TIME HIV/AIDS

Scientists Find a Way to Block HIV from Infecting Healthy Cells

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Getty Images HIV viruses infecting a human immune cell

Researchers overcome a major hurdle in developing the ultimate protection against HIV

Reporting in the journal Nature, scientists describe a new way to potentially block HIV from infiltrating healthy cells. Such interference is key to protecting people from HIV infection, but most efforts so far haven’t been successful.

This time, however, may be different. Michael Farzan, professor of infectious diseases at Scripps Research Institute, and his team used a gene therapy technique to introduce a specific HIV disruptor that acted like gum on HIV’s keys. Once stuck on the virus’s surface, the peptide complex prevents HIV from slipping into the molecular locks on healthy cells. Because the gum isn’t picky about which HIV strain it sticks to—as long as it’s HIV—the strategy works against all of the strains Farzan’s group tested in the lab, including both HIV-1 and HIV-2 versions that transmit among people, as well as simian versions that infect monkeys. In lab dishes containing the virus and human and animal cells, the disruptor managed to neutralize 100% of the virus, meaning it protected the cells from getting infected at all.

MORE: The End of AIDS

The strategy is based on what HIV experts know about how the virus infects healthy cells. HIV looks for a protein, or receptor on immune cells called CD4, which serves as the lock, and uses a specially designed portion of its own viral coat made up of three proteins as the key. Once HIV finds its target and the match is made, the virus changes its shape to better slip inside the healthy cell, where it takes over the cell’s machinery and churns out more copies of itself. Farzan’s gum, called eCD4-Ig, not only seeks out these parts of the key and renders them useless, but by glomming onto the key, also causes the virus to morph prematurely in search of its lock. Once in lock-finding mode, the virus can’t return to its previous state and therefore is no longer infectious.

The encouraging results suggest that eCD4-Ig could provide long-term protection against HIV infection, like a vaccine; in four monkeys treated with gene therapy to receive eCD4-Ig, none became infected with HIV even after several attempts to infect them with the virus. The protection also seems to be long-lasting. So far, the treated monkeys have survived more than a year despite being exposed to HIV, while untreated control monkeys have died after getting infected.

MORE: This Contraceptive Is Linked to a Higher Risk of HIV

The strategy, while promising, is still many steps away from being tested in people. Farzan used a cold virus to introduce the eCD4-Ig complex directly into the muscle of the animals, and it’s not clear whether this will be best strategy for people. Previous gene therapy methods have led to safety issues, and concerns have been raised about controlling where and how much of the introduced material gets deposited in the body. It may also be possible to give the peptide as an injection every few years to maintain its anti-HIV effect.

MORE: HIV Treatment Works, Says CDC

Farzan anticipates that if proven safe, the strategy could help both infected patients keep levels of HIV down, as well as protect uninfected, high-risk individuals from getting infected. But many more tests will need to be done before we might see those results. Four monkeys can provide valuable information, but can’t answer questions about safety and efficacy with any confidence. “Things change when we get to humans and when we get to larger numbers,” he says. “But the data in monkeys are as encouraging as one could hope.”

TIME Heart Disease

Why Your Heart Disease Risk Might Be Lower Than You Think

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Of the five popular tools that doctors rely on to predict whether you’re headed for heart trouble, four of them have a pretty major flaw

For decades, doctors have relied on the undisputed champion of heart disease risk assessment: the Framingham Risk Score. It emerged from a massive study of heart disease risk factors in more than 5,000 men and women and pointed out advanced age, being male, smoking, having diabetes, high total cholesterol, low levels of good cholesterol and high blood pressure. Scoring higher on these factors meant you had a greater chance of developing heart problems in the next 10 years, and most successive models included some version of these core culprits.

Now, scientists led by Dr. Michael Blaha, director of clinical research at the Ciccarone Center for Prevention of Heart Disease at Johns Hopkins Medicine, have published a new study in the Annals of Internal Medicine that finds that those risk calculators—four of which doctors use regularly—tend to overestimate the risk of heart attack in patients.

