M J Manary

Baylor College of Medicine, Houston, Texas, United States

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Publications (34)221.07 Total impact

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    ABSTRACT: This study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet. This was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3-5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Student's t-tests and linear regression analysis. Children had a mean height-for-age Z-score of -3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8±0.4mg/d (mean±SD) both before and after the intervention. Fractional absorption of zinc was 0.38±0.08 and 0.35±0.06 before and after the RS intervention respectively. NAZ was 1.1±0.5 and 0.6±0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention. Consumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Journal of Trace Elements in Medicine and Biology 04/2015; 30. DOI:10.1016/j.jtemb.2015.01.005 · 2.49 Impact Factor
  • Mark Manary
    American Journal of Clinical Nutrition 03/2015; DOI:10.3945/ajcn.115.108399 · 6.50 Impact Factor
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    ABSTRACT: To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA(+) bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 02/2015; 7(276):276ra24. DOI:10.1126/scitranslmed.aaa4877 · 14.41 Impact Factor
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    ABSTRACT: Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. RUTF contains large amounts of linoleic acid and very little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. We conducted a prospective, randomized, double-blinded, clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid (PL) fatty acid status was measured upon enrollment and after 4 weeks and compared between the two intervention groups. Among the 141 children enrolled, 48/71 receiving HO-RUTF and 50/70 receiving RUTF recovered. Plasma PL samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and -25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and -24% in the HO-RUTF and RUTF groups (P < 0.001). For arachidonic acid, the change in content was -3% and 13% in the HO-RUTF and RUTF groups (P < 0.009). The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation as they suggest HO-RUTF support improved PUFA status, necessary for neural development and recovery.
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    ABSTRACT: Globally, zinc deficiency is widespread, despite decades of research highlighting its negative effects on health, and in particular upon child health in low-income countries. Apart from inadequate dietary intake of bioavailable zinc, other significant contributors to zinc deficiency include the excessive intestinal loss of endogenously secreted zinc and impairment in small intestinal absorptive function. Such changes are likely to occur in children suffering from environmental (or tropical) enteropathy (EE)-an almost universal condition among inhabitants of developing countries characterized by morphologic and functional changes in the small intestine. Changes to the proximal gut in environmental enteropathy will likely influence the nature and amount of zinc delivered into the large intestine. Consequently, we reviewed the current literature to determine if colonic absorption of endogenous or exogenous (dietary) zinc could contribute to overall zinc nutriture. Whilst we found evidence that significant zinc absorption occurs in the rodent colon, and is favoured when microbially-fermentable carbohydrates (specifically resistant starch) are consumed, it is unclear whether this process occur in humans and/or to what degree. Constraints in study design in the few available studies may well have masked a possible colonic contribution to zinc nutrition. Furthermore these few available human studies have failed to include the actual target population that would benefit, namely infants affected by EE where zinc delivery to the colon may be increased and who are also at risk of zinc deficiency. In conducting this review we have not been able to confirm a colonic contribution to zinc absorption in humans. However, given the observations in rodents and that feeding resistant starch to children is feasible, definitive studies utilising the dual stable isotope method in children with EE should be undertaken.
    Nutrients 01/2015; 7(1):572-583. DOI:10.3390/nu7010572 · 3.15 Impact Factor
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    ABSTRACT: Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed international and national crop and animal food databases was used to create a global and local candidate ingredient database. The database included information about each ingredient regarding nutrient composition, ingredient category, regional availability, and food safety, processing, and price. An LP tool was then designed to compose novel RUTF formulations. For the example case of Ethiopia, the objective was to minimize the ingredient cost of RUTF; the decision variables were ingredient weights and the extent of use of locally available ingredients, and the constraints were nutritional and product-quality related. Of the new RUTF formulations found by the LP tool for Ethiopia, 32 were predicted to be feasible for creating a paste, and these were prepared in the laboratory. Palatable final formulations contained a variety of ingredients, including fish, different dairy powders, and various seeds, grains, and legumes. Nearly all of the macronutrient values calculated by the LP tool differed by <10% from results produced by laboratory analyses, but the LP tool consistently underestimated total energy. The LP tool can be used to develop new RUTF formulations that make more use of locally available ingredients. This tool has the potential to lead to production of a variety of low-cost RUTF formulations that meet international standards and thereby potentially allow more children to be treated for SAM. © 2014 American Society for Nutrition.
