In a scientific first, researchers gave people BPA — and saw a link to precursor of type 2 diabetes
The controversial study suggests that BPA exposure deemed safe by the feds could alter the amount of insulin released and elevate people's type 2 diabetes risk
A first-of-its-kind study of a small group of people exposed to a very small amount of bisphenol-A (BPA) is raising questions about the federal government's stance that low doses of the common chemical are safe — as well as the ethics of conducting such an experiment on humans.
The authors say their findings, which they emphasize need to be repeated, build on growing evidence that continued exposures over time to BPA — widely used in plastics, canned food linings and receipt paper — might increase a person's risk of developing insulin resistance and type 2 diabetes.
"We're living in an age where type 2 diabetes is rampant. Here is a signal of a new path to explore for what is causing it," said Pete Myers, founder, CEO and chief scientist of Environmental Health Sciences and a co-author on the study published today in the Journal of the Endocrine Society. (Editor's note: Myers is also the founder of Environmental Health News, though the publication is editorially independent).
More than 9 percent of the U.S. population has diabetes — predominantly type 2 diabetes, which means the body struggles to make or use insulin. Multiple factors can raise a person's risk of developing type 2 diabetes including poor diet and lack of exercise.
To this point BPA research has been confined to animal testing and epidemiological studies that compared the health of different populations of people — without purposefully exposing any of them to the chemical. This is the first time researchers have tested BPA on humans, who are exposed daily to the chemicals when they eat, drink and shop.
"We found an effect with a dose of BPA that shouldn't produce an effect"
In the two-part experiment, the researchers tested production of insulin — the hormone that keeps blood sugar levels from getting too high or too low — in response to glucose hitting the bloodstream. Blood samples were taken from each of the 16 participants both after they drank a cocktail containing BPA and at a separate visit, after they drank an identical cocktail that did not contain BPA.
In both cases, the cocktail followed administration of glucose — via a drink for the eight participants in part one of the experiment and via an IV for the eight participants in part two.
The amount of insulin released, on average, differed significantly between the visits — higher with BPA exposure in the first experiment, which focused on the early release of the hormone, and lower with the exposure in the second, which focused on the later phase of insulin response. And participants who already had relatively poor blood sugar control seemed more sensitive to BPA's effects.
"We found an effect with a dose of BPA that shouldn't produce an effect," said Angel Nadal, a professor of physiology at the Miguel Hernandez University of Leche in Spain, and study co-author. The dose his team used — 0.05 milligrams of BPA per kilogram of body weight — is presumed safe by the U.S. Food and Drug Administration and the U.S. Environmental Protection Agency.
The fact that they found any physiological response in people at that dose, the authors concluded, "would indicate that key assumptions in the regulatory process are incorrect."
Dr. Robert Sargis, an endocrinologist at the University of Illinois at Chicago who was not involved in the study, said that, while the experiment confirms what has been seen in earlier studies linking BPA to diabetes, "the results are not a slam dunk."
"They are not saying that BPA causes diabetes in a single dose," he said.
BPA is among chemicals capable of mimicking or blocking the natural messages of insulin, estrogen and other hormones in the body. In late pregnancy, hormonal changes are believed to push a woman into a temporary state of insulin resistance in order to ensure enough sugar gets across the placenta to her rapidly growing fetus. The authors posed the possibility that BPA, if mistaken for a steroid by the body, could trigger similar effects.
The chemical has been linked to a variety of health problems including reproductive disorders, behavioral problems, heart disease and obesity.
Related: Is the FDA short-circuiting a large effort to understand BPA risk?
An association between exposure to BPA and diabetes had been previously found in animal studies and epidemiological studies. However, the FDA and EPA "would not pay attention" to those studies, said Frederick vom Saal, a professor of biology at the University of Missouri-Columbia, and another co-author of the new study.
"So we figured we had to look in people."
Vom Saal and several other scientists have been working with the FDA on another first-of-its kind study to tease out the true impacts of BPA. The project, called Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or CLARITY-BPA, was launched with intent of helping government regulators and academic researchers reach a consensus on BPA's potential health harms.
However, that effort has stirred up its own controversy in recent months. Academic researchers have voiced concerns that government regulators are again discounting their findings in favor of the FDA's own conclusions, which remain that BPA is safe.
Ethics of dosing people
Thermal paper receipts are a source of BPA exposure. (Credit: Chris Phan/flickr)
The American Chemistry Council, which represents chemical manufacturers, called the new human exposure study "speculative" and underscored the point that the results do not demonstrate that the effects of BPA are related to disease.
The Council also questioned the ethics of dosing a group of human volunteers, given "the expectation that effects would occur," said Steven G. Hentges, senior director of the Polycarbonate/BPA Global Group at the ACC.
Sheldon Krimsky, a professor at Tufts University who studies ethics in science and technology, expressed similar concern. "It's the first study of its kind, but it makes me uncomfortable," he said.
"It's a little ironic that they are trying to show very low levels of BPA might be dangerous but using the criteria of agencies that say it's not dangerous," he said. "One of the justifications for doing the test is that the levels they administered were within the federal guidelines."
Vom Saal and colleagues say they took the ethical considerations very seriously — working for more than two years with the Institutional Review Board at the University of Missouri to allay any concerns with the study design. The board ultimately approved the experiment.
Study participants were instructed on ways to reduce their exposure to BPA for two days prior to the experiment. The researchers then administered the low dose, which Americans are thought to experience several times a day. "No one thinks that one pulse in isolation is harmful," said vom Saal. "It's that we're getting pulsed repeatedly with this chemical."
The experimental exposure "just moved their levels back up into the range they would've been," Myers added. "This study needs to be replicated. The implications are too important."
Still, rather than replicating the experiment on more people, Krimsky suggested that researchers seek alternative avenues for collecting human data such as monitoring people who are already exposed to relatively high doses of BPA. Store cashiers who regularly handle receipts could be one target group, as the hormone-scrambling chemical has been shown to leach out of the paper and penetrate the skin — especially in the presence of hand sanitizer or other skin care products.
Sargis, meanwhile, questioned the need for any further study in humans. "How much of a smoking gun do we need before we actually do something about [BPA]?" he said.
"I don't think we should be at point where we have to deliberately do these studies in humans to prove these chemicals are harmful, when really it should be incumbent on manufacturers to actually prove they are safe."