Folic Acid Review Article
Folate is an essential vitamin that is also known as folic acid and folacin. The synthetic form of the vitamin (folic acid), pteroylglutamic acid, is seldom found naturally in food.
Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions. The human body needs folate to synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in biological reactions involving folate. The folates found in nature contain the core chemical structure of pteroylglutamic acid but vary in their state of reduction, the single carbon moiety they bear and/or the length of the glutamate chain attached. At least 50% of whole body folate is stored in the liver. The metabolic role of folate is as an acceptor and donor of one-carbon units in a variety of reactions involved in amino acid and nucleotide metabolism. The carbon can be carried as a methyl, methylene, formyl, formimino or methenyl group. The coenzyme form of the vitamin is typically fully reduced and poly-glutamylated. In the adult, folate is absorbed primarily in the proximal one-third of the small intestine. It is also conceivable that a portion of the large depot of bacterially synthesized folate in the large intestine may be absorbed. A large portion of folate delivered to the liver is secreted into bile and redistributed to peripheral tissues. Polyglutamylation (addition of glutamic acids) of folate is believed necessary to concentrate and store folates in tissues.
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Folic acid was first isolated from the spinach in 1941. Folic acid is also known as vitamin B9. It is a water-soluble vitamin. Folic acid is not an active compound – rather, it is first converted into dihydrofolic acid which is then converted into tetrahydrofolic acid and other compounds. From tetrahydrofolic acid, DNA is synthesized. Thus, a deficiency of folic acid directly leads to decreased synthesis of DNA. Due to decreased DNA synthesis, growth of the different cells of the body slows down. When the growth of the red blood cells decreases then a diseased condition occurs known as anemia. Thus, folic acid directly prevents anemia if it is taken in an adequate amount. Folic acid can be obtained from two major sources: synthetic and natural. The natural source of folic acid refers to our diet while the synthetic source refers to food supplements and fortified food.
Folic acid also has other roles in our health. Let us discuss one by one the different roles of folic acid in our health.
Role of folic acid as an antioxidant and anti-aging agent
It’s well known that vitamins A, C and E function as antioxidants and hence as anti-aging agents, while folic acid’s role in this respect is not so well known. Here we will see the role of folic acid as an antioxidant and anti-aging agent in the light of different studies.
In one study (Singh et al,2011) it was demonstrated that folic acid can enhance memory in aged rats. This is believed to be only because of its anti-oxidant effects. It was observed in the study that folic acid supplementation actually leads to a decrease in the lipid per oxidation content (a marker of aging) in the different regions of the brain; thus helps to improve memory by reducing oxidative stress and maintaining the integrity of neurons during aging.
In another study (Auerhahn et al, 2007) it was observed that folic acid supplements can help slow down the progression of age-related hearing loss in elderly people - especially in those who take a diet high in homocysteine but low in folic acid.
Similarly, in another study (Christen et al,2009), it was shown that folic acid, when given in combination with vitamin B6 and vitamin B12, reduces the risk of age-related macular degeneration (a condition that results in loss of vision due to damage of retina and usually affects elders).
Another study (Aghamohammadi et al, 2011) revealed that folic acid not only lowered plasma homocysteine and serum malondialdehyde (a marker of oxidative stress) levels, but also improved the serum total antioxidant capacity in patients with type 2 diabetes.
Role of folic acid in pregnant women
CDC (center for disease control and prevention) suggests that women should take 400 µg of folic acid daily, starting at least one month before getting pregnant, to avoid any major defects in the brain and the spine (neural tube defects) of the baby. The two most important major neural tube defects are anencephaly and spina bifida. Besides neural tube defects, folic acid deficiency during pregnancy may also cause preterm delivery, low weight of baby and other complications. To avoid all types of complications in pregnancy, folic acid should be taken by the pregnant women in the same manner as discussed previously. There are two easy methods by which a pregnant woman can easily fulfill her folic acid requirement. One method involves the woman taking folic acid supplements daily. The other method involves the woman taking daily a bowl of cereals fortified with 100% of the desired daily value of folic acid.
In 1991, a randomized trial (Nicholas et al, 2004) demonstrated that folic acid supplementation before and during pregnancy reduced the neural-tube defects in newborns up to a larger extent.
Another study conducted in China (Robert et al, 1999) concluded that pre-conceptional intake of 400 μg of folic acid daily can reduce the risk of neural tube defects in newborns.
Another study (Tinker et al, 2010) also observed that folic acid consumption by pregnant women aged 15-44 years can reduce the neural tube defects in newborns.
