TOP 14 best drugs with vitamin B9 (Folic acid) in tablets

The use of folic acid tablets is one of the measures to improve overall well-being and health. The popularity of this product is associated with a number of functions that the substance included in the composition performs. Vitamin B9 acts as an indispensable component in the reproduction of new cells and their division. It is necessary for the preservation and transmission of genetic information, as well as for rapid tissue repair. What else is folic acid used for and what can cause vitamin deficiency? Read more about this.

The role and benefits of vitamin B9

Many people wonder what folic acid tablets help with? To answer it, you need to study the properties of this substance. Vitamin B9 is one of the components of bone marrow. It is known that healthy blood cells are formed only in the presence of a sufficient amount of this B vitamin. Its lack can provoke megaloblastic anemia. Vitamin B9 will help compensate for the deficiency, which also contributes to:

• active production of neurotransmitters that help regulate sleep and appetite, cope with irritation or depression;
• improving reproductive function in women and men;
• launching protein production processes that provide effective protection of the body from pathogens;
• effective prevention of the development of pathogenic cells and their further spread;
• full development of the nervous system in children and adolescents;
• slowing down the onset of menopause in women and bringing the menstrual cycle back to normal;
• preventing the development of diseases of the digestive system.

Both men and women planning to become parents should start taking folic acid tablets several months before conceiving. This measure is an effective way to prevent fetal neural tube defect (). By replenishing vitamin B9 deficiency, the chances of conception also increase. This is facilitated by the appearance of more active sperm and an increase in their quality. Folic acid has also been shown to be effective in reducing the risk of stroke (). This effect is due to its ability to influence the synthesis of homocysteine.

Vitamin B9: dangerous and beneficial

We continue to tell our readers about the benefits and features of essential vitamins, as well as their interactions with medications. We've previously covered vitamin A, vitamin B6, vitamin B1, vitamin C, vitamin E, vitamin H, and vitamin D. Today, the focus is on vitamin B9 and its close and well-known cousin, folic acid. Every young woman probably knows that folic acid is needed by those planning a pregnancy. How to explain to a pharmacy client the difference between folic acid and vitamin B9? What form of this vitamin is best absorbed, when the body needs replenishment with this substance, and why is excess folate dangerous? The answers to these and other questions are in today's review.

