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Global Network

Issue 21 — June 24, 2009

Science News Roundup:

  1. Colorectal Cancer Increasing in Young
  2. Mental Shortcut May Ignore Portions
  3. Eat Your Fruits and Veggies for Your Kidney
Folic Acid suppliments and folate rich foods

The Folate Paradox

For years studies consistently linked high folate levels to decreased risk of certain cancers. Yet recently, an emerging body of evidence suggests that folic acid may – in some cases – accelerate cancer development. Who should take folic acid and how much are questions that AICR scientists are only beginning to unravel.

A Dual Effect

Folic acid is the synthetic form of folate, a B vitamin found naturally in many foods, including green leafy vegetables, whole grains and legumes. Shortly after folate was identified in the 1940s, folic acid was given to children with leukemia. Surprisingly, their cancer worsened. The discovery led to a folate-blocking chemotherapy still used today.

Then in the 1980s and 1990s a steady stream of studies linked high folate levels to decreased risk of colorectal cancer. Recent evidence continues to support these findings.

“Giving folic acid to cancer cells is like putting oil on the fire.”

“In the 1990s, my lab and other labs were doing studies [on folic acid] and what we kept observing in our animal models is that in the early phases of the cancer process, abundant amounts seemed to protect animals,” said Joel Mason, an Associate Professor at Tufts University who presented at AICR’s annual research conference in November. “On the other hand, once a precancerous group of cells existed in the animal, it actually served as fertilizer.”

Feeding a Growth

In 2007, Dr. Mason published a study showing a correlation between government folic acid fortification programs and increased rates of colorectal cancer. The United States and Canada began fortifying grains with folic acid in 1996 and 1997, respectively, in order to decrease neural tube defects. The analysis found a steady decline in colorectal cancer incidence in both countries for approximately 15 years prior to fortification, and then a reversal of the downward trend that parallels the fortification programs. Changes in colorectal screening rates did not appear to account for the increased incidence.

The Epigenetic Effect

One way folate can trigger epigenetic changes is by a process called DNA methylation. During DNA methylation folate releases a small molecule – a methyl group – along certain sections of the DNA. The added methyl group leads to the gene, in effect, being turned off.

Studies now show that DNA methylation can silence or activate a tumor suppressor gene. Because epigenetic modifications are environmental, some are also potentially reversible.

This study does not show cause, notes Dr. Mason, only correlation.

It’s in the Timing

Research explaining the protective effect of folate may also pinpoint the mechanisms behind its cancer-promoting effect. In healthy cells, folic acid ensures DNA replicates normally. But cancer and pre-cancer cells produce new copies of DNA faster than normal cells and thus, need folate to multiply.

“Giving folic acid to cancer cells is like putting oil on the fire,” says Young-In Kim, MD, an Associate Professor in Nutritional Sciences at the University of Toronto who conducted several of his studies with an AICR grant.

Folate also plays a key role in the epigenetic processes. Epigenetics is the study of changes in gene expression without changes in the DNA (see box). There are critical phases of growth when our epigenome is most susceptible to change, says Dr. Kim.

“In utero, the epigenetic patterns are being reprogrammed and folic acid might have a tremendous impact,” he said. Aging is another period where folate deficiency and supplementation can more easily lead to epigenetic changes, says Dr. Kim. The effects of folic acid also appear to be gene specific, he says, where the same manipulation in one gene can give the opposite effect in another. “Right now, there’s a lot of controversy and complexity about folate.”

Eating your Folate

Folate Foods

Dr. Kim and other experts say that more research on folic acid supplementation is needed before any definite conclusions can be drawn. Individuals considering supplementation should consult with their health care provider. But the same concerns do not hold true for the natural form of folate.

“We are operating with incomplete information, and we need further study,” said Dr. Mason. “But there is absolutely no evidence that folate in foods and a diet rich in natural sources of folate is harmful. The evidence shows it is beneficial for you.”

