Vitamin B9

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Brief description

Folic acid is a water-soluble vitamin. She is also known as folate and vitamin B-9… Plays an important role in the process of division and creation of cells in some organs and bone marrow. A key function of folic acid is also to help shape the spinal cord and nervous system of the fetus in the womb. Like other B vitamins, folic acid promotes energy production in the body.

In our body, coenzymes of vitamin B9 (folate) interact with one-carbon units in a variety of reactions that are vital for the metabolism of nucleic acids and amino acids. Folate is needed to maintain the vital activity of all cells.

The terms folate, folate and vitamin B9 are often used synonymously. While folate is present in both food and the human body in a metabolically active form, folate is often used in vitamin supplements and fortified foods.

Other names: folic acid, folacin, folate, pteroylglutamic acid, vitamin B9, vitamin Bc, vitamin M.

Chemical formula: C19H19N7O6

Vitamin B9 rich foods

Indicated approximate availability in 100 g of product:

Turkey liver677 μg
Edamame beans, frozen303 μg
Romaine salad136 μg
Pinto beans118 μg
+ 28 more foods rich in vitamin B9 (the amount of μg in 100 g of the product is indicated):
Rukola97Red beans, cooked47Celery36Honey melon19
Flaxseeds87Chicken egg47Orange30kohlrabi16
Avocado81Almonds44Kiwi25A tomato15
Broccoli63White cabbage43Strawberries24Potatoes15
Curly cabbage62Mango43Raspberry21grapefruit13
Brussels sprouts61Corn42Banana20Lemon11
Cauliflower57Papaya37Carrots19Bell pepper10

Daily requirement for vitamin B9

In order to establish the daily intake of vitamin B9, the so-called “food folate equivalent“(In English – DFE). The reason for this is the better absorption of synthetic folic acid compared to natural folate obtained from food. PFE is calculated as follows:

  • 1 microgram of folate from food equals 1 microgram of PPE
  • 1 microgram of folate taken with or from food fortified equals 1,7 micrograms of PPE
  • 1 microgram of folate (a synthetic dietary supplement) taken on an empty stomach equals 2 micrograms of PPE.

For example: From a meal containing 60 mcg of natural folate, the body receives 60 mcg of Food Equivalent. From a serving of 60 mcg of Synthetic Folic Acid Fortified Pasta, we get 60 * 1,7 = 102 mcg Food Equivalent. And one 400 mcg folic acid tablet will give us 800 mcg of Food Equivalent.

In 2015, the European Scientific Committee on Nutrition established the following daily intake of vitamin B9:

AgeRecommended Amount Male (mcg Dietary Folate Equivalent / day)Recommended Amount, Female (mcg Dietary Folate Equivalent / day / day)
7-11 months80 μg80 μg
1-3 years120 μg120 μg
4-6 years140 μg140 μg
7-10 years200 μg200 μg
11-14 years270 μg270 μg
15 years and older330 μg330 μg
Pregnancy600 μg
Lactating500 μg

Due to the fact that vitamin B9 plays a very important role in pregnancy, the daily intake for pregnant women is several times higher than the usual daily requirement. However, embryonic neural tube formation often occurs before a woman even knows she is pregnant, and it is at this point that folic acid can play a critical role. For this reason, some experts recommend regularly taking vitamin courses that contain 400 mcg of folic acid. It is believed that even with such a dose and the use of foods containing folate, it is almost impossible to exceed the maximum safe amount of vitamin B9 per day – 1000 mcg.

Increasing the body’s need for vitamin B9

Generally, severe B9 deficiency in the body is rare, however, some populations may be at risk of deficiency. These groups are:

  • people with alcohol addiction: alcohol disrupts the metabolism of folate in the body and accelerates its breakdown. In addition, people with alcoholism are often malnourished and do not get enough vitamin B9 from food.
  • women of childbearing age: Women who are fertile should take enough folic acid to avoid the development of a neural tube defect in the embryo in the early stages of pregnancy.
  • pregnant women: During pregnancy, vitamin B9 plays an important role in the synthesis of nucleic acid.
  • people with poor digestibility: Diseases such as tropical fever, celiac disease and sore bowel syndrome, gastritis, may interfere with folate absorption.

