Folic Acid

Folic acid or Vitamin B9 also called Pteroylglutamic Acid, Folate, or Folacin, is a vitamin of the B complex group that is essential for the metabolic processes going on in our body. Folic acid is important in the utilization of proteins (amino acids). It is also involved in one carbon metabolism including the methylation of homocysteine to L-methionine and DNA synthesis. Folic acid also plays an important role in pregnancy.

All B vitamins help the body convert food (carbohydrates) into fuel (glucose), which is burned to produce energy. B complex vitamins are necessary for healthy skin, hair, eyes, and liver. They also help the nervous system function properly.

The word 'folate' derives from the latin 'folium' ('a leaf'). It was first discovered in 1946 to be important in the prevention and treatment of anaemia. Folate is the form of a particular B vitamin found in foods. Folate is the generic term for all forms of this vitamin. Folic acid is the man-made or synthetic form of the vitamin. It is found in fortified foods (a food to which folic acid has been added) and vitamin supplements (a small pill that contains only folic acid). Folic acid is better absorbed and more readily available to the body than folate. In fact, the body absorbs only about 50% of the folate in food. In contrast, about 85% to 95% of the folic acid from supplements and fortified foods is absorbed. Folic acid needs vitamin C, niacin, and vitamin B12 in order to be converted to its biologically active form.

Nutritionists categorize vitamins by the materials that a vitamin will dissolve in. There are two categories: water-soluble and fat-soluble vitamins. Water-soluble vitamins, which include the B-complex group and vitamin C, travel through the bloodstream. Whatever water-soluble vitamins are not used by the body are eliminated in urine, which means you need a continuous supply of them in your food. Vitamin B9 is a water-soluble vitamin.

A deficiency of folic acid can occur when the need for folic acid is increased and when the body excretes (or loses) more folate than usual. The most common folic acid deficiency cause is inadequate daily intake from foods. This may be from a lack of fresh green vegetables, legumes, and enriched grains or from food processing or preparation. Prolonged storage and cooking can cause a 50% to 95% loss of folate.

Other factors that may cause folic acid deficiency are:
• Chronic Alcoholism: Alcohol interferes with the absorption of folic acid and increases excretion of folic acid by the kidney. In addition, many alcohol abusers have poor quality diets that do not provide the recommended intake of folic acid.
• Malabsorption diseases i.e. inadequate absorption of folic acid due to  celiac disease and gastric diseases that cause low stomach acid
• Pharmaceuticals: some drugs may such as anticonvulsant medications and oral contraceptives may impair folic acid absorption and inhibit folate metabolism
• Acquired folic acid malabsorption: a rare hereditary folate malabsorption
• Pregnancy, lactation and infancy, malignancy (e.g. cancer), chronic haemolytic anaemia: all have an increased the requirement of folic acid
• Kidney dialysis and liver disease (e.g. cirrhosis): increases folic acid excretion
• Other nutrient deficiencies: zinc, riboflavin (vitamin B2), niacin (vitamin B3) and vitamin B12. These may affect folate absorption and metabolism
• Age: the elderly are more susceptible due to low intake, malnutrition and existing medical conditions.
• Elevated homocysteine levels in the blood

Some other possible medical causes of folate deficiency
o Bacterial overgrowth of small intestine
o Paraneoplastic syndrome
o Blind loop syndrome

Medications that interfere with your body's ability to use folate may also increase the need for this vitamin. Medications which can interfere with folate utilization include:
• anti-convulsant medications (such as dilantin, phenytoin, and primidone)
• Metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
• Sulfasalazine (used to control inflammation associated with Crohn's disease and ulcerative colitis)
• Triamterene (a diuretic)
• Methotrexate. (used for cancer and other diseases such as rheumatoid arthritis)
• barbiturates (used as sedatives)
• Cimetidine
• Antacids

Deficiency of folic acid can be precipitated by situations wherein the body requires greater than normal amounts of the vitamin, such as pregnancy, infancy, leukaemia, exfoliative dermatitis, and diseases that cause the destruction of blood cells.