MORE: New Guidelines for Cholesterol Treatments Represent “Huge Change”

“It’s not that scientists made mistakes when coming up with the [calculators],” says Blaha, “They did the best job they could with the data they had. But there may be inherent problems in using historical data to predict things now.”

The diet and lifestyle of Americans have changed considerably since the Framingham days, when heart attacks occurred more frequently in younger people and more often in men than women. Americans on average now eat more trans fat and salt and have lower exposure to secondhand smoke, which can all affect heart disease rates.

MORE: Cholesterol Whiplash: What to Make of the New Heart-Risk Calculator

But even the most recent guidelines for predicting heart disease risk, released in 2013 by the American Heart Association and the American College of Cardiology, relied on the Framingham Risk factors. In the current analysis, these guidelines overestimated heart attack risk by 86% in men and 67% in women when Blaha and his team compared the predicted risk to actual rates of heart events in a group of more than 4,000 people aged 50 to 74 years, who were followed up for an average of 10 years. The other models overshot the risk by anywhere from 37% to 154% for men, and from 8% to 67% for women.

That’s a lot of extra heart disease that, under current guidelines, doctors may start treating with blood pressure medications, insulin and cholesterol-lowering drugs. All of those come with potential side effects and complications. In fact, the study found that statins to keep cholesterol in check were least effective among those with the lowest risk of having future heart events, meaning the benefits may not outweigh the risks for many.

MORE: Single Gene Responsible for Group of Heart Disease Risk Factors

“We’re getting close to the idea of re-thinking risk,” says Blaha. Instead of relying on decades-old data that draws conclusions and recommendations on a population level, ideally everyone’s risk should be more individualized and based on his own particular history. The Framingham model, for example, includes data collected from a single measurement of blood pressure and cholesterol, and a yes-or-no answer on whether the patient smokes. But someone who has smoked for years and just quit is physiologically different from someone who never lit up at all, just as having blood pressure that’s under control thanks to medication is not the same as never having hypertension to begin with. The most accurate way to predict someone’s risk of having a heart attack is to survey his blood pressure and cholesterol readings over his lifetime, or at least for many years. That may soon be possible with electronic health records and the popularity of medical monitoring bracelets. But until then, any model that relies on population-based data like Framingham may suffer from overestimating someone’s heart danger, Blaha says.

MORE: Eating Fruit Cuts Heart Disease Risk by 40%

“These data point squarely to the idea that we need to be rethinking risk prediction,” he says. That may require not just combing through more data per patient, but also folding in other factors that may be more sensitive to the health of a person’s heart. Imaging techniques, including coronary calcium scores that measure the amount of calcium—a foundation for the plaques that eventually rupture to cause heart attacks—may provide more valuable and accurate information on a person’s risk, for example.

In the meantime, Blaha isn’t advocating for the elimination of current risk predictors or guidelines that help doctors decide when a patient’s risk warrants treatment with a drug. “The guidelines are still useful, but patients and doctors have to understand the caveats and limitations to them,” he says. Whatever score a patient receives from these calculators, that number should be the starting point of a discussion between doctor and patient about that patient’s particular risk factors—including his family history, whether and how much he smoked, and how much exercise he gets on a regular basis. “Patients need to demand, or ask their doctors to go beyond the number and say, ‘Do you really think I need to starting taking medicine?’ or ‘How much risk do I really have of having a heart attack?’” That kind of conversation is far more valuable than a single-risk calculator will ever be.

TIME Diet/Nutrition

The One Food That Can Spike Weight Loss

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Healthy diets seem complicated and restrictive, but adding one kind of food may be all you need to get healthier

Improving your diet often suggests a daunting revamp of every food you eat, but changing just one thing will help you lose weight and get significantly healthier, finds a new study in the Annals of Internal Medicine.

A group of researchers from the University of Massachusetts Medical School zeroed in on fiber, since previous studies have shown it can help people feel more full, eat less and improve some metabolic markers like blood pressure, cholesterol levels and blood sugar.

