Folic acid debate continues
Doctors have called for bread and flour to be fortified "with folic acid in an attempt to prevent hundreds of babies being born with severe birth defects", according to The Daily Telegraph.
Folic acid is a synthetic form of folate, a B vitamin found in a wide variety of foods including liver and green leafy vegetables which is essential for the healthy development of a baby. It is possible to add folic acid to flour to prevent birth defects, such as spina bifida. Adding folic acid to flour and bread currently takes place in the US, Canada and Chile, where the rate of birth defects have fallen.
In June this year, the Food Standards Agency (FSA) approved fortification with folic acid, however, The Daily Telegraph adds, this plan "was halted after the [Government's] Chief Medical Officer called for another look into possible links with cancer raised by two studies" .
The newspaper story is based on a letter to The Lancet journal, in which the authors argue for the fortification of flour with folic acid. They go on to suggest that "the FSA and the Chief Medical Officer can be confident in recommending that the UK government introduce mandatory fortification of flour" as no causal link between folic acid and colon cancer has been found.
As even naturally-found substances carry risks, it is prudent to examine the strength of evidence for and against any public health proposal such as this carefully.
Where did the story come from?
Doctors Roger Bayston, Andrew Russell, Nicholas Wald and Victor Hoffbrand signed the letter on behalf of the Association for Spina Bifida and Hydrocephalus, the Wolfson Institute of Preventive Medicine and the Royal Free Hospital in London. The signatories to the letter declared no conflicts of interest. It was published in the medical journal: The Lancet.
What kind of scientific study was this?
This letter was unedited and published in full. The authors identify two studies that are likely to be considered by the Chief Medical Officer and the FSA when considering folic acid fortification. The authors analyse the papers with a critical eye. The letter discusses the study design and some of the findings reported in the two studies.
What were the results of the study?
signatories to this letter claim both studies regarding the link between folic acid and colon cancer could be misinterpreted.
The first study, published by Cole in 2007, reports the results of a randomised trial which was set up to see if folic acid could prevent the regrowth of colonic adenomas after removal. Colorectal adenomas are benign and not cancerous, and the letter authors reiterate that this different type of bowel growth is not a cancer. When this study started, it was thought that folate might reduce the rates of colonic adenoma regrowth, however the rate of regrowth of was almost the same in the two groups, one treated with folic acid compared and the other not treated. This study used a secondary analysis where the researchers looked separately at a variety of data which they considered to be less important such as the size, number of adenomas and the rates of cancer. The difficulty with this sort of analysis, the letter authors point out, is that the more different measures are made, the more likely it is that there will be an association by chance. This could produce results that may be statistically significant but incorrect.
In the second study, published by Mason in 2007, a rise in the rates of colon cancer in the US and Canada between 1995 and 2000 is reported, and this rise is potentially linked to the fortification of flour which began in 1998. However, the authors of the letter point out that the rise in the rate of colon cancer started before the introduction of fortification on a large scale, and so could not have been caused by fortification.
What interpretations did the researchers draw from these results?
The signatories to the letter conclude that the first paper has been misinterpreted, as it does not show that folic acid supplementation poses a hazard. They also reiterate that the researchers were primarily interested in how folic acid relates to benign tumours, not cancers.
They also state that it is misleading to suggest the rise in incidence in colon cancer between 1996 and 2000 in the US and Canada was caused by folic acid fortification.
What does the NHS Knowledge Service make of this study?
Several principles should be considered when reviewing claims of this sort, without the benefit of expert knowledge in the field or of reading the original papers. These principles hold true for whatever disease or association is under consideration:
- Randomised trials have advantages in that theories can be tested by designing a trial before the results are known. Some of this advantage is lost if data is then re-analysed to develop other theories because of small differences noted in secondary outcomes after the trial.
- Temporal associations, that is, links demonstrated over time between two factors, in this case folate acid intake and cancer, are particularly prone to confounding. Confounding occurs when there is another factor influencing the results, giving an illusion of cause and effect. In this case, it is quite possible that the increased endoscopy rates from 1996 in the US and Canada could lead to better early detection of colon cancer and therefore the rise in the rate seen. The timing of any increase in cancers reported is critical to such links and is a flaw in the original authors own interpretation of causation in the second study.
Even naturally-found substances may have risks and it seems prudent to carefully examine the strength of evidence for and against any public health proposal such as this. However, once potential risks have been identified and assessed, supported or discounted then citizens should expect public health authorities to act swiftly. The only thing to do in this case is wait for confirmation, as suggested by the authors of the letter, that a simple regulation can prevent 400 pregnancies from being affected by birth defects annually, without any increase in bowel cancer.
Sir Muir Gray adds...
Almost always the evidence does not guarantee 100% safety; science is not about certainty but about uncertainty; the evidence helps in decision making but good judgement is needed for decision taking.
Doctors have called for bread and flour to be fortified "with folic acid in an attempt to prevent hundreds of babies being born with severe birth defects", according to The Daily Telegraph...
Links to Headlines
Doctors dismiss folic cancer fear. The Daily Telegraph, December 14 2007
Doctors urge folic acid progress. BBC News, December 14 2007
Call to add folic acid to flour. Channel 4 News, December 14 2007
Folic acid 'failiure'. The Times, December 14 2007
Links to Science
Bayston R, Russell A, Wald NJ, Hoffbrand AV. Folic acid fortification and cancer risk. Lancet 2007; 370:2004
Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev 2001, Issue 3
Cole BF, Baron JA, Sandler RS, et al. Folic Acid for the Prevention of Colorectal Adenomas: A Randomized Clinical Trial. JAMA 2007; 297:2351-2359
Mason JB, Dickstein A, Jacques PF, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 2007; 16:1325-1329
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