Why We Are Slaves Of Food Obsession.

A 95 years old psychology article holds the key to solving the obesity epidemic. It's not about a long forgotten medicine or an ancient psycho-trick. It's a simple observation about the dynamics of feeding. Vindicated by neurohormonal research, here is what it means to your struggle with extra pounds. [tweet this].

When Wallace Craig dissected the feeding behavior of doves, his experimental animal of choice, he discovered the existence of two distinct phases - an appetitive and a consummatory phase [1].  He defined appetite as "a state of agitation", which continues until food is presented, whereupon phase 2 begins. That's the phase you and I call eating. It's followed by a third phase of relative rest, which Craig called the state of satisfaction. You are forgiven if you now ask "what science nugget could possibly be hidden in this platitude". But the best-hidden gems are often those, which are in plain sight. In this case it's nothing less than the model explaining why so many of us wear dress sizes, ranging from "XL" to "Oh my God, look at this!", while none of us actually wants to be seen in them.  

Before I get to the beauty of Craig's observation, let me also tell you what's the acid test for any biological model: it must make sense in evolutionary biology. If it does, it still may not be the final word, but if it doesn't we can safely discard it into the heap of wishful thinking. Keeping this in mind, let's get cracking.

When Craig published his paper in 1917 he described the behaviors of his doves as instinctive. In other words, being driven by some innate processes which require no conscious decision making nor any degree of intellect. Today we know a lot more about those "innate processes", particularly that they are the result of a complex conversation between neurons and hormones playing out in the recesses of the animal brain. Not only do we know the chains of command running from brain centre to periphery we also know the hormones (at least some of them) by names, such as Neuropeptide Y (NPY) or Leptin. You don't need to remember them. What you need to remember is that "instinctive" has matured from a black box stage to the stage of neurohormonal mechanisms, which can be tested quantitatively in the lab with experimental animals. 

The Truth About The Genetics Of Obesity.

Evolutionary selection favored those who became fat easily. That's the essence of the "thrifty gene hypothesis". It's like Madonna. On the wrong side of 50, and ripe to be dethroned by something with greater sex appeal. In this case the contender's name is the "drifty gene hypothesis". Here is why you shouldn't be too dazzled about it. [tweet this].    

Exactly 50 years ago, Neel suggested that the high rate of diabetes in our society is the result of  evolutionary selection which favored those of our ancestors whose genes made them store fat more efficiently during periods of food abundance [1]. It's such a marvelously simple explanation that it doesn't take the brains of an Einstein to chatter about it at any dinner party where one wants to be remembered as quite the hobby geneticist. But to every party there is a party pooper. In this case two of them. John R. Speakman and Klaas R. Westerterp are telling us that the high prevalence rate of obesity and diabetes actually disproves the thrifty gene hypothesis [2].

In a nutshell their argument goes like this: our human and hominin ancestors have gone through so many feast and famine cycles over the past 2 million years, that, if it was for genetic selection, we should by now all be carriers of the genes that made caveman survive and modern man fat and diabetic. Since this is clearly not the case, the TGH can't be correct. 

I'm a sucker for theories which challenge common wisdoms, so I enthusiastically read the authors' arguments. Now, let's see how this enthusiasm evaporated.

To a considerable extent, obesity is determined by genes. If you want to put a number on it, genetic factors explain about 60% of the variance in obesity metrics, such as the body mass index (BMI). That's the numbers we are getting from studies, which compare such metrics between identical twins and other sibling types [3]. Just as an aside: When you consider genes as the one condition which you can't change, 60% heritability still leaves a lot of wiggling room for you to fashion your own fate. That's good because obesity comes with a host of nasty diseases, none of which makes your life longer or more pleasant. Think diabetes. Of course, you know all that, and it is not really our subject here. We want to know why there is such a high prevalence of obesity prone people.

To answer this question Speakman and Westerterp compiled some insights from genetics and put them through a mathematical blender. That sounds far simpler than it really was. For that blender to give you an intelligent answer you need to feed it with intelligent data. Otherwise it's the old nonsense-in-nonsense-out" paradigm. In our case at hand there are three data segments which need to be considered. 

First, there is biology: what happens to a human organism when it is exposed to fasting? How long will it survive?

Second, there is genetics: what do we know about those 60% of genetic causes? Are they concentrated in a handful of genes, or are they spread over hundreds? And what do we know about the mutation rates of genes?  Obviously, the more causative genes, and the smaller the mutation rates the longer it will take for any genetic mutation (or allele) to become fixed in the genetic pool. "Fixed" being geneticist speak for "(almost) everybody has it".

Third, there is evolution & environment: how often did famines happen, and how many of our ancestors were affected by them at any one event?

Get the figures slightly wrong in any of those three segments and your result will be off track. And so will be your conclusions.  

To get intelligent data, the two authors first went through an exemplary exercise of modeling what happens to a human organism when it is exposed to a zero-intake famine. That's not as straight forward as you might think, because our metabolism goes through at least three distinct phases when fasting in the extreme. These three phases are determined by our organism's way of storing energy reserves. 

First, there is glucose, the building block of virtually all carbohydrates in our food. While our brain thrives almost exclusively on glucose, the body's glucose stores are remarkably small. Glucose is predominantly stored in the form of glycogen in muscle and liver tissue. It is these reserves which are tapped first, and they are typically depleted within 24 hours. If you are a marathon runner you do this depletion business a lot faster, say after 20 miles or so. 

Since your brain still needs glucose, your body then starts to produce its own. Largely from lactate and glycerol, a component of fat. Which brings us to the second phase, where the body metabolizes its fat reserves. But even fat reserves don't last forever. Once they are depleted, the body begins to cannibalize its protein. Actually, weight loss in phase 2 is never a pure loss fat only. Proteins are being burnt at the same time but a at a lesser rate, until fat reserves have been depleted. And that's where fasting gets critical, because to your body, burning proteins for energy is like burning banknotes for warming your house: you go broke in no time. And "broke" means "dead" to your body. 

Since time to death is a critical element in the mathematical model, the authors went through an exemplary effort of mapping the course from fully fed to fully dead. Interestingly, everybody reacts differently to this fasting business. Some people survive longer than others, even when they have the same BMI to start with. That's why Speakman and Westerterp applied three different models to predict survival time, all models representing those known different ways of adapting to starvation. For a severely obese 1.64 m tall female weighing 100 kg, the models predicted a survival time of 249-289 days. Imagine, that's about 8-9 months with no food at all. 

