Entropy

Burn Notes

A Small Matter of Life and Death

Nine-year-olds burn 2,000 kcal; for adults, it’s closer to 3,000 kcal, depending on how much you weigh and how much fat you carry. You breathe most of it out as carbon dioxide, and turn a small fraction of it into water (but not necessarily sweat).

Planet of the Apes

The consensus view, that energy expenditure was basically the same across mammals, was based on measurements of BMR, and that seemed to be a glaring issue. BMR is measured with the subject at rest (nearly asleep), so it doesn’t represent all the calories the organism burns each day, just a fraction. Also, BMR can be tricky to measure. If the subject is agitated, cold, sick or young and growing, the measurement can be elevated—and unsurprisingly, much of the primate data came from very young, tractable monkeys and apes.

A Sloth in the Family Tree

Orangutans were burning just one-third of the energy expected for a placental mammal their size. Their daily energy expenditures fell within the lowest 1 percent of placental mammals. The only species with lower expenditures for their body size are three-toed sloths and pandas.

In the wild, males don’t reach maturity, and females don’t have their first baby, until they’re about fifteen years old. Females reproduce incredibly slowly, with seven to nine years between pregnancies, the longest birth spacing of any mammal. Orangutans depend on fruit, but there can be months with so little fruit available that they’re reduced to tearing the bark from trees and scraping the soft inner layer off with their teeth for sustenance. These food shortages seem to affect their social behavior, as they’re the only ape that lives alone; there’s not always enough food to feed a group.

Their metabolic engines had evolved to run slowly, conserving fuel to fend off depletion and death. But the consequences were stark: growth and reproduction require energy, and a lower metabolic rate inevitably meant a slower life history. This in turn meant orangutan populations were slow to rebound from natural or man-made disasters. Their low metabolic rate made orangutans more vulnerable to extinction in the face of habitat destruction.

Primate Power

Primates burn only half as many calories as other placental mammals. To put that in human terms, consider that the normal daily energy expenditure for human adults is between 2,500 and 3,000 kilocalories per day. They showed that a typical placental mammal our size burns well over 5,000 kilocalories per day. But it’s not like those other mammals are incredibly active; they walk a couple of miles per day at most and spend much of their time eating and resting. Their bodies simply burn energy faster, much faster, than our diminished primate metabolism can sustain.

Primate BMRs were similar to those of other mammals, even though daily energy expenditures differed drastically. We think the discrepancy between BMR and total daily expenditure reflects the large size of primate brains.

This Is Us

Humans have larger brains but smaller livers and guts (the stomach and intestines) than other apes. Brains, guts, and livers are all energetically expensive organs—each ounce of tissue burns a ton of calories because the cells in those organs are incredibly active.

In humans, the energy saved by having a smaller gut and liver perfectly offset the energy cost of our larger brain. Based on that important observation, and the observation that human and ape BMRs were broadly similar to other mammals, Aiello and Wheeler argued that the critical metabolic changes in human evolution were changes in allocation, increasing the calories channeled toward the brain while decreasing energy to the guts. In this scenario, daily expenditure stays the same. Humans didn’t spend more energy than apes, they just spent their energy differently.

Katherine Milton showed that leaf-eating primates, with large guts to digest their fibrous diet, had smaller brains than fruit-eating species in the same forests.

Humans have the highest daily energy expenditure, burning about 20 percent more than chimpanzees and bonobos, about 40 percent more than gorillas, and about 60 percent more than orangutans after accounting for differences in body size. BMR differed, too, by the same proportions. Humans in their sample carried twice as much fat (about 23 to 41 percent body fat) as the other apes (about 9 to 23 percent). 

Darwin and the Dietician

Our metabolic engines were not crafted by millions of years of evolution to guarantee a beach-ready bikini body, to keep us fit, or even necessarily to keep us healthy. Instead, our metabolism has been shaped by the Darwinian directive to survive and reproduce. Rather than keeping us trim, our faster metabolism has led to an evolved tendency to pack on more fat than any other ape.

Demystifying Metabolism

One calorie is defined as the energy needed to raise the temperature of one milliliter of water (one-fifth of a teaspoon) by one degree Celsius (1.8 degrees Fahrenheit). It’s a tiny amount of energy—too small to be a useful unit of measure when we talk about food. Instead, when we talk about “calories” in food, we’re actually talking about kilocalories, or 1,000 calories.

Along the way, life had to confront some major challenges in basic chemistry. Oils had to mix with water. Oxygen, a chemical that burns and kills, had to be harnessed for life. Fats and sugars, holding more energy per gram than nitroglycerin, had to be burned carefully for fuel. All the work our bodies do is powered by mitochondria, living within your cells. Mitochondria have their own DNA and their own two-billion-year evolutionary history, including saving all life on Earth from certain doom. And much of the work done to digest your food into usable bits is done by the microbiome. 

Burn, Baby, Burn

ATP molecules are like microscopic rechargeable batteries, which are “charged” by adding a phosphate molecule onto a molecule of adenosine diphosphate, ADP. A gram of ATP holds about fifteen calories of energy (that’s calories, not kilocalories), and the human body only holds about fifty grams of ATP at any given time. That means each molecule cycles from ADP to ATP and back over three thousand times per day to power our body.

When we use food to make energy, what we’re making is ATP. Let’s start with one molecule of glucose, the predominant form of sugar that our bodies use for energy (the story is essentially the same for fructose and galactose).