Chemical and physical properties

Folic acid is a yellow crystalline substance, slightly soluble in water, but insoluble in fatty solvents. Resistant to heat only in alkaline or neutral solutions. Destroyed by sunlight. Has little or no odor.

 

Structure and shape

Dietary folates exist predominantly in the polyglutamate form (containing several glutamate residues), while folic acid, a synthetic vitamin form, is monoglutamate, which contains only one glutamate portion. In addition, natural folate is a reduced molecular weight molecule, while folic acid is completely oxidized. These chemical differences have serious implications for the bioavailability of the vitamin, with folic acid being significantly more bioavailable than naturally occurring dietary folate at equivalent intake levels.

Folic acid molecule consists of 3 units: glutamic acid, p-aminobenzoic acid and pterin. Molecular Formula – C19H19N7O6… The various B9 vitamins differ from each other in the amount of glutamic acid groups present. For example, folic acid contains one Lactobacillus casei fermentation factor three and a Bc conjugate of 7 glutamic acid groups. Conjugates (i.e., compounds having more than one glutamic acid group per molecule) are ineffective in some species because these species lack the enzyme required to release the free vitamin.

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Useful properties and effects on the body

The benefits of vitamin B9 for the body:

  • affects the course of a healthy pregnancy and the correct development of the fetus: folic acid prevents the development of defects in the nervous system of the fetus, underweight, premature birth, and this occurs in the earliest stages of pregnancy.
  • antidepressant: folic acid is thought to help manage depression and improve emotional well-being.
  • helps in protein metabolism.
  • Against: Vitamin B9 is considered a powerful antioxidant that helps flush out toxins from the body and improve skin condition.
  • Maintaining Heart Health: Consuming folic acid lowers blood homocysteine ​​levels, which can be elevated and can put you at risk of heart disease. In addition, the complex of B vitamins, which includes folic acid, reduces the risk of development.
  • Reducing the risk of cancer: There is evidence that inadequate intake of folate is associated with the development of breast cancer in women.

Folic acid metabolism in the body

Folate functions as a coenzyme in nucleic acid synthesis and amino acid metabolism. Once in the body, dietary folates are hydrolyzed to the form of monoglutamate in the intestine before they are absorbed by active transport substances through the mucous membrane. Before entering the bloodstream, the monoglutamate form is reduced to tetrahydrofolate (THF) and converted to methyl or formyl form. The main form of folate in plasma is 5-methyl-THF. Folic acid can also be found unchanged in the blood (unmetabolized folic acid), but it is not known if this form has any biological activity.

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In order for folate and its coenzymes to cross cell membranes, special transporters are required. These include reduced folate transporter (RFC), proton coupled folate transporter (PCFT), and folate receptor proteins, FRα and FRβ. Folate homeostasis is supported by the ubiquitous proliferation of folate transporters, although their number and significance vary in different tissues of the body. PCFT plays an important role in folate transplantation because mutations affecting the gene encoding PCFT cause hereditary folate malabsorption. Defective PCFT also results in impaired transport of folate to the brain. FRa and RFC are also critical for the transport of folate across the barrier between the circulatory system and the central nervous system. Folate is essential for the proper development of the embryo and fetus. The placenta is known to be responsible for the release of folate into the fetus, resulting in higher concentrations of folate in the baby than in the mother. All three types of receptors are associated with the transport of folate across the placenta during pregnancy.

Interaction with other micronutrients

Folate and together form one of the most powerful micronutrient pairs. Their interaction supports some of the most fundamental processes of cell division and replication. In addition, they together participate in the metabolism of homocysteine. Despite the fact that these two vitamins can be obtained naturally from two completely different types of food (vitamin B12 – from animal foods: meat, liver, eggs, milk, and vitamin B9 – from leafy vegetables, beans), their relationship is very important for the body. They act as cofactors in the synthesis of methionine from homocysteine. If synthesis does not occur, then the level of homocysteine ​​may be elevated, which is often associated with the risk of cardiovascular disease and stroke.

