The new obesity

Obesity has just slipped out of the grasp of mathematical logic: if one burns as many calories as one consumes, one will not gain weight. Today it is easy to spot people in jogging parks, aerobic centres and gymnasiums who defy this logic. Take Sundar Rao of Mumbai who weighs 89 kg. He has been trying hard to shed the extra pounds for the past 15 years. A 53-year-old chartered accountant, he religiously takes out an hour from his busy schedule for exercising and has tried all possible diet regimes he could dig out of the massive literature and studies done on weight loss. Rao has cut down on carbohydrates, increased protein intake and reduced the amount of fat he consumes. Eating out is curtailed, fruits have been added to the plate and packaged foods kicked out, but to no avail. For his height of 170 centimetres, he is 19 kg overweight; worse, he continues to gain weight.

Forty-year-old Sapna Vashista of Delhi has a similar problem. For the past six years, she has maintained a strict diet regime. One hour of yoga or aerobics and evening walks are part of her daily routine. A part-time fashion designer and mother of two, she does most of the housework. Still her weight does not dip below 72 kg. For her height of 165 centimetres, Vashista should not weigh more than 63 kg.

Both Vashista and Rao share the fate of many people who even after hours of slogging on the treadmill and giving a miss to their favourite food are unable to shed those extra pounds. The World Health Statistics released in May by WHO also points to the growing trouble. It shows obesity has doubled across the world between 1980 and 2008. Health experts say overeating and junk food are the biggest reasons behind the rise in obesity world over, but they cannot explain why some people are unable to lose weight when they control these habits.

Moreover, food could hardly be blamed for the increase in weight of babies below six months. Data from a research by Harvard Medical School shows the percentage of overweight infants has nearly doubled from 3.4 to 5.9 between 1980 and 2001 in the US.

Baffled researchers who set out to find the reasons say the toxins in the environment, microbes and rise in temperature also play a role in making people fat. Specifically, exposure to certain toxins, such as pesticides, emissions from vehicles and the material that the plastic bottle is made of, can lead to weight gain. Epidemiological studies suggest everyone, including those not yet born, are at risk. Most such studies have been done in the US.

For instance, a study in the US on pregnant women in New York City showed that women exposed to higher concentrations of polycyclic aromatic hydrocarbons, or PAHs, from vehicular and industrial exhaust and smoke from cigarettes, were more than twice as likely to have children who were obese by the age of seven. The study was conducted by researchers from Mailman School of Public Health at Columbia University.

The National Health and Nutrition Examination Survey in the US shows similar results. When children between six and 19 years of age were tested for the presence of pesticide 2,5-dichlorophenol—commonly used in moth balls, and room and toilet deodorisers, and previously used as an insecticidal fumigant—it was found that obesity was directly proportional to the levels of the chemical in the blood. The study was published in Reviews on Environmental Health in 2011. Adults with higher levels of Bisphenol A (BPA)—commonly used in plastic bottles—were also found to be more prone to general and abdominal obesity by researchers of the Harvard School of Public Health in Boston. Till date, about 20 chemicals have been nailed for inducing weight gaining tendencies and many more may soon make it to the list. Based on their effect, the chemicals have been christened obesogens (see ‘History of obesogens’).

This does not mean diet regimes and treadmill are redundant. Whether obesogen exposure causes permanent changes in the body leading to obesity is currently under study in laboratories across the world, developmental biologist Bruce Blumberg says. Epidemiological studies give only indications. Direct studies are available only on animals. In his lab in the University of California, Irvine, US, Blumberg is analysing the obesogenic impact of a chemical, tributyltin (TBT), on mice. TBT is a biocide that is used in paints in ships to prevent the growth of algae on the hulls. It has now been banned because it leaches into the sea and affects marine life. Blumberg says, “Prenatal exposure to TBT produces irreversible effects in mice.” They get fatter despite a normal diet because TBT alters their metabolism. “So if you were exposed at a sensitive time during your life such that you have more, larger fat cells and stem cells that are predisposed to become fat cells, you will have to fight a lifelong battle against weight gain.”