• First, glucose (C6H12O6) is converted to a molecule called pyruvate (C3H4O3) in a ten-step process that is powered by two ATP molecules but produces four ATP molecules, resulting in a net gain of two ATP. It’s a relatively fast process, and it’s what we use to power short bursts of activity like a 100-meter sprint or to powerlift at the gym.
• This first stage of metabolism is called anaerobic because it doesn’t require oxygen. If there’s not enough oxygen present, either because we’re not breathing effectively or (more likely) because our muscles are working too hard, too fast for oxygen supply to keep pace with all of the pyruvate being produced, the pyruvate gets converted to lactate. Lactate can be reconverted to pyruvate to be used for fuel, but if it builds up, it can also become the dreaded lactic acid, which makes our muscles burn when we’re working hard and pushing our limits.
• The second stage, aerobic metabolism, is where we need oxygen. If there’s sufficient oxygen in the cell, the pyruvate produced at the end of the first stage is pulled into the mitochondria. Pyruvate is converted to acetyl coenzyme A, or acetyl CoA. Along comes oxaloacetate, which is hitched to acetyl CoA and begins to pull it along a circular track called the Krebs cycle. The train will make eight stops, and at each, some carbon, hydrogen, and oxygen passengers get on or off. The coming and going of those atoms generates two ATP. By the final stop, only the oxaloacetate is left. It’s hitched up to another acetyl CoA and the cycle repeats.
• Importantly, some of the passengers are robbed as they get on and off the Krebs cycle train, their electrons stolen away by the molecules NADH and FADH. These NADH and FADH molecules scurry away to the back alleys of the mitochondria and unload their purloined electrons into a special receptor complex in the intermembrane space. When the stolen electrons are deposited into the inner membrane complex, positively charged hydrogen ions chase the negatively charged electrons and end up trapped in the intermembrane space. The hydrogen ions are like fish caught by a weir: they flow through the inner membrane, pulled by the electrons, only to find themselves trapped and crowded in the intermembrane space.
• With all the positively charged hydrogen ions packed together, there is an electrochemical force pushing them out to balance the charge on either side of the inner membrane. But there’s only one way for the hydrogen ions to escape the inner membrane space: a special portal in the inner membrane that’s built like a turnstile. The hydrogen ions stream through the turnstile, driven by the electrical charge. As the turnstile spins, it forces together ADP and phosphate molecules, producing thirty-two ATP. The complex choreography of electrons and hydrogen ions dancing along the inner membrane, called oxidative phosphorylation, is the primary energy generator that powers your body.
• The carbon and oxygen atoms, which make up 93 percent of the mass of a glucose molecule, are converted to carbon dioxide in the conversion of glucose to pyruvate and in the Krebs cycle. The hydrogens bind with oxygen at the end of oxidative phosphorylation, forming water, H2O. We eat carbohydrates only to breathe them out.

Burning Fat, Getting Fat, and Going Keto

We use the exact same steps of aerobic respiration to burn fat. Instead of starting with a glucose molecule, we start with a triglyceride molecule. Triglycerides are broken into fatty acids and glycerol and converted to acetyl CoA (glycerol is transformed to pyruvate first). And just like glucose, the atoms of carbon, oxygen, and hydrogen that make up those fatty acids and glycerols are exhaled as CO2 or formed into water.

If we’re burning a lot of fat, whether we’re on an extremely low-carb diet or starving, some of the acetyl CoA generated will be converted to molecules called ketones. Most ketone production occurs in the liver. Ketones are sort of a traveling version of acetyl CoA, and can travel in the bloodstream to other cells, be reconverted to acetyl CoA, and used to generate ATP. Like a lot of metabolic conversion, most ketone production is done in the liver, but they are used throughout the body.

If you consume no carbohydrates, the only way to generate acetyl CoA is by burning fat. Sure, you can also burn proteins by converting amino acids into ketones or glucose (some amino acids even form molecules that can jump into the middle of the Krebs cycle). But protein is typically a minor player in terms of daily calories. Fat is the main fuel on a low-carb diet, and if you eat fewer calories than you burn, the deficit will be met by burning stored fat for energy. Some of this fat will be processed into ketones prior to burning. The brain generally uses only glucose for metabolism, but if there’s no glucose available, it will switch to burning ketones.

The dark side of converting fats to energy is that the tracks run both ways. A sugar molecule (glucose or fructose) can be converted to acetyl CoA and then jump on the fatty acid track instead of entering the Krebs cycle, and the sugar gets converted into fat. It’s the same process used to convert fat into acetyl CoA, just run in reverse.

Got more sugars than you need? Send the extra glucose and fructose to glycogen. Glycogen stores full? Send the excess sugar to acetyl CoA. If the Krebs cycle train is overcrowded because energy demands are low, start sending acetyl CoA to fat. And there’s always plenty of space available in fat. Glycogen stores fill up, and you can’t store excess protein, but there’s no limit to how much fat you can layer on.

Poisoned by Plants

Oxygen steals electrons and binds to other molecules, altering them completely and often tearing them apart.

At first, the new oxygen produced by plants was absorbed by the iron in dirt and rocks, creating massive, oxidized “red beds” in the Earth’s crust. Then the oceans absorbed as much oxygen as they could hold. After that, the atmosphere began to fill, climbing from 0 percent to over 20 percent oxygen as photosynthetic plants across the globe belched out the noxious stuff unabated and uncaring. As oxygen levels soared, it began to snuff out life, an event known as the Great Oxygen Catastrophe.

Aliens Within: Mitochondria and the O2 Joy

Oxygen-using bacteria swept across the planet, diversifying into new species and families. In the vicious cell-eat-cell world of early, simple life, the proliferating aerobic bacteria would have been a delicious new menu item. When a cell eats another cell (whether it’s an amoeba in a backyard stream gobbling up a paramecium or an immune cell in your bloodstream killing an invading bacterium), it engulfs its prey, bringing the victim inside its membrane to dismantle and burn for fuel. But as uncountable numbers of aerobic bacteria were eaten over hundreds of millions of years, a small handful escaped destruction. Instead, against the odds, they survived intact, living on within their new host. Symbiosis.

With a dedicated energy-producing bacterium on board, these hybrid cells outcompeted others in the battle for turning energy into offspring.

Mitochondria within our cells retain their own strange loop of DNA, a telltale vestige of their bacterial past. And we dutifully feed and tend to them like treasured pets, our heart and lungs dedicated to the task of supplying our mitochondria with oxygen and carting away their CO2 waste. Without them and oxidative phosphorylation, we couldn’t sustain the energetic extravagance we take for granted. 

Oxygen is the final electron acceptor in what is known as the electron transport chain, the bucket brigade that passes electrons along the inner membrane of the mitochondria, pulling hydrogen ions into the intermembrane space. Without oxygen, the electron transport chain stops, the Krebs cycle backs up, and the mitochondria shut down. When electrons jump onto oxygen at the end of the electron transport chain, they attract hydrogen ions, forming water, H2O. Your mitochondria form more than a cup of water each day from the oxygen you breathe in.

