Chen C, Xun P, Kaufman JD, et al. Erythrocyte omega-3 index, ambient fine particle exposure and brain aging. Neurology. 2020;95(8):e995-e1007.
To determine whether omega-3 fatty acid levels modify the potential neurotoxic effects of exposure to particulate matter with diameters less than 2.5 µm (PM2.5) on normal-appearing brain volumes among dementia-free elderly women
A total of 1,315 women (aged 65 to 80 years; average age 70 at the study onset) who were participants in the Women’s Health Initiative Memory Study–Magnetic Resonance Imaging (WHIMS-MRI) study and were free of dementia participated in this observational study between 1996 and 1999. These participants underwent structural brain MRIs in 2005 to 2006. This cohort was a subgroup of the 7,427 individuals enrolled in the Women’s Health Initiative Clinical Trials (WHI-CT) of postmenopausal hormone therapy.
The investigators calculated average PM2.5 exposure for each study participant based on their place of residence for the 3 years prior to their MRI. They determined intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFAs ) and fish consumption using semi-quantitative food frequency questionnaires and then calculating the average amount of fish each woman consumed each week, including broiled or baked fish, canned tuna, tuna salad, tuna casserole, and non-fried shellfish. The investigators did not include fried fish because research has shown deep-frying damages omega-3 fatty acids.
Investigators measured baseline omega-3 PUFA levels in the red blood cells (RBCs) of the participants and compared them with PM2.5 exposure and brain volumes as calculated from the MRIs.
The researchers calculated joint associations of baseline omega-3 PUFAs in red blood cells and PM2.5 exposure with brain volumes in generalized linear models.
After adjustment for potential confounders, women in this cohort who had higher levels of RBC LCn3PUFAs had significantly greater volumes of white matter and hippocampus in their brains. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm3 (P<0.01) greater in the white matter, and 0.08 cm3 (P=0.03) greater in the hippocampus. The associations with RBCs, docosahexaenoic acid (DHA) levels, and eicosapentaenoic acid (EPA) levels were similar. Higher LCn3PUFA levels attenuated the inverse associations between PM2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all P for interaction <0.05), while the associations with other brain regions were not modified. Consistent results were found for a linear association of dietary intakes of LCn3PUFAs and non-fried fish.
These findings suggest that among older women, the benefits of omega-3 PUFAs on brain aging may include protection against the adverse effects of air pollution on white matter volumes.
In recent years we have watched the steady accumulation of evidence that suggests exposure to air pollutants, in particular the super-small PM2.5 generated by combustion, increases risk of various neurological disorders including stroke, cognitive decline, and accelerated brain aging. These fine particulates are also highly associated with cardiovascular disease and overall mortality.1 Exposure to ambient PM2.5 is now considered an environmental risk factor for cognitive decline among the elderly.2 One of the more striking measures of this association is the link between PM2.5 and decreased brain volumes in older women, which the authors of the current study reported in 2015.3
PM2.5 is tiny enough to enter through the respiratory tract directly into the blood circulation system. As the blood flows through the body, these particles trigger inflammation, causing damage to other systems, including the brain. LCn3PUFAs are important components of synaptic membranes and are critical to maintaining brain structure and function as people age, and these specific types of fat are associated with greater total brain volume and gray matter.4,5 Fish oils have also been reported to reduce brain damage from a range of environmental toxins including lead, organic solvents, and mercury.6,7
In this report Chen et al demonstrate that omega-3 fatty acid levels weakened the inverse association seen between PM2.5 and white matter volumes in the brain. A simpler way to state this is that eating fish appears to be protective against the brain damage caused by PM2.5 air pollution.
Even what many would consider to be moderate fish consumption seems to be enough to counter the damage associated with this air pollution: The omega-3 fatty acids in just 1 to 2 servings of fish per week were enough to provide significant benefit.
