Omega-3 PUFAs Offset Adverse CV Effects of Air Pollution in Small, Chinese Study

The addition of omega-3 polyunsaturated fatty acids (PUFAs) appears to offset the short-term cardiovascular risks of air pollution, with investigators reporting new data showing that supplementation with 2.5 g of fish oil had positive effects on biomarkers of inflammation, coagulation, endothelial dysfunction, oxidative stress, and neuroendocrine disturbances.

In extensively polluted industrial areas, adding omega-3 PUFAs to the diet may “represent a simple and effective way to protect cardiovascular health” against the hazardous exposure to emissions, Zhijing Lin, PhD (Fudan University, Shanghai, China), and colleagues report in the April 30, 2019, issue of the Journal of the American College of Cardiology.   

In an accompanying editorial, Sanjay Rajagopalan, MD (University Hospitals, Cleveland, OH), and Robert Brook, MD (University of Michigan, Ann Arbor), state that while these new findings are promising, “given the lack of evidence regarding the efficacy of marine-derived omega-3 fatty acids as well as other personalized interventions to protect against clinical cardiovascular events induced by air pollution, it is premature to recommend their wide-scale use.”

Nonetheless, the editorialists point out that the Chinese study is one of the first to test omega-3 PUFAs in an environment where pollution levels are high. In the present study, the average ambient particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) was 38 µg/m3, which is significantly greater than the annual average ambient air quality standard in the United States and Canada (< 12 µg/m3).

Testing Omega-3 PUFAs Against Sunflower Seed Oil

In the randomized, placebo-controlled trial, 65 healthy college-age subjects were assigned to 2.5 g/day of marine-derived omega-3 PUFAs or placebo (sunflower seed oil) for 4 months. The researchers scheduled follow-up visits every 2 weeks during the last 2 months of the intervention. The two groups had similar blood levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline, but those supplemented with fish oil had higher levels during follow-up.

Overall, treatment with the omega-3 fatty acid was associated with a significant between-group difference in levels of interleukin-6, a marker of inflammation, as well as von Willebrand factor (vWF) and fibrinogen, two markers of coagulation. Additionally, there were significant between-group differences in E-selectin, which is reflective of endothelial function, and biomarkers of oxidative stress and neuroendocrine function, such as oxidized LDL and cortisol, respectively. There was no significant between-group difference in blood pressure, C-reactive protein levels, or markers of insulin resistance.

“Compared with the placebo group, the fish-oil group showed an overall biomarker profile that indicates better cardiovascular health,” write Lin and colleagues.

Daniel Croft, MD (University of Rochester Medical Center, NY), who was not involved in the study, has research interests in the adverse health effects of air pollution and has previously shown that marine-derived omega-3 PUFAs could attenuate increases in fibrinogen levels caused by air pollution. In the present study, Croft said the Chinese investigators “cast a very wide net” when looking at the effects of omega-3 PUFAs.

“They really had an impressive breadth of surrogate markers,” he said, adding that their findings will certainly fuel further research.

He pointed out that sunflower seed oil, which is a source omega-6 fatty acids, did not offer the same protective effects as the marine-derived omega-3 PUFAs. In his group’s previous work, Croft said they also did not see an effect on fibrinogen levels among patients who received plant-derived alpha-linoleic acid. “It’s possible the fish-based and plant-based omega fatty acids have different effects,” he said.

Inflammation Critical

In a 2015 study published in the Lancet, the Global Burden of Disease (GBD) study collaborators estimated that more than 4 million premature deaths each year could be attributed to air pollution, the vast majority of which were cardiovascular deaths. While the exact pathophysiological mechanisms linking air pollution to cardiovascular disease are not fully known, increased blood pressure, inflammation, oxidative stress, endothelial dysfunction, insulin resistance, and thrombotic effects are thought to contribute.

Like Lin and colleagues, Croft stressed that the mechanisms underlying the adverse effects of pollution are quite broad, although most researchers believe increased inflammation is critical.

The main way to reduce mortality and morbidity from air pollution is to reduce air pollution to begin with. Daniel Croft

“It’s central to a few different processes, whether it’s air pollution’s effect on the lungs or vasculature,” he told TCTMD. “In cardiovascular disease, systemic inflammation is very important. When you inhale air pollution, it can damage the tissue it touches, like in the airway, for example. It damages the lining of the airways, but as inflammation spreads through the body, it can damage the endothelium.”

Other detrimental aspects of air pollution include increased coagulation and platelet activation, which can lead to the development of thrombotic events, said Croft. “Air pollution can insert itself in the pathway in a few different areas,” he said. “It’s not just a single mechanism.”

While omega-3 PUFAs reduce inflammation, Croft noted there are still questions about how they exert their influence in reducing cardiovascular outcomes. At the American Heart Association 2018 Scientific Session, the REDUCE-IT investigators showed that a prescription-strength omega-3 fatty acid formulation reduced the risk of major cardiovascular events in patients with high triglycerides, but noted they weren’t exactly sure how the agent worked.

In the editorial, Rajagopalan and Brook call for randomized trials to test the efficacy of omega-3 PUFAs for reducing clinical outcomes induced by air pollution, particularly in patients at highest risk, such as those with ACS or other conditions. Croft agreed but pointed out that the use of omega-3 fatty acids to combat air pollution only emerged given the lack of other viable options.

“The main way to reduce mortality and morbidity from air pollution is to reduce air pollution to begin with,” he said. “I think [omega-3 PUFAs] would be good to study as a temporizing measure, but we need to keep in mind that we need to keep working hard on reducing air pollution overall.”