Through Thick and Thin

kindle helpIn The Real Bathroom Scales, we verified two important facts. First, we confirmed that the body responds to alterations in calorie balance with a combination of adjustments to energy storage (body mass) and to energy usage, the latter being mostly via changes to TEF and NEAT. Second, we saw that there was a wide variance between individuals in their rate and degree of adaption via the energy expenditure variables. In fact, in the Mayo Clinic NEAT study, the change in expenditure in response to an added 1,000 calories per day ranged from a low of +107 cals to a high of +917 cals, a nine-fold difference!1 So what drives these vast differences in our ability to adapt to changes in intake, such that some of us pile on the pounds, while others never seem to gain an ounce? While there are myriad biological abnormalities that can lead to obesity, most of them are uncommon, such as leptin deficiency, adrenal tumors, or genetic diseases such as Prader-Willi Syndrome. Most common obesities, on the other hand, can be directly linked to poor function or signaling of the sympathetic nervous system. The SNS is a primary regulator of many of the body’s homeostatic mechanisms, not the least of which is energy balance. The effects of the SNS on energy balance are achieved through the binding of catecholamines (adrenaline and noradrenaline) to a series of receptors known as the adrenergic receptors. “Greek Alphabet Soup” There are two basic types of adrenergic receptors, the alphas and the betas, and while both play a role in the management of body fat, the beta adrenergic receptors have been much more extensively studied with regard to energy balance, so we’ll start there. There are three beta receptors, and all are involved in the automatic regulation of energy expenditure, with some ability of each to compensate for the others. When these receptors are sufficiently stimulated by endogenous catecholamines or pharmacologic substitutes, the body is relatively resistant to weight gain. High levels of beta adrenergic stimulation probably underlie the “lean ‘n hungry” phenotype referred to in The Calculus of Calorie Counting. Without that stimulation, eating the same amount of food and doing the same amount of exercise, you will simply burn less of it as heat and energy and store more of it as fat. Like the patient in the Mayo Clinic NEAT study who only increased his energy expenditure by 107 calories per day, you would have what researchers call “defective thermogenesis”. Although the concept of thermogenesis has been around for at least half a century, the definitive proof that the beta-adrenergic receptors mediate thermogenesis took some time to develop.
Weight Loss Tablets” width=

Adapted from “beta-AR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance” by Bachman, E.S., et. al. Science, August 2, 2002; 297(5582): 843 – 845.

