Association of urinary glyphosate levels with iron homeostasis among a representative sample of US adults: NHANES 2013-2018.

PURPOSE: Glyphosate and glyphosate-based herbicides (GBH), widely used globally, were initially considered harmless to humans. Experimental studies have suggested that these substances can disrupt iron homeostasis by interfering with iron uptake or triggering inflammatory responses. However, their potential impact on human iron homeostasis remains underexplored. APPROACH AND RESULTS: We analyzed data from 5812 participants aged three and older from the 2013 to 2018 NHANES. We investigated the relationships between urinary glyphosate levels, oral iron intake, and markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor. Higher urinary glyphosate levels were positively associated with oral iron intake (ß = 1.310, S.E. = 0.382, P = 0.001). A one-unit increase in the natural logarithm (ln)-glyphosate was associated with lower serum iron (ß = - 4.236, 95 % CI = - 6.432 to - 2.039, P < 0.001) and ferritin (ß = - 9.994, 95 % CI = - 17.342 to - 2.647, P = 0.009), and higher UIBC (ß = 5.431, 95 % CI = 1.061-9.800, P = 0.018) and transferrin receptor levels (ß = 0.139, 95 % CI = 0.015-0.263, P = 0.029). Increasing glyphosate exposure was associated with significant decreases in serum iron and ferritin across exposure quintiles (trend P-values = 0.003 and 0.018, respectively). CONCLUSIONS: Higher glyphosate exposure is associated with reduced iron availability, suggesting potential disruptions in iron absorption. These findings underscore the need for further research into the health implications of glyphosate exposure on iron homeostasis.

Association between glyphosate exposure and cognitive function, depression, and neurological diseases in a representative sample of US adults: NHANES 2013-2014 analysis.

Glyphosate, the most widely used herbicide globally, has been linked to neurological impairments in some occupational studies. However, the potential neurotoxic effects of glyphosate exposure in the general population are still not fully understood. We conducted analyses on existing data collected from 1532 adults of the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the possible relationship between glyphosate exposure and cognitive function, depressive symptoms, disability, and neurological medical conditions. Our results showed a significant negative association between urinary glyphosate levels and the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD-WLT) trial 3 recall and delayed recall scores in both models, with ß coefficients of -0.288 (S.E. = 0.111, P = 0.021) and -0.426 (S.E. = 0.148, P = 0.011), respectively. Furthermore, the odds ratio did not show a significant increase with the severity of depressive symptoms with a one-unit increase in ln-glyphosate levels. However, the odds ratio for severe depressive symptoms was significantly higher than for no symptoms (odds ratio = 4.148 (95% CI = 1.009-17.133), P = 0.049). Notably, the odds ratio showed a significant increase for individuals with serious hearing difficulty (odds ratio = 1.354 (95% CI = 1.018-1.800), P = 0.039) with a one-unit increase in ln-glyphosate levels, but not for other neurological medical conditions. In conclusion, our findings provide the first evidence that glyphosate exposure may be associated with neurological health outcomes in the US adult population. Additional investigation is necessary to understand the potential mechanisms and clinical significance of these correlations.

Association between serum per- and polyfluoroalkyl substances and thrombograms in young and middle-aged Taiwanese populations.

PURPOSE: Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals used in many products. Recent in vitro and epidemiological reports have found that PFAS exposure can modify the function of platelets. Platelet size has been shown to affect platelet activity, and thrombograms are a simple method of indirect assessment of platelet function. However, there has been no large-scale research investigating the association between PFAS levels and complete thrombograms in humans. APPROACH AND RESULTS: In the current cross-sectional study, we enrolled 1779 Taiwanese subjects (aged between 12 and 63 years) to study the associations between serum PFAS concentrations and thrombograms. There were 1175 men and 604 women with a mean age of 34.5 years. When all four PFAS were fitted by the multiple linear models at the same time, platelet counts decreased significantly with increasing quartiles of perfluorooctanoate acid (PFOA) and perfluorooctane sulfonate (PFOS), while platelet distribution width (PDW), mean platelet volume (MPV), and platelet-large cell ratio (PLCR) also increased significantly with increasing quartiles of PFOS. The mean platelet count was the lowest (264.02 k/µL [95% CI 256.00-272.04]; P < 0.001) when both PFOA and PFOS concentrations were above the 50th percentile. CONCLUSIONS: We report that serum PFAS levels were correlated with thrombograms. If the association is etiologic, PFOA/PFOS may decrease the number of platelets, while PFOS may also increase the variation and the average size of platelets in the subjects of the study. Interestingly, PFOA and PFOS may have synergistic effects on the decrease in platelet counts. Further research is needed to study the effect of PFAS on platelets in humans.

