Folic acid. Instructions for use

Even at the stage of pregnancy planning, a woman needs to think about taking the missing vitamins and microelements, which play an important role in bearing a child. Folic acid is included in the list of mandatory components that should be taken by the expectant mother not only during pregnancy, but also before its onset. How much and how to take folic acid? Doctors recommend drinking 400 mcg per day, but it’s worth looking into this issue in more detail.

Benefits of Vitamin B9

Folic acid (also known as vitamin B9) is extremely beneficial for human health. It is with its help that the body produces new cells, adjusts the functioning of the immune system, and the digestive function and cardiovascular system return to normal. Vitamin B9 has a positive effect on liver function, amino acid synthesis, takes part in protein metabolism, normalizes blood pressure, and reduces the risk of stroke.

And also folic acid:

stimulates appetite;
plays an important role in the synthesis of DNA and RNA;
helps release hydrochloric acid in the stomach;
reduces the risk of ovarian and breast cancer.

Planning a pregnancy

Women who dream of adding to their family should definitely take folic acid. It is necessary to compensate for the vitamin deficiency even when planning pregnancy. How much? It is advisable to start taking folic acid 2-3 months before the expected date of conception.

Vitamin B9 cannot be stocked up for future use, so it is advisable to replenish it daily.

During pregnancy, the need for folic acid doubles, since now both the expectant mother and her baby need this vitamin. It is especially important to drink the required amount of vitamin in the first trimester of pregnancy, when the child’s nervous system is rapidly developing.

A lack of folic acid can lead to:

development of congenital malformations in the fetus;
inability to bear fruit;
placental abruption;
cerebral hernia in the fetus and many other consequences.

To minimize or completely eliminate severe consequences, you should start taking folic acid as early as possible, even when planning pregnancy. We will analyze how much to drink, as well as the norms and dosages of the component further.

When planning a pregnancy, the first step is to normalize the amount of vitamin B9 in the body. The daily requirement is 0.4 mg, or 400 mcg. This norm is enough for the harmonious functioning of the entire body of the expectant mother. At the same time, you don’t have to worry if pregnancy occurs unexpectedly, because folic acid is already entering the body. But if you hear about an “interesting situation,” the dose should be increased to 800 mcg.

During breastfeeding, you should not stop using folic acid, because it is still passed on to the baby, but only through breast milk.

You should take folic acid in the morning with or after meals, washing down the tablet with plenty of water. Taking this drug is a must for all those who are planning to conceive a child.

Contraindications and precautions

Like any other drug, folic acid has contraindications. The presence of malignant tumors may mean a ban on taking this component. The fact is that vitamin B9 can stimulate the growth of tumor cells, which is undesirable for anyone, especially for an expectant mother.

with cobalamin deficiency (vitamin B12),
hemosiderosis (excessive deposition of hemosiderin pigment in tissues),
hemochromatosis (iron metabolism disorder),
pernicious anemia (poor absorption of vitamin B12),
hypersensitivity to drugs included in the drug.

Before taking any tablets, including folic acid, you should consult your doctor.

An overdose of this vitamin is rare.

If a woman takes folacin (vitamin B9) in large doses for a long time, this can lead to the following consequences:

kidney dysfunction,
zinc deficiency,
rash,
metallic and bitter taste in the mouth,
change in mood.

Vitamin complexes and tablets

Nowadays, many vitamin complexes are offered, which include a large list of essential substances, including vitamin B9. This method of consumption is very convenient because you do not need to drink each microelement separately, and then remember what you drank and how much.

For pregnant women, there are also vitamin complexes in which the required components are calculated.

When choosing individual folic acid tablets, the situation is slightly different. Basically, tablets are packaged in 1 mg and 5 mg (5 mg is a therapeutic dose for severe deficiency of the component). In order, for example, to get 0.4 mg of acid, the tablet should be divided approximately in half (extra use of 0.1 mg will not hurt). This method is not very convenient, so vitamin B9 is still often used in conjunction with multivitamin complexes.

The lack of vitamin B9 can also be compensated through food. Even if you take folic acid in tablets and at the same time eat dishes that contain a high content of this microelement, it will definitely not get worse.

In first place for the highest content of folic acid is greens. Spinach, lettuce, parsley, onions - all these products are not only tasty, but also very rich in vitamin B9. A real storehouse of useful substances, and an excellent addition to any meat or side dish. Of all the greens, spinach is worth highlighting.

