Exercise, sports medicine and performance-enhancing drugs

Too little: what inactivity does

The lessons before this one followed the ATP a working muscle needs. This one asks what happens to the whole body when that work is missing, and when there is far too much of it. The specification puts both sides in one statement and asks for the evidence to be read critically, so each claim below comes with the reason it is believed.

Obesity is the most direct consequence. Energy taken in as food and not used is stored, most of it as triglyceride in adipose tissue. An inactive person spends less energy each day, so the same diet leaves a larger surplus, and a small daily surplus held for years becomes a large mass of fat. Exercise also builds and keeps muscle, which uses more energy at rest than adipose tissue does.

Cardiovascular disease (CVD) follows partly through obesity and partly by its own routes. Regular aerobic exercise lowers resting blood pressure, lowers the concentration of triglycerides in the blood and raises HDL relative to LDL. High blood pressure damages the endothelium lining the arteries, and damaged endothelium is where atheroma begins, so a sedentary person loses each of these protective effects at once. The heart muscle of a trained person is also stronger, pumping a larger stroke volume at a lower heart rate.

Type 2 diabetes comes from cells that respond poorly to insulin. Contracting muscle takes glucose out of the blood by moving glucose transporter proteins into its cell surface membrane, and it can do this without insulin. Regular exercise also makes muscle and liver cells more sensitive to insulin for many hours afterwards. Take the exercise away and add the extra fat that usually comes with inactivity, and the cells become resistant: the pancreas must secrete more and more insulin to hold blood glucose down, and when its β cells can no longer keep pace the concentration stays high.

Too much: joints, immunity and overtraining

The costs at the other end are of a different kind. They come from the body being asked to repair itself faster than it can.

Wear and tear on joints. In a synovial joint such as the knee, the ends of the bones are covered with smooth articular cartilage, which reduces friction and absorbs some of the shock of each impact. Synovial fluid lubricates the surfaces, ligaments hold the bones together, and two crescents of cartilage, the menisci, spread the load across the knee. Years of repeated high-impact loading, as in long-distance running on hard surfaces or repeated jumping and landing, can wear the articular cartilage thin. Cartilage has no blood supply, so it repairs slowly and poorly. Once it is worn, bone surfaces begin to rub, and the result is pain, swelling and stiffness: osteoarthritis. Heavy training also tears ligaments and menisci, and inflames tendons and the fluid-filled bursae that cushion them.

The evidence here is less one-sided than the phrase suggests. Most studies of recreational runners have not found more knee osteoarthritis than in people who do not run. The raised rates appear in former elite athletes from high-impact sports, and in anyone who has had a serious joint injury. Injury is a large part of the link, and an exam answer that says running wears out knees in everyone has gone further than the data.

Suppression of the immune system. People who exercise moderately and regularly report fewer upper respiratory tract infections, colds and sore throats, than people who do not exercise at all. After a prolonged, intense effort such as a marathon, more of these infections are reported in the following week or two. Put together, the two observations suggest that infection risk plotted against the amount of exercise has the shape of a letter J. This J-shaped curve is a hypothesis, and the evidence for its rising arm is mixed, as the paragraphs below show.

Describe the drawing

A line graph with no numbers on its axes. The vertical axis is the risk of an upper respiratory tract infection and the horizontal axis is the amount and intensity of exercise, running from sedentary through moderate to very heavy. A dashed horizontal line marks the risk for a sedentary person. The curve starts on that line, dips below it to its lowest point at moderate exercise, then climbs steeply and ends well above the dashed line at very heavy training, giving the shape of a letter J. A note says it is an illustrative, proposed model rather than measured data.

The changes measured in the blood after heavy exercise are the ones the explanation rests on. For some hours, the number and activity of lymphocytes in the blood, natural killer cells among them, fall, phagocytes are less active, and the concentration of the antibody IgA in saliva falls, so the mucosal surfaces of the nose and throat are less well defended. Cortisol and adrenaline, released in large amounts during hard exercise, both suppress parts of the immune response. This period of a few hours to a few days is sometimes called the open window.

Here too the evidence is argued over. Some immunologists point out that lymphocytes leaving the blood after exercise are moving into tissues such as the lungs and gut rather than being lost, and that many studies counted symptoms reported by the athletes rather than infections confirmed in a laboratory. Athletes at a big race have also travelled, slept badly and stood in crowds, all of which raise the chance of catching something.

