Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, and Its Association with Developing Obesity and Diabetes Mellitus: A Narrative Review

Abstract

Bisphenol A, a well-known endocrine-disrupting chemical, has been replaced with its analogs bisphenol S (BPS) and bisphenol F (BPF) over the last decade due to health concerns. BPS and BPF are present in relatively high concentrations in different products, such as food products, personal care products, and sales receipts. Both BPS and BPF have similar structural and chemical properties to BPA; therefore, considerable scientific efforts have investigated the safety of their exposure. In this review, we summarize the findings of relevant epidemiological studies investigating the association between urinary concentrations of BPS and/or BPF with the incidence of obesity or diabetes. The results showed that BPS and BPF were detected in many urinary samples at median concentrations ranging from 0.03 to 0.4 µg·L−1. At this exposure level, BPS median urinary concentrations (0.4 µg·L−1) were associated with the development of obesity. At a lower exposure level (0.1–0.03 µg·L−1), two studies showed an association with developing diabetes. For BPF exposure, only one study showed an association with obesity. However, most of the reported studies only assessed BPS exposure levels. Furthermore, we also summarize the findings of experimental studies in vivo and in vitro regarding our aim; results support the possible obesogenic effects/metabolic disorders mediated by BPS and/or BPF exposure. Unexpectedly, BPS may promote worse obesogenic effects than BPA. In addition, the possible mode of action underlying the obesogenic effects of BPS might be attributed to various pathophysiological mechanisms, including estrogenic or androgenic activities, alterations in the gene expression of critical adipogenesis-related markers, and induction of oxidative stress and an inflammatory state. Furthermore, susceptibility to the adverse effects of BPS may be altered by sex differences according to the results of both epidemiological and experimental studies. However, the possible mode of action underlying these sex differences is still unclear. In conclusion, exposure to BPS or BPF may promote the development of obesity and diabetes. Future approaches are highly needed to assess the safety of BPS and BPF regarding their potential effects in promoting metabolic disturbances. Other studies in different populations and settings are highly suggested.

Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep

“…BPA is ubiquitously present in the environment, air, water, soil, animal feed, wildlife, and humans [ 141 , 142 , 143 ]. While the role of direct BPA exposure in the development of diabetes mellitus and obesity has been explored extensively [ 144 , 145 ], there is a gap in the research on the prenatal effect of BPA on liver pathologies. This study was performed to address causal relationships between prenatal BPA and liver steatosis, as human studies can only point to association and not causality.…”

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) on the available evidence in relation to the potential obesogenic activity of certain chemical compounds that may be present in foods

“…Epidemiological studies on BPA and analogues focus mainly on BPA as an obesogen. Very few human studies have analysed the effect of analogues (Alharbi et al, 2022). Exposure to low doses of bisphenols has been associated with weight gain, altered carbohydrate and lipid homoeostasis, and an effect on brain regions involved in food intake (Boucher et al, 2016) (Verbanck et al, 2017) (Heindel and Blumberg, 2019).…”

Protective Effects of a Red Grape Juice Extract against Bisphenol A-Induced Toxicity in Human Umbilical Vein Endothelial Cells

“…Several studies suggest that BPA has endocrine-disrupting properties and that it can be implied in the pathogenesis of a variety of human diseases mostly affecting reproductive systems [2,3], similar to other environmental pollutants [4], as well as cardiovascular systems [5]. In this frame, epidemiological studies reported that there is an association between exposure to BPA and an increased prevalence of cardiovascular diseases (CVDs), including atherosclerosis [6], coronary and peripheral artery disease [7,8], myocardial infarction [9], and angina pectoris [10], as well as their risk factors, such as hypertension [11] and diabetes [12]. At the basis of the pathogenesis of these illnesses, a pivotal role is played Toxics 2023, 11, 391 2 of 18 by oxidative stress, endothelial activation, and dysfunction, which the latter represents the early step in the development and progression of atherosclerosis [13].…”