Global DNA methylation mediates the association between serum perfluorooctane sulfonate and carotid intima-media thickness in young and middle-aged Taiwanese populations.

PURPOSE: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in the manufacture of many everyday products. Previous reports have shown PFAS exposure may contribute to cardiovascular diseases (CVD). Recent studies have also identified a critical role for DNA methylation, a model of epigenetic regulation, in the pathogenesis of CVD. Additionally, PFAS has been shown to affect DNA methylation. Our previous study reported the positive association between serum perfluorooctane sulfonate (PFOS) levels and mean carotid intima-media thickness (CIMT), a biomarker of arteriosclerosis, in a cohort composed of adolescent and young adult Taiwanese. However, the contribution of DNA methylation in the mechanism of PFOS-induced arteriosclerosis has never been explored in previous literature. APPROACH AND RESULTS: In this cross-sectional study, we included 1425 young and middle-aged Taiwanese individuals (12-63 years) to investigate the correlation between serum PFOS levels, 5mdC/dG (a global DNA methylation marker) and the mean CIMT. We showed that the positive association between serum PFOS levels, 5mdC/dG, and mean CIMT. The regression coefficients of mean CIMT with a one-unit increase in ln-PFOS concentration were higher when the levels of 5mdC/dG were above the 50th percentile in the multiple regression analysis. In the structural equation model (SEM), the results showed that serum PFOS levels were directly correlated with mean CIMT and indirectly correlated with CIMT through 5mdC/dG. CONCLUSIONS: Our results showed that PFOS exposure has direct associations on arteriosclerosis and indirect direct associations on arteriosclerosis through DNA methylation. The results suggest that DNA methylation might regulate the relationship between PFOS and arteriosclerosis in the study subjects. Additional works are required to understand the causal inference between PFOS, DNA methylation, and arteriosclerosis.

Association between the total plasma isomers of per- and polyfluoroalkyl substances and erythrograms in young and middle-aged Taiwanese populations.

PURPOSE: Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals used in daily use products. Recent studies have shown that different perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) isomers may have different biological effects. In vitro studies have also reported that PFAS exposure can alter the structure of hemoglobin (Hb). In epidemiology, however, few studies have investigated the relationship between PFAS exposure and erythrocytes. Additionally, the correlation between PFOA/PFOS isomers and full erythrograms has never been explored. APPROACH AND RESULTS: In cohorts comprising young and middle-aged Taiwanese populations, we enrolled 1483 participants (aged between 12 and 63 years) to analyze the correlations between the plasma levels of PFOA/PFOS isomers and whole-blood erythrograms. The study comprised 868 men and 615 women with a mean age of 31.2 years. When all PFOA/PFOS isomers were entered into the multiple linear regression model, the linear PFOA (L-PFOA) levels were positively correlated with the Hb, hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels while the branched PFOS (B-PFOS) levels were positively associated with the Hb, HCT, and mean corpuscular hemoglobin concentration (MCHC). The mean value of Hb was the highest (14.66 mg/dL (95% CI =14.52-14.80); P for trend <0.001) when both the L-PFOA and B-PFOS levels were above the 50th percentile. CONCLUSIONS: The results imply that PFOA/PFOS isomers may increase the weight and volume of Hb/RBC and that L-PFOA/B-PFOS may have an additive effect on the Hb levels. However, it is also possible PFAS detected at a higher concentration may due to its binding to higher levels of Hb. Further studies are needed to investigate the effects of PFOA/PFOS isomers on RBCs in humans.