On the Shoulders of Giants

Since oxygen and CO2 are indirect measures of energy expenditure, there are some important details that need to be considered when using them to measure metabolism. First, it takes a few minutes of activity before the body reaches a steady state of oxygen consumption and CO2 production. Short bursts of activity, like sprinting or powerlifting, don’t last long enough to reach steady state, and they rely on anaerobic metabolism that doesn’t consume oxygen, making them difficult to measure. Also, the amount of energy burned for a given amount of oxygen consumed or CO2 produced changes a bit depending on whether you’re burning more carbs, proteins, or fats. Conveniently, the mix of fuels can be calculated from the ratio of oxygen consumption to CO2 production (called the respiratory exchange ratio or respiratory quotient) to give an accurate measurement of energy expenditure.

Often, energy expenditures are reported in metabolic equivalents, or METs. One MET is defined as 1 kilocalorie per kilogram of body mass per hour, roughly the energy cost of resting.

• ACTIVITY: METS: NOTES
• Resting: 1.0: Sleeping is a bit lower, 0.95 METs
• Sitting: 1.3: Same for reading, watching TV, computer work
• Standing: 1.8: On two legs
• Yoga: 2.5: Hatha style
• Walking: 3.0: 2.5 mph (4 km/hr) on a firm, level surface
• Sports: 6.0–8.0: Soccer, basketball, tennis, other aerobic sports
• Housework: 2.3–4.0: Cleaning, laundry, mopping, etc.
• High Intensity: 10–13: Navy SEAL training, boxing, vigorous rowing, etc.

Getting Around: The Costs of Walking, Running, Swimming, and Cycling

Walking Cost (kcal per mile) = 0.36 × Weight (pounds)

• Using the equation for walking cost, you’d find that an average 150-pound person burns 54 kilocalories to walk a mile (0.36 × 150 = 54). A smaller person, at 100 pounds, would burn 36 kcal. If we want to factor in the effort to carry a backpack or a baby, we just add the weight of those items to the “Weight” term before multiplying by 0.36. So, a 180-pound person carrying a 20-pound backpack has a total weight of 200 pounds and will burn 72 kcal to walk a mile.

Running Cost (kcal per mile) = 0.69 × Weight (pounds)

Swimming Cost (kcal per mile) = 1.98 × Weight (pounds)

Bicycling Cost (kcal per mile) = 0.11 × Weight (pounds) (at 15mph)

• Cycling costs increase exponentially with speed, and are also affected by factors like wind, road surface, and tire design and pressure (which affect rolling resistance).

A Toyota Prius, at about 3,000 pounds, burns a gallon of gasoline (28,800 kcal) to travel 55 miles, meaning its cost per pound (0.175 kcal per mile) is about 60 percent greater than traveling by bike.

Climbing (kilocalories per foot in elevation) = 0.0025 × Weight (pounds)

Effects of Speed, Training, and Technique

The main way that speed affects cost is straightforward: the faster we move, the faster our muscles have to do the work of moving our bodies, and the faster we burn calories. If running a mile costs 100 kcal, we’ll burn 600 kcal per hour running 6 mph (10-minute mile pace) or 1,000 kcal per hour running 10 mph (6-minute mile pace). In other words, the rate at which we burn energy (kcal per minute, or kcal per hour) will increase directly with speed.

There’s a surprising implication: regardless of how fast you run, you’ll burn the same number of calories per mile. That means you burn the same number of calories to run three miles at your fastest pace as you do to jog it casually—you just burn the calories faster (and finish sooner) when you run fast.

The same isn’t true for swimming, walking, and cycling. For those activities, speed also affects our gas mileage, the energy burned per mile.

Walking at our most economical pace, about 2.5 mph, burns roughly 50 kcal per mile for a 150-pound person. We can think of that as an energetically optimal speed, since it requires the least amount of energy per mile. Walking faster, at 4 mph, will burn roughly 40 percent more energy, about 70 kcal per mile. At around 5 mph, the cost of walking exceeds the cost of running; it’s actually cheaper to run at that speed than it is to walk.

Walking costs (kcal/mile) increase with speed because of the inherent mechanics of a walking gait. We rise and fall with each step, our center of gravity following a roller-coaster trajectory as we walk. That up-and-down movement gets harder to do as we move faster. When we switch to a run, our legs transform from rigid struts to springy pogo sticks, and we bounce from step to step. We still rise and fall with each step, but the springlike mechanics of running result in a flat cost versus speed relationship.

When you swim or bike, you move your body through fluid (water or air), and you lose energy fighting drag. The faster you move, the more drag fights to slow you down. The effect is extremely strong in swimming: increasing your speed just from 2 mph to 3 mph will increase the energy burned per mile by about 40 percent. For cycling, the costs of fighting drag aren’t too noticeable below about 10 mph (which is one reason that air drag isn’t a factor in running). But above 10 mph, the effect of drag really grows. A 150-pound cyclist will spend 15 kcal more per mile to increase her speed from 10 to 20 mph; increasing from 20 to 30 mph will cost 25 kcal more per mile. And all of this assumes there’s no wind, which will affect drag by increasing or decreasing the flow of air relative to the rider. Cycling at 20 mph into a 10-mph headwind will result in the same drag as going 30 mph in still air.

Technique and equipment have similarly unimpressive effects. In Capelli and colleagues’ study of swimming energetics, they report the same costs per mile for athletes swimming freestyle, backstroke, or butterfly (breaststroke was noticeably more costly). Apparently, you can swim in nearly any style and it has little effect on the cost per lap. The same goes for running.

Miles per Donut

Consider a typical 150-pound adult. Even if they get their recommended daily allowance of 10,000 steps per day (about five miles), that’s only about 250 kcal—just about the same number of calories as a 20-ounce bottle of soda (240 kcal) or half of a Big Mac (270 kcal).

A Body at Rest

Background energy expenditure goes by several names: basal metabolic rate, basal energy expenditure, resting energy expenditure, resting metabolic rate, and standard metabolic rate, among others.