100 g of spinach contains 263 mcg of folic acid, which is 65% of its daily requirement for humans.

Meat products also do not lag behind in the content of such a useful substance as folacin. It is present in amounts of 240 mcg in 100 g of beef liver, 225 g in pig liver and 110 g in cod liver. The liver itself is a valuable product. When planning a pregnancy, you should eat at least 100 g of this healthy dish, because how well and nutritiously a mother eats, the stronger and healthier her baby will be.

Separately, it is worth noting asparagus, because it contains 262 g of folacin, as well as copper, iron, calcium, potassium, phosphorus, vitamins A, B, C, E. Asparagus is the leader among all vegetables in terms of folic acid content. In addition, it is an excellent cure for cystitis, prostatitis, and various types of infections.

Everyone knows that nuts are a very nutritious and high-calorie product. But they also contain many useful substances, especially for the female body. The leader in vitamin B9 content is peanuts, which contain 240 mcg per 100 g, which is 60% of the daily requirement. Folic acid is also found in walnuts - 77 mcg, hazelnuts - 68 mcg, pistachios - 51 mcg, cashews - 25 mcg.

Don't forget about the future dad

It is generally accepted that when planning a pregnancy, only one woman should eat right, take vitamins, lead a healthy lifestyle, etc. But after all, two people take part in the conception, including the father of the family, but they forget about his health, and in vain. Taking folic acid will also benefit dad.

The fact is that when consuming folacin, the number of sperm with various defects (chromosome set error, absence of a head or tail) decreases. The quality of sperm improves, which means that the likelihood of conceiving a healthy child increases. If a man smokes, then when planning a pregnancy, it’s time to quit this bad habit.

In addition to the fact that the future father ruins his own health, nicotine also prevents folic acid from being absorbed. Then it turns out that all the efforts on Dad’s part are in vain.

The dosage of vitamin B9 for men is the same as for women – 400 mcg. But you should remember about possible contraindications and overdose of the drug. A man should start taking folic acid several months before conception, just like a woman.

Folic acid is produced in tablet forms. Tablets may contain 1 and 5 mg of acid. Tablets for pregnant women with FC are produced with a dosage of 1 mg or 400 mcg. The dosage of 400 mcg is Folic acid for 9 months. It is specially designed for pregnant women. One tablet of folic acid (1 mg) contains 1 mg of the substance. 1/2 tablet at a dose of 1 mg contains 500 mcg.

Folic acid is involved in the formation of blood cells. Against the background of normal FA concentration, a normal number of red blood cells and hemoglobin is maintained. With insufficient amounts of a microelement, megaloblastic anemia is formed. This disease is accompanied by the formation of underdeveloped red blood cells. Blood cells cannot fully carry oxygen. Against the background of a lack of FA and a deficiency of vitamin B12, B12-deficiency anemia appears. Iron deficiency anemia may also occur.

Folic acid improves the condition of the intestinal mucosa and improves digestive function. This is especially important for children in the neonatal period. In newborns, the intestines are just beginning to work, so a sufficient amount of folic acid is very important.

Folic acid is involved in the formation of cellular structures, DNA and RNA molecules. This property of the drug allows you to accelerate or maintain the normal development of placental tissue during gestation, as well as the growth of the fetus in utero. For a child from birth, folic acid also ensures the constant cell division necessary for growth.

A normal amount of microelement helps prevent the formation of cancer pathologies. FA deficiency increases the risk of cancer. According to the instructions, excessive intake of the pharmaceutical drug FK can provoke the growth of tumor tissue.

Indications and restrictions for use:

You need to take the vitamin at the prescribed dose once a day. The course of therapy is 30 days or more. The microelement is taken after meals.

Folic acid standards

During pregnancy, a woman needs 400 mcg of FA in tablets per day. Together with food, the dose will be 800 mcg of folic acid. A healthy adult needs only 200 mcg of folic acid. When planning a child, men need 400-800 mcg, depending on their health.

Dosages in children:

How much mcg is contained in 1 mg of FA

More often, tablets with a dosage of 1 mg (milligram) are used. 1 mg is 1000 mcg of folic acid. To obtain a dosage of 500 mcg, you need to divide the tablet in half.

