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Too Much Exercise, Revisited

May 21, 2014 By Larry Creswell, MD 2 Comments

The issue of “too much exercise” is in the news again this week. In last week’s edition of the medical journal, Heart, a group of German investigators headed by Dr. Ute Mons from the Division of Clinical Epidemiology and Aging Research at the German Cancer Research Center in Heidelberg reported on “A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coronary heart disease: evidence from a large cohort with repeated measurements.” This study extends our understanding of the importance of exercise in patients with known heart disease and the findings are very much worth noting.

In the popular press, this study received considerable attention in the past few days. In Forbes, we had a short article by Larry Husten, entitled “Exercise: Can There Be Too Much of a Good Thing?” In the Wall Street Journal, we had a short article by Kevin Helliker, entitled “Too Much Exercise May be Harmful to Your Health.” There were many other articles; these are representative. The headlines were all similar.

There was also interest in social media and the blogosphere. The research was shared along with admonitions about exercising too much, all in rather broad strokes.

Let’s take a look at the study….

The Study

Back in 1999-2000, just more than 1100 German individuals were enrolled in a longitudinal study. These were individuals who were undergoing inpatient cardiac rehabilitation (a monitored exercise program) after some sort of aucte heart problem–acute coronary syndrome, heart attack or myocardial infarction (MI), or coronary revascularization (with a stent or bypass surgery). As such, they were all known to have significant coronary artery disease (CAD). At the time of enrollment, they ranged in age from 30 to 70 years.

Over the following 10 years, these individuals answered questionnaires about their health at 1, 3, 4.5, 6, 8, and 10 years. At the time of the 1-year questionnaire, the median age of respondents was 61 years. The typical participant was male, overweight, a current or former smoker, with a history of heart attack, and high blood pressure. On each of the questionnaires, there was a question about physical activity:

“On average, how often have you engaged in physically strenuous and sweat-inducing activity in your leisure time in the past 12 months (ie, cycling, speedy hiking, gardening, sport)?”

And the possible answers included:

Daily
5-6 times per week
2-4 times per week
1-4 times per month
Rarely or never.

The respondents were also asked to estimate the number of hours per week, on average, they spent doing strenuous physical activity.

In addition to physical activity, the investigators collected information about the important outcome measures: major cardiovascular events (MI and stroke); cardiovascular mortality (death due to a heart-related cause); non-fatal cardiovascular events; and all-cause mortality.

The Results

At the time of the 1-year questionnaire, most individuals were physically active, with just 9.1% reporting “rarely or never” exercising. Most (41.3%) were in the “2-4 times per week” category. The “5-6 times per week” group accounted for 15.8% and the “daily” group accounted for 15.3%. For context, the current American Heart Association (AHA) guidelines on physical activity (generally, and not specific to patients with known CAD) call for 3 to 5 days of exercise per week, depending upon the intensity of the exercise. In terms of time, those guidelines suggest 150 minutes (2 1/2 hours) of moderate-intensity exercise OR 75 minutes of vigorous exercise per week.

Perhaps not surprisingly, as the individuals aged over the 10-year period of the study, their activity levels decreased. Perhaps their interest in well-being or focus on their heart condition waned as well. There was a relatively constant percentage of enrollees in the “2-4 times per week” category, but there was a decrease in those exercising more….and an increase in those exercising less.

Statistical analysis was used to try to isolate the influence of physical activity as a variable….and eliminate the influence of other confounding variables (employment status, smoking, obesity, self-reported “poor health,” history of MI, diabetes, high blood pressure, poor heart function, and number of coronary arteries that were diseased) as well as the influence of changes in the amount of exercise over time. Many of these confounding variables would otherwise have influenced the outcome measures.

The primary finding was that individuals who exercised the least (either “rarely or never” or “1-4 times per month) were at greatest risk for all 4 of the outcome measures. This isn’t surprising. This study confirms the findings of many previous studies.

The investigators also found that there was a sweet spot in terms of the frequency of exercise, where there was the greatest benefit, and lowest risk for the outcome measures. For all-cause mortality, cardiovascular mortality, and major cardiovascular events, the sweet spot was “2-4 times per week” of exercise. Either more or less exercise was associated with greater risk. For the outcome measure of non-fatal cardiovascular events, though, there was little association with the frequency of exercise. These results are the ones that received attention in the press this week.

