Archive for the ‘Physiology’ Category
A number of recent posts have focused on what might be called the “geopolitics” of healthcare and the Federal budget in the United States and offered analysis and ideas about how things like sin taxes and insurance plans might incent healthier behavior. Today I want to get back to human performance and elite athletes, topics that were covered in detail last summer during the Olympics. The twist here is that I want to talk about elite 80 year old endurance athletes.
In an amazing scientific paper, scientists from Ball State University in Indiana, along with collaborators in Sweden, found 9 elite cross-country skiers (including an Olympic Champion) who had remained highly physically active and trained throughout life. On average these individuals had VO2 max values of 38 ml/kg/min. This is a value similar to that seen in sedentary men in their teens and twenties. It is also a value about 80% higher than the values seen in sedentary 80 year olds. VO2 max is a marker of the ability of the heart and lungs to deliver oxygen to exercising muscles and also the ability of the muscles to use oxygen. A simple analogy is that VO2 max somewhat similar to a measure of horse power for a car. With more horse power you can do more!
Below is a figure from the paper. The key point is that a VO2 max value of about 15 is required to be functionally independent and that the untrained octogenarians were likely drifting downward toward that value, while the athletes had plenty of reserve and extra capacity. Another key point that my colleague Jill Barnes and I made in an editorial on this paper is that while the high values in the athlete’s likely had a component of “natural ability” or “genetics”, it should be possible for highly active regular guys in their late 70s and 80s to have VO2 max in the high 20s or lower 30s, or about twice the value needed to remain independent.
This paper raises a lot of questions about things like what kept these men motivated to stay so active throughout life. It will also be interesting to see what the data in older women looks like as more women participate in endurance sports throughout life. While there is no fountain of youth, the data in these older elite athletes is just another example of what lifelong exercise can do.
A few weeks ago I pointed out that age associated cognitive impairment and Alzheimer’s disease shared many risk factors with cardiovascular disease. The brain shrinks as it ages and it shrinks faster in people with cognitive impairment and Alzheimer’s disease. There are also other subtle structural changes associated with aging and cognitive decline. A recent paper in the journal Neurology reported on how physical activity affects brain volume in almost 700 people in their 70s who were studied in England.
“A higher level of physical activity was associated with higher fractional anisotropy (a marker of brain structural integrity), larger gray and normal appearing white matter volumes, less atrophy, and lower white matter lesion load. The physical activity associations with atrophy, gray matter, and white matter lesion remained significant after adjustment for covariates, including age, social class, and health status…..”
Conclusions: In this large, narrow-age sample of adults in their 70s, physical activity was associated with less atrophy and white matter lesion. Its role as a potential neuroprotective factor is supported; however, the direction of causation is unclear from this observational study. “
The paper goes on to discuss factors that might be responsible for the positive effects of physical activity on brain size and function. There is evidence that exercise stimulates the growth of new brain cells and improves connections between brain cells, so no major surprises here.
The paper also mentions that exercise may also improve blood flow to the brain. The figure below is from a study done in my lab by Dr. Jill Barnes. It shows using a measurement called CVCi, that the ability of the brain blood vessels to relax and vasodilate (usually a good thing) in response to CO2 is lower in healthy 60 somethings vs 20 somethings. In both age groups a drug called indomethacin reduced the vasodilation in response to CO2. Blood flow at rest was also lower in the older subjects, or as Dr. Barnes put it:
“Young adults demonstrated greater MCAv (index of blood flow) 55 ± 6 vs. 39 ± 5 cm/s and MCAv reactivity 1.67 ± 0.20 vs. 1.09 ± 0.19 cm·s to hypercapnia (CO2) compared with older adults.”
The next figure I want to show you is from a study on aging and brain blood flow in trained and untrained male subjects.
The authors commented that:
This ∼17% difference between trained and sedentary men amounted to an approximate 10 year reduction in MCAv (blood flow) ‘age’ and was robust to between-group differences in BMI and blood pressure. Regular aerobic-endurance exercise is associated with higher MCAv in men aged 18–79 years.