Pregnant women are often prescribed 400 mcg. A dosage of 400 mcg of folic acid is slightly less than half a tablet. It is permissible for a woman to take half the tablet form during pregnancy. If there is a threat of miscarriage or premature birth, gynecologists even prescribe 2-3 tablets of FC. There is no overdose of the drug.

When planning a child, men are also advised to take a dosage of 400 mcg - this is 0.4 mg FA. The dosage is not very convenient to take, so it is permissible to take 500 mcg (half a tablet).

For children, it is inconvenient to divide the tablet, since the dosages are very small. To do this, the 1 mg tablet form is divided into 4 parts. One part is diluted in 25 ml of water. If the dose is 25 mcg, then you need to take 1 ml of solution. If necessary, give the child 50 mcg, take 5 ml of solution. If a child needs a dose of 75 mcg, take 7.5 ml. A new solution must be made each time you take the medicine. Used - throw away.

Children can be given a complex of vitamins. The dosages there are selected according to age. Children are often prescribed Alphabet, Supradin, Complivit. Complexes are much more convenient. They have not only FA, but also other vitamins.

Conclusion

Folic acid is used in gynecology, urology, obstetrics, pediatrics, and neurology. It is indicated for use in cases of FA deficiency, pregnancy, or planning a child (half a tablet - 500 mcg). In children, the drug is indicated for autism, delayed general and speech development, and anemia. Before using FC, you should consult a doctor to clarify the dosage and contraindications.

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PHARMACHOLOGIC EFFECT
Vitamin B (vitamin Bc, vitamin B9) can be synthesized by intestinal microflora. In the body, folic acid is reduced to tetrahydrofolic acid, which is a coenzyme involved in various metabolic processes. Necessary for normal maturation of megaloblasts and formation of normoblasts. Stimulates erythropoiesis, participates in the synthesis of amino acids (including glycine, methionine), nucleic acids, purines, pyrimidines, in the metabolism of choline, histidine.

PHARMACOKINETICS

Suction and distribution
Folic acid is well and completely absorbed from the gastrointestinal tract, mainly in the upper parts of the duodenum. Cmax in blood plasma is achieved after 30-60 minutes.

Almost completely binds to plasma proteins. Penetrates through the BBB and placental barrier and is excreted in breast milk.

Metabolism and excretion
It is activated in the liver under the influence of the enzyme dihydrofolate reductase, turning into tetrahydrofolic acid.

Excreted by the kidneys mainly in the form of metabolites; if the dose taken significantly exceeds the daily requirement for folic acid, it is excreted unchanged.
Eliminated by hemodialysis.

DOSAGE

Use internally after meals.
For folic acid deficiency - 400 mcg (1 tablet)/day.
To prevent the development of neural tube defects in the fetus in the first trimester of pregnancy - 400-800 mcg (1-2 tablets).

OVERDOSE

It may occur with long-term intake (more than 1-2 months) of folic acid in doses over 1000 mcg/day and as a result of combined use with vitamin-mineral complexes.

DRUG INTERACTIONS

When used simultaneously, it reduces the effect of phenytoin (increasing its dose is required).
Analgesics (long-term therapy), anticonvulsants (including phenytoin and carbamazepine), estrogens, and oral contraceptives increase the need for folic acid.
Antacids, cholestyramine, sulfonamines (including sulfasalazine) reduce the absorption of folic acid.
Methotrexate, pyrimethamine, triamterene, trimethoprim inhibit dihydrofolate reductase and reduce the effect of folic acid (patients using these drugs should be prescribed calcium folinate instead).
When used simultaneously with chloramphenicol, polymyxins, tetracyclines, the absorption of folic acid is reduced.

PREGNANCY AND LACTATION

Folic acid is necessary during the period of preparation for pregnancy (1-3 months before the planned pregnancy) and in the first few weeks after conception (first trimester).

SIDE EFFECTS

Allergic reactions: skin rash, itching, bronchospasm, erythema, hyperthermia.
From the digestive system: nausea, bloating, bitterness in the mouth, anorexia.
Other: with long-term use, hypovitaminosis B12 may develop.

CONDITIONS AND DURATION OF STORAGE

The drug should be stored in a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C. Shelf life - 3 years.

