The problem of obesity has now reached epidemic proportions around the world, with more than half of all adults in the UK and USA classified as either overweight or obese (Curr Drug Targets, 2007; 8: 923-34).
What's worse, however, is the fact that childhood obesity is also on the rise. According to the World Health Organization (WHO), in 2007 an estimated 22 million children under five were thought to be overweight worldwide. Such children are more likely to also be overweight as adults, and to develop a host of health problems-from cardiovascular disease and diabetes to various sorts of cancer (Reprod Toxicol, 2007; 23: 290-6).
For the most part, the blame for the obesity epidemic has fallen on diet and lack of exercise, with some pointing the finger at genetic factors, too. But an increasing body of evidence suggests that there may also be something more sinister lying at the root of the problem: toxic chemicals that are commonly found in the environment.
Just as exposure to carcinogens can trigger cancer, scientists are finding that exposure to certain fat-promoting chemicals-especially during critical stages of human development-can potentially lead to excess weight and obesity.
In one of the latest studies to look beyond the traditional explanations for the rising rates of obesity, US researchers discovered a link between body weight and prenatal exposure to dichlorodiphenyl-dichloroethylene (DDE), the break-down product of the formerly widely used insecticide dichlorodiphenyl-trichloroethane (DDT). Although DDT is now banned in most countries, the chemical and its byproducts remain toxic in bodies of water and sediments, and tend to bioaccumulate (build up in organ-isms) in the food chain via marine life and fatty fish.
Using data from more than 250 mothers who live close to-and eat fish from-Lake Michigan, a significant source of DDE, this two-generational study found that daughters exposed to elevated levels of the chemical in the womb were more likely to be overweight as adults. Compared with the group that had the lowest prenatal DDE levels, those with intermediate levels were around 6 kg (13 lb) heavier, and those that had higher levels were nearly 10 kg (22 lb) heavier.
Body mass index (BMI) was also found to be significantly associated with prenatal DDE exposure, increasing by 2.88 in the daughters with the highest vs those with the lowest prenatal levels (Occup Environ Med, 2009; 66: 143-9).
Although these findings are based on a relatively small sample of the US population, according to one of the study's lead authors, Janet Osuch, as reported in a Michigan State University press release (http://news.msu.edu/story/6081/), they apply to any woman exposed to high levels of DDE while still a fetus growing in her mother's womb.
In addition, these findings add to the rapidly expanding research database that suggests that persistent organic pollutants (POPs)-chemical substances that remain in the environment and bioaccumulate through the food web-may play an important role in the obesity epidemic.
Indeed, in a paper published just two months before the new American study, researchers from the University of Antwerp, Belgium, identified prenatal exposures to polychlorinated biphenyls (PCBs)-man-made chemicals formerly widely used in electrical and hydraulic equipment-as a possible cause of childhood obesity.
PCBs, like DDE, are no longer commonly used, but large amounts persist in the environment, and their concentration increases as they work their way throughout the food chain. The Belgian study found that children aged 1-3 years were more likely to be obese if they had been exposed to PCBs in the womb. There was a dose-response relationship: the higher the levels, the higher the BMI. Moreover, they discovered that levels of DDE were also related to BMI, thereby supporting the results of the US study (Environ Health Perspect, 2009; 117: 122-6).
Hexachlorobenzene (HCB), a fungicide used up until the 1970s, is another POP recently linked to obesity. Although it's been banned internationally because of its toxicity, research from Spain suggests that this persistent chemical is still having long-term adverse effects on humans.
In this study, researchers from the Centre for Research in Environmental Epidemiology, in Barcelona, measured levels of HCB in the umbilical cords of 482 children born on the Spanish island of Menorca, and recorded their height and weight at birth, and then at 6 years of age. They found that those children who had the highest levels of HCB in their blood before birth were two to three times more likely to be overweight or obese by the age of six (Acta Paediatr, 2008; 97: 1465-9).
Although such findings do not constitute proof of a cause-and-effect relationship, taken together with the other studies, they do suggest that exposure to POPs in the womb may influence the later development of obesity.