1. Folate, folacin, or vitamin B9, is a water-soluble vitamin that is found in a number of foods in the form of tetrahydrofolate. Typically, folates have additional glutamate residues, being polyglutamates. Folic acid is a fully oxidized monoglutamate form of vitamin B9 of synthetic origin. It is used in food products, as well as in most food additives and drugs. Some dietary supplements contain folate in the biologically active form 5‑methyltetrahydrofolate (5‑MTHF).
2. The name "folate" comes from the Latin folium - "leaf". Indeed, the greatest stores of folate are found in green leafy vegetables, such as spinach and asparagus, as well as broccoli, Brussels sprouts, some types of lettuce, green peas and beans. A rich source of folate and other vitamins is beef liver.
3. For many years, it was believed that folic acid was much better absorbed than natural folates. However, dietary folate has now been shown to be more effective than most supplements. They are quickly and almost completely transformed in the gastrointestinal tract into the active form of 5‑MTHF. But folic acid, unlike natural vitamin B9, is only partially converted into 5‑MTHF in the digestive tract. Some of the folic acid is converted in the liver and other organs and tissues, and this process occurs slowly and not very efficiently [1]. Even a small dose of folic acid per day (200-400 mcg) cannot be completely metabolized within 24 hours. When folic acid is supplied through food fortified with it, this process takes even longer [2].
4. When taking folic acid, due to its insufficiently efficient transformation into the active form, an unmetabolized form is found in the blood [3]. It is known that in combination with other B vitamins, especially vitamin B6, activation of folic acid occurs more effectively
   [3].
5. Folates are coenzymes in the synthesis of nucleic acids, that is, DNA and RNA, as well as in the metabolism of amino acids. One of the most important folate-dependent reactions is the conversion of the amino acid homocysteine ​​to methionine. Another reaction that requires folate is methylation during DNA formation, which ensures proper cell division
   . Folate deficiency leads to disruption of nucleic acid and protein synthesis and, as a consequence, inhibition of cell growth and division, especially in rapidly proliferating tissues - bone marrow and intestinal epithelium [4].
6. The total folate content in the human body is 15–30 mg. About half of the reserves are stored in the liver, and the rest in the blood and body tissues. The average folate intake in different countries, according to statistics, ranges from 210 to 400 mcg/day. According to Rospotrebnadzor standards, the daily folate intake is: for children - 50-400 mcg/day, for adults in general - 400 mcg/day, for pregnant women - 600 mcg/day, and nursing mothers - 500 mcg/day. The upper tolerable intake level is 1000 mcg/day [4].
7. To assess folate status, serum levels of the vitamin are determined. Concentrations above 3 ng/ml are considered normal [5].
8. Since vitamin B9 is involved in the development of red blood cells, folate deficiency can lead to the development of megaloblastic anemia. Its symptoms are weakness, fatigue, difficulty concentrating, irritability, headache, tachycardia and shortness of breath.
9. Folate deficiency can manifest itself as ulcers on the tongue and oral mucosa, deterioration of the skin and nails, as well as pigmentation on the fingernails and digestive disorders [7].
10. Too high levels of unmetabolized folic acid in the body are associated with a number of diseases. Thus, studies indicate that high levels of unmetabolized folic acid are associated with an increased risk of cancer and activation of the growth of precancerous formations
    [8]. In particular, a connection has been confirmed between consumption of folic acid in high concentrations and an increased likelihood of colorectal cancer, lung cancer, pancreatic cancer, stomach cancer, ovarian cancer, breast cancer and some other tumors [9]. The exact mechanism of participation of folic acid in carcinogenesis is unknown, however, it is assumed that it is associated with its participation in DNA replication and cell division.
11. A clinical trial of 3,411 patients with coronary heart disease who received 800 mcg of folic acid and 400 mcg of vitamin B12 for 39 months found that supplementation was associated with a 21% increase in cancer risk and a 38% increase in mortality [10]. .
12. Taking folic acid in a dose of more than 1000 mcg for adults or more than 800 mcg in children and adolescents under 18 years of age helps to mask vitamin B12 deficiency until hypovitaminosis B12 leads to the development of irreversible neurological damage [11].
13. Statistics show that a balanced diet in most cases ensures normal folate levels in the body. Those at risk for developing folate deficiency include alcoholics, people with impaired absorption in the intestines (malabsorption), and pregnant women.
    During this period, the need for folate increases by an average of 50% [5], which is associated with the role of vitamin B9 in the synthesis of nucleic acids.
    In this case, folate should have time to accumulate in a woman’s body by the time the pregnancy test shows two lines. To do this, taking folate should start 2-3 months before the expected conception
    .
14. About 10% of Caucasians and Mongoloids, 25% of Hispanics and 1% of blacks have the 677C>T genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. It is associated with a decrease in the activity of the enzyme that converts folate into the active form 5‑MTHF, and, as a consequence, with a violation of the transformation of folic acid into the active form [12]. In the presence of this polymorphism, supplementation with a special form of folic acid, metafolate, will help increase the reserves of active folates [13].
15. Supplements containing folate in the form of 5-methyltetrahydrofolate (metafolin) are considered an optimal alternative to folic acid
    [14].
16. Taking folic acid 2–3 months before conception at a dose of 400 mcg can reduce the risk of developing fetal neural tube defects
    by 70% [15] and other problems. These defects include abnormalities in the formation of the spine (spina bifida), as well as the bones of the skull and brain (anencephaly). The neural tube of the fetus is formed between 21 and 28 days after conception, so it is important that by this period a woman already has a sufficient amount of folate in her body [16].
17. It has been proven that the risk of developing fetal neural tube defects in women experiencing folate deficiency is 10 times higher compared to women with normal folate status [17].
18. Research suggests that folic acid supplements and supplements help increase the gestational age of the fetus and reduce the risk of preterm birth
    .
    Thus, taking them at least 12 months before conception can reduce the risk of premature birth by 50% [18]. Additionally, taking folic acid before pregnancy in combination with a multivitamin supplement helps minimize the risk of congenital heart defects
    . Studies have shown that the likelihood of heart abnormalities in a child is reduced by 11% if the mother took folic acid supplements or supplements before conception [19].
19. Studies have shown that taking folic acid in combination with a multivitamin supplement before pregnancy can reduce the incidence of [20]: urinary tract abnormalities, facial clefts, limb defects and hydrocephalus.
20. Researchers also suggest that taking folic acid before conception may reduce the risk of a child developing autism spectrum disorder
    (ASD) or reduce the potentially high risk of ASD due to exposure to certain medications or toxic substances during pregnancy. The mechanism by which folate influences these risks is most likely related to the role of vitamin B9 in DNA methylation and neurodevelopment [21].
21. Taking folic acid appears to reduce the risk of stroke
    , which is associated with the ability of folate to reduce homocysteine ​​levels, elevated levels of which increase the risk of cardiovascular disease [22].
22. In a study of 20,702 patients with hypertension, folic acid 800 mcg plus enalapril for 4.5 years was associated with a 21% reduction in the risk of stroke compared with enalapril alone [21]. But, according to the results of three reviews, folic acid, alas, does not reduce the likelihood of developing a myocardial infarction or death from any cause [23].
23. Low folate status is associated with the development of depression and poor response to antidepressant therapy
    . A possible mechanism is related to the role of folate in brain methylation, neurotransmitter synthesis, and homocysteine ​​metabolism [24]. According to a study involving approximately 3000 patients, serum and erythrocyte folate concentrations were significantly lower in depressed patients than in healthy controls [25].
24. Folate supplements may have drug interactions
    with a number of medications. The most common interactions [26]: folates + methotrexate (the former reduce the anticancer effect of the latter), folates + antiepileptic drugs (carbamazepine, valproate and others) - the latter help reduce folate levels [27], folates + sulfosalazine - the latter inhibits the intestinal absorption of folates, which leads to the development of their deficiency [28].

