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The connection between folic acid and colorectal cancer resurfaced this week with the release of a new study from the University of Toronto. Published in the journal Carcinogenesis, the paper reports that folic acid supplementation may promote the progression of aberrant crypt foci (ACF), an early precursor of colorectal cancer.
The research team, led by Gillian M. Lindzon of the Department of Nutritional Sciences, placed 152 male rats at weaning on a control diet that included azoxymethane, a chemical used in cancer research to cause colon tumors in laboratory animals, along with 2 mg folic acid/kg diet. (At this dose alone, each rat’s daily intake is comparable to a 70 kg human ingesting 140 mg/140,000 µg of folic acid each day — an unimaginable excess that far exceeds Health Canada’s tolerable upper intake level of 1 mg/1,000 µg daily.)
Once the researchers successfully induced abnormal colorectal cells, they randomly assigned their test subjects to doses of folic acid ranging from 0 to 8 mg/kg diet, and at 34 weeks, measured a variety of indicators: colorectal tumour parameters, folate and homocysteine levels in the blood (an indication of folate levels in tissue), and the rate of rectal cell growth.
Although the numbers of ACF increased with elevated folic acid levels, the tumour incidence was relatively unchanged among the four dietary groups. In other words, whether the rats ate 0 or 8 mg folic acid/kg diet, the likelihood of developing tumours was about the same. The researchers concluded that the findings indicate folic acid may promote the progression of ACF.
Folic acid is celebrated as an essential nutrient for pregnant women and those planning a pregnancy. Since folic acid helps produce and maintain new cells, it is vital to normal development during the early embryonic and fetal periods when rapid cell division and growth are taking place. According to The Society of Obstetricians and Gynaecologists of Canada (SOGC) as many as half of all birth defects could be prevented if women of childbearing age consumed adequate folic acid.
Based on the most recent research findings, the SOGC released new guidelines in December 2007, compiled by a 15-person expert panel represented jointly by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and The Motherisk Program from The Hospital for Sick Children in Toronto. The guidelines recommend that, barring special health considerations, women in the childbearing years should maintain “a good diet of folate-rich foods and daily supplementation with a multivitamin with folic acid (0.4–1.0 mg) for at least two to three months before conception and throughout pregnancy and the postpartum period (4–6 weeks) and as long as breastfeeding continues.”
The results of a May 2009 McGill University study published in the British Journal of Medicine support this recommendation. The McGill study noted that Canada’s 1998 mandatory folic acid fortification of flour products has not only reduced the number of neural tube defects, but reduced fetal heart malformations as well. In the light of such successes, the SOGC in its recent guidelines urges the federal government to consider doubling the current level of folic acid fortification.
To date, research connecting folic acid and colon cancer has been contradictory. More than 30 case-control and prospective cohort studies have reported that folate could play a role in reducing the risk of colorectal cancer by nearly half.
In the eyes of the expert SOGC panel, the risk of toxicity from either folic acid supplements or fortified foods is low: “[Folic acid] is a water soluble vitamin, so any excess intake is usually excreted in urine.”
Folic acid, also known as folate, pteroyglutamic acid or folacin, is a member of the B complex family. It serves many functions in the human body: as a coenzyme for normal DNA synthesis, as a coenzyme in amino acid and nucleoprotein synthesis, and as a promoter of normal red-blood–cell formation. Health Canada’s Recommended Daily Allowance (RDA) is 400 mcg or 0.4 mg for women, 600 mcg/0.6 mg if pregnant and 500 mcg/0.5 mg if breast-feeding.
In addition to regulating embryonic and fetal development, folic acid is important among the elderly for helping prevent osteoporosis. It also plays a role in the conversion of the amino acid methionine to cysteine. When a folic acid deficiency occurs, or if a defect exists in the enzymes responsible for this conversion, levels of homocysteine, the compound implicated in a variety of conditions, including atherosclerois and osteoporosis, can rise.
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