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Biological Trace Element Research

, Volume 183, Issue 1, pp 49–57 | Cite as

The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men

  • Jacob K. Kresovich
  • Catherine M. Bulka
  • Brian T. Joyce
  • Pantel S. Vokonas
  • Joel Schwartz
  • Andrea A. Baccarelli
  • Elizabeth A. Hibler
  • Lifang Hou
Article

Abstract

Manganese is an essential nutrient that may play a role in the production of inflammatory biomarkers. We examined associations between estimated dietary manganese intake from food/beverages and supplements with circulating biomarkers of inflammation. We further explored whether estimated dietary manganese intake affects DNA methylation of selected genes involved in the production of these biomarkers. We analyzed 1023 repeated measures of estimated dietary manganese intakes and circulating blood inflammatory biomarkers from 633 participants in the Normative Aging Study. Using mixed-effect linear regression models adjusted for covariates, we observed positive linear trends between estimated dietary manganese intakes and three circulating interleukin proteins. Relative to the lowest quartile of estimated intake, concentrations of IL-1β were 46% greater (95% CI − 5, 126), IL-6 52% greater (95% CI − 9, 156). and IL-8 32% greater (95% CI 2, 71) in the highest quartiles of estimated intake. Estimated dietary manganese intake was additionally associated with changes in DNA methylation of inflammatory biomarker-producing genes. Higher estimated intake was associated with higher methylation of NF-κβ member activator NKAP (Q4 vs Q1: β = 3.32, 95% CI − 0.6, 7.3). When stratified by regulatory function, higher manganese intake was associated with higher gene body methylation of NF-κβ member activators NKAP (Q4 vs Q1: β = 10.10, 95% CI − 0.8, 21) and NKAPP1 (Q4 vs Q1: β = 8.14, 95% CI 1.1, 15). While needed at trace amounts for various physiologic functions, our results suggest estimated dietary intakes of manganese at levels slightly above nutritional adequacy contribute to inflammatory biomarker production.

Keywords

Manganese Dietary manganese DNA methylation Inflammation Cytokines 

Abbreviations

BMI

Body mass index

CIs

Confidence intervals

CRP

C-reactive protein

FDR

False discovery rate

FFQ

Food Frequency Questionnaire

ICAM

Intercellular adhesion molecule 1

IL

Interleukin

Mn

Manganese

NAS

Normative aging study

NFKB1

Nuclear factor kappa B subunit 1

NFKB2

Nuclear factor kappa B subunit 2

RELA

Nuclear factor kappa B P65 subunit

NF-κβ

Nuclear factor kappa-light-chain-enhancer of Active B Cells

NFKBIA

NF-κβ inhibitor alpha

NFKBIB

NF-κβ inhibitor beta

NKRF

NF-κβ Repressing factor

NKIRAS1

NF-κβ inhibitor interacting Ras-Like 1

NKIRAS2

NF-κβ inhibitor interacting Ras Like 2

NKAP

NF-κβ activating protein

NKAPL

NF-κβ activating protein like

NKAPP1

NF-κβ activating protein pseudogene 1

REL

Proto-oncogene c-REL

RELB

RELB proto-oncogene NF-κβ subunit

UL

Tolerable upper intake level

TNF-α

Tumor necrosis factor alpha

TNFR

Tumor necrosis factor receptor, superfamily member 1B

VCAM-1

Vascular cell adhesion protein 1

VEGF

Vascular endothelial growth factor

Notes

Author Contributions

JKK, EAH, and LH designed the study. PSV, JS, and AAB supervised study operations. JKK performed the statistical analysis. JKK and CMB drafted the manuscript. BTJ, AAB, EAH, and LH provided critical revisions to the manuscript. All authors read and approved the final manuscript.

Funding Information

The Epidemiology Research and Information Center of US Department of Veterans Affairs (NIEHS R01-ES015172) support the Normative Aging Study. L. Hou received additional support from the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund. A. Baccarelli and J. Schwartz received additional support from the National Institute of Environmental Health Sciences (NIEHS R01-ES021733, NIEHS R01-ES015172, and NIEHS P30-ES00002). J. Kresovich received additional support from the National Cancer Institute Cancer Education and Career Development Program (NIH R25 CA057699).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12011_2017_1127_MOESM1_ESM.docx (14 kb)
Supplemental Table 1 (DOCX 13 kb)
12011_2017_1127_MOESM2_ESM.docx (18 kb)
Supplemental Table 2 (DOCX 18 kb)
12011_2017_1127_MOESM3_ESM.docx (18 kb)
Supplemental Table 3 (DOCX 18 kb)
12011_2017_1127_MOESM4_ESM.png (29 kb)
Supplemental Figure 1 Flow diagram of participant inclusion. (PNG 28 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Jacob K. Kresovich
    • 1
    • 2
  • Catherine M. Bulka
    • 2
  • Brian T. Joyce
    • 1
    • 2
  • Pantel S. Vokonas
    • 3
  • Joel Schwartz
    • 4
  • Andrea A. Baccarelli
    • 5
  • Elizabeth A. Hibler
    • 1
  • Lifang Hou
    • 1
  1. 1.Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Division of Epidemiology and BiostatisiticsUniversity of Illinois at Chicago School of Public HealthChicagoUSA
  3. 3.VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of MedicineBoston University School of MedicineBostonUSA
  4. 4.Department of Environmental Health and Program in Quantitative GenomicsHarvard T.H. Chan School of Public HealthBostonUSA
  5. 5.Departments of Epidemiology and Environmental Health SciencesColumbia University Mailman School of Public HealthNew York CityUSA

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