12 January - 20 June 2016

Folic acid, dietary folate, and potential risks of food fortification

13 August 14

A study from Newcastle University and the Institute of Food Research has investigated how folic acid supplements are processed in the body, as compared to the natural folates found in leafy green vegetables. Its results are particularly relevant right now as the UK government considers mandatory fortification of bread flour with folic acid as a measure to help prevent neural-tube birth defects (NPDs) such as spina bifida.

It has long been advised in the UK that pregnant women and those trying to conceive take folic acid supplements to help reduce the risk of such conditions - and over 70 countries across the world have also introduced forms of mandatory folic acid fortification in foods for the same reason. This fortification helps ensure that the protection provided by the folic acid reaches as much of the population as possible, especially as unplanned pregnancies mean mothers may have less opportunity to take a supplement before conception or early in pregnancy. It has been a successful approach; when Canada, for example, introduced mandatory fortification of many cereal products, NPD prevalence decreased by 46%, from 1.58 per thousand births to 0.86.

So far, so positive, but the recent study - published in The American Journal of Clinical Nutrition - raises some concerns about fortification. These concerns centre around the fact that the synthetic folic acid that is used in supplements and in food fortification is not metabolised in the same way as natural dietary folates, and that there are potential health risks as a result. In the study, participants were given a 500nmol dose of either isotope-labelled folic acid, or isotope-labelled reduced folate 5-formyltetrahydrofolic acid (5-FormylTHF, a dietary folate). 500nmol is a "physiological dosage", meaning that it is lower than a "pharmacological dosage", and more akin to an amount that could be ingested through diet. 15 minutes after receiving the dose, blood samples were taken from the hepatic portal vein; when the labelled folate in each sample was analysed, it was found that for the folic acid group, 80 ± 12% of it was unmodified folic acid, whilst in the 5-FormylTHF group 4 ± 18% was unmodified 5-FormylTHF, with the rest metabolised to 5-MTHF, which is the natural circulating form in the body.

Participants were all patients with stable liver cirrhosis in a programme of follow-up monitoring, which meant that they had a transjugular intrahepatic porto systemic shunt (TIPSS) in situ. This allowed blood to be taken directly from the hepatic portal vein. This vessel runs from the gastrointestinal tract (where nutrients from food etc enter the bloodstream) to the liver, so sampling blood from here allowed the state of the folate immediately after metabolic processing in the digestive tract to be ascertained. This specialised requirement also led to the study having a very small sample size of six patients.

It seems, then, that bread flour fortification leading to people's repeated exposure to folic acid could very well lead to the unmetabolised substance circulating in the body, which could lead to various dangers. One such is the possibility of vitamin B12 deficiency, common in the elderly, being masked and therefore going untreated; this can lead to cognitive decline. Studies have also shown greater incidence of prostate and other cancers, as well as an increase in overall mortality, in those taking folic acid supplements.

The increased risk of NPDs associated with low folate levels during pregnancy can be mitigated either with the synthetic folic acid or with dietary folates, and so study author Paul Finglas recommended that where "fortification does happen...the forms of methyltetrahydrofolic acid (the natural form of the vitamin in food and main circulating form in the body) could be considered as an alternate fortificant to folic acid." [FoodManufacture]

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