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Environ Health Perspect; DOI:10.1289/ehp.1306931

Lead Exposure, B Vitamins, and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Kelly M. Bakulski,1 Sung Kyun Park,1,2 Marc G. Weisskopf,3,4 Katherine L. Tucker,5 David Sparrow,6,7 Avron Spiro III,6,8,9 Pantel S. Vokonas,6,7 Linda Huiling Nie,10 Howard Hu,1,2,11 and Jennifer Weuve3,12
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1Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA; 2Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA; 3Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 4Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; 5Department of Clinical Laboratory & Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA; 6VA Normative Aging Study, Veterans Affairs Boston Health Care System, Boston, Massachusetts, USA; 7Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; 8Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA; 9Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USA; 10School of Health Sciences, Purdue University, Fort Wayne, Indiana, USA; 11Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; 12Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Bakulski KM, Park SK, Weisskopf MG, Tucker KL, Sparrow D, Spiro A 3rd, Vokonas PS, Nie LH, Hu H, Weuve J. Lead Exposure, B Vitamins, and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1306931.

Received: 10 April 2013
Accepted: 4 June 2014
Advance Publication: 6 June 2014

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Abstract

Background: Lead exposure may influence plasma concentration of homocysteine, a one-carbon metabolite associated with cardiovascular and neurodegenerative diseases. Little is known about associations between lead and homocysteine over time, or the potential influence of dietary factors.

Objectives: To examine the longitudinal association of recent and cumulative lead exposure with homocysteine concentrations and the potential modifying effect of dietary nutrients involved in one-carbon metabolism.

Methods: In a subcohort of the VA Normative Aging Study (1,056 men with 2,301 total observations between 1993 and 2011), we used mixed effects models to estimate differences in repeated measures of total plasma homocysteine across concentrations of lead in blood and tibia bone, assessing recent and cumulative lead exposure, respectively. We also assessed effect modification by dietary intake and plasma concentrations of folate, vitamin B6, and vitamin B12.

Results: An interquartile range (IQR) increment in blood lead (3-µg/dl) was associated with 6.3% higher homocysteine concentration (95% CI: 4.8, 7.8%). An IQR increment in tibia bone lead (14-µg/g) was associated with 3.7% higher homocysteine (95% CI: 1.6, 5.6%), which was attenuated to 1.5% (95% CI: -0.5, 3.6%) with adjustment for blood lead. For comparison, a 5-year increase in time from baseline was associated with a 5.7% increase in homocysteine (95% CI: 4.3, 7.1%). The association between blood lead and homocysteine was significantly stronger among participants with estimated dietary intakes of vitamin B6 and folate below (versus above) the study population medians, which were similar to the U.S. Recommended Dietary Allowance intakes.

Conclusions: Lead exposure was positively associated with plasma homocysteine concentration. This association was stronger among men with below median dietary intakes of vitamins B6 and folate. These findings suggest that increasing intake of folate and B6 might reduce lead-associated increases in homocysteine, a risk factor for cardiovascular disease and neurodegeneration.


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