INTRODUCTION

Anemia is a widespread public health problem associated with an increased risk of

morbidity and mortality, especially in pregnant women, women of child-bearing, and young
children. Anemia can be defined as an inadequate condition of the mass of erythrocyte or
hemoglobin in vascular to supply oxygen for tissues. Anemia is also a condition when
hemoglobin concentration below the normal ranges more than two standard deviations for age
and gender.1 Generally, clinical criteria for anemia that used at hospital or private practice in
Indonesia are: (1) hemoglobin <10 g/dl; (2) hematocrit <30%; (3) erythrocyte < 2.8
million/mm3.2
According to WHO, 1.62 billion people are anemia (95% CI: 1.501.74 billion), which
corresponds to 24.8% of the population (95% CI: 22.926.7%).3 Based on Survei Kesehatan
Rumah Tangga on 2004, prevalence of anemia in Indonesia can be described as: under five
years 40,5%, pregnant woman 50,5%, post-partum woman 45,1%, girl teenager 10-18yr
57,1%, and 19-45yr 39,5%. The data figure that woman is at high risk to get anemia.4
The etiology of anemia is diverse. Among the numerous factors, both nutritional (such
as vitamin and mineral deficiencies) and non-nutritional (such as infection and
hemoglobinopathies) contribute to the onset of anemia. Although nutritional anemias are
predominantly caused by iron deficiency in both developed and less developed countries,
other micronutrients like folic acid and vitamin B12 deficiency also have important role as
etiology of nutritional anemia.5
Folic acid is an essential dietary requirement for most people at about 400 g/day. It is a
water soluble member of the B-complex family of vitamins. Because humans cannot
synthesize this compound, it is a dietary requirement.6
Folic acid is synthetic form of folate that added to foods and found in supplements. In
nature, meat, green vegetables, fruits, and beans is a common sources of folate. Folate plays
an essential role in several complex metabolic pathways, including those leading to the
synthesis of DNA and RNA and those involved in methylation. 7 Although folic acid is the
primary form of folate used in dietary supplements or fortified foods, it comprises only 10
percent or less of folates in the diet.6
The best-known morbid effects of folic acid deficiency have been associated with
anemia. Anemia due to folic acid deficiency may be accompanied by vitamin B12 deficiency
or not. Folic acid deficiency anemia is manifest by macrocytic anemia resulting from
B4 | Folate Deficiency Anemia

megaloblastic change in the bone marrow.7

Megaloblastic changes characterize by

megaloblast cell, which is an erythrocyte precursor cell with large size, and contain a
characteristic immature, lacy nucleus, and mature cytoplasm. These abnormalities are caused
by a defect in DNA synthesis that interferes with cellular proliferation and maturation.6
Megaloblastic anemias are a heterogeneous group of disorders that share common
morphologic characteristics. Both folic acid and vitamin B12 deficiency are the most common
causes of megaloblastosis. Overall, in general these deficiencies show nonspecific
manifestation of megaloblastic anemia. Therefore comprehensive assessment on history,
physical examination and appropriate laboratory tests is properly performed to make a precise
diagnosis.
In this paper we will discuss about overview of folic acid and anemia due to its
deficiency including with epidemiology, etiology, pathophysiology, diagnosis, treatment and
prognosis.

B4 | Folate Deficiency Anemia

CONTENTS
A.

Overview of Folic Acid

Folic acid (pteroylglutamic acid) is a water soluble member of the B-complex family of

vitamins. Folic acid composed of a pteridine derivative, a p-aminobenzoate residue, and an Lglutamic acid residue. Both pteridine derivative and p-aminobenzoate residue are called
pteroic acid. In nature, folic acid occurs largely as conjugated in which multiple glutamic
acids are linked by peptide bonds involving -carboxyl group. Conjugates are named
according to the length of the glutamate chain (e.g., pteroylglutamate, pteroyldiglutamate).
Therapeutic folic acid has one glutamic acid.8
To form a functional compound, folate must be reduced to tetrahydrofolate (FH 4). In
this reduction, dihydrofolate (FH2) is an intermediate. A single enzyme, dihydrofolate
reductase, catalyzes both FFH2 and FH2FH4.
Folate family consists largely of FH4 derivate bearing a one-carbon substituent
(symbolized FH4-C). The varieties of FH4-C differ in the identity of the one-carbon unit and
the site of its attachment to FH 4. One carbon substituent include: Formyl CH=O, Formimino
CH=NH2, Methenyl CH=, Methylene CH2, Methyl CH3. These substituent attach to FH4
through N5, N10, or both.
.

