Omega-3 Fatty Acids and Pollution-Induced Cardiac Effects
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/m) 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.
Ambient air pollution exposure is a major environmental risk to human health. The World Health Organization (WHO) has estimated that air pollution causes approximately two million deaths per year worldwide (WHO 2011), and the number is climbing. Epidemiological and experimental studies have demonstrated positive associations between adverse cardiopulmonary effects and acute and chronic exposure to levels of ambient air pollution currently found in major metropolitan areas [Brook et al. 2010; U.S. Environmental Protection Agency (EPA) 2009]. Short-term elevations in ambient particulate matter (PM) concentrations are associated with acute coronary syndrome, stroke, venous thrombosis, arrhythmia, and worsening of heart failure, particularly in certain at-risk populations (U.S. EPA 2009). Cohort studies have reported associations between PM exposure and modulation of the cardiac autonomic nervous system input leading to alterations in heart rate variability (HRV) (Gold et al. 2000; He et al. 2011; Pope et al. 2004). Our previous controlled human exposure studies have shown that concentrated ambient PM exposure changed HRV in healthy adults (Devlin et al. 2003; Samet et al. 2009). Previous studies have also linked PM exposure with elevated blood lipid levels in both humans and animals (Sun et al. 2005; Yeatts et al. 2007).
Ambient PM is a complex mixture of particles of varying size that are classified as coarse (PM2.5–10; 10 μm > PM > 2.5 μm in aerodynamic diameter), fine (PM2.5; PM < 2.5 μm), and ultrafine (PM0.1; PM < 0.1 μm) particles. The strongest associations between adverse health effects and particulate air pollution are observed with PM2.5 (Schwartz et al. 1996). However, PM0.1 is not routinely measured at state monitoring sites nor is it homogenously dispersed throughout an airshed, making it difficult to ascertain the toxicity of these particles in epidemiological studies. However, clinical and toxicological studies have reported that PM0.1 can pass through the lung epithelial cell barrier and enter the circulatory system, where it may directly affect the function of cells or organs (Brook et al. 2010; Nemmar et al. 2004). Therefore, in this study, participants were exposed to a combination of concentrated PM2.5 and PM0.1 ambient air particles (CAP).
Although air pollution regulations have resulted in dramatic decreases in PM levels over the past few decades, tens of millions of persons in the United States are still exposed to levels of PM that are higher than the current U.S. EPA standards (U.S. EPA 2009). If dietary supplements or pharmacological agents can blunt the adverse health effects of air pollution exposure, populations residing in highly polluted areas might be afforded some protection. A number of studies conducted over the last three decades have shown that the omega-3 polyunsaturated fatty acids (n-3 FA), eicosapentaenoic acid and docosahexaenoic acid (DHA), can reduce the risk of cardiovascular events after myocardial infarction (O'Keefe et al. 2006; Saravanan et al. 2010) as well as reduce atrial fibrillation recurrences in patients with persistent atrial fibrillation (Nodari et al. 2011). In general, n-3 FA have several potentially cardioprotective benefits, including suppression of arrhythmias and modulation of autonomic function in addition to antithrombotic, anti-inflammatory, and vasodilatory effects (Lee et al. 2009). Chronically decreased HRV has been used to predict an increased risk of cardiovascular morbidity and mortality (Kleiger et al. 1987; Lahiri et al. 2008; Tsuji et al. 1996), and several studies suggest that the intake of n-3 FA may improve autonomic function, including an increase in vagal activity and baroreflex sensitivity (Mozaffarian et al. 2008; O'Keefe et al. 2006).
A recent cohort panel study reported that the high- and low-frequency (HF and LF) components of HRV were increased among elderly participants after n-3 FA supplementation (Holguin et al. 2005) and that HRV decline associated with PM2.5 exposure before supplementation was not observed after n-3 FA supplementation (Romieu et al. 2005). To our knowledge, no controlled human exposure studies have been conducted to investigate the protective effect of n-3 FA supplementation against the adverse cardiovascular effects of air pollutant exposure. We designed this study to determine whether the cardiovascular effects caused by exposure to CAP could be blunted by supplementation with n-3 FA, compared with supplementation with oil devoid of n-3 FA (olive oil). We report here that supplementation of n-3 FA attenuated some adverse effects on autonomic function, ventricular repolarization, and lipid changes caused by exposure to CAP in healthy middle-aged adults.
