ABSTRACT
BACKGROUND: Short-term exposure to ambient nitrogen dioxide (NO2) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown protection against exposure to fine particulate matter. This study aims to investigate whether habitual omega-3 PUFA intake differentially modify the associations between respiratory and cardiovascular responses and short-term exposure to ambient NO2. METHODS: Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual omega-3 PUFA intake. Each participant was repeatedly assessed for lung function, blood lipids, markers of coagulation and fibrinolysis, vascular function, and heart rate variability (HRV) in up to five sessions, each separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily ambient NO2 concentrations were obtained from an area air quality monitoring station on the day of outcome assessment (Lag0), 4 days prior (Lag1-4), as well as 5-day moving average (5dMA). The associations between short-term exposure to NO2 and the measured indices were evaluated using linear mixed-effects models stratified by omega-3 levels and adjusted by covariates including relative humidity and temperature. RESULTS: The average concentration of ambient NO2 during the study periods was 5.3±3.8 ppb which was below the National Ambient Air Quality Standards (NAAQS). In the high omega-3 group, an interquartile range (IQR) increase in short-term NO2 concentrations was significantly associated with increased lung function [e.g. 1.2% (95%CI: 0.2%, 2.2%) in FVC at lag1, 2.6% (95%CI: 0.4%, 4.8%) in FEV1 at 5dMA], decreased blood lipids [e.g. -2.6% (95%CI: -4.4%, -0.9%) in total cholesterol at lag2, -3.1% (95%CI: -6.1%, 0.0%) in HDL at 5dMA, and -3.1% (95%CI: -5.5%, -0.7%) in LDL at lag2], improved vascular function [e.g. 8.9% (95%CI: 0.6%, 17.2%) increase in FMD and 43.1% (95%CI: -79.8%, -6.3%) decrease in endothelin-1 at 5dMA], and changed HRV parameters [e.g. -7.2% (95%CI: -13.6%, -0.8%) in HFn and 13.4% (95%CI: 0.2%, 28.3%) in LF/HF ratio at lag3]. In the low omega-3 group, an IQR increase in ambient NO2 was associated with elevations in coagulation markers (von Willebrand Factor, D-dimer) and a decrease in HRV (very-low frequency); however, null associations were observed between short-term NO2 exposure and changes in lung function, blood lipids, and vascular function. CONCLUSIONS: The results in this study imply that dietary omega-3 PUFA consumption may offer respiratory and vascular benefits in response to short-term exposure of healthy adults to NO2 levels below the NAAQS. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02921048 ).
Subject(s)
Air Pollutants , Air Pollution , Adult , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/analysis , Eating , Environmental Exposure/analysis , Fatty Acids, Unsaturated , Humans , Lung , Nitrogen Dioxide/analysis , Particulate Matter/adverse effects , Particulate Matter/analysisABSTRACT
Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.
Subject(s)
Aorta/drug effects , Dietary Fats/administration & dosage , Lung Injury/chemically induced , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Ozone/toxicity , Animals , Aorta/physiopathology , Biomarkers/analysis , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Coconut Oil/administration & dosage , Fish Oils/administration & dosage , Foam Cells/cytology , Inflammation , Lung Injury/immunology , Lung Injury/physiopathology , Male , Muscle, Smooth, Vascular/physiopathology , Olive Oil/administration & dosage , Rats, Inbred WKYABSTRACT
BACKGROUND: Exposure to air pollution contributes importantly to excess morbidity and mortality. And while regulatory actions under the "Clean Air Act" have saved millions of lives by improving air quality, there are still millions of people in the U.S. who live in areas where particulate air pollution (PM) levels exceed the U.S. Environmental Protection Agency's National Ambient Air Quality Standards. Therefore, apart from such localities working to attain such standards the protection of the health of public and in particular those at high risk might benefit from interventional strategies that would ameliorate air pollution's adverse health effects. Because inflammation and oxidative stress appear to mediate the health effects of air pollution, one interventional approach to consider is the use of dietary supplementation or medication with anti-inflammatory or antioxidant properties to block the biological responses that initiate the pathophysiological process that culminates in adverse health effects. SCOPE OF REVIEW: This article reviews the capability of dietary supplementation, such as antioxidant vitamins, polyunsaturated fatty acids, and medications as a strategy to mitigate air pollution-induced subclinical cardiopulmonary effects. MAJOR CONCLUSIONS: Antioxidant vitamins C and E protect the lungs against short-term ozone and PM exposure. Polyunsaturated fatty acids, such as fish oil and olive oil appear to offer protection against short-term air pollution-induced adverse cardiovascular responses. GENERAL SIGNIFICANCE: Taking dietary supplements or medications with antioxidant or anti-inflammatory properties has the potential to provide at least partial protection against air pollution-induced adverse health effects in those individuals who are known to be most susceptible, namely those with pre-existing respiratory and cardiovascular diseases. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.