Overtraining is what happens when heavy training continues without enough recovery. Performance falls and does not come back after a few days' rest, and the athlete has persistent fatigue, poor sleep, low mood and frequent minor infections. Overuse injuries to joints and tendons are common in the same athletes.

Osteoarthritis

A joint disease in which the articular cartilage is worn away, so that bone surfaces rub, causing pain, swelling and stiffness.

Overtraining

A fall in performance, with persistent fatigue and frequent infections, caused by heavy training without enough recovery.

Reading the evidence: correlation or cause

Almost all of this evidence is observational. Researchers follow large groups of people for years, record how active they are, and count who develops a disease. What such a study can show is a correlation: the more active group has less disease. A causal relationship, that the activity is what lowers the risk, needs more than that, because three other explanations have to be ruled out.

The first is a confounding variable. Active people, on average, smoke less, eat differently and have higher incomes, and each of those lowers the risk of CVD and diabetes by itself. The second is reverse causation: people who are already unwell, or whose joints hurt, exercise less because of it, so the illness causes the inactivity rather than the other way round. The third is chance, which a large sample makes less likely.

Several things strengthen the case for a cause: a large sample; confounding variables measured and allowed for in the analysis; a dose-response relationship, in which the risk falls steadily as activity rises; the same result in studies of different populations; and a plausible mechanism, such as the glucose uptake and blood pressure effects above. Randomised controlled trials, in which people are allocated to exercise or not, show that exercise lowers blood pressure and improves insulin sensitivity. A trial lasting the decades a disease takes to develop is rarely possible, so the case for exercise rests on trials of these risk factors together with long observational studies of the disease itself.

Causal relationship

A relationship in which a change in one variable brings about the change in the other, rather than both simply varying together.

Keyhole surgery

Medical technology now returns many injured athletes to sport who would once have stopped. The specification names two examples, and the first is keyhole surgery, which on a joint is called arthroscopy.

The surgeon makes two or three small incisions, each about a centimetre long. Through one goes the arthroscope, a narrow tube carrying optical fibres that light the inside of the joint and a camera that shows it on a screen. The joint is filled with sterile saline, which swells it open so there is room to see and work. Fine instruments pass through the other ports to trim or stitch a torn meniscus, smooth damaged cartilage, remove loose fragments, or reconstruct a ligament.

Describe the drawing

A knee joint drawn from the front in simplified form. The femur comes down from the top and ends in two rounded condyles capped with a band of articular cartilage. The tibia rises from the bottom with its own cartilage on its flat upper surface, and a wedge of meniscus sits at each side of the narrow joint space between them. A dashed joint capsule encloses the joint, and the space is labelled as filled with saline. Two straight instruments enter from below on either side: a thick arthroscope carrying light and a camera from the left, and a thinner probe or shaver through a second port from the right, both with their tips in the joint space. A note says both enter from the front of the knee, each through a cut of about a centimetre.

The commonest major repair is of the anterior cruciate ligament, the ACL, which is often torn by a twisting landing. A torn ACL heals poorly because it has a poor blood supply, so it is replaced with a graft taken from the patient's own tendon, usually part of a hamstring tendon or the patellar tendon, threaded through tunnels drilled in the femur and tibia. Because it is the patient's own tissue, there is no rejection. Return to full sport commonly takes nine months or more, because the graft has to remodel into ligament before it can take the loads of competition.

Each advantage in the table follows from the size of the incisions. Less tissue is cut, so less has to heal, less blood is lost, there is less open wound for bacteria to enter, and the patient can start moving the joint sooner, which limits the muscle wasting that inactivity causes. The limits are that the surgeon sees only what the camera shows and works with long, fine instruments, so some repairs still need open surgery.

Keyhole surgery

Surgery carried out through small incisions using a camera on a narrow tube and fine instruments; on a joint it is called arthroscopy.

Prostheses

A prosthesis is an artificial device that replaces a missing or damaged part of the body. Two kinds matter for sport.

A joint replacement is used when osteoarthritis has destroyed the cartilage of a hip or knee. The worn surfaces are removed and replaced with metal alloy components, commonly titanium or cobalt-chromium, bearing on a surface of hard-wearing polyethylene or ceramic. The new joint moves without the pain of bone on bone, so many people return to swimming, cycling, golf and walking. Surgeons usually advise against high-impact running afterwards, because impact speeds up the wear and loosening of the implant.

