Bisphenol A linked to diabetes, heart disease in humans

By Marla Cone
Editor in Chief
Environmental Health News
published 16 September 2008

        People exposed to higher levels of a chemical in plastic food and beverage containers are more likely to develop cardiovascular disease and diabetes, according to a new scientific study published today.

       The research – the first large-scale study of bisphenol A in human beings – adds to evidence from animal tests that the compound may be contributing to an array of diseases and other health problems.

        With about two million tons used worldwide each year, BPA is one of the highest-volume synthetic chemicals in the world, and it is found in the bodies of more than 90% of Americans. Traces of it leach from containers made of polycarbonate, which is a hard, clear plastic, and the epoxy linings of canned foods and beverages.      

       For the 1,455 U.S. adults tested, the more BPA in their urine, the higher their rates of heart disease and diabetes, according to research by a British team of scientists published in the Journal of the American Medical Association. They also found a link between abnormal liver enzymes in people and BPA, suggesting that the chemical alters how the liver functions.

       BPA is among the most controversial chemicals in use today.

       About 200 laboratory studies previously have reported various effects in BPA-exposed animals, including changes in insulin and livers and damage to reproductive systems and brains. However, the results have been highly contentious because some animal studies, mostly funded by the plastics or chemical industries, have suggested that BPA is safe. The controversy has focused on how lab rodents are exposed, and whether the results can be extrapolated to humans.

      Patricia Hunt, Meyer Distinguished Professor at Washington State University’s School of Molecular Biosciences, said she is “blown away” by the findings.

      “This is the smoking gun,” said Hunt, whose own research has found defective eggs and other reproductive effects in mice exposed to low doses of BPA. “There is an avalanche of data indicating that this chemical really shouldn’t be in our lives, and now we have the human data.”

Study questioned

    But representatives of the plastics industry said the findings are not definitive because the human tests take a snapshot in time of people’s exposure and cannot determine what caused their diseases.

    “Overall the new study, because of the inherent study design, cannot support the conclusion that BPA causes any disease,” said Stephen Hentges, director of the American Chemistry Council’s Polycarbonate/BPA Global Group, a trade group for the plastics and chemical industries. “This kind of a study is inherently incapable of developing a cause-and-effect relationship.”

       “Our view is that the science still continues to support the safety of products made from bisphenol A,” Hentges  added. “We have not seen the weight of scientific evidence shifting appreciatively.”

   The new findings will be discussed this morning at a meeting of the U.S. Food and Drug Administration’s scientific panel. The FDA concluded in a draft assessment last month that BPA is safe in food and beverage packaging. The agency based its finding on two industry-sponsored animal studies.

   The data for the new study was collected by the U.S. Centers for Disease Control and Prevention, which has tested thousands of people throughout the U.S. for a long list of chemical compounds.

     Epidemiologists said the study is powerful because it tested a large, randomly selected population. Shanna Swan, an epidemiologist and professor of environmental medicine and obstetrics/gynecology at University of Rochester School of Medicine and Dentistry, called the CDC database “the gold standard worldwide.”

    “The fact that these results are consistent with animal data strengthens these findings and provides strong suggestive evidence of human health effects,” Swan said. “If these data are confirmed, they would imply a very significant impact on the population burden of these major diseases.”

    John Bucher, associate director of the National Toxicology Program, said the new study “is beginning to fill in the data gaps.” Last spring, his agency, part of the National Institutes of Health, concluded after a long, contentious review that there is “some risk” that BPA may harm children’s brains and reproductive systems, while there is negligible or no risk for adults.

   “This is one more piece of the puzzle and there are many, many others that still remain,” Bucher said. “The jury is still out on this paper. Finding comparable data bases somewhere else in the world would be very valuable to try to replicate these findings.”

`Robust’ associations

           While diet, genetics and other factors are important in determining who develops cardiovascular disease, diabetes and other diseases, many scientists believe that environmental factors play a key role, too.

       BPA is an estrogen-like chemical that disrupts normal hormones in lab animals. Hormones control a wide range of functions in the human body and altering them may trigger diseases and  reproductive and neurological damage.

        The connection to heart disease came as a surprise to most scientists. No one has tested BPA-exposed lab animals for cardiovascular effects. However, one study reported last month that low levels of BPA suppressed a hormone, called adiponectin, that protects people from heart attacks and diabetes.

