The Influence and Benefits of Controlling for Inflammation on Plasma Ferritin and Hemoglobin Responses following a Multi-Micronutrient Supplement in Apparently Healthy, HIV+ Kenyan Adults

Abstract

Hemoglobin and ferritin are important biomarkers of iron status but are both altered by inflammation. We used the inflammation biomarkers C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) to adjust hemoglobin and ferritin concentrations to clarify interpretation of iron status. Apparently healthy adults who tested positive twice for HIV but who had not reached stage IV or clinical AIDS were randomly allocated to receive a food supplement (n = 17 and 21) or the food plus a micronutrient capsule (MN; 10 men and 34 women, respectively) containing 30 mg iron/d. Hemoglobin, ferritin, CRP, and AGP concentrations were measured at baseline and 3 mo and subjects were divided into 4 groups (reference, no inflammation; incubating, raised CRP; early convalescence, raised AGP and CRP; and late convalescence, raised AGP). Correction factors (the ratios of the median for the reference group over each inflammatory group) improved the consistency of the ferritin but not the hemoglobin results. After correction, ferritin (but not hemoglobin) increased in both men (48 microg/L; P = 0.02) and women (12 microg/L; P = 0.04) who received MN but not in the food-only group. However, hemoglobin did improve in subjects who showed no inflammation both at baseline and mo 3 (P = 0.019), but ferritin did not increase in this group. In conclusion, ferritin concentrations were more closely linked to current inflammation than hemoglobin; hence, correction by inflammation biomarkers improved data consistency. However, low hemoglobin concentrations were the consequence of long-term chronic inflammation and improvements in response to MN supplements were only detected in subjects with no inflammation.

Interactions between nutrition and immune function: using inflammation biomarkers to interpret micronutrient status

“…It is possible therefore that using CRP to detect subjects in incubation and early convalescence may underestimate subjects with inflammation from viral infections. However, we have used CRP to detect inflammation in apparently healthy HIV+ Kenyan adults (11,16,29,31) and the results did not stand out as unusual when the Kenyan data were compared with other studies in the ferritin meta-analysis (27) . There was also no difference in the proportion of people with inflammation when HIV-infected South African women were compared with HIV-uninfected women at 6 weeks post partum (38) .…”

“…Values are medians. Data are from Mburu et al (31) inflammation appeared to depress any plasma response to the MN supplement. Zinc may have been absorbed even in those with inflammation but diverted to the tissues.…”

“…Percentage changes were calculated using the uncorrected and corrected median values for the men (488, 166) and women (90, 41 μg/l), respectively. Data taken from (11,31) . Data are medians (25th, 75th quartiles; percentage of change) of the changes in ferritin between baseline and 3 months.…”

“…Data are medians (25th, 75th quartiles; percentage of change) of the changes in ferritin between baseline and 3 months. All the subjects received the daily food supplement (500 g maize-soya blend) or the food plus the multi-MN supplement that contained 30 mg iron as ferrous fumarate, 15 mg zinc as zinc gluconate and other MN (16,31) . (25, 75 centiles).…”

The importance of controlling for the acute-phase response in the population-based assessment of vitamin A status: a study in children of pre-school age in Uganda

“…Regardless of the approach, the consensus is that including measurements of APP will improve the interpretation of results when vitamin A status is assessed using retinol and RBP. The application of a correction factor is a logical approach for interpreting levels of serum retinol (12)(13)(14) and other nutritional biomarkers (16)(17)(18) that are influenced by infection, when these indicators are measured in populations with a high burden of infection.We previously reported on the assessment of the prevalence of VAD in the UDHS 2006 using an enzyme immunoassay to measure the levels of RBP in DBS (3) . However, we did not measure any APP at that time.…”