Summary: Exercise and physical activity do good things for your brain as you age. They help you grow new cells and they keep blood flow to the brain high. One idea is that blood flow is higher because the brain remains bigger in those who are active as they age. The other interesting thing to note is the “10 year” anti-aging effects of exercise on blood flow. That number, or perhaps an even higher one, seems to be pretty consistent for the anti-aging effects of exercise on many elements of our physiology.
Last week I had the opportunity to attend the “Integrative Biology of Exercise” conference sponsored by the American Physiological Society. During an excellent talk on how exercise training can modify the changes in heart function with age, Dr. Ben Levine showed classic data from a study done in the middle 1960s known as the Dallas Bed Rest Study.
In this study 5 healthy young men did nothing but bed rest for three weeks while detailed measurements of their cardiovascular function and exercise capacity were measured. Not surprisingly, cardiac function declined and exercise capacity fell dramatically with bed rest. The figure below shows what happened to VO2 max which is considered the gold standard measurement of exercise capacity after bed rest.
What is even more interesting about this figure is that when the same subjects were studied 30 years after the original bed rest study, their VO2 max fell more with just three weeks of bed rest than with 30 years of aging. Below is a video link of Dr. Levine talking about his work on related topics.
If video does not load, click here.
Another interesting video on the topic of inactivity comes from Dr. Bente Pedersen of the University of Copenhagen. Her team has conducted an incredible study showing that just two weeks of minimal physical activity can put previously health young men on the path to what might be described as pre-diabetes. In the video below she discusses these findings and also concepts related to the fit vs. fat topic covered a few posts ago.
If video does not load, click here.
These are terrific talks by scientific leaders who are my friends and colleagues. One of the great things about the electronic environment is that presentations by such outstanding investigators are available to us all.
Today’s post was stimulated by an e-mail exchange with Amby Burfoot of Runner’s World on reports over the past few months suggesting that lifelong intensive exercise training might be “bad” and actually increase the risk of heart problems. The idea is that during exercise adrenaline and related hormones cause the heart to beat faster and harder. Do this day after day for years and the thinking goes that areas of micro damage might occur. In addition to leading to small areas of heart damage, there might also be a buildup of calcium in the blood vessels that supply the heart. So what is the evidence to support these ideas?
First, after extremely prolonged and intense exercise like a marathon or ironman triathlon the pumping ability of the heart can be reduced by a few percent for a few days and there can be a rise in blood levels of substances released from the heart. However, the pumping function of the heart returns to normal within a week and there is no evidence of long term heart damage. The blood levels of substances released from the heart also return to normal. The other tricky thing here is that the skeletal muscles of highly trained athletes undergo biochemical changes that make them more like heart muscle. The wear and tear on skeletal muscles during a competitive event can then cause a rise in the blood levels of so-called cardiac markers that are in fact released from skeletal muscle and set off all kinds of false alarms about heart damage.
Second, no one is sure exactly what finding calcium in the coronary arteries means in asymptomatic people especially older athletes. Also, case reports in a few people are hard to interpret and in more controlled studies it appears that the coronary arteries of lifelong ultramarathon runners are a bit bigger than those of non-runners and can also dilate more. The figure below shows this data, and bigger coronary arteries that relax more are almost certainly a very good thing.
Third, there is some data in animal models that areas of micro damage caused by prolonged intense exercise make the heart more susceptible to dangerous irregular heartbeats. However, in these studies aversive stimuli (tail shock) were used to get the animals to run so there is the added issue of “mental stress” in addition to exercise. Also, the animals were doing a training regimen that was truly heroic in terms of both daily duration and intensity and how this translates to what even the most fanatical human might do over 10 or 20 years is unclear. In other animal models, exercise training tends to protect the heart from irregular beats.
Fourth, when detailed research and data collection is done on who dies during exercise a couple of patterns emerge. Young people who die suddenly typically have congenital problems with the electrical system in their hearts or defective coronary arteries. Middle aged and older people typically have evidence of heart disease that in many cases probably started before they became fit or started to train. There are also cases of heart problems in athletes likely related to acute inflammation of the heart perhaps associated with a viral illness. However, marathon running as a whole appears to be very safe.
