The report, making headlines across global media today, raises doubts about the safety of one of the most widely used and longest established supplements in pregnancy. But the researchers say women should not stop taking the supplements as the findings may be due to chance.
Research has shown that taking folate before conception and during early pregnancy reduces the risk of neural tube defects. A recent study showed that the proportion of babies born with neural tube defects in a region of Canada, dropped by 78 per cent after the Canadian government ruled that folic acid must be added to flour, cornmeal and pasta.
But there is limited evidence on the long-term effects of increased folate intake in pregnancy, say researchers from Aberdeen Maternity Hospital and the University of Bristol.
They followed up 2,928 pregnant women enrolled in a trial of folate supplementation in the 1960s. The women were randomly assigned to receive a daily dose of 0.2mg of folate, 5mg of folate or a placebo. Factors such as age, weight, blood pressure, and smoking habits were also taken into account.
The team found that in women randomised to high dose folate supplements, all cause mortality was around 20 per cent higher and the risk of deaths attributable to breast cancer was two times greater.
However the authors stress that although this was a well-conducted randomised trial, these findings are preliminary and could be due to chance.
Lead author Dr Andy Ness said: "Our paper presents preliminary findings which are intended to point the way towards further research and it is published on that basis. It is entirely possible that this is a chance finding - so further scientific studies are required to examine the association, if there is one, before we reach any conclusions."
"It is important that we don't confuse women about the need to take folic acid supplements early in pregnancy. Women planning to become pregnant should take folic acid supplements as recommended as there is a considerable difference between the Aberdeen trial and the current guidelines to prospective mothers," he added in the BMJ report (vol 329, pp 1375-6).
In an accompanying commentary, Godfrey Oakley and Jack Mandel from Emory University in the US argue that the most likely explanation for these results is indeed chance. They cite several studies suggesting that folic acid is likely to prevent breast cancer rather than to cause it.
They also say that the finding should not deter the fortification of flour with folic acid, which has reduced both birth defects and deaths from heart attacks and strokes in the US and Canada.
"Mandatory fortification should be immediately implemented for the known benefits of preventing birth defects and anaemia," they conclude, adding that "inertia on mandatory folic acid fortification continues to be bad policy".
The UK's Food Standards Agency has declined to introduce such fortification in Britain, citing a risk of masking vitamin B12 deficiency in elderly people. Scientists continue to lobby European governments to introduce a mandatory fortification policy.