To Old Age

To Old Age

Vitamin B12, Folate, and Cardiovascular Disease:

Scientists have long understood that air pollution contributes to cardiovascular disease, but they haven’t been able to pinpoint exactly how the damage happens. Sung Kyun Park, an environmental epidemiologist in the Department of Environmental Health Sciences, suspects a key pathway may be homocysteine—an amino acid in the blood that’s been linked to cardiovascular disease and some neurodegenerative diseases, including Parkinson’s. Park’s research shows a clear association between increased exposure to air pollutants and increased levels of homocysteine. (Smoking, too, he notes, raises homocysteine levels.)

But diet can help mitigate the harm. Folate and vitamins B12 and B6 have been shown to help break down homocysteine in the blood and thus reduce the risk for cardiovascular and other diseases. The American Heart Association, in fact, suggests that patients at high risk for cardiovascular disease be “strongly advised” to get enough folate and vitamins B12 and B6 in their diet. Foods high in these vitamins include green leafy vegetables and grain products fortified with folic acid, the synthetic form of folate. (The Heart Association notes, however, that physicians should consider a patient’s overall risk-factor profile and diet when making nutritional recommendations.)

In his research on air pollution and cardiovascular disease, Park has found that both folate and vitamin B12 significantly offset the effects of airborne pollutants in the blood. This is promising news, he says. Despite considerable work by the Environmental Protection Agency and other entities to lower emissions, air pollution continues to take a toll on human health. “If we consume more B12 and folate,” Park says, “it can make a difference.”

Cancer Prevention and Soy

Scientists know that methylation, the natural process by which methyl groups are added to DNA, can contribute to the development of cancer by silencing tumor-suppressor genes. And they know that nutrition affects methylation. But what they don’t know, says Laura Rozek, assistant professor of environmental health sciences, is “to what extent you can lower a person’s risk of developing cancer by changing their diet.”

Rozek is involved in a UM study that’s looking at soy and its potential to help prevent the recurrence of head and neck cancers. “We know that methylation is very important in these cancers,” says Rozek, “and we know that genistein, a component of soy, has exciting potential anti-tumor activities.” Genistein has been found to help suppress tumors in squamous-cell carcinomas of the oral cavity, bladder, and vulva, so it could very possibly help suppress tumors associated with head and neck cancers as well.

Participants in the UM study, a Phase II trial under the direction of UM Medical School Professors Gregory Wolf and Francis Worden, have all been diagnosed with some form of head or neck cancer. During the three-week period between their diagnosis and the start of treatment, they are supplementing their diets with genistein tablets. Researchers are evaluating their molecular markers before and after supplementation to see what impact, if any, genistein has, and then following the participants for relapse-free survival.

Findings from the study won’t be available until 2014, but Rozek is hopeful that genistein may be found to be helpful in suppressing tumors associated with head and neck cancers. She notes that these cancers are strongly linked to environmental exposures—specifically smoking, alcohol use, and human papillomavirus (HPV). “So down the line,” she says, “soy could be used as a supplement if you’re at risk—if you have a long history of smoking, for instance, or if you’re HPV-positive.”

Fast Food and Stroke Risk

A team of UM researchers, including three SPH faculty members, has found that the risk of stroke increases with the number of fast-food restaurants in a neighborhood. In the study, residents of neighborhoods with the highest number of fast-food restaurants had a 13 percent higher relative risk of suffering ischemic strokes than those living in areas with the lowest number of restaurants. The relative risk of stroke increased one percent for each fast-food restaurant in a neighborhood.

The stroke-risk association emerged from data gathered in the ongoing Brain Attack Surveillance in Corpus Christi project, which has identified strokes occurring in Nueces County, Texas, since January 1, 2000. The report examined 1,247 ischemic strokes that occurred from the study’s start through June 2003.

The implications? Neighborhoods with large numbers of fast food restaurants are prime areas for stroke-prevention programs. The researchers say additional study is needed to confirm the correlation. Lewis Morgenstern, professor of epidemiology and director of the UM Stroke Program, was lead author on the study. Co-authors include Lynda Lisabeth, assistant professor of epidemiology, and Brisa Sanchez, research assistant professor of biostatistics. —from UM Health System

 Fat Tissue: Friend, Foe, or Both

For a long time people regarded fat as an undesirable but inert tissue whose physiologic function was to keep us warm. But in the last ten years, that thinking “has just totally dropped away,” says epidemiologist MaryFran Sowers, who is collaborating with Peter Mancuso, associate professor of environmental health sciences, and others on a series of studies looking at the metabolic correlates of body size, obesity, and fat.

“Fat tissue can be as much an endocrine organ as your thyroid or your pancreas,” Sowers says. That’s because the products that fat cells produce have important biological functions in and of themselves. One such product is leptin, a hormone that regulates homeostasis and the immune response. Laboratory mice in states of acute starvation or fasting—and therefore deficient in leptin—are more susceptible to bacterial pneumonia, for instance.

“This is also very common with people who have a chronic illness or are critically ill and undergo a period of acute energy malnutrition,” Mancuso says. “In both cases, if we give them an injection of leptin, we can partially restore their host-defense capacity.” Thirty percent of Americans over the age of 65 suffer from some form of malnutrition. Leptin has also been shown to play an essential role in vaccination response. On the other hand, people with too much leptin are vulnerable to chronic inflammatory diseases such as atherosclerosis, osteoarthritis, and asthma

Mancuso and Sowers are working to understand the intracellular mechanisms by which leptin influences immune response. They think they’ve identified the pathway that’s most important for host defense.

A particular focus of Sowers’s research is the link between leptin and other substances produced by fat cells with cardiovascular disease and arthritis. One obvious concern, she says, is the role that nutrition plays in these processes. How does the food we eat modulate the behavior that leads to the creation of fat tissues? And how does all of this impact subsequent health?