Air Pollution, Epigenetics and Cardiovascular Health: A Human Intervention Trial

Summary

In this study, the pills formulated are being used to try to ameliorate the effect of air pollution on epigenetic changes, specifically DNA methylation, potentially linked with particulate matter air pollution inhalation and cardiovascular health effects. The way in which this is achieved is that the vitamins, which act as methyl donors, add a methyl group to the DNA to reverse the loss observed on exposure to air pollution. Specifically for this study, the methyl donor supplement has been made by Jamieson Laboratories, and consists of 50mg Vitamin B6 and 1 mg Vitamin B12, (both within Health Canada approved limits) and 2.5 mg folic acid. The non-vitamin ingredients are those commonly used in pill formation. However, the folic acid concentration is 2.5mg, which is above the 1.0mg limit set by Health Canada for a natural health product. This concentration, however, has been used in previous academic studies safely and effectively, and was also formulated by Jamieson Laboratories. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017. HOPE2 study).

Timeline

Start

2013-06

Primary completion

2014-07

Completion

2014-07

Publications

• Background Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010 Jun 1;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1. Epub 2010 May 10.
• Background O'Toole TE, Conklin DJ, Bhatnagar A. Environmental risk factors for heart disease. Rev Environ Health. 2008 Jul-Sep;23(3):167-202. doi: 10.1515/reveh.2008.23.3.167.
• Background Zanobetti A, Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation. 2004 Oct 12;110(15):2184-9. doi: 10.1161/01.CIR.0000143831.33243.D8. Epub 2004 Oct 4.
• Background Brook RD, Rajagopalan S. Particulate matter, air pollution, and blood pressure. J Am Soc Hypertens. 2009 Sep-Oct;3(5):332-50. doi: 10.1016/j.jash.2009.08.005.
• Background Brook RD, Bard RL, Burnett RT, Shin HH, Vette A, Croghan C, Phillips M, Rodes C, Thornburg J, Williams R. Differences in blood pressure and vascular responses associated with ambient fine particulate matter exposures measured at the personal versus community level. Occup Environ Med. 2011 Mar;68(3):224-30. doi: 10.1136/oem.2009.053991. Epub 2010 Oct 8.
• Background Liu L, Ruddy T, Dalipaj M, Poon R, Szyszkowicz M, You H, Dales RE, Wheeler AJ. Effects of indoor, outdoor, and personal exposure to particulate air pollution on cardiovascular physiology and systemic mediators in seniors. J Occup Environ Med. 2009 Sep;51(9):1088-98. doi: 10.1097/JOM.0b013e3181b35144.
• Background O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation. 2005 Jun 7;111(22):2913-20. doi: 10.1161/CIRCULATIONAHA.104.517110. Epub 2005 May 31.
• Background Baccarelli A, Cassano PA, Litonjua A, Park SK, Suh H, Sparrow D, Vokonas P, Schwartz J. Cardiac autonomic dysfunction: effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms. Circulation. 2008 Apr 8;117(14):1802-9. doi: 10.1161/CIRCULATIONAHA.107.726067. Epub 2008 Mar 31.
• Background Adar SD, Gold DR, Coull BA, Schwartz J, Stone PH, Suh H. Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology. 2007 Jan;18(1):95-103. doi: 10.1097/01.ede.0000249409.81050.46.
• Results Zhong J, Trevisi L, Urch B, Lin X, Speck M, Coull BA, Liss G, Thompson A, Wu S, Wilson A, Koutrakis P, Silverman F, Gold DR, Baccarelli AA. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial. Sci Rep. 2017 Apr 3;7:45322. doi: 10.1038/srep45322.
• Results Zhong J, Karlsson O, Wang G, Li J, Guo Y, Lin X, Zemplenyi M, Sanchez-Guerra M, Trevisi L, Urch B, Speck M, Liang L, Coull BA, Koutrakis P, Silverman F, Gold DR, Wu T, Baccarelli AA. B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial. Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3503-3508. doi: 10.1073/pnas.1618545114. Epub 2017 Mar 13.
• Results Zhong J, Urch B, Speck M, Coull BA, Koutrakis P, Thorne PS, Scott J, Liu L, Brook RD, Behbod B, Gibson H, Silverman F, Mittleman MA, Baccarelli AA, Gold DR. Endotoxin and beta-1,3-d-Glucan in Concentrated Ambient Particles Induce Rapid Increase in Blood Pressure in Controlled Human Exposures. Hypertension. 2015 Sep;66(3):509-16. doi: 10.1161/HYPERTENSIONAHA.115.05342. Epub 2015 Jun 29.

Drugs

Indications

No indication recorded.