Hazards in the home
Besides POPs, a number of chemicals commonly found in everyday consumer products have also been tied to obesity. One of them-bisphenol A (BPA)-is so ubiquitous that US studies have found detectable levels of the toxic pollutant in more than 90 per cent of the general population (JAMA, 2008; 300: 1303-10). Used in the production of polycarbonate plastics, and in the epoxy resins that line food and drink cans, BPA has recently been blamed for a number of health problems, including diabetes, birth defects and cancer (see WDDTY vol 18 no 8, pages 20-1). Now, it's also been implicated in the obesity epidemic (Environ Health Perspect, 2008; 116: 1642-7).
According to Frederick vom Saal, a professor in the Division of Biol-ogical Sciences at the University of Missouri in Columbia, MO, prenatal exposure to BPA-even at extremely low doses-"increases differentiation of fat cells and also increases glucose transport, both of which may affect later develop-ment of obesity".
Indeed, vom Saal and his colleagues discovered that a brief period of low-dose BPA exposure during the gestation period in mice-an exposure resulting in BPA blood levels that were much lower than those typically found in pregnant women and their fetuses-led to a faster rate of postnatal growth in both male and female mouse pups (Environ Health Perspect, 2004; 112: A344).
Similarly, Japanese researchers have found that pre- and postnatal exposures of mice to BPA led to the development of obesity and hyperlipidaemia, a state character-ized by excess levels of lipids (fats) in the bloodstream (J Atheroscler Thromb, 2007; 14: 245-52).
Although these animal findings may not necessarily apply to humans, one study which looked at BPA levels in young women did indeed find that concentrations were significantly higher in women who were obese compared with those who were not. BPA levels were also positively correlated with BMI (Endocr J, 2004; 51: 165-9).
But BPA is not the only common chemical of concern. Phthalates are also pervasive in both the environment and people, and may have an effect on obesity as well, according to the research.
Used as plasticizers (to make plastics more pliable), solvents, lubricants and stabilizers in the manufacture of a variety of consumer products, phthalates have recently been linked to increased waist circumference and BMI in men, women and teenagers.
In a study involving more than 4000 participants, aged 6-80 years, from the US National Health and Nutrition Examination Survey (NHANES), researchers measured six phthalates in urine and found that individuals with the highest levels tended to have more abdominal fat and higher BMIs-even after controlling for diet, exercise and other potential confounders.
The most consistent associations were found in men aged 20-59 years, but positive correlations were also observed in women and adolescent girls. Alarmingly, all six phthalates were detected in at least 80 per cent of the study participants (Environ Health, 2008; 7: 27).
Similarly, another study found that the men who had the highest concentrations of phthalates in their urine also had significantly larger waistlines than those who had lower levels of these chemicals. According to the researchers, the findings suggest that exposure to phthalates may contribute to the burden of obesity in the general population and to a host of weight-related clinical disorders (Environ Health Perspect, 2007; 115: 876-82).
The smoking link
Perhaps the most convincing evidence of a connection between chemicals and obesity comes from research on maternal smoking. Studies show that children whose mothers smoked during pregnancy are around twice as likely to be obese compared with children of non-smoking mothers.
Indeed, a review published in the Maternal and Child Health Journal identified a total of eight studies in which prenatal exposure to maternal smoking resulted in significantly increased chances of childhood overweight and obesity, with most odds ratios clustering around 1.5 to 2.0 (Matern Child Health J, 2007; 11: 461-73).
It's possible, of course, that other lifestyle factors also come into play, such as childhood nutrition and socioeconomic status. However, a number of studies have made adjustments for these factors and have still come up with the same results. Crucially, one study found that only smoking before or during-but not after-pregnancy increased the risk of childhood obesity, suggesting that smoking exposure in utero rather than family lifestyle factors are instrumental (Eur J Pediatr, 2002; 161: 445-8).
In addition to studies in humans, there's also an increasing body of animal evidence indicating that maternal smoking has the potential to cause obesity in the offspring. Several studies (in rats and rhesus macaques) found that administration of nicotine to pregnant mothers resulted in offspring that were smaller at birth, but which had more body fat. In other studies, rats prenatally exposed to low doses of nicotine were not smaller at birth, but were heavier by 5-10 weeks of age-and had greater amounts of overall body fat (Int J Obes [Lond], 2008; 32: 201-10).
This experimental evidence, along with the research in people, suggests that obesity is yet another adverse effect of smoking during pregnancy. What's more, it adds further weight to the argument that pollution in the womb can have major effects later in life.