Folic acid deficiency symptoms may very subtle at first, and that can make this vitamin deficiency difficult to diagnose unless a patient and doctor are specifically looking for it. Some early signs of deficiency include:
• Loss of appetite
• Anaemia
• Mental confusion
• Difficulty focusing
• Depression
• Palpitations
• Shortness of breath
• Hair loss
• Poor growth
• Chronic fatigue - macrocytic / megaloblastic anaemia
• Sore tongue
• gingivitis
• Headaches
• Anxiety and irritability
• Digestive problems like stomach pains, diarrhoea, and impaired nutrient absorption
Women with folate deficiency who become pregnant are more likely to give birth to low birth weight and premature infants, and infants with neural tube defects. In adults, anaemia is a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate. Some of these symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

The Three Stages of Folic Acid Deficiency
At the first stage of deficiency the plasma folate levels fall. If the diet does not contain adequate folate, the red blood cell (RBC) folate levels drop after three to four months. With continuing deficiency, the bone marrow cells and other cells become affected. This is stage three, the clinical stage of folic acid anaemia. It occurs after approximately four to five months of deficiency. Folic acid functions in DNA synthesis and therefore cell division. Without this important vitamin, cells such as red blood cells produced in the bone marrow, fail to divide properly. RNA continues to form and build up producing excess haemoglobin. The RBC becomes an immature enlarged non-functioning cell often containing excess haemoglobin.  This folic acid anaemia is calld megaloblastic anaemia.

Folic acid deficiency poses a number of clinical and diagnostic challenges because in the early stages there may be no obvious signs of deficiency. It may take four months before any signs or symptoms. Doctors ask about the patient’s symptoms and medical history, and perform a physical exam. He or she will also perform simple blood tests to confirm a diagnosis of megaloblastic anaemia, and most importantly, determine the cause of the anaemia. It is difficult to distinguish between folic acid deficiency and vitamin B12 deficiency as both deficiencies result in megaloblastic anaemia. Therefore, it is very important to rule out vitamin B12 deficiency before taking folic acid supplements for anaemia. Mistreating an actual vitamin B12 deficiency with supplemental folic acid will mask the vitamin B12 deficiency, meaning the anaemia will be corrected, but the neurological damage associated with vitamin B12 deficiency will progress. In addition, the factors that lead to folate deficiency, such as poor diet, malabsorption and alcoholism, affect other nutrients as well, so singling out folic acid as the cause is often difficult.
However, folic acid deficiency is confirmed only by measuring red blood cell (RBC) folate levels in the blood.

Testing for Folic Acid Deficiency
Serum folate levels reflect recent changes in folate intake whereas RBC folate measures the folate stored in the body. RBC folate is a more reliable test. These tests are available through a standard blood test from the doctor. High homocysteine levels may also reflect low folate status but it may also be indicative of vitamin B12 and vitamin B6 deficiency.
Blood tests may include the following:
a) Haemoglobin—will be lower than normal if any type of anaemia is present
b) Mean corpuscular volume (MCV)—measures the size of the red blood cell and will be larger than normal if folic acid deficiency is present
 c) Colour of the red blood cell—will be normal if folic acid deficiency is present
 d) Serum folic acid—values of less than 5 mg/ml suggest a folic acid deficiency
 e) Red blood cell (RBC) folate—low levels confirm a diagnosis of folic acid deficiency

