts are absorbed by food because it is destroyed by heat.  

In general, the fetal neurocanal is completely developed before most of the women recognize their pregnancy because development and closure of fetal neurocanal takes place at 3~4 weeks of pregnancy. Therefore, uptake of folate before pregnancy is critical in the fetal development.

Folate deficiency causes cell division, damage in proteins, erythrocytes, and cells sin grastro-intestinal tract (anemia, regression of gastro-intestinal tract), and megaloblastic anemia with damage in neurocanal. Folate deficiency can be caused by excessive alcohol, triplet, cancer, skin-degenerative diseases such as measles and chicken pox, burn, loss of blood, damages in gastro-intestinal intima, and chronic use of aspirin and antacids.

Effects

Folates are involved in the synthesis of DNA, RNA, and proteins. It prevents magaloblastic anemia, fatigue, weakness, susceptibility, headache, distractedness, tremor, palpitation, and atrophic glossitis.

1. Decrease birth defect (neurocanal closure)

In animal and epidemic studies, it has been found that folate deficiency is related to the neurocanal closure. This is assumed to be attributed to the nucleic acid synthesis and homocysteine metabolism on methionine. Another hypothesis says that folates may increase the possibility of abortion by cases instead of preventing the defects in neurocanal. Women who gave birth to the babies with neurocanal defects had significantly higher level of homocysteine compared to those with normal babies. Also, increased level of homocysteine can cause teratogenicity by increased oxidative stress. The folate of fetus of birds was suppressed when treated by D, L-homocysteine or L-homocysteine thiolactone leading to the lack of neurocanal. It implicates the lack of homocysteine or excessive homocysteine may cause the defects in neurocanal. In an epidemic study, it was reported that women with low blood folate and vitamin B12 has significantly higher risk to give birth to a baby with neurocanal deficiency. In another study, it was reported that folate supplements in pregnant woman significantly prevented the neurocanal damages.

Since it is important in the development of nerve and blood vessels in fetus, it is recommended to the pregnant women in the early stage and before pregnancy. When the pregnant woman has folate deficiency, megaloblastic anemia, abortion, or even abruption placentae is caused to have critical defects in the development of neurocanal. Therefore, it is more required in the early pregnancy period when cells are actively divided. Especially, it is very important to uptake folates in the initial 28 days of pregnancy when cells are actively divided.

Uptake of folate during pregnancy can decrease the rate of neurocanal defect from 86% to 72%. It was also announced by British medical research committee that folate uptake can decrease neurocanal defects up to 72% in women who already gave birth to babies with neurocanal deficiency. WHO also recommends all the women with child bearing potential to uptake 400µm of folate daily from at least one month before until the first 3 months of pregnancy as essential nutrition supplement program before pregnant. It is a part of mother and child health program for the safe childbirth and health of both mother and child.health of both mother and child.

2. Decrease coronary artery diseases

Uptake of high amount of folate decreases the risk of coronary artery diseases. Increased level of homocysteine increase the oxidation of LDL-cholesterol as well as adhesion of platelets. In a recent meta-analysis, 50µg of daily dietary folate uptake can prevent the death from cardiovascular diseases in 4,000~18,000 people a year. Also, daily uptake of 400µg of folate supplement can decrease the death from cardiovascular diseases in 3,000~12,000 people a year. In another study, 10% of patients with heart disease in USA attributed their diseases to high homocysteine level. More systemic clinical trials and treatments for cardiovascular diseases are required to support all these results.

3. Anti-atherom activity

Folates not only lower the homocysteine level but also have anti-atherom activity. Folates and 5-methyl-tetra-hydrofolate restore the damages in hypercholesterolemia patients.

4. Anti-cancer activity

It was proved that folate uptake is related to cancers in rectum, lung, esophagus, brain, uterine, and breast by an epidemic study. The biggest data support the effects of folate in rectal cancer, however, in unknown mechanism. In folate deficiency, uracil is more synthesized from DNA to play an important role in the synthesis of thymidyl acid. In 20 epidemic studies, the risk of rectal cancer was decreased by 40% in those who were administered of folate the most. In another study, it was also found that long-term uptake of folate decreased the risk of rectal cancer by 62% in chronic colitis patients. In another recent study, it has been suggested that daily uptake of 600µg of folate can prevent the breast cancer in women who drink 15mg of alcohol (a glass of alcohol) daily before and after menopause.

5. Nerve protection activity

Low blood folate level is related to the neurodegeneration of brain which leads to the poor recognition function, dementia, and Alzheimer’s disease. In a study, it was proved that low serum folate level has close relationship to the contraction of cerebral cortex. However, its mechanism of neuroprotection has not been revealed. Increased level of homocysteine from the lack of folate can cause increase in the oxidizing power and neurodegeneration which leads to the cerebral functional disorders. Also, lack of folate is related to other psychopathologic symptoms such as depression. In a recent study, folate has enhanced the antidepressive action of fluoxetine in those without folate deficiency. In a clinical trial, substantial amount of folate (15~20mg daily) caused poisoning instead of improving symptoms in mental disease. There is another recent report implicating the relationship between low serum folate level and the underdevelopment of cerebral cortex in patients with Alzheimer’s disease.

Drug interaction

1. Anticonvulsants (carbamazepine, fosphenytoin, phenytoin. Phenobarbital, primidine valproic acid)

When serum folate level is decreased, serum homocysteine level can be increased. Administration of high dose of folate lowers the serum concentration of the anticonvulsants above. Concomitant administration of folate and cholestyramine or colestipol decreases the absorption of folate. Colchicine lowers the blood folate level. It has been revealed in a study that daily uptake of 500µg of folate reinforces the antidepressive activity of fluoxetine administered 20µg daily. Also, it has been found that daily uptake of 200µg of folate enhances the effects of litium. Long-term administration of metformin increases the level of homocysteine which is decreased when administered with folate. When 1mg of folate administration daily was added to the methotrexate treatment for rheumatoid arthritis, side effect of poisoning can be significantly decreased while maintaining the efficacy. NSAIDs can sustain the anti-folate action in the treatment of multiple agents. Phenytoin can lower the serum folate level with negative influence on the folate status. Large amount of folate can lower the serum phenytoin level. When high dose of folate is administered together with pyrimethamine to prevent the wasting of the bone marrow, side effects may be accompanied pharmacoepidemiologically to the anthelmintic effect of pyrimethamine. Sulfasalazine can inhibit the absorption of folate when administered together.

Nutrition supplement

Concomitant administration of vitamin B6 or B12 with folate has synergic effect in lowering the serum homocysteine level.

Cautions and Side effects

Folates should not be administered to those with hypersensitivity to the products containing folate. Pregnant and nursing women are recommended to take 400µg of folate daily. Most of the nutrition supplements before and after childbirth contains 1mg (1,000µg) of folate daily. The acceptable daily dose of folate is 1mg. People with Vitamin B12 deficiency showed neuropathic signs and symptoms when administered of 5mg of folate daily.

Administration period of folate by pregnant women

From 1~3 months before pregnancy untill 12~14 weeks after pregnancy