      The researchers divided the 1,455 people into four groups, from high exposure to low exposure. When compared to those with the lowest BPA levels, people in the quarter with the highest levels were more than twice as likely to have cardiovascular disease or Type II diabetes, according to the study. They also were likely to have altered liver enzymes. No connection was found to several other diseases, including arthritis, thyroid disease, strokes and respiratory diseases.

       “The associations all seemed pretty robust,” said David Melzer, lead author of the study and a professor of epidemiology at the Peninsula Medical School in Exeter. Scientists from the University of Exeter, University of Plymouth and Iowa College of Public Health also participated.

        Hentges said one factor that throws doubt on the new findings is that people are exposed to very low levels of BPA and it is excreted within 24 hours, while “heart disease and diabetes don’t develop overnight. The onset of those diseases develops over fairly long periods of time.”

     The study authors, however, said years of continuous exposure could be to blame. “If our findings are confirmed, we assume that the disease and liver changes are the result of longer-term BPA exposure, perhaps over several years, and not short-term exposure, for example, eating a lot of tinned food on one occasion,” Melzer and his colleagues wrote.

Call for action

    The British team is already analyzing data from other human populations to see if the results can be replicated.

     “Repeating it is very important, as this type of survey research has been very successful many times, but has also occasionally thrown up a false result,” Melzer said in an interview.

      The new study links adult levels to diseases, which raises the question of whether timing of exposure is important for people’s health. In animals, many of the studies reported that exposure as a fetus, not as an adult, led to health problems later in life.

     Scientists now are studying other human populations over longer periods of time to determine if exposure before birth or in childhood leads to diabetes, obesity or other health problems in adulthood.

    “There will undoubtedly be many follow-up studies given the importance of these results,” Swan said.

     Frederick vom Saal, a reproductive scientist at University of Missouri-Columbia who studies effects of BPA, wrote in an accompanying editorial in JAMA that the new findings “should spur U.S. regulatory agencies” to take “aggressive action to limit human and environmental exposures.”

      Vom Saal directed one of the first animal studies on BPA, in 1997. He has been an outspoken critic of the plastics industry, contending it has tried to manufacture doubt about the chemical’s dangers by attacking the validity of the science.

    The findings call into question the safety of current guidelines set by the Environmental Protection Agency.

     In the new study, scientists estimate that people with the highest BPA measurements were exposed to 50 micrograms per day on average. Those with the lowest were exposed to an average of 10 micrograms per day.

     The large differences may be explained by the amounts of food and beverages people consume from cans and polycarbonate bottles. People between the ages of 18 and 29 had the highest BPA levels, while the oldest group, ages 60 to 74, had the lowest. Blacks had higher concentrations than all other race and ethic groups.

     People with no diabetes or cardiovascular disease were exposed to an estimated 20 micrograms of BPA per day, while those with diabetes and cardiovascular disease averaged 28 to 35 micrograms daily.

    Based on animal data, the EPA says an average adult could safely consume 100 times that level – about 3,200 micrograms of BPA per day.

Minimizing risk

     Hunt said the new data should be enough to prompt the FDA and EPA to change their positions.

     “We can’t afford to wait any longer. Humans beings are tricky to study and how much is enough to be convincing?” said Hunt, whose research showed that when pregnant mice are exposed to low levels of BPA, their offspring produce damaged eggs. Hunt wonders if the chemical also damages human eggs, leading to miscarriages or genetic disorders.

      But Hentges said the link between BPA and the diseases could be a false-positive, confounded by many factors, such as obesity, which the authors acknowledged in their report. “When it comes to sorting out what really causes the diabetes or heart disease, it could be many things,” he said.

    Many manufacturers and consumers have already gotten rid of  baby bottles and sports bottles that contain the chemical, which has been used by industries for about 50 years.  At least 10 states have considered laws banning BPA from children’s products, but none have been adopted.

   “With these results, it is no longer scientifically valid for the FDA or any agency to conclude with certainty that BPA is safe,” Swan said. “Consumers who want to minimize risk to their own and their children’s health, even in the face of uncertainty, will want to avoid BPA containing products.”
 

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Editor’s Note: Environmental Health Sciences CEO and Chief Scientist Pete Myers was co-author of the editorial that accompanied the BPA study in JAMA. He had no role in this story.