July - August 2007

The Latest Information Coming from the Friedman School of Nutrition Science and Policy at Tufts University

Researchers Probe Risks, Benefits of Folic Acid Fortification

BOSTON — 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. Concurrent with the institution of fortification, however, the rate at which new cases of colorectal cancer were diagnosed in men and women increased, report researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University. Joel Mason, MD, director of the USDA HNRCA's Vitamins and Carcinogenesis Laboratory, and colleagues analyze the temporal association between folic acid fortification and the rise in colorectal cancer rates, and present their resulting hypothesis in an article in the July issue of Cancer Epidemiology Biomarkers & Prevention.

"Nationwide fortification of enriched grains is generally considered one of the greatest advances in public health policy," says Mason, who is also an associate professor at the Friedman School of Nutrition Science and Policy at Tufts. "But since the time that the food supply in North America was fortified with folic acid, we have been experiencing four to six additional cases of colorectal cancer for every 100,000 individuals each year compared to the trends that existed before fortification.

"Our analysis suggests that this increase is not explained by chance or by increased cancer screening. 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."

Mason and colleagues analyzed data from national cancer registries, one in the United States and another in Canada. The US data were derived from the nationwide Surveillance Epidemiology and End Results (SEER) registry that publishes cancer occurrence rates and survival data, covering approximately 26 percent of the population. The Canadian data were obtained from Canadian Cancer Statistics, an annual publication by the Canadian Cancer Society and the National Cancer Institute of Canada.

In 1996 and 1998, there were abrupt reversals in the 15-year downward trends in colorectal cancer rates in the United States and Canada, respectively. Since peaking in 1998 in the United States and in 2000 in Canada, the rates have not returned to their earlier levels. 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. After intestinal absorption, folic acid is converted to methyltetrahydrofolate, found naturally in foods such as leafy green vegetables, legumes and citrus fruits. "The body's response to folic acid appears to be complex," says 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. Our report is intended to create a foundation upon which to further explore that possibility."

As Mason and colleagues note, there is a compelling body of scientific evidence suggesting that habitually high intakes of dietary folate are protective against colorectal cancer. Mason explains, however, that "There are several reasons why we may have inadvertently created the opposite effect with folic acid fortification. First, folate's pivotal role in DNA synthesis also makes it a potential growth factor for cancerous or pre-cancerous cells, and when administered in large quantities to individuals who unknowingly harbor cancer cells, it could paradoxically 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," he says. "Second, the fact that a synthetic form of folate is used for fortification may be important," suggests Mason. "As the total amount of folic acid ingested increases, the mechanism that converts folic acid to methyltetrahydrofolate can become saturated. The leftover folic acid in the circulation might have detrimental effects, as it is not a natural form of the vitamin."

At a time when many countries are debating whether or not to institute or enhance folic acid fortification, 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," says Mason. "Improved monitoring and further research in this field is important to our understanding of the long-term public health effects of fortification."


Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. Cancer Epidemiology Biomarkers & Prevention. 2007 (July); 16(7):1-5. "A Temporal Association between Folic Acid Fortification and a Rise in Colorectal Cancer Rates May be Illuminating Important Biological Principles: a Hypothesis."

A Link Between Carbohydrate Quality and Vision Loss is Strengthened by New Data

BOSTON — Age-related macular degeneration (AMD) and its associated vision loss may be connected to the quality of carbohydrates an individual consumes. In a study published in the July issue of the American Journal of Clinical Nutrition, Allen Taylor, PhD, director of the Laboratory for Nutrition and Vision Research at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University, and colleagues confirmed earlier findings linking dietary glycemic index with the risk of developing AMD. 

"Men and women who consumed diets with a higher glycemic index than average for their gender and age-group were at greater risk of developing advanced AMD," corresponding author Taylor says. "The severity of AMD increased with increasing dietary glycemic index."