Onto the genetics assumptions. The one thing we know for sure is that obesity is a multi-gene condition. Very multi-gene in fact, because genome-wide association studies (GWAS) have thrown up about 30 odd genes with a combined effect of explaining only 7% of those 60% of weight variance. So, we are assuming that the unexplained difference resides within another 200 or so genes, which we haven't even identified yet. Speakman translated this knowledge into an assumption of each individual gene having a net effect on fat storage of about 80g. That is, a carrier of a gene's "thrifty mutation" (or allele) would store 80g more fat than his peer with the "lean" version of the gene, with those 80g, translating into a 0.25% better chance of surviving a famine. With these assumptions the authors could then calculate how many famines it would take to weed out the unlucky ones whose "lean" genes didn't give them the 80g advantage. That calculation in itself is no rocket science. The authors took a given population size of 5 million people, exposed them to a virtual famine, after which the population had been appropriately decimated, and the percentage of "thrifty gene" carriers among the survivors had increased. They all mated happily after that until the population again reached 5 million. Then the next virtual famine struck, and so on. 

How many famines would it take to eliminate the lean gene from the gene pool? Under the authors' assumptions about 6000 famine events.  

They then made their final assumption: one famine happening every 150 years. That's 900000 years altogether for those 6000 famine events. Their conclusion: if the thrifty gene hypothesis and its assumption of selection pressure from catastrophic events was correct, we all should be obese today. Since we are not, the TGH is false. 

The alternative explanation, which the authors offer is a "drifty gene hypothesis" as opposed to the thrifty version. "Drifty" referring to genetic drift, meaning that mutations of the genes, which regulate fat storage were never really subject to selection pressure, and what we see today is simply the result of a natural drift of genetic mutations over the eons of human existence. 

The authors argue further that excessive fat storage was a distinct disadvantage for our earliest hominin ancestors, for reasons of predation. Think of it like that: while neither a fat man nor a lean man can outrun a saber toothed tiger, it's enough for the lean guy to run just a little faster than his fat bro'. Call it a stone-age version of the "first come, first serve" principle, at least from the tiger's perspective: the first man I get is the first man to serve me as breakfast. 

The authors then suggest that once our ancestors discovered fire and spears and other things which placed them on top of the food chain, the selective pressure for the lean gene had vanished. Its thrifty sibling started to flourish, not because it was favored by famine-based selection pressure, but simply because man had taken tiger and co. out of the equation, and with it the selective pressure to NOT get fat. During those zillions of generations which separate the man-known-for-throwing-spears from the man-known-for-throwing-tantrum-when-the-iphone-doesn't-work, those 200 odd genes accumulated just enough mutations for many, but not all, of us to become obese and diabetic. 

Up to this point one might buy into Speakman's and Westerterp's story. But here is the twist:  

Speakman has written about the subject before. With a different tagline. In his 2006 paper he suggested that the selection pressure of famines in human history was too small to have caused the effects attributed to it by the thrifty gene hypothesis [4]. According to that paper, famines with severe mortality rates were rare and, most tellingly, a phenomenon of agricultural societies. 

Indeed, the consensus view on famines in pre-agricultural vs. agricultural societies is that our hunter/gatherer ancestors were better fed and better protected against famines than their agricultural descendents. The hunter simply doesn't depend on a crop. Whereas when a crop fails, food shortage is inevitable for the agriculturalist. But even then, a true famine, where there is no food at all, typically requires a back-to-back failure of crops in consecutive years. And even then, as Speakman pointed out in his 2006 paper, mortality rates rarely exceeded 10% of the population, with those 10% coming almost exclusively from those who are either too young or too old to reproduce and thereby contribute to the gene pool after the famine is over. The author's message in 2006:  Genetic mutations towards thrifty genes didn't have sufficient advantage or time to spread. 

This little twist shows us that somebody is taking potshots at TGH: 

Shot 1 (2006): Famines haven't been with us for long enough nor with sufficient severity to have exerted the selective pressure on which the thrifty gene hypothesis rests. Ergo, TGH is wrong.

   

Shot 2: Famines were so numerous and severe during human history that their combined selective pressure on the thrifty genes was sufficient to have made them a fixture in EVERYBODY'S genetic make-up. Since this is not the case, the TGH is wrong.

Science shouldn't be about taking potshots. Science is about the testing of falsifiable hypotheses in reproducible experiments. A mathematical model, such as the one presented in Speakman's most recent paper does not qualify as such.  

Here is why: Given that mutations happen at the rate of 1.1 per 30-100 million base pairs, we all carry about 100 to 200 mutations in our DNA [5].  Not necessarily do those mutations affect actual genes coding for proteins. And if they do, most mutations confer a slight disadvantage, many have no effect on an organism's fitness, and only a few are favorable. Natural selection will weed out the deleterious ones, quickly fix the favorable ones and let the neutral ones accumulate at the given mutation rate. To complicate matters, all those processes happen at vastly different rates depending on the location on the DNA. That much we do know. What we don't know is how much these rates differ. We certainly can't know it for those genes, which we haven't even identified yet, as is the case for most of the hypothesized fat storage genes. That's why the mathematical model with which Speakman supports his argument against the validity of the thrifty gene hypothesis is in all likelihood not reflective of what has happened throughout evolution. Which means, it doesn't add any quantitative or objective evidence against the TGH. 

In my next post I will tell you why I believe that the entire discussion misses the point. What we really want to know now is how to help people avoid becoming fat and diabetic in the first place. Decoding the genome and its evolutionary history doesn't do that trick. Because genes do not make us fat and diabetic, genes make proteins, nothing else. One part of those proteins are the hormones. They drive our moods and emotions, our likes and our dislikes and, believe it or not, all our behaviors, from feeding to physical activity. For those latter two I have suggested an explanatory model in my dissertation thesis. 

This model tries not only to explain why we eat too much and move too little, despite having the best intentions to do otherwise, and while being aware of all the life threatening consequences. But, more importantly, without having to have a complete understanding of all those hormonal happenings, the model suggests a practical and testable solution to oppose those genetically encoded mechanisms for a longer and healthier life. Think of your car: You don't need to understand the mechanism of its gearbox to operate it for an optimal ride. 

