Healthy News for Healthy Nation

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The side effects are part of the reason that GlaxoSmithKline’s Alli, the first over-the-counter diet pill, works for dieters who take it.

When the fat-blocker Alli hit pharmacy shelves last June, hopeful consumers stampeded for the first government-approved over-the-counter weight-loss drug. But it didn’t take long for the troublesome side effects such as not being able to control your bowels, and the lack of real weight loss for some, to convince many dieters that Alli wasn’t the sole answer to their weight problems.

In addition to Alli, there are about six prescription weight-loss drugs on the market. Some, like Alli, block the absorption of fat in the body. Others work in the brain to suppress appetite. But the reality is, no matter how many weight-loss pills you take, they don’t work by themselves.

“The pills we currently have don’t seem to be terribly effective for long-term weight loss,” says registered dietitian Anne Fletcher of Mankato, Minn. “When people go off the pills, many put weight back on.”

Still, the drug industry and many dieters remain convinced that a pill is the answer to the nation’s growing obesity epidemic. Several new prescription diet pills are in late stage trials, including the experimental drug lorcaserin, a variation of Fen-phen which was pulled for causing heart problems. At least 30 companies are developing weight-loss drugs, with experts estimating that in the next few years there will be 10 to 15 medications meant to help dieters in different ways. The pharmaceutical research firm Decision Resources projects that the obesity drug market will grow in the U.S. from $222 million in 2006 to nearly $2 billion by 2016.

When combined with diet and exercise, anti-obesity drugs can help someone lose about 5 to 10 percent more weight, research suggests. But because the various pills affect the body in different ways, it’s possible that certain people may be better suited to using one type of pill over another.

For example, a study looking at the differences between sibutramine (Meridia) and orlistat (Xenical and Alli), found that greater weight loss with orlistat occurred in people who could be described as “conscientious,” that is, their personalities were more order-oriented or deliberate. Therefore, carefully monitoring fat intake works for them. People who have a hard time restraining their eating habits saw a greater impact with sibutramine — which affects serotonin in the brain and makes you feel full sooner when eating.

If at first, you don’t succeed …
In general, the biggest mistake people make in taking diet pills is looking at them as magic bullets.

“People cannot expect a medication to do it for them,” says Gary Foster, director of the Center for Obesity Research and Education at Temple University in Philadelphia. “It’s a 50/50 partnership with the pill being half the equation. Exercise, what we eat and our lifestyle habits … are critical to long-term success.”

When clients request to use a weight loss medication, Fletcher, author of the book “Thin for Life,” tells them to think of it as “one leg of a four-legged stool.”

“One leg is physical activity; one is diet; one is behavior change and the final leg can be diet pills,” she says. “Take out any of the legs that support the diet pill and the stool will fall over.”

From her research Fletcher found that people who lost significant amounts of weight often had made multiple efforts to lose weight before they realized long-term success.

“When we try to change any behavior it takes most of us a few attempts to get it right,” she says.

Side effects
There’s no real data on how safe the pills are long-term, especially for young people. However, the Food and Drug Administration has only approved them for adults for up to two years of continuous use. According to an analysis of 30 trials done on adults taking anti-obesity drugs for one to four years, about 30 to 40 percent stopped taking them after a year, although it wasn’t clear why.

In addition, side effects are common. Sibutramine can increase blood pressure and heart rate in some patients. Orlistat, which alters the absorption of fat in food, can have embarrassing intestinal side effects. Rimonabant (used in Europe, but awaiting approval in this country) may, for some users, cause nausea, anxiety, depression and insomnia.

However, for the obese — people with a body-mass index of 30 or greater— the benefits of prescription diet drugs can outweight the risks, experts believe.

“The people most successful are those who are ready to make a serious commitment to losing weight and willing to take responsibility for their actions and for change,” says Pat Baird, a dietitian and nutrition consultant for GlaxoSmithKline’s Consumer Healthcare division, who serves as an online moderator for people using Alli. She talks with 25 people a day, fielding questions about weight loss, the program and the pill.

Baird concedes that the side effects are part of the reason Alli works for some people. When someone eats more than the prescribed 15 grams of fat per meal, they can experience the not-so-pleasant digestive problems. “It helps keep people honest,” she says.

Susan Moores, R.D., is a nutrition consultant and spokesperson for The American Dietetic Association

© 2008 MSNBC Interactive

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New research suggests that a woman’s waistline may have less to do with rigorous exercise and abstaining from sweets than it does with the genes of her parents. (Credit: iStockphoto/Alexander Novikov)

Your friend can eat whatever she wants and still fit into her prom dress, but you gain five pounds if you just look at that chocolate cake. Before you sign up for Weight Watchers and that gym membership, though, you may want to look at some recent research from Tel Aviv University and save yourself a few hundred dollars.

A woman’s waistline may have less to do with rigorous exercise and abstaining from sweets than it does with the genes of her parents, according to a new study by Prof. Gregory Livshits from the Sackler Faculty of Medicine at Tel Aviv University and colleagues from King’s College in London. Dr. Livshits and his colleagues have found a scientific link between the lean body mass of a woman and her genes. They’ve determined that thinness — like your smile or the color of your eyes — is an inheritable trait.