They recruited 240 people who showed signs of prediabetes and randomly assigned them to the American Heart Association (AHA) diet, which is currently recommended for those at risk of developing diabetes, or to eating more fiber. The AHA group focused on decreasing their daily calorie intake in order to lose weight, and they were provided with goals to limit saturated fat. The fiber group was simply asked to eat more foods rich in fiber, such as fruits, vegetables and whole grains, to reach a quota of at least 30 grams of fiber per day. Neither group was told to change their exercise habits.

MORE Fiber Isn’t Just Good for the Colon Anymore

After a year, both groups lost about the same amount of weight. Even more surprisingly, the people in the study also showed similar drops in cholesterol levels, blood pressure, blood sugar and inflammation. “By changing one thing, people in the fiber group were able to improve their diet and lose weight and improve their overall markers for metabolic syndrome,” says study author Dr. Yunsheng Ma.

While he’s not yet ready to say that people at risk of developing diabetes should ditch the AHA diet and focus just on eating more fiber, Ma’s study does suggest an alternative way of getting healthier. “I think we have to change the paradigm about recommendations,” he says. “Telling people to reduce this or reduce that is just too hard to do.”

MORE This is How Nutritionists Snack at Work

Ma notes that while dietary guidelines to lower the risk of various diseases have been around for decades, obesity, heart problems and diabetes remain the most common conditions affecting Americans. “Very few people reach the goals that are recommended,” he says. Asking them to focus on eating more of a certain food—rather than telling them what not to eat—may help people to think more positively about changes in their diet, and make the goals more achievable. From there, it might be easier to make the other changes, such as those included in the AHA diet. “[Adding fiber] might be one new idea for how to get people to adhere to a diet,” he says. That’s the first step, and perhaps most important, to eating healthier.

Read next: 7 Surprising Ways To Eat Healthy at a Restaurant

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TIME Research

This Is What’s Keeping Teens From Getting Enough Sleep

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The biggest factor keeping teens up at night isn't technology

Up to a third of teens in the U.S. don’t get enough sleep each night, and the loss of shut-eye negatively impacts their grades, mental well-being and physical health. Biologically, adolescents need fewer hours of slumber than kids — but there’s a bigger reason for teens’ sleep loss, according to a new study in the journal Pediatrics.

MORE: The Power of Sleep

Katherine Keyes, an assistant professor of epidemiology at Columbia University, looked at survey data from more than 270,000 eighth-, 10th- and 12th-grade students at 130 public and private schools across the country, gathered between 1991 and 2010. Each student was asked two questions about his or her sleep habits: how often they slept for at least seven hours a night, and how often they slept less than they should.

MORE: School Should Start Later So Teens Can Sleep, Urge Doctors

She found that over the 20-year study period, adolescents got less and less sleep. Part of that had to do with the fact that biologically, teens sleep less the older they get, but Keyes and her team also teased apart a period effect — meaning there were forces affecting all the students, at every age, that contributed to their sleeping fewer hours. This led to a marked drop in the average number of adolescents reporting at least seven hours of sleep nightly between 1991–1995 and 1996–2000.

That surprised Keyes, who expected to find sharper declines in sleep in more recent years with the proliferation of cell phones, tablets and social media. “I thought we would see decreases in sleep in more recent years, because so much has been written about teens being at risk with technologies that adversely affect the sleep health of this population,” she says. “But that’s not what we found.”

MORE: Here’s How Much Experts Think You Should Sleep Every Night

Instead, the rises in the mid-1990s corresponded with another widespread trend affecting most teens — the growth of childhood obesity. Obesity has been tied to health disturbances including sleep changes like sleep apnea, and “the decreases in sleep particularly in the 1990s across all ages corresponds to a time period when we also saw increases in pediatric obesity across all ages,” says Keyes. Since then, the sleep patterns haven’t worsened, but they haven’t improved either, which is concerning given the impact that long-term sleep disturbances can have on overall health.

Keyes also uncovered another worrying trend. Students in lower-income families and those belonging to racial and ethnic minorities were more likely to report getting fewer than seven hours of sleep regularly than white teens in higher-income households. But they also said they were getting enough sleep, revealing a failure of public-health messages to adequately inform all adolescent groups about how much sleep they need: about nine hours a night.

