Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis

Background: The World Health Organization recommends serum ferritin concentrations as the best indicator of iron deficiency (ID). Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated. Objective: The objective was to estimate the increase in ferritin in 32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs). C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP), individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin concentrations. Design: We estimated the increase in ferritin associated with inflammation (ie, CRP >5 mg/L and/or AGP >1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies), and women (16 studies) (n = 8796 subjects). In 2-group analyses (either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups: reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only). Results: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P <0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P < 0.001) higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by approximate to 30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID. Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups. Am J Clin Nutr 2010;92:546-55

Biofortified yellow cassava and vitamin A status of Kenyan children: a randomized controlled trial.

BACKGROUND: Whereas conventional white cassava roots are devoid of provitamin A, biofortified yellow varieties are naturally rich in β-carotene, the primary provitamin A carotenoid. OBJECTIVE: We assessed the effect of consuming yellow cassava on serum retinol concentration in Kenyan schoolchildren with marginal vitamin A status. DESIGN: We randomly allocated 342 children aged 5-13 y to receive daily, 6 d/wk, for 18.5 wk 1) white cassava and placebo supplement (control group), 2) provitamin A-rich cassava (mean content: 1460 μg β-carotene/d) and placebo supplement (yellow cassava group), and 3) white cassava and β-carotene supplement (1053 μg/d; β-carotene supplement group). The primary outcome was serum retinol concentration; prespecified secondary outcomes were hemoglobin concentration and serum concentrations of β-carotene, retinol-binding protein, and prealbumin. Groups were compared by using ANCOVA, adjusting for inflammation, baseline serum concentrations of retinol and β-carotene, and stratified design. RESULTS: The baseline prevalence of serum retinol concentration <0.7 μmol/L and inflammation was 27% and 24%, respectively. For children in the control, yellow cassava, and β-carotene supplement groups, the mean daily intake of cassava was 378, 371, and 378 g, respectively, and the total daily supply of provitamin A and vitamin A from diet and supplements was equivalent to 22, 220, and 175 μg retinol, respectively. Both yellow cassava and β-carotene supplementation increased serum retinol concentration by 0.04 μmol/L (95% CI: 0.00, 0.07 μmol/L); correspondingly, serum β-carotene concentration increased by 524% (448%, 608%) and 166% (134%, 202%). We found no effect on hemoglobin concentration or serum concentrations of retinol-binding protein and prealbumin. CONCLUSIONS: In our study population, consumption of yellow cassava led to modest gains in serum retinol concentration and a large increase in β-carotene concentration. It can be an efficacious, new approach to improve vitamin A status. This study was registered with clinicaltrials.gov as NCT01614483

Interactions and potential implications of Plasmodium falciparum-hookworm coinfection in different age groups in south-central Côte d'Ivoire

BACKGROUND: Given the widespread distribution of Plasmodium and helminth infections, and similarities of ecological requirements for disease transmission, coinfection is a common phenomenon in sub-Saharan Africa and elsewhere in the tropics. Interactions of Plasmodium falciparum and soil-transmitted helminths, including immunological responses and clinical outcomes of the host, need further scientific inquiry. Understanding the complex interactions between these parasitic infections is of public health relevance considering that control measures targeting malaria and helminthiases are going to scale.METHODOLOGY: A cross-sectional survey was carried out in April 2010 in infants, young school-aged children, and young non-pregnant women in south-central Côte d'Ivoire. Stool, urine, and blood samples were collected and subjected to standardized, quality-controlled methods. Soil-transmitted helminth infections were identified and quantified in stool. Finger-prick blood samples were used to determine Plasmodium spp. infection, parasitemia, and hemoglobin concentrations. Iron, vitamin A, riboflavin, and inflammation status were measured in venous blood samples.PRINCIPAL FINDINGS: Multivariate regression analysis revealed specific association between infection and demographic, socioeconomic, host inflammatory and nutritional factors. Non-pregnant women infected with P. falciparum had significantly lower odds of hookworm infection, whilst a significant positive association was found between both parasitic infections in 6- to 8-year-old children. Coinfected children had lower odds of anemia and iron deficiency than their counterparts infected with P. falciparum alone.CONCLUSIONS/SIGNIFICANCE: Our findings suggest that interaction between P. falciparum and light-intensity hookworm infections vary with age and, in school-aged children, may benefit the host through preventing iron deficiency anemia. This observation warrants additional investigation to elucidate the mechanisms and consequences of coinfections, as this information could have important implications when implementing integrated control measures against malaria and helminthiases

