Americans are losing the battle of the bulge. Despite poll results indicating that the majority of us feel that our weight is “just about right,” the scale says otherwise. While just 1 in 20 believe that they are “very overweight,” more than 6-times that many are, by definition, obese (BMI greater than 30). The health problems associated with carrying those extra pounds around include an increased risk of diabetes, heart disease, stroke, degenerative arthritis, dementia, and cancer. Millions are dieting, but does it work? You may have read some doom-and-gloom headlines reporting that upward of 95% of dieters regain all the weight lost and then some in the ensuing months after completing a diet, but the truth is that diets do work. They just don’t work very well. A 2007 meta-analysis that reviewed the results of multiple dieting trials found that the average weight loss reported over the first 6-months corresponded to between 5-9% of the patient’s initial body weight (an amount equaling 11 to 19 pounds), with the majority keeping at least a portion of that weight off over the ensuing 24- to 48-months (on average, between 6.5 to 9 pounds). That may not sound like much, but it’s enough to lower the risk of developing many chronic diseases.

 

 

For some forms of cancer, like those found in the breast, colon, and uterus, the increased risk starts with modest weight gain like that seen in a typical, mildly overweight, American with a BMI of 28. The risk doesn’t increase linearly but proceeds almost logarithmically as weight gain progresses. For instance, while the risk of uterine cancer is 50% higher in overweight women, it is 600% higher in women who are obese. The risk for breast cancer increases 2-fold with increasing weight gain. Men aren’t off the hook either; in a large cohort study, there was a 33% increase in the incidence of colon cancer for every ten pounds of added weight after age 21. Adipose tissue (i.e. fat) leads to both insulin resistance and increased levels of circulating estrogens, the former believed to play a role in the formation of digestive tract malignancies, while the latter has been linked to cancers of the breast and uterus. The good news is that this risk disappears when weight normalizes.

There is also evidence linking obesity to dementia. A large cohort study of Kaiser Permanente patients revealed a 3-fold increased risk of dementia later in life in those patients with large waistlines during mid-life. As it turns out, not all fat is created equal. Visceral fat (i.e. fat lining the internal organs) poses more danger than peripheral fat due to its ability to secrete hormones that lead to insulin resistance, with obesity constituting the foremost risk factor for developing type 2 diabetes. As weight increases so does the risk of hypertension, heart attack, and stroke. Next to not smoking, controlling weight is the best thing a person can do to ensure a long healthy life.

Americans currently spend 75 cents of every healthcare dollar on chronic disease and less than 4 cents on the prevention of those diseases. We seem to have our priorities reversed. The key to spending less on healthcare rests in spending more on health. If you’re healthy you don’t use your insurance except for preventative care, which costs far less to administer than reactive care.

Unfortunately, the way to a healthy weight is not as simple as eat less and exercise more. Although one pound of body weight may equate to 3,500 calories, the body’s ability to burn calories is not linear. The thinner you become, the more your body will resist additional attempts to become thinner still. Our BMR (basal metabolic rate) is the amount of energy required to keep the show running. It’s the cost of pumping blood, breathing, digesting, moving, and thinking, and it varies from person to person, which explains why two people eating the same amount of food may have markedly different weights. It also changes as we age, peaking during the teen years and then declining throughout the rest of our lives. Fortunately, you can increase your BMR (basal metabolic rate) while simultaneously decreasing your BMI (body mass index) via a magic process called exercise.

Our bodies are designed to retain weight—not to lose it—which makes a certain evolutionary sense. But Americans no longer live in an age where local environmental stresses lead to food shortages, and this same ability to store fat, which previously conferred a survival benefit, now actually works against us. For the first time in human history, poor Americans are actually more likely to be obese than their economically privileged neighbors. It’s clear that the evolutionary pace of genetic change has proceeded much slower than the revolutionary pace of our dietary change. In The Secret Life of Fat: The Science Behind the Body’s Least Understood Organ and What it Means for You, author Sylvia Tara, explains why losing weight is so difficult.

