Humans and animals produce energy to fund their daily activity. How much energy we produce at any time depends on what we are doing; our bodies have evolved various pathways to supply the correct amount of energy -- but there are limits.
For example, when we rest or do gentle exercise, aerobic (in presence of oxygen) energy production is sufficient, but in situations where the need to supply lot of energy appears suddenly - as in a 100 metre sprint - the body can produce the extra energy very quickly using anaerobic metabolism without requiring oxygen. While the resting metabolic rate (aka basal metabolic rate or BMR) is of the order of 75 W (or 1550 Calories per day; 1 Calorie = 1000 calories used in physics) for a typical adult male, peak demand in a 100 meter sprint may rise to 2500 W or more - an increase of about 35 times over the BMR value. Energy production by the body at such high levels over an extended period is totally unsustainable (you quickly run out of reserves). Similar situations happen in many other activities, e.g. in long distance endurance running or cycling events, where sustained energy production at a much higher level than BMR is ideally desired but has been found to be limited to only a few times BMR.
BMR is the energy expenditure of a person at rest not having eaten for 12 hours. BMR accounts for more than half of daily energy expenditure and includes normal body cellular homeostatis, cardiac function, brain and other nervous functions etc. The table shows how BMR budget is used by vital organs - meeting this energy demand is an absolute priority for the body.
The aim of this publication is to examine the evidence regarding the limits of energy production in humans during high-endurance/high-demand situations.
World record times in running/walking events are a good place to start:
Swimming records follow a similar trend - swimming requires much greater expenditure of energy - for 100 m freestyle, the world record time is 46.91 seconds.
I shall look at two activities at extreme ends of the endurance spectrum:
(1) One hundred meter sprint is probably the most energy demanding race where an explosive release of energy over an extremely short period of time, of the order of 10 seconds, is required. It will be instructive to see how the runner manages the demand.
(2) Race across the USA (RAUSA) in which athletes run a marathon (42.2 km per day), 6 days per week for 20 weeks to cross the USA from the Pacific to the Atlantic coast. In RAUSA, the runners must sustain a high level of energy production over an extended period.
The slide summarises the observed situation:
100 Meter Sprint: The world record of 9.58 sec. was set by Usain Bolt in 2009 in Berlin. His remarkable sprint has been the subject of many analyses. I discuss the details in the following.
Usain Bolt at, 90 kg and 6'5" or 1.956m is a tall person and during the sprint, his stride averages 2.45 meters.
The 100m sprint is almost wholly anaerobic with aerobic respiration contributing only about 5% of the energy.
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Biochemical Systems of Energy Production in Humans: Muscles need energy to do work. Our bodies have three main pathways for producing energy - in all of them, ATP (adenosine triphosphate - an adenosine molecule with three phosphate groups) is converted to ADP (adenosine diphosphate) in an exothermic (energy generating) hydrolysis (breakdown with water) reaction. In order to meet sudden energy demands, the body keeps a reserve of ATP by converting ADP to ATP with energy from available nutrients. The slide gives a summary:
There is some ATP stored in the muscle cells - about 100 gm - this ATP is available for energy production right away but it lasts for only 2 to 3 seconds.
Muscles also have about 120 gm of the chemical creatine phosphate (PCr) which is converted to ATP by an enzyme present. This can produce energy very quickly but the supply of PCr lasts only about 10 seconds. With available ATP and PCr, the body is capable of producing a burst of energy that can be 60 or 70 times higher than BMR - particularly useful in sprints and weight lifting. One could say that evolution provided this facility to enable a fight or flight syndrome when facing a life-threatening situation.
The next stage is for muscles to use the much larger store of glycogen which is a complex carbohydrate made of many branches, each branch contains 8 to 10 glucose molecular units. The body can break down glycogen into glucose (glycolysis) and produce ATP without using oxygen (anaerobic metabolism). However, in this process lactic acid is produced and causes muscle soreness and fatigue. After 2 minutes, glycolysis is no longer able to meet high energy demands due to the build up of lactic acid in muscle fibre.
