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Folic Acid Deficiency

Acid Deficiencies Folic

The human body needs folic acid to synthesize DNA and new cells. Folic acid deficiency typically causes megaloblastic anemia.


Presentation

The signs and symptoms of folic acid deficiency are non-specific. Subtle signs such as the development of glossitis and oral sores, grey discoloration of the hair, and in case of children, growth abnormalities may be observed; however, as folic acid deficiency leads to megaloblastic anemia, an anemic presentation is most often seen.

The severity of the symptoms is linked to the degree of the anemia and the general health of the individual; for instance, in old age, the symptoms are often much more marked even with a lower deficiency. The symptoms of anemia include fatigue, shortness of breath (especially on exertion) and palpitations. In severe cases, stable angina and intermittent claudication may also result. On physical examination, the skin and conjunctiva is often pale and the patient has a high volume pulse along with tachycardia. In long standing cases, ankle edema, cardiac murmurs and other signs of heart failure also begin to manifest.

In addition to these general signs and symptoms, the clinical manifestations resulting from the underlying etiology (such as anti-folate drug toxocoty, malabsorption, chronic kidney disease, hemolytic anemias, malignancies and homocysteinuria) may also be observed. Folic acid deficiency in pregnant women can predispose to the development of neural tube defects in the developing fetus (such as anencephaly, spina bifida, etc). Women with documented folic acid deficiency or with a history of bearing one or more child with a neural tube defect carry a particularly high risk. As folic acid is necessary for DNA repair, its deficiency may be associated with the development of certain cancers in the body.

Fatigue
  • Folate-deficiency anemia results in immature, abnormally large red blood cells which can lead into disturbing symptoms such as lose of weight and appetite, forgetfulness, lightheadedness, fatigue, and trouble concentrating.[drugsdb.com]
  • If the deficiency progresses then several symptoms may manifest: anemia, fatigue, depression, anorexia, weight loss, diarrhea, forgetfulness, headache, sore and inflamed tongue, heart palpitations, hostility and paranoia.[livestrong.com]
  • Signs of early pregnancy are missed menstrual periods, fatigue, breast enlargement, abdominal distention, and nausea.[mountsinai.org]
  • They include paleness, fatigue, shortness of breath, and palpitations, or heart fluttering, particularly if you exert yourself. In both disorders, your mouth and tongue may be sore, and your skin may become yellow in color.[revivelifelab.com]
  • Also possible with deficiency are decreased growth, fatigue , and more rapid graying of the hair.[diagnose-me.com]
Pallor
  • Thus, images shown on the left were taken after 2 months from the start of the pharmacological treatment; at this time, pallor of the optic nerve was still evident for monkeys B and C.[iovs.arvojournals.org]
  • Infants who have a folic acid deficiency may show signs of chronic fatigue, dyspnea, heart palpitations, weakness, glossitis, nausea, low body weight, headache, fainting, irritability, pallor and jaundice, or a yellowing of the skin.[livestrong.com]
  • On postoperative day 52 it was noted that the patient's tongue was magenta and sore and that she had altered taste, pallor, severe weight loss, diarrhea, and poor appetite and mood.[ncbi.nlm.nih.gov]
  • Symptoms of Folic Acid Deficiency Anemia Severe fatigue and weakness Paleness (pallor) Shortness of breath Heart palpitations or noticeably rapid heartbeat upon exertion Sore, red, and glazed-looking tongue Loss of appetite leading to weight loss Abdominal[healthcommunities.com]
Malnutrition
  • Abstract Polymorphonuclear leukocyte functions were studied in 92 patients with protein-calorie malnutrition. Serum folic acid levels were higher than 3 ng/ml in 38 patients and 3 ng/ml or less in 54 patients.[ncbi.nlm.nih.gov]
  • The oral administration of folic acid produces quick improvement in all symptoms; an adequate diet results in cure in cases due to simple malnutrition .[britannica.com]
  • The oral administration of folic acid produces quick improvement in all symptoms; an adequate diet results in cure in cases due to simple malnutrition. This article was most recently revised and updated by Robert Curley, Senior Editor.[britannica.com]
  • Individuals with low socio-economic status and institutionalized elderly population are also at an increased risk of folic acid deficiency due to inadequate intake of green leafy vegetables, malnutrition and mental status changes. [4] Pathophysiology[ncbi.nlm.nih.gov]
  • Malnutrition . Alcohol excess (also causes impaired utilisation). Poor intake due to anorexia . Food fads.[patient.info]
Vietnamese
  • […] in significant improvements in folate status among women of reproductive age, in areas where folate deficiency is high. [21] Casey et al examined the effects over 1 year of a free weekly iron-folic acid supplementation and deworming program in 52,000 Vietnamese[emedicine.com]
  • A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women. BMC Public Health. 2009 Jul 24. 9:261. [Medline]. [Full Text].[emedicine.medscape.com]
Intermittent Claudication
  • If the anaemia is severe, it can result in angina (chest pain), headache and leg pains (intermittent claudication).[netdoctor.co.uk]
  • In severe cases, stable angina and intermittent claudication may also result. On physical examination, the skin and conjunctiva is often pale and the patient has a high volume pulse along with tachycardia.[symptoma.com]
Respiratory Distress
  • Blood transfusions are given to treat severe cardiac or respiratory distress as a result of severe deficiency.[innvista.com]
Dyspnea
  • Infants who have a folic acid deficiency may show signs of chronic fatigue, dyspnea, heart palpitations, weakness, glossitis, nausea, low body weight, headache, fainting, irritability, pallor and jaundice, or a yellowing of the skin.[livestrong.com]
Nausea
  • Infants who have a folic acid deficiency may show signs of chronic fatigue, dyspnea, heart palpitations, weakness, glossitis, nausea, low body weight, headache, fainting, irritability, pallor and jaundice, or a yellowing of the skin.[livestrong.com]
  • Signs of early pregnancy are missed menstrual periods, fatigue, breast enlargement, abdominal distention, and nausea.[mountsinai.org]
  • Folic Acid Deficiency Anemia Severe fatigue and weakness Paleness (pallor) Shortness of breath Heart palpitations or noticeably rapid heartbeat upon exertion Sore, red, and glazed-looking tongue Loss of appetite leading to weight loss Abdominal swelling Nausea[healthcommunities.com]
  • […] high blood pressure, pallor, depression, muscle weakness and shortness of breath (known as ‘the sighs’) Sore tongue Low grade fevers Difficulty in proprioception Difficulty concentrating and sluggish responses, brain fog Neuropathic pain Heartburn, nausea[revivelifelab.com]
  • Symptoms include the following: progressive fatigue shortness of breath heart palpitations weakness glossitis (inflammation of the tongue) nausea anorexia headache fainting irritability forgetfulness pallor slight jaundice Conventional treatment consists[innvista.com]
Social Isolation
  • Certain elderly people also may be more susceptible to folate deficiency, as a result of their predisposition to mental status changes, social isolation, low intake of leafy vegetables and fruits, malnutrition, and comorbid medical conditions.[emedicine.com]
Cerebral Calcification
  • Two cases of focal occipital epilepsy with cerebral calcifications poorly responsive to antiepileptic treatment are described. In both cases coeliac disease was diagnosed and folic acid deficiency documented.[ncbi.nlm.nih.gov]