Figure 1. Structure Folic Acid.8

1.

Pharmacokinetics
Large oral doses of folic acid substantially raise plasma levels in healthy subjects in a

time- and dose-dependent manner. Subsequent to high-dose oral administration of folic acid
(ranging from 25-1.000 mg/day), red blood cell (RBC) folate levels retain elevated for periods
in excess of 40 days following discontinuation of the supplement. Folic acid is poorly
transported to the brain and rapidly cleared from the central nervous system.8
Folic acid is absorbed in small intestine. From small intestine it makes its way to the
serum, where most of the folic acid is free or loosely and nonspecifically bound to serum
proteins. There is no major role for specific transport protein for folic acid. In most tissue
B4 | Folate Deficiency Anemia

other than the liver, folic acid enters and remains within the cell throughout its life span. 1 The
primary methods of elimination of absorbed folic acid are fecal (through bile) and urinary.
After ingestion, the process of conversion of folic acid to the metabolically active coenzyme
forms is relatively complex. Synthesis of the active forms of folic acid requires several
enzymes, adequate liver and intestinal function, and adequate supplies of riboflavin (B2),
niacin (B3), pyridoxine (B6), zinc, vitamin C, and serine.
After the formation of the coenzyme forms of the vitamin in the liver, these
metabolically active compounds are secreted into the small intestine with bile (the folate
enterohepatic cycle), where they are reabsorbed and distributed to tissues throughout the
body. Despite the biochemical complexity of this process, evidence suggests oral
supplementation with folic acid is able to increase the body's pool of the active reduced folate
metabolites (such as methyltetrahydrofolate) in healthy individuals.
Enzyme defects, malabsorption or digestive system pathology, and liver disease can
result in impaired ability to activate folic acid to the required coenzyme forms in the body.
Evidence indicates some individuals have a severe congenital deficiency of the enzyme
methyltetrahydrofolate reductase, which is needed to convert folic acid to the 5methyltetrahydrofolate coenzyme form of the vitamin. The existence of milder forms of this
enzyme defect is strongly suspected and likely interacts with dietary folate status to determine
risk for some disease conditions. In individuals with a genetic defect of this enzyme (whether
mild or severe), greater dietary exposure to foods rich in folates and supplemental folates in
the form of folinic acid or 5-methyltetrahydrofolate might be preferable to folic acid
supplementation. The minimal daily requirement is about 50g.
2.

Mechanisms of Action
Folic acid primary mechanisms of action are through its role as a methyl donor in a

range of metabolic and nervous system biochemical processes, as well as being necessary for
DNA synthesis. Serine reacts with tetrahydrofolate forming 5,10- methylenetetrahydrofolate,
the folate derivative involved in DNA synthesis. A methyl group is donated to cobalamin
(BI2) by 5-methyltetrahydrofolate, forming methyleobalamin. With the help of the enzyme
methionine synthase, methyleobalamin donates a metil group to the amino acid metabolite
homocysteine, converting it to the amino acid methionine. Methionine subsequently is
converted to S-adenosylmethionine (SAMe). A methyl donor involved in numerous
biochemical processes.9

B4 | Folate Deficiency Anemia

Figure 2. Mechanism Action Folic Acid.9

B.

