There is no need for an upper limit of folate intake, according to a study by Queen Mary University of London and the School of Advanced Study, University of London.
The study shows that the maximum suggested intake of folate (1 mg/day) is based on a 'flawed' analysis. The findings support recent calls1 for the Department of Health to approve the fortification of flour with folic acid, in order to protect babies from having neural tube defects.
Anencephaly and spina bifida (collectively referred to as neural tube defects) are serious and relatively common birth defects, affecting 1 in every 500-1,000 pregnancies. In 1991, a Medical Research Council randomised trial showed that increasing folic acid intake immediately before and early in pregnancy prevented most cases of neural tube defects.
As a result, 81 countries, including the USA since 1998, have introduced mandatory folic acid fortification of cereals, which has been found to reduce the prevalence of neural tube defects, without any evidence of harm. In countries that have introduced fortification, the number of neural tube defects has decreased by up to a half.
Despite successive recommendations, the UK has not introduced mandatory fortification. One reason given is that this might lead to more people having a folate intake above an 'upper limit' suggested by the US Institute of Medicine2 (IOM). However the new research, published in Public Health Reviews, says that the IOM analysis was 'flawed' and there is no need for an upper limit.
The IOM analysed the results of studies, mainly conducted half a century ago, on individuals with B12 deficiency who had been wrongly treated with folic acid, and claimed that neurological damage tended to occur more frequently in patients treated with higher doses of folic acid. The IOM concluded that treating individuals with vitamin B12 deficiency with higher doses of folic acid might lead to an increased risk of neurological damage.
The new re-analysis of the data finds no relationship between dose of folic acid and the development of neurological damage. The neurological damage was not caused by folic acid - it arose by not treating B12 deficiency with vitamin B12. As a result there is no need for a folate upper limit (just as there is no upper limit for other B vitamins such as B1, B2, B5 or B12).
Lead author Professor Sir Nicholas Wald from the Wolfson Institute of Preventive Medicine at Queen Mary, who also led the original 1991 randomised trial, said: "With the upper limit removed there is no scientific or medical reason for delaying the introduction of mandatory folic acid fortification in the UK and other countries that have not yet adopted this proven public health intervention.
"Failing to fortify flour with folic acid to prevent neural tube defects is like having a polio vaccine and not using it. Every day in the UK, on average two women have a termination of pregnancy because of a neural tube defect and every week two women give birth to an affected child."
Women who could become pregnant are advised to start taking a daily folic acid supplement, but most do not do so, emphasising the need for fortification. Even with fortification, women should still be advised to take folic acid supplements to achieve a greater level of protection than that afforded by fortification alone. The importance of fortification is that it provides a protective population safety net.
In the UK, white flour is already fortified with iron, calcium and other B vitamins (niacin and thiamin).
Co-author Professor Joan Morris from the Wolfson Institute of Preventive Medicine at Queen Mary said: "From 1998, when the United States introduced mandatory folic acid fortification, to 2017, an estimated 3,000 neural tube defects could have been prevented if the UK had adopted the same level of fortification as in the US. It's a completely avoidable tragedy."
Co-author Colin Blakemore, former head of the Medical Research Council, said "Spina bifida is one of the most common disabling birth defects, but British research has shown that this tragic condition is a vitamin deficiency that can easily be prevented. Eight-one other countries have benefited from this research, which was funded by the British taxpayer. It's time for the British public to reap the full benefits of that research."
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Notes to the editor
1 The Times, 9 December 2017, LETTERS TO THE EDITOR - 'FOLIC ACID FOR BREAD' by Professor Lesley Regan, president, Royal College of Obstetricians and Gynaecologists; Professor Neena Modi, president, Royal College of Paediatrics and Child Health; Gill Walton, CEO, Royal College of Midwives; Jason Waugh, president, British Maternal and Fetal Medicine Society; Dr Asha Kasliwal, president, Faculty of Sexual and Reproductive Healthcare. URL: https:/
2 The name of the Institute of Medicine was changed in 2015 to the National Academy of Medicine.
Review paper: Wald NJ, Morris JK, Blakemore C. Public health failure in the prevention of neural tube defects: time to abandon the Tolerable Upper Intake Level of folate. Public Health Reviews. doi 10.1186/s40985-018-0079-6
Available here after embargo lifts: https:/
/ doi. org/ 10. 1186/ s40985-018-0079-6
- Folic acid, a vitamin in the B group, is the "core" part of a range of molecules collectively described as folate. Asparagus, broccoli and dark leafy vegetables are sources of folate, but, it is very difficult to consume enough folate in food to protect against neural tube defects. Folic acid is a synthetic molecule that can be taken as pills (vitamin supplements) or added to staple foods such as flour (food fortification).
About Queen Mary University of London
Queen Mary University of London is one of the UK's leading universities with 23,120 students representing more than 160 nationalities.
A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research. In the most recent national assessment of the quality of research, we were placed ninth in the UK amongst multi-faculty universities (Research Excellence Framework 2014).
As well as our main site at Mile End - which is home to one of the largest self-contained residential campuses in London - we have campuses at Whitechapel, Charterhouse Square, and West Smithfield dedicated to the study of medicine and dentistry, and a base for legal studies at Lincoln's Inn Fields.
Queen Mary began life as the People's Palace, a Victorian philanthropic project designed to bring culture, recreation and education to the people of the East End. We also have roots in Westfield College, one of the first colleges to provide higher education to women; St Bartholomew's Hospital, one of the first public hospitals in Europe; and The London, one of England's first medical schools.