Subject(s)
Antioxidants/administration & dosage , Cardiovascular Diseases/prevention & control , Dietary Supplements , Lung Diseases/prevention & control , Ozone/toxicity , Particulate Matter/toxicity , Air Pollution/analysis , Air Pollution/prevention & control , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Fatty Acids, Unsaturated/administration & dosage , Fish Oils/administration & dosage , Humans , Lung Diseases/etiology , Lung Diseases/metabolism , Lung Diseases/pathology , Olive Oil/administration & dosage , Vitamins/administration & dosageABSTRACT
BACKGROUND: Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for cardiovascular disease. Olive oil (OO) and fish oil (FO) supplements have beneficial effects on endothelial function. OBJECTIVE: In this study we evaluated the potential efficacy of OO and FO in mitigating endothelial dysfunction and disruption of hemostasis caused by exposure to particulate matter (PM). METHODS AND RESULTS: Forty-two participants (58 ± 1 years of age) received either 3 g/day of OO or FO, or no supplements (naive) for 4 weeks prior to undergoing 2-hr exposures to filtered air and concentrated ambient particulate matter (CAP; mean, 253 ± 16 µg/m3). Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery preexposure, immediately postexposure, and 20 hr postexposure. Levels of endothelin-1 and markers of fibrinolysis and inflammation were also measured. The FMD was significantly lower after CAP exposure in the naive (-19.4%; 95% CI: -36.4, -2.3 per 100 µg/m3 CAP relative to baseline; p = 0.03) and FO groups (-13.7%; 95% CI: -24.5, -2.9; p = 0.01), but not in the OO group (-7.6%; 95% CI: -21.5, 6.3; p = 0.27). Tissue plasminogen activator levels were significantly increased immediately after (11.6%; 95% CI: 0.8, 22.2; p = 0.04) and 20 hr after CAP exposure in the OO group. Endothelin-1 levels were significantly increased 20 hr after CAP exposure in the naive group only (17.1%; 95% CI: 2.2, 32.0; p = 0.03). CONCLUSIONS: Short-term exposure to CAP induced vascular endothelial dysfunction. OO supplementation attenuated CAP-induced reduction of FMD and changes in blood markers associated with vasoconstriction and fibrinolysis, suggesting that OO supplementation may be an efficacious intervention to protect against vascular effects of exposure to PM. CITATION: Tong H, Rappold AG, Caughey M, Hinderliter AL, Bassett M, Montilla T, Case MW, Berntsen J, Bromberg PA, Cascio WE, Diaz-Sanchez D, Devlin RB, Samet JM. 2015. Dietary supplementation with olive oil or fish oil and vascular effects of concentrated ambient particulate matter exposure in human volunteers. Environ Health Perspect 123:1173-1179; http://dx.doi.org/10.1289/ehp.1408988.