 

 

As opposed to Gary Taubes’s book, The Case Against Sugar (reviewed in my last post), that heaps the lion’s share of the blame for just about everything on sugar, Tara recognizes that there are many factors at play with no single villain. The Pima Indians of the American Southwest make an appearance in both books. Their story perfectly exemplifies the large role that genetics has on weight. Inhabiting a relative land of scarcity, subsisting primarily on squash, corn, beans, and the meat of small game animals, the Pima developed a “thrifty genotype” that allowed them to live on a diet of few calories, and even less sugar and fat. Then the white man arrived, siphoning off water from the Gila River, the main water supply of the Pima. Restricted to reservations, with little water to grow their crops, the Pima became increasingly dependent on the US Government for food, supplied primarily in the form of milk, cheese, bacon, dry cereal, and canned meats—foods higher in calories and fat than the ones that had sustained them for millennia. At the same time that their diet was changing, so, too, was their lifestyle. Prevented from active hunting and farming, the Pima were forced into sedentary jobs, if they had any jobs at all. The result was a catastrophic rise in obesity and diabetes that soon garnered the attention of the NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases, a branch of the National Institutes of Health) who began studying the Pima in 1965. They found that during the span of just a few short decades, the obesity rate of the Indians had soared to 3-times the national average, despite consuming a diet similar in total calories to the predominately Caucasian communities surrounding them.

Meanwhile, a little farther to the south, the Maycoba Pimas continued living in relative isolation, engaging in the same hunting/gathering behaviors as their ancestors. The results are striking: an obesity rate 1/10^th that of the Phoenix Pimas, and a diabetes rate less than 1/5^th that of their northern counterparts. Certainly, the American Pimas wouldn’t have gained weight without the forced introduction of a Western diet, but it was their genetics that caused them to gain weight far in excess of their white neighbors.

Other research also clearly demonstrates the strong role genetics has on weight. (Not that this is an excuse—having overweight parents does not define your destiny.) In the 1980s, Dr. Claude Bouchard conducted a series of studies that included a large data base of twins, and found significant genetic variations affecting everything from resting metabolism to percent body fat to triglyceride and cholesterol levels. In one of Bouchard’s studies, participants consumed an extra 1,000 calories per day for a fixed period of time. All gained weight, but the variance of that weight gain was huge. While the amount of visceral fat gained by twins was essentially identical, the fat gained by non-relatives varied 6-fold. Bouchard found similar genetic variances in a person’s ability to lose weight through exercise, concluding that roughly half of a person’s propensity for exercise-induced weight loss is genetically encoded. So it’s not just sugar. And it’s not just calories in-calories out.

 

 

Genes can even confer food preferences, with people possessing the FTO gene demonstrating a distinct partiality for calorie-dense foods that, after consumption, are more likely to be stored in the form of “white fat” than the metabolically active “brown fat” seen more in lean individuals. Carriers of the FTO gene have a 23% increased risk of becoming obese relative to non-carriers.

Similarly, there are genetic variances that play significant roles in the development of insulin resistance and diabetes. The IRS-1 gene encodes for a protein that mediates insulin sensitivity at the cellular level. Those with the IRS-1 A variant wind up predisposed to elevated blood lipids, insulin resistance and metabolic syndrome, while those with the IRS-1 B variant have higher levels of peripheral fat with lower serum levels of triglycerides and LDL-cholesterol. For some people, it really is all about the genes.

There are also differences in the way our brains respond to food. The right prefrontal cortex is the area of the brain most tightly linked to the cognitive control of food intake. Over-activity in this part of the brain has been linked to anorexic behavior, while under-activity provokes the opposite. There is even a unique eating disorder, known as “Gourmand’s Syndrome,” wherein patients crave fine foods after suffering a stroke to a specific location of the brain. (I guess if you’re going to have a stroke then this is the one to have). Specialized brain imaging studies in obese patients (but not in normal weight controls) have revealed an inverse relationship between the number of dopamine receptors and body mass index. Dopamine is the primary reward neurotransmitter, but because obese patients have relatively fewer receptors, more dopamine (and consequently more food) is required to trigger the same response relative to normal weight individuals. Further observational evidence for the food-as-addiction theory occurs in psychiatric patients who often demonstrate significant weight gain when given dopamine-receptor blockers as part of their treatment. Finally, the down-regulation of dopamine receptors observed in the brains of obese people also occurs in a variety of other addictions (e.g. cocaine, methamphetamine), suggesting that certain individuals may truly be “addicted” to food. Despite the cynical response from a plethora of critics that greeted the AMA’s decision to label obesity a disease, there is plenty of observational evidence to support that notion.

