Associations between Per- and Polyfluoroalkyl Substances Exposures and Blood Lipid Levels among Adults—A Meta-Analysis

Liu, Binkai; Zhu, Lu; Wang, Molin; Sun, Qi

doi:10.1289/ehp11840

Cited by 39 publications

(13 citation statements)

References 81 publications

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“…In contrast, HDL-C does not seem to be strongly associated with PFAS, and associations with triglycerides have been mixed. Accordingly, the strongest connections identified in metaanalyses were between PFOA and PFOS and increased total cholesterol and LDL-C. 127,128 Interestingly, one metaanalysis also supported an association between PFOA and increased serum triglycerides. 127 Overall, a critical survey of all the available published studies provides the strongest evidence for PFOS, as PFAS is associated with an increased risk of atherosclerosis and CVD risk.…”

Section: Dyslipidemia and Atherosclerosismentioning

confidence: 95%

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Schlezinger,

Gokce

2024

Circulation Research

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Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are man-made chemicals that are extensively used in industrial and consumer products worldwide and in aqueous film-forming foam utilized in firefighting. As such, our exposure to PFAS is essentially ubiquitous. Given the long half-lives of these degradation-resistant chemicals, virtually, all people are carrying a body burden of PFAS. Health concerns related to PFAS are growing such that the National Academies of Sciences, Engineering and Medicine has recommended standards for clinical follow-up of individuals with high PFAS blood levels, including prioritizing screening for dyslipidemia. The link between PFAS and dyslipidemia has been extensively investigated, and evidence for associations is compelling. However, dyslipidemia is not the only cardiovascular risk factor with which PFAS is associated. Here, we review the epidemiological evidence for links between PFAS of concern identified by the National Academies of Sciences, Engineering and Medicine and risk factors for cardiovascular disease, including overweight/obesity, glucose intolerance, hypertension, dyslipidemia, and hyperuricemia. Moreover, we review the potential connections of PFAS with vascular disease and atherosclerosis. While observational data support associations between the National Academies of Sciences, Engineering and Medicine PFAS and selected cardiac risk factors, additional research is needed to establish causation and better understand how exposure to PFAS leads to the development of these conditions.

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Section: Dyslipidemia and Atherosclerosismentioning

confidence: 95%

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Schlezinger,

Gokce

2024

Circulation Research

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“…In Table 1, we selected some key studies employing different study designs to illustrate this evidence. Two meta‐analyses indicated mainly associations of PFAS with higher levels of total cholesterol 3,4 . The other studies, despite being high exposure studies, still found the strongest associations in the lower range of PFAS exposure levels 5 .…”

Section: Epidemiological Evidence and Considerationsmentioning

confidence: 96%

“…Evidence for associations of PFAS with other lipid types is scarcer and more inconsistent, but generally, similar to total cholesterol, also positive associations with LDL‐ and HDL‐cholesterol are found (Table 1). 3,4 Interestingly, for triglycerides, the opposite has been observed and the meta‐analyses point mainly towards associations of PFAS exposure with lower blood triglyceride levels (Table 1). 3,4 There could be diverging associations between different PFAS compounds, which could also explain some inconsistencies between studies 3 .…”

Section: Epidemiological Evidence and Considerationsmentioning

confidence: 98%

“… 3,4 Interestingly, for triglycerides, the opposite has been observed and the meta‐analyses point mainly towards associations of PFAS exposure with lower blood triglyceride levels (Table 1). 3,4 There could be diverging associations between different PFAS compounds, which could also explain some inconsistencies between studies 3 . Much less investigated are associations with apolipoproteins, although this could provide more detailed mechanistic information.…”

Section: Epidemiological Evidence and Considerationsmentioning

confidence: 98%

“…For example, although there is still a risk for other bias or confounding, reverse causality is minimized with longitudinal design, while confounding by shared excretion mechanisms is less likely in ecological studies and studies using PFAS exposure based on intake. On the other hand, causality may be disputed as other studies show null or even inverse associations 3,4 . Moreover, a clinical phase 1 trial on cancer patients with extremely high administered perfluorooctanoic acid (PFOA) indicated associations with lower cholesterol 9 .…”

Section: Epidemiological Evidence and Considerationsmentioning

confidence: 99%

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Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Schillemans,

Donat‐Vargas,

Åkesson

2023

Basic Clin Pharma Tox

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Per‐ and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi‐omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

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Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals

Attema,

Kummu,

Pitkänen

et al. 2024

Arch Toxicol

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Environmental exposure to endocrine-disrupting chemicals (EDCs) can lead to metabolic disruption, resulting in metabolic complications including adiposity, dyslipidemia, hepatic lipid accumulation, and glucose intolerance. Hepatic nuclear receptor activation is one of the mechanisms mediating metabolic effects of EDCs. Here, we investigated the potential to use a repeated dose 28-day oral toxicity test for identification of EDCs with metabolic endpoints. Bisphenol A (BPA), pregnenolone-16α-carbonitrile (PCN), and perfluorooctanoic acid (PFOA) were used as reference compounds. Male and female wild-type C57BL/6 mice were orally exposed to 5, 50, and 500 μg/kg of BPA, 1000, 10 000, and 100 000 µg/kg of PCN and 50 and 300 μg/kg of PFOA for 28 days next to normal chow diet. Primary endpoints were glucose tolerance, hepatic lipid accumulation, and plasma lipids. After 28-day exposure, no changes in body weight and glucose tolerance were observed in BPA-, PCN-, or PFOA-treated males or females. PCN and PFOA at the highest dose in both sexes and BPA at the middle and high dose in males increased relative liver weight. PFOA reduced plasma triglycerides in males and females, and increased hepatic triglyceride content in males. PCN and PFOA induced hepatic expression of typical pregnane X receptor (PXR) and peroxisome proliferator-activated receptor (PPAR)α target genes, respectively. Exposure to BPA resulted in limited gene expression changes. In conclusion, the observed changes on metabolic health parameters were modest, suggesting that a standard repeated dose 28-day oral toxicity test is not a sensitive method for the detection of the metabolic effect of EDCs.

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Associations between Per- and Polyfluoroalkyl Substances Exposures and Blood Lipid Levels among Adults—A Meta-Analysis

Cited by 39 publications

References 81 publications

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals

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