Achieving the same thing with your life could turn out to be a gratifying pastime while my geneticist colleagues work on unraveling the enigma of the genetics of obesity. Whatever newer and sexier model they develop to explain the genetic origins of obesity, we might look at it like we look at Madonna and her variants: offering lots of entertainment value, but little of practical use. [tweet this].    

1. Neel JV: Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? Am J Hum Genet 1962, 14:353-362.

2. Speakman JR, Westerterp KR: A mathematical model of weight loss under total starvation and implications of the genetic architecture of the modern obesity epidemic for the thrifty-gene hypothesis. Disease models & mechanisms 2012.

3. Segal NL, Allison DB: Twins and virtual twins: bases of relative body weight revisited. Int J Obes Relat Metab Disord 2002, 26(4):437-441.

4. Speakman JR: Thrifty genes for obesity and the metabolic syndrome--time to call off the search? Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease 2006, 3(1):7-11.

5. Xue Y, Wang Q, Long Q, Ng BL, Swerdlow H, Burton J, Skuce C, Taylor R, Abdellah Z, Zhao Y et al: Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Curr Biol 2009, 19(17):1453-1457.

NEEL JV (1962). Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? American journal of human genetics, 14, 353-62 PMID: 13937884

Speakman JR, & Westerterp KR (2012). A mathematical model of weight loss under total starvation and implications of the genetic architecture of the modern obesity epidemic for the thrifty-gene hypothesis. Disease models & mechanisms PMID: 22864023

Segal NL, & Allison DB (2002). Twins and virtual twins: bases of relative body weight revisited. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 26 (4), 437-41 PMID: 12075568

Speakman JR (2006). Thrifty genes for obesity and the metabolic syndrome--time to call off the search? Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease, 3 (1), 7-11 PMID: 16784175

Xue Y, Wang Q, Long Q, Ng BL, Swerdlow H, Burton J, Skuce C, Taylor R, Abdellah Z, Zhao Y, Asan, MacArthur DG, Quail MA, Carter NP, Yang H, & Tyler-Smith C (2009). Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Current biology : CB, 19 (17), 1453-7 PMID: 19716302

What Infants Teach Us About Preventing Obesity.

Public health has been telling you for years: you are fat because you move too little and eat too much. And yes, it's your fault if you don't break a sweat every day to keep your waist line in check. But research says, that's not the entire truth. In fact, public health might have taken the easy way out, and here is how it could finally make amends. [tweet this].

If an alien scientist came to earth to study us in the same way in which we study lab rats, he would come to the same simple conclusion as we do: give those animals more than enough food, take away the need to move around, and what you'll get is a population of mostly overweight individuals. I say "mostly" because there are always the odd ones who fall away from the norm. What fascinates me most in this image is the fact that, while mice and rats probably do not communicate among each other the benefits of staying slim, we humans do so and still, the result is the same. What our alien researcher sees is biology trumping consciousness. For a good reason. Neither rats nor humans would survive in their natural habitat without the ability to store excess calories as fat, which then sees them through the inevitable lean periods. It gave our ancestors a good shot at survival, with no or little chance to become overweight. At least not then.

Today, obesity is the new normal. I won't bore you with the percentages. You hear and read about them in the media almost daily, with one or the other pundit citing the ever increasing number of people who are overweight or outright fat (the politically correct term being "obese"). Not that any of those pundits offers any solution or view of things other than that too little exercise and too much food are the cause. Those platitudes are typically topped off with denouncing people's weakness to do something about it, such as exercising more and eating less. When you look at the effectiveness of public health calls for exercising more and eating less, you'll find that overweight and obesity have increased nicely alongside those calls. Which simply means one thing: we need to do something differently. 

Now, remember, I said there are always some odd individuals who seem to escape the fate of the majority of our experimental animals, be that rats in the lab or humans in free living conditions. It is here where we ought to look at what makes them so different. And whether this difference is in their genetic program or in their mental ability to override this program.  

The funny thing is, the answer to this question has been relatively clear for years, but hardly anybody seems to draw the right conclusions from it. Just about a week ago, another wonderful study has emerged on this subject. 

  

Britt Eriksson and her colleagues investigated the correlation between body composition development and energy expenditure through physical activity in 1.5 year old infants [1]. That's not a first, but the way they did it is. When you look at energy expenditure of any individual it is necessary to know how much of this energy expenditure comes from basal metabolic rate (BMR). This BMR tells us how much energy an organism needs to maintain life under resting conditions. There are large differences in these rates between individuals, such that two persons who share the same body weight, height and composition and who do the same type of exercise may burn substantially different amounts of calories, simply because one person has a higher basal metabolic rate than the other. So, If you want to know exactly how much of an individual's total energy expenditure is coming from physical activity, you better have accurate knowledge about his basal metabolic rate because you need to subtract it from total energy he or she burns.  In previous studies of infants, physical activity levels (PAL) had been estimated based on predicted BMR rather than on actually measured BMR. Obviously, if your BMR prediction is incorrect so will be your conclusions about PAL. That's why Eriksson and her colleagues objectively measured basal metabolic rates. They did so by analyzing carbon dioxide production and oxygen consumption while infants slept under a ventilated hood system. Add to this the researchers' way of measuring total energy expenditure with the gold standard doubly labeled water method, and what you get is the most accurate differentiation between BMR and PAL possible in living humans.

Our researchers did all those measurements on 44 children aged 1.5 years. All of them had participated in a body composition study when they were 1 and 12 weeks old. Body composition was again measured in the current study. Before we look at the correlation between body fatness and PAL in those 1.5 year old children, let's recall what is normal in human development during infancy. 

Healthy infants typically gain body fat, expressed as a percentage of bodyweight, during the first 6 months of life, after which the total body fat percentage (TBF%) slowly decreases. By the way, that was the case in only about 20% of the infants in this study. The majority increased their body fat percentage but with large differences between individuals. At age 1.5 years TBF% varied between 21% and 35%. And these changes in body fat correlated with the physical activity levels of the infants, such that those with a higher PAL had decreased their body fat percentage more than those with a lower PAL. The beauty of investigating these associations in infants is that you don't need to worry about your study subjects' volitional exercise habits, such as treadmill running, mountain biking or kicking ass instead of writing anonymous comments to blog posts. All their physical activity is non-exercise activity. I'll get to this important distinction in a moment. The point here is: genetic influences show up relatively unmasked.  If there are such large inter-individual differences in body fat development already being evident in the earliest years of life, we have every reason to assume that there is a phenotype and a genotype which is better protected against fat gain than others. We also know that body fat percentage in the youngest years tracks into adolescence and on into adulthood. 