In a revealing study of mice specially bred to lack all three beta receptors, researchers at Harvard Medical School showed how profoundly the beta receptors effect our ability to dispense with our caloric intake. In two separate experiments, these beta-null mice were compared with normals under free-feeding situations with first, ordinary lab chow, and second, with more palatable high-fat chow. All the mice consumed more calories with the more palatable chow, however, in both situations, beta-nulls ate exactly the same amount as normal mice and engaged in similar amounts of activity. The difference in the outcomes, however, was startling. The beta-nulls had consistently lower energy expenditure, and as the graph shows, consistently higher weight gain; on lab chow, it was about 70% higher, and on the palatable diet, it was three times higher! Now, while the beta adrenergic receptors are clearly important to fat-burning, the alpha adrenergics should not be ignored.  The alpha adrenergics are often described as being anti-lipolytic, because the alpha-2 adrenoreceptors reduce levels of cyclic adenosine monophosphate, an important second messenger in the thermogenic process.  This characterization is somewhat lopsided, however, as the alpha-2’s also have a generally inhibitory effect on the pituitary hormones, putting the brakes on excessive levels of insulin, prolactin, cortisol2, and thyroid.  These are not hormones that we necessarily want to inhibit, but neither do we benefit from excess; all of these hormones have optimal levels, and too much is just as problematic as too little.  With regard to controlling our weight, we particularly need to keep our levels of insulin in check. “Insulination” Recall from Dr. Segal’s research in Calculus, how the presence of insulin resistance dramatically reduces the thermic effect of feeding (TEF), in both the lean and the obese.3 Besides just impacting TEF, however, insulin reduces the overall fat-burning ability of the body. In fact, insulin reduces the effect of beta-adrenergic stimulation in a dose-dependent manner; in one study, the calorigenic effect of norepinephrine was decreased by the presence of elevated insulin levels by as much as 50%.4 Just how powerfully does insulin sensitivity impact our ability to burn fat? Consider this interesting study: a group of researchers in Canada bred a strain of mice with a mutation in their insulin receptors, such that the same amount of insulin would keep the receptor active longer, thereby reducing the amount of insulin needed to return blood sugar to basal levels. In other words, these mutant mice were exquisitely insulin-sensitive. The researchers then placed the mutants and a control group of wild-type mice on a high-calorie diet designed to cause weight gain. Weight Loss Tablets While on the diet, the mutant mice maintained slightly lower blood glucose levels, despite secreting approximately half the amount of insulin as the controls. Because of the reduction in insulin, weight gain was significantly lower, too. After 10 weeks on the diet, the mutants had added 27% to their weight, while the wild-types gained 50%–all while eating and exercising in a similar fashion. So here we have two common physiologic aberrations–insulin resistance and decreased adrenergc stimulation–that lead to decreased energy expenditure without any difference in diet or exercise patterns. For those who have any degree of either or both of these conditions, fat will tend to accumulate easily and be difficult to lose, while those on the other end of the spectrum, our (annoying) “lean ‘n hungry” friends, can’t gain weight to save their lives. Now, the important thing is, is there anything we can do about this? Well, it just so happens there is. If nature left a little something out of your gene pool, you can get it back. In my next post, You Can Get There From Here, I’ll start showing you which products, both prescription and OTC, can truly change your metabolism.
  1. Levine, J.A., et. al. Role of Nonexercise Activity Thermogenesis. Science 1999; 283(5399): 212–214.
  2. Price, L.H., et. al. Alpha 2-adrenergic receptor function in depression. The cortisol response to yohimbine. Arch Gen Psychiatry 1986 Sep; 43(9): 849-58
  3. Segal, K.R., et al. Independent Effects of Obesity and Insulin Resistance on Postprandial Thermogenesis in men. J Clin Invest 1992; 89:824-833.
  4. Marette, A. and Bukowiecki, L. J. Stimulation of glucose transport by insulin and norepinephrine in isolated rat brown adipocytes. Am J Physiol Cell Physiol 1989; 257: C714-C721.

