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Folic acid debate continues

‘Adding folic acid to bread could be unnecessary and may even expose many to potentially negative health risks’, The Daily Telegraph has reported. Pregnant women are currently advised to take folic acid to help protect their child from developing birth defects such as spina bifida, and the Food Standards Agency has recommended that the vitamin should be added to flour.

While the US and Canada have introduced mandatory fortification of flour with folic acid, this new research looks at a sample of the population in Ireland, where fortification by manufacturers is voluntary. This new research does not seem to inform the debate about whether fortification of food should be mandatory. The researchers took blood samples from both adults and newborns, and tested for the unmetabolised form of folic acid. They found that many people were already getting folic acid through their daily diet. A small proportion of their total folate was unmetabolised, suggesting it was excess to requirements.

The authors say that excess folic acid may increase the risk of cancer and mask some types of anaemia. However, folate supplementation around the time of conception is known to have a strong protective effect against certain birth defects, and further research will be needed to balance any potential risk from the vitamin in other groups against this clear benefit for the unborn child.

Where did the story come from?

This research was carried out by Dr Mary R Sweeney from the School of Public Health and Population Science at University College Dublin and colleagues from elsewhere in Ireland and the United States. Two of the authors have declared that they have patents on compounds “in the folate field”.
The study was supported in part by a grant from the National Institutes of Health in the US and published in the journal BMC Public Health.

What kind of scientific study was this?

This study featured two separate sub-studies, which were cross-sectional analyses of levels of blood plasma folate, plasma folic acid and red cell folate levels in a selection of men, women and their umbilical cords in Ireland, where fortification of foodstuffs with folic acid is voluntary.

Although adding folic acid to products like bread is a legal requirement in some countries, the authors also explain that folic acid is thought to mask a particular type of anaemia called pernicious anaemia, which can occur when people are deficient in vitamin B12. Folic acid hides some of the signs of this anaemia, but intakes of less than 1mg a day in adults are not thought to have this masking effect.  Research is also ongoing to explore whether folic acid can possibly accelerate the growth of existing cancers.

The main aim of this research was to provide a record of the unmetabolised folic acid levels in Irish adults (both fasted and un-fasted) and newborn infants (fasted) before the proposed implementation of mandatory folic acid fortification.

The researchers also tried to predict the increase in unmetabolised folic acid levels in the blood after fortification. Unmetabolised folic acid appears in blood tests when oral folic acid rises above certain threshold doses (about 200mg). The acid cannot be stored in the body, and must be continually replenished through the diet or from supplements.

Two groups of volunteers were selected. The first group were blood donors attending routine blood donation sessions at the Irish Blood Transfusion Service in Dublin. Whole blood samples were collected from 50 blood donors (42 men and eight women, age range 27-60 years) that had been eating normally before the sampling.

In the second group samples were collected from mothers and babies at the Coombe Women’s and Infant’s Hospital in Dublin. Blood samples were taken from 20 mothers about to undergo routine caesarean section (age range 26-39 years) and from the umbilical cords of their 20 babies immediately after caesarean section. All these women had been fasting for eight hours, and none were taking folic acid supplements.

The researchers wanted to relate the results of blood samples to answers given to a questionnaire on dietary intakes of folic acid. An interviewer administered a questionnaire covering the usual and recent dietary intakes of folic acid to all the adult subjects. This covered the main dietary sources of folic acid supplements and fortified foods available in Ireland.

Standard statistical tests were used and the researchers used regression to model the estimated average increase in plasma folate levels in the population that might occur as a result of mandatory fortification.

What were the results of the study?

The researchers say that unmetabolised folic acid was present in 49 out of 50 unfasted blood donors and that this constituted 2.25% of total plasma folate. In the caesarean group of fasting mothers the unmetabolised folic acid was present in 17 of the 20 babies. This equates to 85% of the babies (95% confidence interval, 62.1% to 96.8%) and 18 out of 20 fasting mothers (90%). This unmetabolised folic acid was 1.31% of total plasma folate.

The authors say there was a significant link between the total folate in the mother’s plasma and the mother’s unmetabolised folic acid concentrations. Levels of folic acid taken in through usual diet (assessed by questionnaires about food) correlated with maternal plasma folate concentrations. 

They also say they found a significant correlation between the maternal folic acid concentrations and cord blood folic acid concentrations.

What interpretations did the researchers draw from these results?

The researchers say that the reported levels of unmetabolised folic acid in the circulatory system are low: 1.31% in the fasting mothers and 2.25% in the unfasting volunteers (mostly men). They conclude that the fact that it was still present immediately after caesarean section in women who had not eaten for eight hours means that in people with cancer there would be a “constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth”, and that “mandatory fortification might exacerbate this”. 

They state that their findings have implications for those with responsibility for drafting legislation in this area.

What does the NHS Knowledge Service make of this study?

This simple study measuring various types of folate in two small groups of men, women and babies does not seem to add anything to the debate about whether folate is harmful. In particular:

  • It is to be expected that women or men who consume a normal diet have detectable levels of plasma folate, plasma folic acid and red cell folate levels in their blood. In fact, it would be unhealthy if they did not. It is not clear form this research what the significance is of the small amounts of unmetabolised folic acid found.
  • Equally, it is unsurprising that lower levels of the unmetabolised form are found in anyone who has been fasting when compared to those who have not. The importance of this finding is not clear.
  • To be useful in informing the fortification debate this study would have needed to compare the levels found in women or men who were taking fortified foods when compared to those who were not.

The researchers report that the evidence supporting harm from folic acid has come from two publications of the same randomised controlled trial. In this trial of people who had undergone treatment for colorectal adenomas (bowel growths), those who consumed folic acid supplements as part of the trial had an increased risk of more severe recurrence than the placebo group. The dose administered in the trial was 1mg (the accepted upper safe limit). In the second publication from this trial the suggestion was that oral folic acid increases the risk of prostate cancer. This and other trials will need to be assessed separately.

This most recent paper has contributed to an understanding of how folic acid is metabolised in the body, but there is a need for high-quality research to test the safety of folic acid fortification.

Links to the headlines

Folic acid in bread ‘could be unnecessary and increase health risks’. The Daily Telegraph, August 18 2009

Links to the science

Sweeney MR, Staines A, Daly L  et al. Persistant circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification? BMC Public Health 2009, 9:295

Further reading

Lumley J, Watson L, Watson M, Bower C, Dowswell T. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database of Systematic Reviews 2001, Issue 3

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