“When we first started looking at that data, I kept saying it had to be wrong,” says Keyes. “We were seeing completely opposite patterns. So our results show that health literacy around sleep are not only critical but that those messages are not adapted universally, especially not among higher-risk groups.”

TIME Obesity

New Genes Mean the Future of Obesity Treatment Could Get Personal

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Scientists have uncovered a trove of new genetic targets that could lead to better treatments for obesity

It took the genomes of nearly 340,000 people and more than 400 researchers in two dozen countries, but we now have the most comprehensive picture so far of the genetic contributors to obesity.

Two new papers in the journal Nature describe the results of two studies that connected the obesity-related factors of body mass index (the ratio between height and weight) and fat distribution to their potential genetic drivers. The studies did not isolate specific genes—at least not yet—but identified areas in the human genome where people with different BMIs and different patterns of fat distribution varied in their genetic code. Those variants will lead scientists to the genes they code for, and eventually to how those genes work in contributing to obesity.

MORE: Healthy-Obesity Gene Found—But Genes Aren’t Everything

“I think we have so many more opportunities now to learn about the biology of obesity through genetic contributions to these traits,” says Karen Mohlke, professor of genetics at University of North Carolina and the senior author of the report focusing on body fat distribution.

Those genetic clues may yield new weight-management treatments that are both more powerful and more personalized. “What the data supports is the fact that there are a lot of different causes of obesity,” says Dr. Elizabeth Speliotes, assistant professor of internal medicine and computational medicine and bioinformatics at the University of Michigan and senior author of the paper on body mass index. “If you’re hoping for one cause of obesity, that’s not reality. What causes you to be obese is probably slightly different from what causes me to be obese.”

Currently, however, all obesity is treated pretty much the same way. With the new knowledge gleaned from the genetics of what’s driving different types of obesity, that may change.

MORE: Gym vs. Genes: How Exercise Trumps Obesity Genes

In the study involving factors contributing to BMI, Speliotes and her team discovered 97 genetic regions, or loci that account for nearly 3% of the variation among people on BMI. Of those, 56 are entirely new. Many of the regions are in areas that code for nervous system functions, or brain systems. Some aren’t so surprising—they confirm previous studies that have implicated genetic regulators of areas that control appetite, for example—but others were more unexpected. They involved regions responsible for learning, memory and even emotional regulation, hinting that some of weight and obesity may be tied to the addiction and reward pathways that help to reinforce behaviors like eating with feelings of pleasure and satisfaction. “There were definitely a lot more loci involving the brain than I would have guessed,” says Dr. Joel Hirschhorn, director of the center for basic and translational obesity research at Boston Children’s Hospital and Harvard Medical School and one of the co-authors. “That makes obesity much more of a neurobehavioral disorder than just the fact that your fat cells are more efficient or less efficient.”

MORE: Study Identifies Four New Genetic Markers For Severe Childhood Obesity

They also uncovered some truly head-scratching connections between some genetic variants that contributed to higher BMI and lower risk of diabetes, heart disease and triglyceride levels. That suggests that there may be some protective genetic factors that counteract the effects of higher BMI, and exploiting these may be an entirely new way of treating obesity.

The group that zeroed in on the genetic factors directing how body fat is distributed had similar findings. Mohlke and her colleagues looked at the waist-hip ratio and found 49 areas in the genome that varied among the participants, 33 of which were entirely new. Most of the variants involved logical processes such as the formation of HDL and LDL cholesterol, triglycerides and processing of insulin.

MORE: New Genes Identified in Obesity: How Much of Weight is Genetic?

What was interesting, however, was the fact that many of these exerted much more power on women than on men, suggesting the need to recognize gender-based differences as a critical factor in future obesity therapies.

