Folic acid, colon & prostate cancers

Folate deficiency during pregnancy leads to neonates being born with neural tube defects. This knowledge led to the introduction of folic-acid fortification of wheat flour in the United States in 1996 and in Canada in 1997. This became mandatory in both countries in 1998. The government of Chile introduced a mandatory programme of folic-acid fortification of wheat flour in 2000 to reduce the incidence of neural tube defects in newborns. Indeed, this has been achieved with stunning results but a recent report from Chile showed that the rate of colorectal cancer in Chile has increased since 2000.  

Researchers from the University of Chile analyzed hospital discharge data for two 4-year periods – before folic-acid fortification (1992 – 1996) and after fortification (2001 – 2004). They found a significant increase in the number of cases of colon cancer in the second period. Among people aged 45 – 64 years, the increase in the rate ratio was 2.6 times while the increase was 2.9 times in people aged 65 – 79 years. While some would argue that the increased rate of obesity (from 19.7% in 1997 to 22% in 2003) in the population may have contributed to the increased rate of colorectal cancer, the lack of consistent patterns of change in other diseases such as cardiovascular diseases would argue against this (Eur J Gastroenterol Hepatol 2009; 21: 436 – 439).

Indeed, similar findings were published by researchers from the Tufts University in Boston 2 years earlier (Cancer Epidemiol Biomarkers Prev 2007; 16: 1325 – 1329). The authors noted that both United States and Canada experienced an abrupt reversal of the downward trend in the colorectal cancer (CRC) incidence seen in the preceding decade. The absolute rate of CRC in the United States began to rise in 1996 and peaked in 1998 and in Canada it rose in 1998 and peaked in 2000. The rates have continued to exceed the pre-1996 / 1997 trends by 4 – 6 additional cases per 100,000 individuals. While this observation did not prove a causal link, it was worrying.

In order to gain some information on the association between folate status and the risk of prostate cancers, researchers studied the occurrence of prostate cancer among the participants in the Aspirin / Folate Polyp Prevention Study (J Natl Cancer Inst 2009; 101: 432 – 435). This study is a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between 6/7/1994 and 31/12/2006. These participants were followed for up to 10.8 years. Among the 643 men who were randomly assigned to placebo or folic acid supplementation, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% in the folic acid group and 3.3% in the placebo group. Aspirin alone had no effect on prostate cancer incidence. Interestingly, in non-multivitamin users, the baseline dietary folate intake and plasma folate level were inversely associated with the risk of prostate cancer. However, this association did not reach statistical significance.

Is natural folate handled differently in our body? Does the folic acid in multivitamin preparations or that used in fortification act differently on our cells? In our quest to build up our body, are we taking too much folic acid as supplements? All these questions are awaiting the definitive answers. For those of us who are not pregnant or suffering from folate deficiency, perhaps we might be better off sticking to natural sources of folate than popping the daily multivitamin pill.

Indeed, natural might be better.