 

An important metabolic interaction in vitamin B9 occurs with riboflavin (). The latter is a precursor of a coenzyme involved in folate metabolism. It converts folate to its active form, 5-methyltetrahydrofolate.

may limit the degradation of natural folate coenzymes and supplemental folic acid in the stomach and thus improve folate bioavailability.

The most useful combinations of foods with vitamin B9

Vitamin B9 is useful to combine with other B vitamins.

For example, in a salad with kale, sunflower seeds, feta, barley, red onion, chickpeas, avocado, and lemon dressing. Such a salad will provide the body with vitamins B3, B6, B7, B2, B12, B5, B9.

A great breakfast or light lunch recipe is a sandwich made from whole wheat bread, smoked salmon, asparagus, and poached eggs. This dish contains vitamins such as B3 and B12, B2, B1 and B9.

Food is the best source of vitamins. Therefore, the possibility of taking vitamins in the form of medicines should be considered if there are appropriate indications. There is evidence that vitamin preparations, if used incorrectly, not only do not benefit, but can also harm the body.

Use in official medicine

Pregnancy

Folic acid is used in medicine for many reasons. First of all, it is prescribed for pregnant women and those who are preparing for conception. The growth and development of the fetus is characterized by active cell division. Adequate folate levels are critical for DNA and RNA synthesis. Due to a lack of folic acid, between the 21st and 27th days after conception, a disease called neural tube defect… As a rule, during this period, a woman does not yet know that she is pregnant and cannot take appropriate measures by increasing the amount of folate in the diet. This disease leads to a number of undesirable consequences for the fetus – brain damage, encephalocele, spinal lesions.

Congenital heart anomalies are a leading cause of death in children and can also lead to deaths in adulthood. According to the European Registry of Congenital Anomalies and Gemini, consuming at least 400 mcg of folic acid per day one month before conception and for 8 weeks afterwards reduced the risk of congenital heart defects by 18 percent.

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Maternal folate levels may influence the risk of developing congenital cleft palate abnormalities. Research in Norway showed that taking a vitamin supplement containing at least 400 mcg of folate reduced the risk of cleft palate by 64%.

Low birth weight is associated with an increased risk of death during the first year of life and may also affect health status in adulthood. A recent systematic review and meta-analysis of eight controlled studies showed a positive association between folate intake and birth weight.

Elevated blood levels of homocysteine ​​have also been associated with an increased incidence of miscarriages and other complications of pregnancy, including preeclampsia and placental abruption. A large retrospective study showed that plasma homocysteine ​​levels in women directly influenced the presence of adverse pregnancy outcomes and complications, including preeclampsia, preterm labor, and very low birth weight. The regulation of homocysteine, in turn, occurs with the participation of folic acid.

Thus, it is prudent to take folic acid, under the supervision of a doctor, throughout pregnancy, even after the neural tube is closed, to reduce the risk of other problems during pregnancy. What’s more, recent studies have found no evidence of an association between folate intake during pregnancy and adverse health effects in children, in particular development of I.

Cardiovascular diseases

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More than 80 studies show that even moderately elevated blood levels of homocysteine ​​increase the risk of cardiovascular disease. The mechanism by which homocysteine ​​may increase the risk of vascular disease is still the subject of much research, but it may include the adverse effects of homocysteine ​​on blood clotting, arterial vasodilation, and thickening of the arterial walls. Folate-rich diets have been linked to a reduced risk of heart disease, including myocardial (heart attack) and stroke. A study of 1980 men in Finland over a 10-year period found that those who ate high amounts of dietary folate had a 55% lower risk of sudden heart disease compared to those who consumed the least amount of folate. Of the three B vitamins that regulate homocysteine ​​concentration, folate has been shown to have the greatest effect on lowering basal concentrations, provided there is no concomitant vitamin B12 or vitamin B6 deficiency. Increasing folate intake from folate-rich foods or supplements has been found to decrease homocysteine ​​concentrations.

