Jump to ContentJump to Main Navigation
Show Summary Details
In This Section

Reviews on Environmental Health

Editor-in-Chief: Carpenter, David O. / Sly, Peter

Editorial Board Member: Brugge, Doug / Diaz-Barriga, Fernando / Edwards, John W. / Field, R.William / Hales, Simon / Horowitz, Michal / Maibach, H.I. / Shaw, Susan / Stein, Renato / Tao, Shu / Tchounwou, Paul B.

4 Issues per year

CiteScore 2016: 1.95

SCImago Journal Rank (SJR) 2015: 0.776
Source Normalized Impact per Paper (SNIP) 2015: 0.676

See all formats and pricing
In This Section
Volume 32, Issue 1-2 (Mar 2017)


Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation

Jessie B. Hoffman
  • Superfund Research Center, University of Kentucky, Lexington, KY 40536, USA
  • Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
/ Michael C. Petriello
  • Superfund Research Center, University of Kentucky, Lexington, KY 40536, USA
  • Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536, USA
/ Bernhard Hennig
  • Corresponding author
  • Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536, USA
  • Superfund Research Center, University of Kentucky, 900 S. Limestone Street, Lexington, KY 40536, USA, Tel.: +1 859-218-1343, Fax: +1 859-257-1811
  • Email:
Published Online: 2017-01-11 | DOI: https://doi.org/10.1515/reveh-2016-0041


Exposure to environmental pollutants is a global health problem and is associated with the development of many chronic diseases, including cardiovascular disease, diabetes and metabolic syndrome. There is a growing body of evidence that nutrition can both positively and negatively modulate the toxic effects of pollutant exposure. Diets high in proinflammatory fats, such as linoleic acid, can exacerbate pollutant toxicity, whereas diets rich in bioactive and anti-inflammatory food components, including omega-3 fatty acids and polyphenols, can attenuate toxicant-associated inflammation. Previously, researchers have elucidated direct mechanisms of nutritional modulation, including alteration of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, but recently, increased focus has been given to the ways in which nutrition and pollutants affect epigenetics. Nutrition has been demonstrated to modulate epigenetic markers that have been linked either to increased disease risks or to protection against diseases. Overnutrition (i.e. obesity) and undernutrition (i.e. famine) have been observed to alter prenatal epigenetic tags that may increase the risk of offspring developing disease later in life. Conversely, bioactive food components, including curcumin, have been shown to alter epigenetic markers that suppress the activation of NF-κB, thus reducing inflammatory responses. Exposure to pollutants also alters epigenetic markers and may contribute to inflammation and disease. It has been demonstrated that pollutants, via epigenetic modulations, can increase the activation of NF-κB and upregulate microRNAs associated with inflammation, cardiac injury and oxidative damage. Importantly, recent evidence suggests that nutritional components, including epigallocatechin gallate (EGCG), can protect against pollutant-induced inflammation through epigenetic regulation of proinflammatory target genes of NF-κB. Further research is needed to better understand how nutrition can modulate pollutant toxicity through epigenetic regulation. Therefore, the objective of this review is to elucidate the current evidence linking epigenetic changes to pollutant-induced diseases and how this regulation may be modulated by nutrients allowing for the development of future personalized lifestyle interventions.

Keywords: anti-inflammatory nutrients; antioxidant response; environmental pollutants; epigenetics; nutrition


  • 1.

    Tang M, Chen K, Yang F, Liu W. Exposure to organochlorine pollutants and type 2 diabetes: a systematic review and meta-analysis. PLoS One 2014;9(10):e85556.

  • 2.

    Taylor KW, Novak RF, Anderson HA, Birnbaum LS, Blystone C, et al. Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review. Environ Health Perspect 2013;121(7):774–83.

  • 3.

    Lim EJ, Majkova Z, Xu S, Bachas L, Arzuaga X, et al. Coplanar polychlorinated biphenyl-induced CYP1A1 is regulated through caveolae signaling in vascular endothelial cells. Chem-Biol Interact 2008;176(2–3):71–8.

  • 4.

    Majkova Z, Smart E, Toborek M, Hennig B. Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent. Toxicol Appl Pharm 2009;237(1):1–7.

  • 5.

    Schlezinger JJ, Struntz WD, Goldstone JV, Stegeman JJ. Uncoupling of cytochrome P450 1A and stimulation of reactive oxygen species production by co-planar polychlorinated biphenyl congeners. Aquat Toxicol 2006;77(4):422–32.

  • 6.

    Kuehn BM. Environmental pollutants tied to atherosclerosis. J Am Med Assoc 2011;306(19):2081.

  • 7.

    Carpenter DO. Polychlorinated biphenyls (PCBs): routes of exposure and effects on human health. Rev Environ Health 2006;21(1):1–23.

  • 8.