Glycemic index is a scale applied to foods based on how quickly the carbohydrates in foods are converted to blood sugar, or glucose. Foods like white rice, pasta and bread are examples of foods with a high glycemic index, meaning that these foods are associated with a faster rise and subsequent drop in blood sugar. Whole wheat versions of rice, pasta and bread are examples of foods that have a low glycemic index. These foods are often considered higher quality carbohydrates because they are associated with a slower and less dramatic rise and fall of blood sugar.

"Our results build upon findings from an earlier, smaller study in which we determined that consuming a diet with a high glycemic index, but not one with a high total amount of carbohydrate, increased the risk of developing early AMD," says first author Chung-Jung Chiu, DDS, PhD, scientist in the Laboratory for Nutrition and Vision Research at the HNRCA and an assistant professor at Tufts University School of Medicine.

In the current study, Taylor, Chiu, and colleagues analyzed data from 4,099 men and women participating in the nationwide Age-Related Eye Disease Study (AREDS). Detailed dietary histories were obtained at the start of the study when participants were 55 to 80 years of age and had varying degrees of AMD. The AREDS was designed to assess the effect of high-dose antioxidant vitamins and zinc on the progression of AMD and cataracts, two of the leading causes of vision loss in older adults.

"Although carbohydrate quality was not the main focus in the AREDS, we were fortunate that the investigators had collected the dietary carbohydrate information we needed to do our analyses," says Taylor, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts and Tufts University School of Medicine. "Our findings suggest that 20 percent of the cases of advanced AMD might have been prevented if those individuals had consumed a diet with a glycemic index below the average for their age and gender," notes Taylor.

AMD typically occurs after middle age, although the events which cause it may begin earlier. A leading cause of irreversible blindness, AMD results from the gradual breakdown of light-sensitive cells in the central region of the eye's retina, called the macula. Although there is no effective therapy for AMD, dietary intervention may delay its progress. Identifying modifiable risk factors for AMD is becoming increasingly important as the population ages. As Taylor and colleagues point out, the number of people in the US with visually impairing AMD is expected to double and reach three million by 2020.

"Our results support our hypothesis," says Taylor, "that dietary glycemic index, which has been related to the risk of diabetes, is also associated with the risk and severity of AMD." Taylor speculates that carbohydrates that comprise a high-glycemic-index diet may provide eye tissue with too much glucose too quickly, and overwhelm the ability of the eye cells to use the carbohydrate properly. "It is possible that the type of damage produced by poor quality carbohydrates on eye tissue is similar in both diabetic eye disease and AMD."

Taylor and colleagues conclude that the risk for AMD may be diminished by improving dietary carbohydrate quality, as defined by dietary glycemic index. This may be achieved by relatively simple dietary alterations, such as replacing white bread with whole grain bread. "However," Taylor cautions, "additional studies are needed before we can recommend dietary carbohydrate management as a prevention strategy for AMD."

The study was supported by the U.S. Department of Agriculture's Agricultural Research Service and by grants from the National Institutes of Health, Johnson and Johnson Focused Giving Program, the American Health Assistance Foundation, and individuals.

Chiu C-J, Milton RC, Gensler G, Taylor A. American Journal of Clinical Nutrition. 2007 (July); 86(1):180-188. "Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in the Age-Related Eye Disease Study."

Links Between Food Cravings, Types of Cravings, and Weight Management

BOSTON — Accepting food cravings and keeping them in check may be an important component of weight management, according to findings from the first six-month phase of a calorie-restriction study conducted at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University. Supplemental results from the Comprehensive Assessment of the Long-term Effects of Restricting Intake of Energy (CALERIE) trial provide new insights into food cravings, specific types of foods craved, and their role in weight control.

"Cravings are really normal; almost everyone has them," says corresponding author Susan Roberts, PhD, director of the USDA HNRCA's Energy Metabolism Laboratory. At the start of the study, 91 percent of the participants reported having food cravings, which are defined as an intense desire to eat a specific food. "Most people feel guilty about having food cravings," says Roberts, "but the results of this study indicate that they are so normal that nobody needs to feel they are unusual in this respect."

