Some families, alas, are fatter than others. But for dieters continually at war with their genes, there’s good news in a study published in this week’s PLoS Medicine: they can burn off 40% of their genetic predisposition to obesity by exercising.

Led by Dr. Ruth Loos from the Medical Research Council Epidemiology Unit in Cambridge, U.K., the study evaluated more than 20,000 Britons aged 39 to 79, asking about their exercise habits and surveying their genes. Researchers focused on 12 genetic variants known to increase the risk of obesity, and calculated a genetic obesity-predisposition score for each individual based on how many variants the person had. (Watch an audio slide show on obesity rehab.)

Researchers then compared the volunteers’ scores with their body mass index (BMI), the commonly used ratio of height and weight that defines obesity, and further examined the impact of exercise on BMI. Unlike many past studies that have only zeroed in on variants of one gene, the well-known FTO obesity gene, the new result is a more complete picture of how physical activity affects a person’s susceptibility to obesity – and one that offers reason for hope. (See three lifestyle changes that can help curb obesity.)

For a 5-ft. 7-in. (1.7 m) person, the study found, each additional genetic variant inherited from either parent led to an extra pound (0.45 kg) of weight on average, compared with people with no genetic predisposition to obesity. Here’s the good news: the more active the person was, the smaller the weight gain. The avowed couch potatoes in the study, who reported working a sedentary job and engaging in zero recreational physical activity, weighed the equivalent of an extra 1.3 lb. (0.59 kg) per variant. “Moderately inactive” people – those who worked at a standing job or reported less than 30 minutes a day of recreational activity on top of a sedentary lifestyle – were comparatively less overweight, logging an extra 0.87 lb. (0.39 kg) per variant.

Moderately active people – those who combined a sedentary job with 30 to 60 minutes a day of physical activity, or had a standing job with less than half an hour a day of exercise – gained even less, with each variant translating to an extra 0.85 lb. (0.38 kg). And active people – those exercising more than an hour a day outside their sedentary job, say, or working in heavy manual labor – were thinnest, gaining an extra 0.8 lb. (0.36 kg) per variant, a full 36% less than their least active peers. Overall, by exercising they had reduced their genetic risk of obesity by 40% compared with their inactive peers. (See how obesity is being traced back to the womb.)

Not surprisingly, a similar relationship between physical activity and obesity risk held for people who were not genetically predisposed to be heavy. But the exercise effect was smaller: regardless of size, a person wired to be heavy will reduce his or her odds of obesity more through physical activity than a person who’s genetically lean. In other words, not only can those wired big benefit from exercise, but also they can actually benefit more by working out than their counterparts with the right genes for skinny jeans.

Scientists hope the findings could pave the way for personalized obesity treatments in the future.

Unlike some past research – such as a 2008 study of about 700 Amish people that found it may take a punishing three to four hours a day of exercise to whip your genes into shape – the new paper suggests that even little boosts (like taking the stairs at lunch and parking a bit farther away from the office) can make a big difference in overcoming your genetic makeup. “You don’t have to run marathons,” says Dr. Loos. “It is sufficient to do some physical activity.”

The authors speculate that the differences in results could be due to characteristics specific to the populations in past studies or the small sample sizes in previous research. The strengths of Loos’ study include its range of included genetic variants and its large sample size. But there is also a notable weakness: the fact that participants were required to self-report their exercise habits rather than actually be observed on the Stairmaster by scientists.

Still, with the number of obese adults worldwide expected to bloat to 700 million by 2015, any suggestion that we can overcome our genes and whittle our waistlines is welcome news.

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With the Food and Drug Administration (FDA) still under fire for failing to monitor the safety of a popular diabetes drug after it hit the market, researchers have released a new study revealing potentially dangerous risks of another widely prescribed medication: the weight-loss drug Meridia (sibutramine).