Sources

1. Sweeney MR et al. Postprandial serum folic acid response to multiple doses of folic acid in fortified bread //British Journal of Nutrition. 2006; 95(1):145–151.
2. Wright AJA, Dainty JR, Finglas PM Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK //British Journal of Nutrition. 2007; 98(4):667–675.
3. Obeid R. et al. Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial //European journal of nutrition. 2016; 55(3):1021–1028.
4. MP 2.3.1.2432-08 “Norms of physiological needs for energy and nutrients for various groups of the population of the Russian Federation.” URL: https://docs.cntd.ru/document/1200076084.
5. Bailey LB, Caudill MA. Folate. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012: 321–42.
6. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998. URL: https://www.ncbi.nlm.nih.gov/pubmed/23193625
7. Carmel R. Folic acid. In: Shils M, Shike M, Ross A, Caballero B, Cousins ​​RJ, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:470-81.
8. Cole BF et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial //Jama.2007;297(21):2351-2359. URL: https://jamanetwork.com/journals/jama/article-abstract/207344
9. Kim YI. Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr 2004; 80:1123–8. URL: https://academic.oup.com/ajcn/article/80/5/1123/4690413
10. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009; 302:2119–26. URL: https://jamanetwork.com/journals/jama/fullarticle/184898
11. Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev 2007;65:451-8.
12. Molloy AM, Pangilinan F, Brody LC. Genetic risk factors for folate-responsive neural tube defects. Annu Rev Nutr 2017; 37:269–91.
13. Greenberg JA, Bell SJ, Guan Y, et al. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol 2011; 4:52–9. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/
14. Scaglione F., Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing //Xenobiotica. 2014; 44(5):480–488.
15. Johnson K. et al. Recommendations to Improve Preconception Health and Health Care—United States: Report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care //Morbidity and Mortality Weekly Report: Recommendations and Reports. 2006; 55(6):1–CE.
16. Wilson RD, Genetics C, Motherisk. Pre-conceptual vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 2007; 29: 1003–13. URL: https://www.sciencedirect.com/science/article/abs/pii/S1701216316326858
17. Daly, L. E., Kirke, P. M., Molloy, A., Weir, D. G. & Scott, J. M. 1995. Folate levels and neural tube defects. Implications for prevention. JAMA, 274: 1698–1702.
18. Bukowski R. et al. Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study //PLoS medicine.2009;6(5): e1000061. URL: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1000061
19. Liu S, Joseph KS, Luo W, et al. Effect of folic acid food fortification in Canada on congenital heart disease subtypes. Circulation 2016; 134:647–55. URL: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.116.022126
20. Wilson RD, Genetics C, Motherisk. Pre-conceptual vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 2007; 29: 1003–13.
21. DeVilbiss EA, Gardner RM, Newschaffer CJ, et al. Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. Br J Nutr 2015; 114:663–72.
22. Bailey LB, Caudill MA. Folate. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012: 321–42.
23. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental Vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018; 71:2570–84. URL: https://www.onlinejacc.org/content/71/22/2570.short
24. Huang X, Fan Y, Han X, et al. Association between serum vitamin levels and depression in US adults 20 years or older based on National Health and Nutrition Examination Survey 2005–2006. Int J Environ Res Public Health 2018; 15.
25. Morris MS, Fava M, Jacques PF, et al. Depression and folate status in the US population. Psychother Psychosom 2003; 72:80–7.
26. Natural Medicines. Folate.external link disclaimer 2022.
27. Linnebank M, Moskau S, Semmler A, et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol 2011; 69: 352–9.
28. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med 1981; 305:1513–7.