From 2009 to 2016, levels of fine particulates in the U.S air decreased about 25%. According to a 2019 working paper from the National Bureau of Economic Research (NBER), this trend suddenly shifted in 2016, and PM2.5 levels began to increase, rising 5.5% by 2018.8 This increase was driven by a nearly 30% increase in air pollutant levels in the Western states. A number of factors contributed to these increases, including increases in driving, the burning of natural gas, and wildfires. The researchers also suggest that a contributor was decreased enforcement of the Clean Air Act from 2009 to 2016 and continuing into 2018. This law, and its updates, had been responsible for the strict air pollution standards set for power plants, factories, vehicles, and other sources of pollution. Enforcement of these laws had greatly improved air quality across the country. A 2011 estimate by the Environmental Protection Agency suggested that these regulations would prevent 230,000 premature deaths by 2020.9 In contrast, the authors for the NBER paper calculated that the 5.5% increase in PM2.5 levels nationwide from 2016 to 2018 was associated with nearly 10,000 additional premature deaths during that time. These calculations do not take into account the risks for illnesses only recently linked with air quality, such as the increased risk of brain volume effects described in Chen et al’s study.
The omega-3 fatty acids in just 1 to 2 servings of fish per week were enough to provide significant benefit.
Two executive orders further weakened environmental protections in early June 2020. The first order temporarily waived environmental reviews of infrastructure projects in order to encourage building during the Covid-19–related economic slowdown. The second rule changed the methodology used by the EPA for cost-benefit analyses resulting from Clean Air Act regulation, greatly limiting the strength of future controls on air pollution.10
Given these actions and numerous other policy changes in recent years, we should assume that air quality in our country will continue to worsen. Encouraging our patients to eat fish regularly—2 servings a week as suggested by Chen et al’s study—is certainly prudent, pragmatic, and advisable. Doing so will provide some “locus of control” to our patients, giving them a sense that they still have some way to influence their future and their health. Still, as a naturopathic doctor who preaches tolle causam (meaning find the cause), this fish-eating promotion feels like focusing our attention in the wrong direction. We should be striving to create a cleaner environment and reducing pollution. The increasing pollution is the problem, not a fish deficiency.
- Pun VC, Kazemiparkouhi F, Manjourides J, Suh HH. Long-term PM2.5 exposure and respiratory, cancer, and cardiovascular mortality in older US adults. Am J Epidemiol. 2017;186(8):961-969.
- Heusinkveld HJ, Wahle T, Campbell A, et al. Neurodegenerative and neurological disorders by small inhaled particles. Neurotoxicology. 2016;56:94-106.
- Chen JC, Wang, X, Wellenius GA, et al. Ambient air pollution and neurotoxicity on brain structure: evidence from Women’s Health Initiative Memory Study. Ann Neurol. 2015; 78(3):466–476.
- Cutuli D. Functional and structural benefits induced by omega-3 polyunsaturated fatty acids during aging. Curr Neuropharmacol. 2017;15:534-542.
- Conklin SM, Gianaros PJ, Brown SM, et al. Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett. 2007;421:209-212.
- Singh PK, Nath R, Ahmad MK, Rawat A, Babu S, Dixit RK. Attenuation of lead neurotoxicity by supplementation of polyunsaturated fatty acid in Wistar rats. Nutr Neurosci. 2016;19:396-405.
- Kaur P, Schulz K, Aschner M, Syversen T. Role of docosahexaenoic acid in modulating methylmercury-induced neurotoxicity. Toxicol Sci. 2007;100:423-432.
- Clay K, Muller NZ. Recent increases in air Pollution: evidence and implications for mortality. National Bureau of Economic Research working paper. 2019. https://www.nber.org/papers/w26381. Accessed September 17, 2020.
- United States Environmental Protection Agency. Benefits and costs of the Clean Air Act 1990-2020, the second prospective study. U.S. Environmental Protection Agency. https://www.epa.gov/clean-air-act-overview/benefits-and-costs-clean-air-act-1990-2020-second-prospective-study. Accessed September 17, 2020.
- Davenport C, Friedman L. Trump, citing pandemic, moves to weaken two key environmental protections. The New York Times. June 4, 2020. https://www.nytimes.com/2020/06/04/climate/trump-environment-coronavirus.html?searchResultPosition=2. Accessed September 17, 2020.