Bad News First, Then the Good

Prof. Livshits, whose findings were published in the Journal of Clinical Endocrinology and Metabolism (2007), says, “The bad news is that many of our physical features, including our weight, are dependent on our genes. The good news is that women still have an opportunity to go against their genetic constitution and do something about it.”

Until now, scientists were not sure to what extent environmental influences and genetics played a role in a woman’s body size. When controlling for the variance of age, the differences in womens’ body sizes can be predicted in the genes more than 50 percent of the time, the researchers found.

Prof. Livshits conducted his study on more than 3,000 middle-aged women in the United Kingdom who belonged to either an identical or fraternal twin pair. He measured their “total lean mass,” one of the three major components of body weight, and compared it to markers in their genes.

A Slim Chance?

Additional collaborative research between the two teams, which builds on the past study, is to be published in the next few months. It may help pave the way for a “skinny gene test,” which one day may help women trying to lose weight understand what kind of battle they can expect.

Those without the lean genes, however, will always find it harder to stay slim, predicts Prof. Livshits. But before your diet falls by the wayside, consider Prof. Livshits’ contention that genetics can be overcome.

Curb Your Enthusiasm

It’s important to not have high expectations, he warns. “Women need to know that what they can do about their body weight — especially when they age — is relatively little, and they will do it only with much difficulty.”

Very few studies to date have been able to associate a body’s lean mass with genetics. The topic is a specialty at the Tel Aviv University lab, one of the top labs in the world to study the genetics of aging of body composition. This area includes the study of bone, fat and lean mass as it develops in a person over time.

Research on body composition components — their growth, degradation and genes — is part of Prof. Livshits’ ongoing work on aging and health. Issues such as weight gain are complex, he says, especially when age is factored in.

So don’t get too jealous of your friend’s dress size. It may be mostly out of your hands — and in your DNA.

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Tart cherries are often sold dried, frozen or in juice form. (Credit: Cherry Marketing Institute, courtesy of University of Michigan Health System)

Tart cherries — frequently sold dried, frozen or in juice — may have more than just good taste and bright red color going for them, according to new animal research from the University of Michigan Cardiovascular Center.

Rats that received whole tart cherry powder mixed into a high-fat diet didn’t gain as much weight or build up as much body fat as rats that didn’t receive cherries. And their blood showed much lower levels of molecules that indicate the kind of inflammation that has been linked to heart disease and diabetes. In addition, they had significantly lower blood levels of cholesterol and triglycerides than the other rats.

The results, which were seen in both lean and obese rats that were bred to have a predisposition to obesity and insulin resistance, were presented Sunday at the Experimental Biology 2008 meeting in San Diego, CA by a team from the U-M Cardioprotection Research Laboratory.

In addition, the obese rats that received cherry powder were less likely to build up fat in their bellies — another factor linked to cardiovascular disease. All the measures on which the two groups of animals differed are linked to cardiovascular disease and Type 2 diabetes.

The new findings build on results that were reported last year at the same meeting by the U-M team. Those data came from experiments involving lean rats that were prone to high blood pressure, high cholesterol and impaired glucose tolerance, but that received a low-fat diet with or without cherries. In that case, cherry-fed rats had lower total cholesterol, lower blood sugar, less fat storage in the liver and lower oxidative stress. However, it was unknown if these benefits would be observed in obesity-prone animals, or in animals fed a higher fat, western-style diet containing elevated saturated fat and cholesterol.

While it’s still far too early to know whether tart cherries will have the same effect in humans, U-M researchers are preparing to launch a pilot-phase clinical trial later this spring. They note that if a human wanted to eat as many tart cherries as the rats in the new study did, they would have to consume 1.5 cups every day.

“These new findings are very encouraging, especially in light of what is becoming known about the interplay between inflammation, blood lipids, obesity and body composition in cardiovascular disease and diabetes,” says Steven Bolling, M.D., a U-M cardiac surgeon and the laboratory’s director. “The fact that these factors decreased despite the rats’ predisposition to obesity, and despite their high-fat ‘American-style’ diet, is especially interesting.”

The results were presented by E. Mitchell Seymour, M.S., a U-M research associate and the senior scientist on the project. “It was recently shown in humans that regular intake of darkly pigmented fruits like cherries is associated with reduced mortality from cardiovascular disease and coronary heart disease,” says Seymour. “The heart-health benefits of these colorful fruits were sustained even when corrected for age and other health conditions. We’re now invested in exploring the specific mechanisms of these benefits.”

The experiments are funded by an unrestricted grant from the Cherry Marketing Institute, a trade association for the cherry industry. CMI has no influence on the design, conduct or analysis of any U-M research it funds.

The correlation between cherry intake and significant changes in cardiovascular risk factors suggests — but does not directly demonstrate — a positive effect from the high concentrations of antioxidant compounds called anthocyanins that are found in tart cherries. The anthocyanins are responsible for the color of these and of other darkly pigmented fruits.

