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.

Controlling Alzheimer’s Risk

elderly coupleOne study shows that physical activity and diet health exert some control over Alzheimer’s risk. Scientists have found possible mechanisms between physical activity and Alzheimer’s risk.

 

 

 

 

Alzheimer’s disease is a brain disease that causes loss of memory and cognitive function. The disease is caused by the build up of toxins in the brain leading to deterioration of brain tissue. The hippocampus, our brain’s memory center, deteriorates as the disease progresses. The National Institute of Health estimates that 5.1 million Americans suffer from Alzheimer’s.

In 2009 a study found negative correlations between the risk of developing Alzheimer’s disease and physical activity and diet health (Physical Activity, Diet, and Risk of Alzheimer Disease, 2009, Nikolaos Scarmeas, et al.). The study looked at 1880 elderly individuals from New York City over an average period of 5.4 years.  Individuals diet score and physical activity score was collected. The study participants were screened to ensure that they were not suffering from dementia before participating in the study. Those reporting significant physical activity had a 37-50% lower risk of developing Alzheimer’s disease. Those in the highest Mediterranean-style diet adherence tertile had a 32-40% reduced risk of developing Alzheimer’s disease.

Good physical activity and a healthy diet were both found to independently reduce risk of developing Alzheimer’s disease. The Godin leisure time questionnaire was administered to determine physical activity. The questionnaire looked at physical activity over a two-week interval. Diet was determine with the 61-item version of the Willett Semiquantitative Food Frequency Questionnaire to determine adherence to a mediterean-type diet (points for fruits, vegetables, fish, grains and lost for meats, dairy, fats). Subsequent questionnaires were administered every 1.5 years to ensure the validity of the initial questionnaire.

Alzheimer Disease (AD) Incidence by High or Low Physical Activity Levels and Mediterranean-Type Diet Adherence Scores

 

The participants were all 77+/-1 years old; as is the case with elderly populations  physically activity was not prevalent in the study participants.  Therefore, the high physical activity corresponded to 1.3 hours of vigorous physical activity, 2.4 hours of moderate physical activity or 4 hours of light physical activity. This demonstrates that even a small amount of physical activity can lead to significant benefits in reducing Alzheimer’s.

How does exercise protect the brain?

The mechanism that exercise influences Alzheimer’s Disease risk may be through various toxins and neuro-factors. Research has shown that brain-derived neurotrophic factor (BDNF) protects against synapse deterioration and may be able to treat Alzheimer’s. Moderate to vigorous physical activity increases BDNF. Low levels of Nerve Growth Factor (NGF) has been shown to be a risk factor for Alzheimer’s. Like BDNF, exercise increases the brain’s NGF. Reactive oxygen species in the brain may be another risk factor for Alzheimer’s. Exercise takes care of reactive oxygen species via two pathways: exercise reduces their production and exercise raises antioxidant levels, which detoxify reactive oxygen species. Exercise has been shown in mice models to reduce expression of several genes that have been found to correlate with Alzheimer risk.

Another mechanism exercise may influence Alzheimer’s risk is through cerebral blood flow and metabolism. Both cerebral blood flow and metabolism decrease with the onset of Alzheimer’s. Exercise significantly increases both. Exercise increases vascular endothelial growth factor (VEGF) in the brain. VEGF spurs the development of nigral microvessels, countering the decrease in nigral micro vessel density, an effect of aging. Exercise, especially high intensity exercise, at a young age has been shown to have a tremendous impact on the the promotion of VEGF.

For more information about the biological mechanisms behind exercises reduction in Alzheimer’s risk read Exercise Plays a Preventive Role Against Alzheimer’s Disease (Z. Radak, et al., 2010).

In summary, physical activity and diet exert significant influence on Alzheimer’s Disease risk. Although the mechanism is not exactly known, researchers speculate that it may be through neuro-factors, toxins, cerebral blood flow and cerebral metabolism, all of which are controlled by some extend through exercise. Please share your thoughts!

Exercise Reduces Parkinson’s Disease Morbidity

neurons

 

Two studies suggest exercise may reduce risk of Parkinson’s Disease and reduce the behavioral effects after onset.

 

 

Parkinson’s disease affects over a million Americans is the second most prevalent neurodegenerative disease following Alzheimers disease.  Parkinson’s disease is a dopaminergic brain disorder that leads to slow movements (bradykinesia), rigidity, tremor and postural instability. Parkinsons patients often develop problems with speech, memory, general cognition and smell. As a result of these symptoms, Parkinson’s disease is a dehibilating disease burdening life for both patient and family. However, patients can remain functional with treatment for over 30 years after diagnosis, it is a slowly progressing disease unlike some other neurodegenerative diseases. Parkinson’s disease results from a loss of dopaminergic neurons in the substantia nigra (a region in the midbrain of the brainstem). An etiology is not known, although several genes have been implicated including alpha-synuclein (which forms lewy bodies in neurons, a pathologic characteristic of Parkinsons) and DJ1 (related to mitochondria function). Reactive oxygen species, calcium signaling, proteinaupathy, and viruses have all been discussed as possible etiologies. Several different treatments are available to mask the symptoms, but there is currently no cure. These treatments include dopamine (prescribed as Levodopa), dopamine agonists (Mirapex) and deep brain stimulation (DBS).