The report, published on Wednesday in the New England Journal of Medicine (NEJM), found that among nearly 10,000 overweight or obese patients, those who used Meridia had a 16% greater risk of having a heart attack or stroke over an average 3.4 years than patients taking a placebo. None of the events were fatal, but the finding was especially worrisome since the trial included only patients with a previous history of heart disease or diabetes, or both, which put them at high risk of a second event. Being overweight, they were also already at a higher risk of heart-related health problems. (Does the FDA have a drug problem?)

The study was commissioned by the European Union’s European Medical Agency, after initial studies of Meridia users, conducted prior to 2002, found that the drug raised blood pressure and pulse rates, both well known risk factors for heart disease. When Meridia, which suppresses appetite by regulating the brain chemicals serotonin and norepinephrine, was approved for use in the U.S. in 1997, the FDA included a warning about these risks on the label. (See TIME’s quick guide to the FDA.)

The new trial did not address the question of whether such heart risks would outweigh the weight-loss benefit for people without a history of heart disease. But Dr. Gregory Curfman, executive editor of the NEJM, who wrote an editorial accompanying the study with several colleagues, says the risks are significant for all patients, according to the evidence. “With sibutramine we have a risk-benefit picture that is not favorable,” he says. “In my opinion, it’s time for regulatory action on the drug.”

That may come after Sept. 15, when an FDA advisory committee is scheduled to meet to review the latest data on Meridia’s safety and to decide whether it should remain on the market. In January, the European Medical Agency recommended banning the medication from its member nations, based on preliminary results from the current trial. The agency’s experts noted that the weight loss seen among Meridia users – about 9 lb. over the course of the study – did not justify the potential health risks associated with the drug. And given the patients’ heightened risk of heart problems, the 9-lb. loss was clearly not sufficient to reduce the risk of any weight-related health issues. (See a study on how exercise can counteract obesity genes.)

The study’s authors disagree with that interpretation, however, noting that the elevated risks were limited to those with a history of heart disease. Among patients with diabetes but no history of heart attack or stroke, the authors say, there was no increase in heart problems compared with the control group. In fact, in additional data gathered since the paper was submitted, they say there is evidence that this group of Meridia takers actually lowered their risk of heart events. “What I am saying is that we have got to have some perspective,” says lead author Dr. Philip James of the London School of Hygiene and Tropical Medicine. “I am saying we should not give this drug to people with a history of heart attack or stroke. But the best evidence we have at the moment is that among people who followed the prescription recommendations, not only do they not appear to have any greater risk of heart events, but they seem to have substantial benefit as well.”

That perspective will likely be the subject of intense debate among the FDA’s advisory committee members. “Nobody got better, and some people got worse, and the amount of weight loss wasn’t that much,” says Curfman. “With that profile, we have a lot of difficulty seeing what the argument would be for keeping the drug on the market.”

Dr. Steve Nissen, a cardiologist at the Cleveland Clinic Foundation who has been a vocal critic of recent FDA handling of drug safety concerns, agrees. “We’ve got a drug here that shows little benefit – a few pounds of weight loss – and we trade that for a 28% increased risk of heart attack and 36% increased risk of stroke. For a modest amount of weight loss, what are the health outcome benefits?”

That’s the question that the FDA will have to answer once again. Commissioner Margaret Hamburg is still weighing similar evidence regarding the diabetes drug Avandia, or rosiglitazone. An advisory committee recommended in July that the drug remain on the market with restrictions on its use, despite strong evidence that users were at increased risk of heart events. Experts in favor of keeping Avandia available to consumers argued that diabetes patients had few other options for controlling blood sugar, and that the evidence was not conclusive about Avandia’s harms. Hamburg has yet to decide whether to follow the committee’s advice or pull the medication from the market. She may have another tough decision on her hands with Meridia.

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WEDNESDAY, Sept. 1 (HealthDay News) — A new study is linking the popular weight loss drug Meridia to an increased risk of non-fatal heart attacks and stroke, although taking the drug did not seem to up the risk of death in patients with a history of heart problems.

The finding is stirring mixed reactions from experts.