    American Journal of Clinical Nutrition 12/2014; 100(6):1551-8. DOI:10.3945/ajcn.114.090670 · 6.50 Impact Factor
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    ABSTRACT: Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantified in the urine. Multiple micronutrient (MN) deficiency morphologically mimics EE, and ω-3 (n-3) polyunsaturated fatty acids reduce mucosal inflammation in Crohn disease. We tested the hypothesis that supplementary MNs, with or without fish oil (FO), would improve L:M in rural Malawian children aged 1-3 y compared with a control (C) group receiving a placebo. The MNs and FO provided the Recommended Dietary Intake for 26 vitamins, minerals, eicosapentaenoic acid, and docosahexaenoic acid. This was a 3-arm, randomized, double-blind, placebo-controlled clinical trial, with the primary outcomes being the change in L:M (ΔL:M) after 12 and 24 wk of supplementation. Comparisons were made for ΔL:M after 12 and 24 wk within each group by using a Wilcoxon matched pairs signed rank test, because the data are not normally distributed. A total of 230 children had specimens adequate for analysis; all had an abnormal baseline L:M, defined as >0.10. After 12 wk, children who received MNs + FO had a ΔL:M [mean (95% CI)] of -0.10 (-0.04, -0.15; P = 0.001), and children receiving only MNs had ΔL:M of -0.12 (-0.03, -0.21; P = 0.002). After 24 wk, children who received MNs + FO had a ΔL:M of -0.09 (-0.03, -0.15; P = 0.001); children receiving only MNs had a ΔL:M of -0.11 (-0.02, -0.20; P = 0.001), and the C group had ΔL:M of -0.07 (0.02, -0.16); P = 0.002). Linear growth was similar in all groups, ∼4.3 cm over 24 wk. Although the effect was modest, these data suggest MNs can transiently ameliorate EE in rural African children. The trial was registered at clinicaltrials.gov as NCT01593033. © 2014 American Society for Nutrition.
    Journal of Nutrition 12/2014; 144(12):2059-65. DOI:10.3945/jn.114.201673 · 4.23 Impact Factor
  • Indi Trehan, Mark J Manary
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    ABSTRACT: Kwashiorkor and marasmus, collectively termed severe acute malnutrition (SAM), account for at least 10% of all deaths among children under 5 years of age worldwide, virtually all of them in low-income and middle-income countries. A number of risk factors, including seasonal food insecurity, environmental enteropathy, poor complementary feeding practices, and chronic and acute infections, contribute to the development of SAM. Careful anthropometry is key to making an accurate diagnosis of SAM and can be performed by village health workers or even laypeople in rural areas. The majority of children can be treated at home with ready-to-use therapeutic food under the community-based management of acute malnutrition model with recovery rates of approximately 90% under optimal conditions. A small percentage of children, often those with HIV, tuberculosis or other comorbidities, will still require inpatient therapy using fortified milk-based foods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Archives of Disease in Childhood 11/2014; DOI:10.1136/archdischild-2014-306026 · 2.91 Impact Factor
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    ABSTRACT: Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6-59 months old with MAM, defined as a weight-for-height Z-score (WHZ) between -2 and -3, were provided supplementary feeding for a fixed duration of 12 weeks. The children were then followed for 12 months to assess long-term nutritional status, and compared to children initially treated only until they first reached WHZ >-2. Compared to children treated until they reached WHZ > -2, children treated for 12 weeks were more likely to remain well-nourished (71% vs. 63%, P = 0.0015) and maintain more normal anthropometric indices during 12 months of follow-up; there was also a trend towards lower rates of severe acute malnutrition (7% vs. 10%, P = 0.067) and death (2% vs. 4%, P = 0.082). Regression modeling showed that mid-upper arm circumference and WHZ at the end of supplementary feeding were the most important factors in predicting which children remained well-nourished (P < 0.001 for each). The duration of supplementary feeding for children with MAM may not be as important as their anthropometry in terms of remaining well-nourished after initial recovery. The currently accepted recovery criteria of WHZ of -2 may be insufficient for ensuring long-term nutritional health; consideration should be given to setting higher recovery criteria.
    Journal of Pediatric Gastroenterology and Nutrition 11/2014; DOI:10.1097/MPG.0000000000000639 · 2.87 Impact Factor