Role of folic acid in heart diseases
A study (Forman et al, 2005) showed that folic acid reduces the risk of hypertension. Dr Peter Coleman of The Stroke Association observed that folic acid supplements may reduce the risk of stroke in certain individuals but not in all people. Another study (Ebly et al., 1998) also observed that folic acid reduces the risk of stroke. In another study (Morrison et al, 1996) it was observed that lack of folic acid significantly increases the risk of deaths from coronary health disease.
Dual role of folic acid in cancer
Evidence suggests that folic acid supplementation may enhance the development and progression of already existing, undiagnosed premalignant and malignant lesions (Kim et al, 2004).
It is also believed that folic acid plays a significant role in cancer prevention. This was suggested when folic acid in the diet of a number of people protected them against different forms of cancer - like cancer of the breast, colon, pancreas and stomach. But it is still not completely understood how folic acid prevents from cancer. Some researchers thought that folic acid helps us maintain healthy DNA and prevents mutations, thus also preventing cancer. In a study (Eichholzer et al, 2001) it was observed that folic acid intake decreases the risk of colorectal, breast and cervix cancer.
Thus, it can be concluded that folic acid not only prevents cancer, but high levels of it may also cause cancer. This was also observed in a specific study (Ulrich et al, 2007) where folic acid prevented cancer in people having low folic acid level in early carcinogenesis, but it promoted carcinogenesis when taken at high doses in later stages of carcinogenesis. So, before using folic acid, always consult a doctor or a pharmacist in order to prevent its misuse.
Side effects of folic acid
High doses of folic acid usually do not harm us as folic acid is water soluble and can be rapidly removed from our body through the urine.
The Food and Nutrition Board of the Institute of Medicine recommends the following daily intakes of folic acid for the different age groups:
For 0 to 6 months: 65 µg per day
For 7 to 12 months: 80 µg per day
For 1 to 3 years: 150 µg per day
For 4 to 8 years: 200 µg per day
For 9 to 13 years: 300 µg per day
For 14 to 18 years: 400 µg per day
For 19 years and above: 400 µg per day
Aghamohammadi V, Gargari BP, Aliasgharzadeh A., 2011, Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus, J Am Coll Nutr, 30(3):210-5.
Auerhahn C., 2007, Daily folic acid supplementation for 3 years reduced age related hearing loss, Evid Based Nurs, 10(3):88.
Berry RJ, Li Z, Erickson D, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LC, Gindler J, Hong S, Hao L, Gunter E, Correa A,1999, Prevention of Neural-Tube Defects with Folic Acid in China, N Engl J Med, 341:1485-1490.
Christen WG, Glynn RJ, Chew EY, et al., 2007, Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women, Arch Intern Med, 169:335-41.
Correa A, 1999, Prevention of Neural-Tube Defects with Folic Acid in China, N Engl J Med, 341:1485-1490.
Ebly, Erika M., et al., 1998, Folate status, vascular disease and cognition in elderly Canadians. Age and Aging, 27:485-91.
Eichholzer M, L?thy J, Moser U, Fowler B.,2001, Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence, Swiss Med Wkly, 131(37-38):539-49.
Forman, J P et al., 2005, Folate Intake and the Risk of Incident Hypertension Among US Women, Journal of the American Medical Association, 293:320-329.
Kim YI., 2004, Will mandatory folic acid fortification prevent or promote cancer?, Am J Clin Nutr, 80(5):1123-8.
Koren G, 2007, Medication safety in pregnancy and breastfeeding, McGraw-Hill Professional.
Morrison, Howard I., et al., 1996, Serum folate and risk of fatal coronary heart disease, Journal of the American Medical Association, 275(24):1893-96.
Nicholas J. Wald D., 2004, Folic Acid and the Prevention of Neural-Tube Defects, N Engl J Med, 350:101-103.
Rimm, Eric B., et al., 1998, Folate and vitamin B-6 from diet and supplements in relation to risk of coronary heart disease among women, Journal of the American Medical Association, 279: 359-64.
Singh R, Kanwar SS, Sood PK, Nehru B., 2011,Beneficial effects of folic acid on enhancement of memory and antioxidant status in aged rat brain, Cell Mol Neurobiol ,31(1):83-91. Epub 2010 Dec 18.
Tinker SC, Cogswell ME, Devine O, Berry RJ, Folic acid intake among U.S. women aged 15-44 years, National Health and Nutrition Examination Survey, 2003-2006, Am J Prev Med, 38(5):534-42. Epub 2010 Mar 28.
Ulrich CM, 2007. Folate and cancer prevention: a closer look at a complex picture, Am J Clin Nutr , 86(2):271-3.
Antioxidants and Vitamines
Folic Acid Review Article