Getting enough folate during pregnancy lowers the risk of neural tube defects in newborns. Neural Tube Defects can manifest themselves as a number of different conditions upon birth, including spina bifida and anencephaly. Spina bifida is a condition where the spine of the baby is left open. This is because the neural tube does not close in the embryonic stage. The developing brain or spinal cord is exposed to the amniotic fluid in the woman's uterus.This condition may result in the paralysis of the lower limbs, poor cognitive development and poor bladder control. Anencephaly is another serious condition where the brain and the skull of the child is under developed. Such children are born still or do not survive for more than a few days after birth
Folate is crucial during the first 18 to 30 days of pregnancy. The baby's brain and spinal column are in a critical stage of development during this period. A woman may not even know that she is pregnant at this early stage. Many pregnancies are unplanned, which makes it very important for women to consume enough folate before conception. Supplementing folic acid, especially in the first trimester of pregnancy, is a mother's best way of being proactive and protecting her child against certain birth defects. Folic acid deficiency also results in macrocytic anaemia of pregnancy. This is because blood volume increases during pregnancy. At the same time there is increased urinary folate excretion and decreased intestinal absorption of folate leading to its deficiency
There are other complications, too, which may be avoided if folic acid intake is sufficient, and these include:
Cleft lip and palate
 Limb defects
 Heart defects
 Blood clots
 Placental abruption
Folic acid is a form of the B vitamin that aids in the regular cellular development and regeneration, and is especially crucial within the first weeks of the unborn baby’s development. It helps to ensure proper formation of the brain and spinal cord, without which there is a higher chance of miscarriage, and a 1 in 1000 chance that the child will end up with a Neural Tube Disorder (NTD).
It is important to know that folic acid is a water-soluble vitamin, thus the body will naturally flush out excess quantities present in the system and will not harm the mother or the baby

Homocysteine is a by-product of the metabolizing of protein that we take in our food. More specifically it is released when the body breaks down methionine, an amino acid and a component of protein. Homocysteine is toxic to the lining of our blood vessels and though it is a part of the breakdown process of protein, normally we have enough folic acid present in our systems to help convert homocysteine into another compound. Those who have a deficiency of folic acid can also develop a high level of homocysteine over long periods of time. So by taking folic acid it is possible to help prevent a build up of homocysteine in the blood. The damage to the blood vessel walls caused by homocysteine leads to arteriosclerosis or a stiffening of the walls.  Arteriosclerosis can lead to other cardiovascular diseases by making the heart pump harder and keeping parts of the body from getting enough blood and oxygen. This also leads to an increased risk of heart attack.
Hence, anyone suffering from high cholesterol, should ask the doctor to check their homocysteine blood level, as high levels of this substance with the added problem of high cholesterol can multiply the risk of suffering from heart problems. Homocysteine levels seem to be lower in people who get plenty of folate or folic acid in their diets.

B vitamins, along with folic acid are probably the best hair vitamins because they facilitate in transport of haemoglobin (the iron containing part of your red blood cells). Thus, they are primarily responsible for carrying oxygen from the lungs into the other parts of the body, including the hair.
Healthy and strong hair depends on the constancy of the supply of oxygen and blood in the hair and scalp areas. Folic acid also maintains hair thickness and colour.
Excessive hair loss can be curtailed if increased amounts of iron along with B-vitamins, particularly folic acid and vitamin B12 is taken.

Adults, women and men alike, experience health benefits from regular folic acid intake as well. Individuals who take adequate amounts of folic acid experience:
• Proper cellular division and proper formation of haemoglobin
Folic acid is required for DNA synthesis and cell growth and is important for red blood cell formation, energy production as well as the forming of amino acids. Folic acid is essential for creating haeme, the iron containing substance in haemoglobin, crucial for oxygen transport.
It is important for healthy cell division and replication, since its involvement as coenzyme for RNA and DNA synthesis. It is also required for protein metabolism and in treating folic acid anaemia. The body needs it to produce red blood cells, as well as norepinephrine and seratonin (chemical components of the nervous system).
• Reduced risk of heart attack and stroke
It does appear to decrease chances of people getting high blood pressure because it relaxes blood vessels. Due to lower blood pressure, the supplement may be indicated as good stroke prevention.
• Protection against certain types of cancer, including colon and cervical cancer
• Possible reduced risk of Alzheimer’s disease
• Folic acid also assists in digestion
• Helps in improving mental as well as emotional health. It helps make DNA (the body's genetic material), which normalises the brain's functions, and is a critical component of spinal fluid.
• Reduced chances of arthritis
• Low risk of Osteoporosis
• Reduced signs of aging by helping people to retain memory and mental activity
• Women on birth control pills or busy with hormone replacement therapy may benefit from folic acid
• Children benefit if they are on goat’s milk instead of cow’s milk.