—Excerpted from a feature in ScienceNow.

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News Break

Six out of every ten breast cancer patients report taking antioxidant supplements during treatment despite the possible harmful consequences, reports a new study in Cancer. This link will open in a new window.

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Science News Roundup

Colorectal Cancer Increasing in Young

Colon Rectum

In sharp contrast to the overall decline in colorectal cancer rates, a new study finds that rates are rising in young adults – a population not typically screened for this cancer. The study, published in this month’s issue of Cancer Epidemiology Biomarkers & PreventionThis link will open in a new window., looked at trends in colorectal cancer incidence between 1992 and 2005 among young adults. Rates of colorectal cancer among 20-49 year old non-Hispanic Whites increased for every 10-year age group under 50 and for every stage of diagnosis. The largest yearly percent increase occurred among the youngest age group (20-29 years), in whom incidence rates rose by 5.2 percent in men and 5.6 percent in women.

Overall incidence rates for colorectal cancer have declined over the past two decades, with the largest drops occurring in recent years. Rates are now dropping 2.8 percent per year in men and 2.2 percent per year in women, a drop largely attributed to increased screening among those ages 50 and older. The authors theorize that the increasing rates among the young may, in part, be due to changes in lifestyle. Consumption of red and processed meats and obesity are two major risk factors associated with increased risk of colorectal cancer and both have risen over the past decade.

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Mental Shortcut May Ignore Portions

An old and handy cognitive shortcut that causes people to ignore vital information in a quick decision-making process may also lead us to mistakenly calculate portion sizes, according to a new study. The effect, suggest the authors, may be contributing to the increasing rates of obesity. Yet the findings also suggest that people may not notice modest decreases in portion sizes.

3 Apples in 3 sizesIn a series of tests published in this month’s Journal of Experimental Psychology: AppliedThis link will open in a new window., one of the studies asked college students to estimate the calories of one of two meals, once in each of two dining halls. Both dinners contained the same foods on the same plate displayed in the same setting – on a table with only the meal and list of the foods – but one had significantly larger portions than the other. The larger meal was more similar to what the students would normally eat.

The effect, suggest the authors, may be contributing to the increasing rates of obesity. In a series of tests published in this month’s one of the studies asked college students to estimate the calories of one of two meals, once in each of two dining halls. Both dinners contained the same foods on the same plate displayed in the same setting – on a table with only the meal and list of the foods – but one had significantly larger portion than the other. The larger meal was more similar to what the students would normally eat.

Drawing from about 650 guesses – students were offered a $25 prize for coming the closest to actual calories – researchers found that participants assumed portion sizes were typical and guessed almost no caloric differences between the large and small dinners. The large meal was estimated at only an average of 53 calories more than actual caloric value; the small meal was overestimated by over 300 calories.

The phenomenon is an evolutionary one, note the authors, similar to when we hear a bark and see the tip of a furry tail our brain jumps to the assumption it’s a dog. This keeps our brain from mulling over the countless possibilities and provides correct information about 97 percent of the time. But it also can lead to ignoring or devaluing other critical information, which can also help promote healthy changes, write the authors.

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Eat Your Fruits and Veggies for Your Kidney

Fruits and Veggies

Eating plenty of fruits and vegetables may lower the risk of the most common type of kidney cancer, according to a new analysis of 13 studies. Published in Cancer Epidemiology Biomarkers & Prevention, the study analyzed questionnaires from almost three-quarters of a million study participants on their fruit and vegetable intake. After following the participants for 7 to 20 years and finding about 1,500 cases of renal cell cancer, the researchers found that participants who ate the most total fruit and vegetables had significantly lower risk of renal cell cancer than those who ate the least. Specific foods pulled out as decreasing risk were root vegetables, broccoli, and carrots (the primary root vegetable eaten), but overall, note the authors, there are likely multiple healthful compounds in a wide variety of fruits and vegetables that contribute to the lower risk of renal cell cancer.

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