Abstract and Introduction
Abstract
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/m) 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.
Introduction
Ambient air pollution exposure is a major environmental risk to human health. The World Health Organization (WHO) has estimated that air pollution causes approximately two million deaths per year worldwide (WHO 2011), and the number is climbing. Epidemiological and experimental studies have demonstrated positive associations between adverse cardiopulmonary effects and acute and chronic exposure to levels of ambient air pollution currently found in major metropolitan areas [Brook et al. 2010; U.S. Environmental Protection Agency (EPA) 2009]. Short-term elevations in ambient particulate matter (PM) concentrations are associated with acute coronary syndrome, stroke, venous thrombosis, arrhythmia, and worsening of heart failure, particularly in certain at-risk populations (U.S. EPA 2009). Cohort studies have reported associations between PM exposure and modulation of the cardiac autonomic nervous system input leading to alterations in heart rate variability (HRV) (Gold et al. 2000; He et al. 2011; Pope et al. 2004). Our previous controlled human exposure studies have shown that concentrated ambient PM exposure changed HRV in healthy adults (Devlin et al. 2003; Samet et al. 2009). Previous studies have also linked PM exposure with elevated blood lipid levels in both humans and animals (Sun et al. 2005; Yeatts et al. 2007).
Ambient PM is a complex mixture of particles of varying size that are classified as coarse (PM2.5–10; 10 μm > PM > 2.5 μm in aerodynamic diameter), fine (PM2.5; PM < 2.5 μm), and ultrafine (PM0.1; PM < 0.1 μm) particles. The strongest associations between adverse health effects and particulate air pollution are observed with PM2.5 (Schwartz et al. 1996). However, PM0.1 is not routinely measured at state monitoring sites nor is it homogenously dispersed throughout an airshed, making it difficult to ascertain the toxicity of these particles in epidemiological studies. However, clinical and toxicological studies have reported that PM0.1 can pass through the lung epithelial cell barrier and enter the circulatory system, where it may directly affect the function of cells or organs (Brook et al. 2010; Nemmar et al. 2004). Therefore, in this study, participants were exposed to a combination of concentrated PM2.5 and PM0.1 ambient air particles (CAP).
Although air pollution regulations have resulted in dramatic decreases in PM levels over the past few decades, tens of millions of persons in the United States are still exposed to levels of PM that are higher than the current U.S. EPA standards (U.S. EPA 2009). If dietary supplements or pharmacological agents can blunt the adverse health effects of air pollution exposure, populations residing in highly polluted areas might be afforded some protection. A number of studies conducted over the last three decades have shown that the omega-3 polyunsaturated fatty acids (n-3 FA), eicosapentaenoic acid and docosahexaenoic acid (DHA), can reduce the risk of cardiovascular events after myocardial infarction (O'Keefe et al. 2006; Saravanan et al. 2010) as well as reduce atrial fibrillation recurrences in patients with persistent atrial fibrillation (Nodari et al. 2011). In general, n-3 FA have several potentially cardioprotective benefits, including suppression of arrhythmias and modulation of autonomic function in addition to antithrombotic, anti-inflammatory, and vasodilatory effects (Lee et al. 2009). Chronically decreased HRV has been used to predict an increased risk of cardiovascular morbidity and mortality (Kleiger et al. 1987; Lahiri et al. 2008; Tsuji et al. 1996), and several studies suggest that the intake of n-3 FA may improve autonomic function, including an increase in vagal activity and baroreflex sensitivity (Mozaffarian et al. 2008; O'Keefe et al. 2006).
A recent cohort panel study reported that the high- and low-frequency (HF and LF) components of HRV were increased among elderly participants after n-3 FA supplementation (Holguin et al. 2005) and that HRV decline associated with PM2.5 exposure before supplementation was not observed after n-3 FA supplementation (Romieu et al. 2005). To our knowledge, no controlled human exposure studies have been conducted to investigate the protective effect of n-3 FA supplementation against the adverse cardiovascular effects of air pollutant exposure. We designed this study to determine whether the cardiovascular effects caused by exposure to CAP could be blunted by supplementation with n-3 FA, compared with supplementation with oil devoid of n-3 FA (olive oil). We report here that supplementation of n-3 FA attenuated some adverse effects on autonomic function, ventricular repolarization, and lipid changes caused by exposure to CAP in healthy middle-aged adults.