The recommended dietary allowance (RDA) of folic acid for women planning a baby and those already pregnant is 400 mcg daily. Most pregnancies in India are not pre-planned and little attention is paid to the importance of a proper prenatal diet. Few women are aware that folic acid supplements should be taken prior to conception and during the first 12 weeks for all pregnancies.
Women, who have had one child with a neural tube defect, have a higher risk of having another child with the same disability. In this case, and for those who are prescribed certain medications, doctors will prescribe these women to take a much higher dose of folic acid -- a five milligram (mg) tablet -- starting one month before conception, if possible, and continuing through the first three months of pregnancy. If possible, it is important that the supplements are taken before conception because development is rapid and the foetus's neural tubes close during the first four weeks of pregnancy.

How much is needed
• For most women the recommended dosage for everyday health and pre-pregnancy preparation is 400 micrograms per day. Because spina bifida and similar birth defects occur in the first two weeks of pregnancy, women need to build up their folate stores long before they become pregnant. Once they realize they are pregnant, it is too late. After conception the dosage should be increased to at least 600mcg, however the doctor may recommend 1000mcg, and most prenatal vitamins contain this amount. If  any of the risk factors for NTDs are exhibited it might be beneficial to take 4000 micrograms, up to 10 times the normal dosage. Discuss any potential problems with the doctor and he or she will help determine if an increased dosage is essential
• Adult men and older women need 400 micrograms (μg) of folate.
• For individuals unable to get enough folic acid from the diet, a vitamin supplement is strongly recommended.
• Grain foods and breakfast cereals contribute over 62 percent of dietary folic acid. Most people (except pregnant women) should be able to get adequate folic acid from their diet.
It is important to check with a knowledgeable health care provider before taking folic acid supplements or giving them to a child.
Daily recommendations for dietary folic acid are listed below:
• Infants under 6 months: 65 mcg (adequate intake)
• Infants 7 - 12 months: 80 mcg (adequate intake)
• Children 1 - 3 years: 150 mcg (RDA)
• Children 4 - 8 years: 200 mcg (RDA)
• Children 9 - 13 years: 300 mcg (RDA)
• Adolescents 14 - 18 years: 400 mcg (RDA)
• 19 years and older: 400 mcg (RDA)
• Pregnant women: 600 mcg (RDA)
• Breastfeeding women: 500 mcg (RDA)
Amounts recommended for heart disease range from 400 - 1,200 mcg. However, high levels of folate can mask a vitamin B12 deficiency, and should be taken only under a doctor's supervision.

Can One Have Too Much or Too Little?
Regarding whether or not one should take Vitamin B9 supplements, it should be noted that folic acid is water-soluble (one absorbs only about half of the folic acid one eats), and is easily destroyed by microwaving, processing, overcooking, or reheating. This makes it hard to get the RDA from diet alone. Interestingly, folic acid found in most vitamin supplements is more efficiently absorbed into the blood than folate. Because of this, the Food and Nutrition Board of the Institute of Medicine created a unit called the Dietary Folate Equivalent (DFE).
• 1 microgram (mcg) of folate found in food provides 1 mcg of DFE
• 1 mcg of folic acid taken with meals or within a fortified food provides 1.7 mcg of DFE
• 1 mcg of folic acid (supplement) taken on an empty stomach provides 2 mcg of DFE
However, it is important to note that although folic acid is absorbed into the blood more efficiently than folate found in whole foods, folic acid requires the presence of vitamin C, niacin, and vitamin B12 in order to be converted to its biologically active form.
On a practical level, this means that if one is eating a nutrient-dense, whole food, minimally processed diet, then taking a folic acid supplement can help one meet one’s daily needs, for then there will be sufficient availability of vitamin C, niacin, and vitamin B12. This is particularly relevant to a pregnant and/or nursing mom, as the rapidly dividing cells of a growing baby increases a mom's requirement for folate.