Which of course also means that we should see such differences in adults, too. In fact we have been seeing them for more than 10 years, but somehow these observations don't make it into the media where the doom and gloom prophets of obesity have our ears and eyes but no solutions to offer.

Back to those studies: Levine and colleagues put 16 non-obese young adults, aged 25-36, on an 8-weeks supervised diet which provided a daily excess of 1000 Kcal over what each individual needed for weight maintenance [2]. The participants had to maintain their usual level of exercise throughout the experiment. Physical activity and body composition were measured with the same gold standard methods, which the Eriksson group used on their infants. As a group, the participants of the overfeeding experiment stored 44% of the excess kcal as fat, and dissipated 53% through increased energy expenditure. 

But those average values over a group of people don't interest us here. What we want to know is how much difference was there between participants. Well, fat gain varied more than 10-fold from a minimal increase of 360 Grams to a whopping 4.23 kg. Think about this for a moment: you let 16 people gorge themselves on a daily excess of 1000 kcal for 8 weeks and what you get is one whose weight remains virtually the same, while another gains more than 9 pounds, and all the other 14 show up anywhere in between those two.

The laws of physics tell us that energy cannot be lost or created, it can only be converted from one form to another. What this means to our weight gain experiment is that those who didn't store the energy as fat must have burned it somehow through physical activity. But how could that have happened if all participants kept their exercise on an even keel throughout the experiment? Had an enormous increase of BMR protected them against weight gain? Our researchers didn't think so, because experiments on BMR response to over- and underfeeding have been fairly consistent, showing only small changes in the range of 5%. Levine's participants were no exception to that rule. So, what happened? 

The answer is in the details of what constitutes physical activity. There are two components, one of which you certainly know: exercise. Then there is the other, which I just mentioned a few lines earlier. It's called NEAT, which is short for non-exercises activity thermogenesis. In a less convoluted way it means the energy you burn through acitivities of daily living, fidgeting, spontaneous muscle contractions and maintaining or adjusting posture while not lying down. In other words, the energy you burn through physical activity which is not volitional exercise.  

NEAT accounted for over 70% of the increase in daily energy expenditure, with an average increase of 336kcal/day. Mind you, this was the average over the entire group. Far more interesting, again, is the range, which spanned from a decrease of 98 kcal/day to an increase of 692 kcal/day. It's the same picture we saw in the fat weight development. And yes, the larger a participant's increase in NEAT the smaller his weight gain. The fellow with the 692 kcal/ increase subconsciously moved around more often. He had increased his strolling-equivalent activity by an average of 15 minutes per waking hour! Interestingly, the 4 female participants in this study had the smallest changes in NEAT. While this study is certainly underpowered to tell us anything about gender differences, its observations fits neatly with an another observation: The age-dependent increase of obesity risk is steeper for women than for men. 

Now, back to the study results. If NEAT is NON-VOLUNTARY activity energy expenditure, then conscious rationally driven behavior has nothing to do with it. It's purely physiology talking. It's our genes' handwriting. And if this handwriting reveals such a substantial effect on weight development, shouldn't we look at means to increase NEAT, rather than keeping our current tunnel vision on exercise, which we already know is so difficult to adopt for most people? Let's put some effort into designing "obligatory" NEAT into our life. Or rather, designing NEAT killers (such as remote controls) out of it. 

To our alien researcher, this might just be the next experiment, as it is for his human peers who are already experimenting with running wheels and wheel locks in their lab rats' cages. After all, a 332 kcal/day deficit translates into almost 14 kg of fat over a year. That's certainly something which public health ought to be interested in. 

  

1. Eriksson B, Henriksson H, Löf M, Hannestad U, Forsum E: Body-composition development during early childhood and energy expenditure in response to physical activity in 1.5-y-old children. The American Journal of Clinical Nutrition 2012.

2. Levine JA, Eberhardt NL, Jensen MD: Role of Nonexercise Activity Thermogenesis in Resistance to Fat Gain in Humans. Science 1999, 283(5399):212-214.

Eriksson B, Henriksson H, Löf M, Hannestad U, & Forsum E (2012). Body-composition development during early childhood and energy expenditure in response to physical activity in 1.5-y-old children. The American journal of clinical nutrition PMID: 22836033

Levine JA, Eberhardt NL, & Jensen MD (1999). Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science (New York, N.Y.), 283 (5399), 212-4 PMID: 9880251

Can A Genetic Test Say Why You Are Fat?

With the decoding of the human genome came the hope of getting a lever on the chronic diseases, which kill most of us today: heart disease, stroke, diabetes and many cancers. And since overweight and obesity are a common cause of those diseases, many obese people were, and still are, yearning for that exculpatory headline: "It's all in your genes!" Why and how this headline is unlikely to ever appear in any serious media, was a subject of my earlier post "It's not your genes, stupid!".

Now, a group of researchers have looked at the data of a 30-year investigation of health and behavior, ...
which you might call the New Zealand equivalent of the famous U.S. Framingham study [1]. If you ever wondered whether it would make sense to get your children, or yourself, tested for your genetic risk of obesity, you will be surprised to learn what this study tells you. But one step at a time. Let's first have a look at this outstanding piece of research. [tweet this].

The study population consists of all the 1037 babies born in Dunedin, New Zealand, between 1st April 1972 and 31st March 1973 at the Queen Mary Maternity Hospital. Comprehensive health assessments were done at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38. These investigations will be extended into the future and into the next generation. This is a massive and admirable effort. With data having been collected about virtually all aspects of health and behavior, this project provides a rare opportunity to match those data with genetic information. While genetic profiling wasn't possible in the seventies, it is possible and feasible now. And since study participants' genetic make-up hasn't changed since the time of their conception, we can retrospectively look at the correlation of biomarkers and genes, in this case those that correlate with obesity. To understand this study let me familiarize you with some facts and terms first.

So-called genome-wide association studies (GWAS) have thrown up more than 30 individual single-nucleotide polymorphisms (SNP, pronounced 'snip'), that's geneticists' speak for a variation of a single building block (nucleotide) of a gene. The draw-back: Those SNPs individually correlate only very weakly with obesity. That is, while there is a statistical correlation with obesity, there are obese people who don't carry the SNP, and there are carriers of the SNP who are not obese. To complicate matters a little further, not all SNPs which show statistical correlations in one population, say the U.S., do so in another, say New Zealand. Which is why the Dunedin researchers developed a risk score from the 32 SNPs known from other studies. Of those 32 they could find 29 in their study cohort, and so they developed their score from those 29 SNPs. Participants were grouped according to their score into either high- or low-risk.