Overview of Folic Acid Deficiency Anemia

Folic acid deficiency anemia is one kind of megaloblastic anemia because of folate

deficiency. This megaloblastic cell is because of disturbance of DNA synthesis. DNA

synthesis makes the maturation of the nucleus slower, therefore the chromatin become loose.
Megaloblast is destroyed when still in bone marrow cause of abnormal function, named
hemolysis intramedullary. This hemolysis makes an ineffective erythropoiesis and life span of
erythrocyte become shorter, lead to anemia. The cause of folate deficiency anemia can be
nutritional intake/need, malabsorption, pregnant, etc.2
C.

Epidemiology
The prevalence and the magnitude of folate deficiency across the world are unclear.

National surveys conducted in several countries show that folate deficiency has the potential
to be a public health problem. The primary age groups affected include pre-school children
(33.8% of the folate-deficient population in Venezuela), pregnant women (48.8% in Costa
Rica and 25.5% in Venezuela), and older people (15% in the UK). In the US, folate deficiency
was present in school-age children (2.3% of the folate-deficient population), adults (24.5%),
and older people (10.8%) before folic acid fortification. Mandatory folic acid fortification of
enriched cereal-grain products was initiated in the US in 1996. Subsequently, surveys of
regional and nationally representative populations have shown that serum and RBC folate
concentrations have increased in every age group in the general population in the US.10
D.

Etiology of Folic Acid Deficiency

B4 | Folate Deficiency Anemia

Folic acid deficiency can results from a number of abnormalities in folic acid
metabolism. The main cause of folic acid deficiency is inadequate intake, which may occur
alone or in combination with increase requirement, malabsorption, drugs, or other causes.1,11
The bodys reserves of folate, unlike vitamin B12, are low (about 10mg). On a deficient diet,
folate deficiency develops over the course of about 4 months, but folate deficiency may
develop rapidly in patients who have both a poor intake and excess utilization of folate.11
Inadequate Nutrition
Inadequate diet is the major cause of folate deficiency because folates reserves are small,
deficiency develop rapidly in malnourished person typically the old, the poor and alcoholic.
In premature infant especially with infection and diarrhea and infant raise on goat milk which
is poor of folate may result in folic acid deficiency.11-14 Destruction of folate through excessive
cooking can aggravate folic deficiency.11-14 Folates are very thermolabile. Therefore, excessive
heating can lead to inactivation, especially when foods are diluted in water. 15 Cooking causes
a loss of about 60-90% of the folate.11
Impaired Absorption
Impaired absorption can be caused by tropical sprue, non-tropical sprue, or other intestinal
disorder.1,12,16 Non-tropical sprue (celiac disease in children) is related to the ingestion of
wheat gluten. Pathologically non-tropical sprue show atrophy and chronic inflammation of the
small intestine mucosa, most severe proximally findings may include weight loss, glositis as
typical of folic deficiency.13 Other intestinal disorders: malabsorption of folic acid commonly
occurs in regional enteritis, after extensive resection of the small intestine, in lymphomatous
or leukemia infiltration of the small intestine, in Whipple disease, amyloidosis, and diabetes
mellitus. Systemic bacterial infections and Croch disease also impair folate absorption.1,13,16
Increased Folate Requirement
Physiologic conditions such as pregnancy, lactation and prematurity will increase the
requirement of folic acid which can lead to folic acid deficiency, megaloblastic anemia.
During pregnancy, folate requirement increase five to ten fold because of transfer of folate to
the growing fetus, which will draw down maternal folate stores. Further increase may result
from the presence of multiple fetuses. Physiologic anemia develops during pregnancy because
of an increase in plasma volume that is only partly offset by an accompanying increase in red
cell mass. Hemoglobin levels may fall to 10g/dl with physiologic macrocytosis raises in MCV
B4 | Folate Deficiency Anemia

of 20 fl. occur, although the average at term is 4 fl. Serum and red cell folate level falls
steadily during pregnancy even in well-nourished woman which then result in false clue that
suggest folate deficiency even when folate level are normal.12
In pathological condition, folate requirement increase because of excessive utilization occurs
during hyperallimentation or hemodialysis, where folate is loss in the dialysis, psoriasis,
exfoliative dermatitis, malaria, and hemolytic anemia in children.13
Alcoholism
Alcohol interferes with folate metabolism in the liver, resulting in a profound depletion of
folate stores. In alcoholic, alcohol may acutely depress serum folate even if folic store are full
and will accelerate development megaloblastic anemia in someone with early folate
deficiency. Alcohol causes acute marrow suppression with decline in reticulocyte platelet and
granulocyte level.11-14
Other causes
Other causes of folic acid deficiency are medications including anticonvulsants, sulfa drugs,
ethanol, and defective cellular uptake with rare case.1,15
E.

