Folic acid
Folic acid, or the so-called
vitamin B9, plays a key role in the production of new cells in the body, and it
also has a role in the metabolism of homocysteine, an amino acid linked to the
risk of cardiovascular disease and neurodegeneration, and folic acid is One of
the vitamins of the B group, and it is classified as a water-soluble vitamins,
which means that we need it daily in our diet, because it cannot be stored in
the body, and it is found in small quantities in many foods. [1,2]
It is worth noting that both
folate and folic acid are two different forms of vitamin B9; As folate is the
natural form found in food for vitamin B9, most of it is transformed in the
digestive system before entering the bloodstream into the active form of this
vitamin, or what is known as levomefolic acid or simply called 5-MTHF, while
folic acid is the synthetic form of it, and it is used In supplements, and in
manufactured food products such as flour and breakfast cereals, and unlike
folic acid, folic acid does not convert to its active form of vitamin B9 in the
digestive system, but rather this process occurs in the liver, and this
transformation may be less effective in some people, which may cause the
accumulation of acid in the body. Unchanged folate in the bloodstream causes
various health problems.[3]
Folic acid is one of the
water-soluble B vitamins, which are found in many foods, and is known by
several names, including folate, folacin, and petroleum-glutamic acid, and it
is one of the vitamins very necessary for the human body; For its role in the
formation of blood (hematopoiesis) and red blood cells. Folic acid is
characterized by its complex chemical structure, as it bears the molecular
formula (C19H19N7O6); Which means that it is made up of carbon, hydrogen,
nitrogen, and oxygen.[1]
Folic acid consists of three
compounds linked together; They are pyridine ring, para-amino-benzoic acid, and
glutamic acid.[2]
Folic acid properties
The following are the most
important physical and chemical properties of folic acid:[1]
1. Molecular weight: 441.404 g/mol.
2. Actual weight: 441.14 g/mol.
3. Normal condition: solid.
4. Taste and Odor: No taste or odor.
5. Colour: orange-yellow
crystals.
6. Melting point: 250 degrees Celsius.
7. Solubility:
solubility in water (1.6 g / liter at a temperature of 25 ° C), slightly
soluble in methanol, and to a lesser extent in ethanol and butanol.
8. Stability: Aqueous
solutions of folic acid are sensitive to heat, and degrade rapidly in the
presence of light and riboflavin. Folic acid crystals are also relatively
stable in alkaline solutions, but they are less stable in acidic solutions.
Importance of folic acid
The following are the most
important benefits that the human body obtains from folic acid: [3]
1. Eating folic acid during the first weeks of pregnancy
reduces the risk of neural tube defects in infants, including abnormalities of
the brain, spine, and spinal cord. It is worth noting that 90% of women suffer
from a lack of folic acid concentration; Therefore, all women of childbearing
age are advised to take at least 400 micrograms of folic acid daily.
2. Reducing the risk of developing some types of cancer;
Including breast, bowel, lung and pancreatic cancer, knowing that high doses of
folic acid can promote tumor growth in people who already have cancer.
3. Among its benefits, folic acid also controls high
levels of homocysteine in the blood; This reduces the risk of heart disease.
Sources of Folic Acid
Folate is available in many
different food sources, including: [4][5]
· Green leafy vegetables: They are one of the richest natural sources of this vitamin.
· Fortified foods: such as bread, pasta, and breakfast cereals; Fortified bread and pasta
contain twice the amount of folate before fortification, but when using
fortified breakfast cereals it is worth paying attention to the amount of sugar
they contain.
· Cooked lentils: Lentils contain high amounts of folate in addition to many important
nutrients such as iron, fiber, and slow-absorbing carbohydrates.
· Broccoli: Broccoli
is a rich source of folate, in addition to vitamin C, calcium, iron, and
dietary fiber.
· Asparagus:
Asparagus contains low calories and low levels of fat and is a rich source of
folate, calcium, and dietary fiber.
· White Beans: Most
types of beans are a rich source of many nutrients such as: protein, potassium,
calcium, folate, and dietary fiber.
· Cantaloupe: This
fruit contains ample amounts of folate in addition to vitamin C and vitamin A.