A limb prosthesis replaces part of a leg or arm. It is attached through a socket moulded to the residual limb, and the fit matters, because a poor socket concentrates the load on small areas of skin and damages it. For running, the lower leg is replaced by a curved blade of carbon fibre. The blade bends as the runner's weight comes onto it, storing elastic strain energy, and springs back as the foot leaves the ground, returning much of that energy to the stride. Knees controlled by a microprocessor adjust their resistance to bending many times a second, so the leg stays stable when walking on slopes and stairs. Running blades let athletes with a leg amputation compete in Paralympic sprints and long jump.

They also bring a question to sports' governing bodies: whether a blade gives its user an advantage over a biological leg. The question has been argued in sport's courts, and it is the same question of fairness that runs through the debate on drugs.

Prosthesis

An artificial device that replaces a missing or damaged part of the body, such as a joint replacement or an artificial limb.

Performance-enhancing substances

A performance-enhancing substance is one taken to improve performance beyond what training and diet achieve. The World Anti-Doping Agency (WADA) publishes a Prohibited List each year. A substance is considered for the list when it meets any two of three criteria: it can enhance performance, it carries a risk to the athlete's health, and its use is against the spirit of sport. Two examples come up repeatedly in exam questions, and both work through biology covered elsewhere in the course.

Anabolic steroids are testosterone and synthetic drugs related to it, such as nandrolone. Like other steroid hormones they are lipid-soluble, so they diffuse through the phospholipid bilayer of the muscle cell. Inside, each binds a receptor protein, and the hormone-receptor complex enters the nucleus and acts as a transcription factor: it binds DNA and switches on the genes for muscle proteins. More mRNA is transcribed, more protein is synthesised, and the muscle fibres grow larger and stronger. Recovery between sessions is also faster, so the athlete can train harder.

EPO, erythropoietin, is a glycoprotein hormone made by the kidneys when the oxygen concentration of the blood is low. It stimulates the bone marrow to produce more red blood cells. Made by genetically modified cells, it is a medicine for the anaemia of kidney failure. In an endurance athlete, injected EPO raises the proportion of the blood that is red cells, so each litre carries more haemoglobin and more oxygen, aerobic respiration in the muscles can continue at a higher rate, and less of the work depends on anaerobic respiration and its lactate.

Not everything that improves performance is banned. Caffeine is permitted, creatine is sold legally as a supplement, and some asthma inhalers are allowed up to a set dose. An athlete with a diagnosed condition can apply for a therapeutic use exemption to take a prohibited medicine, provided it does no more than return them to normal health.

Anabolic steroid

A drug related to testosterone that enters muscle cells, binds a receptor and switches on genes for muscle protein, increasing muscle mass and strength.

EPO

Erythropoietin, a hormone made by the kidneys that stimulates the bone marrow to produce red blood cells.

Should doping be allowed? The ethical positions

The specification asks for the different ethical positions, not for a verdict. An absolutist position holds that an action is right or wrong whatever the circumstances: doping is cheating and always wrong. A relativist position judges each case by its circumstances and consequences, which is the reasoning behind the therapeutic use exemption. Four ethical frameworks are commonly used to organise the arguments.

The arguments against allowing doping. It is cheating: an athlete gains an advantage by breaking rules every competitor agreed to. It harms health, sometimes years later, and athletes often take doses far above medical ones. It removes other people's choice, because once some competitors dope, clean athletes must either take the same risks or accept losing, which is coercion. Young athletes copy their heroes. And it replaces talent and effort, the things spectators come to see, with pharmacology.

The arguments for allowing it. Adults should be free to take informed risks with their own bodies. The line between permitted and banned is hard to draw: sleeping in an altitude tent raises red cell numbers legally, as EPO does illegally, and expensive equipment, coaching and diet already make competition unequal, as do genes. Testing never catches everyone, so undetected users win anyway, and if use were permitted it could be supervised by doctors, which might be safer than covert doping with drugs of unknown quality.

Therapeutic use exemption

Permission for an athlete with a diagnosed condition to take a prohibited medicine, provided it only restores normal health.

Utilitarianism

The ethical position that the right action is the one producing the greatest good for the greatest number of people.