Symptoms, causes and consequences of deficiency

Vitamin B9 deficiency for the body is most often observed when it is insufficiently supplied with food or with the development of pathologies associated with digestion. A shortage of a substance is also provoked by an increase in the need for it. This condition is observed in pregnant and lactating women, adolescents, as well as in children during the period of active growth. A deficiency state in adults can be caused by excessive consumption of alcoholic beverages or long-term use of anticonvulsants.

The following symptoms may indicate the need to use vitamins in folic acid tablets:

• blanching of the skin and mucous membranes;
• fatigue after minor and short-term exertion;
• constant irritability;
• respiratory dysfunction;
• acceleration of heartbeat;
• drop in blood pressure in the arteries;
• loss of appetite;
• the appearance of tinnitus.

If you discover these signs, you need to consult a doctor to make a diagnosis. If vitamin B9 deficiency is confirmed, measures must be taken to eliminate the problem. Otherwise, you may encounter consequences such as a decrease in the amount of iron in the blood, disruption of the functioning of the musculoskeletal system, delayed sexual development in adolescents and infertility in men. Taking folic acid tablets in case of deficiency is also necessary, since a lack of vitamin provokes disruptions in the functioning of the nervous system. In this case, disorders associated with defective brain function are noted.

Indications for the purpose of the study

Folic acid (from the Latin folium - “leaf”) is a water-soluble vitamin B9, part of the group of folates, which can be of both natural and synthetic origin.
When entering the body, folic acid and other folates are converted into biologically active substances involved in metabolism. The terms "folate" and "folic acid" are often used interchangeably. The composition of medications and vitamin complexes in the vast majority of cases includes folic acid (vitamin B9).

The level of folate in the body depends on food preferences, cooking methods and the state of the gastrointestinal tract.

The largest amount of folic acid is found in leafy vegetables (lettuce, spinach), legumes, mushrooms, eggs, organ meats (liver, kidneys), and yeast.

During cooking, some folates are destroyed - when cooking vegetables and meat, the loss of folic acid reaches 70-90%, when cooking eggs - 50%. Folate starvation occurs in newborns who are fed goat's milk.

Folic acid is absorbed in the duodenum and proximal jejunum. In blood plasma it binds to transport proteins. Vitamin B9 is included in the composition of red blood cells, and its main depot is the liver, where it is in an inactive state and turns into an active form as the body needs.

