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.
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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
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Funding
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).
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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.
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Flow diagram of participant inclusion. (PNG 28 kb)
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Kresovich, J.K., Bulka, C.M., Joyce, B.T. et al. The Inflammatory Potential of Dietary Manganese in a Cohort of Elderly Men. Biol Trace Elem Res 183, 49–57 (2018). https://doi.org/10.1007/s12011-017-1127-7
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DOI: https://doi.org/10.1007/s12011-017-1127-7