Pathophysiology
Deficiency of folate causes megaloblastic anemia, a disease in which pancytopenia

results from differentiating hematopoietic cells dying before reaching maturity. Folate is
cofactors in several important metabolic pathways in the cell. Folate integrates with
cobalamin plays an important role in the metabolism of homocysteine and MMA. The
conversion of homocysteine to methionine requires folate as cofactors.6
Folate, in the form of tetrahydrofolate (FH4) coenzymes, plays a role in the synthesis of
thymidylate and purines and is indirectly involved in the methylation of cytosine in DNA.
FH4 is an intermediate in reactions involving the transfer of one-carbon units from a donor XC to acceptor Y:
X-C + FH4 = FH4-C + X
FH4-C + Y = Y-C + FH4
Sum X-C + Y = Y-C + X
Among the one carbon transfer mediated by folic acid, the one that appears to be
clinically the most important is the methylation of deoxyuridylate to thymidylate, catalyzed
B4 | Folate Deficiency Anemia

by the enzyme thymidylate synthase. Thymidylate synthesis is an essential preliminary step in

the synthesis of DNA. The coenzyme of this reaction is N5, N10-mathylene-tetrahydrofolate, is
unique among folate coenzyme because it transfers a one-carbon group and serves as
hydrogen donor in reducing the transferred group to a methyl group. The reaction generates
FH2 which must be reduced again to FH4 by dihydrofolate reductase before it can again be
utilized as a coenzyme. Thus, the following thymidylate synthesis cycle exist, in which the
hydroxymethyl carbon of serine is transformed into the methyl carbon of thymine as FH4 is
regenerated from FH2 at the expense of NADPH.12
Serine +FH4 N10-hydroximethyl FH4 + glycine
N10-hydroxymethyl FH4 N5,N10-methylene FH4 + H2O
dUMP + N5,N10-methylene FH4 FH2 + dTMP
FH2 + NADPH + H+ FH4 + NADP+
Defective thymidylate synthesis leads to defective DNA synthesis, causes uracil to be
incorporated into DNA instead of thymine, increased levels of p53 and p21 proteins. The latestage accumulation of p21 protein in folate-deficient erythroblasts, which is more prominent
at 44 hours, may be due to altered nucleotide pools, increased uracil disincorporation or
relative persistence of undifferentiated cells at this time. The p53 accumulation in folatedeficient erythroblasts occurs temporally with the p21 accumulation, which, in turn, may
inhibit cell cycle progression. The cell cycle cannot progress from the G2 growth stage to the
mitosis (M) stage. This leads to continuing cell growth without division, may leads to
immature nucleus but mature cytoplasm, which presents as macrocytosis. This arrest of cell
cycle in folate-deficient erythroblasts may prevent their apoptosis and leads increased
reticulocyte size.12
At normal erythropoiesis process, the number of erythroid progenitor cells increases at
each step of differentiation. Normal erythrocyte production results in normal tissue
oxygenation and maintains normal erythropoietin levels. Normal erythropoietin levels result
in apoptosis of some cells at the CFU-E and proerythroblast stages. Apoptotic cells are shown
by condensed and fragmented nuclei. In megaloblastic erythropoiesis the CFU-E and
proerythroblast

population

predominate

because

apoptosis

of

basophilic

and

polychromatophilic erythroblasts in response to DNA damage greatly reduces their numbers.