The Real Bathroom Scales

In The Biggest Medical Myth of All Time and The Calculus of Calorie Counting, we examined research exploring the futility of low-calorie dieting and exercise as methods of long-term weight loss. In this post, we’ll delve into a few more specifics on how our bodies actually react to alterations in calorie intake. “The lean ‘n hungry type” kindle epubBesides a flashback to a musical era I’d just as soon forget, the phrase “lean and hungry” has been used in obesity research to describe those naturally thin folks who have difficulty gaining weight, no matter how much they eat—much like Sims’ prisoners in Medical Myth. That such a type exists at one end of the body-fatness spectrum is rarely denied by medical science nowadays, though it’s generally assumed that those folks are some sort of natural super-athletes who are always engaging in sports and exercise activities. As Sims’ research showed, however, that assumption is incorrect; these folks stay thin even if they sit around with a TV remote growing out of their arm. In fact, a 1985 study analyzing data from the National Health and Nutrition Survey (NHANES) examined the relationship between ordinary dietary intake and body weight and showed the distinct lack of positive correlation there. The NHANES gathers information about the diet and exercise habits of the entire U.S. population via a statistical sampling method. The data is collected by experienced interviewers, trained to request information in multiple forms, so that the validity of the responses can be verified. In other words, it’s as reliable as self-reported data can be. The following chart displays results for caloric intake by relative weight class (as a percentage of ideal body weight) for adult men and women. Weight Loss Tablets As you can see, it appears that the leannest individuals actually eat the most. Even if you have doubts about self-reported intake, it’s pretty clear that weight is not proportional to consumption; that is, people who are 30, 40, or 50% above normal weight eat nowhere near 30, 40, or 50% more than their lean ‘n hungry counterparts. So how are variations in caloric intake actually dealt with by our bodies? “A calorie is a calorie is a calorie…NOT!” In Calculus, we looked at each of the elements that make up daily energy expenditure, culminating in the equation: Total Energy Expenditure (TEE) = Resting Energy Expenditure (REE) + the Thermic Effect of Food (TEF) + the energy expended in activity, exercise (EE) and non-exercise (NEAT). The response of each of these elements to a situation of extended overnutrition was explored in a 1998 Mayo Clinic study. In this study, sixteen weight-stable, non-obese subjects had 1,000 extra calories added to their daily diet for eight weeks, while simultaneously agreeing not to engage in any exercise outside of normal daily activities (that is, EE=0). Traditional wisdom holds that the human body has a relatively fixed rate of energy expenditure, like a car, so any major change in intake would automatically be converted to added body mass, mostly fat.  In this situation, that would be: 1,000 extra calories X 56 days, divided by 3,500 calories per added pound = 16 lbs of added mass. Even if we refine the calculation to allow for 10% of the calories to be used in food processing (TEF), we’re still looking at more than a 14 lb. gain. In theory. In reality, the researchers found two things. One, the average weight gain was considerably less than predicted, and two, the pattern of weight gain varied greatly between individuals and depended largely on changes in NEAT and TEF. The average gain was 10.4 lbs, only half of which was fat (5.26 lbs), with one person gaining less than a single pound of fat. So what happened to all the “missing” calories? Well, that is precisely what these researchers were after. During the run-in period, when subjects’ intake and weight were stable, their energy expenditure variables were measured by the most reliable scientific methods available (doubly-labeled water, indirect calorimetry, etc.). The same was done at the conclusion of the study, and the comparison was remarkable. Weight Loss Tablets Total energy intake was increased by 35%, from 2,824 to 3,824 kcal/day, while total energy expenditure increased by just over half that amount, from 2,824 to 3,350 (18.6%), by the end of the eight weeks.  If the subjects were not exercising (a fact verified by accelerometer use), how did their daily energy expenditure increase? The measurement processes showed the following: REE increased 4.8% for a total of 79 calories, which is about what we’d expect from the increase in body mass. Calories attributable to TEF increased by an impressive 62%, moving from 218 to 354 calories per day. And the calories burned in Non-Exercise Activity Thermogenesis (NEAT), changed from 913 to 1,224 per day, an increase of 311 kcal, or 37%.  Thus, TEE, after eight weeks of eating 1,000 additional calories, was automatically raised by the body to the tune of 527 calories per day, or 53% of the increase in intake—the equivalent of a 4-5 mile walk.  To summarize:
VariableMean Change%Std DeviationMinimumMaximum
Weight Gained (lbs)10.47.2%
Fat Gained (lbs)5.3N/A2.50.89.3
TEE Change (kcal)+527+18.6%+264+107+917
REE Change (kcal)+79+4.8%+126-100+360
TEF Change (kcal)+137+63%+83+29+256
NEAT Change (kcal)+311+37%+276-172+696
“Time in a bottle” Now there are two points I want to make here.  The first is that this study only looked at two time points—baseline and eight weeks.  It would have been really nifty if the measurements had been taken weekly to show how the variables changed over time, and it would have been super cool to see what happened during the next eight weeks, but alas, research costs money, and there was no blockbuster drug at the end of this rainbow, so they did what they could.  In all likelihood, the change in energy expenditure was a gradual adaptation over the study period, with most of the weight gain coming early and slowly decreasing, as seen in other studies, and if I make my guess, the energy expenditure rate would have continued to increase in the following weeks to the point that all the excess calories were being burned and no more weight was being gained. My other point is with regard to the NEAT.  As the researchers pointed out, despite the inter-subject variability in changes to energy expenditure, the change in NEAT correlated very tightly and negatively with the change in fat gain (R=-.7).  That is, subjects whose NEAT increased the most gained the least. Contrast this with what we saw in the Thomas and Miller rat study in Calculus, where forced exercise was met with a concomitant decrease in NEAT. From these data, it can be surmised that NEAT is a primary defense mechanism against exogenous alterations in energy balance. Changes you make to diet and exercise will be countered with adjustments to NEAT—your body’s subconscious drive to fidget, wiggle, whistle, talk, laugh, dance, hug, kiss, and yes, even change the channel. Weight Loss TabletsWhat we’ve shown here is that the difference in people’s weights has precious little to do with how many cheeseburgers we eat or how many marathons we run, but rather much to do with energy expenditure variables we cannot voluntarily control—TEF and NEAT.  All we have proven so far is that when our bodies sense a surfeit or deficit in energy supply, they attempt to balance it with changes to both energy storage and energy use, the relative percentages of which are highly variable between individuals.  But what makes some folks more prone to the storage side and others more prone to “use”?  We’ll explore that question in my next post, Through Thick and Thin.

