Folic acid

• Vitamin B9
• Vitamin B11
• Vitamin M

• Folic acid
• Pteroyl mono -glutamic acid
• L- folic acid
• (2S)- N-(4 - (( (2- amino-4- hydroxypteridine -6-yl ) methyl ) amino) benzoyl) glutamic acid (IUPAC)

B03BB01

250 ° C ( decomposition)

The folic acid [ from Latin folium = leaf ( due to the presence in green plant leaves )] ( the synthetic form of the B vitamin, with a monoglutamate, see picture with n = 1), also: Vitamin B9, Vitamin M ( uncommon ) vitamin B11 ( uncommon) or folate (the sum of folatwirksamen compounds, ie: with both a mono- or more glutamate residues attached polyglutamate ), is a 1941 discovered, heat-and light-sensitive vitamin of the B complex. It 's chemical composed of a pteridine derivative, para- aminobenzoic acid and L- glutamic acid.

• 4.1 Recording and Storage
• 4.2 Physiological needs
• 4.3 Folic acid deficiency and malformations

• 5.1 Germany
• 5.2 Switzerland
• 5.3 U.S. and Canada

Occurrence

Among the natural folate suppliers include, in particular yeasts with up to 2500 micrograms per 100 g, wheat germ and bran, with up to 400 micrograms per 100 g, as well as veal and chicken liver with around 100 micrograms per 100 g Small amounts are found in whole grains, green leafy vegetables, avocado, beetroot, broccoli, carrots, asparagus, radishes, brussel sprouts, arugula, spinach, tomatoes, egg yolks, nuts, fruit, fish and meat.

Production

Folic acid is produced in the chemical industry by the ton. First, the 6 -hydroxy-2 ,4- diaminopyrimidine to synthesized from guanidine and ethyl cyanoacetate, which is then reacted with nitrous acid to give the nitro derivative, and then reduced ,4,5- triaminopyrimidine of 6-hydroxy -2. As reducing agent, this tin ( II) chloride, sodium dithionite or hydrogen can be used in conjunction with a hydrogenation catalyst (palladium on charcoal).

In a three-component - reaction, the 6-hydroxy -2 ,4,5- triaminopyrimidine followed by 1,1,3- trichloroacetone, and N- (4- aminobenzoyl )-L -glutamic acid under weakly acidic conditions, and with the aid of sodium bisulfite to the folic acid implemented. Instead of 2,3- Trichloracetons Dibrompropionaldehyd or methylglyoxal can be used.

Chemical and physical properties

Acidity

Folic acid is a triple proton acid. The associated negative decadic logarithm of acid constants ( pKa values ​​) under normal conditions be in water 4.65; 6.75; 9.00.

Stability

The vitamin are sensitive to light (particularly UV rays), oxygen, heavy metals, as well as elevated temperatures ( albeit very small) with respect to water. Therefore should be avoided too intense watering and excessive storage and cooking times of foods. Also on human skin striking intense solar radiation reduces the folic acid in the body. In fair-skinned people, the effect is particularly strong.

Physiological significance

Folic acid is the precursor of the coenzyme tetrahydrofolic acid (THF ), which is present under physiological conditions as anion tetrahydrofolate. This has a central role in C1 metabolism. THF is particularly as a source of methyl ( - CH3 ), methylene ( CH2 =), and formyl groups ( - HCO ), with the synthesis of purine and deoxy- thymidine monophosphate ( dTMP ), which are necessary for DNA replication,. THF also is a coenzyme of the methylation of homocysteine ​​to methionine. Delivered the C1 building blocks of THF and Others of the amino acids serine, glycine and histidine. A stress test with histidine is used for diagnosis of folate deficiency. Because of the involvement in the synthesis of DNA building blocks folic acid, therefore, particularly in pregnancy, as well as with frequently dividing cells ( eg, bone marrow ) plays a crucial role.

Receiving and storing

Folic acid is - like all vitamins - essential for the human organism and can not be produced by him. Therefore, folic acid must be taken with food. To enter first into the cell interior, starting with the intestinal mucosal cells, the folic acid molecule proton coupled to the presence of the transport protein Folattransporter is dependent, which is also responsible for export into the bloodstream. THF and 5- derivatives of THF use the Folattransporter 1 for the import, even and especially in the gut. Folate, dihydrofolate (DHF ) and THF can switch to the mitochondria via the mitochondrial Folattransporters.

Folate and its derivatives are stored by binding to polyglutamate in the cytosol and the mitochondria of the cells. Only the number of carbon transferred reactions can take place. In particular for the binding of DHF, and THF Folylpolyglutamat the enzyme synthetase is required.

Folatüberschuss resulted in cell cultures resulted in a significant decrease in the expression of all folattransportierenden proteins ( PCFT, RFC, folate receptor ) in intestinal cells. In the human organism folic acid excesses may conceal a vitamin B12 deficiency.

