Folic acid supplementation not associated with colon cancer: Meta-analysis

By Nathan Gray

- Last updated on GMT

Related tags: Folic acid

New research analysing data from the three largest trials of folic acid and the risk of colon cancer has suggested that supplementation has no effect on the risk of developing the disease.

The research, published in, International Journal of Cancer, ​analysed combined data from the three largest randomized clinical trials of folic acid supplementation for the prevention of colorectal adenomas (tumours that may progress to cancer), finding that after up to 3.5 years of folic acid use, “there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma.”

“Daily use of folic acid supplements […] does not prevent the occurrence of new colorectal adenomas in the large bowel among men and women with a previous history of adenomas,”​ said the researchers, led by John Baron, Professor of Medicine at Dartmouth Medical School, USA.

“We found no differences in the rates of adverse events while comparing folic acid and placebo treatment group in terms of myocardial infarction, stroke, colorectal cancer and all cancer types combined.

“Interestingly, we observed a potential beneficial effect of folic acid supplements on overall mortality,”​ they added,

Cancer association

Prof. Baron and colleagues noted that observational data suggests low folate status is associated with an increased risk of colorectal cancer, “implying that folate may be useful as a chemopreventive agent.”

For example, previous research​ has suggested that increasing intakes of folate can reduce a woman’s risk of colorectal cancer by around 50 per cent. Whilst research from a team of Harvard scientists found that supplementation may reduce the recurrence of colorectal cancer in people with low levels of the nutrient, but not people who already have adequate amounts (reported here​).

However, some epidemiological and animal studies have also provided evidence suggesting that folic acid supplementation, and high blood levels of folate, may be associated with an increased risk of colorectal cancer.

To obtain more precise clinical evidence on the effects of folic acid supplementation on the occurrence of new adenomas in patients with a history of adenomas, the researchers conducted a pooled analysis of the three large randomised trials. The analysis focused on 3.5 years of treatment.

Study details

The analysis, of 2,632 men and women with a history of adenomas randomized to either 0.5 or 1.0 mg per day of folic acid or placebo, used a random-effects meta-analysis to estimate risk ratios.

Baron and colleagues reported that folic acid was associated with a non significant decrease in the risk of all cancers among those with the lowest plasma levels of folate, and adverse effects among those with the highest.

The authors also reported that during early follow-up, more deaths occurred in the placebo group than in the folic acid group.

Prof. Baron and co-workers said that daily use of alcohol – a known folate antagonist – did not significantly modify the effect of folic acid supplementation on cancer risk.

“However, we did observe a non-significant trend of decreasing risk of all adenomas associated with folic acid with increasing number of drinks,”​ they added.

The researchers said that their data, together with other findings, “dampen enthusiasm for the potential chemopreventive effects of folic acid.”​ However they added that more follow-up data is needed “to assess the longer-term effects of folic acid use.”

Source: International Journal of Cancer
Volume 129, Issue 1, ​Pages 192–203, doi: 10.1002/ijc.25872
“Folic acid and prevention of colorectal adenomas: A combined analysis of randomized clinical trials”
Authors: J.C. Figueiredo, L.A. Mott, E. Giovannucci, K. Wu, B. Cole, M.J. Grainge, R.F. Logan, J.A. Baron

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