Multiple counties increased bowel screening at a time when measuring any change from folic acid is really important
Dr Clare Craig
The first trial to raise a question about bowel cancer risk from folic acid found an increased risk of pre-cancerous growths called polyps. A small proportion of these progress to cancer over years. Bowel screening tests for blood in the faeces and if present the person undergoes a colonoscopy at which polyps might be found. The level of blood needed to trigger the colonoscopy began to be reduced to two-thirds from February 2026, phased across England to March 2028. The number of polyps that will be found is about to rocket. As well as there being no monitoring of bowel outcomes there is also therefore no good way of measuring the impact of folic acid exposure secondary to the government mandating it in our food. The mandate comes in in December 2026, but most manufacturers complied well in advance of that deadline. One country, Chile, added folic acid to flour with no bowel screening at all. That is the best test of the impact there is but it has been ignored.
What the trial found
As with every folic acid trial the Aspirin/Folate Polyp Prevention Study was designed to see if folic acid would be beneficial. They gave 1 mg of folic acid a day to 1,021 people who had recently had pre-cancerous bowel tumours. Significantly more of the treated group had three or more adenomas on follow up. The risk was more than doubled with a confidence interval that ranged from a 15 to 321 percent increase. Advanced lesions were 67 percent more common but that finding was no longer significant after adjustments were made. It was this increased risk of polyps which caused the UK’s Scientific Advisory Committee on Nutrition (SACN) concern.
The trial itself illustrates the problem this article is about. Participants were recruited between 1994 and 1998. Voluntary fortification of American flour began in 1996 and became mandatory in 1998, so by the second phase of the trial the placebo group was eating fortified flour too. Any genuine effect would be diluted by treating the placebo group. SACN noted that the folic acid group were therefore taking more than the 1 mg a day the trial gave them.
The Chief Medical Officer asked the SACN to examine that signal in October 2007. They agreed it raised concerns but the pooled randomised evidence from trials all designed to look for benefit was too weak to draw conclusions. The trials had 13 percent power to detect a 10 percent higher risk of colorectal cancer, and the Committee on Carcinogenicity agreed there was no realistic way of reducing that uncertainty. SACN supported adding folic acid to our flour but said voluntary fortification should be restricted, supplements should be capped at 200 micrograms a day for the over fifties and for anyone with a history of adenomas, and there should be careful monitoring to measure adverse effects after the horse has bolted. One member dissented from this advice because of their concerns regarding colorectal cancer risk.
The safety test on the whole population
Having failed to carry out adequate safety testing, is the monitoring set up ready to show what impact folic acid has?
With the UK’s lower threshold for colorectal cancer screening many more people will be referred to colonoscopy. Modelling for the Department of Health and Social Care estimates that this change will result in 36 percent more positive tests and 2,017 more high risk polyps being detected along with 663 more bowel cancers every year. The short term effect is a rise. However, longer term the intention is that the detection and removal of polyps means that the proportion that would have become cancer never get a chance to and the number of cancers would then reduce. The reduction in cancer was estimated to be around 20 percent after 13 years in the NordICC trial. The rise then fall will happen independent of any effect of folic acid but could hide its impact.
There are three interacting variables here:
1. The change in the numbers of adenomas and cancers actually developing.
2. Changes to the tests used to detect them.
3. The number recorded in official data.
Screening changes the number detected even if nothing else changes.
Under these circumstances a simple before and after comparison of bowel cancer incidence cannot separate the effect of folic acid from the effect of screening.
The monitoring plan does not look
The published impact assessment covers neural tube defects, blood folate, vitamin B12 and intakes of calcium, iron, thiamin and niacin. No bowel polyp or cancer monitoring is planned even though colorectal cancer was one of the specific reasons SACN asked for careful monitoring of adverse effects. Asked in June 2026 how the policy would be assessed, the Government replied that it was still exploring how to evaluate the impact.
What happened elsewhere?
Perhaps we could look to other countries that have added folic acid to their flour and see what happened to their risk of colorectal polyps and carcinoma.
The idea that a mandate presents a sharp before and after date is not true. Manufacturers were given a two year lead in to change their processes in the UK and similar lead in times were present elsewhere.
In multiple instances, bowel cancer screening criteria changed right at the time that folic acid was introduced.
| Country | Folic acid added to flour | What happened to detection at the same time |
|---|---|---|
| United States | Permitted March 1996, mandatory January 1998 | Medicare screening cover began January 1998, the same month |
| Australia | Permitted 1996, mandatory September 2009 | Invitation age extended to 50 in July 2008, 14 months before. Programme suspended May to November 2009 then everyone affected reinvited |
| New Zealand | Mandatory August 2023 | National rollout completed 2022, about 15 months before |
| United Kingdom | Milling began September 2025, mandatory 13 December 2026 | Age extension completed January 2025. Threshold cut from February 2026 |
When fortification arrived in each country and what changed in bowel cancer detection alongside it.