INDICATIONS

- folic acid deficiency;
- prevention of the development of neural tube defects in the fetus in the first trimester of pregnancy.

CONTRAINDICATIONS

- pernicious anemia;
- malignant neoplasms;
- cobalamin deficiency;
- childhood;
- hypersensitivity to the components included in the drug.

SPECIAL INSTRUCTIONS

To prevent hypovitaminosis, a balanced diet is most preferable. Foods rich in folic acid - green vegetables (lettuce, spinach, tomatoes, carrots), fresh liver, legumes, beets, eggs, cheese, nuts, cereals.

Folic acid is not used to treat B12 deficiency (pernicious), normocytic and aplastic anemia, as well as anemia refractory to therapy. In pernicious (B12-deficiency) anemia, folic acid, improving hematological parameters, masks neurological complications. Until pernicious anemia has been ruled out, the administration of folic acid in doses exceeding 100 mcg/day is not recommended (with the exception of pregnancy and lactation).

It should be kept in mind that hemodialysis patients require increased amounts of folic acid.
During treatment, antacids should be used 2 hours after taking folic acid, cholestyramine - 4-6 hours before or 1 hour after taking folic acid.

It should be borne in mind that antibiotics can distort (provide deliberately underestimated indicators) the results of microbiological assessment of the concentration of folic acid in plasma and erythrocytes.
When using large doses of folic acid, as well as therapy for a long period, a decrease in the concentration of vitamin B12 is possible.

USE IN CHILDREN

Contraindicated in children.

Is a medicine. A doctor's consultation is required.

Self-medication can be harmful to your health.
You should consult your doctor and read the instructions before use.

Folic acid: instructions for use

Compound

Active ingredient: folic acid - 1 mg; excipients: powdered sugar, potato starch, stearic acid.

Description

Flat-cylindrical tablets from pale yellow to yellow, with a chamfer and a score. The presence of inclusions of darker and lighter colors is allowed.

Indications for use

Treatment of macrocytic (folate deficiency) anemia.

Hypo- and avitaminosis of folic acid, incl. with tropical and non-tropical sprue, malnutrition, pregnancy, in patients taking antiepileptic and contraceptive drugs.

Contraindications

Hypersensitivity.

Carefully

Pernicious anemia and other megaloblastic anemias with cyanocobalamin deficiency.

Directions for use and doses

Inside. Before eating.

For the treatment of macrocytic (folate deficiency) anemia, the following is prescribed: for adults and children of any age, the initial dose is up to 1 mg/day (1 tablet). When large doses are used, resistance may occur. Maintenance treatment: children over 4 years of age and adults - 0.5 mg (1/2 tablet), during pregnancy and lactation - up to 1 mg / day.

For pregnant women, to prevent the development of neural tube defects in the fetus - from 0.5 mg/day (1/2 tablet) to 2.5 mg/day (2.5 tablets) for 4 weeks before the expected pregnancy. Reception is continued during the first trimester of pregnancy.

For therapeutic purposes (depending on the severity of vitamin deficiency) for adults - up to 5 mg / day (5 tablets) for 20-30 days, for children - depending on age. Therapeutic doses of folic acid are determined by the doctor.

With concomitant alcoholism, hemolytic anemia, chronic infectious diseases, simultaneous use of anticonvulsants, after gastrectomy, malabsorption syndrome, liver failure, liver cirrhosis, stress, the dose of the drug should be increased.

Side effect

Allergic reactions - skin rash, itching, bronchospasm, erythema, hyperthermia.

If any side effects not described in these instructions occur, you should inform your doctor.

Overdose

Doses of folic acid up to 4 - 5 mg are well tolerated. Higher doses may cause: disorders of the central nervous system (irritability and insomnia) and gastrointestinal tract (nausea, abdominal pain, flatulence).

Interaction with other drugs

Reduces the effect of phenytoin (increasing its dose is required).

Analgesics (long-term therapy), anticonvulsants (including phenytoin and carbamazepine), estrogens, and oral contraceptives increase the need for folic acid. Antacids (including calcium (Ca 2+), aluminum (Al 3+) and magnesium (Mg 2+) preparations), cholestyramine, sulfonamines (including sulfasalazine) reduce the absorption of folic acid.

In order to prevent the development of megaloblastic anemia in patients taking cytostatics (methotrexate) or antiepileptic drugs, concomitant administration of folic acid is recommended.