The findings, all of the authors stress, are just the beginning of a deeper understanding of what is driving obesity in its many forms, and how best to intervene with more personalized and potentially more effective treatments. Genes, they say, only play a part in obesity, but these studies are the first step toward a better appreciation of how genes are involved in behaviors that influence what and how much we eat. “We don’t know how much impact each of these genetic loci are going to have on whether people will need different treatments,” says Hirschhorn. “But these papers provide the tools to start answering that question. It’s possible that if we know a lot more about how somebody came to be obese, then we will know more about what to do about it.”

TIME Diet/Nutrition

Where Dietary-Fat Guidelines Went Wrong

A new review argues that there was no evidence to support the low-fat message that has been the mantra for good health since the 1970s

A little fat may not be harmful, while too much of it can be unhealthy, and even fatal. But in the latest review of studies that investigated the link between dietary fat and causes of death, researchers say the guidelines got it all wrong. In fact, recommendations to reduce the amount of fat we eat every day should never have been made.

Reporting in the journal OpenHeart, Zoe Harcombe, a researcher and Ph.D. candidate at University of the West of Scotland, and her colleagues say that the data decisionmakers had in 1977, when the first U.S. guidelines on dietary fat were made, did not provide any support for the idea that eating less fat would translate to fewer cases of heart disease, or that it would save lives.

“The bottom line is that there wasn’t evidence for those guidelines to be introduced,” she says. “One of the most important things that should have underpinned the guidelines is sound nutritional knowledge, and that was distinctly lacking.”

When the recommendations were made, in the 1970s, heart disease claimed more U.S. lives than any other cause of death (and has retained that distinction for most of the ensuing years), so public-health and government officials were eager to get on the low-fat bandwagon. National guidelines, endorsed by health experts and expected to be followed by physicians in doctors’ offices around the country, sent word to the American public — trim fat to about 30% of your total daily calories, and cut saturated fat, from red meat and dairy products like milk, egg and cheese, in particular down to no more than 10% of total calories.

The problem, as Harcombe notes in her study, is that advice was “arbitrary. The 30% wasn’t tested, let alone proven,” she says. In fact, some data even contradicted the idea that the fat we took in from food had anything at all to do with the artery-clogging plaques that caused heart disease. In one study, men who were fed copious amounts of high-fat foods (butter, eggs, portions of cream and the like) did not show higher levels of blood cholesterol, suggesting that the fat from food had little to do with the cholesterol circulating in the body and produced by the liver. In fact, says Judith Wylie-Rosett, a professor of epidemiology and population health at Albert Einstein College of Medicine and a spokesperson for the American Heart Association (AHA), roughly a third of the cholesterol from food becomes part of the circulating cholesterol that can potentially build up in heart vessels — “not a major driver,” she says.

That’s why the AHA, among other groups, has gradually revised its guidelines and moved away from the strict guidance to lower fat intake. Instead, they focus on the types of fats in our foods, and on the diet as a whole. For example, Harcombe argues that the focus on fat, and on cholesterol and saturated fat in particular, has had a boomerang effect on the health of Americans. When we cut the fat, we replaced it with carbohydrates, which are broken down by the body into sugars and into a different form of fat, triglycerides, which may actually do more harm to the heart than cholesterol from animal products like red meat and dairy.

MORE Ending the War on Fat

So the AHA, while still urging people to be aware of how much saturated fat they eat, are not as focused on limiting total fat intake. “The message is still to use lean meats and fish, but the emphasis is not so much on total fat,” says Wylie-Rosett.

Harcombe would argue that even that doesn’t go far enough, according to her results. In her analysis of six trials in which people were randomly assigned to eat higher or lower amounts of dietary fat, she found no difference in heart attacks and mortality rates among the two groups. “What we are saying is that dietary interventions did not provide the evidence that dietary fat is associated with heart disease outcomes,” she says.

MORE Dietary Guidelines Are Not So Sustainable, Study Says

Does that mean a diet of daily steak and eggs won’t harm the heart? Harcombe admits that she also doesn’t have evidence for that position, but says that her findings do expose the shortcomings of current recommendations and the need for more rigorous studies. Given the current state of knowledge, she says “We are not doing our best by the consumer at the moment.” Wylie-Rosett agrees. “We don’t need to restrict fat to below 30% of daily calories, but do we want to allow up to 70%? We don’t know.”

