Exposure & Disease Burden
The broad range of conditions associated with exposure to bisphenols (used in many plastics, polycarbonates, coatings, etc.) has grown at a disturbing rate. Most people living in the U.S. are likely to have detectable levels of at least one bisphenol, and the harm appears not to be limited to the nearly ubiquitous bisphenol A (BPA), but now also to its highly prevalent replacements, including bisphenol S (BPS) and bisphenol F (BPF). Over 95% of adults and children in the U.S. have detectable levels of BPA in their urine, 89% have BPS, and 66% have BPF.
Many analyses of NHANES (National Health and Nutrition Examination Surveys) have been done to try to understand the potential risk; for example, a sample of nearly 9,000 adults indicate that those in the highest quartile of exposure (defined as a urinary level of BPA > 2.94 ug/g creatinine) had an adjusted 73% greater risk for heart attack, a 61% greater risk for stroke when compared to the lowest quintile (equal to or less than 1 ug/g creatinine), as well as increases in heart failure, angina, etc. A French cohort of nearly 800 participants found nearly a 2-fold increase in risk for type 2 diabetes when comparing the highest quintile of BPA to the lowest, but even detection of a BPS metabolite in the urine was associated with an almost 3-fold increase in risk for diabetes. A previously published systematic review found nearly a 50% increase in risk for diabetes with higher BPA exposure.
An NHANES sample of ~750 adolescents found a 74% increase in risk for obesity in the highest quintile of BPA exposure, as well as a 54% and 36% higher risk linked to BPF and BPS, respectively. Children in the ongoing NHANES study were found to have a nearly 6-fold increase in risk for ADHD with higher BPA exposure, which increased to almost 11-fold among boys. A study recently published in Sweden found that 90% of pregnant women had all three bisphenols detected in their urine; BPF was associated with a drop in IQ in their children by age 7, as well as declines in other markers of cognitive function, such as working memory and verbal comprehension. Prenatal exposure to BPA has been linked to changes in thyroid function. Bisphenols have been associated with asthma and hay fever in both adults and children per NHANES data; BPF detection, for example, was associated with a 54% increase in risk for asthma.
In a recent analysis of NHANES data, no association was found between bisphenols and depressive symptoms in the general population. However, higher urinary levels of BPS carried almost a 3-fold increase in risk among men, and nearly a 29-fold increase in risk among elderly men. Surprisingly this association was inverted among elderly women. Although solid data is lacking, bisphenols are likely to play a role in infertility in both men and women. Recent data also suggests a possible pathogenic role in Crohn’s disease; BPA correlated with markers of bacterial translocation as well as serum endotoxin levels, with a likely effect on systemic inflammation.
Most research analyses assess urinary levels, which represent acute exposure. Unfortunately, most labs do not offer an option to test urinary levels of all 3 bisphenols, though Quest Diagnostics does offer urinary BPA. Reference ranges associated with cardiovascular disease (CVD) were given above; a previous study in JAMA found a nearly 40% increase in risk for both CVD and diabetes per each standard deviation above the mean, which at the time was 4.53 and 4.66 ng/mL in adult men and women, respectively. It is also important to note that none of the studies mentioned are able to show causality. Although they typically adjust for exposure to other chemicals, many of the plastics which contain bisphenols also contain a mixture of toxins and other plasticizers (such as phthalates) which may interact with bisphenols to modulate risk, and may help to explain some of the risk associated with processed food.
Certainly understanding the many sources of exposure to bisphenols is necessary for limiting exposure, with diet being the chief contributor. Given that not only plastics, but dental sealants, thermal receipt paper, food container linings all are likely to use bisphenol, this is no small task. In a surprising study published in JAMA, consuming only 1 serving of canned soup per day over 5 days was associated with a 1000% increase in urinary BPA levels, far exceeding the 95th percentile NHANES levels. Additionally, “BPA free” almost certainly means that BPF or BPS are used instead.
While clinical trials are very much needed, supporting detoxification pathways (particularly glucuronidation) for individuals with likely exposure also seems indicated. Antioxidants such as vitamin C, vitamin E, vitamin A, lycopene, N-acetylcysteine, glutathione, superoxide dismutase, catalase, and melatonin have all been shown to help mitigate BPA damage in animal models, but data is lacking for the other bisphenols. Similarly, models suggest that certain probiotics including Bifidobacterium strains, may help alleviate BPA toxicity.