Vitamin B12, Folic Acid and Homocysteine
Vitamin B12 and folic acid (also folate, vitamin B9) are very closely connected in the metabolism. Both play an important role together in methionine synthase; the conversion of dangerous homocysteine to methionine.
Vitamin B12 is responsible for reactivating folic acid, by converting it through various reactions back into tetrahydrofolate, the form of folic acid which the body can use. A vitamin B12 deficiency thus leads to an indirect folic acid deficiency: even if enough folic acid is provided for the body, it cannot be used unless a supply of vitamin B12 is present; its simply sits in its inactive form.
On the other hand, vitamin B12 cannot fulfill its role in the deconstruction of homocysteine without folic acid – the two vitamins are dependent on one another. Before we explore this relationship in detail, it is important first to touch upon the most important information regarding the role of folic acid.
Folic Acid and Folate
Folic acid is a synthetic compound which cannot be directly used by our body. The natural and bioactive form of folic acid is folate, which is used in various chemical forms in the body. Normally, the body is capable of absorbing folic acid well and converting it into folate. However, since this isn’t always the case, supplements which contain the bioactive folate instead of folic acid are now also available.
A Vitamin B12 Deficiency Causes a Folic Acid Deficiency
Since a lack of vitamin B12 also leads to a folic acid deficiency, vitamin B12 has a doubly important position in cell metabolism. Both vitamins fulfill important functions and are essential for maintaining health. Folic acid is responsible for the following tasks:
- Cell division
- Hematopoiesis (blood formation)
- Mucosal structure
- DNA synthesis
- Protein metabolism
- Fat metabolism
A lack of folic acid can hence lead to many grave symptoms, such as anemia, depression, stomach and/or intestinal problems and weight loss.
Folic Acid and Pregnancy
The most serious consequences of a folic acid deficiency can be seen during pregnancy. Here it can lead to abortions, malformations, premature births, heart defects and development disorders.1 Folic acid plays an important role in the development of the neural tube – the first development stage of the nervous system, as well as in cell growth processes and in DNA synthesis. Finally, folic acid is also the only vitamin that can prevent spina bifida. These reasons highlight the need for pregnant women to ensure a good supply of folic acid and vitamin B12 especially.2
The folic acid daily intake requirement almost doubles in pregnancy and is difficult to meet through a normal diet, which is why a folic acid deficiency is especially common here. Gynecologists in most cases recommend taking folic acid supplements of around 400 – 800 µg of folic acid during pregnancy.
During breastfeeding, the body’s requirement for folic acid remains high – so it can be advisable to take supplements at this time as well.
Folic Acid When Trying to Conceive
Women who are trying should be sure to check their folic acid supply before pregnancy starts, because often women who fall pregnant remain unaware for the first two to four weeks, before pregnancy tests available over the counter can confirm this. This period in time, however, is a critical phase for the development of the embryo, during which folic acid is needed urgently.
Consequently, folic acid supplies should be optimal from the moment that the decision to try for a child is made. This way, a folic acid store is already being built up, through which a stabile folic acid status can be ensured during the pregnancy.
The rumor that folic acid increases the chance of conception is not applicable here.
Meeting the RDA for Folic Acid and Vitamin B12
1-4 /4-7 years
120 µg /140 µg
7-10 /10-13 years
180 µg / 240 µg
From 13 years
Foods Containing Folic Acid
Folic acid is sensitive to heat, meaning that foods often lose a large part of their folic acid content (40-70%) during cooking. Fresh, raw vegetables, salads and herbs are thus the best sources of folic acid. Instead of cooking vegetables, it can be better to stew them, through which they maintain at least some of their folic acid content.
Many food charts don’t factor in this loss during cooking and thus the statistics for raw vegetables can be misleading. Red cabbage, for example, contains 100 µg of folic acid, but after cooking contains around 45 µg.
Folic Acid Foods Chart
The following foods contain particularly high quantities of folic acid:6
Folic Acid Content (µg/100g)
Bean sprouts (tinned)
Olives (in oil)
Folic Acid B12 Supplements
As a result of the close relationship between vitamin B12 and folic acid, there are many supplements which combine the two vitamins.