The United States
Mason and colleagues reported that American bowel cancer incidence rose from 1996 and peaked in 1998. Part of that rise will be because of colonoscopy displacing sigmoidoscopy from about 1995. Medicare cover, which applies to all over 65 year olds, began on 1 January 1998, the day fortification became compulsory. It started with high risk people and expanded to everyone from July 2001.
SACN examined whether screening could explain the American and Canadian rise and set out exactly the mechanism described above: an immediate increase as cancers are found earlier, then a return to background, unless screening keeps increasing, in which case the return is delayed. They concluded that the available data were insufficient to confirm whether screening changes could explain what happened.
Australia
Australia extended their screening in 2008 and it is estimated that screening prevents 92,200 cases over 2015 to 2040. Every year had more screening than the year before. There is one study of the impact of folic acid by Van der Pols et al. They did not adjust for the increase in screening and concluded there was no evidence that the September 2009 mandate influenced bowel cancer incidence. The control period included voluntary fortification which had been permitted since 1996, so it was not clean.
Then there is what happened in the year of the mandate itself. Australia’s screening programme was suspended in May 2009 because the faecal occult blood test kits were faulty. It resumed in November 2009 and everyone affected was reinvited. Fortification became mandatory in September 2009, in the middle of that gap.
Incidence rose from 2009 to 2010 in exactly two age bands, 55 to 59 and 65 to 69, by 12 percent and 9 percent, both statistically significant. The authors attribute this to the suspension: fewer cancers found in 2009, then a catch up in 2010.
That explanation creates three problems for their own conclusion.
Having accepted that a six month interruption to screening can move national age-specific incidence by 9 to 12 percent, then the rest of the analysis must account for it. The continuous expansion of the same programme from 2008 onwards would have an effect. The screening issues cannot be applied only when the answer is convenient.
It does not fit the ages. The people eligible for screening in 2009 were those turning 50, 55 and 65. All three groups were affected by the suspension and the reinvitation. Two of the three age bands rose. The paper reports that other age groups changed very little, so the 50 to 54 band, which contains the third eligible age, did not show the effect at all.
It puts the pivot of the analysis on an artefact. Their evidence of safety is that the decline in incidence accelerated after 2010, from 0.4 percent a year to 2.2 percent a year. The joinpoint sits at 2010. If 2010 was inflated by catch up screening, as they themselves argue, then the decline measured from that inflated year is steeper than the truth.
The authors also note that the lag between exposure and a colorectal cancer diagnosis is estimated at anywhere between 4 and 20 years, which they use to argue that an effect in 2010 would be surprising. Their reassurance rests on the seven years from 2010 to 2016, the very bottom of that range.
New Zealand
New Zealand mandated fortification in August 2023. Its national screening programme finished rolling out in 2022, so the preventive effect of removing polyps was only just beginning when the flour changed. The starting age has since been lowered from 60 to 58 and is due to fall again to 56 in September 2026. Given a latency of at least 4 years, there is nothing to see yet, and the screening programme will have changed twice more before there is.
We have found no study of the population impact of folic acid on bowel cancer that controls for changes in screening.
Is there any control group?
Canada and Chile both introduced folic acid without a step change in their bowel screening.
Canada
The key provincial programmes providing access to screening did not arrive until 2007 and 2008, nine years after the November 1998 mandate. A national survey in 2003 found that endoscopy use had risen roughly six-fold over the preceding decade. There was no particular stepwise change like in the USA. There is therefore still a confounding issue but nevertheless an age-stratified analysis of Canadian bowel cancer incidence controlling for endoscopy usage has never been done.
Chile
There was no bowel cancer screening in Chile when they introduced their folic acid mandate in 2000. The first pilot screening programme did not begin until 2007 and colonoscopy coverage among 50 to 75 year olds was only 8.7 percent a decade after fortification. The problem is Chile had no cancer registry to record cancer incidence. Hirsch and colleagues therefore compared hospital discharges for colon cancer before and after and found a rise. Discharges were 2.6 times higher in those aged 45 to 64 and 2.9 times higher in those aged 65 to 79. This is the largest rise that has been reported related to folic acid and none of the rise can be blamed on screening. The same analysis found breast cancer discharges rising too, which the authors attributed to new breast cancer programmes. SACN’s working group reviewed the paper in 2009 and agreed that no conclusions could be drawn from it, because of methodological limitations, missing information and the unclear way the results were presented. They did not offer another explanation to explain the rise.
The Chile data is important and no-one has commissioned better. Nothing has been published in the seventeen years since.
Chile is the closest thing to an unconfounded test of the effect of folic acid on bowel cancer that the world has produced. It showed a 2.6-fold increase.
The Australian data showed a null result when it was confounded by the effects of a screening programme but it gets cited as reassurance. By contrast, Chile’s rise was free of the confounding effect of screening and gets dismissed as inconclusive. Why is evidence suggesting harm held to a different standard to evidence suggesting safety?
Instead of carrying out a full safety trial the UK is mandating the addition of folic acid amidst this immense uncertainty of the size of the risk. By changing the bowel screening at the same time, it is doing it in a way that harm will not be measurable.
