Emerging Picture on Role of EDCs, Microbiome in Obesity, Diabetes

Veronica Hackethal, MD

December 18, 2015

NEW YORK — In the week when the European Court of Justice ruled that the European Commission has not been quick enough in identifying and banning potentially harmful endocrine-disrupting chemicals, one expert said the true role such substances play in the development of obesity and type 2 diabetes is only just emerging.

For years, Americans have been told that they eat too much and exercise too little. And while these two factors are still vitally important, there may be more going on than meets the eye, Deborah Kurrasch, PhD, assistant professor at the University of Calgary, Alberta, told the recent Endocrine Society Hormones & Health Science Writers Conference in New York City

And coupled with the role of endocrine-disrupting chemicals is the contribution of the gut microbiome to this mix, the conference heard.

"Your gut flora may be a primary factor for your health and longevity," Elena Barengolts, MD, professor of medicine at the University of Illinois at Chicago, told assembled journalists.

BPA-Free: Not Necessarily Any Better

The detrimental effects of endocrine-disrupting chemicals on the female and male reproductive systems — including links to hormone-related cancers like prostate and thyroid cancers — and on cognitive and behavioral problems like attention-deficit/hyperactivity disorder and autism have been recognized for some time, said Dr Kurrasch.

But the role these chemicals have likely played in the burgeoning rates of obesity and diabetes seen in the United States over the past 3 decades is only just becoming clear, she noted.

A recent study has found that the same caloric intake and amount of exercise would result in a body mass index (BMI) that is 2.3 kg/m2 higher in 2006 than in 1988, she noted, suggesting that maintaining the same weight as in the 1980s now requires more intense workouts and consumption of fewer calories (Obes Res Clin Pract. 2015; DOI:10.1016/j.orcp.2015.08.007).

Dr Kurrasch went on to describe the knowledge base to date on the more than 100 known endocrine-disrupting chemicals, which are believed to interfere with hormone systems, either by mimicking hormones or blocking normal hormonal signaling. And while bisphenol A (BPA) is the "poster child" of endocrine-disrupting chemicals, in fact there are 13 types of bisphenols and more than 100 known endocrine-disrupting chemicals.

A European study reported earlier this year suggested that health effects from endocrine-disrupting chemicals cost the European Community €157 billion annually, and this report linked prenatal exposure to BPA to childhood obesity, with associated lifetime costs of €1.54 billion.

Chemicals such as BPA have a similar molecular structure to endogenous human hormones and therefore may be mistaken as such by the human body, Dr Kurrasch explained. As fatty molecules, BPAs easily cross membranes like the placenta, where they can potentially act on fetal hormone receptors.

A major problem with BPAs is that they require linker molecules to form plastic and the latter break down over time and with repeated exposure to stresses like heat and sunlight, allowing BPA molecules to leach into food and drink ingested by humans.

Knowledge of this leaching effect has increased consumer demand for BPA-free products. In response, companies have found a "sneaky" way around the issue, one that does not necessarily mean these products are safe, Dr Kurrasch pointed out.

"What we're finding is that BPA-free does not mean bisphenol-free or endocrine-disrupting-free," she stressed.

"The manufacturers can replace molecules and not do any safety profile testing. It's completely legal. They don't have to disclose what they use, and they don't have to disclose whether it's safe," she emphasized.

Finding a Safer Path

Against the backdrop of this increasing concern about endocrine-disrupting chemicals, the FDA, European Union, and Canadian authorities have all said that BPA exposure likely does not pose health risks.

One argument runs that humans excrete these compounds, so they must be safe. But years of research and the fact that BPA has been found in adult and fetal blood refute this argument, Dr Kurrasch said.

The understanding lies in the correct interpretation of toxicology studies, she emphasized.

Many studies have assumed that if higher doses of endocrine-disrupting chemicals are not harmful, then lower doses must be safe, but the endocrine system does not follow this linear pattern — hormones have biphasic dose-response curves, she explained.

Solving the problem represents an almost overwhelming challenge, given the ubiquitous nature of plastics, not to mention the $375 billion plastics industry.

Rather than forcing companies to get rid of bisphenols altogether, Dr Kurrasch suggests encouraging attempts to find a safe alternative.

"We need to be realistic on what we're willing to accept," she emphasized, "There's responsibility on our side as consumers."

Role of the Gut Microbiome

Meanwhile, Dr Barengolts discussed the other end of the spectrum — what lies inside the gut and how this may also play a role in the development of obesity and diabetes.

Ninety-five percent of the bacteria in the human body live in the gastrointestinal tract, she explained. Some can produce a specific toxin called lipopolysaccharide (LPS) endotoxin that causes inflammation, and studies have shown that LPS endotoxin causes obesity and diabetes in animal models, Dr Barengolts pointed out.

And research in humans has shown that lean and obese people have different types of gut microbiota and that, importantly, certain foods — like a high-fat diet — can change the gut microbiota, affecting local immunity, permeability of the gut, and gut hormones.

The net effect is higher fat absorption and fat deposition in the wrong places, like the pancreas.

Nutrition can make a "huge difference" in bringing the microbiome back into balance, Dr Barengolts advised. "Fruits and vegetables time after time in prospective longitudinal studies have been shown to decrease all-cause mortality," she said.

And eating probiotics — foods that contain live bacteria like yogurt and pickled vegetables — can also help, keeping in mind the high-fat content of dairy and high salt in certain fermented foods.

And prebiotics — foods like fiber that only gut bacteria can metabolize — also play an important role. People who have problems digesting these types of foods should introduce them in small amounts, Dr Barengolts recommended, and increase portions slowly over time.

"We evolved eating plenty of fiber, and we evolved with our bacterium; that's why it's so important for health," she concluded.

The Endocrine Society Hormones & Health Science Writers Conference was sponsored by Janssen Pharmaceuticals.


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