On the face of it, though, these findings about frequency of exercise might be deceiving.

The investigators also reported on the amount of exercise–the number of hours spent per week in physical activity. Again, there appeared to be a sweet spot where the risk of the outcome measures was least: 10-11 hours per week, for all-cause mortality and cardiovascular mortality and ~9 hours per week for major cardiovascular events. In each of these cases, a broad range in the amount of exercise, perhaps 5 to 16 hours per week, conveyed a benefit over no exercise at all. And similar to their findings for the frequency of exercise, the investigators found very little relationship between the amount of exercise and the outcome measure of non-fatal cardiovascular events. I don’t recall seeing these results reported in the media.

Take Home Messages

There’s always more to the story than the headlines suggest.
This study is a longitudinal, observational study. It is not a prospective trial, or experiment. Because of the study design, some will be critical about the results and conclusions. But realize that, for a variety of reasons, there will never be a 10-year trial where one group is told to exercise and another group is told not to exercise. As a result, the current study is the type of investigation that will continue to inform us about the issue of “too much exercise.” We should pay attention to the results.
This study involves individuals with known CAD. And recall that the typical enrollee was male, age 61, overweight, current/former smoker, with a history of MI and high blood pressure. Remember to keep in mind, then, that the results and conclusions apply to THIS group of individuals. This study does NOT speak to the issue of “too much exercise” for healthy individuals.
The greatest risk for the outcome measures was identified for those individuals who exercised the least. This is the most important finding of the study. This finding is consistent with my personal experience caring for such patients. In this group of patients, like elsewhere in our society, we have a problem of too little exercise, not too much. Don’t lose sight of this message.
CAD is common. For the very large group of patients with CAD, there is a real and practical issue of how much exercise to recommend, or to “prescribe.” We want patients to derive the most benefit possible. And we want them to avoid unnecessary risk. This study suggests that “2-4 times per week” is the sweet spot for frequency of exercise but that a rather generous ~9-10 hours per week is the sweet spot for the amount of exercise. We should pay attention to these findings when we make recommendations to patients with CAD.
For patients with CAD who choose to exercise beyond these sweet spots, I’d advise caution. Obviously, “2-4 times per week” and ~9-10 hours is quite a bit of exercise, and possibly far in excess of what is recommended by the AHA guidelines. So there’s obviously room for considerable activity and sports participation up to these sweet spots. For any level of planned exercise, individuals with known CAD ought to work with their doctor(s) to settle on what is safe and appropriate given their particular circumstances, realizing that the benefits and risks will not be the same for every individual. Beyond these sweet spots, though, the motivation for additional exercise is probably something other than one’s health. In that situation, judgements need to be made about the trade-off between additional exercise and additional risk.

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Adderall, Athletes, and the Heart

November 2, 2013 By Larry Creswell, MD 2 Comments

Last week I got an inquiry from a reader about the prescription drug Adderall, asking in particular about the heart risks for athletes who might be taking the drug.

Although we’ll be talking about Adderall in particular, much of the information here will apply to other stimulants as well.

My quick take….

Like any drug, there’s both good and bad with Adderall. For athletes who legitimately need the drug, though, the heart risks appear to be small provided that the athlete doesn’t have any serious underlying heart problems. The drug can probably be used safely if both athlete and physician are aware of the potential risks.

What is Adderall?

Adderall is the brand name for a central nervous system stimulant composed of a 3:1 mixture of the salts of d-amphetamine and l-amphetamine. The U.S. Food and Drug Administration (FDA) has approved its use for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.

The drug is available in immediate release and extended release forms (Adderall XR) in dosages of 5-30 mg. Generic formulations are also available.

The U.S. Drug Enforcement Agency (DEA) has placed Adderall on its Schedule 2 list of drugs–those with a high potential for abuse, with the potential for leading to severe psychological or physical dependence. There are both federal and state regulations that apply to prescriptions for Schedule 2 drugs. In my home state of Mississippi, a handwritten prescription is required, refills are not permitted, and the prescription must be filled by a pharmacy within 90 days. There are stiff penalties for trafficking in Schedule 2 drugs.

In the United States, the prevalence of ADHD in children age 4-17 is nearly 10% and the prevalence in adults is nearly 5%. About two thirds of affected children are treated with prescription drugs.

