Vitamin Information Center

Launched a decade ago, the federal program requiring folic acid to be added to widely consumed foods has been hailed as one of the great public-health success stories. Harnessing a seemingly harmless vitamin, it helped slash the number of babies born with spina bifida and other devastating “neural-tube” defects.

But scientists are beginning to debate whether Canadians’ growing consumption of the nutrient may also be taking a terrible, unplanned toll, triggering hundreds of extra cancers annually, even as it makes pregnancies safer.

One Canadian specialist says the federal government should now consider abandoning fortification altogether, and focus folic-acid efforts more narrowly on the young women who unquestionably benefit from the vitamin.

“It’s a double-edged sword,” said Young-In Kim, a gastroenterologist and folic-acid researcher at the University of Toronto.

“It was meant to prevent neural-tube defects, and it did a wonderful job. [But] for people with pre-cancerous cells, or undiagnosed colon cancer tumours, giving high-dose folic acid or having high folate levels might actually make their condition worse.”

Other experts, though, argue that fortifying food offers well-proven health advantages, while evidence of any cancer risk is inconclusive at best. In fact, the Society of Obstetricians and Gynecologists of Canada has advocated higher intake of folic acid supplements for some women, while the March of Dimes and American Medical Association in the United States have called for doubling the level of folic acid - or folate - that must be added to flours and other raw grains.

“You need more substance to show harm [from folate fortification], and there has been a clear absence of substance,” said Dr. Joel Ray, a scientist at St. Michael’s Hospital in Toronto who has studied folic acid. “We shouldn’t backtrack and change the direction of the program right now.”

Health Canada has reviewed what it calls the “inconsistent” evidence on the issue, and has no plans to alter or cancel the program, said Alastair Sinclair, a department spokesman.

“It is not possible to conclude that fortification has increased the rates of colorectal cancer incidence in Canada,” he said.

The folic-acid story revolves around birth defects, specifically those where the fetus’s neural tube, which becomes the brain and spinal cord, develops improperly, sometimes resulting in major disabilities. Folic acid seems to have a powerful preventive effect. A 2007 study concluded that rates of spina bifida and other neural-tube defects fell by about 50% - or about 110 babies a year - in the wake of the fortification program.

Adding the vitamin to food started on a voluntary basis in this country in 1996, and became mandatory for white flour, enriched pasta and cornmeal in late 1998. Evidence had shown that many women of child-bearing age did not heed expert advice to take folic acid pills, which have limited effect if started after a woman becomes pregnant.

The target was younger women, but the fortification program, following on the heels of one in the U.S., led to a doubling on average in the level of folic acid in all Canadians. Some experts suggest that is not a bad thing: There is evidence that it actually protects people against certain cancers.

Two hotly contested studies published last year, however, have fuelled concerns that elevated levels in North American bloodstreams may be having the opposite effect. A trial published in The New England Journal of Medicine had been designed to test whether folic acid prevented pre-cancerous colorectal polyps. In fact, it found that those subjects taking folate supplements were slightly more likely to have multiple polyps and to develop prostate cancer.

Animal studies, meanwhile, have suggested that the vitamin can prevent colorectal cancer in healthy individuals, but can also make it more likely that pre-cancerous polyps will convert into malignancies and that existing cancers will develop faster.

Then there is the history of folate. In the 1940s, physicians experimented with giving it to children suffering from leukemia, only to find that it accelerated the disease. That discovery led to the development of the first chemotherapy drugs - ones that actually countered the effects of natural folate, said Kim.

He was among the experts consulted by U.K. officials recently as they considered implementing fortification. The British decided last year to put the plan on hold.

Another 2007 study, meanwhile, noted that colorectal cancer rates rose suddenly in both Canada and the U.S. in the years after folic acid fortification started, and suggested there could be a link. The rates here climbed to almost five extra cases per 100,000 annually, before sliding back to a level that was still somewhat higher than before fortification.

That means that as many as 1,500 additional Canadians were diagnosed with colorectal cancer yearly after folate levels started to soar.

Dr. Joel Mason of Tufts University in Boston, who spearheaded the study, said there is not yet enough evidence to justify actually cancelling the fortification program, but called for more research on the possible cancer connection. He also suggests that anyone who is not a woman in her reproductive years think twice about taking folic acid supplements, which only add to the levels provided by fortification.

