Folic Acid Does Not Prevent Colorectal Tumours New Study Suggests

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Folic Acid Does Not Prevent Colorectal Tumours New Study Suggests

06 Jun 2007

A new US study suggests that folic acid supplementation does not

reduce the risk of benign colorectal tumours and may even increase

the risk of higher grade tumours.

The study is published in the Journal of the American Medical

Association (JAMA).

Some epidemiological and animal studies have suggested that folic

acid supplementation may prevent colorectal tumours.

Dr Bernard F Cole of Dartmouth Medical School, Hanover, New Hampshire

and colleagues conducted a nine-centre trial in the US and Canada

between 1994 and 2004 involving 1,021 patients of average age 57 who

had recently had at least one colorectal adenoma removed within three

months of enrollment but with no history of colorectal cancer.

Adenomas or polyps are benign growths that form singly or in clumps

and may become malignant over time.

The patients were randomly assigned to receive either folic acid

supplement (1 mg per day) or placebo and underwent colonoscopy about

3 years afterwards. 607 of the patients had a second colonoscopy at

the 6 year mark.

Cole and colleagues were surprised to find more adenomas in the

patients who had received folic acid although the risk did not differ

significantly between the two groups.

At the first follow up, 44 per cent of the folic acid group had

adenomas versus 42 per cent in the placebo group. At the second

follow up, these figures were 42 versus 37 per cent respectively.

The folic acid group also showed a trend toward more advanced and

multiple adenomas. In the first follow up 11 per cent of the folic

acid group had advanced adenomas compared with 9 per cent in the

placebo group and in the second follow up these figures were 12 and 7

per cent respectively.

The incidence of noncolorectal cancers in the folic acid group was

significantly greater than in the placebo group ((11 versus 6 per

cent). This was mainly due to an increase in prostate cancer.

Cole and colleagues concluded that:

" our study indicates that folate, when administered as folic acid for

up to 6 years, does not decrease the risk of adenoma formation in the

large intestine among individuals with previously removed adenomas. "

And in regard to increased risk they said that the evidence was

unclear and called for further research. However, they went to say

that:

" In view of the fortification of the US food supply with folate, and

some suggestions that folate could conceivably increase the risk of

neoplasia even outside the colorectum, this line of investigation

should have a high priority. "

In an accompanying editorial, Dr Cornelia M Ulrich and Dr D

Potter, from the Fred Hutchinson Cancer Research Center in Seattle,

said that this study may be raising an issue of timing. If taken

early, then perhaps folic acid prevents adenomas from forming, but if

taken once they are formed, it could accelerate their development

into cancer.

" The most likely explanation for the increased risk of advanced and

multiple adenomas in the intervention group is that undetected early

precursor lesions were present in the mucosa of these patients (who

are at increased adenoma risk), and that folic acid promoted growth

of these lesions, " they wrote.

They said this idea was supported by experimental studies where folic

acid was given after lesions were present.

However, they said this study does not say anything about whether

folic acid prevents adenomas in the first place, since all the

patients had already had at least one when they were enrolled. It

would cost a lot of money and take a long time, to prove that folic

acid prevented tumours.

" The question of efficacy of folate in cancer prevention is not

resolved, and animal experiments showing chemopreventive effects of

folate, as well as the strong observational epidemiological evidence,

speak to the potential of folate as a chemopreventive agent, if taken

early. Unfortunately, primary prevention trials that start in

childhood would be lengthy, expensive, and logistically nearly

impossible, " said Ulrich and Potter.

This is not the first time that trials with single agents has thrown

up these issues, and Ulrich and Potter draw comparisons with the

problem of showing betacarotene benefits in lung cancer prevention.

Lessons could be learned from chemotherapy, where multiple agents are

used. They said the time has come to:

" Be as thoughtful about the need for multiagent chemoprevention, not

forgetting that diet is one version of this, as about the use of

multiagent chemotherapy. "

The question of whether to include folic acid in bread and flour has

been the subject of some controversy in the UK and Australia. Experts

claim that such a move would reduce the incidence of babies born with

spina bifida and other conditions. Others say that high doses of

folic acid interfere with treatments for malaria, and some studies

suggest it may protect against heart disease and stroke.

" Folic Acid for the Prevention of Colorectal Adenomas: A Randomized

Clinical Trial. "

Bernard F. Cole; A. Baron; S. Sandler; W. Haile;

Dennis J. Ahnen; S. Bresalier; Gail McKeown-Eyssen; W.

Summers; I. Rothstein; Carol A. Burke; Dale C. Snover;

R. Church; I. ; J. on; Gerald J.

Beck; H. Bond; Tim Byers; Jack S. Mandel; Leila A. Mott; Loretta

H. Pearson; L. Barry; Judy R. Rees; Norman Marcon; Fred

Saibil; Per Magne Ueland; E. Greenberg; for the Polyp

Prevention Study Group.

JAMA 2007 297: 2351-2359

Vol. 297 No. 21, June 6, 2007

Written by: Catharine Paddock

Writer: Medical News Today

Article URL: http://www.medicalnewstoday.com