The Calculus of Calorie Counting

In The Biggest Medical Myth of All Time, we reviewed some of the evidence that losing excess body fat is not as simple as the supposedly tried-and-true formula of eating less and exercising more.  And that’s because our bodies are not simple machines, like cars or televisions or the iPhone 3GS. In this post, we’re going to examine the calorie balance theory:   Calories In – Calories Out = Fat Lost/Gained, and build an understanding of why we can’t fool our fat-o-stats with a step-aerobics video and a freezerful of Lean Cuisines.

“The New Math” Weight Loss TabletsAs far back as the beginning of the last century, scientists were questioning the simple calorie balance theory.  In 1902, researcher R.O. Neumann, experimenting on himself, showed that his body could adjust to significant changes in caloric intake, with only minimal changes in weight.  He theorized that the apparently lost calories were being given off as greater or lesser amounts of heat by his body, and called this phenomenon “luxuskonsumption” (luxury consumption).1 Since that time, the subject has been studied exhaustively, with both support and refutation for the idea that the human body can adjust to differing levels of calorie intake without fulling accounting for the ingested energy differential through changes in body mass and/or energy output.  When you sift through it all, two conclusions seem irrefutable:  1) that our bodies do indeed have the ability to adjust to sustained alterations in intake, though not in the fashion Neumann first proposed, and 2) that the means and methods of accomplishing this task are highly variable between individuals. To begin understanding the real mathematics behind calorie balance, we need to understand the parts that make up our daily total energy expenditure—the “Calories Out”—because this is the piece over which we lack voluntary control.  The acronyms and terms are constantly changing, but the currently accepted model for daily total energy expenditure looks something like this: TEE = REE + TEF + EEE + NEAT, where:
  • TEE=Total Energy Expenditure.
  • REE=Resting Energy Expenditure, the rate of oxygen consumption when fasting and completely at rest.
  • TEF=Thermic Effect of Food, the increment in oxygen consumption seen just before, during, and after a meal.
  • EEE=Exercise Energy Expenditure, the increment in oxygen consumption attributable to volitious exercise, such as jogging, playing hockey, etc.
  • NEAT=Non-Exercise Activity Thermogenesis, all non-volitious activity over and above lying completely still.
Now, I should say that even this equation is a vast oversimplication, since the relationships among these variables are not independent.  EEE and NEAT both depend on REE and can be effected by TEF, and interact with each other, as well.  TEF is most often thought of as a function of REE, but also varies with the volume and types of foods eaten, as well as proximity to exercise.  That said, however, the equation makes a decent model for a given individual at a given point in time, so let us consider each of these in turn.

Resting Energy Expenditure (REE)

Much research has compared the REE between lean and obese persons, and, while slight differences are sometimes reported, for the most part, REE can be attributed to the maintenance of lean body mass—muscle, bone, skin, hair, etc.  Even highly trained athletes don’t show a significantly higher REE than couch potatoes of the same size and body composition.2 When people alter their intake acutely for a short period of time, or modestly for a long period of time, however, the REE, when measured per unit of lean body mass, will show a commensurate adjustment, albeit a small one.  Let me make that clear:  if a person has dieted (or gorged) for a suitable length of time, he will burn a different number of calories at complete rest than will a person of exactly the same size and body composition who hasn’t altered his diet.  Some studies will fail to show this, but likely only due to methodological differences (sample size, study length, measurement technique). Weight Loss Tablets As an example, in 2006, researchers showed that the metabolic rate of mildly overweight people during non-movement sleep (a decent proxy for REE) decreased after just three months of a 25% calorie deficit, created through diet alone or diet + exercise.  In the graph, you see sleep energy expenditure (SEE) predicted from baseline SEE and three-month LBM, compared to the actual three-month SEE.  The difference is small, but significant:  7.7% for the diet-only group, and 4.9% for the diet+exercise group.  The difference persisted over the next three months, when the subjects were fed the amount necessary to maintain the three-month loss.