In the human body, folate is contained in an amount of 5-10 mg. The daily requirement is 50-100 mcg, increasing during pregnancy, lactation, and heavy physical labor. Folic acid reserves are depleted 1-4 months after it stops entering the body.

Folic acid is necessary for the full development of the embryo, hematopoiesis, renewal of the intestinal mucosa, and for wound healing.

With folic acid deficiency, megaloblastic anemia, leukopenia (decrease in the number of white blood cells), growth retardation, impaired renewal of the small intestinal mucosa, and slow wound healing develop. Vitamin B9 is also necessary for the synthesis of substances that transmit nerve impulses from one neuron to another, and the functioning of the immune system.

Impaired folate metabolism leads to an increase in the total level of homocysteine ​​in the plasma, which can cause an increased risk of thrombosis and the development of coronary heart disease, myocardial infarction, and stroke. There is a connection between high levels of homocysteine ​​and pregnancy complications (recurrent miscarriage, placental insufficiency, developmental delay and intrauterine fetal death, placental abruption, premature birth), fetal development defects (Down syndrome, encephalomeningocele, myelomeningocele, etc.).

Folic acid testing is prescribed:

• to determine the sufficient level of vitamin B9 in the body;
• pregnant women to determine the risk of congenital defects of the fetus;
• as part of the diagnosis of anemia;
• to monitor folic acid levels during treatment.

You need to know that independent and uncontrolled intake of folic acid is unacceptable, since an overdose of the drug can lead to serious consequences.

Thus, pregnant women with an overdose of folic acid may give birth to children with weak immunity and a tendency to bronchial asthma and colds. Long-term intake of high doses of folic acid provokes digestive disorders, causes disturbances in kidney function, leads to a decrease in the level of vitamin B12 and the development of anemia.

How to take folic acid tablets correctly?

The dosage of folic acid in tablets is calculated based on the patient’s age and gender, as well as taking into account his state of health. For children, the drug is prescribed in case of deficiency after breastfeeding. So for children under 3 years of age, the required daily intake of the drug corresponds to 70 mcg. In the period from 4 to 6 years it is 0.1 mg. The dosage of the drug is gradually increased. So, to make up for the deficiency, every 3 years another 0.05 mg is added to 0.1 mg, and by the age of 18 the recommended norm reaches 0.3 mg.

The daily dose of folic acid in tablets for women varies from 0.2 to 0.4 mg. The norm of vitamin B9 for men whose body is prone to microelement deficiency is 1 mg. In old age, it is recommended to take 0.4 mg of the drug. Speaking about how many folic acid tablets to take per day, it is worth noting that each of them most often contains approximately 2 daily doses. The concentration of the active substance in them may vary depending on the manufacturer.

Preparation for the procedure

• It is recommended to donate blood in the morning from 8 to 11 o’clock, on an empty stomach (at least 8 hours of fasting, you can drink water as usual).
• Please consult with your doctor first about the advisability of conducting the study while you are taking medications or the possibility of stopping medications before the study.
• You should avoid drinking alcohol on the eve of the test and do not smoke for 1 hour before the test.
• It is advisable to exclude physical and emotional stress on the eve of the study.
• After arriving at the laboratory, rest for 10-20 minutes before drawing blood.
• It is not advisable to donate blood for laboratory testing soon after physiotherapeutic procedures, instrumental examination and other medical interventions.
• When monitoring laboratory parameters over time, it is recommended to conduct repeated studies under the same conditions - in the same laboratory (using the same method), at the same time of day.

Contraindications and side effects

According to the instructions for use of folic acid, the use of the drug should be discontinued if an allergic reaction is detected or estrogen levels are exceeded. This drug should not be taken by patients with bronchial asthma or those who have symptoms indicating malignancy. If you violate the instructions for use of vitamin B9 and use it in excess of the recommended dosages, you may encounter side effects such as increased body temperature, nausea, vomiting, stool disorders, bloating, bronchospasms, excessive irritability and the appearance of muscle cramps. Sometimes allergic symptoms are observed in the form of itching and rash on the skin.