Scientists have once again found that people with higher levels of bisphenol A (BPA) in their urine are more likely to have heart disease than those with lower urinary BPA levels.

Used to make some plastic drinks bottles and the inner coatings of food cans, BPA can mimic the effects of oestrogen and has been associated with a number of conditions in animal studies, including low sperm count, prostate cancer and fetal developmental problems. In 2008, researchers first linked BPA to diabetes and heart disease in humans(1), but industry lobby groups such as the American Chemistry Council in Arlington, Virginia, have vigorously disputed those findings.

Now, the same researchers are back with a second report in PLoS ONE(2), which uses an independent data set to come up with broadly similar, if weaker, results. "It's only the second data set from a big population to be released," says lead author David Melzer of the Peninsula Medical School at the University of Exeter, UK. "It shows that our first paper wasn't a statistical blip."

Divided opinion

Melzer and his co-authors analysed data from the 2005–06 US National Health and Nutrition Examination Survey of 1,493 adults, who provided urine samples and completed questionnaires about their health. Higher concentrations of BPA in the subjects' urine were associated with cardiovascular disease, but not with diabetes or high levels of liver enzymes, which indicate liver damage. However, BPA concentrations were 30% lower in this survey than in the 2003–04 survey used in the team's previous study, although when the two samples were pooled, diabetes and liver-enzyme associations remained statistically significant. Based on the data, a 60-year-old man with the lowest levels of BPA in the survey had about a 7.2% chance of developing cardiovascular disease whereas a similar subject with levels three times higher faced about a 10.2% risk.

The results add to a limited number of human studies on the effects of BPA, but are unlikely to bring together the two sides of the highly charged debate on the chemical's safety. Toxicologist Frederick vom Saal of the University of Missouri in Columbia, a long-time critic of the regulations governing the use of BPA, says that identifying such an association from epidemiological data is alarming. "The important issue is there have got to be 100 plus factors involved in any one of these diseases, and you are looking at one chemical, one time in a spot urine collection, and it's popping up as a significant variable," he says, "That's impressive because that's something you can do something about."

But Steven Hentges of the American Chemical Council says that the fact that some of the team's original results were not independently supported raises more questions than it answers. "The weight of scientific evidence continues to support the view that BPA is not a health concern," he says. "If you think that this study raises a hypothesis – fair enough – but the fact that they have not been able to replicate most of what they reported before is very telling."

Missing mechanism

Indeed, other scientists agree that what is still missing from the research is a demonstration of the mechanism of action. "Association studies show something really is going on, but getting to a definite mechanism of cause and effect is what we can add with animal studies," says Scott Belcher of the University of Cincinnati in Ohio, who has begun a series of studies on mice and rats funded by the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.

Scientists have long known that oestrogen has the potential to affect heart function through the oestrogen beta receptor, and Belcher is looking at how BPA affects calcium levels, which control heart contractions. His early results show that BPA, like oestrogen, causes an irregular heartbeat in female rats, which could increase the risk of a heart attack. Belcher is planning further studies in rodents to look directly at the risks of heart attack, obesity and changes in the cardiovascular system.

The policy on BPA in the United States seems to be caught in a loop. The Food and Drug Administration has delayed a promised 'update' on its position that the chemical is safe. "We'll be making an announcement soon," says agency spokeswoman Meghan Scott, although she was unable to be more specific about the timing of the announcement.

• References

  1. Lang, I. A.et al. J. Am. Med. Assoc.300, 1303-1310 (2008).
  2. Melzer, D.et al. PLoS ONE5, e8673 (2010).