Bisphenols: Safe and HazardousOral administration of bisphenol A (BPA), a synthetic chemical used in consumer products, results in reduced peripheral insulin sensitivity in adults with normal weight, a study has found.
“Five days of oral BPA administration at the US EPA reference dose reduced peripheral insulin sensitivity in adults with normal weight,” the investigators said. “These results carry important clinical and public health implications, suggesting that BPA exposure, even at doses currently considered safe, may contribute to the development of insulin resistance.”
Forty sedentary but healthy adults (mean age 21.3 years, 22 females, BMI 22.1 kg/m2, 85 percent non-Hispanic White) participated in this study and completed a 2-day baseline energy-balanced diet low in BPA. Their urine, blood, and peripheral insulin sensitivity were assessed via 120 min euglycaemic hyperinsulinaemia clamp technique (40 mU/m2/min; 90 mg/dL).
The investigators randomized participants to receive 5 days of oral BPA administration at 50 µg/kg body weight (BPA-50) or placebo. All participants received the same energy-balanced diet. A two-way repeated-measures ANOVA was used to assess outcomes, with adjustments for baseline sex, BMI, physical activity, and ethnicity.
Participants in the BPA-50 group had significantly higher urine BPA levels after treatment than those in the placebo group (268,700 vs 8,893 pg/mL; p=0.009). Body weight and fasting glucose did not significantly differ between the two groups (p>0.05). [J Clin Endoc Metab 2026;111:2610-2619]
However, BPA administration resulted in a 0.02-mg/kg/min/uU/mL decrease in peripheral insulin sensitivity compared with a 0.02-mg/kg/min/uU/mL increase following placebo exposure (p=0.01).
“These data provide the first experimental evidence in humans that BPA administration may reduce insulin sensitivity,” the investigators said.
Earlier studies
Associations between urinary BPA and markers of insulin resistance and diabetes across the human lifespan have previously been shown in epidemiological studies. However, few experimental studies have explored the direct effects of oral BPA administration on indices of insulin resistance and glucose metabolism. [J Clin Endocrinol Metab 2011;96:3822‐3826; J Hazard Mater 2024;476:135000]
“Both our previous pilot study and Stahlhut [and colleagues] showed that a single oral dose of BPA at 50 µg/kg acutely lowered insulin and glucose responses,” the investigators said. [J Endocr Soc 2019;3:643‐654; J Endocr Soc 2018;2:1173‐1187]
“However, this prior work was unable to discern the direct effects of insulin sensitivity from those of insulin secretion, given that an oral glucose tolerance test was used,” they added.
The present study provides further evidence by showing that 5-day BPA administration reduced peripheral insulin sensitivity by about 9 percent. Although stable isotopes were not used to disentangle skeletal muscle from hepatic glucose production, no difference was observed in homeostatic model assessment of insulin resistance.
“This suggests that BPA may have interfered with insulin-stimulated glucose metabolism in skeletal muscle,” the investigators said. “Interestingly, we observed a trend for fasting glucose to rise by approximately 1 mg/dL following BPA, compared with a nearly 7 mg/dL drop after placebo.”
This can be potentially explained by the slightly reduced fasting insulin levels following BPA exposure, consistent with the literature suggesting that BPA may impair beta-cell function. [Environ Health Perspect 2006;114:106‐112]
“When considered alongside prior epidemiological, animal, and human studies, the present findings add to the growing body of evidence that regulatory agencies should critically reevaluate the established reference dose for BPA,” the investigators said. [J Endocr Soc 2019;3:643‐654; J Endocr Soc 2018;2:1173‐1187; Environ Health Perspect 2006;114:106‐112; Endocrine Disruptors 2013;1:e25078]