Exposure to obesogens at any age can lead to obesity, but foetuses and young children have been found to be the most vulnerable. The chemicals enter the developing foetus through the mother’s blood and cause modifications in the expression of genes. These are called epigenetic changes and lead to “foetal programming”. For example, under the influence of the toxins the stem cells may be programmed to make fat cells instead of bone cells, predisposing the unborn child to be plump. A study published in the May issue of PNAS found that epigenetic changes caused by a fungicide, vinclozolin, can be passed on to as many as three generations.

In children and adults, however, the obesogenic effect of chemicals manifests as changes in metabolism through regulation of hormones. For instance, the chemicals affect the functioning of the thyroid gland, which controls metabolism. This lowers the metabolic rate and the body burns fewer calories. Other hormones affected by obesogens are leptin that regulates the feeling of satiety and resistin that reduces insulin sensitivity and leads to type 2 diabetes. These hormones are produced by the adipose tissue which till recently was believed to be just a storage space for fat. Studies have found that this tissue too has become a target of obesogens such as the fungicide, tolylfluanid. It increases the formation of fat cells and reduces leptin secretion and results in higher food intake. Another chemical, tributyltin chloride affects production of fat cells by controlling a receptor protein on the nucleus of the stem cells called peroxisome proliferator-activated receptor gamma (PPARγ). It stimulates the receptor and predisposes stem cells to become fat cells.

The WHO’s health statistics reveal that women are more likely to be obese than men. This was established by a study published in the May issue of Environmental Health Perspectives where the researchers studied 665 Danish women who reported pregnancy in the late 1980s. The levels of perfluorooctanoate (PFOA)—a chemical used to make non-stick cookware—were measured in their blood. The researchers analysed Body Mass Index (BMI), an indicator of body fat, of their offspring 20 years later in 2009. They found daughters of women, who had about 6 nanogram/millilitre (ng/ml) of PFOA in their serum, had on average 1.6 kg/m2 higher BMI compared to daughters of women who had about 2 ng/ml of the chemical in their blood. They did not find the BMI difference in male offspring.

Researchers say the reason behind women being more susceptible could be that they have more fat deposits in the body. This makes them more vulnerable to the fat-soluble environmental toxins. Women have 25-31 per cent body fat, while men have 18-25 per cent, according to American Council on Exercise.

What is more worrisome is the fact that the obesogenic effect of the chemicals is evident even at very low doses. The same chemical at high doses becomes toxic and leads to weight loss. The obesogens do not follow the long held principle of toxicology which suggests that chemicals follow a linear curve—the larger the amount of the chemical, the more the effect on people. In case of obesogens lower doses can have more effect. This means regulators are unlikely to set appropriate safe limits for chemicals since they test them taking into consideration their linear pathway.

Frederick S vom Saal, professor at the University of Missouri in the US, who has done pioneering work on BPA, including analysing its association with obesity, says that most of the studies show that the human body carries between 0.5 and 4 ng/ml (parts per billion) of BPA in the serum. This range can be harmful, he says. The chemical can mimic estradiol and cause breast cancer even at amounts below one part per trillion, 1,000 times lower than found in the human body, he explains.

Research on obesogens is still in its infancy. Scientists are looking at all kinds of chemicals with suspicion. A decade of research has identified about 20 chemicals present in the environment as obesogens. A look at some of the chemicals and how they make one fat

There is no escaping the ubiquitous obesogens but their effects can be reduced in two ways. One, by understanding the cellular and molecular mechanisms of obesogens and then controlling their action. Two, by curbing their release into the environment. But far from taking any action, India remains oblivious to the very presence of obesogens. Even obesity does not receive due attention.

India does not have an estimate of the number of people who are overweight or obese, while considerable research is being carried out across the world to understand the obesity mechanism. There are only a few independent indicative studies in India. A study by National Diabetes, Obesity and Cholesterol Diseases Foundation, a non-profit in New Delhi, shows that prevalence of obesity among adolescent youth between 14 and 17 years of age in the state increased from 9.8 per cent in 2006 to 11.7 per cent in 2009. During this period, the chances of a person being underweight decreased from 11.3 per cent to 3.9 per cent.

An Indian Council for Medical Research (ICMR) survey on risk factors for non-communicable diseases in 2011 also suggests that the problem is increasing. Among the seven states studied, more overweight and obese people were seen in urban areas than in rural areas. Kerala had the highest numbers of both overweight and obese people—more than 25 per cent of the population was overweight there (see ‘Obesity burden’).

