Kara A. Bresnahan

Undernutrition, the Acute Phase Response to Infection, and Its Effects on Micronutrient Status Indicators

Infection and undernutrition are prevalent in developing countries and demonstrate a synergistic relation. Undernutrition increases infection-related morbidity and mortality. The acute phase response (APR) is an innate, systemic inflammatory reaction to a wide array of disruptions in a hosts homeostasis, including infection. Released from immune cells in response to deleterious stimuli, proinflammatory cytokines act on distant tissues to induce behavioral (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR. Cytokines act to increase energy and protein requirements to manifest fever and support hepatic acute phase protein (APP) production. Blood concentrations of glucose and lipid are augmented to provide energy to immune cells in response to cytokines. Additionally, infection decreases intestinal absorption of nutrients and can cause direct loss of micronutrients. Traditional indicators of iron, zinc, and vitamin A status are altered during the APR, leading to inaccurate estimations of deficiency in populations with a high or unknown prevalence of infection. Blood concentrations of APPs can be measured in nutrition interventions to assess the time stage and severity of infection and correct for the APR; however, standardized cutoffs for nutrition applications are needed. Protein-energy malnutrition leads to increased gut permeability to pathogens, abnormal immune cell populations, and impaired APP response. Micronutrient deficiencies cause specific immune impairments that affect both innate and adaptive responses. This review describes the antagonistic interaction between the APR and nutritional status and emphasizes the need for integrated interventions to address undernutrition and to reduce disease burden in developing countries.

Comparative Intake of White- versus Orange-Colored Maize by Zambian Children in the Context of Promotion of Biofortified Maize

Background Vitamin A deficiency is associated with poor health outcomes related to reproduction, growth, vision, and immunity. Biofortification of staple crops is a novel strategy for combating vitamin A deficiency in high-risk populations where staple food intakes are high. African populations are proposed beneficiaries of maize (Zea mays) biofortified with provitamin A carotenoids, often called “orange maize” because of its distinctive deep yellow-orange kernels. The color facilitates ready recognition but presents a cultural challenge to maize-consuming populations, including those in much of Africa, who traditionally eat white varieties. Objective This study explores the intake patterns of, as well as adaptation to, traditional foods made with provitamin A–biofortified maize compared with white maize in rural Zambian children 3 to 5 years of age (n = 189) during a 3-month feeding trial. Methods The subjects were fed a breakfast of maize porridge (sweet mush), a lunch of maize nshima (stiff mush) with various side dishes, and an afternoon snack based on a 6-day rotating menu. The trial was conducted in 2010. The orange maize used in the trial came from three different sources. O1 maize was from the 2009 harvest and was stored in a freezer until use in 2010. O2 maize was also from the 2009 harvest and was stored in a cold room until 2010. O3 (“fresh”) maize was from the 2010 harvest and was fed immediately after harvest in week 9 of the study and then stored in a freezer until milling for the final four weeks. Results Consumption of menu items, except snacks, was influenced by week (p < .0084). The intakes of porridge and nshima made with orange maize equaled those of porridge and nshima made with white maize from week 2 onward. The intakes of porridge and nshima prepared from O1 and O2 did not differ, but intakes became significantly higher when meals made from O3 were introduced (p < .014 for porridge and p ≤ .013 for nshima). Conclusions These results demonstrate quick adaptation to orange maize, a preference for recently harvested maize, and an optimistic outlook for similar adaptation patterns in other biofortified-maize target countries.

The Acute Phase Response Affected Traditional Measures of Micronutrient Status in Rural Zambian Children during a Randomized, Controlled Feeding Trial

The acute phase response (APR) to infection can alter blood-based indicators of micronutrient status. Data from a 3-mo randomized, controlled feeding trial in rural Zambian children (n = 181, aged 3-5 y) were used to determine the impact of the APR on indicators of vitamin A and iron status using baseline and final blood samples. Concentrations of acute phase proteins were categorized as raised C-reactive protein (CRP; >5 and >10 mg/L) only, both raised CRP and α1-acid glycoprotein (AGP; >1.2 g/L), raised AGP only, and neither CRP nor AGP raised to identify the respective stages of infection: incubation, early convalescence, convalescence, and healthy state. Data were insufficient to examine the incubation stage of infection. A CRP concentration of >5 mg/L was an effective elevation cutoff point in this population to show impact on micronutrient markers. Time did not affect hemoglobin, serum ferritin, or serum retinol concentrations (P > 0.05). During early convalescence, hemoglobin decreased (14-16%; P ≤ 0.05), serum ferritin increased (279-356%; P ≤ 0.05), and serum retinol decreased (20-30%; P ≤ 0.05). Serum retinol concentrations did not change during convalescence; however, hemoglobin remained depressed (4-9%) and serum ferritin was elevated (67-132%) (both P ≤ 0.05). Modified relative dose response values were unaffected by the APR (P > 0.05) but increased between time points (16%; P ≤ 0.05), indicating a decrease in liver vitamin A reserves on the background of a semiannual vitamin A supplementation program. The observed prevalence of anemia and vitamin A deficiency assessed by serum retinol concentration was higher during the APR (P ≤ 0.05). It is important to consider the impact of infection on dietary interventions and to adjust for acute phase proteins when assessing iron status or vitamin A status by serum retinol concentration alone in children.

Quantification of food and nutrient intakes in Zambian children with and without malaria under controlled feeding conditions.