Aerobic energy production is always present and uses glucose (in the blood stream or from the breakdown of glycogen) to produce ATP in presence of oxygen. It is a much slower process and not able to provide the burst of energy required in, for example, 100 meter dash. Supply of oxygen to muscles is a complex process involving breathing, heart rate and flow of haemoglobin in the blood - a faster rate of breathing, an increased heart rate, higher pumping force for the blood are required for increasing supply of oxygen. It is estimated that aerobic energy production rate is limited to about 15 times BMR. More on this later...
Aerobic energy production supports long distance runners as in a marathon where a continuous steady rate of energy production over a long period of time is sought. For exercise to continue, the exercise level needs to drop to a level that allows the aerobic metabolism (aka respiration) to be able to produce enough energy to meet the demands made.
Aerobic Respiration: For majority of sports and human activities, aerobic respiration (AERESP) is the main energy production pathway and warrants a more detailed discussion - particularly also due to its relevance for long duration endurance exercise.
In AERESP, glucose is the fuel that 'burns' in oxygen to produce carbon di-oxide (CO2) and water as the end waste products with release of energy. Oxygen is taken up by lungs from the atmospheric air, diffuses to the alveoli and binds to haemoglobin (HG) of the red blood cells (RBC) in the capillaries. The heart pumps the oxygen-rich blood to the muscles, where oxygen diffuses to the mitochondria of the muscle cells. In the mitochondria, oxygen is metabolised to form ATP and produce energy. CO2 is cleared into the atmosphere following a reverse transport path. In the muti-step gas transport system, the capacity of each step is important in determining the maximum energy production possible in AERESP. Factors like lung capacity, breathing rate, oxygen diffusion rate in the region of the alveoli, haemoglobin concentration in the blood, blood volume, and heart pumping rate determine the amount of oxygen that can be delivered to the mitochondria in muscle cells. If any of the above factors are below par then the overall efficiency of oxygen transport will be reduced with corresponding effect on the amount of energy produced.
Blood, Haemoglobin & Red Blood Cells: Human blood is 45% RBC and 55% blood plasma and optimally contains 150 gram haemoglobin per litre (humans have 65 mL of blood per kilogram of body mass; ~6.5% of body volume). Higher concentrations of haemoglobin would increase the viscosity of the blood and can be problematic in causing additional burden on the heart.
How much and how strongly oxygen may be bound to haemoglobin is an interesting question. How strongly oxygen is bound to the haemoglobin is a compromise due to the need to release oxygen from haemoglobin to the mitochondria in the cells. In humans, haemoglobin is completely saturated at an oxygen partial pressure of 100 mmHg. In atmospheric air, the partial pressure of oxygen is 21/100 * 760 = 276 mmHg and blood haemoglobin is fully saturated in the lungs. Haemoglobin releases half of its oxygen in muscle cells where the partial pressure of oxygen is about 25 mmHg. Dissociation of oxygen also depends on the temperature of the tissue - active muscles are warmer and more oxygen is released from the haemoglobin.
A final interesting observation in the gas transport system is the size of the red blood cells which is 0.0075 mm (7.5 microns) in humans (RBC is of constant size of about 5 to 8 microns in most mammals). This determines the lower limit of the blood capillary diameter in the lungs as 0.01 mm (or 10 microns) to allow efficient blood flow in these constricted spaces.
Glycogen: Glucose and glycogen are the primary fuels for AERESP.
Human blood stream contains about 4 gram glucose that is available for immediate use by all organs. The hormones insulin and glucagon maintain blood glucose homeostatis (normal state) to satisfy the energy needs of various organs in the body.