Yet obesogens have not even caught the attention of researchers and doctors in the country. Most researches still focus on diet-related aspects of obesity. To find out if research on obesogens is being undertaken, Down To Earth, contacted premier institutes of the country, including the Indian Institute of Science in Bengaluru, Annamalai University in Chennai and University of Calcutta. It drew a blank.



Researchers at medical colleges, such as the Christian Medical College at Vellore and All India Institute of Medical Sciences in Delhi, were also contacted. Many doctors had not even heard the word obesogen. “This concept of obesogens is fairly new,” says Surender Kumar, chairperson of the department of endocrinology and metabolism at Sir Ganga Ram Hospital. He is one of the few doctors aware of the new science.

The subject has not attracted the attention of either the Council of Scientific and Industrial Research, the organisation that controls all basic and applied research in the country, or ICMR, the premier government body that governs medical research in the country, similar to the National Institute of Health in the US. “We should not ape the West. Instead, we should come up with our own ideas for studies. Whatever is happening in the US may not be relevant to India,” V M Katoch, director general of ICMR, says.

Meanwhile, Prashant Mathur, scientist with the non-communicable diseases division at ICMR, points out while the agency has not funded any project on obesogens per se, two studies are analysing changes in animals due to endocrine disruptors. The research under way at the National Institute for Research in Reproductive Health at Mumbai is looking at epigenetic changes in the male rat’s germ line following neonatal exposure to BPA and the chemical’s genotoxic and mutagenic activity. P K Nag, director of the National Institute of Occupational Health at Ahmedabad, an ICMR unit, points out the short-sightedness of such research, “We have been looking at lots of endocrine disruptors, but we have not found any impact on obesity or diabetes. Perhaps we have not looked at these aspects. We do consider this an important topic and will study in the near future.”

The omission is glaring because obesity triggers several non-communicable diseases (NCDS) like heart attack, arthritis, diabetes, hyper- and hypo-thyroidism and cancer. A study in Australia published in the July 2009 issue of Cell Metabolism, for instance, found that fat cells release a protein called pigment epithelium-derived factor, which triggers events that lead to type 2 diabetes. An analysis by Centres for Disease Control in the US shows that a 61 per cent increase in diabetes between 1991 and 2001 coincided with a 74 per cent increase in obesity during the same period, thus suggesting a correlation between the two.

Non-communicable diseases are expensive to treat and developing countries like India are not equipped to tackle them. Even developed countries find it difficult. A recent projection in the US also suggests that 42 per cent of the people in the country are likely to end up obese by 2030. This is a rise of six per cent from 2010. Health economists at Duke University Global Health Institute in the US predict that if the obesity rate stays at the 2010 level instead of rising then the country could save more than $549.5 billion in weight-related medical expenditure from now till 2030. At present, the country spends $147 billion on it.

Although South East Asia seems to be least affected by obesity, according to WHO’s health statistics, there is evidence that the problem is increasing. Experts say that if these regions take immediate steps, the problem of obesity can be contained.

If doctors continue to ignore the role of toxins in obesity and refer patients to strict diet regimes and bariatric surgery (cutting or banding portions of stomach), the problems resulting from obesity-related diseases will increase. “Reports show reducing weight raises levels of obesogens in the serum,” says Hong Kyu Lee of the department of internal medicine, Eulji University School of Medicine, in Korea who has studied the obesogenic effect of atrazine, a herbicide. “This in turn causes a yo-yo phenomenon with increased cardiovascular diseases later in life.”

Researchers at French National Institute of Health and Medical Research have also proved this effect. They estimated the amounts of persistent organic pollutants (POP) in 71 obese people and compared them with that in 18 lean women. They found that the total POP burden was two to three times higher in obese persons. When these people lost weight through bariatric surgery, the amount of POP in the serum increased. There was evidence of liver toxicity in them. The study was published in Environmental Health Perspectives in March 2011.

Similarly, when researchers from Canada studied two groups of obese individuals who were either following a diet programme or underwent surgery, they found that levels of organochlorine, a component found in common pesticides, increased by 23.8 per cent in their blood compared to the control group, which comprised normal weight individuals who did not undergo any weight loss intervention.

