Folate, colorectal cancer study could sway fortification debate

By Jess Halliday

- Last updated on GMT

Related tags: Folic acid, Colorectal cancer

A new study from Sweden suggests that low folate levels may exert a
protective effect against colorectal cancer, a finding that could
have some bearing on discussions over mandatory folic acid
fortification in Europe.

Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.

This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.

While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table. The new study, published in the October issue of Gut​ (2006;55:1461-1466. doi 10.1136/gut.2005.085480), could have implications for the debate, claim the researchers from Umea University, Sweden.

The main reason not to proceed that is cited by those not in favour of the measure is that upping folate levels across the entire population may mask a form of aenemia in elderly people that is cause by vitamin B12 deficiency, and can cause dementia.

But first author Dr Bethany Van Guelpen and colleagues say that colorectal cancer risk is also a factor, and people with low folate levels may actually have some protection.

The conclusions seem to go against the grain of current research in this area, since several studies investigating the link between folate intake and colorectal cancer have concluded that the B vitamin reduces risk. But Van Guelpen argues that very few studies have looked at folate levels​. People who are not supplementing their diets are likely to have lower folate levels than those who are.

"We speculate that inadequate folate status in the background population allowed us to investigate associations at the lower end of the biological folate spectrum,"​ she wrote.

The study, which was prospective in design, was based on the Northern Sweden Health and Disease Cohort, under which 130,000 blood samples had been donated by some 85,000 individuals by 2002. Under two of the three subcohorts participants also completed lifestyle and food frequency questionnaires.

A total of 260 cases of colorectal cancer were identified by matching up data from the cohort with the National Cancer Register. Of these, 226 met no exclusion criteria.

Van Guelpen observed a "bell-shaped"​ association between plasma folate concentrations and colorectal cancer risk, with subjects in the lowest quintile seen to be half as likely to develop the disease as those in the middle quintile.

In subjects who were followed for more than 4.2 years, plasma folate concentrations were "strongly positively related to colorectal cancer risk"​.

"Without negating the possibility of a protective effect for high folate levels, our findings suggest that low folate status may reduce the risk of colorectal cancer,"​ they concluded.

But they also said: "The possibility of a detrimental component to the role of folate in carcinogenesis would have implications in the ongoing debate in Europe concerning mandatory folate fortification of foods."

In an accompanying editorial, Dr Y-I Kim of the University of Toronto calls mandatory folic acid fortification "probably the most important science drive intervention in nutrition and public health in decades"​.

But given that certain segments of the population may benefit less and may even experience adverse effects, he said that wavering over fortification "should not be construed as public health malpractice but should be regarded as public health prudence".

In Dr Kim's opinion, long term follow-up studies into the relation between folic acid supplementation and fortification and cancer risk are "urgently warranted"​.

In the UK, the Food Standards Agency's Scientific Advisory Committee on Nutrition has asked the board for more time before delivering its final report on the fortification question. A spokesperson for the FSA told NutraIngredients.com in May that the ongoing investigations relate to increasing folate intake over 1mg per day.

In July Ireland's National Committee on Folic Acid Fortication today recommended that most In July white, brown and wholemeal breads sold in the country be fortified with 120 micrograms of folic acid per 100g of bread - a move which will require legislative change and minor modifications to the bread-making process.

Food Standards Australia New Zealand (FSANZ) has also embarked on the path towards fortification, last month calling for public comment on a proposal that would require all bread-making flour to be fortified with folic acid.

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