According to the authors of the trial, which was funded by Meridia’s maker, Abbott, the findings are generally in line with what has been known about the drug and shouldn’t change how it is used.

“The only time you’ve got an increase in heart attacks or strokes were in those patients who had had previous heart disease or strokes, in other words, the people who . . . should never have received the drug in the first place,” said Dr. Philip T. James, a professor at the London School of Hygiene and Tropical Medicine in England, and first author on the paper, which appears in the Sept. 2 issue of the New England Journal of Medicine.

Since January, Meridia (sibutramine), has carried a label warning that it should not be used by people with preexisting heart disease, so “the current prescription is entirely appropriate,” James said.

However, not everyone agrees. The U.S. Food and Drug Administration is slated to meet in September to decide if more regulatory action — perhaps a tougher “black-box” warning or even removing Meridia from the market — should be taken.

According to Dr. Greg Curfman, executive editor of the NEJM and co-author of an accompanying editorial, the FDA’s January warning was based on preliminary information only. The new study results represent the first hard data, “the first outcomes trial,” he said.

Based on the findings, he and others wonder if the drug is worth keeping around.

The drug did not seem to make people healthier, Curfman said. “Some people were actually made worse,” he said. “All this taken together results in an unfavorable risk-benefit profile and, based on that, we don’t see a rationale for keeping this on the market.”

Also, he said, “the efficacy of producing weight loss with the drug is very unimpressive. In this trial, patients lost on average less than 4 kilograms [about 9 pounds] and we know that that’s not going to translate into a real health benefit over time. It’s not enough weight loss. The FDA has a benchmark of about 5 percent loss of baseline body weight to consider a weight loss drug [effective].”

A University of Rochester expert concurs.

“I have never really found that people taking Meridia had obtained a real substantive weight loss,” said Dr. J. Chad Teeters, assistant professor of clinical medicine, cardiology division at the University of Rochester Medical Center. “It seems that a lot of these ‘quick fix’ weight loss drugs don’t really live up to the hype and they come with risks. I think there’s probably going to be a significant downturn in the use of the drug given the low efficacy and increased risk of side effects.”

This trial involved almost 11,000 older overweight or obese adults with type 2 diabetes or heart disease or both who were randomized either to take Meridia or a placebo and followed for about 3.4 years.

In the group taking Meridia, 11.4 percent had a heart attack, stroke or died as the result of a heart problem, versus 10 percent in the control group, a 16 percent increase.

People taking Meridia also had a 28 percent higher risk for nonfatal heart attack and a 36 percent raised risk for nonfatal stroke, compared to those taking placebo, the authors found.

All trial participants were also engaged in a diet-and-exercise program to lose weight, whether they were taking the drug or not, said study author James. “Meridia is not a wonder drug that guarantees people lose weight but it is a major additional help for people who change their diet and increase their physical activity,” he said.

But Teeters narrowed the prescription. “Good old-fashioned diet and exercise is the only substantive sustained therapy that’s shown to be helpful,” he said. “There’s no quick-fix pill.”

More information

There’s more on Meridia at the U.S. National Library of Medicine.

WASHINGTON (Reuters) – A study funded by Abbott Laboratories offered more detailed evidence that its weight-loss drug Meridia increases heart risks, prompting renewed calls by consumer advocates and others to pull the drug from the market.

Final data from the so-called SCOUT study, published on Wednesday, showed Meridia increases the risk of heart attacks and strokes in patients who already have heart disease. Patients taking the drug lost an average of 8.8 pounds (4 kg).

Patients given Meridia had a 16 percent increased risk of heart problems such as heart attack or stroke compared to those given a placebo, the study showed. There was no increased risk of death, although Meridia patients also saw an increase in blood pressure and heart rate, it said.

The findings come two weeks ahead of a U.S. Food and Drug Administration public hearing to discuss whether to take further action against the drug, which is already withdrawn in Europe.