Basal metabolic rate, or BMR, is the most well-defined measurement: it’s the rate of energy expenditure measured in early morning with the subject lying down, awake but calm, with an empty stomach (no food for the previous six hours), in a comfortable temperature. If one or more of these criteria isn’t met, the measurement is usually called resting energy expenditure or some variant, with an explanation of the conditions in which the measurement was taken. Basal metabolic rate is the energy your body burns when it isn’t doing any physical work, digesting any food, or working to stay warm.

The bigger you are, the bigger your organs are, and the more work they do each day. It’s not surprising, then, that BMR (in kcal per day) increases with body weight (in pounds) as:

• Infants (0 to 3 years): BMR = 27 × Weight − 30
• Children (3 years until puberty): BMR = 10 × Weight + 511
• Women: BMR = 5 × Weight + 607
• Men: BMR = 7 × Weight + 551

Energy expended per pound is much steeper for small organisms (including small humans) than for large ones. That’s why the slope for infants in the equation above (27) is four or five times steeper than it is for men (7) and women (5). Second, our metabolism changes as we mature and our bodies shift their physiology from growth to reproduction. Body composition also changes at puberty, with women putting on more body fat than men. Fat doesn’t expend as much energy as other tissues, and so, on average, the calories burned per pound is lower for women (5) than men (7).

If most of your weight is fat, your BMR will probably fall below the predicted value. If most of your weight is lean tissue, you’ll likely land above. That’s one big reason people notice their metabolisms “slowing down” as they grow old: we tend to trade muscle for fat as we hit middle age and beyond.

Muscle, Skin, Fat, and Bone

For a typical U.S. adult, muscle accounts for 42 percent of body weight but only 16 percent of BMR, about 280 kcal per day (about 6 kcal/day per pound). Your skin weighs 11 pounds but burns only 30 kcal per day; your skeleton weighs a bit more but burns even less. Fat cells are more active than you might think. They make hormones and traffic in glucose and lipids to maintain energy supply to the body. Still, each pound of fat burns only about 2 kcal per day, for a total of about 85 kcal per day for a typical 150-pound adult with 30 percent body fat.

Heart and Lungs

During exercise, your heart’s output can easily triple. Amazingly, all this work is done for the low, low cost of about 2 calories per beat. Not kilocalories, just 2 calories (0.002 kcal). With a resting heart rate of 60 beats per minute, your heart burns about 8 kcal per hour, the energy equivalent of two M&M’s. The heart accounts for about 12 percent of BMR. Lungs, for comparison, are more than twice as large but burn only about 80 kcal per day, or about 5 percent of BMR.

Kidneys

In addition to maintaining precisely the right amount of water in your body, the kidneys handle the enormous task of clearing out waste and toxins, filtering 180 liters of blood a day. Millions of microscopic sieves (the nephrons) clean every drop of blood thirty times per day, pumping salts and other molecules in and out to eliminate the bad stuff and keep the good. The kidneys also perform an important metabolic task called gluconeogenesis, converting lactate, glycerol (from fat), and amino acids (from proteins) into glucose. All of this metabolic work takes a lot of energy. Together, your kidneys weigh only half a pound, but they burn about 140 kcal per day, accounting for 9 percent of BMR.

Liver

It is the main storage depot for glycogen, and does most of the work converting glucose to glycogen and glycogen back into glucose. It metabolizes fructose into fat for storage or into a burnable form of glucose. The liver breaks apart unused chylomicrons and stores the fat or repackages it into other lipoprotein containers (including the low-density lipoproteins, or LDLs, and the high-density lipoproteins, or HDLs). The liver is the main site of gluconeogenesis, converting fats and amino acids to glucose when needed, and turning the nitrogen-bearing head of amino acids into urea to excrete in the urine. The liver is also the primary site of ketogenesis and it breaks down a wide range of toxins, from alcohol to arsenic. All this ceaseless metabolic work burns about 300 kcal per day, 20 percent of BMR.

Gastrointestinal Tract

The human gastrointestinal tract weighs about 2.5 pounds and burns about 12 kcal per hour, and that’s just at rest on an empty stomach. Digestion costs much more, about 10 percent of the daily calories consumed, or 250 to 300 kcal per day for the typical adult. It’s unclear how much of the energy burned by the gut is attributable our microbiome. A recent study in mice by Sarah Bahr, John Kirby, and colleagues suggests the calories burned by the microbiome might account for as much as 16 percent of BMR in humans, which would mean that the resting energy expenditure of the gastrointestinal tract (about 12 kcal per hour) is attributable almost entirely to gut bacteria.

Brain

Your brain weighs a little less than 3 pounds but burns about 300 kcal per day, accounting for 20 percent of BMR. The high cost of brain tissue is the main reason large brains are so rare among animals. Only under rare circumstances does evolution favor channeling tons of energy into a large brain rather than directly into survival and reproduction.

It runs almost entirely on glucose. Neurons, the gray-matter cells that do the work of cognition and control, sending and receiving signals, do little of their own housekeeping. Instead, the glial cells (white matter), which outnumber the neurons nearly 10 to 1, do much of the support work, providing nutrients and cleaning up waste.

Most of the work the brain does lies entirely outside of our conscious experience. The brain is ceaselessly busy sending and receiving signals to regulate and coordinate every aspect of life, from body temperature to reproduction. Thinking accounts for a tiny fraction of this work, and consequently the costs of cognition are small.

But while thinking is incredibly cheap, learning is quite energetically expensive. Learning is a physical process within the brain. Neurons, with their sinuous dendrites and axons stretching out like the branches of trees, form new connections (called synapses) with other neurons to make new neural circuits. Other synapses and circuits are broken, or “pruned.” Our brains form, strengthen, and prune synapses throughout our lives but by far the most active period is in childhood, when we’re soaking up the world around us. Work by Christopher Kuzawa and colleagues has shown that in children three to seven years old, the brain accounts for over 60 percent of BMR, three times more than in adults.