Harcombe’s own solution to the confusion is to stick with the basics. “It’s one message, in three words — eat real food,” she says. The less adulterated and processed your diet is, the more nutrients and healthy fats, proteins and carbohydrates your body will get, and the less you’ll have to worry about meeting specific guidelines or advice that may or may not be based on a solid body of evidence.

MORE Uh Oh, Unsaturated Fats May Not Be as ‘Good’ as We Thought

Read next: Should I Eat Red Meat?

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TIME Mental Health/Psychology

Millennials and Gen Xers Feel the Most Stress About Money

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Even with the improving economy, one population of Americans is more stressed about financial concerns than they were nearly a decade ago

In the latest survey of Stress in America conducted by the American Psychological Association (APA), money remained the top causes of stress reported by a group of more than 3,000 adults aged 18 years or older, followed by work, family and health concerns. Overall, the average level of stress, reported on a 10-point scale, is at its lowest since the APA began the survey in 2007.

But 29% of participants said that their anxiety over money matters increased in the past year, and younger generations and parents seem to be feeling the pinch most. More than one-third of parents reported higher stress levels over the past year (at 5.8) compared to non-parents (at 4.4).

Millennials and Gen Xers (aged 18 to 49 years) felt more stress than the average American about money. “Where Millennials are concerned, we know that the cost of education is pretty high in this country, and student debt is higher,” says Katherine Nordal, executive director of Professional Practice at the APA. “The job market until recently has also been problematic.”

The gap between financial stress between lower and higher income families is also widening; in 2007 both groups reported the same amount of anxiety over money, but in the current survey, those making less than $50,000 a year were twice as likely as those in higher income groups to feel stress about financial matters all or most of the time.

While the overall rate of stress about money is declining, Nordal says the trends involving younger generations and lower income households is concerning, because strategies for coping with stress aren’t improving, despite greater awareness of its health risks. One in five Americans said they did not have anyone to turn to for emotional support; 27% of those in lower income households fall into this category, compared to 17% of those in higher income groups. “Good support systems seem to be good for reducing stress — it’s not an inoculation against stress but it can be a stress reduction factor,” says Nordal.

Lack of emotional support can also drive people to unhealthy coping mechanisms, including over-eating, not sleeping well and becoming more sedentary. Forty-two percent of respondents said they indulged in such behaviors to cope with their stress in the past month. “Excessive alcohol use, smoking, eating the wrong kinds of foods, not exercising and being too sedentary we know are behaviors that lead to disease states, and unhealthy states,” says Nordal. “And these health risks are very real. We’d like to see people doing things that are more proactive to cope with stress, such as meditation, relaxation techniques and exercise.”

TIME public health

Only 40% of Ebola Donations Have Reached the Affected Countries

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The latest study shows the gap between what the world pledged to give, and what the affected countries really got

Of all the money pledged by well-intentioned individuals, organizations and nations, only 40% has actually reached the countries hardest hit by the Ebola epidemic in West Africa—Guinea, Liberia and Sierra Leone.

The new calculation comes from Karen Grepin, an assistant professor of global health policy at New York University, in a report published in the BMJ. Using data collected by the United Nations Office for the Coordination of Humanitarian Affairs, Grepin looked back and found that the World Health Organization’s requests for aid changed constantly since the Ministry of Health in Guinea first reported the 49 cases and 29 deaths that launched the current Ebola outbreak. From an early ask of $4.8 million in April, the agency, along with the governments of the three affected nations, revised that need to $71 million in August and to $600 million soon afterward to contain the epidemic. By the end of 2014, the UN was requesting $1.5 billion.

MORE: The First Ever Large-Scale Ebola Vaccine Trial Begins in Liberia

The global community responded, pledging nearly $2.9 billion by December. Only $1.09 billion of this support has actually been paid, however, and Ebola-stricken countries only began receiving some of this aid in October, a full seven months after the first cases were reported. The U.S. has been the largest donor, pledging more than $900 million, of which 95% has been funded, followed by the U.K., with $307 million, and the World Bank at $230 million. (Only half of the World Bank pledge has been funded.)

