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Cited by 54Iron Metabolism and DisordersTrace Elements in HealthHeavy Metal Exposure and Toxicity

Serum markers of stored body iron are not appropriate markers of health effects of iron: a focus on serum ferritin

Lee, Duk-Hee, Jacobs, David R·2004·Medical Hypotheses
DOI 10.1016/s0306-9877(03)00344-x
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Abstract

Experimental studies have consistently shown that iron is a critical catalyst in generating oxygen free radicals via Fenton chemistry. Nevertheless, epidemiologic studies conflict on the association between stored body iron markers and disease outcomes, including coronary heart disease. We hypothesize that stored body iron markers common in epidemiologic studies, such as serum ferritin, transferrin saturation, iron, or iron-binding capacity, are inappropriate to investigate harmful health effects related to iron overload. Oxygen free radicals are produced only by free iron, but stored body iron markers reflect iron bound to ferritin or transferrin, which are produced to sequester catalytically active free iron. Moreover, increased serum ferritin may occur as a defense mechanism in response to oxidative stress; such increase might eventually minimize oxidative stress and consequent pathology due to free iron. Therefore, though highly correlated with stored body iron, a measure of bound iron will fail to identify any harmful effect, unless it is also a marker of free iron. It is generally believed that free iron rarely exists, except in iron-overload with 100% transferrin saturation. However, some recent studies find non-transferrin bound iron (NTBI) or the intracellular labile iron pool (LIP) in the presence of triggers disturbing iron homeostasis, such as alcohol consumption. In contrast to the tight bond in ferritin or transferrin, free iron is more likely to dissociate from a looser bond. Therefore research on the relation of iron with disease outcomes should investigate NTBI or the intracellular LIP. Any positive influence of iron on coronary heart and other diseases might be observable only when a trigger is present. These factors may explain why there have been conflicting results between serum markers of stored body iron and disease outcomes in epidemiological studies.

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  • Exposure to vitamin D increases de-phosphorylation of activated extracellular signal-regulated kinases, a subset of the mammalian MAPK family involved in inflammatory processes.

    “Exposure to vitamin D increases the rate of the de-phosphorylation of activated extracellular signal-regulated kinases (739) , a subset of the mammalian MAPK family involved in inflammatory processes.”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [739]

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Authors
Lee, D.-H., & Jacobs, D. R.
Affiliations
  • University of Minnesota (US)
  • University of Oslo (NO)
Corresponding author
Jacobs, David R
ORCID
Venue
Medical Hypotheses
Publisher
Elsevier BV
Published
2004-03
Volume
62
Issue
3
Pages
442-445
ISSN
0306-9877 (ISSN-L)
DOI
10.1016/s0306-9877(03)00344-x
OpenAlex
W2113227870
Cited by
54
References
36
Citations by year
2025: 1 · 2023: 1 · 2021: 2 · 2020: 1 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 4
FWCI
3.57
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Medical Hypotheses (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL053560)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Keywords
serum ferritin, free iron, iron overload, non-transferrin-bound iron, labile iron pool, Fenton reaction, oxygen free radicals, oxidative stress, transferrin saturation, iron-binding capacity, coronary artery disease, iron homeostasis, alcohol consumption
MeSH terms
Coronary Artery Disease, Ferritins, Humans, Iron, Biomarkers, Iron Overload

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