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Statins With Exercise Warrant Monitoring

By Mike Bassett

For physicians treating older patients whose cholesterol levels have been creeping above normal levels, a typical response is to prescribe statins and suggest that these patients—particularly those who are overweight and inactive—begin some kind of exercise regimen.

But what if it turns out that statin use actually could curtail the benefits of exercise? A recent study published in the Journal of the American College of Cardiology suggests that could be the case.

In the study, researchers from the University of Missouri School of Medicine analyzed 37 obese and previously sedentary individuals who followed an exercise program for 12 weeks. These individuals were divided into two groups: one exercise-only group and one group that combined exercise with statin use.

“What we found, surprisingly, is that if these individuals started exercising and [taking] statins at the same time, the statins seemed to block exercise-induced improvement in cardiorespiratory fitness,” says John Thyfault, PhD, a study author and associate professor at the University of Missouri School of Medicine’s Clinical Research Center.

Study results indicated that those who followed an exercise-only program increased their cardiovascular fitness by 10%, while those who followed an exercise program combined with statin use experienced just a 1.5% increase in cardiovascular fitness.

In addition, those who followed the exercise-only program experienced an increase in skeletal muscle mitochondrial content while the exercise-statin group showed a decrease in mitochondrial content. Thyfault says this suggests that statins curtail improvements in response to exercise training by blocking the increase in mitochondrial content in the muscle.

As the researchers pointed out, these findings have “clinical ramifications as patients at risk for the metabolic syndrome are commonly prescribed statins to lower blood lipids and at the same time advised to exercise to improve fitness, both of which are independently proven to lower cardiovascular disease risk.”

These findings could have particular significance for older adults who, studies have shown, are taking statins with increasing frequency. According to the Health, United States, 2010 report from the National Center for Health Statistics, during the period between 2005 and 2008, 50% of men aged 65 to 74 took statins, as did 36% of women in the same age range. All told, according to the report, about one in four Americans over the age of 45 takes statins.

Acknowledged Efficacy
The good news is that statins seem to lower cholesterol. According to a study from the Centers for Disease Control and Prevention published last year in The Journal of the American Medical Association, total cholesterol, on average, declined from 206 mg/dL between 1988 and 1994 to 196 mg/dL between 2007 and 2010. According to the study, the decline in cholesterol rates was associated with statin use as well as behavioral changes, such as those involving diet.

And clearly exercise has a major impact on cholesterol levels and general heart health as well. “Cardiorespiratory fitness is an extremely important measure when you look at longevity and mortality,” Thyfault says. “It has long been known that people with high fitness are protected from early mortality and a number of chronic diseases. So if you do exercise, it’s important to get an increased fitness response.”

Studies have shown that both high levels of fitness and statin use are independently associated with low mortality, says Michael Joyner, MD, a Mayo Clinic anesthesiologist and exercise physiology researcher. “And people who are both physically fit and take statins have a still lower risk of disease, so there are apparently positive and negative interactions between statins and exercise.”

One negative interaction, he explains, is that some people experience muscle pain when taking statins. “And you can get it with one drug and not another,” he says. “But the risk of some muscle soreness or some subclinical muscle issues with statins goes up with people who are involved with relatively healthy exercise. You have situations where you have professional athletes who have very bad blood lipids as a result of family history who get started on these statins and have to stop because they feel like it reduces their performance.”

By the same token, “Statins are really safe and effective,” Joyner notes. So while he expressed concern about individuals who experienced side effects such as muscle pain, he suggests that individuals—even those over the age of 50—who are taking statins and are involved in an exercise program continue taking their prescribed statins,  “although you may want to think about it if you are some kind of master athlete or you’re training to run a marathon because it may influence your performance.”

There is evidence that the over-the-counter supplement called coenzyme Q10 could help replace the enzymes depleted by statins as a result of vigorous exercise, says Mark Coggins, PharmD, CGP, FASCP, director of pharmacy services for Golden Living Centers. “Supplementing these enzymes could improve muscle functioning and help offset the effects on mitochondrial dysfunction that are noted in the study. 

There also are alternatives to statins, Coggins points out, adding that it’s important to understand that all medications carry risks and these alternatives may not meet the cholesterol-lowering benefits associated with statins.

Niacin can be used to increase HDL or good cholesterol, Coggins says, but it also has the “uncomfortable side effect of causing a flushing sensation and reddening of the skin.” Niacin can increase the risk of liver damage and increase glucose levels as well.

Fish oil, which is high in omega-3 fatty acids, can help lower triglycerides but is a natural blood thinner, so it’s important for patients to watch for increased bruising, Coggins adds.

It’s important to remember that “statins are very potent agents and are able to provide significant lowering of cholesterol, and many alternatives may not allow patients to meet treatment goals,” he notes. “It is important for health care professionals to discuss the risks and benefits of both statins and alternatives when developing [these] goals.”

Age, Statins, and Exercise
The study by Thyfault and his colleagues focused on individuals who were obese, sedentary, between the ages of 25 and 59, and just beginning an exercise program. But what about adults over the age of 50 who exercise consistently and take statins because of concerns about increasing cholesterol levels?

Thyfault says animal studies have suggested that if an individual already is highly fit and then starts taking statins, it won’t limit that person’s ability to maintain his or her fitness level. This differs from his study in which the subjects started taking statins and began exercising at the same time. “So if your doctor wants you to start exercising and to take statins, one strategy could be to start exercising for 10 to 12 weeks, or something like that, and then start taking the statins,” he says.

However, waiting to start a statin therapy program may not work for all patients, Coggins says. “For example, a diabetic patient with an LDL of 170 is unlikely to be able to achieve a goal LDL level of 100 through diet or exercise alone. For these patients, until more is understood about the effects of statins on exercise intolerance, waiting to start statin therapy is probably not appropriate.”

Joyner and Thyfault agree that it’s unclear whether age exacerbates the negative interaction between exercise and statin use. “There are all sorts of potential interactions here,” Joyner says, and the fact that people react differently to different statins complicates these potential interactions. He says the manifestation of potential interactions occurs on an individual basis. “Are you going to be a responder?” Joyner asks. “Not a responder? An adverse responder? So there’s a bit of the roll of the dice.”

“Could the effects we see be even bigger in an aged cohort?” asked Thyfault. “We don’t know, but that’s a good question, and it’s worth studying.”

But Thyfault notes that “the trend among cardiologists for a long time has been to put everyone over the age of 50 on statins, and that may have to be more carefully thought out now, particularly if the individual [in question] is already highly fit and active.”

The risks associated with statin use and exercise, such as muscle pain and potential limits to the benefits of exercise, should be “put on the table and discussed openly,” he says. And while pointing out that he’s “a PhD researcher and not a physician,” Thyfault suggests that if someone has a moderately high or borderline cholesterol level and wants to start or maintain a vigorous exercise regime, statins may not be needed or may be taken at a lower dose.

“But if you’re a person who hasn’t been experiencing any side effects, and you think you can exercise to your highest capacity, then I wouldn’t worry about it,” he says. “And we have to remember that statins are really important for individuals who have a lot of risk factors for cardiovascular disease or have already had an event. The benefits are much more important than the risks at that point.”

— Mike Bassett is a freelance writer based in Holliston, Massachusetts.