Is folic acid fortification harmful?

Fortifying bread with folic acid in an attempt to reduce the chances of birth defects in pregnant women could in fact be damaging to our health, reported The Daily Telegraph . New research has shown that the “synthetic supplement can easily saturate the liver and the body will struggle to break it down, leading to health problems”, the newspaper said.

The newspaper story is based on a review that discusses the absorption and metabolism of folic acid in the body, and highlights an important area for further research and understanding. However, this review has not specifically examined the breakdown of folic acid in the body in quantities that are to be found in fortified bread and it does not report on any adverse health effects that occur because of folic acid. Instead, based on evidence from other studies, this review suggests that folic acid is broken down in the body in a different way than has been assumed and the authors discuss some of this research to support their theory.

As this is not a scientific study but a narrative discussion, further work will be needed to confirm this theory. Importantly, folate (the naturally occurring form of folic acid) is an essential vitamin for the human body, and folic acid supplementation around the time of conception and early pregnancy, in particular, is known to reduce the risk of spinal defects in the baby such as spina bifida.

Where did the story come from?

This research was carried out by Anthony Wright and colleagues of the Institute of Food Research, Norwich. The study was supported by funding from the UK Biotechnology and Biological Sciences Research Council. It was published in the peer-reviewed British Journal of Nutrition .

What kind of scientific study was this?

This was a narrative article where the authors discussed the absorption and metabolism of folic acid in the body, drawing on evidence form both human and animal studies.

The authors challenge the theory that folic acid (a form of folate – a vitamin that occurs naturally in certain foods and is essential for the production of cells, including blood cells) is believed to be broken down by cells in the small bowel. They suggest instead that the breakdown takes place in the liver. They say that the liver has a limited capacity to break down folic acid and this may mean it  struggles to process (or becomes saturated with) folic acid, particularly if more of this is included in the diet, such as through fortification in foods.

What were the results of the study?

The researchers explain that naturally occurring folate and folic acid are both absorbed in the small bowel and are transported to the liver where further breakdown occurs. However, liver cells have a limited capacity to process the by-products above a certain dose level of folic acid. If the folic acid is not broken down, this will lead to an amount circulating in the body and this could be harmful, as other recent studies have linked high levels of folic acid with bowel cancer.

The researchers report various studies to explain their theory. One was a  study of three people where blood was obtained from the main vein that delivers blood to the liver from the bowel. It was found that the intestine may not be responsible for the first step in breaking down folic acid, possibly because the enzyme needed has a low activity level in the intestine. They say that there is evidence from blood samples that folic acid is being absorbed from the intestine unchanged and they propose that the liver is the initial site for the chemical breakdown of folic acid. Low activity levels of the enzyme needed to break down folic acid are a particular feature of human livers. They report that another study of 105 postmenopausal American women found high levels of the unconverted folic acid form to be present in fasting blood samples.

What interpretations did the researchers draw from these results?

The authors conclude that folic acid is not broken down in the intestine, but is transferred to the liver to be broken down and removed. They say that because of the low activity of the enzyme in the liver, it is possible that  “regular daily intake of physiological doses of folic acid may eventually result in its chronic appearance in the systemic circulatory blood system”. They suggest that before mandatory folic acid fortification is introduced in the UK, all concerns about risks and benefits should be carefully addressed.

What does the NHS Knowledge Service make of this study?

This research paper was a complex narrative discussion about the absorption and metabolism of folic acid in the body. These important findings call for much further research. However, when reading the newspaper headlines of the hidden dangers of folic acid supplementation, there are several important points to bear in mind:

• This study has not looked directly at fortified flours or breads and whether the quantity of folic acid contained in them would or would not be able to be broken down by the liver. The authors talk about there being signs of the liver having a saturation point for conversion of folic acid when a certain high dose is given (much above levels naturally occurring in foods). We have no information to compare how this dose relates to the quantity of folic acid that would be found in a slice of fortified bread, for example.
• Folate is an essential vitamin for the human body, and folic acid supplementation around the time of conception and early pregnancy is known to reduce the risk of spinal defects in the baby such as spina bifida.
• Any possible adverse health effects of excess folic acid are only speculative at the moment and further research would be needed to prove a firm link.
• The understanding of the absorption and metabolism of folate in its various forms, through supplements, fortified foods or naturally occurring is developing. Further study and research will answer the question of whether it is possible and beneficial to fortify flour in the best way in order to try to reduce the levels of disease related to folate deficiency.

Sir Muir Gray adds...

Reports of risk always have to be taken seriously; we will wait to see what the response to this article says. Often, we wait to see what other scientists say in the correspondence before deciding what to do, or if anything needs to be done.