Liver stores about 120 gm of glycogen which can be broken down into glucose and introduced into the blood stream. Muscle cells store about 400 to 500 gram of glycogen solely for use to produce energy in the muscles. It is not shared with other cells in the body. Small amounts of glycogen are also present in other tissues and cells, including kidneys, red and white blood cells and gilia cells in the brain. The uterus also stores glycogen during pregnancy to nourish the embryo.
An observation: Anaerobic energy production is quite inefficient - producing only 2 ATP molecules from each glucose molecule that is metabolised. Aerobic respiration, on the other hand, produces 35 ATP molecules. Our planet's atmosphere only became oxygen rich (21%) about 1.5 billion years ago. Prior to that for 2 billion years life was still abundant, supported by anaerobic energy production. Availability of oxygen (which was toxic to the then-existing life forms and caused the so-called oxygen catastrophe until organisms learnt to metabolise oxygen for energy generation) gave various life forms much enhanced capabilities to grow in size with far superior mechanical performance - evolution of more complex life forms became possible.
Three Stages of Cellular Metabolism: Humans mainly use two macronutrients - carbohydrates and fats for energy production. Proteins are primarily used to build & repair tissue, make enzymes, hormones, muscles, skin, blood, bones etc. As a last resort, proteins can also be metabolised to produce energy. Ths subject of cellular metabolism is highly complex; in the following, I present a brief and uncomplicated description as to how macronutrients are metabolised by the body to produce energy. Detailed discussion of the subject is available in 1, 2, 3, 4.
The metabolism of macronutrients proceeds in 3 main stages. I have prepared the following three slides to explain the process.
Stage 1: In the digestive system, the large macromolecules of carohydrates, fats and proteins are broken down to their simple subunits of glucose and fructose; fatty acids and glycerol; and amino acids respectively. These are stored in the liver and muscle cells. Fructose can only be processed in the liver where it is converted to glucose and stored as glycogen. Extra fructose is efficiently converted to fatty triglycerides and stored in fat and muscle cells (a potent route for non-alcoholic fatty liver disease!).
Stage 2: The simple subunits produced in the digestive system are transported to the muscle cells by the blood stream. In a 10 step process, called glycolysis, initially enzymes use 2 molecules of ATP to produce 4 units of ATP and 2 pyruvate molecules. The net gain of ATP makes this process energy generating and is the basis of anaerobic (without oxygen) energy production as in the case when a sudden demand for energy is made. Pyruvate is excreted from the muscle cell in the form of lactates. Build up of lactic acid causes muscle soreness and fatigue.
Stage 3: Pyruvate molecules formed in the cytosol are transported into the mitochondria where enzymes convert pyruvate, fatty acids and amino acids into acetyl CoA. Carbon di-oxide is also released and is transported to the lungs for expiration.
Now it gets complicated:
Acetyl CoA enters the citric acid cycle - also called the Krebs Cycle (Hans Krebs was awarded the 1953 Nobel Prize for discovering the citric acid cycle). In this process, which is cyclic, Acetyl CoA is converted to other molecules (NADH and FADH2) with large amount of chemical energy. Carbon di-oxide is also produced. Figure 3 in Kreb's Nobel Lecture describes the citric acid cycle and is worth reading.
The citric acid cycle products are fed into the oxidative phosphorylation or electron transport chain. Oxygen is required for this process to work (aerobic respiration). Peter Mitchell was awarded the 1978 Nobel Prize for elucidating the many steps of the process. I must say that his Nobel lecture is quite difficult to read.
Essentially, electrons from NADH and FADH2 enter the electron transport chain (a complicated series of chemical reactions mediated by enzymes), and in several steps they are passed on to acceptors with release of energy. In the final step, electrons from the last receptor are passed on to oxygen (most electro-negative of all acceptors) which then forms water - a waste product of the reaction.
A small percentage of electrons do not complete the whole series and instead directly leak to oxygen, resulting in the formation of the free-radical superoxide, a highly reactive molecule that contributes to oxidative stress and has been implicated in a number of diseases and aging.
