Examining the Controversy: Is too much exercise bad for the heart?

swimming in triathlon  

The mainstream media claims recent research may show vigorous exercise is unhealthy. That isn’t the complete picture.

 

 

A flurry of studies  a few years ago suggesting too much exercise is detrimental to one’s health sparked fierce debate over the legitimacy of the claims. The mainstream media jumped into the fray. The Wall Street Journal published an article “One Running Shoe in the Grave” arguing too much exercise stresses the heart enough to erase any physical activity health gains. What did the studies actually find, and is it a cause for concern?

One study tracking 52,000 adults for 15 years found that runners had a 19% decrease in all-cause mortality. However, when it was broken down by mileage a U-shaped curve emerged. Those exercising moderately for 2-5 days a week had the lowest mortality. The extremes had the highest mortality. In fact, the people running more than 25 miles a week had almost as high a mortality rate as those not exercising at all. The figure below shows this “U-curve” from the study (Running and all-cause mortality risk: is more better? 2012. Lee J, et al.)

However this does not give the complete picture. Another study, published in 2011, found that vigorous exercise and moderate exercise had differing amounts of benefit towards reducing mortality risk. The authors found that moderate exercise showed a gentle, increasing curve when plotted against mortality risk.  Meanwhile, vigorous exercise had far higher marginal returns up to about 50-60 minutes a week when it began to plateau. For both vigorous and moderate exercise, diminishing returns was observed as expected. However, no negative relationship was seen with extreme durations of daily exercise. The relationship can be seen in the figure below (Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study, 2011. Wen CP, et al.)

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So although the relationship cannot be fully established, if vigorous exercise does cause an increase in mortality risk past a certain point what is the cause?  According to a review by cardiologist James O’Keefe and colleagues, the cause is a problem with heart function.  (Potential Adverse Cardiovascular Effects From Excessive Endurance and Exercise, 2012.  James O’Keefe, et al.). Athletes develop an enlarged left ventricle to enable increased circulation. This remodeling does not disappear for at least several years following retirement from vigorous exercise. Several biomarkers for myocardial damage appear to be elevated following intense, prolonged races such as triathlons or marathons.  Myocardial scarring from vigorous exercise may lead to problems. Endurance athletes have been shown to have a higher rate of electrocardiogram problems.  Endurance athletes may have a five-fold increase in prevalence of atrial fibrillation. The increase in atrial size from endurance training may be responsible for atrial fibrillation.

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Other problems with the cardiovascular system that show up in endurance athletes include coronary artery calcification, diastolic dysfunction, aorta wall stiffening and myocardial fibrosis. Despite all these potential problems the authors add that lifelong vigorous exercisers generally have low mortality and great cardiovascular function; its an interesting paradox.

In conclusion, if health is your sole reason for exercising it may be best to limit exercise to 2-5 days a week of moderate exercise. However, the risks of vigorous exercise are highly speculative until more research comes out. The mainstream media is likely exaggerating the findings of recent studies or drawing hypothetical conclusions. When carefully looking at the data and the papers collectively, the research says vigorous exercise is still good for the body. Regardless of which side ultimately wins the debate, exercise is undoubtedly good for the mind and collective well-being.

Aging, Physical Activity and Blood Flow

quadriceps muscle anatomy 

Physical activity diminishes age’s affect on the reduction of the potent vasodilator NO. Elevated NO in the blood results from or causes a reduction in the amount of dangerous radical oxygen species in the blood.

 

Many physiology studies have shown that reactive oxygen species increase in humans with age. Reactive oxygen species have been impacted in the age-related deterioration of the brain. Fortunately, physical activity has been shown to decrease the concentration of reactive oxygen species. The role that physical activity has on preventing Alzheimer’s Disease through reactive oxygen species reduction was discussed in a previous post on ExerciseMed.org. The focus here is the effect that physical activity has on the concentration of reactive oxygen species in the skeletal muscle.

Nitric oxide (NO) is a key regulator of vasodilation in blood vessels feeding the skeletal muscles. When reactive oxygen species are present, nitric oxide gets catabolized. One of the reasons antioxidants are so popular in the health food industry is because, as their name suggests, antioxidants eliminate reactive oxygen species. Older sedentary humans should show the greatest increase in NO following treatment with antioxidants because antioxidants are more prevalent in older patients who abstain from physical activity. One recent Danish study tested this hypothesis by treating subjects with the antioxidant N-acetylcysteine (Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans, 2012.  Michael Nyberg, et al.).

The study placed 8 subjects into each group: a sedentary youth group (mean age: 23), a sedentary older group (mean age: 66) and a physically active older group (mean age: 62). The subjects performed knee extensions for the exercise variable. The study found that the sedentary youth group had the highest concentration of NO metabolites, NOx. The physically active older group, although lower than the youth group, had a higher concentration of NOx in muscle tissue than the sedentary older group. When the older sedentary group was provided with antioxidant N-acetylcysteine (NAC) their NOx levels rose to the active older group with out antioxidants (Control, CON). Both older groups saw a significant increase in NOx concentration, suggesting that NO was compromised by radical oxygen species. At 45% of maximum power output only the older sedentary group saw increases in muscle interstitial NOx concentration following injection of antioxidant NAC. The results can be seen in the figure below.

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Figure 1. Muscle interstitial NOx at rest and during 12 W and 45% Wmax without and with infusion of NAC. Exercise was performed at the same absolute workload of 12 watts and at a relative workload corresponding to 45% Wmax without (CON) or with (NAC) infusion of N-acetylcysteine in young sedentary, older sedentary and older active subjects. †Significantly different from young sedentary within same condition, P < 0.05; ∗significantly different from control conditions, P < 0.05; #significantly different from rest within same condition, P < 0.05.

