Environmental “Obesogens”
Rebecca is a five-year-old girl who has gained 20 pounds in one year and is referred to us for premature breast development. An MRI of her head rules out a brain tumor. A pituitary evaluation to look for the onset of puberty is unrevealing, and tests show no estrogen in the blood. A more detailed history reveals that Rebecca’s mother has recently taken to bathing her daughter in Victoria’s Secret bath gel. The bottle says in large block lettering, “FOR ADULTS ONLY.” The assumption is that the bath gel contains a plant estrogen. The mother is counseled to stop the bath gel, and subsequently Rebecca’s weight gain and breast development both cease.
In 1990 no U.S. state had an obesity rate higher than 14 percent. In just twenty years, not one state is absolved from having a population with a lower obesity rate than 20 percent; thirty-six states have a prevalence of 25 percent or more. These numbers continue to climb, with no signs of abating. Perhaps the most bizarre thing about the obesity pandemic is its spread over time. To think that this national trend is purely a mass alteration in behavioral change, state by state, is to ignore the pattern of this pandemic. Rather, it is more akin to an infectious disease, a contagion, or some other mass environmental exposure. But what can have that effect and that sort of reach?
One of the issues that directed attention to the childhood obesity epidemic, and the possibility of some grand and overwhelming exposure, is the fact that girls have been starting puberty at increasingly younger ages.1 Understandably, this is causing parents undue distress. Studies have demonstrated that, across ethnicities, girls are exhibiting breast development as young as seven years of age: Caucasians (10 percent), African Americans (23 percent), and Latinos (15 percent).2 Many studies have since corroborated the finding of earlier-onset puberty in girls (but not in boys; we don’t know why). Coinciding with the epidemic of early breast development in girls is the epidemic of obesity. Could the two be related? Could it be that the breast development (and perhaps also obesity) is not being caused by the ovary (true puberty), but rather some kind of estrogen exposure?
For hundreds of years the timing of puberty in girls has been advancing earlier and earlier. This advancement has been attributed to improved nutrition and increased weight and fat at younger ages. Higher BMI clearly predicts earlier menarche,3 which suggests that obesity may be the culprit of the recent early-onset puberty. Furthermore, we know that children who constantly exercise vigorously and don’t gain weight, such as gymnasts and ballet dancers (many of whom also suffer from eating disorders), won’t enter puberty at all until they slow down. In addition, their growth is often stunted. This is a perfect example of how the hormone leptin is a permissive factor in the onset and progression of puberty; you have to gain a certain amount of fat to generate the leptin needed to start the process—no leptin, no puberty.4
Due to all this obesity, leptin levels are increasing at younger ages—but is puberty really occurring as early as age seven or not? We’re still not sure how to interpret the data because there are two questions that have yet to be answered. First, is the appearance of breast tissue in girls always a true sign of the onset of puberty? Could it just be fat tissue making the breasts look bigger? You would have to palpate (feel) the breast tissue to be sure; and many of these studies used visual inspection only. (Many doctors feel uncomfortable palpating the breasts of young girls.) Second, how do we know that breast development truly means that puberty has begun? This is not always clear because it depends on the source of the estrogen, and we don’t always know where the estrogen is coming from.
Three sources of estrogen can promote breast development: First, the ovary—when the hypothalamus gets the leptin signal, it can allow the pubertal process to begin. Second, the fat cells, which have the enzyme that makes estrogen—the more fat, the more estrogen. This is true in both women and men (hence obese men get “man boobs” and sometimes need the “manzierre”). Third, any chemical in the environment that resembles estrogen, which could induce breast tissue formation and fat storage. A chemical that disrupts the endocrine system. An environmental obesogen.
What Is an Obesogen?
Scientists have coined the term obesogen to refer to any endocrine-disrupting chemical (EDC) that promotes weight gain and obesity in people. Obesogens can promote obesity in various ways. Like estrogen, they can increase the number of, or promote fat storage into, existing fat cells. Obesogens can alter energy balance to favor the storage of calories and reduce the amount of calories burned at rest (REE; see chapter 13). They can change the mechanisms through which the body experiences appetite or satiety. In other words, obesogens can insidiously hijack the body’s energy balance system, making energy go places that are detrimental to your metabolic health.