· Citruses: Citrus
fruits such as oranges, grapefruit, and lemons are rich in folate, in addition
to containing ample amounts of vitamin C.
· Okra and flower: They are rich sources of this vitamin, and the flower also contains
vitamin C.
· Seeds and nuts: such as sunflower seeds, flax seeds, peanuts, walnuts, and almonds.
· Corn and chickpeas: Corn and chickpeas are great sources of folate.
· Tropical fruits: such as bananas, mangoes, kiwis, pomegranates, papayas, and avocados.
· Liver and eggs: These foods are an abundant source of many vitamins, including folate.
· Beetroot: With its
red color, beetroot is a successful way to color food dishes and salads, in
addition to being a great source of folate, manganese, potassium, and vitamin C.
· Wheat germ: Wheat
germ is one of the food sources rich in many vitamins and fiber, including
folate, but it is worth noting that when making wheat flour, the wheat germ is
removed from it.
Recommended amounts of folic acid
This table shows the recommended
daily amounts (RDI) of folate for different age groups: [6]
Age
Group
|
Recommended
Daily Intake (mcg)
|
Infants
0-6 months
|
65 |
Infants
7-12 months
|
80
|
Children
1-3 years
|
150
|
Children
4 - 8 years
|
200
|
9-13 years old
|
300
|
14 years and over
|
400
|
Pregnant
|
600
|
lactating
|
500
|
Functions of folic acid
Eating adequate amounts of folic
acid is important for the body; It is considered a coenzyme in the following
processes: [7]
1. Use of amino acids; whereas, amino acids are the basic
units for building proteins.
2. Production of nucleic acids; It is the genetic
material in the body (DNA).
3. Formation of blood cells in the bone marrow.
4. Rapid cell growth in childhood, adolescence and
pregnancy.
5. Regulating levels of the amino acid homocysteine in the blood with the help of
vitamin B12 and vitamin B6.
6. Growth is normal for the mother's tissues during
pregnancy.
7. Normal metabolism in the immune system.
Benefits of folic acid according to the degree of effectiveness
Folic acid provides the body with
many health benefits, including:
Reducing folic acid deficiency: Eating folic acid improves its levels in the body.[8]
1. Likely effective
Reducing high levels of
homocysteine in the blood: (Hyperhomocysteinemia), as folic
acid enters the process of converting homocysteine into another compound called
methionine, so taking folic acid supplements contributes to reducing
homocysteine by between 20% to 30% in people who have normal levels or Slightly
higher than it, although this effect did not correspond to a decrease in heart
disease rates, and those who suffer from a large increase in homocysteine levels in the blood are
advised to take folic acid supplemented with vitamin B12, and it is worth
noting that homocysteine levels are high in about 85 On the other hand, there is insufficient
evidence to prove the benefit of folic acid in reducing the high levels of
homocysteine caused by fenofibrate. [9][10]
Reducing symptoms resulting from
the use of Methotrexate: This drug is used in low
doses to treat rheumatoid arthritis; These patients are advised to take folic
acid to reduce the symptoms that accompany the use of this drug, such as
stomach problems and mouth ulcers. Folic acid supplements are not recommended
for cancer patients who are being treated with this drug.[13][11]
Prevention of neural tube defects: Low levels of folate during the first weeks of pregnancy are associated
with congenital defects of the fetus, such as: malformations in the brain, spine,
or spinal cord. Their children with these defects are fewer. Since 90% of women
do not have sufficient folate levels to prevent neural tube defects, all women
of childbearing age are recommended to take at least 400 micrograms of folate
supplements daily.[9][10]
Possibly Effective
Reducing the risk of vision loss
due to age-related macular degeneration: Taking folate
in addition to other vitamins, including: vitamin B6 and vitamin B12, may
reduce the risk of age-related vision loss.[14]
Reducing symptoms of depression: There are some studies that have indicated that the use of folic acid
with antidepressant medications has improved symptoms associated with
depression. [14]
Reducing high blood pressure: taking folic acid daily for 6 weeks can contribute to reducing pressure
in patients with high blood pressure, but taking it with medications to reduce
pressure did not enhance their effectiveness, [15] On the other hand, a study
conducted at Harvard University in 2005 Women reported that eating more folic
acid reduced their risk of developing high blood pressure.[16]
