At a time when many countries are debating whether or not to institute or enhance folic acid fortification, Professor Joel Mason and colleagues urge caution and debate. "We must examine the effects of folic acid fortification on the population as a whole, which includes better defining the nature of the relationship between folic acid fortification and colorectal cancer," said Mason. "Improved monitoring and further research in this field is important to our understanding of the long-term public health effects of fortification." Since the institution of nationwide folic acid fortification of enriched grains in the mid 1990s, the number of infants born in the United States and Canada with neural tube defects has declined by 20 percent to 50 percent. However, during the same period, the rate at which new cases of colorectal cancer were diagnosed in men and women increased, report the researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts. They claim that since the North American food supply began being fortified with folic acid, there have been four to six additional cases of colorectal cancer for every 100,000 individuals each year compared to previous trends. "Our analysis suggests that this increase is not explained by chance or by increased cancer screening," said Mason. "Therefore, it is important to analyze risks and benefits of fortification, and encourage scientific debate in countries that are considering instituting or enhancing folic acid fortification." Although folic acid fortification of enriched grains - including bread, cereal, flour, rice, and pasta - did not become mandatory until 1998, large food companies began voluntary fortification in 1996, first in the United States and later in Canada. Folic acid is the synthetic form of folate, a B vitamin that is essential for cell growth. "The body's response to folic acid appears to be complex," said Mason. "While fortification of the food supply is clearly beneficial for women of child-bearing age and their offspring, it is possible that it may, coincidentally, be linked to the increase in colorectal cancer rates." According to Mason's hypothesis, folate's role in DNA synthesis could make it a growth factor for cancerous or pre-cancerous cells. When given in large quantities to individuals who unknowingly harbor cancer cells, it could enhance cancer development. "The addition of substantial quantities of folic acid into the foodstream may have facilitated the transformation of benign growths into cancers, or small cancers into larger ones," said Mason. After intestinal absorption, folic acid is converted to methyltetrahydrofolate, which is found naturally in foods such as leafy green vegetables, legumes and citrus fruits. "As the total amount of folic acid ingested increases, the mechanism that converts folic acid to methyltetrahydrofolate can become saturated," said Mason. "The leftover folic acid in the circulation might have detrimental effects, as it is not a natural form of the vitamin." The researchers said their report is intended to create a dialogue to look further into the possibility of the link between folic acid and colorectal cancer.