Folic Acid Supplementation

Since the discovery of the link between insufficient folic acid and neural tube defects (NTDs), governments and health organizations worldwide have made recommendations concerning folic acid ''supplementation'' for women intending to become pregnant.

This has led to the introduction in many countries of ''fortification'', where folic acid is added to flour with the intention of everyone benefiting from the associated rise in blood folate levels. This is controversial, with issues having been raised concerning individual liberty , and the masking effect of folate fortification on pernicious anaemia (vitamin B₁₂ deficiency). However, several western countries now fortify their flour, along with a number of Middle Eastern countries and Indonesia. Mongolia and a number of ex-Soviet republics are amongst those having widespread voluntary fortification; about five more countries (including Morocco, the first African country) have agreed but not yet implemented fortification. To date, no EU country has yet mandated fortification.

Folates can be produced by engineering Lactococcus lactis strains using a rodent depletion-repletion bioassay and the bioavailabilities of these folates are comparable with commercial folic acid currently being used for food fortification. These engineered folates can potentially help alleviate the effects of folate deficiency in the diet. Hematologic studies show an improvement in megaloblastic anemia after the addition of L. lactis strains; this again suggests that lactic acid bacteria can potentially reverse some of the harm done by folate deficiency by acting as an essential, bioavailable vitamin.

Effects of fortification and plasma folate and homocysteine levels

A study has shown that folate fortification will substantially increase in folate status, particularly for the elderly. In the study group, the subjects who did not use vitamin supplements has increased folate concentrations of 4.6 ng/mL to 10.0 ng/mL (11 to 23 nmol/L) (P<0.001) from the base-line visit to the follow-up visit. The prevalence of low folate concentrations (<3 ng/mL nmol/L) decreased from 22.0% to 1.7% (P< 0.001). The mean total homocysteine concentration has decreased from a value of 10.1 µmol/L to 9.4 µmol/L during this period (P<0.001), while the prevalence of high homocysteine concentrations (>13 µmol/L) has been reduced from 18.7% to 9.8% (P<0.001). To further clarify the study methods, there were no statistically significant changes in concentrations of folate or homocysteine for the control group.

Australia

There has been previous debate in Australia regarding the inclusion of folic acid in products such as bread and flour.

Australia and New Zealand have jointly agreed to fortification though the Food Standards Australia New Zealand. Australia will fortify all flour from 18 September 2009. Although the food standard covers both Australia and New Zealand, an Australian government official has stated it is up to New Zealand to decide whether to implement it in New Zealand, and they will watch with interest..

The requirement is 0.135 mg of folate per 100g of bread.

Canada

In 2003, a Hospital for Sick Children, University of Toronto, research group published findings showing that the fortification of flour with folic acid in Canada has resulted in a dramatic decrease in neuroblastoma, an early and very dangerous cancer in young children. In 2009, further evidence from McGill University showed a 6.2% decrease per year in the birth prevalence of severe congenital heart defects.

Folic acid used in fortified foods is a synthetic form called pteroylmonoglutamate. It is in its oxidized state and contains only one conjugated glutamate residue. Folic acid has a higher bioavailability than natural folates and are rapidly absorbed across the intestine The purpose of fortification was to decrease the risk of neural tube defects in newborns. A 7 province study from 1993 to 2002 showed a reduction of 46% in the overall rate of neural tube defects after folic acid fortification was introduced in Canada.

The fortification program was estimated to raise a person’s folic acid intake level by 70-130 ug/day, however an increase of almost double that amount was actually observed. It is still unknown the amount of folic acid supplementation that might cause harm, and the Green Party have opposed mandatory fortification, describing it as "mass medication". Food Safety Minister Kate Wilkinson reviewed the decision to fortify in July 2009, citing links between overconsumption of folate with cancer . The New Zealand Government is reviewing whether it will continue with the mandatory introduction of folic acid to bread.

United Kingdom

There has been previous debate in the United Kingdom regarding the inclusion of folic acid in products such as bread and flour.

The Food Standards Agency has recommended fortification.

United States

The United States Public Health Service recommends an extra 0.4 mg/day, which can be taken as a pill. However, many researchers believe that supplementation in this way can never work effectively enough since about half of all pregnancies in the U.S. are unplanned and not all women will comply with the recommendation. Approximately 53% of the US population uses dietary supplements and 35% uses dietary supplements containing folic acid. Men consume more folate (in dietary folate equivalents) than women and non-Hispanic whites have higher folate intakes than Mexican Americans and non-Hispanic blacks.

This ruling took effect on January 1, 1998, and was specifically targeted to reduce the risk of neural tube birth defects in newborns. There are concerns that the amount of folate added is insufficient . In October 2006, the Australian press claimed that U.S. regulations requiring fortification of grain products were being interpreted as disallowing fortification in non-grain products, specifically Vegemite (an Australian yeast extract containing folate). The FDA later said the report was inaccurate, and no ban or other action was being taken against Vegemite.

As a result of the folic acid fortification program, fortified foods have become a major source of folic acid in the American diet. The Centers for Disease Control and Prevention in Atlanta used data from 23 birth defect registries that cover about half of United States births, and extrapolated their findings to the rest of the country. These data indicate that since the addition of folic acid in grain-based foods as mandated by the FDA, the rate of neural tube defects dropped by 25% in the United States. The results of folic acid fortification on the rate of neural tube defects in Canada have also been positive, showing a 46% reduction in prevalence of NTDs; the magnitude of reduction was proportional to the prefortification rate of NTDs, essentially removing geographical variations in rates of NTDs seen in Canada before fortification.

When the U.S. Food and Drug Administration set the folic acid fortification regulation in 1996, the projected increase in folic acid intake was 100 µg/d. Data from a study with 1480 subjects showed that folic acid intake increased by 190 µg/d and total folate intake increased by 323 µg dietary folate equivalents (DFE)/d.

More epidemiologic and clinical studies are need to be done on human tumor sample to fully understand the role of folate receptor alpha in tumor etiology, progression, and patient survival.