Reducing the risk of stroke in
some areas: Taking folic acid may reduce the
risk of strokes in people who live in areas that do not fortify cereal products
with this acid,[9] and a study conducted at Harvard University and Brigham and
Women's Hospital revealed ) in 2002 that eating folate has reduced the risk of
stroke.[17]
Improving Vitiligo Symptoms: Taking folic acid orally can improve the symptoms of vitiligo,[15] and
a study conducted at Uppsala University Hospital indicated that it is possible
to take folic acid with vitamin B12 and exposure to the sun improve the
restoration of normal skin color in patients. Better than just exposure to the
sun.[18]
Possibly ineffective
Improving iron deficiency anemia
in the body: A study conducted at the Aga Khan
University in 2011 showed that taking folic acid with iron supplements does not
increase its effectiveness in treating iron deficiency anemia in pregnant women. [19]
Improve intellectual skills and
reduce their decline: A 2012 review at the University
of Western Australia showed that taking folic acid does not help reduce these
conditions.[20]
Reducing and preventing heart
disease: Taking folic acid alone or with vitamin B6
and vitamin B12 did not contribute to reducing the risk of death or health
complications in people with heart disease.[14]
Cataract disease: Taking folic acid with other supplements such as vitamin B6 and vitamin
B12 does not prevent cataract disease or the so-called cataract, but may
increase the need for cataract surgery.[21]
Reducing the risk of leukemia: Eating folate during pregnancy did not reduce the risk of leukemia in
children.[15]
Reducing the risk of stillbirths: or children who were born early; The intake of folic acid during
pregnancy had no role in reducing the risk of fetal death before birth or after
birth, and this vitamin is often ineffective in reducing the risk of premature
birth.[15][14]
There is insufficient evidence for its effectiveness.
Autism prevention: The results of studies are conflicting about this benefit, and a study
conducted at the University of California in 2012 showed that taking folic acid
in the early or pre-pregnancy period is likely to reduce the risk of autism
spectrum disorder for people with folate malabsorption. in the body.[22][12]
Slowing the progression of chronic
kidney disease: The intake of folic acid by those
who suffer from this disease is likely to contribute to slowing the progression
of the disease in countries whose products are not fortified with folic acid.[23]
Reducing epileptic seizures: taking folic acid does not reduce the frequency of epileptic seizures in
people with it, but some preliminary evidence indicates that it can reduce
these seizures in children with a deficiency of this vitamin.[9]
Reducing the risk of deafness: Taking folic acid may reduce the progression of hearing loss in elderly
people who suffer from low levels of folate, but it is not known whether it
reduces this condition in people with normal levels of it.[9]
Reducing the risk of cleft lip
defects: A review published in the British Journal of
Orthodontics in 2014 showed that taking folic acid supplements may reduce the
risk of cleft lip.[24][12] While other studies have shown that folic acid does
not have this effect.[9]
Reducing the risk of congenital
heart defect: A 2016 study conducted by the
Public Health Agency of Canada showed that women's intake of folic acid is
likely to reduce the risk of having children with congenital heart disease.[25]
Possibility of contributing to
improving the weight of the fetus: taking folic
acid during pregnancy does not prevent the birth of children with a lower
weight than normal, but it can improve the average birth weight of children.[9]
Reducing the risk of pre-eclampsia: There is little evidence to suggest the benefit of folic acid in
reducing the risk of pre-eclampsia; It is a condition in which a pregnant
woman's blood pressure rises, in addition to the appearance of a percentage of
protein in her urine during pregnancy.[9]
Folic acid deficiency
Inadequate intake of folate in the
diet leads to a decrease in its levels in the blood, and here are some other
reasons for this deficiency, in addition to its symptoms, complications and
treatment: [26]
1. The reasons:
Folate deficiency is rare; Because
it is present in a wide range of foods, however, some conditions that are
likely to increase the risk of deficiency, including: [26][27][12]
1. Pregnancy; As the
need for folate increases during pregnancy; Because it plays an important role
in the development of fetal cells.