Workup

The diagnosis of folic acid deficiency is easily made through a careful history and simple physical examination of the individual. A number of simple tests can help confirm the diagnosis. These include the following.

  • Hemoglobin level and hematocrit: A reduction in the hemoglobin level below 12.5 in males and 10.5 in females is indicative of anemia. Reduction in the hematocrit also confirms anemia.
  • Complete blood count (and peripheral film): Once anemia is confirmed, a complete blood count and/or peripheral film is used to determine the type of anemia. In megaloblastic anemia (as is seen in folic acid deficiency and vitamin B12 deficiency), there is reduction in the total red cell count coupled with an increase in the mean corpuscular volume (MCV). 
  • Bone marrow biopsy: This is an invasive procedure and is unnecessary for the diagnosis of folic acid deficiency; however, in certain cases, it may be indicated and will show a megaloblastic picture in the bone marrow.
  • Red cell and serum folate levels: It is not possible to differentiate vitamin B12 deficiency and folic acid deficiency on the basis of blood picture alone. For this reason, red cell and serum folate levels are measured and if found to be low, folic acid deficiency is documented.
  • Vitamin B12 levels: This test may sometimes be indicated even if red cell and serum folate levels are found to be low. Vitamin B12 deficiency is rare because the human body contains abundant stores of it; however, in case of highly macrocytic picture, co-existing vitamin B12 and folic acid deficiency must be suspected and has to be ruled out. This is necessary because folic acid administration in case of vitamin B12 deficiency can precipitate the neurological features of vitamin B12 deficiency.
Macrocytic Anemia
  • CONCLUSION: In addition to macrocytic anemia (2.0%), FAD patients may have concomitant normocytic (23.7%) or microcytic (11.1%) anemia. Copyright 2015. Published by Elsevier B.V.[ncbi.nlm.nih.gov]
  • FOLATE deficiency has been recognized for some time to be the cause of most cases of macrocytic anemia of pregnancy. 1 2 3 The association of megaloblastic anemia with hemorrhage during pregnancy was first noted by Hourihane et al. 4 and by Coyle and[nejm.org]
  • These manifestations may occur in any combination; many patients have the neurologic defects without macrocytic anemia.[mayomedicallaboratories.com]
  • Evaluation Patients being evaluated for folic acid deficiency should also be evaluated for Vitamin B12 deficiency as both cause macrocytic anemia. Initial laboratory tests should include a complete blood count (CBC) and a peripheral smear (PS).[ncbi.nlm.nih.gov]
  • ) anemia caused by a lack of folic acid in the diet. folic acid deficiency anemia Anemia resulting from a deficiency of folic acid.[medical-dictionary.thefreedictionary.com]
Howell-Jolly Bodies
  • The 18 patients with folic acid deficiency had a significantly higher rate of megaloblasts, binucleate erythropoietic precursors, Howell-Jolly bodies, giant myelocytes, and giant metamyelocytes in bone marrow smears than the remaining 23 patients (P less[ncbi.nlm.nih.gov]