The potential for protective effects from antioxidant-rich foods and food extracts is a promising area of research, says Bolling, who is the Gayle Halperin Kahn Professor of Integrative Medicine at U-M.

The team performed the study using 48 obesity-prone rats, half of which were obese, and a diet in which 45 percent of calories came from fat and 35 percent came from carbohydrates. All the rats were six weeks old when study began. For the next 90 days they were fed either a cherry-enriched diet in which cherries made up 1 percent by weight, or a diet that contained an equivalent number of carbohydrates and calories.

At the end of the study, the rats had blood tests for glucose, cholesterol and triglyceride levels, received DEXA scans to measure their body fat and to see where the fat had collected, and had tests for two plasma inflammation markers: TNF-alpha and interleukin-6.

These two molecules are related to the level of vascular inflammation, or immune-system reaction to blood-vessel walls, that is often seen in people and animals with cardiovascular disease. While inflammation is a normal process the body uses to fight off infection or injury, according to recent science, a chronic state of inflammation may increase the risk for a number of diseases.

The cherries were Montmorency tart cherries grown in Michigan, which is the nation’s largest producer of tart cherries. They are different from the sweet Bing cherries that are often eaten fresh. Tart cherries have higher concentrations of antioxidant anthocyanins than sweet cherries.

By the end of the study, the rats that received the cherries had lower body weight, fat mass, total cholesterol, triglyceride, TNF-alpha and IL-6 than the rats that did not receive cherries. In all, TNF-alpha was reduced by 50 percent in the lean rats and 40 percent in the obese rats and IL-6 was lowered by 31 percent in the obese rats and 38 percent in the lean rats.

The obese rats that received cherries also had lower-weight retroperitoneal fat, a type of belly fat that has been associated with especially high cardiovascular risk and inflammation in humans.

In addition to Seymour and Bolling, the research team includes Daniel Urcuyo-Llanes, Ara Kirakosyan, Peter B. Kaufman, and Sarah K. Lewis of U-M, and Maurice Bennink of Michigan State University.

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Biochemical signals associated with atherosclerosis may damage other organs, researchers say. Shown is a blood vessel viewed under a high-powered microscope. (Credit: National Science Foundation, Michigan State University)

Many scientists view atherosclerosis, or hardening of the arteries, as a localized disease characterized by the build up of fatty plaques in the arteries, which can eventually cause heart attacks and strokes. Now, in a finding that challenges conventional knowledge, researchers in New York and North Carolina report that plaques formed in arteries are associated with certain harmful chemical reactions that can contribute to damage in the lungs, liver, and other organs.

The findings suggest that the effects of atherosclerosis are more widespread than previously believed, the researchers say. The study could lead to new targets for developing drugs that could help prevent or reduce these chemical changes that appear to accompany heart disease, the number one cause of death in the U.S. Their study was presented today at the 235th national meeting of the American Chemical Society.

“Our findings add new knowledge to the big melting pot of this complex disease called atherosclerosis,” says study leader Rita Upmacis, Ph.D., a chemist at Weill Medical College of Cornell University in New York. “I anticipate that future research will establish whether the harmful protein modifications we observed in animal organs can be prevented and provide the basis of new treatments for the disease.”

Scientists are closing in on the root causes of the disease. One of the more promising lines of research focuses on the interaction between certain highly reactive nitrogen molecules and proteins. Under certain conditions, this interaction produces nitrotyrosine, which has been linked to Alzheimer’s, arthritis, cancer, and other disorders. However, scientists know little about the role of nitrotyrosine in atherosclerosis.

In the new study, Upmacis and colleagues worked with laboratory mice that have atherosclerosis. These mice are widely used in atherosclerosis research that cannot be done in humans. Mice that are genetically prone to atherosclerosis and fed a high-fat diet developed high levels of nitrotyrosine in their heart, lung, liver, and kidney. By contrast, mice that were fed regular diets showed no such increase. The rise in nitrotyrosine levels suggests that high-fat diets in animals with atherosclerosis can help trigger nitrotyrosine accumulation in the proteins of various organs, the scientists say.

Upmacis and colleagues also conducted a related experiment in atherosclerotic mice lacking the gene that makes nitric oxide synthase (iNOS), an enzyme that orchestrates accumulation of nitrotyrosine in proteins. In association with prior findings that iNOS gene deletion limits the formation of atherosclerotic plaques, the new study showed that nitrotyrosine accumulation in proteins is reduced in diverse organs when iNOS is absent.

“The findings support an emerging view that iNOS could be a new target for treating atherosclerosis and that limiting nitrotyrosine accumulation in the lungs, liver, and other organs could help fight the damaging effects of the disease,” Upmacis says. “But the trick will be to develop a drug to block this pathway without causing any unwanted side effects.”

Potentially, the accumulation of nitrotyrosine in the blood can be utilized as a diagnostic test to track atherosclerosis and provide a clearer picture of damage to organs, the researchers say.

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