MORE: TIME Person of the Year: The Ebola Fighters

The delay in dispatching resources to West Africa may have contributed to the spread of the virus and further increases in the financial needs of those countries, whose health systems have been strained by the volume of Ebola cases, Grepin argues. “We need a mechanism to enable more rapid disbursement of funds to fight public health threats such as Ebola, such as a dedicated fund that could be rapidly deployed for any emergency,” she writes. “Although quantity of funding is important, so is the quality of the response.” Learning from what worked to support the nations affected by Ebola, and which strategies proved too inefficient, could help to streamline and optimize efforts for the next public health threat.

TIME Exercise/Fitness

When Exercise Does More Harm than Good

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A new study shows that running too much can be just as unhealthy as not being active at all

Americans as a whole don’t exercise enough—at least that’s what the latest studies show—and so the message is clear: get more active, take walks, Let’s Move! Basically anything is better than sitting on the couch. But how much exercise is enough? That’s a hotly debated question for which experts still don’t have a satisfactory answer. But given that most of us are starting from a sedentary position, the assumption has long been the more the better.

But in a report published Monday in the Journal of the American College of Cardiology researchers from Denmark say that people who push their bodies too hard may essentially undo the benefit of exercise. Those who ran at a fast pace more than four hours a week for more than three days a week had about the same risk of dying during the study’s 12-year follow up as those who were sedentary and hardly exercised at all. The link held even after the researchers accounted for potentially confounding factors such as age, sex, whether the participants had a history of heart disease or diabetes, or whether they smoked and drank alcohol.

MORE This Is How Much Exercise Experts Really Think You Need

In fact, those with the lowest risk of dying during the study period were people who ran less than three times a week for one to 2.4 hours, at a slow to moderate pace. Even people who ran slightly more, for 2.5 hours to four hours a week at an average pace less than three times a week, showed slightly higher mortality risk, at 66%, something that came as a surprise to the authors.

“I would expect the light joggers to have really low risk,” says Jacob Marott, a researcher at the Copenhagen City Heart Study at Frederiksberg Hospital and one of the study’s co-authors. “But regarding the moderate joggers, I was a little surprised they didn’t have a bigger benefit from jogging than the light joggers. It made me think that if it’s really true, then exercise recommendations should take that into account.”

MORE It Doesn’t Matter How Much You Exercise If You Also Do This

What Marott and his team found was that both too little running and too much running are linked to higher rates of death. The most intense runners ended up with a risk of dying that was similar to that of those who opted to stay on the couch. Somewhere in between is the Goldilocks amount that’s just right to maintain heart health, burn off excess calories and keep blood sugar levels under control. And according to his results, that sweet spot is closer to the ‘less’ side of the curve than the ‘more’ side.

That dovetails with the mounting research that so-called micro-workouts—high intensity but brief workouts that could be as short at 1 minute, according to another recent paper—may be better for the body than long and continuous workouts.

That still means that some exercise is better than no exercise, but scientists may be getting more sophisticated about understanding that more isn’t always better, and that there may be a tipping point at which the harms of running start to outweighed its benefits.

Those negative effects might include things like changes in the structure and function of the heart and its vessels; previous studies showed that marathoners and long distance cyclists, for example, tend to be at higher risk of developing abnormal heart rhythms, and may be more vulnerable to enlarged hearts, which are less efficient at pumping blood and delivering oxygen and removing waste than normal-sized organs.

MORE Short Bursts of Exercise Are Better Than Exercising Nonstop

Marott acknowledges that it’s also possible that some other behaviors or factors common to avid runners, such as their exposure to the sun, which can increase their risk of skin cancer, might be explaining their higher risk of dying during the study. Other studies will have to investigate whether that’s the case, but in the meantime, Marott says “if you want to do something good for yourself, you don’t have to be extreme. Jogging one to four hours a week for no more than three days a week at a slow to moderate pace is actually achievable. And that’s a positive take-home message.”

Read next: 7 Reasons Why You’re Working Out and Still Not Losing Weight

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