Estrogens
It doesn’t take much for any chemical to be an estrogen. The human estrogen receptor is extraordinarily promiscuous; it’ll hook up with just about any chemical that strikes its fancy. And there loads of chemicals that make the estrogen receptor go wild and lose all its inhibitions, promoting breast development and inducing fat cell differentiation, which means weight gain as well.
Estrogens are everywhere. They are in our food, our plastics, and our water supply. Until recently they were used in our pesticides. Perhaps the most famous of these compounds is the pesticide DDT. Used in great abundance during World War II to control malaria and typhus among the troops, this chemical worked to kill off insects because it was an estrogen. Rachel Carson’s 1962 book Silent Spring indicated that DDT was a cause of animal disease and human cancer. The pesticide was banned in the United States in 1972 and in Mexico in 1997. Here’s the kicker: DDT has been absent from the United States for four decades, yet its metabolite DDE can still be found in the urine of pregnant women, even those who were born after 1972. Among the many implications for health, the concentration of DDE in pregnant women’s urine predicts the weight of their children at age three.5 Almost assuredly, DDE is creating extra fat cells before the baby is even born! Could this be driving childhood obesity?
Another well-known estrogen is our newest environmental bogeyman, bisphenol-A, or BPA. This compound is leeched out every time an acid touches a polycarbonate plastic bottle. In other words, every consumable liquid in America. BPA is used in a multitude of commercial products. The BPA-cancer link is strong enough that the state of California has passed a ban of BPA in baby bottles and kids’ toys that will go into effect in 2013. BPA is associated with fat cell differentiation, and urine BPA concentrations are correlated with BMI in adults.6 But remember, correlation is not causation.
The last of our big-time estrogen exposures is genistein, a soy and alfalfa estrogen. Genistein drives fat cell differentiation in rats; exposure at birth predicts increased fat deposition at three and four months. And because it’s in soy, it’s in everything we eat. Even if you’re a carnivore, the meat you consume will be from animals that were fed soy products. If you are a vegetarian, you’ll still be ingesting it in your milk and cheese. And vegans are likely eating lots of soy products anyway (e.g., tofu), so no one is immune. Whether genistein contributes to human obesity is still unknown, and the data are being collected now. However, given the ubiquity of soy products in our food supply, it’s still a cause for concern.
Like that new shower curtain smell? Those are phthalates, plasticizers that render plastics soft and pliable. Phthalates are used in a large variety of items, from the coatings on pharmaceutical pills and nutritional supplements to personal care products, to children’s products such as rubber duckies. In adults, urine phthalate levels correlate with adiposity, waist circumference, and insulin resistance. And most recently, phthalate levels in the urine correlated with waist circumference in New York City children.7Again, while this is correlation and not causation, it is still highly worrisome.
Atrazine and Other Organochlorines
Atrazine is an example of an organochlorine, a pesticide that is highly teratogenic, that is, causing structural malformations in living things (e.g., tadpoles). This has implications for human developmental abnormalities and childhood cancer. Atrazine use has been banned in Europe but not in the United States. Iowa is awash in atrazine because it is the chief pesticide for the state’s corn crop. For the past two decades, there has been a “dead zone” in the northern Gulf of Mexico, killing nearly all the fish in the Delta, due to the atrazine runoff down the Mississippi River. Blood atrazine levels correlate with adiposity and insulin resistance in adults. But again, showing that atrazine causes human obesity is still a long way off.
Tributyltin (TBT)
Tributyltin, or TBT, is not a well-known compound, but it is particularly egregious when it comes to obesity. TBT is a fungicide, used in painting ships to prevent rotting and keep barnacles from sticking to the hull. Because it’s on boats, it’s also in our general water supply, meaning that everyone is exposed to it. When it comes to making fat, TBT does double duty.8 First, it mimics the signals that tell fat cells to multiply; and second, it activates cortisol metabolism so that more visceral fat accumulates (see chapter 6). Bad news all around. Worse yet, a single exposure for a pregnant rat promotes fatty liver in her offspring right at birth, dooming them to a lifetime of obesity and metabolic syndrome. Although we can measure TBT in human urine (so we know we’re exposed), the jury is still out as to whether TBT is a primary driver of obesity in either children or adults.
Smoking and Air Pollution
Everyone knows that smoking is bad news. Yet despite Surgeon General Luther Terry declaring that smoking was harmful to health in 1964, it took thirty years for society to care enough to do anything about it. Why has society enacted these changes now? Thanks to the rights of the nonsmoker, we now have no-smoking laws in public buildings. All this because of secondhand smoke. And no one suffers more than the unborn child.