“We don’t know whether taking vitamin supplements and fortifying food [with folic acid] … actually accelerates cancer risk among susceptible people, but there is certainly a scientific basis for that possibility,” Mason said.

“We can’t afford to ignore it. It’s not a trivial phenomenon.”

Yet his and the New England Journal study have both come under stiff criticism.

British experts on spina- bifida argued in a letter to The Lancet last year that the trial published in the New England Journal showed no significant evidence that folate can be carcinogenic. And, like Ray, they said the increased cancer rates identified in Mason’s study were likely just a result of stepped-up screening for colorectal cancer.

In the meantime, a study published last month in the World Journal of Gastroenterology offered a much rosier view of the vitamin. It found that after three years, patients who took folic acid supplements actually had a third as many of the polyps that can lead to colorectal cancer as those taking a placebo.

ATLANTA, April 14 (UPI) — U.S. researchers say they are learning how vitamins and minerals can stimulate or prevent the development of colon cancer.

Emory University researchers in Atlanta find in a study of 92 patients that supplementing a diet with calcium and vitamin D appears to increase the levels of a protein call Bax — which controls programmed cell death — that may push pre-cancerous cells to self-destruct.

In another, 200-patient, case-control study, led by Dr. Robert Bostick of Emory University, high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells’ movement and proliferation.

A third study on the same 200-patients shows high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.

All three studies — scheduled to be presented at the American Association for Cancer Research meeting in San Diego — use colorectal biopsy samples and are part of a larger effort to identify a portfolio of measurements which taken together could predict the risk of colon cancer.

“We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease,” Bostick says in a statement.

ATLANTA, April 14 (UPI) — U.S. researchers say they are learning how vitamins and minerals can stimulate or prevent the development of colon cancer.Emory University researchers in Atlanta find in a study of 92 patients that supplementing a diet with calcium and vitamin D appears to increase the levels of a protein call Bax — which controls programmed cell death — that may push pre-cancerous cells to self-destruct.

In another, 200-patient, case-control study, led by Dr. Robert Bostick of Emory University, high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells’ movement and proliferation.

A third study on the same 200-patients shows high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.

All three studies — scheduled to be presented at the American Association for Cancer Research meeting in San Diego — use colorectal biopsy samples and are part of a larger effort to identify a portfolio of measurements which taken together could predict the risk of colon cancer.

“We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease,” Bostick says in a statement.

Researchers at Emory University are learning how vitamins and minerals in the diet can stimulate or prevent the appearance of colon cancer.

Emory investigators will present their findings on biological markers that could influence colon cancer risk in three abstracts at the American Association for Cancer Research meeting in San Diego.

In a clinical study of 92 patients, supplementing diet with calcium and vitamin D appeared to increase the levels of a protein called Bax that controls programmed cell death in the colon. More Bax might be pushing pre-cancerous cells into programmed cell death, says Emory researcher Veronika Fedirko, who will present her team’s results (abstract 464).

Previous studies have shown that calcium and vitamin D tend to reduce colon cancer risk.

“We were pleased that the effects of calcium and vitamin D were visible enough in this small study to be significant and reportable,” Fedirko says. “We will have to fully evaluate each marker’s strength as we accumulate more data.”

The studies of colorectal biopsy samples are part of a larger effort to identify a portfolio of measurements that together can gauge someone’s risk of getting colon cancer, says Roberd Bostick, MD, MPH, professor of epidemiology at Emory’s Rollins School of Public Health.

“We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease,” Bostick says. “These measurements will describe the climate of risk in the colon rather than spotting individual tumors or cells that may become tumors.”

More about Bostick’s plans for developing non-invasive blood or urine tests for colon cancer risk is available in an Emory Health Sciences Magazine article: http://whsc.emory.edu/_pubs/hsc/winter08/pdf/hold_out_your_finger.pdf

Another abstract from Bostick and his colleagues (565) demonstrates in a 200-patient case-control study that high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells’ movement and proliferation.

A third abstract on the same case-control study (5504) shows that high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.

Bostick and his colleagues are participating in a ten-year multi-center study of the effects of increased vitamin D and calcium and biomarker-guided treatment of colon cancer recurrence. The study involves almost 2,500 people nationwide who have regular colonoscopies.