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    ABSTRACT: Zinc deficiency is a major cause of childhood morbidity and mortality. The WHO/UNICEF strategy for zinc supplementation as adjunctive therapy for diarrhea is poorly implemented. A conference of experts in zinc nutrition and gastrointestinal disorders was convened to consider approaches that might complement the current recommendation and what research was needed to develop these approaches. Several key points were identified. The design of novel zinc interventions would be facilitated by a better understanding of how disturbed gut function, such as environmental (or tropical) enteropathy, affects zinc absorption, losses, and homeostasis. Because only 10% of zinc stores are able to be rapidly turned over, and appear to be rapidly depleted by acute intestinal illness, they are probably best maintained by complementary regular supplementation in a primary prevention strategy rather than secondary prevention triggered by acute diarrhea. The assessment of zinc status is challenging and complex without simple, validated measures to facilitate field testing of novel interventions. Zinc bioavailability may be a crucial factor in the success of primary prevention strategies, and a range of options, all still inadequately explored, might be valuable in improving zinc nutrition. Some therapeutic actions of zinc on diarrhea seem attributable to pharmacologic effects, whereas others are related to the reversal of deficiency (ie, nutritional). The distinction between these 2 mechanisms cannot be clarified given the insensitivity of serum zinc to identify subclinical deficiency states. Why zinc seems to be less effective than expected at all ages, and ineffective for secondary prevention of diarrhea in children <12 mo of age, remains unclear. It was concluded that a reframing of the current recommendation is warranted with consideration of how to better optimize and deliver zinc and whether to provide a complementary public health primary prevention zinc strategy. This requires careful consideration of the zinc product to be used as well as strategies for its delivery.
    American Journal of Clinical Nutrition 08/2014; Am J Clin Nutr October 20-14 ajcn.075036(4). DOI:10.3945/ajcn.113.075036 · 6.50 Impact Factor
  • Ellen Murray, Mark Manary
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    ABSTRACT: Severe acute malnutrition is a devastating condition afflicting under-5 children in many developing countries, but concentrated in sub-Saharan Africa. This paper examines the development of home-based lipid-nutrient therapeutic foods for the treatment of acute malnutrition in sub-Saharan Africa and the adoption of these therapies as a standard of care for non-complicated cases of acute malnutrition. Several of the early key clinical and operational effectiveness trials are discussed as well as the adoption of home-based treatment as a standard operating procedure in regions where malnutrition is present.
    Annals of Tropical Paediatrics International Child Health 07/2014; DOI:10.1179/2046905514Y.0000000135 · 0.92 Impact Factor
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    Mark Manary
    Food and nutrition bulletin 06/2013; 34(2):247-8. · 1.50 Impact Factor
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    Mark Manary
    Food and nutrition bulletin 06/2013; 34(2):256-8. · 1.50 Impact Factor
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    ABSTRACT: Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.
    Science 01/2013; DOI:10.1126/science.1229000 · 31.48 Impact Factor
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    ABSTRACT: The family Polyomaviridae is comprised of circular double-stranded DNA viruses, several of which are associated with diseases, including cancer, in immunocompromised patients. Here we describe a novel polyomavirus recovered from the fecal microbiota of a child in Malawi, provisionally named STL polyomavirus (STLPyV). We detected STLPyV in clinical stool specimens from USA and The Gambia at up to 1% frequency. Complete genome comparisons of two STLPyV strains demonstrated 5.2% nucleotide divergence. Alternative splicing of the STLPyV early region yielded a unique form of T antigen, which we named 229T, in addition to the expected large and small T antigens. STLPyV has a mosaic genome and shares an ancestral recombinant origin with MWPyV. The discovery of STLPyV highlights a novel alternative splicing strategy and advances our understanding of the complex evolutionary history of polyomaviruses.
    Virology 12/2012; DOI:10.1016/j.virol.2012.12.005 · 3.28 Impact Factor
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    ABSTRACT: We have discovered a novel polyomavirus present in multiple human stool samples. The virus was initially identified by shotgun pyrosequencing of DNA purified from virus-like particles isolated from a stool sample collected from a healthy child from Malawi. We subsequently sequenced the virus' 4,927-bp genome, which has been provisionally named MW polyomavirus (MWPyV). The virus has genomic features characteristic of the family Polyomaviridae but is highly divergent from other members of this family. It is predicted to encode the large T antigen and small T antigen early proteins and the VP1, VP2, and VP3 structural proteins. A real-time PCR assay was designed and used to screen 514 stool samples from children with diarrhea in St. Louis, MO; 12 specimens were positive for MWPyV. Comparison of the whole-genome sequences of the index Malawi case and one St. Louis case demonstrated that the two strains of MWPyV varied by 5.3% at the nucleotide level. The number of polyomaviruses found in the human body continues to grow, raising the question of how many more species have yet to be identified and what roles they play in humans with and without manifest disease.
    Journal of Virology 06/2012; 86(19):10321-6. DOI:10.1128/JVI.01210-12 · 4.65 Impact Factor
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    ABSTRACT: Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.
    Nature 06/2012; 486(7402):222-7. DOI:10.1038/nature11053 · 42.35 Impact Factor