Cigarette smoke harbors a host of ugly compounds, one of which is thiocyanate, a relative of cyanide. Thiocyanate inhibits the function of the thyroid gland and is known to reduce thyroid levels in school-age children whose parents smoke. This might alter cognitive performance in school. Worse yet, thiocyanate crosses the placenta to the fetus and is also found in breast milk. Cigarette smoking is a well-known cause of SGA (small for gestational age) in newborns and, as elaborated on in chapter 7, SGA infants are at high risk for developing obesity and metabolic syndrome in later life.
But the chemicals you breathe in every day could be even more insidious than someone else’s smoke. One of the most sobering associations, and one that may play a huge role in the worldwide obesity and diabetes pandemics, is air pollution. There is no question that obesity and diabetes rates have increased progressively in industrialized countries. The counterpart to the “a calorie is a calorie” argument is that we now drive everywhere instead of walk, so we don’t burn the energy. Another dogma to be shattered. We’ve long known that asthma, obesity, and diabetes like to congregate in the same individual. Several new studies have shown that living near freeways or other highways is a major risk factor for developing all three. A long-term study of ten-year-olds in Southern California showed that the level of traffic within 150 meters of a child’s home predicted that child’s BMI by age eighteen.9 What is not clear is whether the air quality had direct effects, or whether the degree of traffic altered the child’s level of physical activity and thus promoted weight gain.
Or Is It an Infection?
This whole book is about the obesity pandemic—and a pandemic it is. But when we talk about pandemics, we’re usually talking about some contagion such as influenza, plague, ebola, or something equally movie-worthy. The pattern of obesity propagation looks like some grand exposure. Could it be due to some sort of infection?
Enter adenovirus-36 (Ad-36). This virus starts by giving you standard cold symptoms and then takes over your fat cells. Ad-36 does just what some of these EDCs do: it differentiates your fat cells and makes them divide. Standard transmission studies have shown that infection of monkeys with Ad-36 makes them gain weight. And like any other adenovirus (respiratory infections), Ad-36 is contagious through coughing and sneezing. For obvious reasons, proving causation in humans is a little harder to do. However, Ad-36 antibody levels correlate with BMI in certain populations, particularly in children.10 In one study, 15 percent of obese children were Ad-36-positive, compared to 7 percent of normal-weight children. But within the obese population, those who were Ad-36-positive weighed, on average, 35 pounds more than those who were not. This suggests that Ad-36 might make the obese get obeser. But all these correlations are still not causation. We have a long way to go before we can prove that Ad-36 is a bona fide contributor to human obesity.
You Can Run, but You Can’t Hide
I could go on—the list of offending agents seems endless. And of course, let’s not forget the most ubiquitous toxin of them all: fructose, the Evil Queen/Witch of this story, peddling the poison we just can’t get enough of.
No one can escape. These EDCs are everywhere. We’ve got toxins in the water, plastics, grocery store, and in the very air we breathe. Rebecca may have been affected by obesogens in her bath gel. Indeed, even animal species that drink our water, breathe our air, and eat chow made from the same adulterated foodstuffs (corn, soy) are also getting fatter11 (see chapter 3).
You still don’t want to try to argue that obesity is due to gluttony and sloth, do you?
The obesogen hypothesis makes two important points. First, susceptibility to obesity is part of the human (and animal) condition. These chemicals love to make fat cells, and fat cells love to get filled. Second, obesogens can alter developmental programming of fat cells or the hypothalamus in utero, and thus change the set point for gaining weight as early as birth. Even though the exposure might end, the damage appears to last forever. And there are more of them around today than ever before.
Finally, back to our obese six-month-old. Soy infant formulas are packed with these compounds, and consuming soy formula is a well-known contributor to weight gain. The formula Isomil is 10.3 percent sucrose (Coca-Cola is 10.5 percent sucrose). It’s a baby milkshake! Add to that the genistein in the soy formula, and put all that in a baby bottle containing bisphenol-A. Is that six-month-old looking more like a perpetrator or victim?
How can we reduce our exposure to EDCs? Sadly, reducing such environmental exposure usually requires governmental legislation and public health intervention. Does any government agency have the stomach for that? We’ll address the public health implications of the obesity pandemic in Part 6.