Although much more research is needed, studies to date certainly appear to suggest that chemical exposures-particularly those early in life-play an important role in the development of obesity. But how is it that common chemicals can make us fat?
No one knows the answer for sure, but the leading theory is that certain chemicals can wreak havoc on our hormones, which are key factors in maintaining metabolism and controlling body weight.
In fact, phthalates, BPA and POPs-along with a range of other chemicals that have also been linked to obesity (see box, page 7)-all belong to a class of compounds known as 'endocrine disruptors', as they are known to interfere with hormones that govern important biological processes. In the past, exposure to endocrine-disrupting chemicals (EDCs) has been associated with reproductive problems and cancer, but now obesity is emerging as yet another serious consequence (Mol Nutr Food Res, 2007; 51: 912-7).
According to Retha Newbold, a developmental biologist with the US National Institute of Environ-mental Health Sciences (NIEHS) Environmental Toxicology Program, there is already compelling evidence that exposure to EDCs during critical phases of cell differentiation-such as during fetal development in the womb-may have permanent or long-lasting effects, some of which may not even be expressed or detected until later in life. Of course, adult exposures remain a subject of concern, but the fetus is especially vulnerable to EDCs as the pro-tective mechanisms that are available to the adult are not yet fully functional (see box, page 8) (Reprod Toxicol, 2007; 23: 290-6).
"These [prenatal] exposures likely alter mechanisms involved in weight homeostasis," says Newbold. "We're still trying to determine if it's a direct effect on the adipose cells and how they differentiate or proliferate, or whether it's a disruption of the endocrine feed-back loops" (Environ Health Perspect, 2004; 112: A344).
As for smoking, scientists reckon that nicotine exposure in utero could be altering appetite-regulating neurological systems in the brain as well as in the peripheral noradrenergic system, which is involved with metabolic control over adipose tissue (fat) (Environ Health Perspect, 2004; 112: A344). There is also the possibility that other chemicals in cigarette smoke, such as cadmium and lead, could have deleterious developmental effects too, eventually leading to excess weight gain (J Altern Comple-ment Med, 2002; 8: 185-92; Toxicol Lett, 1999; 104: 1-9).
Whatever the mechanism, however, it's becoming increasingly clear that numerous chemicals in the environment have the capacity to promote obesity, even at low levels. The presence of these so-called 'obesogens' means that it's more important than ever to steer clear of chemicals as much as we can-not just for our own health, but for the health of future generations to come.
Other chemical culprits
Diethylstilboestrol (DES). This synthetic oestrogen-widely prescribed from the 1940s to the 1970s for pregnancies at risk of miscarriage-has been shown in several experiments to promote obesity in mice, although the results may not apply to humans. Mice exposed to DES in the womb or shortly after birth were smaller as newborns than their untreated controls, but became significantly larger than the controls by the time they had reached puberty. Food consumption and activity levels were similar for obese DES-exposed mice and normal-weight controls, yet the DES mice accumulated more body fat and, in some cases, had a harder time processing glucose (Reprod Toxicol, 2007; 23: 290-6).
- Tributyltin (TBT). Found in PVC plastics and marine antifoulant paints, TBT is an organotin (a chemical compound based on tin) that may also be an important 'obesogen', according to research conducted by Bruce Blumberg, associate professor in the department of developmental and cell biology at the University of California at Irvine. Laboratory tests of pure TBT showed that the chemical altered receptor activity in animals that eventually led to permanent physiological changes that predisposed them to gaining weight.
"They were not treated with any more tributyltin after that prenatal exposure," explains Blumberg, "they had a normal diet, normal exercise, and yet they were significantly fatter" (Environ Health Perspect, 2007; 115: A242). Although research in humans is lacking, studies suggest that a significant portion of the general population may be exposed to TBT's obesogenic effects (Endocrinology, 2006; 147 [6 Suppl]: S50-5).
- Polybrominated diphenyl ethers (PBDEs). A recent study in rats (so the findings may not be applicable to humans) found that daily exposure to these common, endocrine-disrupting, flame-retardant chemicals-found in everything from carpets and computers to TVs and toasters-led to the development of several "hallmark features of metabolic obesity" (Obesity [Silver Spring], 2007; 15: 2942-50).