There are differences between the sexes when it comes to weight. As author, Sylvia Tara, notes: “On all continents of the world, and in every race and culture, women store more fat than men do.” Not only do they store more fat but it’s also harder for them to lose it. Fat is less metabolically active than muscle, so a man weighing 160 pounds with 20% body fat will burn more calories both at rest and during exercise than a woman weighing an equal amount with 30% body fat. On average, across a host of populations, men consume 51% more calories than women. It’s not all bad news for the smarter sex, however, as the “pear” shape of overweight women is healthier than the “apple” shape of overweight men.

Both sexes start out with a nice coat of baby fat that is primarily “brown fat,” the metabolically active kind that burns calories to generate heat while also providing insulation against heat loss. Things percolate along nicely during childhood until the storm of adolescence hits where the difference in hormones between women and men exert their effects, resulting in fat deposition around the hips and breasts of women (without which menstruation does not occur), while promoting muscle deposition and fat loss in men.

It turns out that fat is far from being just a depot for extra calories. Fat has receptors to “listen” with, including binding sites for insulin, cortisol, testosterone, estrogen, progesterone, growth hormone, and thyroid hormone. Insulin stimulates fat cells to take up glucose, converting it to more fat. But here is where it’s especially true that not all fat is created equal. Visceral fat (i.e. fat adjacent to our internal organs and infiltrating the liver) leads to all sorts of harmful effects like chronic inflammation, metabolic syndrome, diabetes, heart disease and dementia, while that in the periphery mostly just affects our appearance. Stress hormones, like cortisol, shunt fat to the viscera, while exercise (particularly high intensity training) stimulates the release of testosterone and growth hormone that do the opposite. This occurs because, in addition to “listening,” fat can also “talk,” releasing both leptin, a key satiety hormone that signals the brain to stop eating, and adiponectin that promotes the uptake of glucose and fat into the periphery and away from the viscera. These are both good things.

The body is all about checks and balances. For every signal, there is a counter-signal, and Tara discusses what happens when these signals go awry. A tiny percentage of obese patients are genetically unable to synthesize leptin, effectively negating their physiologic “off switch.” These people eat merrily on, but when given supplemental leptin their weight decreases dramatically. One such patient described in the book becomes progressively more obese and food obsessed, as her svelte sisters and parents watch helplessly, until an astute physician discovers the missing link and begins providing her with leptin. The treating physician describes what happened next: “She went from being a completely focused eating machine into a normal kid.” In patients with a normal leptin gene, however, administering extra leptin doesn’t work because, like the boy who cried wolf, a body constantly signaled with leptin gradually learns to ignore the message. There is no miracle pill for those of us with a normal leptin gene.

And just as the body is equipped with a signal to suppress appetite (leptin), it is also supplied with another to stimulate it. An empty stomach secretes ghrelin, a chemical that stimulates the appetite centers in the brain. Distending the stomach with food turns the signal off but the process takes time, which is why those who eat slowly ultimately eat less. Solid foods work better than liquids, another reason to avoid high-calorie soft drinks. The presence of ghrelin and the absence of leptin triggers hunger.

And here’s something you probably didn’t know: obesity can be contagious. Chickens injected with the SMAM-1 virus soon become obese. What’s more is that when infected chickens are placed into cages with uninfected ones, the previously uninfected chickens also become obese, indicating that a propensity toward fatness may be spread from one animal to another (at least in chickens). There is good reason to believe this also holds true for humans. Researcher, Nikhil Dhurandhar, found that when he tested his obesity clinic patients for the same chicken virus noted above (not previously thought to infect humans) a surprising 20% of them tested positive. In additional to chicken adenoviruses, there are also human adenoviruses linked to obesity. While 36% of obese patients test positive for the Ad-36 virus, only 11% of non-obese patients do, and in a study of 28 sets of discordant twins where only one tested positive for virus exposure and the other didn’t, there was a clear correlation between antibodies to the virus and subsequent obesity.