Urinary heavy metals, DNA methylation, and subclinical atherosclerosis.

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

Degradation of alachlor using an enhanced sono-Fenton process with efficient Fenton's reagent dosages.

In this study, an enhanced sono-Fenton process for the degradation of alachlor is presented. At high ultrasonic power, low pH, and in the presence of adequate Fenton's reagent dosages, alachlor degradation can reach nearly 100%. The toxicity of treated alachlor wastewater, which was measured by changes in cell viability, slightly decreased after the Fenton or ultrasound/H2O2 process and significantly decreased after the enhanced sono-Fenton process. A satisfactory relationship was observed between the total organic carbon removal and cell viability increment, indicating that alachlor mineralization is a key step in reducing the toxicity of the solution. The formation of alachlor degradation byproducts was observed during the oxidation process, in which the first step was the substitution of a chloride by a hydroxyl group. In conclusion, the enhanced sono-Fenton process was effective in the degradation and detoxification of alachlor within a short reaction time. Thus, the treated wastewater can then be passed through a biological treatment unit for further treatment.

Decontamination of alachlor herbicide wastewater by a continuous dosing mode ultrasound/Fe(2+)/H2O2 process.

We used a ultrasound/Fe(2+)/H2O2 process in continuous dosing mode to degrade the alachlor. Experimental results indicated that lower pH levels enhanced the degradation and mineralization of alachlor. The maximum alachlor degradation (initial alachlor concentration of 50 mg/L) was as high as 100% at pH 3 with ultrasound of 100 Watts, 20 mg/L of Fe(2+), 2 mg/min of H2O2 and 20°C within 60 min reaction combined with 46.8% total organic carbon removal. Higher reaction temperatures inhibited the degradation of alachlor. Adequate dosages of Fe(2+) and H2O2 in ultrasound/Fe(2+)/H2O2 process not only enhance the degradation efficiency of alachlor but also save the operational cost than the sole ultrasound or Fenton process. A continuous dosing mode ultrasound/Fe(2+)/H2O2 process was proven as an effective method to degrade the alachlor.

Association between urinary glyphosate levels and hand grip strength in a representative sample of US adults: NHANES 2013-2014.

Introduction: Glyphosate, a widely utilized herbicide globally, has been linked to various health issues, including cancer, birth abnormalities, and reproductive issues. Additionally, there is growing experimental support indicating potential harm to skeletal muscles. Despite this, the impact of glyphosate on human muscle health remains unclear. Methods: We examined information gathered from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which included 1466 adults aged 18 or older. Our primary aim was to investigate the relationship between glyphosate exposure and hand grip strength, as well as its influence on lean muscle mass. Results and discussion: Our investigation uncovered a detrimental correlation between glyphosate exposure and all measures of grip strength, except for the second test of the first hand. Specifically, we observed a statistically significant adverse association between glyphosate exposure and combined grip strength, which is calculated as the sum of the highest readings from both hands (ß coefficient of -2.000, S.E. = 0.891, p = 0.040). We did not observe a significant correlation between glyphosate levels, lean muscle mass, and the likelihood of reaching maximum grip strength meeting sarcopenia criteria. Additionally, we observed an interaction between age and glyphosate, as well as between body mass index (BMI) and glyphosate, concerning the association with combined grip strength. In this comprehensive analysis of NHANES data, our study reveals a potential association between glyphosate exposure and hand grip strength in the adult population. Our findings suggest the need for deeper exploration into the health effects of glyphosate exposure and its impact on muscle strength, shedding light on possible public health concerns.

The relationship between serum monoterpene levels and bone health: a retrospective cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) data.