Just like with vitamin B12, there are also a number of active ingredients for folic acid. A promising and very recent development is the direct use of L-5-methyltetrahydrofolate (also L-5-methylTHF, L-methylfolate, MTHF and 5-methylTHF) in food supplements. This is the form of folate which is transported in the blood and which works together with vitamin B12.
The direct use of L-5 MTHF makes sense, since the other synthetic forms of folic acid must first be converted by the small intestine in a multilevel process before they form 5-methylTHF (see diagram below). The final step of this process, in which 5.10-methyltetrahydofolate is converted into L-5-methylTHF, is particularly difficult as a result of impairment caused by enzyme disorders in many people, which is why the direct use of MTHF is recommended.
A practical dosage for such supplements should be between 200 and 800 µg per dose.
Folic Acid Pills, Capsules and Injections
Folic acid supplements occur most commonly in the form of folic acid pills, but capsules are also widely available. Injections are also used particularly in treatment of anemia patients.
Capsules and injections have the advantage of being very pure in most cases, whilst tablets commonly contain a variety of additives.
Folic Acid and Vitamin B Complex
Folic acid is also known as vitamin B9 and belongs to the vitamin B complex. However, since folic acid is much more well known by its actual name, it is often mentioned alone and relatively few people are aware that folic acid and vitamin B9 in fact describe the same vitamin.
The vitamins of the B complex all work very closely together. However, vitamin B12, folic acid and vitamin B6 work particularly closely in tandem, all playing a role in the deconstruction of homocysteine.
Folic Acid, Folate and Vitamin B12
What does the interaction between vitamin B12 and folic acid actually look like? This can be easily understood with a little simple chemistry. As previously discussed, folic acid cannot be used directly by out body, it must first be converted into various folate forms in the small intestine before absorption. The active form of folic acid found in the body is known as tetrahydrofolate (THF).
However, the folic acid which circulates in the blood is 5-methyltetrahydrofolate (5-MethylTHF, MTHF). Through the use of vitamin B12, this MTHF plays a sort of methyl group ping pong:
MTHF gives off its methyl group to vitamin B12 (cobalamin), which becomes methylcobalamin. At the same time, the MTHF folic acid is converted back into its bioactive form, tetrahydrofolate, through the same reaction. The methylcobalamin then gives off its methyl group in a further step to homocysteine, which is then converted to methionine.
Then the cycle begins again as new, with the newly free cobalamin reacting with the next MTHF molecule, and so on. The result of this is twofold; firstly the dangerous homocysteine is converted into the very important methionine, and secondly the folic acid is regenerated into its bioactive form once more. This reaction plays a key role for many metabolic processes which are very relevant to health and wellbeing in the body.
S-Adenosyl methionine (SAM)
The methionine from this reaction is converted in further steps to S-adenosyl methionine (SAM) – one of the most important things for the production of various neurotransmitters and for DNA methylation. The latter specifies how certain genes in our genome are selected and thus has very profound effects on the body as a whole organism.
In this reaction, SAM gives off its methyl group and thus becomes homocysteine, starting the whole cycle mentioned above again as new.
1 Scholl TO, Johnson WG: Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 71, Suppl 5 (2000) S1295-S1303
2 Greenberg JA, Bell SJ, Guan Y, Yu YH: Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol 4 (2011) 52-59
3 Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für Ernährung, Schweizerische Gesellschaft für Ernährungsforschung, Schweizerische Vereinigung für Ernährung (Hrsg.): Referenzwerte für die Nährstoffzufuhr. Folat. Neuer Umschau Buchverlag, Neustadt a. d. Weinstraße, 1. Auflage, 5., korrigierter Nachdruck (2013)
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6 Prof. Dr. Helmut Heseker, Dipl. oec. troph. Beate Heseker; Die Nährwerttabelle, 2. Aufl., 2012, Neuer Umschau Buchverlag