Beyond BMR

Thermoregulation:

• Mammals and birds have evolved to run hot, and this ramped-up metabolic rate enables us to grow and reproduce more quickly. But there’s a catch: the complex metabolic stew of chemical reactions that keeps us alive needs to be kept within a narrow range of temperatures. If our body temperature rises or falls just a few degrees from normal (98.6°F, or 37°C), we can die. All birds and mammals have a thermoneutral zone, a range of environmental temperatures where body temperature is maintained without any effort. For humans, the thermoneutral zone is roughly between 75°F and 93°F.
• Humans are masters of creating thermoneutral microenvironments next to our skin using clothing and our built environment. Our natural insulation, fat, can shift our thermoneutral zone as well. Adults who are obese have a thermoneutral range that’s a couple of degrees colder than adults who aren’t.
• We can burn brown adipose tissue or brown fat, which makes up a tiny proportion of your body fat. Brown fat creates heat by modifying the electron transport system in its mitochondria: the protons sequestered in the intermembrane space are allowed to leak back through the membrane without producing any ATP. The energy that would be captured in the ATP is lost as heat. 
• The second way we can generate heat is through shivering, which is simply involuntary muscle contraction. Mild cold exposures, like hanging out in shorts and T-shirt in a 65°F room, can raise your metabolic rate 25 percent above your BMR (that’s an additional 16 kcal per hour for most of us). In extreme cold, shivering can cause our resting metabolic rate to climb above three times our BMR, a much larger effect than burning brown fat.

Immune Function:

• We are under constant assault from bacteria, viruses, and parasites.
• To respond to infection, immune system cells proliferate and manufacture a broad range of molecules. All of that metabolic work burns calories. A study of twenty-five U.S. college men who reported to a student health clinic found their BMRs were 8 percent higher, on average, than normal. Notably, the study excluded men who were running a fever. Ramping up body temperature to kill an infection with fever—an ancient mammalian defense—would increase BMR even more.
• Sam Urlacher found that Shuar kids five to twelve years old have BMRs that are about 200 kcal per day higher than kids in the United States and Europe, a 20 percent difference. The energy demand of fighting infection steals calories away from growth. When our immune system responds to an infection, it makes a number of molecules (immunoglobulins, antibodies, and other proteins) that circulate in the blood. Sam found that Shuar kids with more of these markers in their blood grew slower than those who had fewer. The cost of immune response, in terms of both calories and growth, is probably one big reason that indigenous populations like the Shuar, Tsimane, and Hadza tend to be short-statured.

Growth and Reproduction:

• Our bodies are built from a conglomerate of protein, fat, and carbohydrates. The energy content of those building blocks is the same as it is in food: 4 kcal per gram of carbohydrate (like glycogen) or protein (like muscle), 9 kcal per gram of fat. Living tissue also holds a good deal of water (about 65 percent of its weight), which has no calories. As children grow, the energy content of new tissue, which is a mix of about 75 percent lean tissue and 25 percent fat, works out to about 1,500 kcal per pound. To that we have to add the energy burned to do the work of disassembling the nutrients from our diet and reassembling them into tissue, which comes to about 700 kcal per pound. The cost of growth, then, is about 2,200 kcal per pound.
• Adding a higher proportion of fat costs more, whereas adding a higher proportion of lean tissue costs less, because the energy content of fat is more than twice that of protein. One way to see that difference is to look at the energy burned when we lose weight. The energy we expend to lose weight has to be equal to the energy content of the tissue that’s been lost. Since the tissue we lose during weight loss is mostly fat, the general rule is that it takes about 3,500 kcal to burn off one pound.
• For mothers, the cost of growth is only a fraction of the cost of pregnancy and nursing. A newborn baby weighs, on average, between seven and eight pounds. The cost to grow that much baby is only about 17,000 kcal. But the mother also adds tissue of her own (typical weight gain during pregnancy is about twenty-five to thirty pounds) and has to pay the daily metabolic cost of keeping all that new tissue—the fetus plus herself—alive. The total cost of a healthy nine-month pregnancy is about 80,000 kcal. That’s 27 percent more energy than the typical Hadza woman spends walking over the course of a year.
• Milk production for mothers whose children are exclusively breastfeeding costs about 500 kcal per day, which comes out to about 180,000 kcal per year— more than hiking the Appalachian Trail. Some of that energy comes from fat stores built up during pregnancy (about 3,500 kcal per pound lost). And, just as in pregnancy, most of that energy fuels the baby’s BMR and other expenditure. Only a small portion goes to the growth of new tissue.

The Game of Life

More energy for growth and reproduction can also mean larger offspring, which have a better chance of surviving to reproduce themselves. Any other expenditures—immune defense, brains, digestion—are worthwhile only to the extent that they improve the ability, over the long term, to channel energy into reproduction.

Mammals and birds evolved turbocharged metabolisms, burning ten times more calories per day than their reptilian ancestors. In each case, this radical metabolic acceleration was favored by natural selection because it increased energy for growth and reproduction. Mammals grow five times faster than reptiles and channel about four times more energy into reproduction. Birds have similarly high rates of growth and reproductive output.

Reptiles, fish, insects, and other cold-blooded, slow-metabolism groups remain incredibly successful despite the advance of mammals and birds. The earliest members of our group, the primates, evolved a much slower metabolic rate and life history around sixty-five million years ago. Short-term growth and reproduction were reduced, but the slower metabolic rate also stretched out the life span, and lifetime reproductive success improved. 

For each of the major groups of vertebrates—placental mammals (primates and non-primates), marsupials, reptiles, birds, fish, amphibians— metabolic rate increases with body size in a distinct curve. Just as we saw with human BMR, calories per day rises steeply among small animals but grows shallower with larger species. This is Kleiber’s law of metabolism.

• Using measurements of BMR for a range of species, Kleiber argued that metabolic rate increased with body mass to the ¾ power, or mass0.75. Nearly a century later, we now know that the same is true for total daily energy expenditures, not just the portion spent on BMR. Groups differ in the height of the curve (e.g., reptiles have lower curves than mammals) but all have an exponent (the shape of the curve) around 0.75.
• Daily energy expenditure is a function of body size: larger animals burn more calories per day. But an exponent less than 1 means that small animals burn a lot more energy per pound of tissue than large animals. For reasons that still aren’t well understood, the cells of small animals work harder and burn energy faster than the cells of large animals.