The next step was to look at how the participants' genetic risk score (GRS) correlated with BMI in each decade, starting from 15-18 years of age, followed by 21-26 years, and then from 32-38 years. In the second decade (ages 15-18), people with a high risk score had 2.4 times the risk of being obese than those who scored low on the GRS. Had this been you, having a high risk score would have made you almost two and a half times more likely to be obese as a teenager compared to your buddies of the low-risk persuasion. That sounds like a lot, and you might be tempted to think that screening your child for genetic risk would help you to be more vigilant in watching over his or her BMI while he or she is still under your care.

The authors certainly seem to think so when they say that "These findings have implications for clinical practice..." and that "the results suggest promise for using genetic information in obesity risk assessments." I respectfully disagree, and so might you.

Let's simply take your point of view for a moment, and not the one of public health, where we are interested in one patient only, the population under our care. In contrast, the only patient you are interested in is you, or maybe your child. This value of a relative risk of 2.4 doesn't tell you much. What you rather want to know is, what a high- or low-risk score means to you. And the right question to ask would be along the line of "what are the chances of becoming obese when my risk score is high?". And also, "what are my chances of not becoming obese when my risk score is low?". The answers to these 2 questions come in the shape of values, which we call positive predictive value (PPV) and negative predictive value (NPV). Unfortunately the Dunedin researchers don't report those values. But we can calculate them, which I did.

And here is the surprising answer: if you had a high score, your risk of being obese as an adolescent is just about 10%. In other words, even with a high-risk score, you stand a 90% chance of not being obese as an adolescent. And if your risk score had been low you would have a 95% chance of not becoming obese. Beats me, but I can't see the benefit of genetic testing.

I deliberately talk only about the risk at the age of adolescence. There is a simple reason for this. The researchers found that the relative risk of obesity between the high- and low-risk categories diminished progressively from 2.4 in the second decade to 1.6 in the fourth (ages 32-38). That means, our looking at adolescents affords us a look at a time when study participants' exposure to environmental and behavioral influences had been relatively short. Over the years, environment and behavior further diminish the predictive power of the genetic score. Which is akin to saying: your lifestyle choices give you a greater power over your BMI than your genes. And by extension, the choices you make for your children's lifestyle beats their genes easily, too. In other words, it's not so much the luck of the draw, which determines your body weight, but rather your skill of playing the deck of (genetic) cards, which we have been dealt at the moment of conception. The study's data say the same thing just in other words: At birth the high-risk babies were not any heavier than their low-risk peers. Only once they were exposed to the outside world, did BMI careers begin to divert. For some of them.

This tells us one thing: when it comes to obesity, habits and environment are the key, not a potpourri of SNPs. Of course, if you are in the business of peddling genetic tests, you will disagree. And also when selling guilt-free conscience to obese readers is what pays your bills. Which is why I'm curious to see how the media will portray this study. Let's stay tuned. [tweet this].

1.    Belsky, D.W., et al., Polygenic Risk, Rapid Childhood Growth, and the Development of ObesityEvidence From a 4-Decade Longitudinal StudyPolygenic Risk for Adult Obesity. Archives of Pediatrics and Adolescent Medicine, 2012. 166(6): p. 515-521.

Belsky DW, Moffitt TE, Houts R, Bennett GG, Biddle AK, Blumenthal JA, Evans JP, Harrington H, Sugden K, Williams B, Poulton R, & Caspi A (2012). Polygenic Risk, Rapid Childhood Growth, and the Development of Obesity: Evidence From a 4-Decade Longitudinal StudyPolygenic Risk for Adult Obesity. Archives of pediatrics & adolescent medicine, 166 (6), 515-21 PMID: 22665028

Who says being fat is bad?

Would you have guessed that, one fine day, health insurers will regret the demise of big tobacco and its contribution to health care costs? Would you have guessed that, when that day arrives, health insurers would also learn to love other frowned-upon-vices of their policy holders, such as getting fat and lazy? Your answer is probably "no, I wouldn't have guessed that in my dreams.". 

And also very probably this answer is based on what you typically read in the media, such as this piece of news titled "Obesity Adds More to Health Care Costs Than Smoking, Study Suggests." released on April 3, 2012, on sciencenews.com. The article text wraps the title message into a substantially larger amount of unsubstantial words, before it concludes what you would probably subscribe to blindfolded: the  "...study [1] provides new insights into the long-term costs of obesity and smoking, showing that both risk factors lead to persistently higher health costs throughout a seven-year follow-up period.". Dah, what else is news?

Well, for one, that the Joe Camels and the lardbuckets, with all their vices, cost their health insurers actually LESS money than Mr. and Mrs Healthy. For one simple reason: the "vice guys" die earlier.

But let's hold that thought for a moment and let's look at the figures. In a Dutch study performed by Pieter van Baal and colleagues, the authors compared the annual and lifetime health care costs of three cohorts, namely the obese, the smokers, and the healthy living people [2]. As the basis of their calculations they used the Dutch National Institute's of Public Health and the Environment (RIVM) chronic disease model, which, the authors assure us, has been widely used and validated in disease and cost projection analyses.

To make their results more comparable internationally, they ran their analyses with altogether 7 different scenarios, to account for different health care systems and for different mortality risk estimates. The latter had been drawn from observations in the U.S. published by Flegal and colleagues [3] who had found declining mortality risks in the obese cohorts. I mention this because I don't want you to suspect that the Dutch authors had based their calculations on an unrealistically high keeling-over rate for the obese. Now, fast forward to the astonishing results.

In all 7 models, as well as in the unadjusted base case scenario, the financially most attractive "villains" to health insurers are the smokers. The most expensive are always the goody-two-shoes healthy-living people. Somewhere in-between are the fat ones. In the model which assumed a yearly 1% increase in health care costs, the lifetime costs for an obese person amounted to € 399,000, compared to which the smoker comes at a 14% discount of € 341,000, but the healthy living person with a 17% premium at € 468,000.