Thermic Effect of Food (TEF)

Now here’s where things get interesting.  As far back as the 19th century, scientists were fascinated by what was then called Specific Dynamic Action, the significant increase in metabolic rate that occurs when we eat and for several hours after.  Early researchers observed that TEF varied with the size and composition of the meal and so logically drew the conclusion that TEF represented the energy cost of digestion and assimilation of the meal, which is how it is still often defined today.  This isn’t entirely accurate, however.  Researchers began to notice that there were significant variances in TEF between individuals, even when eating the same exact meal under the same circumstances.  That fact suggested that TEF was not solely the processing cost of food. Weight Loss Tablets In fact, many studies found that TEF was consistently higher in lean vs. overweight folks, which led to explorations of what else might be involved in TEF.  In a series of elegantly designed experiments, Dr. Karen Segal and her team showed that insulin resistance and body fatness are independently and negatively associated with TEF.  In this image, we can see that insulin-sensitive, lean persons burn considerably more calories in response to a given meal than do insulin-resistant or obese persons, matched for LBM and RMR.  Clearly, there is much we have to learn from studying TEF, even if it is a relatively small portion of our daily TEE, and I’ll get into that more deeply in another post.

Exercise Energy Expenditure (EEE) and Non-Exercise Activity Thermogenesis (NEAT)

The calories burned as a result of activity over and above REE can be divided into Exercise Energy Expenditure (jogging, tennis, pilates, etc.) and Non-Exercise Activity Thermogenesis (showering, fidgeting, channel-changing).  The former is pretty straight-forward; it’s basic physics:  work = mass X distance and force=mass X acceleration.  The distance you move something—like your arm or a barbell—through space, and the force you use to do so can be combined to calculate the calories burned in the process.  Okay, there’s a bit more to it than that, as there are effects from exercise training and efficiency, and interactions with the fuel source (sugar or fat), but for the most part, moving a given weight a given distance at a given intensity has a set value, regardless of our body’s fat content. The same could be said of NEAT, except for one important difference.  For most of us, EEE is the result of a willful, conscious act; whether we enjoy the activity or not, we make the decision to spend 30 minutes or an hour or the whole afternoon playing golf, painting the den, or using the elliptical trainer.  NEAT is much more about unconscious movements—the number of times we get up and walk to the window to look outside, how often we feel the urge to head to the water cooler for a gossip-fest, whether or not we are drumming out our favorite song on our desk while reading email—in short, how inclined we are to fidget, pace, or otherwise “waste” energy. So why do we make this distinction?  Because our inclination toward non-exercise activity is a key element in balancing the energy expenditure equation.  Let’s look at some science behind that statement.  A group of researchers at Mayo Clinic was given a great deal of credit for their research into the NEAT concept about a decade ago, but in reality, the idea of compensatory changes in NEAT goes way back to the mid-twentieth century. Weight Loss Tablets In a delightful study performed just down the road at UNC-Chapel Hill, a group of Sprague-Dawley rats (a strain of rat disinclined to high levels of activity) showed researchers what happens to NEAT when sudden changes are made in EEE.  The scientists forced the rats to run on little rat treadmills for a specified distance and at a specified speed for the first three days of each week, then allowed them to rest the other four.  This experiment went on for five weeks, and during the final week, spontaneous activity of the animals was measured during their non-exercise period and compared to matched controls.  What the researchers discovered was quite fascinating.  Spontaneous activity was greatly reduced on the three exercise days and modestly reduced on the four non-exercise days.  That is, the forced increase in EEE was compensated for by an unconscious decrease in NEAT.  Furthermore, following cessation of the experiment, there was a “persistent depression of spontaneous activity” for “a very considerable period of time”.  The rats’ little bodies were battling back against the attempt to use a lot more energy than they were naturally designed for. “The dieter’s playground” So what is all this telling us?  Well, the next time someone refers to weight loss dieting as a roller coaster, you can correct them—it’s not a roller coaster, or a merry-go-round, and it’s certainly not “The Fun House”.  It’s more like a see-saw—the harder you push down on your end, the higher up you’re going to bounce when your body pushes back.  In my next post, The Real Bathroom Scales, I’ll review a detailed example of how the elements of the energy expenditure equation respond to overeating in different body types.


  1. Neumann R.O. Experimental determination of human food requirements with particular consideration of essential protein need. Arch Hyg 45: 1–87, 1902
  2. Schulz, LO. Effect of endurance training on sedentary energy expenditure measured in a respiratory chamber. Am J Physiol. 1991 Feb;260(2 Pt 1):E257-61.