Adderall and the Athlete

For athletes, there seem to be 3 relevant questions:

What are the rules governing the use of Adderall by athletes?
Does Adderall provide a competitive advantage?
What are the risks?

The Rules

For NCAA athletes, all stimulants are banned. There is a policy which allows for medical exceptions for banned substances that are used for legitimate medical purposes. In the case of Adderall, pre-approval from the NCAA is not needed for use, but the athlete must maintain documentation from his/her physician in the on-campus medical record that includes the diagnosis, course of treatment, and current prescription. If such an athlete is tested positive for the stimulant, the documentation is then used, after the fact, to obtain an exception from penalty.

All stimulants are included in the World Anti-Doping Agency’s list of substances that are banned in-competition. The WADA banned substance list has been adopted by all sports federations of the Olympic movement and many others as well. A complete list of signatories can be found at the WADA website. Athletes with a legitimate medical need for a banned substance can apply for a therapeutic use exemption (TUE). Information about the process for obtaining a TUE is posted at the WADA website. WADA recommends reassessment for the need for continued treatment every 3-4 months.

Adderall and other stimulants are banned by the National Football League (NFL), Major League Baseball, National Basketball Association (NBA), Major League Soccer, but athletes can obtain a therapeutic use exemption. Interestingly, nearly 10% of Major League Baseball players have obtained such an exemption. The drug is banned completely in the National Hockey League (NHL).

Competitive Advantage?

When used to treat ADHD, particularly as part of an comprehensive treatment plan that includes psychological, educational, and social measures, Adderall can be effective in reducing the inattentive or hyperactive-impulsive symptoms that are characteristic of the disorder.

In individuals without ADHD, the effects of Adderall are not characterized as completely. Nonetheless, there is reportedly increasing use of Adderall in this situation, particularly among college students and various athlete groups. In the college setting, students take stimulants like Adderall to increase their attentiveness and reduce their fatigue, especially in situations such as studying for exams or completing end-of-term projects.

There is also ample reason to believe that stimulants such as Adderall might provide a competitive advantage for athletes. From my vantage point, this issue doesn’t seem to be very well studied (in large part because of the bans), but there is at least some evidence to show that these drugs can produce increases in both strength and endurance, better concentration, and improve reaction time, especially when fatigued.

The Risks

For Adderall, like any prescription drug, information about the known risks can be found in the drug’s package insert.

Let me quote the entire black box warning:

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.

A variety of side effects are mentioned in the package insert, including emergence of new psychotic or manic symptoms, aggression, long-term suppression of growth, seizures, and visual disturbances. Mention is also made that the effects of long-term usage are not well studied and that the usefulness of the drug for any particular patient should be carefully assessed periodically.

The package insert goes on to discuss cardiovascular warnings.

In children and adolescents, sudden death has been reported in patients treated with Adderall who also have heart problems like structural heart abnormalities, cardiomyopathy, or heart rhythm abnormalities. Patients with any of these heart problems are advised NOT to take Adderall.

In adults, sudden death, stroke, and heart attack have all been reported in patients taking Adderall at typical prescription dosages. It is recommended that patients with structural heart abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or coronary artery disease should NOT take Adderall.

For any patient with high blood pressure, special precaution is advised when prescribing Adderall. Because Adderall is known to increase both the heart rate and blood pressure, special caution and careful follow-up is recommended.

Recommendations are offered for the cardiac evaluation of patients who are being considered for treatment with Adderall. Attention should be devoted to a careful medical history, family history (with particular attention to sudden death, ventricular arrhythmias), and physical exam that focuses on heart and vascular health. Additional investigation with EKG and echocardiogram may be indicated depending on the findings. Finally, patients treated with Adderall who develop any serious warning signs of heart disease (eg, exertional chest pain/discomfort, syncope or blacking out) should be re-evaluated.

Summary

In summary, Adderall is a stimulant that is effective for the treatment of patients with ADHD. Although prescription use of the drug is tightly controlled, there is ample prescription mis-use of the drug among individuals without ADHD or other medical reason for its use. For athletes, the drug is performance-enhancing and is banned by many sports organizations. Whatever its use, Adderall carries a small but real risk of serious cardiovascular side effects, especially among users with underlying heart conditions, whether known or unknown. Athletes and their doctors should be aware of these risks and consider cardiovascular screening and careful cardiovascular follow-up when this drug is used.

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