“When you put those … things together, you have to wonder if the drug should be on the market any longer,” said Dr. Gregory Curfman, executive director of the New England Journal of Medicine, which published the study.

“That’s what you’re trying to prevent through weight loss. You’re trying to prevent people from having heart attacks, and here this drug caused more,” said Curfman, a cardiologist.

Preliminary results from Abbott’s study were initially disclosed to both U.S. and European health officials in late 2009 and led to Meridia’s removal from the European market.

At the same time, the FDA strengthened the drug’s warning about risks to patients with pre-existing cardiovascular disease and called for a public meeting with its outside advisers.

An FDA advisory panel is to meet on September 15 to discuss the drug.

NOT A BIG SELLER

Meridia is not a big seller for the Illinois-based drugmaker, but has drawn attention to the controversial area of prescription diet drugs ever since its U.S. approval in 1997. The company expects Meridia’s 2010 U.S. sales to be less than $30 million.

The trial looked at 10,744 overweight or obese patients who were at least 55 years old and had either heart disease, diabetes or both conditions. It ran from 2003 to March 2009.

Abbott has defended continued use of the drug in the United States, where two out of three people are overweight or obese. The company, along with the study’s authors, said Meridia should still be used, just not by people with heart problems.

Abbott spokesman Scott Davies said the company only studied the drug in riskier patients because regulators required it as a condition for approval, and that Meridia already clearly warns heart disease patients against using the drug.

“If you look at all of the data involved, in the approved patient population there is certainly a positive risk-benefit profile,” he said. Those who are obese with no heart problems and have not lost weight with diet and exercise are ideal candidates for the drug, also known as sibutramine, he said.

Consumer groups and an FDA whistle-blower have long called on FDA to pull Meridia, in part because so many people have undiagnosed heart disease and are at greater risk.

Public Citizen’s Health Research Group Director Sidney Wolfe said the journal’s detailed data shows the FDA should have acted long ago.

“FDA has unconscionably allowed this drug, which should not have been approved in the first place, to stay on the market,” said Wolfe, who petitioned the FDA for Meridia’s removal in 2002. “The agency appears immobilized to act against drugs that have no unique benefits but unique, serious dangers.”

The FDA denied his request, in part saying it would await the results from the SCOUT trial.

FDA spokeswoman Karen Riley said the FDA advisory panel would review the company’s latest analysis, among other information. “There’s going to be a lot more data than what’s being provided in the journal piece,” she added.

(Editing by Mohammad Zargham)

TUESDAY, Aug. 31 (HealthDay News) — Exercise can reduce a person’s genetic predisposition to obesity by 40 percent, finds a new English study.

Researchers looked at 20,430 people in Norwich and focused on genetic variants known to increase the risk of obesity. Most people had inherited 10 to 13 of these variants from their parents, but some had more than 17 while others had fewer than six.

The participants also provided information about their levels of physical activity.

Overall, each additional obesity-related genetic variant was associated with an increase in body mass index (BMI) equivalent to 445 grams (0.98 pounds) for a person 1.70 meters (5 feet, 6 inches) tall. BMI is a measurement that takes into account a person’s height and weight.

However, this effect was greater in sedentary people than in active people, the researchers found. For those with a physically active lifestyle the increase was 379 grams (0.84 pounds) per genetic variant. That’s 36 percent less than the increase of 592 grams (1.3 pounds) per genetic variant for inactive people.

The researchers also found that each additional obesity susceptibility variant increased the odds of obesity by 1.1-fold. But this risk was 40 percent lower for active people compared to inactive people, the findings revealed.

The study shows that adopting a healthy lifestyle can benefit people at increased genetic risk of obesity, the authors explained.

“Our findings further emphasize the importance of physical activity in the prevention of obesity,” Dr. Ruth Loos, of the Medical Research Council’s epidemiology unit in Cambridge and colleagues wrote in the article published online this week in PLoS Medicine.

More information

The U.S. National Heart, Lung, and Blood Institute offers a guide to physical activity.