Rates of growth and reproduction follow these same distinctive curves. Within birds, mammals, and reptiles, rates of growth and reproduction increase with body mass with exponents in the neighborhood of Kleiber’s 0.75, ranging from 0.45 to 0.82. That means that, for their body size, small animals grow faster and reproduce more than larger animals. A 220-pound caribou female will produce one 14-pound calf each year, equivalent to 6 percent of her own body weight. In that same amount of time, a 1-ounce female mouse will produce about five litters of seven pups each, equivalent to 500 percent of her body weight. The difference corresponds fairly well with the mouse’s ten times higher rate of cellular metabolism. Growth rates compare the same way. Mice grow to thirty times their birthweight in just forty-two days; caribou grow to fifteen times their birthweight and it takes them nearly two years.

One Billion Heartbeats

The biology of death is an area of intense and active research, but researchers have long been aware of an apparent connection to metabolism: the slower a species burns energy, the longer it tends to live.

We know now that faster metabolic rates don’t inevitably mean a shorter life. Small birds, for example, tend to have faster metabolic rates than mammals of the same body size, but generally live longer.

The free radical theory proposes that aging is the accumulation of damage caused by toxic by-products of oxidative phosphorylation. In the electron transport chain, the end process of making ATP in the mitochondria, oxygen molecules are occasionally transformed into free radicals (also called reactive oxygen species), which are oxygen molecules that have lost an electron. These mutant oxygen species are voracious, and they rip electrons from surrounding molecules, causing damage to DNA, lipids, and proteins. Harman argued that aging is the accumulation of damage (sometimes called oxidative stress or oxidative damage) from these free radicals. Since free radicals are an unavoidable by-product of making ATP, it follows that our cells’ metabolic rates (which are also their rates of ATP production) determine how quickly we age and die.

• The free radical theory of aging has its problems. For one, studies of antioxidant consumption in humans and other animals don’t always show the expected effects on life span. The difficulties in finding clear, strong links between metabolism and longevity have left some researchers lamenting whether such links exist at all.

The Devilish Arithmetic of Daily Energy Expenditure

The factorial method, is crude, but it seems to give reasonable results. And it remains alive and well today: it’s still used by the World Health Organization to figure out daily caloric needs for populations they work with, and it’s the math behind every online calculator that estimates your daily calorie needs from some combination of height, weight, age (all used to estimate your basal metabolic rate) and your level of physical activity (used to assign an average daily PAR value). However, it’s just a good guess.

• It assumes that daily energy expenditure is simply BMR plus the costs of physical activity and digestion. That view has become so accepted and widespread that it’s hard to imagine any other perspective. It’s what every student in nutrition and metabolism is taught, what every aspiring doctor learns in medical school, and it’s the guiding faith of every exercise weight-loss program. The bottom line is that your daily activity level has almost no bearing on the number of calories you burn each day.

Don’t Bother Asking:

• In a recent study of 324 men and women across five countries, adults underreported actual food intake by 29 percent on average. That’s the equivalent of forgetting an entire meal every day. Reported energy intake didn’t track expenditure whatsoever. Diet surveys are just random number generators, and the data they provide on daily calorie consumption are useless. The only way to make them worse than useless is to treat them like real data and base a nutritional program on them.

The Ballad of Nathan Lifson:

• The hydrogen and oxygen atoms in our body water pool are in constant flux, entering the body water in our food and drink and leaving the body as urine, feces, sweat, and the water vapor in our breath. In his early work, Lifson figured out that the oxygen atoms in the body water pool have an alternative way to leave the body. When carbon dioxide is formed during the metabolism of some carbon-based molecule, one of the oxygen atoms in the new CO2 molecule is taken from the body water. That oxygen atom is then exhaled in the CO2 that we breathe out. The bottom line is this: hydrogens leave the body only as water; oxygens leave as both water and CO2.
• Lifson realized that if he could track the rate of hydrogen and oxygen atoms leaving the body, he would be able to calculate the rate of CO2 production. And since you can’t burn energy without making and exhaling CO2, Lifson knew that if he could measure the rate of CO2 production, he could measure energy expenditure. As long as he could track their rates of hydrogen and oxygen flow with the occasional urine sample, the subjects could do whatever they liked.
• If 10 percent of the hydrogens in the subject’s body water were deuterium on Monday, but only 5 percent of them were deuterium on Wednesday, he would know that half of the body water from Monday had been flushed out and replenished with normal H2O. He then could use those measurements to calculate the rate at which hydrogen atoms were lost. The same approach would tell him the rate of loss for oxygen atoms. The difference between those two rates had to reflect the rate of CO2 production. 
• The amount of isotope needed for the measurement is proportional to body size. That made studies in mice or other small animals relatively cheap, but posed a challenge for human work. In 1955, the amount of isotope needed for a 150-pound human would cost more than $250,000 in today’s dollars. By the 1980s, deuterium and oxygen-18 were cheap enough to measure an adult human for just 1 percent of what it would have cost in the 1950s or ’60s.

The Doubly Labeled Water Revolution

These days, labs like the author’s can measure a person’s daily energy expenditure using doubly labeled water for about six hundred dollars.

The biggest predictors of daily energy expenditure are the size and composition of your body. Bigger people are made of more cells, and more cells doing more metabolic work burn more calories each day. Some of our organs and tissues burn more calories than others. Most importantly, fat cells burn a lot less energy each day than lean tissue, the cells that make up our muscles and other organs. If fat cells make up a larger proportion of your body weight, you will burn fewer calories each day than a person who weighs the same but is leaner. Since women tend to carry more body fat than men, women tend to burn fewer calories each day than men who weigh the same.

You can plug your body weight into the appropriate equation and calculate an estimated daily energy expenditure. Notice, though, the ln function in each equation. That means you need to take the natural logarithm of weight before multiplying the result by 786 (females) or 1,105 (males) and subtracting the appropriate intercept value. A 140-pound woman has an estimated daily energy expenditure of 2,300 kcal per day. For a 160-pound man, expected daily energy expenditure is 3,000 kcal per day.