Despite controversy over the role of lowering homocysteine ​​in the prevention of cardiovascular disease, several studies have examined the developmental effects of folate supplementation, a known risk factor for vascular disease. Although recent trials have not shown that folate directly protects the body, low folate intake is a known risk factor for heart disease.

Cancer

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Cancer is thought to be caused by DNA damage due to an excessive amount of DNA repair processes, or by improper expression of key genes. Due to the important role of folate in DNA and RNA synthesis, it is possible that insufficient intake of vitamin B9 contributes to genome instability and chromosome defects that are often associated with the development of cancer. In particular, DNA replication and repair is critical to maintaining the genome, and a lack of nucleotides caused by folate deficiency can lead to genome instability and DNA mutations. Folate also controls the homocysteine ​​/ methionine cycle and S-adenosylmethionine, a methyl donor for methylation reactions. Thus, folate deficiency can disrupt DNA and protein methylation and alter the expression of genes involved in DNA repair, cell division and death. Global DNA hypomethylation, a typical sign of cancer, causes genome instability and chromosomal fractures.

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Consuming at least five servings of fruits and vegetables a day has been associated with a decrease in cancer incidence today. Fruits and vegetables are excellent sources of folate, which may play a role in their anti-carcinogenic effects.

Alzheimer’s disease and dementia

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Alzheimer’s disease is the most common form. One study found an association between increased intake of fruits and vegetables rich in folate and a reduced risk of dementia in women.

Due to its role in the synthesis of nucleic acids and providing enough methyl for methylation reactions, folate affects the normal development and function of the brain, not only during pregnancy and after birth, but also later in life. In one cross-sectional study of older women, Alzheimer’s patients had significantly higher homocysteine ​​levels and lower blood folate levels compared to healthy people. In addition, the scientist concluded that long-term blood folate levels, rather than recent use, are responsible for preventing dementia. A two-year, randomized, placebo-controlled study in 168 elderly patients with mild cognitive impairment found benefits of a daily intake of 800 mcg folate, 500 mcg vitamin B12, and 20 mg vitamin B6. Atrophy of certain areas of the brain affected by Alzheimer’s disease was observed in individuals of both groups, and this atrophy was correlated with cognitive decline; however, the group treated with B vitamins experienced less gray matter loss compared to the placebo group (0,5% versus 3,7%). The most beneficial effect was found in patients with higher baseline homocysteine ​​concentrations, suggesting the importance of lowering circulating homocysteine ​​in the prevention of cognitive decline and dementia. Despite its promising effect, B-vitamin supplementation needs to be further explored in larger studies that evaluate long-term outcomes, such as the incidence of Alzheimer’s disease.

Depression

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Low folate levels have been linked to depression and poor response to antidepressants. A recent study of 2 people aged 988 to 1 in the United States found that serum and red blood cell folate concentrations were significantly lower in severely depressed individuals than in those who had never been depressed. Studies in 39 men and women diagnosed with depressive disorder found that only 52 in 1 patients with low folate levels responded to antidepressant treatment, compared with 14 of 17 patients with normal folate levels.

Although supplemental folic acid has not been suggested as a replacement for traditional antidepressant therapy, it may be useful as an adjunct. In a UK study, 127 depressed patients were selected to take either 500 mcg of folate or a placebo in addition to 20 mg of fluoxetine (an antidepressant) daily for 10 weeks. Although the effects in men were not statistically significant, women who received fluoxetine plus folic acid did much better than those who received fluoxetine plus placebo. The study authors concluded that folate “may have a potential role as an adjunct to mainstream treatment for depression.”

Dosage forms of vitamin B9

The most common form of folic acid is tablets. The dosage of the vitamin can be different, depending on the purpose of the drug. In vitamins for pregnant women, the most common dosage is 400 mcg, since this amount is considered sufficient for the healthy development of the fetus. Often folic acid is included in vitamin complexes, along with other B vitamins. Such complexes can be in the form of tablets, and in the form of chewing plates, soluble tablets, as well as injections.