The older active group showed no decrease in NO2 in their arteries when treated with antioxidant NAC. The young and old sedentary groups both saw increases in arterial NO2 (as shown in the figure below only the older sedentary group saw a significant increase in arterial NO2). This means that only the older active group was able to contain the radical oxygen species.

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Figure 2. Plasma NO2− and NOx at rest without and with infusion of NAC. Femoral arterial blood samples collected during rest without (CON) or with (NAC) infusion of N-acetylcysteine in young sedentary, older sedentary and older active subjects. ∗Significantly different from control conditions, P<0.05

Although antioxidants increased the amount of NO in the blood, the blood flow to the legs did not increase following antioxidant administration. The increase in NO concentration did not cause an increase in leg muscle blood flow. This result is surprising because NO is known to be a potent vasodilator. Thus, exercise-induced hyperemia (increased blood flow) must occur through a pathway other than NO in the legs.

Figure 3. Leg haemodynamics at rest and during 12 W and 45% Wmax. Exercise and rest without (CON) or with (NAC) antioxidant in young sedentary, older sedentary and older active subjects. †Significantly different from young sedentary within same condition; #significantly different from rest, ‡significantly different from older sedentary within same condition.

This study showed that one mechanism by which NO is increased in physically active elders is through a decrease in radical oxygen species. Another mechanism is an increase in Nitric Oxide Synthase (NOS), a protein that synthesizes NO. The physically active older subjects were found to have a significantly higher amount of endothelial NOS and neural NOS. The authors suggest that the elevated amount of NOS in active older subjects could act as a radical oxygen species scavenger. The increase in NO production may compensate for the age-related increase in radical oxygen species.

In conclusion, the discussed study found that physical activity decreased age’s affect on nitric oxide (NO) decline in the blood. NO is a vasodilator, it opens up blood vessels. The concentration of radical oxygen species was lower in the physically active older subjects than the sedentary older active subjects. The older active subjects had the highest amount of nitric oxide synthase (NOS).  Since radical oxygen species decrease NO concentration, NO concentration may be elevated in the physically active because the combined effects of lower radical oxygen species and higher NOS. Another possibility is that NO scavenges radical oxygen species. This means that the low concentration of radical oxygen species is the product, rather than the cause, of high NO levels in the blood. In addition, nitric oxide was found to play no role in hyperemia during physical activity. Regardless, physical activity is important for maintaining vascular health by maintaining nitric oxide levels with aging.

Physical Activity, Stress and Telomere Length

telomeresTelomeres (highlighted red in the photo to the left) are protective stretches of DNA and the end of a chromosome. Their length has been shown to shorten as a result of both age and stress. Physical activity has been shown to act as a buffer against stress-induced shortening.

 

In a previous post the affect of stress on telomere length was discussed. As explained in that post, telomeres are stretches of DNA at the end of chromosomes responsible for protecting the chromosome. Every time a cell divides its telomeres are shortened. In some cells an enzyme named telomerase replenishes the lost telomerase, but in other cells the telomeres gets continually shorter. Therefore, telomere length can be a good predictor of aging. Eventually, the telomere protection disappears and unprotected genetic material would get cut with each division.  Usually, at this point the cell dies.

Individuals scoring high on a stress test have been shown by many studies to have shorter telomeres. For a more in depth look at the stress-telomere length studies visit this the Stress and Telomere Length post.

In 2010, a study (The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length, Puterman E, Lin J, Blackburn E, O’Donovan, Adler N, et al.) found that the negative effect of stress on telomere length disappeared when the subject was deemed to be physically active.

The study broke subjects into groups based on physical activity reported: sedentary and physically active. Each subject completed a Perceived Stress Scale.  Subjects categorized as sedentary tended to score higher on the Perceived Stress Scale. Sedentary subjects showed an inverse correlation between stress score and telomere length, confirming results found in previous studies.  Surprisingly, subjects categorized as physically active (equal or more than 75 minutes of exercise per week) did not show a decrease in telomere length when stress level was increased. The relationships are shown below. Notice that the sedentary group shows a noticeably negative relationship between telomere length and perceived stress; conversely, the active group shows no relationship.

Interestingly, 75 minutes of exercise per a week is the recommendation of the Center of Disease Control and Prevention. Shorter telomeres have been shown by many studies to correlate with an increased risk of developing chronic illnesses like cancer and heart disease. Therefore, 75 minutes of weekly exercise may decrease risk of developing a chronic illness through telomere length. Although a relationship has been found between exercise and risk of developing many chronic diseases, telomere length has not been established as the pathway for exercise’s effect on chronic illness risk.

The authors of the study theorized that the pathway by which exercise buffers against stress-induced telomere shortening is through telomerase activity. As mentioned above, telomerase is an enzyme that lengthens telomeres shortened by cell division. Stress has been shown to inhibit telomerase activity (Accelerated telomere shortening in response to life stress, 2004, Elissa S. Epel, Elizabeth H. Blackburn, et al.). Exercise has been shown to increase telomerase activity in mononuclear cells from rats and human leukocytes (Werner C, et al., 2009, Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall).

In summary, physical activity acts a buffer against the telomere shortening effects of stress. The biological pathway this may occur is through the exercise proliferation of telomerase, an enzyme responsible for extending telomeres.