    Dirinck E, Jorens PG, Covaci A, Geens T, Roosens L, et al. Obesity and persistent organic pollutants: possible obesogenic effect of organochlorine pesticides and polychlorinated biphenyls. Obesity 2011;19(4):709–14.

  • 9.

    Goncharov A, Pavuk M, Foushee HR, Carpenter DO. Blood pressure in relation to concentrations of PCB congeners and chlorinated pesticides. Environ Health Perspect 2011;119(3):319–25.

  • 10.

    Sergeev AV, Carpenter DO. Hospitalization rates for coronary heart disease in relation to residence near areas contaminated with persistent organic pollutants and other pollutants. Environ Health Perspect 2005;113(6):756–61.

  • 11.

    Baker NA, Karounos M, English V, Fang J, Wei Y, et al. Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice. Environ Health Perspect 2013;121(1):105–10.

  • 12.

    Dirinck E, Dirtu AC, Jorens PG, Malarvannan G, Covaci A, et al. Pivotal role for the visceral fat compartment in the release of persistent organic pollutants during weight loss. J Clin Endocr Metab 2015;100(12):4463–71.

  • 13.

    Kim MJ, Marchand P, Henegar C, Antignac JP, Alili R, et al. Fate and complex pathogenic effects of dioxins and polychlorinated biphenyls in obese subjects before and after drastic weight loss. Environ Health Perspect 2011;119(3):377–83.

  • 14.

    Uemura H, Arisawa K, Hiyoshi M, Kitayama A, Takami H, et al. Prevalence of metabolic syndrome associated with body burden levels of dioxin and related compounds among Japan’s general population. Environ Health Perspect 2009;117(4):568–73.

  • 15.

    La Merrill M, Emond C, Kim MJ, Antignac JP, Le Bizec B, et al. Toxicological function of adipose tissue: focus on persistent organic pollutants. Environ Health Perspect 2013;121(2):162–9.

  • 16.

    Chiuve SE, Sampson L, Willett WC. The association between a nutritional quality index and risk of chronic disease. Am J Prev Med 2011;40(5):505–13.

  • 17.

    Wang L, Reiterer G, Toborek M, Hennig B. Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells. Chem-Biol Interact 2008;172(1):27–38.

  • 18.

    Kopelman PG. Obesity as a medical problem. Nature 2000;404(6778):635–43.

  • 19.

    Baum SJ, Kris-Etherton PM, Willett WC, Lichtenstein AH, Rudel LL, et al. Fatty acids in cardiovascular health and disease: a comprehensive update. J Clin Lipidol 2012;6(3):216–34.

  • 20.

    Kuipers RS, de Graaf DJ, Luxwolda MF, Muskiet MH, Dijck-Brouwer DA, et al. Saturated fat, carbohydrates and cardiovascular disease. Neth J Med 2011;69(9):372–8.

  • 21.

    Grun F. Obesogens. Curr Opin Endocrinol Diabetes, Obes 2010;17(5):453–9.

  • 22.

    Hennig B, Slim R, Toborek M, Robertson LW. Linoleic acid amplifies polychlorinated biphenyl-mediated dysfunction of endothelial cells. J Biochem Mol Toxicol 1999;13(2):83–91.

  • 23.

    Wahlang B, Falkner KC, Gregory B, Ansert D, Young D, et al. Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice. J Nutr Biochem 2013;24(9):1587–95.

  • 24.

    Wu J, Liu J, Waalkes MP, Cheng ML, Li L, et al. High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Exp Biol Med 2008;233(3):377–84.

  • 25.

    Harris DL, Washington MK, Hood DB, Roberts LJ, 2nd, Ramesh A. Dietary fat-influenced development of colon neoplasia in Apc Min mice exposed to benzo(a)pyrene. Toxicol Pathol 2009;37(7):938–46.

  • 26.

    Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect 2014;122(3):277–83.

  • 27.

    McGill HC, Jr., McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Circulation 2008;117(9):1216–27.

  • 28.

    Perkins JT, Petriello MC, Newsome BJ, Hennig B. Polychlorinated biphenyls and links to cardiovascular disease. Environ Sci Pollut Res Int 2016;23(3):2160–72.

  • 29.

    Petriello MC, Han SG, Newsome BJ, Hennig B. PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling. Toxicol Appl Pharm 2014;277(2):192–9.

  • 30.

    Petriello MC, Newsome B, Hennig B. Influence of nutrition in PCB-induced vascular inflammation. Environ Sci Pollut Res Int 2014;21(10):6410–8.

  • 31.

    Senthong V, Li XS, Hudec T, Coughlin J, Wu Y, et al. Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden. J Am Coll Cardiol 2016;67(22):2620–8.

  • 32.

    Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 2013;17(1):49–60.

  • 33.

    Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med 2015;66:343–59.

  • 34.

    Seldin MM, Meng Y, Qi H, Zhu W, Wang Z, et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-kappaB. J Am Heart Assoc 2016;5(2). pii: e002767.

  • 35.

    Senthong V, Wang Z, Li XS, Fan Y, Wu Y, et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a courage-like patient cohort. J Am Heart Assoc 2016;5(6). pii: e002816.

  • 36.

    Petriello MC, Hoffman JB, Sunkara M, Wahlang B, Perkins JT, et al. Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors. J Nutr Biochem 2016;33:145–53.

  • 37.

    Majkova Z, Layne J, Sunkara M, Morris AJ, Toborek M, et al. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls. Toxicol Appl Pharm 2011;251(1):41–9.

  • 38.

    Newsome BJ, Petriello MC, Han SG, Murphy MO, Eske KE, et al. Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes. J Nutr Biochem 2014;25(2):126–35.

  • 39.

    Petriello MC, Newsome BJ, Dziubla TD, Hilt JZ, Bhattacharyya D, et al. Modulation of persistent organic pollutant toxicity through nutritional intervention: emerging opportunities in biomedicine and environmental remediation. Sci Total Environ 2014;491–492:11–6.

  • 40.

    Romieu I, Garcia-Esteban R, Sunyer J, Rios C, Alcaraz-Zubeldia M, et al. The effect of supplementation with omega-3 polyunsaturated fatty acids on markers of oxidative stress in elderly exposed to PM(2.5). Environ Health Perspect 2008;116(9):1237–42.

  • 41.

    Slim R, Toborek M, Robertson LW, Hennig B. Antioxidant protection against PCB-mediated endothelial cell activation. Toxicol Sci 1999;52(2):232–9.

  • 42.

    Sun TL, Liu Z, Qi ZJ, Huang YP, Gao XQ, et al. (-)-Epigallocatechin-3-gallate (EGCG) attenuates arsenic-induced cardiotoxicity in rats. Food Chem Toxicol 2016;93:102–10.

  • 43.

    Tong H, Rappold AG, Diaz-Sanchez D, Steck SE, Berntsen J, et al. Omega-3 fatty acid supplementation appears to attenuate particulate air pollution-induced cardiac effects and lipid changes in healthy middle-aged adults. Environ Health Perspect 2012;120(7):952–7.

  • 44.

    Guida N, Laudati G, Anzilotti S, Secondo A, Montuori P, et al. Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death. Toxicol Appl Pharm 2015;288(3):387–98.

  • 45.

    Baker NA, English V, Sunkara M, Morris AJ, Pearson KJ, et al. Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes. J Nutr Biochem 2013;24(12):2168–74.

  • 46.

    Siriwardhana N, Kalupahana NS, Moustaid-Moussa N. Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid. Adv Food Nutr Res 2012;65:211–22.

  • 47.

    Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr 2012;3(1):1–7.

  • 48.

    Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Br Med J 2008;337:a1344.

  • 49.

    Turunen AW, Jula A, Suominen AL, Mannisto S, Marniemi J, et al. Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis. Environ Res 2013;120:43–54.

  • 50.

    Murphy MO, Petriello MC, Han SG, Sunkara M, Morris AJ, et al. Exercise protects against PCB-induced inflammation and associated cardiovascular risk factors. Environ Sci Pollut Res Int 2016;23(3):2201–11.

  • 51.

    Choi JJ, Eum SY, Rampersaud E, Daunert S, Abreu MT, et al. Exercise attenuates PCB-induced changes in the mouse gut microbiome. Environ Health Perspect 2013;121(6):725–30.

  • 52.

    Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9(5):313–23.

  • 53.

    Kinross JM, Darzi AW, Nicholson JK. Gut microbiome-host interactions in health and disease. Genome Med 2011;3(3):14.

  • 54.

    Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012;489(7415):242–9.

  • 55.

    Arguin H, Sanchez M, Bray GA, Lovejoy JC, Peters JC, et al. Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies. Br J Nutr 2010;103(10):1433–41.

  • 56.

    Jandacek RJ, Genuis SJ. An assessment of the intestinal lumen as a site for intervention in reducing body burdens of organochlorine compounds. ScientificWorldJ 2013;2013:205621.

  • 57.

    Jandacek RJ, Tso P. Enterohepatic circulation of organochlorine compounds: a site for nutritional intervention. J Nutr Biochem 2007;18(3):163–7.

  • 58.

    Jandacek RJ, Heubi JE, Buckley DD, Khoury JC, Turner WE, et al. Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial. J Nutr Biochem 2014;25(4):483–8.

  • 59.

    Jandacek RJ, Rider T, Keller ER, Tso P. The effect of olestra on the absorption, excretion and storage of 2,2’,5,5’ tetrachlorobiphenyl; 3,3’,4,4’ tetrachlorobiphenyl; and perfluorooctanoic acid. Environ Int 2010;36(8):880–3.