How can that be? The answer is not where you and I would have looked first: The diseases which directly associate with smoking and obesity (heart disease, cancer, diabetes, pulmonary diseases, musculoskeletal disorders). They account only for 20% of total disease costs. The remaining 80% are for ailments and conditions, which come with age. But when that age doesn't come, because you die earlier, then those costs don't come either. And Joe Camel and Ronald McDonald are rather effective in cutting years out of your life, and thereby costs out of your health insurers balance sheet. For 7 and 5 years respectively, to be precise.   

So, where are the premium discounts for the obese and the smoking policy holders? Why are the healthy living people permanently miffed about not getting premium discounts, when they actually cost more? I have to admit, I belong to the latter, too. But recently, after having listened to one of my talks at a conference, a friend of mine, the CEO of a German health insurer, took me aside and told me, that my indignation about the healthy people having to share the cost burden of their willfully negligent peers, was unfounded.

As much as I wanted to disbelieve, I also knew that these insurance guys do one thing very well: calculating risk and premiums. So I had to give him the benefit of the doubt. Which is why I began to check. And by checking, I came to know about quite a number of studies confirming my friend's argument. One of those studies was van Baal's, which I chose to quote from because he is actually working for the Dutch National Institute of Public Health and the Environment. Not that I'm biased in favor of the Dutch. I'm biased in favor of anyone who articulates a viewpoint which is in stark contrast to what I would expect merely on the basis of his association. I mean, here you have someone telling you to NOT confuse health with health care cost savings, when his employer is actually trying to make everyone with a cigarette or a burger in his mouth feel guilty about sending health care costs sky high.  

So what now? Shall we promote the vices and lower our health care costs in a decade-long smoking and feeding frenzy? Well, it's your choice, but I'm not convinced that we have got the reasoning or the arguments right just yet. We need to do a little more detective work to solve this case.

Now, you know how the French, at least in their novels, dish out that piece of advice to the detective: Cherchez la femme (look for the woman)? Maybe it works in the French universe. In mine, I have always found this one to work better: "Cherchez l'argent" (look for the money).

Which will lead us to another few surprising discoveries in the next post. And, of course, a couple more reasons to believe that there are quite some powerful players around who yearn for the good old times when Marlboro Man and Ronald McDonald delivered us from the risk of a costly long life.

PS: To meaningfully pass the time until the next post, watch this video on the calorie cartel

1.           Moriarty, J.P., et al., The effects of incremental costs of smoking and obesity on health care costs among adults: a 7-year longitudinal study. Journal of Occupational and Environmental Medicine, 2012. 54(3): p. 286-91.

2.           van Baal, P.H.M., et al., Lifetime Medical Costs of Obesity: Prevention No Cure for Increasing Health Expenditure.PLoS Med, 2008. 5(2): p. e29.

3.           Flegal, K.M., et al., Excess deaths associated with underweight, overweight, and obesity. Jama, 2005. 293(15): p. 1861-7.

Moriarty, J., Branda, M., Olsen, K., Shah, N., Borah, B., Wagie, A., Egginton, J., & Naessens, J. (2012). The Effects of Incremental Costs of Smoking and Obesity on Health Care Costs Among Adults Journal of Occupational and Environmental Medicine, 54 (3), 286-291 DOI: 10.1097/JOM.0b013e318246f1f4
van Baal PH, Polder JJ, de Wit GA, Hoogenveen RT, Feenstra TL, Boshuizen HC, Engelfriet PM, & Brouwer WB (2008). Lifetime medical costs of obesity: prevention no cure for increasing health expenditure. PLoS medicine, 5 (2) PMID: 18254654
Flegal, K. (2005). Excess Deaths Associated With Underweight, Overweight, and Obesity JAMA: The Journal of the American Medical Association, 293 (15), 1861-1867 DOI: 10.1001/jama.293.15.1861

Screw Your Health?!

So, what's your excuse for not exercising enough, for smoking, for not watching your diet, for getting fatter every year, and therefore having high blood pressure, and too much glucose and cholesterol in your blood?

 That's what the American Heart Association has been telling you for so many years NOT to do. How can I be sure that you, dear reader, are one of those people who only pay lip service to health? I can't, but as a numbers guy I go with the statistics. 

And when health is concerned the statistics tell me that there are obviously only two types of people. Those who do enough for their health, and those who merely think they do. The latter make up 98.8% of the population [1]. That is, only one in a hundred meets all 7 health metrics: not smoking, eating a healthy diet, no overweight, sufficiently physically active, normal blood pressure, normal levels of glucose and cholesterol. Four out of every 5 Americans meet 4 or less of those metrics. Actually, only one in four meets 4 metrics. How can that be when having at least 6 of those metrics will cut your risk of dying from cardiovascular disease by 75% compared to those who meet one criterion or none? How much more incentive do you want?

That's the frustrating question I'm asking myself every day. Because whether it is in the US, in Germany or anywhere else in this world, maintaining health and preventing disease is a frustrating service to provide. I used to think this is so, because when you don't feel it, it is health. And what you don't feel, you don't appreciate. But if that was true, the first diagnosis of a chronic condition, such as heart disease or diabetes, should surely be a wake-up call. But it isn't. Only 40% of smokers quit when  being told that they have such a chronic disease, and that smoking will make it worse [2]. That's still a lot compared to the behavior change in exercise: Nil, no change at all.  And for every American who quit smoking in 2011 another American became obese. 

If you have read my earlier blog posts, you'll remember that I'm a strong advocate of recognizing the autonomic neurohormonal mechanisms which certainly drive our eating and exercising behaviors. But we are not exclusively controlled by those. We still have a few brain centers which give us the abilities and skills that make us human: volition, reasoning, intelligence. Of course you can use them to find the most elaborate excuses for your health behaviors, or rather for the lack thereof. But he who is good for making excuses is seldom good for anything else. That's what Benjamin Franklin said. Are you good for something else? Make that something your health. And start today. Here!

1.           Yang, Q., et al., Trends in Cardiovascular Health Metrics and Associations With All-Cause and CVD Mortality Among US Adults. JAMA: The Journal of the American Medical Association, 2012.

2.           Newsom, J.T., et al., Health Behavior Change Following Chronic Illness in Middle and Later Life. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 2011.

