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Folates not folic acid for flour fortification, urge researchers

By Lynda Searby , 25-Jul-2014
Last updated on 28-Jul-2014 at 16:25 GMT2014-07-28T16:25:22Z

Researchers: "...the gut lining doesn’t metabolise folic acid to 5-MTHF anywhere near as efficiently as it metabolises natural folates..."

New findings that the body is less efficient at metabolising folic acid than natural folates could inform policy-making decisions as the UK government considers mandatory fortification of flour with folic acid.

Researchers from the Institute of Food Research and Newcastle University found that the body processes synthetically-produced folic acid differently to folates – the form found in vegetables. This leads to unmetabolised folic acid circulating in the bloodstream which is eventually metabolised by the liver, but the process is slow and inefficient.

A double-edged sword

In countries with mandatory folic acid fortification programmes, neural tube defects such as Spina Bifida and Anencephaly, which are associated with low folate levels, have fallen by up to 46%.

However, the flipside to such policies is the risk of over-exposure - one study found that three quarters of post-menopausal women had folic acid circulating in their bloodstream.

A number of studies have flagged potential problems with excess folic acid, including compromising the immune system, masking vitamin B deficiency and increasing the risk of some forms of cancer.

As the UK considers whether to follow the example of the USA, Canada and Australia and 70+ other nations in introducing mandatory folic acid fortification programmes, the researchers are urging the government to either consider using a different folate form, or further investigate the implications of excess folic acid.

Fortify with folates

“We only carry out studies and don’t make policy decisions, but we’d hope that future decisions about fortification with folic acid take into account our central finding – that we don’t metabolise folic acid in the same way as natural folates,” research leader Paul Finglas, of the IFR, told NutraIngredients.

“Where fortification does happen, we’d suggest 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 now that more stable synthetic forms have been made available commercially.”

The folate forms he is referring to are Merck’s Metafolin and Quatrefolic from Gnosis, both of which have been decreed safe for use in supplements and foods by the EFSA (European Food Safety Authority).

Folic acid metabolism

The researchers reported that 86% of folic acid in the hepatic portal vein (which carries blood from the gut to the liver) was unmetabolised, whereas almost all of the natural folate was converted correctly.

“Folates are taken up by the cells lining the gut and are metabolised by an enzyme called 5,10-methylene THF into a form called 5-Methylformate (5-MTHF) – the biologically active form,” said Finglas, explaining the metabolism process.

He said the assumption, based on studies in rats, was that the gut lining could do the same with folic acid, using an enzyme called Dihydrofolate reductase (DHFR).

“However, what the study showed was that the gut lining doesn’t metabolise folic acid to 5-MTHF anywhere near as efficiently as it metabolises natural folates, as we could see much unmetabolised folic acid in the hepatic portal vein. The liver becomes overloaded and unmetabolised folic acid enters the blood circulatory system,” explained Finglas.

He said that although the liver does eventually metabolise the folic acid that has entered the circulatory system, the effect this has on the health is unknown.


American Journal of Clinical Nutrition

2014; vol 100: pp 593-9 (doi:10.3945/ajcn.113.080507 )

'Folic acid handling by the human gut: implications for food fortification and supplementation'

Authors: Imran Patanwala, Maria J King, David A Barrett, John Rose, Ralph Jackson, Mark Hudson, Mark Philo, Jack R Dainty, Anthony JA Wright, Paul M Finglas, and David E Jones

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