2. Intestinal surgeries or digestive disorders
that cause malabsorption; As having wheat allergy or
inflammatory bowel disease can lead to malabsorption of folate, as well as
surgeries in the digestive system or operations that reduce the normal level of
stomach acid may reduce its absorption.
3. Use of certain medications that affect the absorption and levels of folic acid.[28]
4. Genetic variants; People who carry a type of gene known as MTHFR cannot convert folate
into its active form for use by the body.[28]
5. Smoking and alcoholism; Smoking and alcohol interfere with the absorption of folate and
accelerate its breakdown and excretion from the body, and alcoholics tend to
eat low-quality meals that do not contain good amounts of folic acid.[27]
2. Symptoms:
Symptoms of folic acid deficiency
may usually be subtle, and include the following:[29][28]
1. Fatigue and weakness.
2. Gray hair.
3. Sores in the mouth or on the tongue.
4. Tongue swelling.
5. Growth problems.
6. Headache.
7. Difficulty concentrating.
3. Complications:
This deficiency may increase the
risk of pregnant women having a child with neural tube defects, and in some
cases, it is possible to lead to a type of anemia called megaloblastic anemia,
which can reduce the delivery of oxygen to the body's organs and tissues. It
may lead to problems in the development of the fetus during pregnancy,
including serious abnormalities of the brain and spinal cord or low birth
weight.[29][28]
4. Diagnosis and treatment:
It is not possible to rely solely
on symptoms to diagnose folic acid deficiency; Therefore, a comprehensive blood
count test and other tests are used that show the number and shape of red blood
cells, and red blood cells in people with folic acid deficiency are usually
large and incomplete, and the treatment of deficiency is by increasing the
dietary intake of folate, and folic acid supplements can be taken, and people
with People with a genetic mutation known as (MTHFR) need to take methyl folate
supplements to avoid deficiency.[29][28]
Increased folic acid
It is very rare for people to
reach the toxicity level of folate from food sources. As for supplements, users
should not take more than one milligram; i.e. 1,000 micrograms daily; As taking
large doses of it may be harmful, and it can mask vitamin B12 deficiency in the
body, and in this case, if large amounts of folate are continued, it will mask
the symptoms of vitamin B12 deficiency for a long time, and may cause
irreversible damage to the brain and nervous system. [27][2]
The following table shows the
Tolerable Upper Intake Levels for folate from supplements or fortified foods
for different age groups: [6]
Age
Group
|
Maximum
Tolerable Daily (µg)
|
Infants
0-12 months
|
cannot
be determined
|
Children
1-3 years old |
300
|
Children
4 - 8 years
|
400
|
9-13 years old
|
600
|
14-18 years old |
800
|
19 years and over
|
1000
|
Folic acid supplements
It is preferable to obtain folate
from food sources for most people, and a balanced diet can provide the body’s
need for it most of the time, however it is recommended to use folic acid
supplements for pregnant or planning women, as well as for lactating women, and
folic acid supplements can also be prescribed for people Those who do not
follow a balanced diet, or who suffer from some conditions that interfere with
the body's ability to absorb folate. In general, folic acid supplements are
likely to be safe when used orally in appropriate doses, but they may cause
some potential side effects and drug interactions, including: [13]
Side effects: including the following:
1. Nausea.
2. Anorexia.
3. Feeling of bad taste in the mouth.
4. Suffering from sleep disturbances.
5. The emergence of allergic symptoms in some people who
suffer from allergies to folic acid supplements, and it is recommended to
consult a doctor urgently in the event of these symptoms, including: rash,
itching; skin redness; and difficulty breathing.
Drug interactions: Taking folic acid supplements may interact with many medications,
including:
1. Anticonvulsants; Taking folic acid with these medications may reduce the concentration
of the drug in the blood.
2. barbiturates; Taking
folic acid with this drug, which acts as a central nervous system depressant,
may reduce its effectiveness.
3. Pyrimethamine; It is an antimalarial medicine, and taking folic acid with this
medicine can reduce its effectiveness.
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