In 2010, a study was published finding that adults who participated in physical activity had a reduced risk of developing parkinson’s disease in the next four to ten years (Physical Activities and Future Risk of Parkinson Disease, 2010, Q. Xu, Y. Park, et al.). This study looked at the physical activity of 200,000 plus participants in a NIH-AARP study. Doctor diagnosed Parkinson’s disease rates were collected ten years later. Those who were diagnosed with Parkinson’s in the four years immediately following the initial physical activity survey were left out of the statistical analysis. The study found that adults who reported participating in physical activity over each of the two survey periods had a 40% lower risk of being diagnosed with Parkinson’s disease ten years later. Interestingly, the study found that physical activity at early ages had no link to risk of developing Parkinson’s. Exactly why physical activity is correlated with a reduced risk of developing Parkinson’s is not exactly known. Most likely, exercise was delaying onset of symptoms and progression of disease, rather than fully preventing diagnosis. However, several studies provide some light on possible explanations.

A study published in 2003 found that mice forced to run on a treadmill after being injected with a dopamine toxin, 6-hydroxydopamine, showed less loss of motor control and better retention of neurochemicals that play a role in the dopamine pathway (Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson’s disease, 2003, J.L. Tillerson, et al.).

The study looked at the levels of DAT, VMAT2 (vesicular monamine transporter) and TH (tyrosine hydoxalase). DAT is responsible for dopamine re-uptake in the synapse.  VMAT2 is responsible for the vesicle that transports dopamine between the synapses. TH is the rate-limiting enzyme in the synthesis of dopamine. Studies have shown that people with Parkinson’s have reduced levels of VMAT2. When mice were treated with the toxin MPTP significant decreases in VMAT2, DAT and TH were observed.  However, as figure A shows, mice forced to run on a treadmill showed a reduced drop in DAT, VMAT2 and TH.

Figure A. Mice treated with MPTP had significant losses of neurochemicals DAT, VMAT2 and TH relative to the control. However, mice treated with MPTP and forced to run on a treadmill showed less loss of all three measured neurochemicals.

In addition, motor function was measured in the neurotoxin-treated mice using a forepaw test. Parkinsons-model mice running on a treadmill showed significantly better performance in motor function than sedentary mice. This suggests that exercise could be used to reduce the behavioral consequences of Parkinson’s disease.

In summary, a large human study demonstrated exercise reduces risk of being diagnosed with Parkinson’s disease over the next ten years. In addition, a study of mice treated with a parkinsons-inducing neurotoxin found that exercise reduced dopamine neurochemical drop and motor function. Researchers will find a cure for parkinson’s disease, but in the meantime exercise may be the only option for delaying the progression.

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.

Stress and Telomere Length

telomeres

In the image above, telomeres are highlighted at the ends of each chromosome.

Recent studies show that telomere length, a measure of cellular aging, is strongly influenced by stress.

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.

Elizabeth H. Blackburn, a researcher at the University of California, San Francisco, shared the 2009 Nobel Prize in Physiology or Medicine for her work on the process of telomere shortening. Blackburn’s current research is looking at telomere length and its association with risk of developing chronic diseases like cancer, heart disease and other illnesses. In addition, Blackburn’s work has contributed to a growing plethora of research showing that various lifestyle decisions influence telomere length.

In the Science Talk section of the October 2011 Scientific American, Blackburn says that unpublished research shows that people with higher blood levels of omega-3 fatty acid had much less telomere shortening.

Stress has been shown to accelerate telomere shortening. A study published in August 2011 found that women who worked full-time had significantly shorter telomeres than those who were not employed (Employment and work schedule are related to telomerase length in Women, CG Parks, et al.). A study published in 2004 found a negative correlation between the number of years a woman spends raising a chronically ill child and that woman’s telomere length (Accelerated telomere shortening in response to life stress, Elissa S. Epel, Elizabeth H. Blackburn, et al.). In addition, women who perceived them to be under greater stress were found to have shorter telomeres. In fact, a person under high stress could expect to see on average a 550 base pair loss in telomere length. Telomere length correlates linearly with age. This study found that the average person sees a 31-63 base pair reduction in telomere length per a year. Therefore, someone with high stress ages the equivalent of 9-17 years more than their equivalent with low stress! The results of the study are shown below:

Telomere Length v. Stress (Years Caring for Terminally Ill Child)

As the studies mentioned in this article demonstrate, a low-stress lifestyle is important for controlling cellular aging and the chronic illnesses that have been shown to be associated with shortened telomeres: cancer, heart disease. However, all hope is not lost if you are in a situation where stress cannot be controlled. In my next post on this blog I will previewing a 2010 study that found that physical activity may control the shortening effect on telomeres in people with stress.