Because of this late stage apoptosis, reticulocyte production is decreased. Those few
B4 | Folate Deficiency Anemia

erythroblasts that do complete their differentiation produce reticulocytes that are larger than
normal, and the total population of blood erythrocytes eventually develops an increased MCV.
The decreased erythrocyte production leads to tissue hypoxia and increased erythropoietin
levels. The increased erythropoietin level expands the populations of its target cells, the CFUE, and proerythroblasts and thereby further shifts the erythropoietic population toward these
earlier stages. The shift in the population toward immature erythropoietic progenitor cells is
characteristic of megaloblastic hematopoietic tissue.12-14
Deficiency of folate also diminishes purine biosynthesis by slowing (1) The folatedependent formylation of glynamide ribotide to N-formylglycinamide ribotide, the reaction
that places the C-8 in the purine ring and (2) The folate-dependent conversion of 5-amino-4imidazole carboxamide ribotide (AICAR) to 5-formamido-4-imidazole carboxamide ribotide,
the reaction that places the C-2 in the purine ring. The decrease in purine synthesis however is
offset by the ability of AICAR to slow purine degradation by inhibiting both adenosine
deaminase and adenylate deaminase. This may explain why no clinical manifestation has thus
far been traced to the block in purine synthesis. Interference with the breakdown of histidin
leads to the excretion of formininoglutamic acid (FIGlu) in the urine of folate-deficiency
patients.13

Figure 4. Folic Acid Scheme

F. Diagnosis
Diagnosis of folic acid deficiency anemia required a systematic approach. It should begin
with comprehensive history and physical examination followed by appropriate laboratories
examination.
1. Clinical Presentation

B4 | Folate Deficiency Anemia

The onset is usually insidious with gradually progressive symptoms and signs of anemia.
Folic acid deficiency anemia may shows general signs and symptoms of anemia including
shortness of breath particularly on exercise, weakness, lethargy, palpitation, and headache,
pallor of mucous membranes which occurs if the hemoglobin level is less than 9-10g/dL. But
in some patients, it remains asymptomatic until being confirmed by laboratory test.16
For specific signs, the patient may be mildly jaundiced/icterus (lemon yellow tint) because
of the excess breakdown of hemoglobin resulting from increase ineffective erythropoiesis in
bone marrow. Glositis (a beefy-red sore tongue), angular stomatitis and mild symptoms of
malabsorption with loss of weight may be present because of the epithelial abnormality.
Purpura as result of thrombocytopenia and widespread melanin pigmentation are less frequent
presenting features. It should keep in mind that folic acid deficiency anemia does not have
neuropsychiatric manifestation as in other megaloblastic anemia due to cobalamin
deficiency.1,16
2.

Laboratory finding

a.

CBC

Hemoglobin level decrease from mild to severe (3-4 g/dl).2

The reticulocyte count is normal or low.2,16

The reticulocyte count is low due to the abnormal maturation process.

Total white cell and platelet counts may be moderately reduced, especially in severely
patients.16

Macrocytosis with MCV increases 110-125 fl.2

Macrocytosis is the earliest abnormality seen in patients with folate deficiency which can
be identified both by reviewing automated RBC indexes and/or by peripheral blood smears.
The peripheral blood smear is more sensitive than RBC indexes for identifying early
macrocytic changes because the MCV represents the mean of the distribution curve and is
insensitive to the presence of small numbers of macrocytes.6
b.

Peripheral Blood Smear

From peripheral smear will show anemia with macrocytic (MCV >115 fl) and the

macrocytes are typically oval in shape. There is also hypersegmented neutrophil (with six or
more lobes). For patients who present with disordered immaturity, hypogranulated or
hyposegmented neutrophils, and cytopenias, a bone marrow examination is necessary to rule
out or confirm a primary bone marrow disorder such as a myelodysplastic syndrome or
leukemia.6
B4 | Folate Deficiency Anemia

10

c.

Bone marrow examination

The marrow is usually hypercellular and erythroid elements being dominant on the

marrow aspirate smear preparations. The erythroblasts become large, oval shaped and contain
a characteristic immature, lacy nucleus, while cytoplasmic maturation is more advanced.
These bone marrow features are called megaloblastic.6 Giant and abnormally shaped
metamyelocytes are characteristic.16 There is also increase in hemosiderin in bone marrow.2
d.