Yang, Q., Cogswell, M., Flanders, W., Hong, Y., Zhang, Z., Loustalot, F., Gillespie, C., Merritt, R., & Hu, F. (2012). Trends in Cardiovascular Health Metrics and Associations With All-Cause and CVD Mortality Among US Adults JAMA: The Journal of the American Medical Association, 307 (12), 1273-1283 DOI: 10.1001/jama.2012.339 

 Newsom, J., Huguet, N., McCarthy, M., Ramage-Morin, P., Kaplan, M., Bernier, J., McFarland, B., & Oderkirk, J. (2011). Health Behavior Change Following Chronic Illness in Middle and Later Life The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 67B (3), 279-288 DOI: 10.1093/geronb/gbr103

Are fat people just lazy?

Are fat people just lazy? Or is it in their genes?

Let's look at an unlikely place for the answer: an AA meeting. If you get up and say "My name is Jane, and I'm not really an alcoholic, I don't drink that much..." they throw you out. They welcome you back, once you say "My name is Jane and I'm an alcoholic". The same should be true for fat people. And I'm using this politically incorrect term deliberately. Because unless you wake up to the reality, you won't be able to change that reality.

 AA have long ago realized that fact. And they have a 50% long-term success rate. That is, half the alcoholics who join AA stay dry for the rest of their lives. That's way more than what public health, clinical and commercial weight loss programs achieve with obese participants. We are happy if 10% of those who enter these programs achieve a 10% weight loss AND keep it for more than 2 years. It's that bad. Is it because of the genes? A study published recently in Nature Genetics, might supply another excuse to some overweight people. But before we look at this study, let's look at some other facts first.

One thing we all know for sure: if you are overweight, you obviously have taken in more calories than you have expended. Over quite some time, because it takes a while to accumulate all those energy reserves on your waist and hips. Boils down to one of the tenets of a universal law of physics that says: Energy can neither be destroyed nor miraculously created. Not even on your hips.

Now I know all the objections raised by so many overweight people, like "But, I hardly eat anything. How can I be fat? Even my friends say, from what you eat nobody can get fat." Believe me, I've heard them all.  And my heart sinks, when I do, because I know there goes the hopeless case. The Jane who goes to AA and tells them she is different. The study published in Nature Genetics might just deliver her the next excuse. Not because the researchers tell her so, but because some media genius might just read it the wrong way. As they often do. So, let's look a what the researchers say.

The researchers conducted a meta-analysis of some 14 genome wide association studies involving altogether 14,000 children, one third of which were obese. They found 7 genetic markers which correlated with obesity and which also turned out to correlate with obesity in adults. The beauty of looking at genetics in kids is, that they haven't been exposed to decades of lifestyles which may obscure such links. 

So, the results clearly point into the direction of some genetic signature predisposing a person to become obese. But having this signature doesn't mean you'll inevitably become obese. Because most kids who have the signature are not obese. It's only that this signature shows up a little more often in the obese kids than in their non-obese peers.  And there is one more thing, you need to keep in mind. Over the past 20 years the human genetic make-up hasn't changed at all. But the obesity rate in US kids has. In fact it has tripled during that period. And health behavior has changed, too. And so did our environment.

What makes me always frustrated in all this debate about genes vs. environment vs. behavior is my scientist colleagues' and the media's inability to educate their audience about the complete picture. Genes make up the blueprint to your organism. True. But they don't make that organism. Genes make proteins, but whether they make them or whether they are silenced into not making them, that depends on epigenetics, on the interaction with your environment, and on your behavior, which again is influenced by all the others. It is a very complex relationship, and I'm afraid, genetics will not help us, to solve the obesity epidemic. But neither will the stigmatization of the obese. 

What we need, is a way to help those who recognize their fatness as a resolvable reality, resolve it. That's why I'm working on the GPS tochronic health, because I know that once the health behaviors put you on track to chronic health and longevity, your overweight problem will resolve automatically. As a side effect. But only if the obese person works with us. 

So did that answer the question? You decide for yourself.   

The three hidden barriers to chronic health, weight loss and weight maintenance.

Into The Age of Chronic Health

The most amazing thing about modern health care systems is that they let most of us die from chronic diseases which we know how to prevent. So why don't we?

As a public health scientist I have devoted the past 15 years of my life to answering this question. Many of my colleagues outdo each other with doom and gloom predictions of aging societies buckling under the economic burden of aging related diseases. I believe that the age of chronic health and longevity is about to begin. With you. And with a radically new approach to make the prevention of heart attacks, strokes diabetes and cancers finally work.     

Because, until now, it doesn't. But don't just take my word for it, let's look at some of the facts first:

You have probably heard that obesity is the new smoking. In fact for every American who stopped smoking in 2011 another one became obese.   

Today, for the first time in human history there are more overfed than malnourished people walking this planet. And their lifestyles of too much food and too little exercise have become the number one risk factor for the number one chronic disease and killer: cardiovascular disease with its most well-known end points - heart attack, stroke and heart failure. With nasty other diseases on the side: diabetes, kidney failure and certain cancers.

You probably also heard about major studies, like the U.S. government funded Diabetes Prevention Program, and the Look AHEAD trial, which proudly, and correctly, report weight loss and major reductions in cardiovascular risk factors among participants in the lifestyle arms of these trials. What you don't hear so often, is that within 3-4 years after enrollment, most participants will have regained not only most of their weight but also all their risk factors.

Ok then, lifestyle change prevents disease. But what prevents lifestyle change?

Why is it that over the last 30 years of public health efforts we have not seen a demonstration of any program that results in a clinically meaningful weight loss that can be maintained for more than 2-3 years in the majority of participants and at low cost?  That's the question which Dr. Richard Khan threw at an assembly of public health advocates, who had gathered earlier this year under the event's message "Prevention works!".  Dr. Khan, who teaches medicine at the University of North Carolina, was the chief scientific officer of the American Diabetes Association for 25 years. The man certainly knows what he is talking about. 

Now think about the implication. If you chose a lifestyle of which you know might increase risk of disease and premature death, then you make that choice either willingly or it is not your free will which makes that choice.

My money is on the latter. Because how else could we explain that an obese child maintains her fattening habits despite experiencing the same psychological agony as a child with cancer? How else could we explain that obese adults maintain their bulk when it significantly reduces their chances of getting an academic education, a job and a mate? How else could we explain that over the past 20 years the obesity rate in the US went up by 60% when, during the same period, Americans doubled their spending on weight loss products to US$ 60 billion annually? They WANT to lose weight, but they don't. The explanations are called addiction, hormones and hyperbole.  

