Dov Michaeli
Posted 2/17/12 on The Doctor Weighs In

In my marathon-running days (I’ve got 13 under my belt) I used to train as I was told: put in the miles. Going out at five in the morning to run my daily allocation of 10-15 miles, with weekends of 20 miles, put me in great cardiorespiratory shape, and wrecked my body. I was constantly battling aches and pains, achilles tendinitis, and the blahs of overtraining. Despite all this dogged effort I was stuck in a frustrating plateau that I just couldn’t improve on. Until I stumbled oninterval training. It came in the form of a short hill, off the trail of my daily run. Just for fun (weird what runners consider fun) I decided to run up the hill (about 300ft) at maximum speed. I did, and was literally doubled over from breathlessness and exhaustion. But I also had a sense of euphoria, elation at the accomplishment. Well, when you hear euphoria, think endorphins (which are the endogenous morphins) and addiction. I kept coming to that hill and regularly increased the number of those short bursts of maximum effort, about a minute in duration each. I felt high. More important, I had a quantum jump in my next marathon time. So what happened?
The biochemistry of exercise
When a muscle is exercised several events take place, all aimed at providing the required energy from the metabolism of glucose. This process is made up of two parts: the first part takes place in the cell cytoplasm. It is anaerobic, which means that it does not require oxygen, and is calledglycolysis. It produces a net of 4 ATP molecules from one molecule of glucose. The product of glycolysis (pyruvate) then enters the mitochondria and undergoes further degradation through an oxygen-requiring process (aerobic) that is called oxidative phosphorylation. This process yields 32-34 ATP molecules per one glucose molecule. So now we have a real quantitative idea why we need oxygen to survive; without it the cell machinery grinds to halt because of lack of fuel ( i.e. ATP).
Where is the glucose going to come from? as we start the exercise the muscles uses plasma glucose. But if we depended on blood glucose only we’d run out of supply within minutes. Therefore, the exercising muscle starts breaking down its stored glycogen for a longer term supply of glucose. In addition, about 20 minutes into the exercise the muscle starts using fatty acids as an alternative source of energy.
so now we know what is needed for exercise: glucose and oxygen. And indeed, different forms of aerobic exercise, be it walking, running, swimming or cycling require lots of oxygen. Accordingly, chronic exercise increases the maximum oxygen consumption (VO2 max) to better deliver large volume on oxygen via red blood cells, increases the number of capillaries to deliver the oxygen to the cells, increases the number of mitochondria in muscle cells, and the amount of enzymes involved in oxidative phosphorylation in order to increase the rate of producing ATP from glucose.
After a while these processes reach their maximum, regardless how much you exercise, or as exercise physiologists call it the volume of exercise.
This is the biochemical basis for the plateau experienced by weekend warriors and trained athletes alike.
Interval training
Trainers have been experimenting with all kinds of training schedules in an attempt to break the shackles tying down an athlete to his plateau. the one schedule that proved most effective is interval training. What it means is 1-minute bursts of maximum effort interspersed with 2-3 minutes recovery periods of low intensity. What you are basically doing is exercizinganaerobically and then allowing the cells to recover. Regardless how great your oxygen capacity is, if you exercise at your maximum the requirement demand for oxygen will outrun your capacity to deliver enough od it to the mitochondria that are working furiously to provide ATP to the muscle.
So what’s a muscle to do? Evolution actually provided for hypoxic situations. Just think of organisms that can live miles above sea level or thousands of feet underwater, where the oxygen concentration is very low. We humans dealt with the problem with scuba equipment, but other organisms needed a more “physiological” solution. It came in the form of a master molecule called Hypoxia-Induced Factor or HIF. Think of a conductor of a symphony orchestra. This “conductor” is a transcription factor, meaning that it can regulate and orchestrate the expression of genes; an orchestra of about a hundred genes. HIF senses when a cell becomes hypoxic and turns on all the genes that help the cell cope with the hypoxic stress. It turns on EPO, a protein that stimulates the production of red blood cells. It induces the synthesis of VEGF, a peptide that regulates production of new capillaries to provide increased blood supply to the muscle. It induces the synthesis of a glucose transporter, GLUT4, which does what a transporter is supposed to do-bind to glucose in the plasma and transport it into the interior of the cell. It increases the synthesis of the enzymes that participate in glycolysis. This is the first part of glucose metabolism that is anaerobic and delivers only 4 ATP molecules; Meager, but absolutely necessary to survive the hypoxic environment. And one of the long term effects of HIF stimulation is genesis of a lot more mitochondria, to maximize the capacity to make ATP.
And that’s not all, but enumerating all of HIF’s responses to hypoxia would tax the attention span of the most dedicated scientist. But you can already get the picture: exercise-induced hypoxia activates a multitude of adaptive responses. The physiological result is increased endurance and speed.
Even heart patients?
Scientists at McMaster University went a step further. They wanted to see if short bursts of maximal activity could benefit patients with heart failure. They found that cardiac function improved significantly. I have to admit, I wouldn’t have had the courage to try it on such patients. But as Dr. McDonald, one of the investigators, stated to the New York Times, “It appears that the heart is insulated from the intensity” of the intervals, she said, “because the effort is so brief.” Furthermore, “Almost as surprising, the cardiac patients have embraced the routine. Although their ratings of perceived exertion, or sense of the discomfort of each individual interval, are high and probably accurate, averaging a 7 or higher on a 10-point scale, they report enjoying the entire sessions more than longer, continuous moderate exercise”. Strike one for endorphins.
Type 2 diabetes
The effects of interval training seem perfect for people with type 2 diabetes; it increases glucose uptake into the cells, which reduces blood glucose concentration. Seven patients (small study) with type 2 diabetes undergoing interval training showed postprandial glucose control improved not only on the exercise day, but the following day as well. They also showed overall improvement in hyperglycemia. As the cliché goes, more study is necessary; but the results are highly promising.
Last but not least