Folate and Folic Acid

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim (Chapter 4)

Role of folate and folic acid in human metabolic processes

Bio-availability of Folic Acid and Food Folate

Differences in bio-availability of folic acid and food folate

The RNIs suggested food folate as the source of dietary folate

because most societies in developing countries consume folate from naturally occurring sources. As discussed in the introduction, natural folates are found in a conjugated form in food, which reduces its bio-availability by perhaps as much as 50 percent. In addition, natural folates are much less stable. If chemically pure folic acid (pteroyl monoglutamate) is used to provide part of the RNI, by way of fortification or supplementation, the total dietary folate, which contains conjugated forms (pteroyl polyglutamates), could be reduced by an appropriate amount. On average the conjugated folate in natural foods is considered to be only half as available as synthetic folic acid. For example, the recommendation of usual mixed forms of folate in the diet is 400 μg/day, but 100 μg of this given as pure folic acid would be considered to be equivalent to 200 μg of dietary mixed folate. Hence, only an additional 200 μg of dietary folate would be needed.

The FAO/WHO expert group agreed with the findings of the Food and Nutrition Board of the US National Academy of Sciences: 

Risk of Folate Deficiency

Definition of populations at risk for folate deficiency

Nutritional deficiency of folate is common in people consuming a limited diet. This can be exacerbated by malabsorption conditions, including coeliac disease and tropical sprue. Pregnant women are at risk of folate deficiency because pregnancy significantly increases the folate requirement, especially during periods of rapid foetal growth (i.e., in the second and third trimester. During lactation losses of folate in milk also increase the folate requirement.

Role of Folate and Folic Acid

Role of folate and folic acid in human metabolic processes

Folates accept one-carbon units from donor molecules and passes them on via various biosynthetic reactions. In their reduced form cellular folates function conjugated to a polyglutamate chain. These folates are a mixture of unsubstituted polyglutamyl tetrahydrofolates and various substituted one-carbon forms of tetrahydrofolate (e.g., 10- formyl, 5,10-methylene, and 5-methyl). The reduced forms of the vitamin, particularly the unsubstituted dihydro and tetrahydro forms, are unstable chemically. They are easily split between the C-9 and N-10 bond to yield a substituted pteridine and p-aminobenzoylglutamate, which have no biologic activity. Substituting a carbon group at N-5 or N-10 decreases the tendency of the molecule to split; however, the substituted forms are also susceptible to oxidative chemical rearrangements and, consequently, loss of activity. The folates found in food consist of a mixture of reduced folate polyglutamates.

Vitamin B12 Interaction with Folate or Folic Acid

One of the vitamin B12 – dependent enzymes, methionine synthase, functions in one of the two folate cycles – the methylation cycle. This cycle is necessary to maintain availability of the methyl donor S-adenosylmethionine; interruption reduces the wide range of methylated products. One such important methylation is that of myelin basic protein. Reductions in the level of S-adenosylmethionine seen in PA and other causes of vitamin B12 deficiency produce demyelination of the peripheral nerves and the spinal column, called subacute combined degeneration. This neuropathy is one of the main presenting conditions in PA. The other principal presenting condition in PA is a megaloblastic anaemia morphologically identical to that seen in folate deficiency. Disruption of the methylation cycle should cause a lack of DNA biosynthesis and anaemia.

Folate and Folic Acid

Role of folate and folic acid in human metabolic processes

Folates accept one-carbon units from donor molecules and passes them on via various biosynthetic reactions. In their reduced form cellular folates function conjugated to a polyglutamate chain. These folates are a mixture of unsubstituted polyglutamyl tetrahydrofolates and various substituted one-carbon forms of tetrahydrofolate. The folates found in food consist of a mixture of reduced folate polyglutamates.

Food-based Approaches to Meeting Vitamin and Mineral Needs - Folate

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 2).

Folate is now considered significant not only for the prevention of macrocytic anaemia, but also for normal foetal development. Recently, this vitamin was implicated in the maintenance of cardiovascular health and cognitive function in the elderly. Staple diets consisting largely of cereal grains and tubers are very low in folate but can be improved by the addition of legumes or green leafy vegetables. 

For example, a regular portion of cooked lentils (95 g) added to a rice-based diet can provide an amount of folate sufficient to meet the desirable nutrient density for this vitamin. Other legumes such as beans and peas are also good sources of this vitamin, but larger portions are needed for folate sufficiency (100 g beans and 170 g peas). Cluster bean and colacasia leaves are excellent folate sources used in the Indian diet.