LDL level
The ineffective erythropoiesis which occurred in folic acid deficiency anemia is

accompanied by intramedullary hemolysis causing an elevated lactate dehydrogenase (LDH)

and indirect bilirubin in the serum.6
3.

Specific Examination to Differentiate Folic Acid and Vitamin B12 Deficiency

a.

Serum Folate Levels

In folic acid deficiency anemia, the serum folate level is low (< 3 ng/ml).2 Although

tissue stores may be normal, serum folate levels can decrease within a few days of dietary
folate restriction.6 Besides that, recent folate intake in a previously folate-deficient individual
with normal absorptive capacity for folate could result in the misleading finding of an
apparently normal plasma folate.17 Thus, patients should fast prior to testing for serum folate
levels.6
Because of the high concentration of folate within the RBC, mild degrees of hemolysis
can falsely elevate serum folate levels. Pregnancy, certain anticonvulsant drugs, and alcohol
intake may also cause a decrease in serum levels despite adequate tissue stores. Serum folate
levels tend to be increased in patients with vitamin B12 (cobalamin) deficiency, presumably
because of impairment of the methionine synthase pathway and accumulation of
methyltetrahydrofolate, the principal form of folate in the serum.6
b.
RBC Folate
Because of the limitations of measuring serum folate, RBC folate levels have been
advocated as a more reliable source of measuring tissue stores of folate. RBC folate levels
remain constant throughout the lifespan of the cell and are not affected by short-term dietary
changes that can alter serum levels (Green R, 2008). In the condition of anemia of folic acid
deficiency, RBC folate falls. However, we should be careful because low RBC folate levels
have been reported with alcohol use, pregnancy and anticonvulsant medications. Another
important cause of low RBC folate levels is vitamin B12 deficiency. It is estimated that
approximately 60% of patients with pernicious anemia have low RBC folate levels,
presumably because vitamin B12 is necessary for normal transfer of methyltetrahydrofolate
from plasma to RBCs.6
B4 | Folate Deficiency Anemia

11

c.

Full clinically response to therapy with physiologic doses of folic acid

The occurrence of full therapeutic response following administration of a physiologic

dose of folic acid (i.e.,200-400 g daily) distinguishes folic acid deficiency from vitamin B12
deficiency, in which response to folic acid occurs only after pharmacologic doses (i.e., 5 mg
daily). The folic acid-deficiency patient is likely to have a spontaneous response to dietary
folic acid unless the hospital diet is restricted in vegetables and liver. Thus a long control
period, which includes the administration of vitamin B12 in small doses, is necessary for
definitive diagnosis by this method.11-14
d.
Elevated excretion of FIGlu after a loading dose of histidine
The elevation FIGlu excretion after a histidine-loading dose provides a useful and
simple test for folic acid deficiency. However, it is less specific diagnostically than serum
folate determination. It becomes abnormal later than serum serum folate and thus gives better
measure of tissues coenzyme level. Its greatest usefulness is in subjects taking antifolate
drugs, in whom serum folate levels may be normal and tissue coenzyme level drastically
reduced.13
e.
Methylmalonic Acid (MMA) and Homocysteine Serum Concentration
The conversion of homocysteine to methionine requires folate and vitamin B12 as
cofactors. However, the metabolism of L-methylmalonyl CoA to succinyl CoA, an enzymatic
pathway involved in oxidative phosphorylation reactions within the cell, only requires vitamin
B12. In cobalamin deficiency both of these metabolites are elevated. In folate deficiency
patients, serum homocysteine levels are markedly increased, while serum MMA levels are not
elevated. Therefore, MMA is more sensitive for identifying non-anemic cobalamin deficiency
patients than homocysteine.6 However, there both of these tests are not really specific and is
difficult to establish normal level in different age groups. These test also not widely
available.16
G.