In addition, the results indicate that cravings don't go away during dieting. "In fact, 94 percent of the study participants reported cravings after six months of dieting. However," Roberts says, "participants who lost a greater percentage of body weight gave in to their cravings less frequently. Allowing yourself to have the foods you crave, but doing so less frequently may be one of the most important keys to successful weight control," she adds.

Roberts and colleagues observed that successful weight loss was related not only to how often people gave in to their cravings, but also to the types of foods they craved. "Participants with a higher percentage of weight loss actually craved foods with higher energy (calorie) density, compared with those who lost a lower percentage of body weight," says Roberts, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts University. "Energy-dense foods, such as chocolate and some salty snacks, are those that pack the most calories per unit of volume," explains Cheryl Gilhooly, PhD, MPH, research dietitian and first author of the study, "as compared to less energy-dense foods like fruits and vegetables, which have fewer calories per unit of volume."

"These findings suggest," says Roberts, "that cravings are for calories, not carbohydrate, as is widely assumed. What is commonly called carbohydrate addiction should probably be relabeled as calorie addiction," she added. Some of the most commonly craved foods among study participants were foods that have high sugar plus fat, such as chocolate, and salty snacks, such as chips and French fries. "The craved foods do have carbohydrate, but they also have fat, and some protein, too. The most identifiable thing about the foods people crave is that they are highly dense in calories," Roberts deduces.

The study, which was part of the one-year CALERIE trial, involved 32 overweight but otherwise healthy women, 20 to 42 years of age, who were randomly assigned to two diets that differed in glycemic load, a measurement of how quickly the carbohydrates in a person's diet are converted to blood sugar.

Participants completed food craving questionnaires that assessed the foods craved, the frequency and strength of cravings, and how often cravings led to eating the desired food. Researchers collected information from these questionnaires, along with data from dietary intake records and measures of weight change over time. Primary results from the CALERIE study were reported in an earlier issue of Friedman Nutrition Notes.

"This is the first study of long-term changes in food cravings in a calorie-restriction program," Roberts says. "If individuals understand that they can expect cravings and that those cravings will be for calorie-dense foods, it might help in their weight management. One thing to do is to substitute foods that taste similar but have fewer calories, since the craving can be satisfied by related tastes."

Roberts and colleagues conclude that cravings for energy-dense foods are common. Although they caution that additional long-term studies are needed to confirm their findings, they write that their results "...suggest that people attempting to lose weight and maintain weight loss may benefit from advice to accept that food cravings may not decrease in frequency." Controlling the frequency of giving in to cravings, rather than suppressing them, they say, may be an important area of emphasis in future weight control programs.

This work was supported by the Agricultural Research Service of the U.S. Department of Agriculture, and by grants from the National Institutes of Health and the Boston Obesity Nutrition Research Center. For more information about ongoing recruitment in Boston for the second phase of the CALERIE study at Tufts, visit http://hnrc.tufts.edu/1192109692477/HNRCA-Page-hnrca2w_1192109692483.html

Gilhooly CH, Das SK, Golden JK, McCrory MA, Dallal GE, Saltzman E, Kramer FM, Roberts SB. International Journal of Obesity; Advance Electronic version 26 June 2007; doi: 10.1038/sj.ijo.0803672. "Food cravings and energy regulation: the characteristics of craved foods and their relationship with eating behaviors and weight change during 6 months of dietary energy restriction."

If you are a member of the media interested in learning more about these topics, or in speaking with a faculty member at the Friedman School of Nutrition Science and Policy at Tufts University, please contact Siobhan Gallagher at 617-636-6586.

The Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University is the only independent school of nutrition in the United States. The school's eight centers, which focus on questions relating to famine, hunger, poverty, and communications, are renowned for the application of scientific research to national and international policy. For two decades, the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University has studied the relationship between good nutrition and good health in aging populations. Tufts research scientists work with federal agencies to establish the USDA Dietary Guidelines, the Dietary Reference Intakes, and other significant public policies.