Daily expenditure rises steeply with body size in children. Their cells burn much more energy each day than larger, older people. If you’ve ever held a baby close and felt her heartbeat thrumming in her tiny chest, you have a sense of how hard her body is working. Each pound of a typical three-year-old kid burns about 35 kcal per day. That number steadily declines through childhood and adolescence, flattening out at around 15 kcal per pound each day in our early twenties. The curved relationship between body weight and daily energy expenditure means that we need to be thoughtful when we compare energy expenditures among individuals.

Often, people simply divide energy expenditure by weight as a way of comparing metabolic rates among different-sized people. The assumption underlying that approach is that energy expenditure per pound ought to be the same for everyone. But that’s not how it works. Because the relationship between size and expenditure is curved the way it is, smaller people inherently burn more energy per pound than larger people.

Many populations fall above or below the trend line—their expected daily expenditure—by 300 kcal per day or more. This is the dirty little secret of online BMR and daily expenditure calculators: there is a ton of variation in metabolic rates even after we account for body size and gender. When you plug your info in and get a daily expenditure or BMR back, you need to take that number with a large pinch of salt.

Hard Living

Our ancestors were hunting and gathering only a few hundred generations ago. In the industrialized human zoos that we’ve built for ourselves in the United States, Europe, and other developed societies, we have become much more sedentary. Modernization has brought with it a number of important innovations that improve and extend our lives, from indoor plumbing to vaccines and antibiotics. But by several measures we’ve also become much less healthy. Obesity, type 2 diabetes, heart disease, and the other major killers in the developed world are virtually unheard of among hunter-gatherers and subsistence farmers. Many in public health believe that these diseases of civilization are due in part to a reduction in daily energy expenditure resulting from our sedentary modern lifestyles.

Things Get Weird

Hadza men and women were burning the same amount of energy each day as men and women in the United States, England, the Netherlands, Japan, Russia. Somehow the Hadza, who get more physical activity in a day than the typical American gets in a week, were nonetheless burning the same number of calories as everyone else.

Constrained Daily Energy Expenditure

Daily energy expenditure wasn’t simply responding to differences in daily activity. Instead, the body seemed to be maintaining daily energy expenditure within some narrow window, regardless of lifestyle. I call this view of metabolism “constrained daily energy expenditure.”

Like the Hadza, the Shuar live an incredibly active lifestyle, hunting, fishing, and gathering plant foods from the wild. They also farm a bit, using hand tools and a lot of hard work to grow and harvest starchy staples like manioc and plantain. Sam measured daily energy expenditures among five- to twelve-year old Shuar kids and compared them to kids from the United States and U.K. The Shuar kids were more physically active, and they also had elevated BMRs due to higher levels of parasites and other infection. Nonetheless, their daily energy expenditures were identical to those of U.S. and British children.

Further south, in Bolivia, Mike Gurven and his team measured daily energy expenditure in men and women among the Tsimane, who, like the Shuar, make a living hunting, fishing, and farming in the Amazonian rain forest. We analyzed the doubly labeled water samples in my lab. The Tsimane rack up as much physical activity each day as the Hadza, roughly ten times that of Americans. Tsimane men and women showed slightly elevated daily expenditures, but not due to physical activity. Like Shuar kids, Tsimane adults have elevated BMR because of their high rates of parasitic and bacterial infection—their immune systems are working overtime. Once you account for their incredible immune activity, there’s no evidence of higher daily energy expenditures as a consequence of their strenuous lifestyles.

Even among industrialized countries, there’s no correspondence between measured physical activity and daily energy expenditure, activity energy expenditure, or PAL ratios. People who work harder don’t necessarily burn more calories.

They pooled everyone together and adjusted their daily energy expenditure to account for the effects of body weight, fat percentage, age, and other characteristics, and plotted their adjusted expenditures against daily physical activity. There was a ton of variability among people even after accounting for body size and body fat. The effect of activity was weak and it petered out at higher activity levels. People who were moderately active burned about 200 kilocalories more, on average, than total couch potatoes, but there was no difference between moderately active adults and those with the highest levels of physical activity.

Constrained daily energy expenditure seems to be the rule among warm-blooded animals. Several laboratory studies in rodents and birds have measured daily energy expenditures while increasing daily physical activity—not so different from Westerterp’s half-marathon study. Again and again, we see the same result: daily energy expenditure doesn’t change even as the animals work harder and harder.

Trying to Outrun Obesity

The modern explosion in obesity and all its downstream effects can’t be blamed on decreasing energy expenditures in industrialized countries. Doubly labeled water studies in the industrialized world, which stretch back to the 1980s, seem to confirm this: daily energy expenditures and the PAL ratio have stayed the same in the United States and Europe for the past four decades, even as obesity and metabolic disease have skyrocketed.

Second, constrained daily energy expenditure means that increasing daily activity through exercise or other programs will ultimately have little effect on the calories burned per day. Weight change is fundamentally about energy balance: if we eat more calories than we burn, we gain weight; if we burn more than we eat, we lose weight. The widespread evidence that daily energy expenditure is constrained tells us that durable, meaningful changes in daily energy expenditure are extremely difficult to achieve through exercise. If the energy burned is really difficult to budge no matter how much we exercise, we’d be better off battling obesity by focusing on the amount of energy we eat. Exercise will keep you healthy and alive. It just won’t do much for your weight.

Our metabolic engines are exquisitely tuned to match the energy we burn each day with the energy we eat, and vice versa. (In fact, that’s probably why animals evolved constrained daily energy expenditure in the first place: to match expenditure to the amount of food available.) Even transient increases in daily energy expenditure are met with increases in energy intake. When we burn more, we eat more.

All studies that try to achieve weight loss through exercise show the same pattern: the longer the study lasts, the less that weight loss meets expectations. For the first couple of months in a new exercise program, results are all over the place. People generally lose weight, but there’s a huge amount of variability in how they respond in the short term (some people even gain weight). But after a year, even with someone watching them exercise so they don’t skip or cheat, the average amount of weight lost is less than half of what’s expected. By two years, the average amount of weight lost is less than five pounds, and many, as we see with the Midwest studies, will lose nothing.

The other important change is that exercising drives us to eat more. Our brains are exceptionally good at adjusting our hunger levels so that we make up for any increase in expenditure by increasing intake.