But it is not yet time to press the panic button for those who want to lose weight. “This is a new area where there is very little data that shows weight loss can release POPs from the body’s fat stores. The data is also insufficient to determine the health effects of the released toxins,” says Jerrold J Heindel of National Institute of Environmental Health Sciences. “It is likely that the health benefits of weight loss will outweigh the toxic effects of the released toxins.”

Stopping obesogens from being released into the environment is no easy task. Efforts to reduce the use of several of these chemicals in India and elsewhere have met with little success. The Stockholm Convention on Persistent Organic Pollutants (POPs), effective from May 2004, has till date mandated phasing out the use of 22 toxic chemicals—including DDT, an insecticide, and dioxins, released by burning plastics, that have obesogenic effects. But DDT continues to be used in anti-malarial sprays, while dioxins continue to be produced.

In many countries, cases have been filed against manufacturers using these chemicals and the government. The Natural Resources Defense Council, an environmental action group in the US, had petitioned the Food and Drug Administration (FDA) in 2008 to ban BPA used in baby bottles and beverage packaging. Despite the fact that many manufacturers have phased out the chemical due to consumer demands and countries such as Canada, Japan and China have banned it, FDA, in March 2012, ruled out the need to ban BPA. It said the evidence of harm was available only from animal studies. They also suggested that the risk was little because humans metabolise and eliminate BPA much more quickly than lab animals. Moreover, organisations like American Chemistry Council, which represents 85 per cent of the chemicals manufacturing capacity in the US, have been lobbying with FDA to recognise BPA as a safe product.

In India, very few studies have measured the level of toxins like BPA in humans. One such study led by Kurunthachalam Kannan of the department of environmental health sciences, State University of New York analysed the levels of these chemicals in humans. His team found 2.90 μg/day of BPA in the urine of Indians. This is significantly lower than the tolerable daily intake recommended by the US Environmental Protection Agency of 50 μg/kg/day.

The levels of the toxins are, however, high in air, water and soil. Researchers from Japan collected air samples from cities in India as well as elsewhere. They found that in Mumbai and Chennai the levels of BPA were 10 times higher than in China, Japan and New Zealand. BPA is released into the environment when plastics, electronics and other waste material are burnt and during the manufacturing of products containing it.

An analysis by National Institute of Oceanography in Goa showed that marine fish, shrimps, squids and crabs collected from Mumbai, Goa and Karwar had high concentrations of organotins that affect stem cell differentiation. Another study by the institute earlier in July had found that organotins were high in soil samples from the Sundarbans mangrove wetland and the Hugli river basin.

Is this chemical load harming us? There will be more clarity on the link between obesogens and weight gain once the results of a multi-nation study funded by the European Commission are released sometime in 2013. The OBELIX project (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). The study was kicked off in May 2009 in Belgium, the Netherlands, Norway and Slovakia and is investigating six groups of endocrine disrupting chemicals—dioxin-like compounds, non-dioxin-like compounds, organochlorine pesticides, brominated flame retardants, phthalates and perfluorinated compound. The researchers are collecting samples of cord blood and breast milk to estimate the level of chemicals in them and determine their impact on the weight of offspring. Other studies under the project will be on mice and characterise the effects of the chemicals on the body.

Even the US is rising to the challenge. One of the recommendations of the task force set up by its President Barack Obama in 2010 to solve the problem of childhood obesity within a generation suggests that federal and state agencies should look at the possible role of obesogens in childhood obesity. The March 2011 Strategic plan for National Institute of Health’s Obesity Research suggests that impacts of environmental toxins on obesity be studied.



Obesogens’ role also needs to be included in the ongoing NCDs debate. At the 2012 World Health Assembly in May in Geneva, countries did say that NCDs should be addressed through a multi-pronged approach but the focus was on food. Discussions also stressed considering the links between social determinants of health—toxins can be one—and NCDs. Reducing exposure to toxins requires efforts at the individual and policy level, says Andrew Rundle, associate professor of epidemiology at Columbia University in the US. He gives the example of PAH that is present in both cigarette smoke and vehicle exhaust. While individuals can avoid cigarettes, the government can switch buses from diesel to less polluting fuels, he adds.

There are other ways as well. Choosing the right nutrition can be one. Bruce Blumberg, development biologist, says that diets should not have high amounts of storable calories (carbohydrates, for example). “No one is doomed,” quips Blumberg.