Fifth, all the news is not positive. There is some evidence that lifelong training is associated with a condition known as lone atrial fibrillation. However, the data are only suggestive and much bigger and better controlled studies are required on this topic. This condition while bothersome is typically not life threatening and can be treated.
Perspective: Over the last few months I have been making the case that one of the biggest public health and ultimately medical problems out there is inactivity. Is there a cardiac risk associated with being super fit and training a whole lot? To the extent there is comprehensive and well controlled data the answer appears to be no. It does appear that in terms of health there are diminishing returns and that people who train “a whole lot” (say more than an hour almost every day) are not better off than people who just do “a lot” (30-60 minutes most days). However, people who do a whole lot of training are probably doing it for reasons other than health that include things like a need to compete, a need for time alone, or the need for some sort of big challenge in life. Not exercising enough is extremely common and dangerous. By contrast, a life time of exercising “too much” is extremely rare and the evidence to suggest it does long term harm to the heart is pretty speculative.
For the last month or so I have been focused on the twin problems of inactivity and obesity. Today I want to turn the tables on these problems and ask what we know about people who live a long time and remain independent.
It turns out a lot is known about who makes it into their later 80s, 90s or 100. In other words who lives a long time and remains independent and engaged in life One of the first people to study this topic was Dr. Lester Breslow who died earlier this year at age 97. His obituary in the Lancet pointed out that he was a pioneer in public health showing that:
“45-year-olds who adopted six healthy habits—exercise, non-smoking, weight control, adequate sleep, moderation in alcohol use, and breakfasting well—lived longer than people with three or fewer healthy habits.”
Midlife fitness is also important because it reduces the burden of chronic disease as people age and limits the slow drift into disability and functional limitations seen in many older people. So if you want to be a vigorous older person, be a vigorous middle-aged person.
One of the most interesting studies on this topic comes from the Honolulu Heart Project that has followed about 8,000 Japanese American males born in the early 1900s. The study started in the middle 60s and has found that only a couple of factors explain who lives a long time and who remains healthy. Recently the more than 2,000 men who are still alive were studied and it was found that:
“Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times more often to the highest third of grip strength in midlife, were never smokers, had participated in physical activity outside work, and had a long-lived mother (≥80) Associations for nonagenarians (90 year olds) and octogenarians (80 year olds) were parallel, but weaker. Statistical modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity.”
Clearly we can’t pick our mothers, but we can chose not to smoke and to remain physically active. Studies of the Seventh Day Adventists in California who have incorporated the ideas outlined above also live long lives and remain independent into old age. The slide below show that Adventist men live about 7-8 years longer than other men in California, for women it was about 4-5 years. About 70% of Adventists men make to age 80 but only 40% of the male population as a whole makes it to age 80.
Summary: Dr. Breslow was right a few simple behaviors can have a big impact on both how long we live and how well we live.
In several recent posts I have focused on physical activity and health and also the link between obesity and inactivity. Not a lot of good news if you look at the population statistics, but good news if you think about just how protective exercise and physical activity are both in terms of obesity and also general health. So, what to do about it?
Perhaps the easiest, cheapest and most convenient form of exercise for most people, especially middle aged (40-65) and older (>65) people is simply walking. One of the best and most effective ways to get the most out of your walking is to do something called Interval Walking Training (IWT). This program was developed in the Japan by my close friend and colleague Hiroshi Nose, and his research team to help thousands of people get into better shape.
The idea is to use the same principles that elite endurance athletes and Olympians do when you go for a walk. To get in the best shape possible the elites do work outs that include multiple 3-5 minute efforts that are nearly all out followed by 2-3 minutes of recovery several times or more per week. Both scientific studies and practical experience suggests that this is a key to getting in the best possible shape. It also gives you incredible “bang for the buck” in terms of time, and what works for the elite athletes can work for us all.
The IWT program consists of 5 or more sets of 3 minutes of low-intensity walking followed by fast walking for 3 minutes four or five times per week. Low intensity walking should be a bit faster than a stroll (40% effort) and higher intensity walking should be at greater than 70% of maximum effort. Hiroshi’s team has used this approach in a number of their studies and they use heart rate monitors and tracking devices called accelerometers to set and measure exercise intensity.