Physiological needs

The recommended daily allowance RDA is 200 micrograms. The reference values ​​for nutrient intake ( 1st edition, 3rd corrected reprint 2008 of the German Society for Nutrition Association) recommend a daily intake of 400 micrograms of folic acid ( women wishing perikonzeptionell 800 micrograms ). In view of the additional prevention against atherosclerosis were formerly 600 micrograms for healthy adults, recommended 800 mcg for pregnant women and nursing mothers. The supply of more than 1,000 micrograms of folic acid daily health has no additional effect and only results in a cycle of non- metabolizable folic acid in the body. This is due to the extremely limited activity of the so-called dihydrofolate reductase ( DHFR) and its associated rapid saturation. This occurring in the liver enzyme helps the supplied folic acid in a useful form for the human body ( tetrahydrofolic acid ) to convert. After administration of larger amounts of folic acid, these are excreted largely unchanged in the urine as Pteroylmonoglutamat. The risks of over supply of folic acid are, however, now considered critical. Thus, an excess of folic acid mask a vitamin B12 deficiency, from the damage to the nervous system can follow.

Folic acid deficiency and malformations

A folic acid deficiency in the human body has an effect on the blood picture by can lead to macrocytic hyperchromic anemia. Man can store a maximum of 12 to 15 mg of folic acid; this corresponds to a storage for three to four months. Normally, the blood serum contains from 5 to 20 g / L, the red blood cells 160 to 640 g / L of the vitamin. A deficiency of serum levels drops first, which is why most of this is about performance liquid chromatography ( HPLC) or determined by chemiluminescence. Very often enters folic acid deficiency as a consequence of increased alcohol consumption, diseases of the small intestine or liver disease. In women, folic acid requirements are increased with intake of contraceptives, as well as within the pregnancy.

In the embryonic folic acid deficiency promotes the development of neural tube defects such as spina bifida or anencephaly a. He should also have an impact on preterm delivery and seems to be involved in the development of congenital heart defects. Each year about 800 children are born with a neural tube defect in Germany, thus about one in a thousand newborns is affected; be added because of spina bifida are aborted pregnancies. An adequate supply of folic acid during pregnancy seems to also play well with regard to the language development of the child an important role. A prospective observational study from Norway also shows an association between folate deficiency and autism, which is why folic acid should be taken already at the request of a pregnancy.

Folic acid deficiency leads to pernicious anemia ( hyperchromic macrocytic anemia). The responsibility of folic acid on the cell maturation, differentiation and division, especially the red and white blood cells and mucous cells is currently under investigation in several universities and research laboratories. In diseases of the cardiovascular system, such as atherosclerosis, is also to be paid to the sufficient supply of folic acid. The value of the amino acid homocysteine ​​in the blood is considered as a cardiovascular risk factor. Homocysteine ​​is converted to methionine by means of folic acid and vitamin B12. The positive effects of increased folate gifts - the lower the homocysteine ​​levels among other things - on the course of cardiovascular disease are not well documented.

Legal Aspects

Germany

From the perspective of the Ministry of Consumer Protection in Germany there is no need admixture duty. Even nutrition experts of the consumer centers, inter alia, have spoken out against a mandatory fortification of flour with folic acid, since consumers receive sufficient folic acid in a natural way with fruit, vegetables and whole grain bread and also at liberty to him, offered a dietary supplement or commercially, folic acid fortified cereal bars to purchase beverages, dairy products, or saline.

Since two -thirds of adults in Germany take on average less than 300 micrograms daily, call on some pediatricians and some health officials, the staple flour ( if it is not wholemeal flour ) to mix folic acid. In this way, in particular defects in Neuralrohrbildung to prevent entering the first three weeks of pregnancy, and thus at a time when the pregnancy is usually not yet known. From medical advocates of folic acid fortification is argued that the number of pregnancies with neural tube defects in Germany in international comparison is particularly high ( 12.36 / 10.000 births, compared to the international average of 7,88 / 10 000 births). Every year in Germany there are about 800 pregnancies with neural tube defects that are aborted in the majority after a positive screening test. Herrmann / Obeid are of the opinion that the incidence of neural tube defects could be reduced by 20 to 60% by periconceptional folic acid administration.

Switzerland

In January 2000, the Foundation began a national folic acid campaign Switzerland prevention campaign with the aim to close the gap folic acid according to the fourth Swiss Nutrition Report 98 of the Federal Office of Public Health. About three hundred products have since been fortified with folic acid, which are distinguished with the logo vitamin folate life. Thanks to this campaign of awareness of folic acid prevention from 2000 to 2010 increased from 38 % to 76 %.

U.S. and Canada

In the U.S. and Canada, a folic acid supplement is required by law in flour. Since then, only about half as many children come to Canada with spina bifida into the world, anencephaly decreased by 38%, encephalocele by 31%. In the U.S., a decline in 1-34 percent was (average about 20%) for spina bifida observed depending on population, similar results are in anencephaly before.

Trade names

Andreafol (CH), DreisaFol (D), Drossafol (CH), Fertifol (CH), Folarell (D), Folcur (D), Folgamma mono ( D), Folsan (D), Folverlan (D), Folvite (CH), Gravi -Fol (D), Lafol (D), RubieFol (D)

AKTIFERRIN -F ( CH ), baby Forte Folic Acid Plus ( D), Duofer -Fol (CH), Eryfer comp. (D) Femibion ​​(D), Fero - Folic (CH), Ferro - Folgamma (D), Ferro - Folsan (D), Ferro Sanol comp. / Gyn (D), Folgamma (D), Folicombin (D), Gyno- Tardyferon (CH), Hämatopan F ( D), folic Kendural (D), Maltofer -Fol (CH), Plastulen Duo ( D), Tardyferon -Fol (D), folic acid, prenatal - No. 1 ( D), Vitaverlan (D)