To lower blood homocysteine ​​levels, usually 200 mcg to 15 mg of folate is given per day. When treating depression, take 200 to 500 mcg of vitamin per day, in addition to the main treatment. Any dosage must be prescribed by the attending physician.

Folic acid in traditional medicine

Traditional healers, like doctors in traditional medicine, recognize the importance of folic acid for women, especially pregnant women, and its role in preventing heart disease and anemia.

Folic acid is found, for example, in. Its fruits are recommended for diseases of the kidneys, liver, blood vessels and heart. Besides folate, strawberries are also rich in tannins, potassium, iron, phosphorus, cobalt. For medicinal purposes, fruits, leaves and roots are used.

Folate, along with essential oils, vitamin C, carotene, flavonoids and tocopherol, is found in seeds. The plant itself has a bile and diuretic effect, relieves spasms and cleanses the body. Infusion and decoction of seeds helps with inflammation of the mucous membrane of the urinary tract. In addition, parsley infusion is prescribed for uterine bleeding.

A rich source of folic acid in folk medicine is considered. They contain 65 to 85 percent water, 10 to 33 percent sugar, and a large amount of useful substances – various acids, tannins, potassium, magnesium, calcium, manganese, cobalt, iron, vitamins B1, B2, B6, B9, A, C, K, P, PP, enzymes.

Latest scientific research on vitamin B9

  • Consuming high doses of folic acid does not affect the risk of developing preeclampsia. It is a serious medical condition characterized by the development of abnormally high blood pressure during pregnancy and other complications. This condition is dangerous for both the mother and the child. It has previously been suggested that high doses of folate may reduce the risk of developing folate in women who are predisposed to the disease. These include those who have high blood pressure chronically; women suffering from or; pregnant with twins; as well as those who have had preeclampsia in previous pregnancies. The study involved more than 2 thousand women who were pregnant between 8 and 16 weeks. It was found that taking 4 mg of folic acid daily did not affect the risk of developing the disease compared with those who took a placebo in addition to the standard 1 mg of folate (14,8% of cases and 13,5% of cases, respectively). However, doctors still recommend taking a low dose of folate before and during pregnancy to prevent the development of congenital diseases.
  • Irish scientists have determined that a significant number of people over 50 are deficient in vitamin B12 (1 in 8 people) and folate (1 in 7 people). The degree of deficiency varies with lifestyle, health and nutritional status. Both vitamins are essential for the health of the nervous system, brain, red blood cell production, and DNA division. It was also found that the percentage of folate deficiency increases with age – from 14% among people 50-60 years old, to 23% among those over 80 years old. It was most often found in smokers, obese people and those who lived alone. Vitamin B12 deficiency was more common in those who smoke (14%), live alone (14,3%), and in people from low socioeconomic backgrounds.
  • British scientists insist on enriching flour and other foods with folic acid. According to the authors of the study, every day in Britain, on average, two women are forced to terminate their pregnancies due to a neural tube defect, and two babies are born with this disease every week. Britain is one of the countries where folate fortification is not the norm, unlike the United States and other countries. “If Britain had legalized folate fortification in 1998, as in America, about 2007 birth defects could have been avoided by 3000,” says Professor Joan Morris.

Use in cosmetology

Folic acid plays a very important role in. It contains a concentration of antioxidants that reduce the activity of oxidative processes and neutralize free radicals present in the environment. Folic acid’s skin-nurturing properties also help maintain skin hydration by strengthening the skin’s barrier. This traps moisture and reduces dryness.

In cosmetics, folate foods are most often included in moisturizing lotions and creams, which, when applied topically, can help improve the overall quality and appearance of the skin.