Introduction: Monoterpenes, a subset of the terpene family composed of two isoprene units, have garnered significant attention in research circles owing to their potential medicinal benefits. Recent experimental studies indicate that they might exert positive effects on bone health. Nevertheless, the impact of monoterpenes exposure on bone health remains unexplored in humans. Methods: We examined 748 adults (age ≥ 40 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to explore the correlation between three monoterpenes (α-pinene, ß-pinene, and limonene), bone mineral density (BMD) in the total lumbar spine and proximal femur, FRAX® scores, and prior bone fracture history. Results and discussion: Our analysis unveiled a significant inverse association between a one-unit increase in the natural logarithm (ln) of α-pinene and limonene and total proximal femur BMD (ß = -0.027, S.E. = 0.008, P = 0.004 and ß = -0.019, S.E. = 0.007, P = 0.016, respectively). As serum α-pinene levels ascended across quintiles, there was a notable decrease in total proximal femur BMD (P for trend = 0.025). The inverse relationship between ln α-pinene levels and total proximal femur BMD was more pronounced in women, especially pre-menopausal women. Compared to subjects with α-pinene and limonene levels at or below the 50th percentiles, those exceeding this threshold exhibited the lowest mean value of total proximal femur BMD (0.8628 g/cm2, S.E. = 0.026, P = 0.009). However, the trend was not statistically significant (P = 0.070). Additionally, all three monoterpenes were linked to a higher prevalence of previous spine fractures, whereas ß-pinene showed a reduced incidence of other types of fractures. In this comprehensive survey of American adults aged 40 and above, higher serum levels of α-pinene and limonene correlated with decreased total proximal femur BMD. Furthermore, our findings suggest a potential combined effect of α-pinene and limonene on total proximal femur BMD. Further investigation is essential to elucidate the clinical relevance and causative nature of our findings.

Examining the impact of polyfluoroalkyl substance exposure on erythrocyte profiles and its related nutrients: Insights from a prospective study on young Taiwanese.

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects.

Examining a decade-long trend in exposure to per- and polyfluoroalkyl substances and their correlation with lipid profiles: Insights from a prospective cohort study on the young Taiwanese population.

Per- and polyfluoroalkyl substances (PFAS) are artificial chemicals extensively utilized in everyday products, and numerous cross-sectional epidemiological studies consistently link PFAS exposure with lipid profiles across diverse populations and age groups. In longitudinal studies, the findings also indicate a positive correlation between PFAS and lipid profiles; however, this association remains unexplored in adolescents and young adults. Notably, previous research has predominantly focused on conventional lipid biomarkers, with limited exploration of the relationship between PFAS and diverse lipoprotein subfractions. Furthermore, there is a lack of comprehensive investigation into the temporal trends in PFAS concentrations in Taiwan. To address this research gap, we conducted a prospective study following 592 adolescents and young adults (12-30 years old at enrollment) from the YOung TAiwanese Cohort (YOTA) over a duration of 10 years. During the follow-up period, we measured 11 types of PFAS and various lipid profile biomarkers (low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein triglyceride (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, lipoprotein(a), triglyceride). Our results revealed a general decline in PFAS concentrations in the study population. Regarding the correlation between the average levels (averaged across the initial and second tracking periods) of PFAS and lipid profiles (during the second tracking period), we observed positive correlations with total cholesterol and LDL-C for perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), N-methylperfluorooctane sulfonamide acetic acid (N-MeFOSAA), and the sum of PFAS (sum of the 11 kinds of PFAS). Additionally, average levels of PFUdA, N-MeFOSAA, and the sum of PFAS exhibited positive associations with sdLDL-C. This study unveiled an overall decrease in PFAS concentrations and underscores a potential link between PFAS exposure and adverse changes in lipid profiles among young populations, emphasizing the need for further exploration into the mechanisms of PFAS on lipid metabolism and atherosclerosis.

Association between urinary glyphosate levels and serum neurofilament light chain in a representative sample of US adults: NHANES 2013-2014.