Obese people burn just as much energy each day as thin people, after accounting for differences in body size and composition (in fact, if you don’t correct for body size, obese people tend to burn more calories each day simply because they’re larger). And daily energy expenditure, high or low, doesn’t predict anything about your likelihood of gaining weight.

We Are All the Biggest Loser: Metabolic Responses to Overeating and Undereating

By week 30, Biggest Loser contestants’ BMRs had dropped nearly 700 kcal per day, or about 25 percent. The reduction in BMR wasn’t just a function of weighing less; it was far greater than expected from weight loss alone. Their cells had reduced their metabolic rate, working and burning energy more slowly. And the changes weren’t temporary. When Hall and colleagues checked in with the contestants again six years after the show, their BMRs were still lower than expected. 

There are ancient, evolved responses to negative energy balance in humans and other animals. When our bodies sense that we’re not eating enough to meet our daily energy requirements, we start throttling things down. The body struggles to balance its energy budget so that expenditure doesn’t exceed intake. Our thyroid gland reduces the amount of thyroid hormone produced, which is like taking your foot off the gas pedal. Our cells slow down, which lowers BMR and daily energy expenditure. At the same time, the hormones and brain circuitry that control hunger increase our drive for food. We become ravenous, fixated on food as our body directs our mental energies toward finding something to eat. 

Ancel Keys and colleagues at the University of Minnesota took thirty-two young men and put them on a semi-starvation diet for twenty-four weeks. The men ate just 1,570 kcal per day, less than half of their estimated daily energy expenditure at the start of the study. They lost 25 percent of their body weight. Unsurprisingly, their irritability and moodiness increased, while their interest in sex and other activity fell. They were constantly hungry, obsessed with food. BMR dropped 20 percent below that expected for their body weight.

• All of these changes went away when the men were allowed to eat again. As their weight came back, their bodies called off the alarm. Unlike the Biggest Loser contestants, their BMRs returned to normal, as did their mood and interest in sex and other hobbies. They were no longer in starvation mode. Notably, the men overshot their initial weight when they regained after the study, putting on a couple more pounds of fat than they had had at the start of the study.

BMR and daily energy expenditure don’t dictate weight change, they respond to weight change. The Biggest Loser contestants were in starvation mode during and after the competition. Their lower BMRs and daily expenditures were a desperate, evolved strategy to keep expenditures in line with their severely reduced intake. In the years following the show, contestants who ate the most and regained the most weight gave their bodies the strongest signals that the danger of starvation had passed. Their BMR and daily expenditures rebounded along with their body weight.

The Brains Behind the Operation

In concert with your brain stem, the hypothalamus senses energy coming in by monitoring the blood for factors like glucose and leptin, and neural signals from the taste buds, stomach, and small intestine that relay information on the size and macronutrient content of a meal. The hypothalamus can also sense when we’re in negative energy balance, monitoring levels of ghrelin, leptin (which decreases when fat cells are depleted), and other cues. In response, the hypothalamus can crank our metabolism up or down by controlling the activity of the thyroid gland and the production of thyroid hormone. It can also change our hunger levels, adjusting the amount of food we need to eat to feel full.

The variables (leptin, ghrelin, blood glucose, stomach fullness, food flavors) are the same for everyone, but our immediate environment, genetics, and past experience shape the way the system weighs each variable and responds. For example, lower leptin levels generally push the hypothalamus to activate the hunger response, but the precise threshold at which leptin will trigger your hunger response will have a lot to do with your genes, eating habits, and the typical levels of leptin circulating in your blood.

When we’re in starvation mode, the hypothalamus acts quickly. The objective is to survive the lean period to reproduce sometime in the future when conditions improve. Within days, thyroid hormone plummets. BMR goes way down. If food restriction is severe and lasts for a long time, our organs will actually shrink. But not all organ systems are hit equally hard. We know from careful studies of the bodies of victims starved to death in war and famine that the brain is spared. The spleen, on the other hand, shrinks dramatically.

The hypothalamus controls nearly every system in the body, from stress response to reproduction, and can manipulate specific functions. For example, humans are quick to put reproduction on the back burner when times are tough. Subjects in starvation experiments lose their interest in sex. Women often see a decline in estrogen levels and, if the food restriction is sufficiently severe, will stop ovulating.

In the immediate term, hunger is increased in order to match intake to expenditure (exercise). If high levels of daily activity persist for weeks or months, though, other changes are made. Other systems, including reproduction, immune function, and stress response, are suppressed, making room in the budget for greater activity costs. 

Behavior may change as well, inducing us to rest more and fidget less. We should expect these responses to follow an evolutionary logic, cutting nonessential tasks first and prioritizing our long-term reproductive success. In three to five months, we’ll be acclimated to our new exercise regimen. Daily energy expenditure will be nearly the same as before we started.

Today, in the grips of an obesity epidemic, the average American adult gains about half a pound per year, an error of around 1,750 kcal. That’s only about 5 kcal per day, or less than 0.2 percent of daily energy expenditure. In other words, without thinking much about it, we match our daily energy intake to within 99.8 percent of our daily expenditure (and vice versa).

A Smarter Way of Thinking About Metabolism and Obesity

Our Paleolithic brain is overwhelmed by our modern environment. Rather than perfectly matching intake to expenditure, we have a tendency to overeat—not by much, usually, but the error is consistent and it adds up over time as fat.

When we blame our metabolism for our struggles with obesity, or we rely on exercise to increase daily expenditure and lose weight, or we fall for the latest metabolism-boosting scam, we are making a fundamental mistake about the way metabolism works. The global obesity epidemic cannot be a problem of energy expenditure. For one thing, as we see with the Hadza, daily energy expenditures are the same today in the industrialized world as they were in our hunter-gatherer past. Our bodies are incredibly adept at responding to changing activity levels to keep daily energy expenditures within a narrow window. But more crucially, blaming obesity on slow metabolism gets the cause and effect of weight change completely backward. Our metabolism doesn’t dictate energy balance, it responds to energy balance.

It’s still the case that obesity is fundamentally a problem of taking in more fuel than our engines burn. But rather than pretending we’re in the driver’s seat, we should be asking why the evolved mechanisms that normally match intake precisely to expenditure are failing in our industrialized world.