Folate linked to lower colorectal cancer risk: Study

By Stephen Daniells

- Last updated on GMT

Related tags: Folic acid, Colorectal cancer

Increased intakes of folate from the diet may reduce a woman’s risk of colorectal cancer by about 50 per cent, according to new findings from Korea.

The highest intakes of folate, a B-vitamin found in green leafy vegetables, chick peas and lentils, were associated with a 66, and 70 per cent reduction in a woman’s risk of cancers of the colon and rectum, respectively, report researchers in the European Journal of Clinical Nutrition ​(EJCN).

However, men did not benefit from the vitamin, said the researchers from Korea’s National Cancer Center, Hallym University, Inha University College of Medicine, and Seoul National University.

The study adds to an ever-growing body of case-control and prospective cohort studies have reported that increased intakes of folate may reduce the risk of colorectal cancer by 40 to 60 per cent.

Benefits for babies

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.

Preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence. In Chile, the measure has been associated with a 40 per cent reduction in NTDs. Parallel measures in European countries, including the UK and Ireland, are still on the table.

Contradictory results

Over 30 case-control and prospective cohort studies have reported colorectal cancer risk reduction associated to the vitamin. Similar risk reductions have also been reported for the lesion that precedes the cancer, the adenomatous polyp. However, some studies have linked folic acid intakes to an increased​ risk of the disease.

A review paper published in the April issue of Nutrition Reviews​ by Joel Mason from USDA Human Nutrition Research Center on Aging at Tufts University addressed the potential Janus effect of folate on colorectal health.

“Under most circumstances, adequate intake of folate appears to assume the role of a protective agent against cancer, most notably colorectal cancer,”​ wrote Dr Mason. “However, in select circumstances in which an individual who harbours a pre-cancerous or cancerous tumour consumes too much folic acid, the additional amounts of folate may instead facilitate the promotion of cancer.”

The complex links between folate and cancer have created a “global dilemma”​, said Dr Mason, with regards to instituting folic acid fortification programs in other countries.

Korean data

The Korean researchers analysed data obtained from 596 men and women with colorectal cancer, and compared this to data from 509 people free of the disease. All the participants were aged between 30 and 79.

According to the EJCN report, the overall data showed that the highest levels of folate intake were linked to a 53, 58 and 52 per cent reduced risk of colorectal, colon, and rectal cancer, respectively for all the people studied.

However, when the researchers focussed on the sex of the participants, only women were found to benefit, with the highest levels of folate intake were linked to a 64, 66, and 70 per cent reduced risk of colorectal, colon, and rectal cancer, respectively.

“We found a statistically significant relationship between higher dietary folate intake and reduced risk of CRC, colon cancer and rectal cancer in women,”​ concluded the researchers.

Folic acid versus folate

A possible explanation for the contradictory results of studies with the vitamin and colorectal cancer may be the difference between the synthetic and natural forms of the vitamin. “The fact that folic acid, which is not a naturally occurring form of the vitamin, is used by food and pharmaceutical industries for fortification and supplementation is potentially of importance,”​ wrote Tufts University’s Mason in Nutrition Reviews​.

On passage through the intestinal wall, folic acid is converted to 5-methyltetrahydrofolate, the naturally circulating form of folate. However, some studies have suggested that oral doses of folic acid in high doses may overwhelm this conversion pathway, leading to measurable levels of folic acid in the blood.

“There has been some concern that this oxidized, non-substituted form of folate might feasibly be detrimental because it is not a naturally occurring co-enzymatic form of the vitamin,” ​he added.

Source: European Journal of Clinical Nutrition
Published online ahead of print, doi:10.1038/ejcn.2009.37
“Folate intake and the risk of colorectal cancer in a Korean population”
Authors: J. Kim, D.H. Kim, B.H. Lee, S.H. Kang, H.J. Lee, S.Y. Lim, Y.K. Sun, Y.O. Ahn

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