Subject(s)
Air Pollutants/adverse effects , Fish Oils/administration & dosage , Olive Oil/administration & dosage , Particulate Matter/adverse effects , Aged , Blood Flow Velocity , Brachial Artery/physiology , Dietary Supplements , Endothelin-1/analysis , Endothelium, Vascular/physiology , Female , Fibrinolysis , Healthy Volunteers , Humans , Male , Middle Aged , Tissue Plasminogen Activator/analysis , Vasodilation/physiologyABSTRACT
BACKGROUND: Air pollution exposure has been associated with adverse cardiovascular health effects. Findings of a recent epidemiological study suggested that omega-3 fatty acid (fish oil) supplementation blunted cardiac responses to air pollution exposure. OBJECTIVES: We conducted a randomized, controlled exposure study to evaluate the efficacy of fish oil supplements in attenuating adverse cardiac effects of exposure to concentrated ambient fine and ultrafine particulate matter (CAP). METHODS: Twenty-nine healthy middle-aged participants (mean, 58 ± 1 years of age) were supplemented in a randomized, double-blinded manner with 3 g/day of either fish oil or olive oil for 4 weeks before sequential chamber exposure to filtered air and CAP (mean mass concentration 278 ± 19 µg/m3) for 2 hr. Cardiac responses were assessed by comparing time and frequency domain changes in heart rate variability (HRV) and electrocardiographic repolarization changes measured before, immediately after, and 20 hr after exposure. Changes in plasma lipids were also evaluated at these time points. RESULTS: Fish oil supplementation appeared to attenuate CAP-induced reductions in high-frequency/low-frequency ratio, as well as elevations in normalized low-frequency HRV and prolongation of the QT interval corrected for heart rate (QTc). Very low-density lipoprotein and triglyceride concentrations increased significantly immediately after exposure to CAP in participants supplemented with olive oil, but not in those supplemented with fish oil. CONCLUSIONS: Exposure of healthy middle-aged adults to CAP for 2 hr induced acute cardiac and lipid changes after supplementation with olive oil, but not fish oil. Our findings suggest that omega-3 fatty acid supplements offer protection against the adverse cardiac and lipid effects associated with air pollution exposure.
Subject(s)
Fatty Acids, Omega-3/therapeutic use , Fish Oils/therapeutic use , Heart/drug effects , Particulate Matter/toxicity , Dietary Supplements , Female , Heart Rate/drug effects , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: The goal of the present study was to localize and quantify immunoreactive prostaglandin H synthase 1 (PGHS-1), PGHS-2, and Fos expression by immunohistochemistry in the fetal brain 30 minutes and 2 hours after the onset of a 10-minute period of cerebral hypoperfusion in barodenervated and chemodenervated fetal sheep. METHODS: Fetal sheep of known gestational age were studied intact or sinoaortic denervated. Fetuses were sacrificed and tissues recovered for immunohistochemistry or real-time polymerase chain reaction measurements of protein and mRNA, respectively. Some fetuses were subjected to brachiocephalic occlusion, produced by inflation of an extravascular balloon occluder around the brachiocephalic artery. Immunohistochemistry results were quantified using image analysis, and mRNA was quantified by estimation of cycle threshold in generation of PGHS-1 or PGHS-2 amplicons. RESULTS: Sinoaortic denervation by itself did not alter the abundance of PGHS-1 or PGHS-2 protein in any brain region, although the denervation did reduce the abundance of PGHS-1 mRNA in hypothalamus. We assessed PGHS-1, PGHS-2, and Fos immunoreactive protein abundance by image analysis of histologic sections stained for the respective proteins using immunohistochemistry. Cerebral hypoperfusion increased the intensity of staining of immunoreactive PGHS-1, PGHS-2, and Fos in the anterior pituitary, hippocampus, and cerebellum. In the cerebral microvasculature, the intensity of PGHS-1 and Fos was significantly greater, and in the cerebral cortex, the intensity of PGHS-2 was significantly greater. Changes in the amount of immunostaining in the nucleus of tractus solitarius and paraventricular nucleus were not statistically significant. CONCLUSION: Cerebral hypoperfusion altered the expression and distribution of prostaglandin biosynthetic enzymes in ovine fetal brain by a mechanism that is independent of baroreceptor and chemoreceptor afferent activity.