Dr C P Ravikumar

Introduction:
Folates or Vitamin B9 are water soluble vitamins that are present in a variety of foods . They are components of multi-vitamins and pre-natal vitamins as they are  incredibly important for the development of babies during pregnancy, responsible for cell division and growth and the generation of red blood cells.
There are two forms of Vitamin B9, Folic Acid and Folinic Acid , which are both classified as folates.  Folinic acid (5-formyl tetrahdrofolate or Leucovorin)  is an active form of vitamin B9 which occurs naturally in different foods, whereas folic acid is a synthetic form of folate. Even though they are structurally different, they perform similar function s in the body. Individuals who do not have sufficient levels of folic acid or Folinic acid are considered “Folate Deficient”

Required Daily amount: The recommended daily allowance of folic acid is calculated as micrograms of Dietary Folate Equivalents (mcg DFEs)

Life Stage Recommended Amount
Birth to 6 months 65 mcg DFE
Infants 7–12 months 80 mcg DFE
Children 1–3 years 150 mcg DFE
Children 4–8 years 200 mcg DFE
Children 9–13 years 300 mcg DFE
Teens 14–18 years 400 mcg DFE
Adults 19+ years 400 mcg DFE
Pregnant teens and women 600 mcg DFE
Breastfeeding teens and women 500 mcg DFE
This is because the  body absorbs  more folic acid from fortified foods and dietary supplements, than folate found in natural food supply. All pregnant women are advised to take folic acid supplementation and fortified foods, irrespective of diet.
DFE were developed to reflect the higher amount of folic acid in supplements that is absorbed by the body, as opposed to the amount absorbed from natural sources.  Therefore, the measurement of DFE was formulated as:
  • 1 mcg DFE = 1 mcg food folate
  • 1 mcg DFE = 0.6 mcg folic acid from fortified foods or dietary supplements consumed with foods
  • 1 mcg DFE = 0.5 mcg folicacid from dietary supplements taken on an empty stomach

Sources
a. Natural: Folate is naturally present in a wide variety of foods, including vegetables (especially dark green leafy vegetables like spinach), fruits and fruit juices, nuts and seeds , beans, peas, seafood, eggs, dairy products, meat, poultry, and grains. In India, the most common sources of vitamin B9 are dals, soya bean and peanuts . India also has a natural program where cereals and grains are fortifies with vitamin B9 , to improve its availability.
b. Supplements: Folic acid is consumed as multivitamins and prenatal supplements containing other B-complex vitamins, or only folic acid as a component.

Health Benefits of Folic Acid
Folic acid is necessary for the synthesis of DNA and RNA (genetic material) of each cell, in effective cell division, in metabolism of proteins and amino acids as well as formation of red blood cells in the body. It is especially important during pregnancy as it helps in the development of the baby in the uterus.

Deficiency of Folic Acid
a.Nutritional defect Isolated folic acid deficiency is rare as it usually occurs due to inadequate intake of nutrients in the diet, causing concurrent vitamin B12 deficiency as well.
b.Decreased absorption: Individuals with alcohol disorder usually have decreased nutrient absorption including folate. Alcohol also increases breakdown of folic acid in the liver followed by rapid excretion through the kidneys, further decreasing blood levels.
People suffering from malabsorption disorders like ulcerative colitis, Crohn’s disease, gastritis etc. have reduced folate absorption through the intestine.
c.Genetic factors Mutations in the MTHFR gene, (methylenetetrahydrofolate reductase) decreases the individual’s ability to convert folate to its active form, 5-MTHF, because the methylenetetrahydrofolate reductase enzyme needed for this reaction is less active. These patients require supplementation with 5-methyl-THF (the “active” form of folic acid) and are more at risk for Neural Tube defects.

 Folic Acid deficiency:
  • Individuals may exhibit signs of anemia due to defect in red blood cell production in the marrow (called megaloblastic anemia), resulting in weakness, pallor, heart palpitations, shortness of breath
  • Women who do not have adequate folic acid levels during pregnancy may give birth to babies with Neural Tube defectslike spina bifida or anencephaly (major defects in the baby’s spine or brain) or babies with low birth weight and are at risk for premature deliveries, or congenital cardiovascular defects.
  • Studies have shown that people with folic acid deficiency have an increased risk of depression, heart disease, stroke and autism spectrum disorder, although more conclusive evidence is required.

Excessive Intake of Folic Acid: While high levels of folate in the body have not been known to cause any harmful effects, it could help to mask an underlying, co-existing vitamin b12 deficiency. The folic acid will help to improve the anemia caused due to the low b12 levels but will not improve the neurological effects of vitamin b12 deficiency, which untreated may cause permanent damage to the nervous system.

Interactions with other medications
  • Folate supplements could interfere with methotrexate, which may be given during treatment of some cancers.
  • Taking anti- seizure medications, such as phenytoin carbamazepine and valproate could reduce blood levels of folate, while those on folate supplements could have reduced serum levels of these medications as well.
  • Sulfasalazine which is taken for ulcerative colitis, could reduce the body’s ability to absorb folate, resulting in deficiency.

Diagnosis
Serum folate  levels can be used to determine the folate status in the body.
This test is sensitive to recent intake of folic acid and so does not reflect the long term status of the individual. Therefore, Erythrocyte folate concentration levels are used as a more effective indicator of folic acid deficiency.
An adjuvant test like Plasma homocysteine concentration can be used as functional indicator of folate status as homocysteine levels increase if folic acid levels are low. However, they can be elevated due kidney dysfunction and deficiencies of vitamin B12 and other micronutrients, and should therefore be corelated with clinical symptoms and other tests.

Management
Prophylactic doses of folic acid are prescribed to pregnant women as prenatal medications. Nutritional intake and supplements can be advised.

Disclaimer:
The above information is for awareness and education purposes only and cannot be used for diagnosis or treatment of any condition. Please consult with a physician for any concerns or questions

Dr C P Ravikumar

Dr C P Ravikumar

CONSULTANT – PEDIATRIC NEUROLOGY
Aster CMI Hospital, Bangalore