Iron deficiency and biomarkers of inflammation: a 3-year prospective analysis of the DO-HEALTH trial

Abstract

Background The longitudinal association between iron deficiency and inflammatory biomarkers levels has not been fully explored among relatively healthy older adults. Aims To assess whether iron deficiency at baseline and at any yearly follow-up time point, with or without anemia, was associated with changes from baseline in high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels over 3 years. Methods This is a post-hoc observational analysis of DO-HEALTH, a double-blind, randomized controlled trial including 2157 European community-dwelling adults age 70+. The outcomes were changes from baseline in hs-CRP and IL-6 levels, measured at 12, 24, and 36 months of follow-up. Iron deficiency was defined by soluble transferrin receptor levels > 28.1 nmol/L and baseline anemia by hemoglobin levels < 130 g/L for men and < 120 g/L for women. Results In total, 2141 participants were included in the analyses (mean age: 74.9 years, 61.5% of women, 26.8% with iron deficiency). Baseline iron deficiency was associated with greater increase in IL-6 levels (mean difference in change: 0.52 ng/L, 95%CI 0.03–1.00, P = .04) over 3 years. Iron deficiency at any yearly time point was associated with higher increases in hs-CRP (mean difference in change: 1.62 mg/L, 95%CI 0.98–2.26, P < .001) and IL-6 levels (mean difference in change: 1.33 ng/L, 95%CI 0.87–1.79, P < .001) over 3 years. No significant interaction between iron deficiency and anemia was found, suggesting that the results are independent of the anemic status. Conclusions These findings suggest that iron deficiency may play a role in low-grade chronic inflammation among relatively healthy older adults.

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores

“…Virtually, every immune activation results in functional iron deficiency ( 4 , 104 – 108 ), where, despite sufficient iron stores in the liver and mononuclear phagocyte system (macrophages), iron mobilization is inhibited and dietary iron absorption is decreased by hepcidin, the master regulator of iron uptake. As such, even in healthy adults, iron deficiency is a driver of low-grade chronic inflammation ( 109 ).…”

Prevalence and incidence of iron deficiency in European community-dwelling older adults: an observational analysis of the DO-HEALTH trial

“…Iron deficiency is suggested to be the most important contributor to nutrient deficiency anemia at older age [4]. Previous studies among older adults suggest that reduced iron store, independent of anemia status, may be associated with inflammation [11], an increased risk of physical and cognitive impairment [12,13] and an increased overall morbidity and mortality [14][15][16][17]. In fact, all-cause mortality among severely iron deficient subjects (aged ≥ 65 years, living in long-term care facilities) is estimated to be almost twice as high as in iron sufficient persons of the same age and living conditions [15].…”

Iron Deficiency and Reduced Muscle Strength in Patients with Acute and Chronic Ischemic Stroke

“…The majority of clinical studies investigating ID in patients with acute and chronic diseases report ID prevalence obtained as a cross-sectional value only. Previously, a longitudinal multicenter clinical trial investigating an association between ID and unspecific inflammation in otherwise healthy adults showed a 12% increase to 39% in prevalence of ID within three years in community-dwelling older individuals [24]. Previous observations in patients with acute conditions, including acute exacerbation of chronic obstructive pulmonary disease, acute coronary syndrome, or acute HF, reported a prevalence of ID ranging between 20% and 80% [25][26][27].…”