The figure below is one that shows a typical heart rate response and calorie consumption pattern with this type of training in one of the subjects in Japan. It was sent to me by Dr. Shizue Masuki and the data was collected by Dr. Ken Miyagawa, they are both key members of the Nose team. Hiroshi had the following comments about the data:
“As shown in the figure, HR increases to ~130 beats/min during fast walking, but decreases during slow walking, This slow walking or recovery period is important because it motivates a subject to walk at high intensity again. Moreover, because the interval walking training was performed in a hot environment (atmospheric temperature=32 C, RH=60%), HR level increases with increasing body temperature, which makes it difficult to estimate walking intensity from HR accurately. Therefore, it is important to monitor walking intensity with a tri-axial accelerometer.”
Does this work? To quote one of the early papers on IWT:
“In the IWT group, isometric knee extension increased by 13%, isometric knee flexion by 17%, peak aerobic capacity for cycling by 8%, and peak aerobic capacity for walking by 9%, all of which were significantly greater than the increases observed in the moderate-intensity continuous walking training group. Moreover, the reduction in resting systolic blood pressure was higher for the high-intensity interval walking training group.”
Below is a figure from a collaborative study that we did with the team from Japan. It shows what happens to selected inactivity associated risk factors when 26 previously sedentary people (average age 54) followed the program about four days per week for three months. The people with the worst initial values for HbA1c (a diabetes related marker), HDL cholesterol, LDL cholesterol and glucose showed the biggest improvements with IWT. We also found big increases in exercise capacity and reductions in blood pressure. So, it worked!
In an article in the New York Times on what the best form of exercise Professor Nose put what IWT can do for people in laymen’s terms.
“Physical fitness — maximal aerobic power and thigh muscle strength — increased by about 20 percent which is sure to make you feel about 10 years younger than before training…….symptoms of lifestyle-related diseases (hypertension, hyperglycemia and obesity) decreased by about 20 percent, and depression scores dropped by half.”
I am closing with a shot of a beautiful park in Matsumoto, Japan where the Nose team is located and where many of the subjects he studies do their walking.
This post is on how inactivity is a major player in the obesity epidemic. It is data rich so fasten your seat belts. That having been said, I want to make three main points:
- Physical inactivity is an extremely recent experience for humans as a species.
- People with high levels of physical activity are protected from obesity.
- A loss of physical activity at work as we all become desk jockeys is a big reason why we are getting fatter as a population.
Inactivity is recent.
Dates vary but modern humans emerged out of Africa and began to spread to the rest of the world about 40,000 years ago. For the next 30,000 years essentially we were all hunter gatherers. Based on a variety of estimates, including observations in the few remaining hunter gatherer societies, it appears that many adults hunter gatherers walk between 10 and 20km (6-12 miles) per day. There also appears to be essentially no obesity in these societies. There are complex potential interactions between their activity levels and what they were eating, but many groups of hunter gatherers had access to plenty of food. Granted the variety might have been minimal, but for many there were plenty of calories.
About 10,000 years ago agriculture emerged during something called the Neolithic Revolution. We have at least some idea about the activity levels associated with muscle power (human or draft animal) farming from the Old Order Amish who practice agriculture without the benefit of electricity or tractors but do use horses! It is also pretty clear that they eat an awfully lot of what could be called traditional high calorie farm food. Here is a quote from adapted a classic study on the Old Order Amish.
“The average number of steps per day was 18,425 for men versus 14,196 for women. Men reported 10.0 hours per week of vigorous physical activity, 42.8 hours per week of moderate physical activity, and 12.0 hours per week of walking. Women reported 3.4 hours per week of vigorous physical activity, 39.2 hours per week of moderate physical activity, and 5.7 hours per week of walking. Men had higher levels of energy expenditure than women. A total of 25% of the men and 27% of the women were overweight (BMI > or = 25), and 0% of the men and 9% of the women were obese (BMI > or = 30).”
High levels of physical activity protect against obesity.