  • 60.

    Jandacek RJ, Anderson N, Liu M, Zheng S, Yang Q, et al. Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene. Am J Physiol Gastrointest Liver Physiol 2005;288(2):G292–9.

  • 61.

    Jandacek RJ. Intervention to reduce PCBs: learnings from a controlled study of Anniston residents. Environ Sci Pollut Res Int 2016;23(3):2022–6.

  • 62.

    Moser GA, McLachlan MS. A non-absorbable dietary fat substitute enhances elimination of persistent lipophilic contaminants in humans. Chemosphere 1999;39(9):1513–21.

  • 63.

    Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004;429(6990):457–63.

  • 64.

    Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res 2007;61(5 Pt 2):24R–9R.

  • 65.

    Vrijens K, Bollati V, Nawrot TS. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect 2015;123(5):399–411.

  • 66.

    Liu D, Perkins JT, Petriello MC, Hennig B. Exposure to coplanar PCBs induces endothelial cell inflammation through epigenetic regulation of NF-kappaB subunit p65. Toxicol Appl Pharm 2015;289(3):457–65.

  • 67.

    Deng Q, Dai X, Guo H, Huang S, Kuang D, et al. Polycyclic aromatic hydrocarbons-associated microRNAs and their interactions with the environment: influences on oxidative DNA damage and lipid peroxidation in coke oven workers. Environ Sci Technol 2014;48(7):4120–8.

  • 68.

    Hou L, Barupal J, Zhang W, Zheng Y, Liu L, et al. Particulate air pollution exposure and expression of viral and human microRNAs in blood: the Beijing truck driver air pollution study. Environ Health Perspect 2016;124(3):344–50.

  • 69.

    Wahlang B, Petriello MC, Perkins JT, Shen S, Hennig B. Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases. Toxicol In Vitro 2016;35:180–7.

  • 70.

    Rozek LS, Dolinoy DC, Sartor MA, Omenn GS. Epigenetics: relevance and implications for public health. Annu Rev Publ Health 2014;35:105–22.

  • 71.

    Ayissi VB, Ebrahimi A, Schluesenner H. Epigenetic effects of natural polyphenols: a focus on SIRT1-mediated mechanisms. Mol Nutr Food Res 2014;58(1):22–32.

  • 72.

    Ross SA, Davis CD. The emerging role of microRNAs and nutrition in modulating health and disease. Annu Rev Nutr 2014;34:305–36.

  • 73.

    Yun JM, Jialal I, Devaraj S. Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem 2011;22(5):450–8.

  • 74.

    Liu D, Perkins JT, Hennig B. EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-kappaB target genes in human endothelial cells. J Nutr Biochem 2016;28:164–70.

  • 75.

    Barres R, Yan J, Egan B, Treebak JT, Rasmussen M, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 2012;15(3):405–11.

  • 76.

    Davalos A, Goedeke L, Smibert P, Ramirez CM, Warrier NP, et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci USA 2011;108(22):9232–7.

  • 77.

    Pareja-Galeano H, Sanchis-Gomar F, Garcia-Gimenez JL. Physical exercise and epigenetic modulation: elucidating intricate mechanisms. Sports Med 2014;44(4):429–36.

  • 78.

    Yang Z, Cappello T, Wang L. Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B 2015;5(2):145–50. [Crossref]

  • 79.

    Monsalve FA, Pyarasani RD, Delgado-Lopez F, Moore-Carrasco R. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediat Inflamm 2013;2013:549627.

  • 80.

    Huang CW, Chien YS, Chen YJ, Ajuwon KM, Mersmann HM, et al. Role of n-3 polyunsaturated fatty acids in ameliorating the obesity-induced metabolic syndrome in animal models and humans. Int J Mol Sci 2016;17(10). pii: E1689.

  • 81.

    Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008;105(44):17046–9.

  • 82.

    Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, et al. Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond) 2015;39(4):650–7.

  • 83.

    Vickers MH. Early life nutrition, epigenetics and programming of later life disease. Nutrients 2014;6(6):2165–78.

About the article

Received: 2016-08-09

Accepted: 2016-11-09

Published Online: 2017-01-11

Published in Print: 2017-03-01

Research funding: This work was supported by the National Institute of Environmental Health Sciences at the National Institutes of Health [P42ES007380], and the University of Kentucky Agricultural Experiment Station.

Conflict of interests: The authors declare that there are no competing financial interests.

Citation Information: Reviews on Environmental Health, ISSN (Online) 2191-0308, ISSN (Print) 0048-7554, DOI: https://doi.org/10.1515/reveh-2016-0041. Export Citation

Comments (0)

Please log in or register to comment.
Log in