Food addiction

The neurohormonal architecture which drives an addict to crave and consume his drug, despite knowing and hating the consequences, is exactly the same architecture that keeps us going for the sweet, fatty and salty stuff in restaurants, hawker centers and vending machines. Does that explain, why the food industry adds sugars to so many foods in which you least expect it? You bet. In fact we shouldn't be afraid of calling ourselves food addicts, because this is what Mother Nature intended us to be all along. With this addiction she drove our ancestors for millions of years to what is naturally sweet in the natural human habitat: fruits. They deliver not only the carbohydrates for which we have very little storage capacity in our bodies and without which our brain can't function. Fruits also pack a punch of essential micronutrients. Unlike the cokes and cakes and cookies which deliver more sugar than we need and no other nutrients with it.  

Hormones

Once you have changed your figure into the shape of a beached whale, you will also have changed the way the hormones of your gut and of your fat tissue work. It's a rather complicated picture unfolding in the labs of biomedicine, but one emerging theme is a colossal malfunction of the satiety and appetite signaling pathways. Instead of feeling full, you are now ready to add a tiramisu to a lunch that would have satiated a family of four in rural Bangladesh.

Hyperbole

Actually it's called hyperbolic discounting, and it's a simple mathematical formula, which behavioral scientists have found to neatly describe why we will still grab that tiramisu tomorrow even though we swear today that we won't. It has to do with how we more steeply discount the relatively larger but more distant reward of staying healthy against the relatively smaller but immediate reward of enjoying the tiramisu. It doesn't operate only in humans. The behaviors of rats, pigeons and apes, for example, follow the same formula. Which means, Mother Nature must have found out early during evolution that this principle is a recipe for survival in her species. We simply inherited this survival tool.   

With all these issues stacked in favor of an ever expanding population of chronically ill people, why do I believe that we might be close to the age of chronic health and longevity? For three reasons: Because Wall Street is getting into the act, because we can outfox our brain, and because biomedical science has got the tools ready.

How we will enter the age of chronic health is the subject of the next episode, so stay tuned!

In the meantime, visit my crowd funding campaign, watch the videos, recommend the campaign to your friends and, if you like what you see, participate in our chronic health project: www.indiegogo.com/adiphea

How to admire obese people? The Token Fat Girl

Yesterday, on a whim, I started searching the web for sites where obese people present themselves and how they deal with obesity. My expectation was:  I won't find much. Boy was I wrong. In fact I was so wrong, that I decided to discuss some of the outstanding people whose sites I have seen. Before I get to The Token Fat Girl, let me explain why I didn't expect to find what I found:

There is a stigma attached to being overweight. Interpersonal and work related discrimination against overweight people pervades our society [1]. Whether it's finding a sex partner or a salary, if you are female and have a BMI north of 30, your weight alone reduces your chances compared with a peer of normal weight. And don't think for a moment that my colleagues from the health and medical sciences are free from such bias. One in 4 nurses reports being repulsed by obese patients [2], and exercise science students show a strong bias against obese people, equating obesity with laziness [3]. The frequently used before-after portraits of successful weight reducers have been found to reinforce the belief that weight loss is a matter of volition, which in turn reinforces the stigmatization of the overweight [4]. This bias has become so pervasive in our society that even obese people themselves now endorse the fat=lazy equation [5]. Uncharacteristically for my otherwise more colloquial blog I include here the references to my statements. For one simple reason: To take the wind out of the sails of those who would otherwise eloquently try to summarily refute my statements.  

Now, what's my point? With this type of agony load, wouldn't we rightly expect the obese person to simply change her lifestyle if this change was really up to her free will - her volition - to make? Yes we would. The fact that most obese people really WANT to be slim but never seem to get there should, however, make us question the power of free will over our health behaviors, particularly the dietary and exercise behaviors. Let me illustrate that point a little more.

If the volition-behavior assumption was true, children would change their fattening behaviors once the agony load from being obese crosses a threshold at which they would be motivated to actively pursue weight loss. This agony load is indeed high for the obese child. In fact it has been found to be equal to that of child cancer patients receiving chemo therapy [6]. Yet the percentage of obese children and adolescents has more than tripled over the past 40 years.

So my question to the stigmatizers, to those who believe in the fat=lazy equation, is: if obesity was a result of behavior, and if health behavior is a matter of choice, then why do children and adults choose to be ostracized, stigmatized and victimized?

Obviously our health behaviors are driven by something more powerful than volition alone. I will address this issue in a separate blog entry.

What I want to highlight here is the extraordinary guts of people like The Token Fat Girl, who proudly present themselves and address their weight openly and publicly. Not only is her courage admirable, but so is the frankness with which she approaches her life. I quote from her site: " I've struggled with being overweight or obese my entire life and while I don't agree that I can be obese and healthy, I do believe that it shouldn't stop me from living a pretty decent life." Here is a girl with an admirable sense of reality. A girl with that attitude would certainly solve her weight issues if those were solvable by volition only. 

This issue is at the core of my work. I have a pretty clear model about what drives our health behaviors. That model was part of my dissertation work. I also believe that our strategy of helping people to train a 6th sense for their daily calorie balance is a promising alternative to diets and weight loss fads. I would love to enroll people like the Token Fat Girl into our chronic health project. So if you know somebody who fits this description, give them my contact.  

   

1.           Carr, D. and M.A. Friedman, Is obesity stigmatizing? Body weight, perceived discrimination, and psychological well-being in the United States. J Health Soc Behav, 2005. 46(3): p. 244-59.

2.           Puhl, R. and K.D. Brownell, Bias, Discrimination, and Obesity. Obesity Res, 2001. 9(12): p. 788-805.

3.           Chambliss, H.O., C.E. Finley, and S.N. Blair, Attitudes toward obese individuals among exercise science students. Med Sci Sports Exerc, 2004. 36(3): p. 468-74.

4.           Geier, A.B., M.B. Schwartz, and K.D. Brownell, "Before and after" diet advertisements escalate weight stigma. Eat Weight Disord, 2003. 8(4): p. 282-8.

5.           Wang, S.S., K.D. Brownell, and T.A. Wadden, The influence of the stigma of obesity on overweight individuals. Int J Obes Relat Metab Disord, 2004. 28(10): p. 1333-7.

6.           Schwimmer, J.B., T.M. Burwinkle, and J.W. Varni, Health-Related Quality of Life of Severely Obese Children and Adolescents. JAMA, 2003. 289(14): p. 1813-1819.