BACKGROUND: Glyphosate, the herbicide with the highest global usage, has been found to have links to neurological impairment in some occupational studies. Neurofilament light chain (NfL) is a protein that is released into the bloodstream following neuroaxonal damage and has emerged as a reliable biomarker for various neurological disorders. However, no research has investigated the potential link between glyphosate exposure and neurological damage or serum NfL levels in the general population. OBJECTIVE: The objective of this study was to assess the possible correlation between glyphosate exposure and serum NfL levels in a population that is representative of the United States. METHODS: We analyzed data from 597 adults (aged ≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the potential correlation between urinary glyphosate levels and serum NfL levels. RESULTS: We found a significant positive association between urinary glyphosate levels and serum NfL levels (ß-coefficient = 0.110; S.E. = 0.040; P = 0.015), indicating that higher levels of glyphosate exposure may be linked to higher levels of neuroaxonal damage. Furthermore, when glyphosate levels were divided into quintiles, we observed a significant trend of increasing mean NfL concentrations with increasing quintiles of glyphosate exposure (P for trend = 0.036). Notably, the association was more pronounced in certain subgroups, including those aged ≥40 years, non-Hispanic whites, and those with a BMI between 25 and 30. IMPACT STATEMENT: This is the first research to suggest an association between glyphosate exposure and biomarkers indicative of neurological damage in general U.S. adults. If the correlation observed is causal, it raises concerns about the potential effects of glyphosate exposure on neurological health among U.S. adults. The study is noteworthy due to its representation of American adults aged 20 and above, as well as the use of reliable and comprehensive data from the NHANES database.

Association between Glyphosate Exposure and Erythrograms in a Representative Sample of US Adults: NHANES 2013-2014.

Glyphosate is the most commonly utilized herbicide globally, and a growing body of experimental research has linked its exposure to red blood cell damage. However, the potential toxicity of glyphosate exposure on erythrocytes in the general population remains poorly understood. Therefore, we analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) of 1466 adults (≥ 18 years) to explore the potential relationship between glyphosate exposure and erythrocyte profiles. Our results indicated a significant negative association between urinary glyphosate levels and hemoglobin (Hb) and hematocrit (Hct) in multiple regression analysis, with ß coefficients of -0.157 (S.E. = 0.055, P = 0.012) and -0.431 (S.E. = 0.195, P = 0.043), respectively. Additionally, the odds ratio showed a significant increase in individuals with anemia with a one-unit increase in ln-glyphosate levels (odds ratio = 1.523 (95% CI = 1.301 - 1.783), P < 0.001 in the final model). The negative correlation between glyphosate and Hb was more pronounced in subjects older than 60 years, non-Hispanic white ethnicity, lower income, and those with a body mass index (BMI) < 25 and ≥ 30. In conclusion, our results provide preliminary evidence of a plausible association between glyphosate exposure and anemia in a subset of the adult population in the United States. However, further research is necessary to understand the underlying mechanisms and clinical implications of this association.

The Association among Urinary Lead and Cadmium, Serum Adiponectin, and Serum Apoptotic Microparticles in a Young Taiwanese Population.

Previous studies reported that lead (Pb) and cadmium (Cd) exposure are linked to changes in serum adiponectin; an adipokine that promotes glycolysis and inhibits gluconeogenesis to regulate glucose metabolism. However, no study has ever explored the relationship between exposure to these two heavy metals and adiponectin in adolescents and young adults. Additionally, the role of adiponectin in the relationship between Pb and Cd exposure and vascular endothelial cell apoptosis has never been investigated. In this study, 724 Taiwanese participants, aged 12 to 30 years, were enrolled to investigate the association among urinary lead and cadmium, serum adiponectin, and apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). The results of the current study revealed a statistically significant inverse association between urine Pb and Cd levels and adiponectin levels, as well as a positive association with apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). Adiponectin was also inversely correlated with CD31+/CD42a- and CD31+/CD42a+. Moreover, when subjects with both Pb and Cd levels above the 50th percentile were compared to those below it, the former group exhibited the lowest average adiponectin value. Additionally, a more pronounced positive association between heavy metals and apoptotic microparticles (CD31+/CD42a- and CD31+/CD42a+) was observed when adiponectin levels were lower. Furthermore, an interaction between adiponectin and heavy metals was identified in the relationship between these metals and CD31+/CD42a-. In conclusion, these findings suggest that Pb and Cd exposure may have an adverse effect on adiponectin, and it may play a role in the link between heavy metal exposure and the dysfunction of vascular endothelial cells. Future studies are needed to establish whether a causal relationship exists.