A sustained energy production rate of about 5 times the resting metabolic rate (generally called sustained metabolic scope or SusMS) is considered the limit in human endurance activities. This limitation is generally assumed to be due to the CR system - the nutrients (glucose and fatty acids) are assumed to be available in sufficient quantity.
The availability of nutrients is obviously not a problem in short duration exercise as the body stores glycogen in the muscles and fat in the adipose tissue in sufficient quantities. However, these are quickly reduced in endurance events lasting several weeks. The body also has to prioritise nutrient availability to ensure that vital functions like brain, heart, breathing, thermoregulation etc. have sufficient resources to operate effectively. A recent study finds that in endurance events like race across the USA (RAUSA) lasting 14 to 20 weeks where athletes run one marathon per day, six days per week, SusMS is limited to about 2.5 times BMR. An endurance event, completely different from athletics, is a mother's high energy demand during pregnancy and lactation where metabolic scope peaks at about 2.2 times BMR.
The RAUSA study attributes the limiting value of SusMS to the inability of body's digestive system to metabolise food at a rate fast enough to match the cardio-respiratory system. I find this a surprising, somewhat counterintuitive finding as one would think that there are always enough nutrients available and the limitation is the CR system's ability to transport and deliver sufficient oxygen to the mitochondria. The situation is obviously more complex.
The idea in the RAUSA study was quite straightforward. Twenty three athletes received food as and when they needed, but six of the athletes were overfed. The study measured their metabolic scope (how much energy they are generating in units of BMR) and also monitored any weight gain or loss. The energy intake for an athlete is just the sum of the measured metabolic scope and the energy equivalent of weight loss (a negative number) or weight gain (a positive number).
Weight loss studies give 7650 Calories as the energy equivalent to one kilogram of weight change (usually quoted in popular literature as 3500 Calories needed to make a difference in weight by 1 pound).
The slide shows the results obtained:
Discussion: Evidence that most human endurance activities are capped at 2.5 BMR appears counterintitive and does not immediately make good sense. However, our physiological functions have been optimised over many million of years and it is interesting to speculate why we might have evolved this way. This is what I think:
First, let us look at the survey of physical activity levels (PAL) of populations distributed on our planet. People in developing countries (low human development index - HDI) work hard in farming and other physically demanding chores. In the rich countries (high HDI), people have sedentary life style and many labour saving gadgets - they do not move about as much. One would think that PAL in developing countries will be much higher than in developed countries. That is not the case at all - as I show in the following table: The data is for people with a body mass index in the range from 23 to 27 (healthy active people - not obese).
Mean PAL Values in units of BMR
Men in Low HDI countries PAL = 1.88 ± 0.06
High HDI countries 1.79 ± 0.02
Women in Low HDI countries 1.70 ± 0.03
High HDI countries 1.71 ± 0.02
These numbers suggest that energy demand is pretty constant for most populations and this is what our bodies evolved to supply in a secure way. There might be situations, like confronting a lion, when we need to boost energy almost instantly - this is no different than the situation in a 100 meter sprint - and the body has mechanism to look after that. Taking the mean PAL as 1.85 x BMR, it seems that we are capable of sustained work output at about 35% more intensely than the average demand. Of course, short term extra demands over a few days may be met by drawing on nutrient reserves in the body. It appears that evolution has designed the human system optimally.
While the RAUSA study points to the digestive system's failure to support higher SusMS, it is not clear if other factors like the waste disposal organs work as efficiently after many weeks of operation at an elevated level. The cardio-respiratory system involves many enzymes and muscles and when called upon to function at an elevated level for long periods - will it show some sort of fatigue affecting overall metabolic efficiency?
The body also needs a minimum level of vitamins and minerals to synthesize essential hormones, enzymes and other chemicals. It is not clear, if during periods of sustained elevated demand, the nutrition requirements were fully met in the RAUSA study. There are many unanswered questions that I am sure will be addressed in future studies.
We look forward to much interesting research in this context.
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