Treatment

The treatment of folic acid deficiency is folic acid supplementation which is usually done orally. For mild cases, a diet containing high levels of folate (such as citrus fruits and green, leafy vegetables) can be adequate; however, supplementation using folic acid tablets is usually carried out. The dosage of these supplements depends upon the etiology and the severity of the deficiency. In case of anemia due to folic acid deficiency, a daily dose of 1 to 5 mg is usually administered and the hemoglobin, red cell folate and serum folate levels are repeated after some duration. Once the deficiency has been overcome, a maintenance dose of 5 mg per week is often given.

The dosage and duration of folic acid supplementation in folic acid deficiency due to other etiologies is different. In case of gastrointestinal malignancies, up to 5 mg of folic acid is taken for 3 to 8 years; whereas in other malignancies, doses as high as 40 mg may be taken for the same duration depending upon the severity. Folic acid deficiency resulting from overuse of methotrexate may require doses as high as 20 mg for up to 12 weeks [3] [4] [5]. In chronic kidney disease, supplementation of up to 15 mg is taken on alternate days for several years; whereas in homocysteinuria, up to 5 mg of folic acid is required for 1 to 6 months.

In case of overuse of phenytoin, gum hypertrophy may occur which is treated by supplementation along with the topical application of folic acid over the affected gums [6] [7]. Pregnancy related gum disease is also treated in a similar fashion. Prophylactic folic acid supplementation is recommended to all women of child bearing age. Supplementation starting from 2 months prior to pregnancy and during the first two months of pregnancy is very effective in preventing the development of neural tube defects in the fetus [8].

Prognosis

The prognosis of folic acid deficiency itself is very good; however, the underlying etiology (such as any malignancy) may have a prognosis of its own. In the absence of any pathology, folic acid deficiency is completely reversible and does not carry any permanent effects.

The deficiency of folic acid caused due to poor nutrition, pregnancy or lactation is easily treatable with folic acid supplementation. Similarly, folic acid deficiency resulting from excessive alcohol intake rapidly responds to alcohol withdrawal. Folic acid deficiency due to pathological states responds to folic acid supplementation; however, the recovery is not permanent and the underlying pathology always has to be dealt with. Folic acid deficiency resulting from anti-folate drug use responds to folic acid supplementation and/or drug withdrawal.

Etiology

Folic acid is not stored in the human body in good amounts due to which a daily intake of folic intake is required. Males require about 400 micrograms of folic acid daily whereas females require 400 to 600 micrograms. Plant sources of folic acid in the human diet include bananas, melons, citrus fruits, green leafy vegetables, tomatoes, peas and mushrooms whereas pork, poultry and kidney and liver meat are the animal sources. By far, the most common cause of folic acid deficiency is dietary deficiency. A diet low in folic acid may lead to folic acid deficiency over the course of a few weeks.

In addition to the consumption of unbalanced diets, dietary deficiency may result from poor intake due to starvation and old age. A number of disease states such as acute hepatitis, depression and anorexia nervosa lead to decreased appetite and can also cause inadequate dietary intake of folic acid. Excessive intake of alcohol interferes with the absorption of folic acid in the gastrointestinal tract and also increases its excretion in the urine. For this reason, folic acid deficiency is common in alcoholics [1]. Folic acid is absorbed from the entire gastrointestinal tract; therefore, malabsorption is a very rare cause of folic acid deficiency. However, a number of gastrointestinal diseases such as celiac disease, Crohn disease and cancers can lead to malabsorption severe enough to cause folic acid deficiency in advanced cases.