Want more? There are multiple species of bacteria in our gut that assist in the digestion of sugars and nutrients, the absorption of which contributes to the likelihood of our becoming obese. For example, Firmicutes species are more efficient at starch digestion than Bacteroidetes species, and, as it turns out, the same Western diets that are associated with diabetes are the ones that promote growth of the former at the expense of the latter. More starch digested in the gut means more sugar available for absorption and a larger insulin response. More insulin = more insulin resistance. The good news is that it might be possible to tip the profile of our gut microbiome to advantage. Diets high in prebiotics (non-digestible plant carbohydrates that promote healthy gut bacteria) result in higher concentrations of Bacteroidetes species, in addition to promoting the growth of other bacteria critical for maintaining a healthy gut mucosa. Still, we’re a long way off from being able to dial in the right proportion and types of bowel microflora necessary to prevent diabetes or any other chronic disease. Weight loss won’t be coming in pill form any time soon.

The most interesting chapter is probably the one where Tara discusses “how fat fights to stay on you.” When obese people lose weight, it’s much harder for them to keep that weight off than it is for someone who was never heavy to begin with. This is a big reason why diets so often fail. For example, consider a non-obese woman weighing 145 pounds who loses 10% of her body weight through 6 months of hard work, finally achieving her desired weight of 130 pounds. Unfortunately, to stay there she will have to consume 22% fewer calories than a woman naturally weighing 130 pounds who had never gained weight to begin with. As folks lose weight, so does the amount of leptin they release in response to a meal, meaning that previously overweight individuals not only have to eat fewer calories to maintain their lower weight, but also have to deal with more hunger than their naturally thin, never overweight, counterparts. There are other ways in which fat fights to stay. The release of both thyroid hormone and epinephrine decline with weight loss, resulting in a slower metabolism that, in turn, promotes weight gain. While these effects may be helpful to ensure survival in times of starvation, they aren’t particularly helpful in a society where fast food restaurants lurk on every corner.

 

 

In a Pew Research Center survey, Americans overwhelmingly believed that a lack of exercise (75%) and a lack of willpower (59%) were the most important factors contributing to weight gain. While I am a huge proponent of eating less and exercising more, it is unlikely that this strategy is going to work for many Americans. Despite 45 million gym memberships, obesity rates haven’t declined. Although 65% percent of men and 78% of women report they are attempting to either maintain or lose weight, fewer than a quarter are actually successful in doing so. One study which enrolled overweight women into an exercise program found that, while all exercise participants reduced their waist circumference, the law of diminishing returns applied; those exercising the most reported only half the expected weight loss relative to those who exercised less. Why? Because exercise stimulates appetite. More exercise = more food.  Running 5 miles to burn off 500 hundred calories won’t help much if followed by a 200-calorie energy drink and a 400-calorie muffin. Although the health benefits of exercise are myriad, significant weight loss isn’t necessarily one of them.

One thing that clearly doesn’t work is blaming the victim. Labeling overweight individuals as gluttonous, lazy, or disgusting has far-reaching negative consequences. One survey revealed that overweight individuals were 12-times more likely to report employment discrimination than their normal weight colleagues, while obese and very obese individuals reported rates 37-times and 100-times higher, respectively. In studies of obese women and bariatric surgery candidates roughly half reported having received inappropriate comments regarding their weight from physicians. The consequences of stigmatization include binge eating, diet abandonment, exercise avoidance, depression, and social phobia. In one study of extremely overweight women, more than two-thirds reported delaying healthcare because of their weight, and 80% reported that their weight represented a barrier to receiving appropriate care.