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    ABSTRACT: Typical treatment of moderate acute malnutrition, simple wasting, in sub-Saharan Africa consists of dietary counselling and/or general or targeted distribution of corn/soy-blended flour (CSB). A randomised clinical effectiveness trial in 2007 showed CSB to be less effective than ready-to-use supplementary food (RUSF). To determine the operational effectiveness of treating moderate acute malnutrition with RUSF. Children aged 6-59 months were recruited in rural southern Malawi. Each child received 65 kcal/kg/d of locally produced soy/peanut RUSF, a product that provided about 1 RDA of each micronutrient. Anthropometric measurements were taken every 2 weeks and additional rations of RUSF were distributed at this time if the child remained wasted. Study participation lasted up to 8 weeks. Of the 2417 children enrolled, 80% recovered, 4% defaulted, 0.4% died, 12% remained moderately wasted and 3% developed severe acute malnutrition. Weight, length and MUAC gain were 2.6 g/kg/d, 0.2 mm/d and 0.1 mm/d respectively. Cost per child treated was $5.39. This intervention proved to be robust, maintaining high recovery rates and low default rates when instituted without the additional supervision and beneficiary incentives of a research setting.
    Annals of Tropical Paediatrics International Child Health 06/2010; 30(2):103-8. DOI:10.1179/146532810X12703901870651 · 0.92 Impact Factor
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    M J Ndekha, M J Manary, P Ashorn, A Briend
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    ABSTRACT: To determine if home-based nutritional therapy will benefit a significant fraction of malnourished, HIV-infected Malawian children, and to determine if ready-to-use therapeutic food (RUTF) is more effective in home-based nutritional therapy than traditional foods. 93 HIV-positive children >1 y old discharged from the nutrition unit in Blantyre, Malawi were systematically allocated to one of three dietary regimens: RUTF, RUTF supplement or blended maize/soy flour. RUTF and maize/soy flour provided 730 kJ x kg(-1) x d(-1), while the RUTF supplement provided a fixed amount of energy, 2100 kJ/d. These children did not receive antiretroviral chemotherapy. Children were followed fortnightly. Children completed the study when they reached 100% weight-for-height, relapsed or died. Outcomes were compared using regression modeling to account for differences in the severity of malnutrition between the dietary groups. 52/93 (56%) of all children reached 100% weight-for-height. Regression modeling found that the children receiving RUTF gained weight more rapidly and were more likely to reach 100% weight-for-height than the other two dietary groups (p < 0.05). More than half of malnourished, HIV-infected children not receiving antiretroviral chemotherapy benefit from home-based nutritional rehabilitation. Home-based therapy RUTF is associated with more rapid weight gain and a higher likelihood of reaching 100% weight-for-height.
    Acta Paediatrica 02/2005; 94(2):222-5. DOI:10.1111/j.1651-2227.2005.tb01895.x · 1.84 Impact Factor
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    ABSTRACT: The present study compared leucine kinetics and acute-phase-protein concentrations in three groups of marasmic, acutely infected Malawian children fed one of three isoenergetic diets. These were: an enhanced-protein-quality diet (egg-white+tryptophan, providing 1.2 g protein/kg per d; n 14); an increased-protein-content diet (egg-white+tryptophan, providing 1.8 g protein/kg per d; n 14); a standard-protein diet (1.2 g milk protein/kg per d; n 25). The hypotheses tested were that children receiving a diet with more protein would have greater rates of non-oxidative leucine disposal and that children receiving an isonitrogenous diet with a higher protein quality would have lower rates of leucine oxidation. The children were studied after 24 h of therapy using standard [(13)C]leucine stable-isotope tracer techniques. The children receiving the higher-protein-content diet had greater leucine kinetic rates than those receiving the standard-protein-content diet; non-oxidative leucine disposal was 170 (sd 52) v. 122 (sd 30) mumol leucine/kg per h (P<0.01). Leucine oxidation was less in the children receiving the enhanced-protein-quality diet than in those receiving the standard-protein-quality diet; 34 (sd 12) v. 45 (sd 13) mumol leucine/kg per h (P<0.05). The children receiving the high-protein-content diet increased their serum concentration for five of six acute-phase proteins 24 h after starting therapy, while those receiving the standard-protein-content diet did not. These data suggest that there was greater whole-body protein synthesis, and a more vigorous acute-phase response associated with the higher-protein-content diet. The clinical benefits associated with a higher protein intake in marasmic, acutely infected children need further study.
    British Journal Of Nutrition 10/2004; 92(4):589-95. DOI:10.1079/BJN20041242 · 3.34 Impact Factor

Publication Stats

1k Citations
221.07 Total Impact Points

Institutions

  • 2014–2015
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, Texas, United States
    • CSU Mentor
      Long Beach, California, United States
  • 1997–2015
    • Washington University in St. Louis
      • • Department of Medicine
      • • Department of Pediatrics
      San Luis, Missouri, United States
  • 1995–2015
    • University of Malawi
      • College of Medicine
      Zomba, Southern Region, Malawi
  • 2004
    • St. Luke's Hospital (MO, USA)
      Saint Louis, Michigan, United States
  • 1996–2000
    • University of Washington Seattle
      • Department of Pediatrics
      Seattle, WA, United States