Folic acid

Synonym: folate, folacin, vitamin B9, folic acid

Characteristics: Folic acid (FA) is a water-soluble B vitamin that occurs naturally in some foods, is added to others, and is available as a dietary supplement. Folate, the active form of folic acid, is a general term for a large family of chemically similar trace compounds that fall into the vitamin B group. Folate functions as a coenzyme or cosubstrate in one-carbon transfers in nucleic acid (DNA and RNA) synthesis and amino acid metabolism.

Absorption: Folate found in animal sources is present in "free form" and is easily absorbed. Unfortunately, animal products are poor sources of folate. Folate present in plant foods exists in a conjugated form that requires deconjugation by zinc-dependent enzymes before absorption. All forms are eventually converted to the active form, eg tetrahydrofolate (THF). The total body folate content is estimated to be 15 to 30 mg; about half of this amount is stored in the liver and the rest in the blood and body tissues.

Supplements: KL is available in multivitamins and prenatal vitamins, supplements containing other B-complex vitamins, and supplements containing only folic acid. Common doses range from 400 to 800 µg of KL in adult supplements and 200 to 400 µg in children's multivitamins. Approximately 85% of supplemental KL when taken with food is bioavailable.

Natural sources: Folate is naturally present in a wide variety of foods, including vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy products, meat, poultry and grains. Spinach, liver, asparagus and Brussels sprouts are among the foods with the highest folate content. The average bioavailability of natural folate is half that of the synthetic form. A small amount of folate is produced by bacteria in the gut, but unused appears to be lost in the stool. Food preparation and processing can destroy up to 100% of naturally occurring folate because it is sensitive to light and air, but especially to heat; therefore, raw foods are considered the best sources.

Effect: Folate is involved in a number of important biochemical pathways essential for health, especially cell development and growth. It is considered the most important supplement that women take in the weeks before conception and during the first 12 weeks of pregnancy. Its other uses include lowering homocysteine levels (often in combination with vitamins B12 and B6), reducing the risk of cardiovascular disease and cancer in general, and is used in the treatment of depression, schizophrenia and vitiligo. Deficiency: Isolated folate deficiency is uncommon because it usually coexists with other nutrient deficiencies due to poor diet and alcoholism. Megaloblastic anemia, which is characterized by large, abnormally nucleated erythrocytes, is the primary clinical symptom of folate or vitamin B12 deficiency. Its symptoms include weakness, fatigue, difficulty concentrating, irritability, headaches, palpitations and shortness of breath. Folate deficiency can also cause painful ulcers on the tongue and oral mucosa, changes in skin, hair or nail pigmentation and gastrointestinal symptoms. Women with insufficient folate intake are at increased risk of giving birth to babies with neural tube defects. Inadequate maternal folate status is also associated with low infant birth weight, preterm birth, and fetal growth retardation. Among the most endangered groups of people who should supply the body with sufficient amounts of KL are alcoholics, women planning pregnancy and pregnant women, as well as patients with diseases of the digestive system and people with MTHFR (methylenetetrahydrofolate reductase) polymorphism.

Recommended daily dose: adult: 400 µg for men, 400 µg for women (600 µg during pregnancy, 500 µg during breastfeeding). About 85% of folate is available when taken with food, while only about 50% is available to the body when taken on an empty stomach. To make it possible to compare foods containing different forms of vitamin B9, so-called folate equivalents (sometimes the abbreviation DFE from the English term dietary folate equivalent) were introduced: 1 μg of DFE thus corresponds to 1 μg of folate in food or 0.5 μg of synthetic acid leaf, which is taken, for example, in the form of a dietary supplement on an empty stomach.

Adverse effects: They are limited to oral doses higher than 5 mg/day. Reactions include hives associated with an allergic response, nausea, flatulence, bitter taste in the mouth and irritability.

Interactions: Methotrexate, used to treat cancer and autoimmune diseases, is a folate antagonist. Patients taking methotrexate for cancer should consult their oncologist before taking KL, as it may interfere with the anticancer effects of methotrexate. However, dietary folate supplements may reduce the gastrointestinal side effects of low-dose methotrexate used to treat rheumatoid arthritis or psoriasis. Antiepileptic drugs such as phenytoin, carbamazepine, and valproate are used to treat epilepsy, psychiatric illnesses, and other medical conditions. These drugs may decrease serum folate levels. In addition, folate supplements may decrease serum levels of these drugs, so patients taking antiepileptic drugs should consult their physician before taking folate supplements. Sulfasalazine is primarily used to treat ulcerative colitis. It inhibits the intestinal absorption of folate and can cause its deficiency. Antacids and proton pump inhibitors to reduce stomach acidity reduce folate absorption, so take them separately after 2‒3 hours. Oral contraceptives reduce folate levels, especially with long-term use of higher doses of estrogen. Pancreatin reduces the absorption of folate, so take it separately after 2‒3 hours.

Pregnancy: safe in usual doses.

Breastfeeding: safe in usual doses.

Toxicity: Some experts are concerned that high intake of KL supplements may "mask" vitamin B12 deficiency. KL intake that exceeds the body's ability to reduce it to THF leads to unmetabolized folic acid in the body, which is associated with reduced numbers and activity of natural killer cells, suggesting it could affect the immune system. In addition, some researchers hypothesize that unmetabolized KL may be related to cognitive impairment in the elderly. There has also been concern that a high intake of KL could accelerate the progression of preneoplastic lesions, thereby increasing the risk of colorectal and possibly other cancers in some individuals. In addition, intake of 1,000 µg per day or more of folic acid from supplements during the periconceptional period was associated with lower scores on several tests of cognitive development in children aged 4–5 years than children of mothers who took doses below or recommended.