The Association between 4-Tertiary-Octylphenol, Apoptotic Microparticles, and Carotid Intima-Media Thickness in a Young Taiwanese Population.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12-30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a- and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a- and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

Urinary di-(2-ethylhexyl) phthalate metabolites are independently related to serum neurofilament light chain, a biomarker of neurological diseases, in adults: results from NHANES 2013-2014.

Di (2-ethylhexyl) phthalate (DEHP) is a chemical commonly used in the manufacturing of plastics and can pose human health risks, including endocrine disruption, reproductive toxicity, and potential carcinogenic effects. Children may be particularly vulnerable to the harmful effects of DEHP. Early exposure to DEHP has been linked to potential behavioral and learning problems. However, there are no reports to date on whether DEHP exposure in adulthood has neurotoxic effects. Serum neurofilament light chain (NfL), a protein released into the blood after neuroaxonal damage, has been shown to be a reliable biomarker for many neurological diseases. To date, no study has examined the relationship between DEHP exposure and NfL. For the present study, we selected 619 adults (aged ≥ 20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the association between urinary DEHP metabolites and serum NfL. We reported higher urinary levels of ln-mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), ln-mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and ln-mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and ln-ΣDEHP levels were associated with higher serum levels of ln-NfL (ΣDEHP: ß-coefficient = 0. 075; S.E. = 0.026; P = 0.011). When we divided ΣDEHP into quartiles, mean NfL concentrations increased with quartiles of MEHHP (P for trend = 0.023). The association was more pronounced in males, non-Hispanic white race, higher income, and BMI < 25. In conclusion, higher DEHP exposure was positively associated with higher serum NfL in adults from NHANES 2013-2014. If this finding is causal, it is possible that DEHP exposure in adulthood may also induce neurological damage. Although the causality of this observation and the clinical significance are uncertain, our findings suggest that additional research is needed on DEHP exposure, serum NfL, and neurological disease in adults.

Association of Urinary Lead and Cadmium Levels, and Serum Lipids with Subclinical Arteriosclerosis: Evidence from Taiwan.

BACKGROUND: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. METHODS: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). RESULTS: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. CONCLUSION: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population.

BACKGROUND: Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. METHODS: This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12-30 from Taiwan. RESULTS: Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (- 0.095 vs. - 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. CONCLUSIONS: In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Urine Di-(2-ethylhexyl) Phthalate Metabolites Are Independently Related to Body Fluid Status in Adults: Results from a U.S. Nationally Representative Survey.

PURPOSE: Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many daily products for decades. Previous studies have reported that DEHP exposure could induce renin-angiotensin-aldosterone system activation and increase epithelial sodium channel (ENaC) activity, which contributes to extracellular fluid (ECF) volume expansion. However, there is also no previous study to evaluate the association between DEHP exposure and body fluid status. METHODS: We selected 1678 subjects (aged ≥18 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003-2004 to determine the relationship between urine DEHP metabolites and body composition (body measures, bioelectrical impedance analysis (BIA)). RESULTS: After weighing the sampling strategy in multiple linear regression analysis, we report that higher levels of DEHP metabolites are correlated with increases in body measures (body weight, body mass index (BMI), waist circumference), BIA parameters (estimated fat mass, percent body fat, ECF, and ECF/intracellular fluid (ICF) ratio) in multiple linear regression analysis. The relationship between DEHP metabolites and the ECF/ICF ratio was more evident in subjects of younger age (20-39 years old), women, non-Hispanic white ethnicity, and subjects who were not active smokers. CONCLUSION: In addition to being positively correlated with body measures and body fat, we found that urine DEHP metabolites were positively correlated with ECF and the ECF/ICF ratio in the US general adult population. The finding implies that DEHP exposures might increase ECF volume and the ECF/ICF ratio, which may have adverse health outcomes on the cardiovascular system. Further research is needed to clarify the causal relationship.