In fact, next to family members, physicians are the most likely group to stigmatize people about their weight. In a survey of more than 620 primary care physicians, more than half viewed their obese patients as “awkward,” “unattractive,” “ugly,” and/or “non-compliant.” Other studies have clearly demonstrated that physicians consistently cite physical inactivity, overeating, food addiction, and personality flaws as the leading contributors to weight gain. These attitudes serve neither party well, because while it is nearly impossible to shame people into losing weight, it is readily possible to shame them into gaining it. Here’s hoping that the next generation of physicians adopts a more enlightened approach to this ubiquitous societal problem.

A few final thoughts:

• Diets that vilify a single food don’t work.
• Diets that champion a single food don’t work either.
• While not all calories are created equal, no diet works without restricting them.
• The success of any diet varies markedly within a population.
• Trust but verify. When it comes to healthy eating, there is no “one size fits all.”

In addition to Gary Taubes’s The Case Against Sugar, and Sylvia Tara’s The Secret Life of Fat, I highly recommend Michael Moss’s Salt, Sugar, Fat and Michael Pollan’s wonderful books, The Omnivore’s Dilemma and In Defense of Food.

 

 

 

References:

1. Sylvia Tara, The Secret Life of Fat: The Science Behind the Body’s Least Understood Organ and What It Means for You, (W.W. Norton & Company Ltd., New York, NY, 2017).
2. Marion Franz et al., “Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Weight-Loss Clinical Trials with a Minimum 1-Year Follow-Up,” Am. Diet. Assoc. 2007; 107: 1755-67.
3. Eugenia E. Calle et al., “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults,” NEJM 2003; 348 (17): 1625-38.
4. Jiyoung Ahn et al., “Adiposity, Adult Weight Change, and Postmenopausal Breast Cancer Risk,” Arch.of Internal Med. 2007; 167 (19): 2091-2102.
5. Caspar Thygesen et al., “Prospective Weight Change and Colon Cancer Risk in Male US Health Professionals,” International Journal of Cancer 2008; 123 (5): 1160-65.
6. Kenneth F. Adams, et al., “Body Mass and Colorectal Cancer Risk in the HIH-AARP Cohort,” Am. J. of Epid. 2007; 166 (1): 36-45.
7. Rachel A. Whitmer, et al., “Obesity in Middle Age and Future Risk of Dementia: A 27 Year Longitudinal Population Based Study,” BMJ 2005; 330: 1360-62.
8. B. Vodusek, “Tackling the Burden of Chronic Disease in the USA,” Lancet 2009; 373: 185-86.
9. Miguel Alonso-Alonso and Alvaro Pascual-Leone, “The Right Brain Hypothesis for Obesity,” JAMA 2007; 297 (16): 1819-22.
10. John Cloud, “Why Exercise Won’t Make You Thin,” Time, Aug. 9, 2009, www.time.com.
11. Nancy E. Adler and Judith Stewart, “Reducing Obesity: Motivating Action While Not Blaming the Victim,” Milbank Quarterly 2009; 87 (1): 49-70.
12. : M.V. Roehling et al., “The Relationship Between Body Weight and Perceived Weight-Related Employment Discrimination: The Role of Sex and Race,” J. of Vocat. Behavior 2007; 71: 300-18.
13. Rebecca M. Puhl and Kelly D. Brownell, “Confronting and Coping with Weight Stigma: An Investigation of Overweight and Obese Adults,” Obesity 2006; 14 (10): 1802-15.
14. A. Anderson and T.A. Wadden, “Bariatric Surgery Patients’ Views of Their Physicians: Weight-Related Attitudes and Practices,” Obesity Res. 2004; 12: 1587-95.
15. Rebecca M. Puhl and Chelsea A. Heuer, “The Stigma of Obesity: A Review and Update,” Obesity 2009; 17 (5): 941-64.
16. K. Amy, et al., “Barriers to Routine Gynecologic Cancer Screenings for White and African-American Obese Women,” Internat. J. of Obesity 2006; 30: 147-55.
17. D. Foster et al., “Primary Care Physicians’ Attitudes About Obesity and Its Treatment,” Obesity Res. 2003; 11: 1168-77.