The fragile fetus
Although adult exposure to endocrine-disrupting chemicals is, indeed, cause for concern (as shown by the recent studies on phthalates), much of the research on the link between chemicals and obesity focuses on the fetus, as developing organisms are extremely sensitive to chemicals with hormone-like activity.
As a recent scientific review by Retha Newbold and colleagues explains, "Adverse effects may be most pronounced in the developing organism and occur at concentrations of the chemical that are far below levels that would be considered harmful in the adult. . . . The protective mechanisms that are available to the adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism, and the blood/brain barrier are not fully functional in the fetus or newborn. In addition, the developing organism has an increased metabolic rate as compared to an adult which, in some cases, may result in increased toxicity" (Reprod Toxicol, 2007; 23: 290-6).
Numerous studies show that developmental exposure to hormone-disrupting chemicals can lead to adverse effects later in life, such as reproductive problems and even cancer (Mol Nutr Food Res, 2007; 51: 912-7). Now, there's convincing evidence to suggest that this type of exposure might also play a role in the development of obesity-specifically, by altering developmental programming.
As Newbold's review states, "Since a recent study found evidence for a role for developmentally expressed genes in the origins of obesity and body fat distribution, it is indeed possible that early exposure to environmental chemicals with hormonal activity may be altering the genetic programming of adipocytes [fat cells] and their distribution" (Reprod Toxicol, 2007; 23: 290-6).
Cutting out the chemicals
Pregnant women should especially avoid these agents.
- Persistent organic pollutants (POPs). Most exposure to POPs is through consumption of animal fats, particularly fatty fish and high-fat meats. Reducing the amount of such fats in your diet and choosing organic produce will help to keep your POP levels to a minimum.
- Bisphenol A (BPA). Found in polycarbonate plastics as well as food-can linings and dental sealants, there are several ways to minimize your exposure to this hazardous compound.
- Consume fresh, unprocessed foods and avoid canned goods as much as possible.
- Avoid polycarbonate plastic food containers marked with the number '7' in the recycling logo, as these usually contain BPA. In general, they are rigid, transparent, plastic containers. Plastics that are numbered 1, 2 and 4 are safer, as they don't contain BPA.
- Use glass baby bottles, or those made with polypropylene and polyethylene plastics. These pliable, opaque plastics don't contain BPA. Medela-brand bottles used to store breast milk are also BPA-free.
- Choose glass instead of plastic for water bottles, too, or get your water from the tap (filtered). Also, avoid metal water bottles as they may be lined with BPA-containing plastic.
- Avoid using plastic containers in the microwave. Ceramic, glass and other microwaveable dishware are healthier alternatives.
- Avoid storing food and drink in plastic containers. Glass and stainless steel are better, safer choices.
- Phthalates. Produced in huge volumes, phthalates are found in everything from cosmetics to food packaging to children's toys. Exposure can occur through ingestion of food and water, by skin absorption or by inhalation of polluted air (Environ Health, 2008; 7: 27). According to Pollution in People, a report by the Toxic-Free Legacy Coalition in the US (see www.pollutioninpeople.org), you can reduce exposure to phthalates by using:
- PVC-free building products. Avoid vinyl windows and doors, and choose wood instead. For flooring, choose linoleum, cork, bamboo or wood rather than vinyl. Adhesives, caulk, grout and sealants may also contain phthalates, so always check the ingredients before purchase.
- PVC-free shower curtains. Avoid vinyl shower curtains in favour of natural fibres, polyester or nylon.
- PVC-free packaging. Examine the recycling symbol on products you purchase in plastic packaging, as plastics marked with the number '3' in the symbol contain PVC.
- PVC-free toys. Although the use of certain phthalates has been restricted in some countries
in children's toys, it's still a good idea to select products from manufacturers who've pledged to stop using phthalates altogether, such as Lego, Brio and Chicco.
- PVC-free food storage. Buy plastic wrap and storage bags made from polyethylene rather than PVC. For storing food, use glass containers or plastic containers marked with recycling symbols with numbers other than '3' and '7' (to avoid BPA, too).
- phthalate-free cosmetics. Check out ingredient lists and avoid products that include 'fragrance' or phthalates. Choose products from companies such as Dr Hauschka, Lavera and Green People, which make a point of using natural ingredients.