Pyrimethamine, triamterene, trimethoprim inhibit dihydrofolate reductase and reduce the effect of folic acid (patients using these drugs should be prescribed calcium folinate instead).

Regarding zinc preparations (Zn 2+), there is no clear information: some studies show that folates inhibit the absorption of Zn 2+, while others refute this data.

Features of application

The drug is not intended for the prevention of hypo- and vitamin deficiency in children (due to the discrepancy between the daily requirement and dosage of the drug).

To prevent hypovitaminosis B 9, a balanced diet is most preferable. Foods rich in vitamin B 9 - green vegetables (lettuce, spinach, tomatoes, carrots), fresh liver, legumes, beets, eggs, cheese, nuts, cereals.

Folic acid is not used to treat B12 deficiency (perniciousness).

noah), normocytic and aplastic anemia, as well as anemia refractory to therapy. In pernicious (B 12 deficiency) anemia, folic acid, improving hematological parameters, masks neurological complications. Until pernicious anemia is excluded, the administration of folic acid in doses exceeding 0.1 mg/day is not recommended (with the exception of pregnancy and lactation).

It should be kept in mind that hemodialysis patients require increased amounts of folic acid.

During treatment, antacids should be used 2 hours after taking folic acid, cholestyramine - 4 to 6 hours before or 1 hour after taking folic acid.

When using large doses of folic acid, as well as therapy for a long period, a decrease in the concentration of vitamin B 12 (cyanocobalamin) in the blood is possible. Long-term use of folic acid is recommended to be combined with vitamin B12.

Use during pregnancy

The drug is used according to indications during pregnancy and lactation. Taking folic acid daily in early pregnancy can prevent fetal neural tube defects (anencephaly, spina bifida). If the drug is started after the fourth week of pregnancy, folic acid is not effective in preventing neural tube defects.

Impact on the ability to drive a car and work with moving mechanisms: does not affect.

Release form

5 blister packs of 10 tablets per pack.

Storage conditions

In a place protected from light and moisture, at a temperature not exceeding 25°C. Keep out of the reach of children.

The tablet contains 1 or 5 mg of active substance.

Other components: dextrose (in the form of monohydrate), sucrose, talc, stearic acid.

Release form

The drug is available in tablet form. Tablets with a chamfer have a flat-cylindrical shape. Their color can vary from yellowish to yellow, the presence of small inclusions of yellow is allowed.

The tablets are packaged 10 pieces in blister packs made of aluminum foil and PVC or 50 pieces in plastic jars. Outline packages and cans are placed in cardboard packaging for consumer packaging.

pharmachologic effect

Metabolic. The drug stimulates erythropoiesis and compensates for the body's need for folic acid when it is deficient.

Pharmacodynamics and pharmacokinetics

Indications for use

Indications for the use of Folic acid are:

anemia associated with deficiency vitamin B9 (including medicinal, megaloblastic, radiation, post-resection);
hypovitaminosis and vitamin deficiency f. acids (including in childhood, during pregnancy and lactation, as well as due to tropical diarrhea , malnutrition, intake antiepileptic drugs , celiac disease and a number of other factors);
intestinal tuberculosis ;

Contraindications

Contraindications to the use of the drug are:

for folic acid;
hypersensitivity to the excipients contained in the tablets;
anemia associated with a deficiency in the body;
fructosemia ;
sucrase and isomaltase deficiency;
malabsorption of glucose and galactose.

Folic acid should be prescribed with caution to persons with B9-vitamin anemia accompanied by symptoms of deficiency vitamin B12 (cyanocobalamin) .

Side effects

Side effects associated with taking Folic acid manifest themselves in the form of hypersensitivity reactions: erythema , bronchospasm , fever , skin rashes, hyperthermia .

Folic acid, instructions for use

How to take Folic acid for medicinal purposes?

For the treatment of acute and severe B9-vitamin deficiency The patient is advised to take 5 mg of F. acid per day. In pediatrics, the dosage of folic acid tablets is selected depending on age.

The duration of treatment is from 3 weeks to 1 month.

Instructions for the use of Folic acid for the prevention of hypo- and vitamin deficiency

For warning hypovitaminosis conditions related to the shortage vitamin b9 , the patient is prescribed to take from 20 to 50 mcg of F. acid per day.