Interaction between Folic acid and Vitamin B12 : Intake of supplemental folic acid should not exceed 1,000 micrograms (μg) per day to prevent folic acid from triggering symptoms of vitamin B12 deficiency. Folic acid supplements can correct the anaemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12deficiency is not treated.
It is very important for older adults to be aware of the relationship between folic acid and vitamin B12because they are at greater risk of having a vitamin B12 deficiency.It is advisable to consult a physician to check the B12 status before taking a supplement that contains folic acid if one is 50 years of age or older. When taking a supplement containing folic acid, read the label to make sure it also contains B12 or speak with a physician about the need for a B12 supplement.
It is always better to take vitamins and minerals together rather than on their own. This has been shown to be the best way to yield the optimal health benefits for your body, for many reasons:
1) Many vitamins and minerals work synergistically together, and in fact some cannot work at all without each other.
For example, although folic acid is essential for the body, long term use can decrease the amount of zinc and Vitamin B12 in the body. So it is important to take zinc and Vitamin B12 with folic acid.
2) Many vitamins, minerals and other nutrients can enhance the therapeutic benefits of each other.
For example, folic acid can help prevent heart disease much more effectively with cholesterol lowering nutrients such as policosanol, and ginger extract that can improve circulation.
3) Folic acid is more effective when taken with the B group vitamins – especially vitamin B12 and vitamin B6. Vitamin C is also good to have around folic acid.

Other possible Interactions:
If you are currently being treated with any of the following medications, you should not use folic acid supplements without first talking to your health care provider.
1) Antibiotics, Tetracycline -- Folic acid should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. Folic acid either alone or in combination with other B vitamins should be taken at different times from tetracycline. (All vitamin B complex supplements act in this way and should therefore be taken at different times from tetracycline.)
2) Drugs That Lower Levels of Folic Acid -- These drugs may interfere with the body's absorption of folate, and may mean you need to take a folic acid supplement. Consult your doctor first.
o Antacids, H2 blockers, proton pump inhibitors
o Bile acid sequestrants
o Carbamazepine
o Nonsteroidal anti-inflammatory drugs (NSAIDs)
o Sulfasalazine
o Triamterene
When taken for long periods of time, these medications, as well as other anti-inflammatory medicines, can increase the body's need for folic acid.
3) Birth Control Medications, Anticonvulsants, and Cholesterol-lowering Medications -- Birth control medications, anticonvulsants for seizures (namely, phenytoin and carbamazapine), and cholesterol-lowering medications (namely, bile acid sequestrants, including cholestyramine, colestipol, and colesevelam) may reduce the levels of folic acid in the blood, as well as the body's ability to use this vitamin. When taking any of these medications, your doctor may recommend taking extra folate. When taking bile acid sequestrants for cholesterol, you should take folate at a different time of day.
4) Methotrexate -- Methotrexate, a medication used to treat cancer, rheumatoid arthritis (RA), and psoriasis, reduces the amount of folic acid in the body. People who take methotrexate for RA or psoriasis may be prescribed higher doses of folic acid, which helps reduce the side effects of methotrexate. People taking methotrexate for cancer, however, should avoid folic acid supplements unless directed by their doctor because folic acid may interfere with methotrexate's effects on cancer.

