Analysis of data from almost 100,000 men and women indicated that “there is no evidence that dietary fortification or supplementation with this vitamin increases colorectal cancer risk”,
The study, published in Gastroenterology, should go some way to allaying fears that increased intakes of folic acid – the synthetic form of folate – are linked to colorectal cancer risk.
“[Most] importantly, no increased risk of colorectal cancer was found, suggesting that the high levels of this vitamin consumed by significant numbers of Americans should not lead to higher incidence rates of this cancer in the population,” wrote the researchers, led by Victoria Stevens, PhD.
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. A total of 51 countries now have some degree of mandatory fortification of flour with folic acid.
Concerns that folic acid may increase the risk of colorectal cancer have surfaced over recent years, with some experts noting that folic acid, and not folate, may promote the formation of cancers under select circumstances where a person may already have a pre-cancerous or cancerous tumor.
This has led to some finger pointing at the synthetic form of the vitamin. 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 (Nutrition Reviews, 2009, Vol 67, pp. 206-212).
Dr Stevens and her co-workers analyzed data from 56,011 women and 43,512 men participating in the Cancer Prevention Study II (CPS-II) Nutrition Cohort. The age of the participants ranged from 50 to 74.
The data showed that folate intakes from dietary sources ranged from 175 to 354 micrograms per day, while average folic acid intakes from fortified foods, supplements, and/or multivitamins ranged from about 71 to 660 micrograms per day. In addition, the Atlanta, Georgia-based scientists report that just over 2,000 participants had intakes greater than the Tolerable Upper Intake Level (UL) of 1,000 micrograms of folic acid per day.
Between 1999 and 2007 there were 1,023 cases of colorectal cancer diagnosed. After crunching the numbers, Dr Stevens and her team found that neither high intakes of natural folate nor folic acid were associated with an increased risk of colorectal cancer.
In addition, total folates (from all sources) were associated with a 19 percent reduction in colorectal cancer risk.
“Our findings are consistent with […] results from the only trial to assess colorectal cancer, rather than adenoma, as the endpoint, suggesting that folate intakes in the range of 800 micrograms per day should not be expected to increase risk of colorectal cancer,” wrote the researchers.
The researchers do note, however, that other unknown factors that affect colorectal cancer risk may influence risk, but they do state that “many known colorectal cancer risk factors were accounted for in the study”.
Published online ahead of print, doi:10.1053/j.gastro.2011.04.004
“High Levels of Folate, from Supplements and Fortification, Are Not Associated with Increased Risk of Colorectal Cancer”
Authors: V.L. Stevens, M.L. McCullough, J. Sun, E.J. Jacobs, P.T. Campbell, S.M. Gapstur