Folic acid might be losing its sheen

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http://www.latimes.com/features/health/la-he-folate11-2009may11,0,4656570.story

Folic acid might be losing its sheen

Credited with lowering the rates of some birth defects, the vitamin also has

been linked to a higher likelihood of some cancers.

By Sohn

May 11, 2009

Folic acid is one of those great public health success stories. In the decade

that followed the fortification of cereal grains and other foods, along with

educational campaigns, the rate of certain birth defects dropped dramatically.

As studies beginning in the 1980s started showing that folic acid could also

help prevent some cancers, it started to seem like a wonder-vitamin.

Now, however, folic acid's heyday may be over. New studies suggest that getting

too much folic acid might fuel certain cancers in some people.

And with the vitamin showing up in ready-to-eat cereals, bread, snack bars,

multivitamins and more, some health experts fear that it's easy to far exceed

the recommended daily intake of 400 micrograms.

There is now an urgent need, experts say, to figure out how much folate is

enough but not too much for different segments of the population.

" Too little folic acid we know is not good, and too much folic acid is probably

not good, " said Connie Motter, a genetic counselor at Akron Children's Hospital

in Ohio and co-chair of the National Council for Folic Acid, a coalition of

advocacy groups. " The answer is not going to be easy. "

Folic acid is the synthetic version of folate, or vitamin B9, one of eight B

vitamins. The vitamin -- found naturally in leafy greens, orange juice and

legumes, among other foods -- helps the body make and maintain new cells. That's

important for a number of processes, including growing a baby.

The United States began requiring the fortification of flour, and several other

cereal grains in 1998, after clinical trials linked folic acid deficiency with

spina bifida and anencephaly, two potentially devastating birth defects. Since

then, the rate of both defects has declined by 20% to 50%, depending on which

studies you look at.

No one disputes the need for women to have adequate amounts of folic acid in

their bodies at the time of conception. The first few weeks of pregnancy, in

particular, are a critical period for a baby's brain and spine development. And

because more than half of pregnancies are unplanned, doctors recommend that all

women of childbearing age take a daily supplement of up to 800 micrograms of

folic acid.

But for other people, the evidence for folate's benefits is mixed.

On the plus side, getting enough folate protects against anemia. It may promote

heart health, though that link is controversial. And it keeps hair, skin and

nails healthy.

On the downside, scientists know that excess folic acid can cover up a shortage

of the vitamin B12. B12 deficiency is a common condition in older patients that

can cause dementia if not addressed.

The story grows even more complex in the case of cancer.

" For the last 20 years, I've been publishing papers and doing research that

demonstrates that if you don't get enough folate, you have a higher risk for

several types of cancer, " said B. Mason, professor of nutrition science and

policy at Tufts University in Boston. " More recently, what has emerged is that

it's not as simple of a relationship as we thought. "

In some ways, folic acid appears protective. The vitamin plays an essential role

in the formation and repair of DNA and can help prevent development of certain

cancers, particularly in the colon, where cells replicate especially fast.

Studies show that people who get plenty of folic acid reduce their risk of

developing colorectal cancer and precancerous polyps by 40% to 60%. But folic

acid doesn't just help healthy cells grow. It also helps cancerous cells grow.

Studies in animals have shown that once cells are on the path to becoming

cancers, the vitamin makes things worse.

As far back as the 1940s, folic acid supplements were found to accelerate

leukemia in children who were given the vitamin in the hope that it might help.

(Such studies helped lead to a class of antifolate drugs that are among today's

most common cancer treatments.)

More recently, researchers noticed that rates of colorectal cancer went up in

North America around the same time that fortification began. One study,

published by Mason and colleagues in 2007 in the journal Cancer Epidemiology

Biomarkers & Prevention, acknowledged that the link could be a coincidence. But

according to another study published this year, the same thing happened in Chile

after fortification began there in 2000.

Mason estimates that excess folic acid consumption may cause an extra 15,000

cases of colorectal cancer each year in the U.S. and Canada. By comparison,

fortification with the vitamin prevents an estimated 2,000 to 3,000 brain and

spinal cord defects in both countries.

Folic acid's effects have also been tested in clinical trials. In the largest

one completed, scientists studied almost 1,000 people who had had precancerous

polyps removed from their colons. Half of the patients were randomly assigned to

take a daily supplement of 1 milligram of folic acid (2.5 times the recommended

intake of 400 micrograms). The others took a placebo.

Several years later, people in the folic acid group were more than twice as

likely to have three or more polyps in their colons, the researchers reported in

2007 in the Journal of the American Medical Assn. The men in the study who had

taken folic acid supplements were nearly three times as likely to develop

prostate cancer up to a decade later, researchers reported in March in the

Journal of the National Cancer Institute.

The overall number of cases was small --there were 34 cases of prostate cancer

in more than 600 men -- but the difference was large enough to cause concern.

" It's probably the most damning evidence to date, " Mason said. " We're presented

with this horrible dilemma that on the one hand, taking ample quantities of

folate in the diet is helpful. On the other hand, it might be accelerating the

risk of developing certain cancers in certain people. "

And so governments face a tricky problem: how to make sure that the people who

need folic acid are getting enough without putting another segment of the

population at risk. More than a dozen countries currently have mandatory

folic-acid fortification. Many others are considering it, including the European

Union.

The United Kingdom decided to fortify about three years ago but pulled the plug

on their program when they saw the new cancer data emerging.

Several years ago, the March of Dimes was pushing for higher levels of

fortification, but the organization is now supporting current levels.

Brain and spinal cord defects cost the United States $20 million every year,

says Motter, the genetic counselor.

But clearly, she adds, the folic acid research illustrates how one nutrition

policy can affect different groups of people in dramatically different ways.

" Do we know whether the risk to an adult male is the same as the risk to a woman

in her childbearing years? " she said. " The answer is no. . . . There is always a

risk and balance with anything you do. "