Vitamin A supplementation improves status, which may protect against malarial infection. Provitamin A carotenoid biofortified staple crops may provide a more sustainable approach to alleviate vitamin A deficiency than supplementation, but the impact of febrile illness on food intake must be considered in malaria endemic regions. Morbidity data and food logs from a three-month efficacy trial on provitamin A biofortified (orange) maize in preschool Zambian children (n = 181, age 3–5 years) were systematically analyzed over time to determine the impact of malaria on food intake. Nutrients examined included macronutrients, iron, zinc, and vitamin A. Comparisons based on individual intakes in healthy and malarial states over three-day intervals were made including children from both the orange and white maize groups (n = 100). Malaria prevalence did not differ overall or between treatment groups over time (all P > 0.05). Lower nutrient intakes were observed for all variables during malaria outbreaks (food 289 ± 412 g; energy 248 ± 346 kcal; carbohydrate 42 ± 62 g; protein 8 ± 12 g; fat 5 ± 7 g; iron 1 ± 2 mg; zinc 1 ± 1 mg; vitamin A 58 ± 100 retinol activity equivalents; all P < 0.05). No differences were observed between nutrient decreases in orange and white maize groups (P > 0.05). Considering the impact of malaria on food and nutrient intakes and increased vitamin A utilization and excretion due to the acute phase response, biofortification targets for provitamin A carotenoids may need to be elevated in malaria endemic regions.

Relative vitamin A values of 9- cis - and 13- cis -β-carotene do not differ when fed at physiological levels during vitamin A depletion in Mongolian gerbils ( Meriones unguiculatus )

Provitamin A biofortification of staple crops may decrease the prevalence of vitamin A (VA) deficiency if widely adopted in target countries. To assess the impact of processing methods on the VA value of plant foods, the unique bioefficacies of cis-βC isomers (formed during cooking) compared with all-trans (at) β-carotene (βC) must be determined. The bioefficacies of 9-cis (9c)- and 13-cis (13c)-βC isomers were compared with those of the at-βC isomer and VA positive (VA+) and negative (VA - ) controls in VA-depleted Mongolian gerbils (Meriones unguiculatus) in two experimental studies (study 1, n 56; study 2, n 57). A 3- or 4-week depletion period was followed by a 3- or 4-week treatment period in which the groups received oral doses of the 9c-, 13c- or at-βC isomers in cottonseed oil (study 1, 15 nmol/d; study 2, 30 nmol/d). In study 1, the βC isomers did not maintain baseline liver VA stores in all groups (0.69 (SD 0.20) μmol/liver) except in the VA+group (0.56 (SD 0.10) μmol/liver) (P= 0.0026). The βC groups were similar to the VA+group, but the 9c- and 13c-βC groups did not differ from the VA - group (0.39 (SD 0.09) μmol/liver). In study 2, the βC isomers maintained baseline liver VA stores in all the βC groups (0.35 (SD 0.13) μmol/liver), and in the VA+group, the VA supplement (0.54 (SD 0.19) μmol/liver) exceeded the baseline VA status (0.38 (SD 0.15) μmol/liver) (P< 0.0001); however, the 9c-βC group did not differ from the VA - group (0.20 (SD 0.07) μmol/liver). In vivo isomerisation of βC was confirmed in both experimental studies. Lower VA bioconversion factor values were obtained for the cis-βC isomers in study 2 when compared with study 1, but higher values were obtained for the at-βC isomer. Dose and VA status clearly affect bioconversion factors. In conclusion, the cis-βC isomers yielded similar liver VA stores to the at-βC isomer in Mongolian gerbils, and liver VA stores of the 9c- and 13c-βC groups did not differ when the doses were provided at physiological levels over time in two studies.

Cooking Enhances but the Degree of Ripeness Does Not Affect Provitamin A Carotenoid Bioavailability from Bananas in Mongolian Gerbils

Banana is a staple crop in many regions where vitamin A deficiency is prevalent, making it a target for provitamin A biofortification. However, matrix effects may limit provitamin A bioavailability from bananas. The retinol bioefficacies of unripe and ripe bananas (study 1A), unripe high-provitamin A bananas (study 1B), and raw and cooked bananas (study 2) were determined in retinol-depleted Mongolian gerbils (n = 97/study) using positive and negative controls. After feeding a retinol-deficient diet for 6 and 4 wk in studies 1 and 2, respectively, customized diets containing 60, 30, or 15% banana were fed for 17 and 13 d, respectively. In study 1A, the hepatic retinol of the 60% ripe Cavendish group (0.52 ± 0.13 μmol retinol/liver) differed from baseline (0.65 ± 0.15 μmol retinol/liver) and was higher than the negative control group (0.39 ± 0.16 μmol retinol/liver; P < 0.0065). In study 1B, no groups differed from baseline (0.65 ± 0.15 μmol retinol/liver; P = 0.20). In study 2, the 60% raw Butobe group (0.68 ± 0.17 μmol retinol/liver) differed from the 60% cooked Butobe group (0.87 ± 0.24 μmol retinol/liver); neither group differed from baseline (0.80 ± 0.27 μmol retinol/liver; P < 0.0001). Total liver retinol was higher in the groups fed cooked bananas than in those fed raw (P = 0.0027). Body weights did not differ even though gerbils ate more green, ripe, and raw bananas than cooked, suggesting a greater indigestible component. In conclusion, thermal processing, but not ripening, improves the retinol bioefficacy of bananas. Food matrix modification affects carotenoid bioavailability from provitamin A biofortification targets.