Deficiency of folic acid can also occur in certain physiological states involving a high folic acid demand such as pregnancy and lactation. In pregnancy, the growing fetus has many rapidly dividing cells for which folic acid is required in excess. Similarly in lactation, folic acid is secreted into the mother’s milk and excess folic acid is required in the diet to make up for this loss. Up to 200 micrograms of folic acid may be needed in addition to the basal requirement of 400 micrograms.

A number of pathological states also confer a high folic acid demand in the body due to rapid cell turnover. These include hemolytic diseases, malignancies and severe inflammatory diseases. Advanced chronic renal diseases also increase the breakdown of red blood cells and ultimately to folic acid deficiency. High levels of homocysteine (as seen in homocysteinuria) are also known to cause the deficiency of folic acid. The use of certain drugs (such as methotrexate, phenytoin, pyrimethamine, sulfasalazine and trimethoprim) can lead to folic acid deficiency [2]. These drugs are therefore referred to as anti-folate drugs.

Epidemiology

Dietary folic acid deficiency is more common in the people belonging to the poor social class, especially in the third world countries where people face starvation and often do not get adequate levels of folic acid in their food.

Deficiency of folic acid is much more common in women due to their increased folic acid demand in pregnancy and lactation. In developed countries, alcohol intake is a very common precipitating cause of folic acid deficiency.

Sex distribution
Age distribution

Pathophysiology

Folic acid is necessary for the synthesis of DNA and RNA; and therefore, the production of new cells. It is also needed for the repair of DNA. All the processes and conditions that require a high cell turnover essentially require folic acid. In case of folic acid deficiency, DNA synthesis and cell division can not take place. The most common physiologic manifestation in adults is the development of megaloblastic anemia.

Prevention

Consuming a well balanced diet with a good amount of fruits and vegetables is sufficient to prevent the deficiency of folic acid in both genders. Women of childbearing age should take folic acid supplements; especially before and during the first two months of pregnancy [9] [10]. Supplementation should also be taken during the period of lactation. The people suffering from disease conditions that involve a high cellular turn over should consider taking folic acid supplementation prophylactically.

Summary

Folic acid is essential for the synthesis of DNA and the division of cells. Deficiency of folic acid usually results from inadequate dietary intake; however, a number of pathological conditions may also precipitate this deficiency. The most common manifestation of folic acid deficiency is megaloblastic anemia. Oral supplements are the mainstay for the management of folic acid deficiency.

Patient Information

The human body essentially requires folic acid for the synthesis of DNA and the formation of new cells. Most commonly, lack of folic acid in the diet leads to folic acid deficiency. The symptoms of folic acid deficiency develop due to reduced number of circulating red blood cells. Supplementation of folic acid using tablets or pills is often sufficient to resolve the deficiency.

References

Article

  1. Cylwik B, Chrostek L. [Disturbances of folic acid and homocysteine metabolism in alcohol abuse]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. Apr 2011;30(178):295-299.
  2. Brubakk O. [Phenytoin-induced folic acid deficiency]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. Jun 30 1973;93(18):1385-1388.
  3. Shea B. Folic acid or folinic acid for reducing side effects of methotrexate for people with rheumatoid arthritis. Journal of evidence-based medicine. Aug 2013;6(3):202-203.
  4. Singh JA. Folic acid supplementation for rheumatoid arthritis patients on methotrexate: the good gets better. The Cochrane database of systematic reviews. 2013;7:ED000063.
  5. Al-Dabagh A, Davis SA, Kinney MA, Huang K, Feldman SR. The effect of folate supplementation on methotrexate efficacy and toxicity in psoriasis patients and folic acid use by dermatologists in the USA. American journal of clinical dermatology. Jun 2013;14(3):155-161.
  6. Brown RS, Di Stanislao PT, Beaver WT, Bottomley WK. The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study. Oral surgery, oral medicine, and oral pathology. May 1991;71(5):565-568.
  7. Arya R, Gulati S, Kabra M, Sahu JK, Kalra V. Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children. Neurology. Apr 12 2011;76(15):1338-1343.
  8. Bestwick JP, Huttly WJ, Morris JK, Wald NJ. Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women. PloS one. 2014;9(2):e89354.
  9. Dolezalkova E, Unzeitig V. [Folic acid and prevention of the neural tube defects]. Ceska gynekologie / Ceska lekarska spolecnost J. Ev. Purkyne. Apr 2014;79(2):134-139.
  10. Fonseca EB, Raskin S, Zugaib M. Folic acid for the prevention of neural tube defects. Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia. Jul 2013;35(7):287-289.

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Last updated: 2019-07-11 21:02