The use of adjustment factors to address the impact of inflammation on vitamin A and iron status in humans

Abstract

Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein (CRP), and α1-acid glycoprotein (AGP). With the use of CRP and AGP we identified 4 groups in each study: reference (CRP ≤5 mg/L, AGP ≤1 g/L), incubation (CRP >5 mg/L, AGP ≤1 g/L), early convalescence (CRP >5 mg/L, AGP >1 g/L), and late convalescence (CRP ≤5 mg/L, AGP >1 g/L). For each biomarker, ratios of the geometric means of the reference to each inflammation group concentration were used to calculate adjustment factors for retinol (1.13, 1.24, and 1.11) and ferritin (0.77, 0.53, and 0.75) for the incubation, early, and late convalescent groups, respectively. The application of the meta-analysis factors in more recent studies compares well with study-specific factors. The same method was used to calculate adjustment factors for soluble transferrin receptor (sTfR) and body iron stores (BISs) in Lao children. We found no advantage in adjusting sTfR for inflammation; in fact, adjustment decreased iron deficiency. Neither adjusted (10% <0 mg/kg) nor nonadjusted (12% <0 mg/kg) BISs detected as much iron deficiency as did ferritin (18% <12 μg/L) and adjusted ferritin (21% <12 μg/L) unless the cutoff for BISs was increased from 0 to <3 mg/kg. However, we could find no evidence that the larger number of children identified as having BISs <3 mg/kg had risks of anemia comparable to those identified by using ferritin <12 μg/L. In conclusion, both corrected and uncorrected ferritin concentrations <12 μg/L are associated with more iron deficiency and anemia than either sTfR >8.3 mg/L or BISs <0 mg/kg in Lao children.

Keywords: acute phase proteins; ferritin; iron; retinol; soluble transferrin receptor.

FIGURE 1

Changes in plasma retinol and C-reactive protein concentrations in a group of nutritionally adequate patients in response to uncomplicated orthopedic surgery. A rapid decrease in plasma retinol concentration (solid line) coincides with an increase in C-reactive protein (dashed line) in the first 48 h after surgery. Data from reference (7).

FIGURE 2

Model of the behavior of the plasma acute phase proteins CRP and AGP and retinol concentrations after an infection or trauma. The ordinate axis indicates arbitrary % values where zero represents normal and 20% the inflammation threshold of CRP (>5 mg/L) and AGP (>1 g/L); 100% represents a normal serum retinol concentration or the maximum increase in CRP or AGP concentrations. The figure shows the rapid increase in CRP (line with short dashes) and decrease in retinol concentrations (solid line) after an infection stimulus at time zero (A). The CRP concentration reaches a plateau when clinical evidence of sickness appears and retinol reaches its nadir. AGP (line with combination of short and long dashes) concentrations increase more slowly from time zero and only pass the inflammation threshold 2–5 d later. As sickness wanes, concentrations of CRP decrease, retinol increases, and AGP reaches a plateau. In the final stage of convalescence, CRP concentrations return to normal (B), leaving only AGP elevated. The horizontal solid line at 20% is an arbitrary inflammation threshold. See text for details. The model is used to categorize subjects in the following groups: I, reference (no elevated acute phase proteins); II, incubation (only CRP increased); III, early convalescence (CRP and AGP both above the inflammation threshold); and IV, late convalescence (only AGP is raised). AGP, α₁-acid glycoprotein; CRP, C-reactive protein. Modified from reference .

FIGURE 3

Relation between ferritin and body iron stores in preschool-aged Lao children. Plasma ferritin and soluble transferrin receptor concentrations were used to calculate body iron stores with the use of the Cook et al. equation (32). The plot shows that a cutoff of 3 mg/kg body iron stores is required in order to include all ferritin concentrations <12 μg/L (20).