Folic acid may increase risk of colorectal tumours

By Philippa Jones

- Last updated on GMT

Related tags Folic acid Us

Folic acid does not decrease the risk of benign colorectal tumours
and may increase the likelihood of contracting some types
of tumours, say researchers - but the supplements industry urges
caution in light of documented benefits.

A team of scientists from Dartmouth Medical School has suggested that previous studies indicating that folate supplementation may help to prevent colorectal tumours are misleading, and that supplementation may even aggravate the risk of such tumours.

"Our study indicates that folate, when administered as folic acid for up to six years, does not decrease the risk of adenoma formation in the large intestine among individuals with previously removed adenomas," said Bernard Cole and his colleagues.

They admitted that "the evidence for an increased risk of adenomas is equivocal and requires further research", but urged "in view of the fortification of the US food supply with folate...this line of investigation should have a high priority".

US dietary supplements industry association, the Council for Responsible Nutrition (CRN) encouraged people "not to jump to conclusions that would undo the important strides made in recent years in encouraging supplementation and food fortification with folic acid".

Mandatory fortification of certain foods with folic acid was introduced in the US and Canada in 1998 in a bid to reduce the incidence of pregnancies affected by neural tube defects.

The measure appears to have been a success, with NTD-affected pregnancies reported to have fallen by 26 per cent.

Cole and his colleagues evaluated the effect of folate in preventing colorectal adenomas - benign tumours that are the precursors of most colorectal cancers - in people with a history of these types of lesions.

The trial was conducted at nine clinical centres in the US and Canada between July 1994 and October 2004 and included 1,021 men and women with a recent history of colorectal adenomas but no previous large intestine cancerous tumour.

Participants were randomly assigned to receive 1 mg/day of folic acid or placebo and to receive aspirin or placebo and were then examined three and six or eight years later.

In the first follow-up, adenomas occurred in 42.4 per cent of the participants in the placebo group and in 44.1 per cent of those in the folic acid group.

In the second follow-up, adenomas occurred in 37.2 per cent of the participants in the placebo group and in 41.9 per cent of those in the folic acid group.

In both interviews, participants in the folic acid group also tended to have higher rates of advanced adenomas (larger in size and having an increased risk of developing into colorectal cancer) and multiple adenomas.

Cornelia Ulrich and John Potter from the Fred Hutchinson Cancer Research Center, Seattle, suggested in an editorial accompanying the research, that "undetected early precursor lesions were present in the mucosa [a type of membrane] of these patients (who are at increased adenoma risk), and that folic acid promoted growth of these lesions."

They said the study showed more generally that "the principle of chemoprevention with single agents is problematic" , and urged all in the medical profession to be "thoughtful about the need for multiagent chemoprevention, not forgetting that diet is one version of this."

Andrew Shao, vice president of scientific and regulatory affairs for the CRN concurred, saying: "Folic acid alone may not prevent the recurrence of adenomas".

He suggested that "perhaps in combination with other related nutrients or in subjects without previous adenomas we would have seen more promising results."

He said the study's negative results could also be attributed to the use of folic acid "like a drug to treat pre-existing disease, rather than as a nutrient" .

He stressed that the research should not be used to bring about the end of folic acid supplementation.

"The benefits of folic acid are well-documented, particularly in the area of reducing the risk of neural tube birth defects… There is also promising scientific evidence for folic acid in reducing the risk of congenital cardiovascular defects, stroke and Alzheimer's disease.

"It would be a huge public disservice potentially resulting in extremely negative health consequences if scientists, the media or government rushed to judgment based on this study."

Source: Journal of the American Medical Association (JAMA) 6 June 2007, Volume 297, Issue 21, Pages 2351-2359 "Folic acid for the prevention of colorectal adenomas" Authors: B. Cole, J. Baron, R. Sandler, R. Haile, D. Ahnen, R. Bresalier, G. McKeown-Eyssen, R. Summers, R. Rothstein, C. Burke, D. Snover, T. Church, J. Allen, D. Robertson, G. Beck, J. Bond, T. Byers, J. Mandel, L. Mott, L. Pearson, E. Barry, J.Rees, N. Marcon, F. Saibil, P. Magne Ueland, E. Greenberg, Source: Journal of the American Medical Association (JAMA) 6 June 2007, Volume 297, Issue 21, Pages 2408-2409 "Folate and Cancer - Timing is everything" Authors: C.Ulrich, J. Potter

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