VALIDATION OF WEIGHED RECORDS AND OTHER METHODS OF DIETARY ASSESSMENT USING THE 24-H URINE NITROGEN TECHNIQUE AND OTHER BIOLOGICAL MARKERS

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion: dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1·13 Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r - 0·62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0·74 and 0·82, and between dietary vitamin C and β-carotene and plasma vitamin C and β-carotene 0·86 and 0·48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0·78–0·87). Those between N from estimated food records and urine N were r 0·60–0·70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0·01 to 0·5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy

Clinically Unapparent Infantile Thiamin Deficiency in Vientiane, Laos

Infantile beriberi, or clinical thiamin (vitamin B1) deficiency in infants, is a forgotten disease in Asia, where 100 years ago it was a major public health problem. Infants with this deficiency, commonly aged ∼ 2–3 months, present in cardiac failure but usually rapidly improve if given thiamin injections. It remains relatively common in Vientiane, Lao PDR (Laos), probably because of prolonged intra- and post-partum food avoidance behaviours. Clinical disease may be the tip of an iceberg with subclinical thiamin deficiency contributing to sickness in infants without overt clinical beriberi. We therefore recruited 778 sick infants admitted during one year at Mahosot Hospital, Vientiane, without clinical evidence of beriberi, and performed erythrocyte transketolase (ETK) assays. 13.4 % of infants had basal ETK<0.59 micromoles/min/gHb suggesting biochemical thiamin deficiency. Mortality was 5.5% but, among infants ≥2 months old, mortality was higher in those with basal ETK<0.59 micromoles/min/gHb (3/47, 6.4%) than in those with basal ETK≥0.59 micromoles/min/gHb (1/146, 0.7%) (P = 0.045, relative risk = 9.32 (95%CI 0.99 to 87.5)). We conclude that clinically unapparent thiamin deficiency is common among sick infants (≥2 months old) admitted to hospital in Vientiane. This may contribute to mortality and a low clinical threshold for providing thiamin to sick infants may be needed

Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration

PURPOSE: To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale). RESULTS: At 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2—1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1—15.15 c.p.d.; and Group 3—6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed. CONCLUSION: In early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement

Traits associated with innate and adaptive immunity in pigs: heritability and associations with performance under different health status conditions

There is a need for genetic markers or biomarkers that can predict resistance towards a wide range of infectious diseases, especially within a health environment typical of commercial farms. Such markers also need to be heritable under these conditions and ideally correlate with commercial performance traits. In this study, we estimated the heritabilities of a wide range of immune traits, as potential biomarkers, and measured their relationship with performance within both specific pathogen-free (SPF) and non-SPF environments. Immune traits were measured in 674 SPF pigs and 606 non-SPF pigs, which were subsets of the populations for which we had performance measurements (average daily gain), viz. 1549 SPF pigs and 1093 non-SPF pigs. Immune traits measured included total and differential white blood cell counts, peripheral blood mononuclear leucocyte (PBML) subsets (CD4+ cells, total CD8α+ cells, classical CD8αβ+ cells, CD11R1+ cells (CD8α+ and CD8α-), B cells, monocytes and CD16+ cells) and acute phase proteins (alpha-1 acid glycoprotein (AGP), haptoglobin, C-reactive protein (CRP) and transthyretin). Nearly all traits tested were heritable regardless of health status, although the heritability estimate for average daily gain was lower under non-SPF conditions. There were also negative genetic correlations between performance and the following immune traits: CD11R1+ cells, monocytes and the acute phase protein AGP. The strength of the association between performance and AGP was not affected by health status. However, negative genetic correlations were only apparent between performance and monocytes under SPF conditions and between performance and CD11R1+ cells under non-SPF conditions. Although we cannot infer causality in these relationships, these results suggest a role for using some immune traits, particularly CD11R1+ cells or AGP concentrations, as predictors of pig performance under the lower health status conditions associated with commercial farms