With concomitant chronic infection, alcoholism, malabsorption syndrome, hemolytic anemia , at liver failure , after gastrectomy , under stress, the daily dose of the drug should be increased.

Daily value of vitamin B9

Children of the first year of life are prescribed to take 25 mcg in the first 6 months, and 35 mcg of F. acid in the next six months.

For children aged 12 months to 3 years, the dose is 50 mcg/day. At the age of 3 to 6 years, the drug is taken at a dose of 75 mcg, at the age of 7 to 10 years - 100 mcg, at the age of 11 to 14 years - 150 mcg per day.

The optimal dosage for children over 15 years of age, according to the annotation, is 200 mcg of F. acid per day.

Overdose

The use of the drug in a dose not exceeding 4-5 mg per day is not accompanied by toxic effects. A dose significantly exceeding 5 mg per day can cause dysfunction of the central nervous system and gastrointestinal tract.

In children, symptoms of overdose manifest themselves in the form of increased excitability and digestive disorders. Adults may also suffer from sleep disorders.

Interaction

Absorption of F. acid is reduced when used in combination with:

antacids (including magnesium, calcium and aluminum containing preparations);
sulfonamides (for example, with);
Cholestyramine ;
alcohol.

A decrease in the effectiveness of folic acid preparations results from their simultaneous use with bacteriostatic antibiotic And antiprotozoal drug Pyrimethamine .

This is due to the fact that the above drugs inhibit the activity of dihydrofolate reductase, an enzyme that plays an important role in intracellular metabolism folate .

For patients taking Trimethoprim or Pyrimethamine , it is recommended to prescribe instead of folic acid calcium folinate .

Corticosteroid hormones , oral contraceptives , nitrofuran And anticonvulsants (including Carbamazepine i) reduce the concentration of f. acids in the blood.

There is no unambiguous information regarding drugs that contain Zn++: some studies show that folic acid inhibits the absorption of this microelement, others refute this data.

Folic acid and Methotrexate. Why is folic acid needed in the treatment of rheumatoid arthritis?

Wikipedia states that areas of intense cell division and, in particular, have a special need for phosphorus acid. malignant neoplasms . In this regard, the mechanism of action of individual antitumor drugs - including Methotrexate - is based on the creation of obstacles to the metabolism of folates.

This, in turn, significantly reduces the likelihood of encountering the problem of impaired maturation of a full-fledged egg, which is one of the most common causes of infertility in women.

Thus, summarizing the benefits for women from taking the drug, it should be noted that the vitamin in the quantities necessary for the body helps normalize the menstrual cycle, prevents, smoothes the severity of unpleasant symptoms, increases intellectual abilities and the chances of getting pregnant, and ensures the normal course of pregnancy.

In addition, folic acid is rightly called the “beauty vitamin”. The vitamin is indispensable for hair, skin, and nails: its deficiency leads to hair growth slowing down, dulling, breaking and falling out, nails becoming weaker and more fragile, and the skin more often suffering from acne .

Thus, regular use of folate for a woman can improve not only her general well-being, but also her appearance.

Folic acid is no less important for men. Many pathologies leading to problems with conception are caused by the content of an incorrect set of chromosomes in sperm.

The phenomenon is called aneuploidy and is observed even in healthy men: about 4% of the sperm of an absolutely healthy person without bad habits and with no genetically bad predisposition contains an excess or insufficient number of chromosomes.

Aneuploidy not only makes fertilization of the egg impossible, but also in some cases causes various forms genomic pathologies in a child (including Down syndrome And Klinefelter syndrome ).

It is believed that the reason for the appearance of defective sperm may lie in poor nutrition and an unhealthy lifestyle, but scientists today find it difficult to say exactly why the composition of sperm changes.

However, studies have shown that men whose diets contain foods rich in folic acid have higher levels of aneuploidy significantly lower (by about 20-30%) than in men whose need for vitamin B9 not fully compensated. Consequently, they have a much higher chance of successfully conceiving and producing healthy offspring.

For this reason vitamin B9 along with vitamin E included in all complexes that have been developed for the prevention and treatment of male infertility.

Using them in combination can significantly improve hormonal levels and blood circulation, as well as increase the quantity and quality of sperm.

The optimal dosage of folic acid for men is 700-1100 mcg per day.