Low folate levels may boost colorectal cancer risk

By Stephen Daniells

- Last updated on GMT

Related tags Folic acid

A diet low in folate may increase the risk of developing colorectal
cancer, says an animal study from Canada, backing up previous
studies and highlighting potential additional benefits of folic
acid fortification.

"This research, which is consistent with previous epidemiological studies in humans, demonstrates a clear link between low dietary folate and the initiation of colorectal cancer in animal models,"​ said lead researcher, Dr. Rima Rozen, from McGill University Health Centre-Montreal Children's Hospital.

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 journal Cancer Research​ (Vol. 66, pp. 10349-10356), claims to be the first to demonstrate directly that diets low in folate cause colorectal cancer, and follows on the heels of earlier research by the same team that revealed how high folate diets can protect against heart disease.

It also appears to contradict a recent Swedish study that reported that low folate status may offer protection from colorectal cancer (Gut​, October 2006, Vol. 55, pp. 1461-1466).

The McGill researchers used a mice model that was developed to spontaneously develop tumours as a model for human colorectal cancer, which accounts for nine per cent of new cancer cases every year worldwide.

The mice were also developed to be with or without a null allele in a key folate-metabolizing enzyme, called methylenetetrahydrofolate reductase (Mthfr), that causes the development of intestinal tumours due to low dietary folate alone.

The Mthfr positive and negative mice were then fed a folate-deficient diet or a control diet, and the researchers report that, on the folate-deficient diet, 12.5 per cent of the Mthfr positive developed tumours compared to 28.1 per cent of the Mthfr negative mice. Mice on the control (folate-replete) diets did not develop tumours.

"None of the mice fed a control diet developed tumours whereas one in four mice on the folate-deficient diet developed at least one tumour,"​ said Rozen.

A mechanistic study was also undertaken and the researchers reported that folate deficiency was associated with increased DNA damage, which plays a role in the development of tumours, and decreased expression of two genes, polo-like kinase 1 (Plk1) and cell division cycle 25c (Cdc25c), both of which are expressed during the body's response to DNA damage.

"Our data suggest that folate deficiency can initiate tumour development, [and] that Mthfr mutation can enhance this phenomenon,"​ concluded the researchers.

Dr. Rozen said that these results were "not a reason to consume excessive amounts of folate, but rather to ensure that the recommended daily amount is taken through a healthy diet or a vitamin supplement."

Dr. Philip Branton, scientific director of the Canadian Institutes of Health Research (CIHR), Institute of Cancer Research said: "The result of this study highlights how simply adding a supplement to your daily diet could have tremendous long-term benefits to the individual and the health care system."

"While these results are encouraging, much more research will be needed before we will know for certain if folate has any protective effect for colorectal cancer in men,"​ he added.

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.

Funding for the McGill study was provided by the CIHR.

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