Treatment and Management

An optimal hematologic response occurs if 50 to 100 microgram of folic acid is given

daily per oral. Such doses are useful for therapeutic trials and, in the absence of standard oral
preparations of these doses, may have to be prepared individually by dilution of parenteral
folate.
For replenish of stores, however, larger amounts are required. A daily dose of 1mg for
2-3 weeks should be ample, even in patients with malabsorption. A patient who fails to
respond to oral administration will probably not respond to injections. The parental forms are
useful chiefly for patients who are unable to take medications by mouth.
B4 | Folate Deficiency Anemia

12

Once stores are replete, the need for maintenance therapy must be considered in the
light of the underlying condition that produced the folate deficiency. If those conditions can
be corrected, normal dietary sources of folate should suffice. When the causative condition
cannot be reserved, such as when requirements are increased because of persisting severe
hemolytic anemia or in pregnancy; when malabsorption cannot be corrected, as by a gluten
free diet, or when dietary habits are inadequate and immutable, appropriate supplements in the
range of 0.25 to 0.5mg daily must be given.18
The overarching and long-term strategy recommended for the control of folate
deficiency is the consumption of a diet that meets the recommended intakes of these vitamins.
However, in populations where it is unlikely that diet will provide recommended intakes of
these nutrients, strategies such as supplementation and fortification should be considered.19
There are some strategies to improve folate intake:
1.

Diet
The many folate compounds are widely distributed in nature. Green leaves are rich

sources and presumably the sites of active synthesis. The richest vegetable sources are
asparagus, broccoli, spinach, and lettuce, each of which contains >1 mg of folate per 100 mg
day weight. Folates are also found in liver, kidney, yeast, and mushrooms. The vitamin is
synthesized by many bacteria. Sulfonamide drugs attack bacteria by interfering competitively
with the incorporation of p-aminobenzoic into pteroid acid, an intermediate that reacts with
glutamate in the presence of ATP to form pterylglutamate, the most commonly for therapy.12
2.
Supplementation
The usual recommendation for supplemental folic acid is 0.4 mg/day. The supplements can be
given daily, or as a larger dose less frequently, e.g., 0.4 mg folic acid daily versus 5 mg once
weekly.

3.
Fortification
The level of folic acid or vitamin B12 that should be added to food can be calculated based on
the prevalence of inadequate intakes in a sample of the target population(s).
H.

Prognosis
The hematologic response is similar to that seen after replacement of B12 deficiency.

Therere a brisk reticulocytosis after about 4 days, followed by correction of the anemia over
the next 1 to 2 months. The duration of therapy depends on the basis of deficiency states.
B4 | Folate Deficiency Anemia

13

Patients with a continuously increased requirement (such as hemolytic anemia) or those with
malabsorption or chronic malnutrition should continue to receive oral folic acid indefinitely.20

SUMMARY
Folic acid (pteroylglutamic acid) is a water soluble member of the B-complex family of
vitamins. Folic acid has function in DNA synthesize. Deficiency in folic acid lead to
disturbance of maturing DNA, make the cell become megaloblast. This megaloblast has short
life span because intramedullary hemolysis. The etiology of folate deficiency anemia maybe
come from several factor, there are impaired absorption, increase folate requirement, alcohol,
and other cause such as medications, sulfa drugs, anticonvulsant, and etc. To diagnose the
B4 | Folate Deficiency Anemia

14

anemia, comprehensive history, physical examination followed by appropriate laboratories

examination such as CBC, peripheral blood smear, bone marrow aspiration, RBC folate, and
MMA should be performed. To treat the patient, folic acid per oral should be given. Otherwise
if there is no preparation of folate per oral, or no respond from patient to medication, dilution
or per parenteral should be performed.

The

overarching

and

long-term

strategy

recommended for the control of folate deficiency is the consumption of a diet that meets the
recommended intakes of these vitamins. However, in populations where it is unlikely that diet
will provide recommended intakes of these nutrients, strategies such as supplementation and
fortification should be considered. The duration of therapy depends on the basis of deficiency
states. Patients with a continuously increased requirement (such as hemolytic anemia) or those
with malabsorption or chronic malnutrition should continue to receive oral folic acid
indefinitely.20

B4 | Folate Deficiency Anemia

15