Folic acid: properties – importance – Sources – amounts – Functions - deficiency

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]

 

 

 

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]

 

 

 

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.

 

 

 

References

1.      Ivan Robles (15-11-2010), "vitamin B11"، www.hopes.stanford.edu, Retrieved 12-11-2019. Edited.

2.     "VITAMIN B9", www.foodstandards.gov.scot, Retrieved 12-11-2019. Edited.

3.     Atli Arnarson (19-8-2019), "Folic Acid vs. Folate — What’s the Difference?"، www.healthline.com, Retrieved 5-10-2019. Edited.

4.     "Folic acid", pubchem.ncbi.nlm.nih.gov, Retrieved 19-5-2019. Edited.

5.     "Folate", www.ncbi.nlm.nih.gov,2013، Retrieved 19-5-2019. Edited.

6.     Erica Julson (19-10-2018), "Folic Acid: Everything You Need to Know"، www.healthline.com, Retrieved 19-5-2019. Edited.

7.     Blank Children's Hospital (7-1-2015), "18 Foods Filled with Folate Every Woman Should Know (Infographic)"، www.unitypoint.org, Retrieved 5-10-2019. Edited.

8.     Rachael Link (22-5-2018), "15 Healthy Foods That Are High in Folate (Folic Acid)"، www.healthline.com, Retrieved 5-10-2019. Edited."

9.     Folate Fact Sheet for Health Professionals", www.ods.od.nih.gov,19-7-2019، Retrieved 5-10-2019. Edited.

10.  "Vitamin B9 ", www.nutri-facts.org, Retrieved 5-10-2019. Edited.

11.  Carmen Fookes (10-1-2019), "Folic acid: 6 things you should know"، www.drugs.com, Retrieved 4-11-2019. Edited."

12.  FOLIC ACID", www.webmd.com, Retrieved 3-11-2019. Edited.

13.  Erica Julson (19-10-2018), "Folic Acid: Everything You Need to Know"، www.healthline.com, Retrieved 9-10-2019. Edited.

14.  SUSAN INCE (3-6-2019), "Taking Folic Acid with Methotrexate for Arthritis: 9 Things You Must Know"، CreakyJoints, Retrieved 4-11-2019. Edited

15.  .Adam Felman (27-10-2017), "What to know about folic acid"، www.medicalnewstoday.com, Retrieved 9-10-2019. Edited.

16.  Mayo Clinic Staff, "Folate (folic acid)"، www.mayoclinic.org, Retrieved 12-10-2019. Edited.

17.  "FOLIC ACID", www.rxlist.com, Retrieved 6-11-2019. Edited

18.   "Folic Acid", www.medicinenet.com, Retrieved 6-11-2019. Edited. ↑ John Forman, Eric Rimm, Meir Stampfer And Others (19-1-2005), "Folate Intake and the Risk of Incident Hypertension Among US Women", The Journal of the American Medical Association, Issue 3, Folder 293, Page 320-9. Edited.

19.  Lydia Bazzano, Jiang He, Lorraine Ogden And Others (1-5-2002), "Dietary Intake of Folate and Risk of Stroke in US Men and Women", Journal of the American Heart Association, Issue 5, Folder 33, Page 1183–1189.

20.  Juhlin L1, Olsson MJ (1997), "Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure", Acta Dermato-Venereologica, Issue 6, Folder 77, Page 460-462. Edited.

21.  Mohammad Yakoob, Zulfiqar Bhutta (13-4-2011), "Effect of routine iron supplementation with or without folic acid on anemia during pregnancy.", BMC Public Health, Issue S3, Folder 11, Page S21. Edited.

22.  Ford, Andrew, Almeida Osvaldo (2-3-2012), "Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials.", Journal of Alzheimer's Disease , Issue 1, Folder 29, Page 133-49. Edited.

23.  William Christen, Robert Glynn, Emily Chew And Others (20-1-2016), "Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women.", Ophthalmic Epidemiol, Issue 1, Folder 23, Page 32-9. Edited.

24.  Rebecca Schmidt, Daniel Tancredi, Sally Ozonoff And Others (7-2012), "Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study", The american journal of clinical nutrition, Issue 1, Folder 96, Page 80–89. Edited.

25.  Norra MacReady (24-8-2016), "Modest Doses of Folic Acid Slow CKD Progression"، www.medscape.com, Retrieved 5-11-2019. Edited.

26.  T Hartridge, H Illing, Sandy JR (26-6-1999), "The Role of Folic Acid in Oral Clefting", British Journal of Orthodontics, Issue 2, Folder 26, Page 115-20. Edited.

27.  Shiliang Liu, K S Joseph, Wei Luo And Others (30-8-2016), "Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes", (Public Health Agency of Canada, Issue 9, Folder 134, Page 647–655. Edited

28.  Jane Higdon, Linus Pauling Institute, Oregon State University (2000), "Folate"، lpi.oregonstate.edu, Retrieved 12-10-2019. Edited. "

29.  Folate (Folic Acid) – Vitamin B9", www.hsph.harvard.edu, Retrieved 12-10-2019. Edited.

30.  Jennifer Berry (29-5-2019)"What to know about folate deficiency"، www.medicalnewstoday.com, Retrieved 12-10-2019. Edited.

31.  Elaine Luo (31-7-2019), "Folate Deficiency"، www.healthline.com, Retrieved 12-10-2019. Edited.