Title: The Case for Folic Acid Fortification

Key words: folic acid deficiency, folic acid supplementation, folate, Vit B12

Date: July 2000

Category: 4. Food Data

Type: Article

Author: Dr van Rhijn


The Case for Folic Acid Fortification



Preventative medicine may make it possible to improve the quality of health in an ageing population and simultaneously alleviate the burden upon already stretched NHS resources. One simple, non-invasive and cost effective intervention would be to fortify bread with folic acid. This is an essential vitamin, often deficient in the population. Deficiency contributes to a number of preventable chronic diseases. This article provides a brief outline in favour of enrichment of bread with folic acid.


What is Folic Acid?

The collective name for the group of derivatives of folic acid is the water-soluble B vitamin Folate. It is involved in various metabolic reactions in the body. It is also essential for the synthesis of thymidine for DNA. This in turn is required for the growth and development of new and rapidly dividing cells, such as in the gastro-intestinal tract, hair follicles and haemopoietic cells of the bone marrow.

Sources, Absorption and Storage of Folate

Folate is synthesised by bacteria within the GI tract. Other sources include green leafy vegetables (sprouts, broccoli and spinach), green beans, peas, pulses, milk and fortified cereals and liver. It is absorbed in the duodenum and jejenum. Only a small amount (approximately 10%, sufficient for 2-3 months supply) is stored, mainly in the liver.

Metabolism of Folate

The active form of folate is 5,6,7,8-tetrahydrofolate (THF). This is a carrier for a number of one-carbon units which bind to its nitrogen units. THF receives these one-carbon fragments from donors such as serine, glycine or histidine and transfers them to intermediates in the synthesis of other amino acids, purines, pyrimidines, glycine, methionine and thymidine. THF is formed by the two-step reduction of folate by dihydrofolate reductase (DHF).

Reactions involving the transfer of methyl groups result in the formation of interconvertible N5-methyl THF, therefore the THF cannot be released and is trapped. The methionine salvage pathway, which requires Vit B12 as an essential cofactor, releases the THF again by methylation of homocysteine into methionine. The enzyme homocysteine methyltransferase is therefore Vit B12 dependent and in Vit B12 deficiency, this pathway is inhibited and the folate becomes trapped, resulting in secondary deficiency, despite adequate dietery intake of folate. Thus the metabolism of folic acid is closely linked to that of Vit B12.




Deficiency of Folic acid

Deficiency of folic acid is quite common, especially in the elderly (12%) and can devlop within 2-3 months, because the store is small relative to the daily requirement. Suspicion of deficiency, resulting in Megaloblastic anaemia can be confirmed with a blood sample.

- Low serum levels or more accurately red cell folate (normal = 135-750 mg/mL).

- Blood film: macrocytes – MCV > 100 fL & megaloblasts in bone marrow.

This is the same haematological profile as in Vit B12 deficiency, from which it must be distinguished.

Causes of Folate deficiency

Decreased intake: Poor diet (Poverty, elderly, anorexia, alcoholics)

Malabsorption: IBD (Coeliac, Crohn’s), small bowel resection, sprue

Gluten-induced enteropathy, Whipple’s disease

Increased requirements: Pregnancy, infancy, adolescence, dialysis, diarrhoea

Haemolytic anaemias, sickle cell disease, psoriasis

Cancer, menorrhagia, inflammatory states, recuperation

Impaired utilisation: Vit C deficiency; liver disease

Drugs: Anticonvulsants (Phenytoin, phenobarbitone), Asprin

Dihydrofolate reductase inhibitors (methotrexate)

Lithium carbonate, Contraceptive pill

Antimalaria drugs (pyrimethamine)

Secondary: Due to Vit B12 deficiency

Excessive endogenous oestrogen production

Exogenous factors Alcohol; Electromagnetic radiation; Light

Food processing: (Heat & Freezing)

Minerals Copper, Zinc

Requirements and Health benefits of Folate

The normal dietary reference value (COMA 1991) is set at 100-200 m g per day, but 400 m g during pregnancy. Folic acid is safe and toxicity is extremely rare.There is ample research evidence to suggest that folic acid has a protective and even preventative role in the diseases listed below:


There is a clear link between folate deficiency and elevated plasma levels of homocysteine, and hence a strong correlation with cardiovascular disease mortality. It is also a powerful risk factor for stroke and peripheral vascular disease due to a negative influence on thrombogenesis and lipid peroxidase-mediated arterial damage.

There is also evidence that deficiency can influence cancer risk, especially cervical, bronchial and colorectal cancers. It is exactly these diseases that are currently increasingly prevalent in the population, especially the elderly who are most commonly deficient in folic acid.

Several studies suggest that folic acid supplementation may be an effective intervention in the prevention of the occurrence and recurrences of neural tube defects (Spina bifida and anencephaly). The Department of Health recommends that all women planning a pregnancy should be encouraged to take a prophylactic folate supplement combined with iron to reduce the risk. Supplementation should start before the critical time (first few weeks after conception) and continue until the twelfth week of pregnancy. The dose of folic acid recommended for a woman hoping to conceive is 5 mg daily to prevent recurrence and 400 m g daily to prevent first occurrence. The consumption of folate-rich foods should be encouraged, except for liver, which despite being a rich source carries a risk of of Vit A toxicity.

Fortification of Food

As a result of the research evidence, public policies to promote awareness of the importance of this vitamin prior to, and in the early stages of pregnancy, have been proposed in a number of countries, including the UK (Health Education Authority). However, increased consumption of folate from dietary sources alone is not sufficient to boost folate status adequately. There is therefore a widespread fortification programme in the United States (FDA mandate) where folic acid is added to numerous food products, but controversy and resistance continues within the UK to introduce a similar compulsory fortification programme.

However, compulsory fortification may effectively increase the intake of folic acid in the population, especially in women who do not realise they are pregnant, and in the elderly, who often have a very restricted diets. Folate is safe, and the only concern about single supplementation with folic acid is masking a Vit B12 deficiency in pernicious anaemia. Adding Vit B12 simultaneously to the bread can easily prevent this, and would not put the elderly (deficient in Vit B12) at risk. This is despite the fact that Vit B12 is poorly absorbed orally, easily destroyed by Vit C and iron in the diet as well as the objection raised that it may colour fortified food pink. Synthetic folic acid is stable in fortified foods and 100% absorbed.


Fortification of bread with folic acid could have far reaching health consequences, by altering the risk/benefit ratio dramatically for cardiovascular diseases, cancers and the prevention of neural tube defects, not to mention the beneficial effect on psychiatric disorders. This single preventative measure could dramatically improve the health of the population at large and reduce the expenditure of the health service for these diseases.