The data above mean that most Old Order Amish are essentially physically active all day long most days. Contrast their BMI values with the values for the U.S. population as a whole that I reviewed earlier this week, 35% obese and 60-70% overweight. Another interesting thing about the Old Order Amish is that their high levels of activity protect them from two gene variants that seem to predispose sedentary people to higher BMIs. The left panels on the figure below show that for Old Order Amish in the bottom 50% of physical activity there is a relationship between the gene variants and BMI. The right panels show that for those in the top 50% of physical activity there is no relationship between the gene variants and BMI. Genetic predispositions get blamed for all sorts of things but the environment, culture and lifestyle typically has an even bigger role for most common conditions. Again high levels of physical activity are protective against obesity.
Physical activity at work matters.
The Old Order Amish are people who are clearly active all day long with farming and household chores. They are probably as active or even more active than hunter gatherers were. However, in the last hundred years a muscle powered way of life has vanished for most of us. So, what about the rest of us? It turns out that over the last 50-100 years most of us are doing less and les physical activity at work. The slide below is from a terrific scientific paper on this topic. It shows that as over the last 50 years the number of people employed in jobs associated with moderate physical activity has declined from about 50% to 20%. As the authors note:
“From 1960 to 2008 there was an approximate drop in occupation-related daily energy expenditure of 140 calories for men and 124 calories for women.”
For most of us that is like walking (or not walking) 1 to 1.5 miles during the day. What is even more amazing is how these missing calories add up and explain population based weight gain over the last 40 or 50 years. The figure below also from this paper shows the impact of the missing calories on estimated changes in body weight over time and how the match up with the NHANES population surveys in the U.S. It is incredible how well the numbers match up. It is also incredible what a big impact just over 100 hundred calories a day has.
Hunter gatherers and traditional farmers were very active and almost none were fat even when there was plenty of food around. However, you don’t have to be that active to avoid the being a statistic in the current obesity epidemic. The data on occupational energy expenditure from the last 50 years shows that burning an extra 100-150 calories a day can have a huge impact on population based body weight statistics. From a practical perspective what would happen if everyone went for a brisk 20-30 minute walk at lunch every day?
A couple of days ago I discussed whether deconditioning should become a distinct medical diagnosis because it is the root cause of so many devastating chronic diseases. In this short post I want to briefly review how much structured exercise or physical activity is enough and whether people are getting enough?
First, let me briefly comment on exercise and physical activity. They are related but not exactly the same thing. Structured exercise includes things like going to the gym, playing in a sports league of some type, or a planned walk or run. In general, anything that is organized and designed as a workout. Physical activity is a broader way to look at things. In addition to formal exercise, it includes things like riding your bike to work, taking the stairs, household chores, unstructured play and other recreational activities.
Second, what are the guidelines? I am attaching a link to the most recent U.S. guidelines for physical activity. They are designed to prevent the development of many of the chronic conditions that result from inactivity. The key numbers are:
“Adults (18-64) should do 2 hours and 30 minutes a week of moderate-intensity, or 1 hour and 15 minutes (75 minutes) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic physical activity. Aerobic activity should be performed in episodes of at least 10 minutes, preferably spread throughout the week.”
There are other ideas and numbers out there, but when you look at them in detail most are pretty similar. The guidelines also include specific recommendations for children and older adults along with ideas about strength training.
Third, how is the population doing as a whole in meeting these guidelines? The short answer is terrible. The next link is to a paper that used accelerometers to measure physical activity as part of the NHANES study and the bottom line is that:
“Among adults, adherence to the recommendation to obtain 30 minutes per day of physical activity is less than 5%.”
Fourth, the chart below from the U.S. Centers for Disease Control shows just how many people get no leisure time physical activity at all. Things appear to be getting a bit better over the last 10 years, but 25% of people are completely inactive and as we saw in the chart from a couple days ago, the biggest improvements in health occur when people go from being completely inactive to doing something.
These statistics are a snapshot of just how bad things are. In my next few posts I am going review how much physical activity is “normal” for humans and what can be done about this huge problem. There are many innovative solutions that are working out in the real world, so there is no need to “sit around” and wait for them to happen.
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