Our study supported the hypothesis that the dietary intake of some OCPs from plant-based foods is associated with interference of serum lipid levels and affects inflammation responses among childbearing-age women in a typical agricultural region. In addition, we did not find any associations between nutrient intakes and serum biomarkers here, which can partly support our findings. The study is the first to assess the potential impacts of dietary OCPs exposure from plant-based foods on serum lipid and inflammation biomarkers using a multiple follow-up study in North China.
We observed overall no associations between nutritional intakes and serum biomarkers among 10 intensively studied women. This is inconsistent with previous studies that reported the potential influence of food nutrients on lipid metabolism and inflammation. Patel et al. identified and validated several environmental factors correlated with TG, LDL, and HDL levels using the National Health and Nutrition Examination Survey (NHANES) [19]. In their study, vitamins A and E were positively associated with TG and LDL but negatively associated with HDL, and carotenoids were associated with lower TG levels and higher levels of both HDL and LDL. As Calder et al. reported, among the components of a healthy diet, whole grains, vegetables, fruits, and fish are all associated with lower inflammation, and vitamin C, vitamin E, and carotenoids decrease circulating concentrations of inflammatory markers [22]. Large-scale and long-term survey or dietary intervention methods were used in the previous studies to investigate the links between nutrients and lipid metabolism and inflammation, which was different from our study. Our target population was childbearing-age women recruited in a small county, resulting in a similar dietary pattern between individuals. The women recruited had neither a significant change in dietary structure nor nutritional supplements throughout the study period. Relatively fixed dietary patterns are unlikely to cause obvious inter- and intra-individual variation in levels of lipid and inflammation biomarkers, which may be the reason for the negative results observed in this study. Thus, this can provide a good study scenario to explore the relationship between dietary OCP intake and effect biomarkers.
Cereals, fruits, and vegetables are the primary foods in local diets and comprised more than 75% of the women's daily food consumption. As reported previously, plant-origin foods may play an important role in exposure to OCPs due to the relatively higher ingestion amounts of such foods [33, 34]. Specifically, vegetables dominate the dietary exposure dose for the sum of DDT and its metabolites (ΣDDT) and the sum of HCH isomers (ΣHCH) for the Nanjing population [33]. From this perspective, OCP exposure from plant-origin foods may play an essential role in disturbing the metabolic and immune systems rather than nutrients in our target population. The potential influence of dietary OCP intake by local women on lipid metabolism and inflammation is hence mainly discussed in this context.
In the present study, significant negative links between dietary exposure to p,p′-DDT and o,p′-DDE and serum HDL were found. These results suggest that OCPs may disrupt lipid metabolism and contribute to dyslipidemia, which is in line with previous studies. Exposure to persistent organic pollutants, especially OCPs, may alter genome-wide gene transcription related to energy metabolism [7, 17] and induce mitochondrial dysfunction [35, 36], thus affecting the metabolites of crucial metabolic processes mainly related to human lipid metabolism [37]. Lee et al. observed significant associations of serum p,p′-DDE with higher TGs and lower HDL during a 20-year follow-up study [38]. Dusanov et al. also found that participants with elevated levels of organochlorine compounds (i.e., HCB, β-HCH, trans-nonachlor, p,p′-DDT, and p,p′-DDE) in serum also exhibited decreased HDL in a cross-sectional study [8]. Conversely, no association with HDL was observed that could be attributed to DDTs and their metabolites in serum in a case-control study in Shandong Province in East China, although TG, TC, and LDL disturbances were observed in the study [9]. A 5-year prospective analysis from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort of elderly adults in Sweden found only a positive association between serum p,p′-DDE and LDL, whereas no significant results were reported for TG, TC, and HDL [39]. The discrepancies among various studies may be explained by the variations in population characteristics and living habits, which are inevitably related to lipid metabolism [5, 6, 40]. We have verified that some OCP exposure can be related to interference with blood lipid levels, although there are differences in significantly associated markers across different studies. Here we report the association between dietary OCP exposure due to plant-origin food consumption and lipid metabolism in humans, providing evidence for the influence of long-term low-dose OCP exposure on human lipid metabolism from another perspective.
Furthermore, an association between dietary o,p′-DDE exposure and serum lipid disorder was found in this study instead of exposure to p,p′-DDE, which is a major metabolite of p,p′-DDT that has been commonly considered in previous studies [7, 9]. Qiu et al. had identified dicofol formulation, which contains a high ratio of o,p′-DDT/p,p′-DDT, as a key and sometimes dominant DDT source in the air in China in recent years [41]. Therefore, the regulation of o,p′-DDTs and its epidemiologic study are necessary for population health in China. Further longitudinal studies with measures of OCPs over time are needed.
Our study showed that serum IL-8 was positively associated with dieldrin, endosulfan-β, ΣES, and ΣOCP intake, but negatively associated with p,p′-DDE intake. IL-8 is a well-known pro-inflammatory cytokine and has been reported to increase in patients with various autoimmune diseases, infections, cancers, and psychiatric diseases [42, 43]. An association between persistent organochlorine pollutant exposure and elevated cytokine levels has been reported [44, 45]. Exposure to endosulfans and dieldrin can increase the expression levels of the pro-inflammatory factors IL-6, IL-8, IL-1β, and TNF-α, as evidenced in molecular studies [13, 46]. Female mice and rats had increased levels of pro-inflammatory cytokines when exposed to doses ranging from 2–50 mg/kg of endosulfans [18, 47], which is consistent with our results. However, no significant associations were found between serum dieldrin, endosulfan-α, and endosulfan-β and cytokines (i.e., IL-2, IL-4, IL-6, and IL-10) in preterm birth cases in a case-control study in India, and only endosulfan-β was positively correlated with IL-2 in the controls [48]. The difference can be attributed to the geographic, demographic, and targeted biomarker variances among studies and requires further investigation. Overall, we observed an association between the intake of specific OCPs from plant-origin foods and inflammation factors in this study, indicating a disruption of homeostasis due to these compounds. As far as we know, there is little evidence of the influence of dietary OCP intake on pro-inflammatory responses from population studies. Considering its various hazardous health outcomes, inflammation caused by the dietary intake of OCPs from plant-origin foods deserves further attention.
The following limitations should be considered when interpreting our results. First, the bioavailability of OCPs among foods was not considered. Second, only limited serum biomarkers of lipids and inflammatory effects were measured. Further comprehensive information is needed to provide an in-depth investigation. However, our study also had several advantages. First, our study focused on dietary OCP exposure from plant-origin foods in childbearing-age women in a typical agriculture area, providing a unique insight into OCP exposure toxicity. Second, the dietary intake of nutrients was considered simultaneously, providing comprehensive food-borne exposure information. Third, we adopted a multiple follow-up study to effectively reduce the influence of confounders.