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Livestock use

Folic acid deficiency has been experimentally detected in many animal species, manifested in the form of anemia, a decrease in the number of leukocytes. Mostly tissues with a high rate of cell growth or tissue regeneration are affected, such as the epithelial membrane of the gastrointestinal tract, epidermis and bone marrow. In dogs and cats, anemia is most commonly associated with folate deficiency caused by intestinal malabsorption syndromes, malnutrition, folate antagonists, or increased folate requirements due to blood loss or hemolysis. For some animals such as guinea pigs, monkeys and pigs, having enough folate in the diet is essential. In other animals, including dogs, cats, and rats, the folic acid produced by the intestinal microflora is usually sufficient to meet needs. Therefore, signs of deficiency can develop if an intestinal antiseptic is also included in the diet to inhibit bacterial growth. Folate deficiency occurs in dogs and cats, usually only with antibiotics. It is likely that most of the daily requirement for folate is met by bacterial synthesis in the intestine.

Interesting Facts

  • In some countries, the name of folic acid differs from the generally accepted one. For example, in the Netherlands it is referred to as vitamin B11.
  • Since 1998, folic acid has been fortified in the United States in foods such as bread, breakfast cereals, flour, corn foods, pasta, and other grains.

Contraindications and cautions

About 50-95% of folic acid is destroyed during cooking and preservation. The effects of sunlight and air are also detrimental to folate. Store foods high in folate in a dark vacuum container at room temperature.

Signs of a folate deficiency

Deficiencies in folic acid alone are rare and are usually associated with other nutrient deficiencies due to malnutrition or absorption disorders. Symptoms are usually weakness, trouble concentrating, irritability, heart palpitations, and shortness of breath. In addition, there may be pain and ulcers on the tongue; problems with skin, hair, nails; problems in the gastrointestinal tract; high levels of homocysteine ​​in the blood.

Signs of excess vitamin B9

In general, excess folate intake does not have any side effects. In rare cases, very high doses of folate can harm the kidneys and cause loss of appetite. Taking large amounts of vitamin B9 can hide a vitamin B12 deficiency. The established maximum daily dose of folate for an adult is 1 mg.

Some medicines affect the absorption of vitamin B9 in the body, among them:

  • oral contraceptives;
  • methotrexate (used in the treatment of cancer and autoimmune diseases);
  • antiepileptic drugs (phenytoin, carbamazepine, valproate);
  • sulfasalazine (used to treat ulcerative colitis).

History of discovery

Folate and its biochemical role were first discovered by British researcher Lucy Wills in 1931. In the second half of the 1920s, active research was carried out on the nature of pernicious anemia and methods of its treatment – thus vitamin B12 was discovered. Dr. Wills, however, chose to focus on a narrower subject, anemia in pregnant women. She was criticized for such a narrow approach, but the doctor did not abandon her attempts to find the cause of the severe anemia that pregnant women in the British colonies suffered. Studies in rats were not producing the desired results, so Dr. Wills decided to conduct an experiment on primates.

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Having tried many substances, and by the method of elimination, rejecting all possible hypotheses, in the end, the researcher decided to try using cheap brewer’s yeast. And finally, I got the desired effect! She determined that a nutrient in yeast is essential to prevent anemia during pregnancy. Some time later, Dr. Wills included in her research attempts to consume various substances in pregnant women, and brewer’s yeast again worked. In 1941, folic acid derived from spinach was first named and isolated. That is why the name folate comes from the Latin folium – leaf. And in 1943, the vitamin was obtained in pure crystalline form.

Since 1978, folic acid has been used in combination with the anticancer drug 5-Fluorouracil. First synthesized in 1957 by Dr. Charles Heidelberger, 5-FU has become an effective drug against several types of cancer, but has severe side effects. Two of the doctor’s students discovered that folic acid can significantly lower them while increasing the effectiveness of the drug itself.

In the 1960s, scientists began investigating the role of folate in preventing neural tube defects in the embryo. It has been found that a vitamin B9 deficiency can have very serious consequences for a child, and that a woman usually does not get enough of the substance from food. Therefore, in many countries it has been decided to fortify foods with folic acid. In America, for example, folate is added to many grains – bread, flour, cornstarch, and noodles – as they are the staple foods for most of the population. As a result, the incidence of neural tube defects has been reduced by 15-50% in the United States.


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