The side effects of folic acid are not very common. Some people have reported experiencing mild side effects which usually occur with relatively large doses of folic acid supplements. These mild side effects include nausea, insomnia, decreased appetite, flatulence, abdominal distension, difficulty concentrating and some bitter taste in the tongue. If there are severe side effects to Folic acid such as difficulty breathing, closing of the throat, swelling of lips, tongue or face, or hives then immediately seek medical attention and stop taking the Folic Acid. Other side effects that have been noted include fever, general weakness or discomfort, reddened skin, shortness of breath, skin rash or itching, and wheezing and they can vary in severity.
It has been said that taking too much folic acid can lead to B-12 deficiency masking that can possibly lead to irreversible damage. Also, overdose can be quite dangerous to epileptics as they have been seen to cause seizures. Allergic reactions have also been reported in a few cases.
However, generally speaking, there is no report of excess folic acid toxicity in men and women. Because folate is a water-soluble vitamin that does not get stored in your fat tissues, there is little chance that one can consume toxic levels of folate or folic acid. In fact, folic acid intake of up to 20 grams per day reportedly does not cause any dangerous side effects. But, nevertheless it is best to seek a doctor's advice and follow the prescribed dose.

1 large orange: 54 mcg
large hard-boiled egg: 22 mcg
medium sized papaya: 115 mcg.
2 spears steamed broccoli: 61 mcg
1/2 cup chickpeas: 140 mcg
1/2 cup cooked spinach: 130 mcg
3/4 cup cooked white rice: 60 mcg
1 cup tomato juice: 50 mcg
11 Brussels sprouts: 127 mcg
1/2 cup cooked lentils: 175 mcg
1 cup Macaroni, cooked: 140-160 mcg
I cup noodles cooked: 160 mcg
large jacket potato: 39 mcg
4 tbsp black eyed beans: 220 mcg
1/2 cup kidney beans: 115 mcg
7 tbsp bran flakes: 113 mcg
25g / 1oz wheat germ: 100 mcg
4 spears steamed or boiled asparagus: 88 mcg
75g / 3oz tinned salmon: 17 mcg
fortified breakfast cereals: 100-400 mcg (read labels)
Enriched wheat tortilla 98/one 8” tortilla
Whole wheat tortilla 24/one 8” tortilla
Enriched white bread 39/slice
Enriched pasta, cooked 92/half cup
Whole wheat bread 14/slice
Whole wheat pasta 23/half cup
Sunflower seeds, dry-roasted 152/half cup
Okra, cooked 37/half cup
Orange juice 60-100/cup
Spinach, raw 58/cup
Asparagus 110/5 spears
Collards, frozen 88/half cup
Grapefruit/pineapple juice 23/cup

Other sources:
a) Vegetables Leafy green vegetables are a good source, so try to have a large bowl of salad daily. Other folate rich vegetables are peas, corn, cauliflower, green pepper, beetroot, mustard greens, ladyfinger.
b) Nuts such as almonds, cashew nuts, peanuts, walnuts, sesame seeds.
c) Legumes like soya bean, lobhia, kidney beans, dried peas, chickpeas, lentils.
d) Fruits  such as strawberries, honeydew or cantaloupe melons, bananas, pineapple, papaya, oranges, raspberries.
e) Grains Whole grain flour and pasta, whole meal bread, oats.

Hence in addition to a supplement, one can make a few small changes to the diet by:
• Including orange juice at breakfast or chopped fruit with your breakfast cereal.
• Adding a fresh green leafy salad at lunch.
• Choosing a bowl of fruit salad at snack time.
• Including a serving of stir-fried vegetables in sesame oil at dinnertime.
Remember delicate folic acid in foods is destroyed by overcooking, so cook in a covered pan with the minimum amount of boiling water. Try to eat vegetables lightly steamed, microwaved, or raw.

To get the most vitamins possible from food refrigerate fresh produce and keep milk and grains away from strong light. Vitamins are easily destroyed and washed out during food preparation and storage. Vitamin supplements should be stored at room temperature in a dry place that’s free of moisture.

Thus, folic acid is an integral component of several enzymatic functions in the human body. It is also vital to the formation of red blood cells and without it the development of bone marrow would be stunted. Folic acid is also useful in the proper functioning of the entire central nervous system. However, the most important function of folic acid is in growth and reproduction. Without folic acid, the manufacture of nucleic acids - the stuff cells are made of - would not be possible. Hence it can be safely said that the good effects of folic acid certainly outweigh its possible side effects and gives the body much more benefit than harm.

Article 5/71.
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