![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
,2
* Division of Gastroenterology and Nutrition, Children’s Hospital, Boston, MA;
Department of Nutrition, Harvard School of Public Health, Boston, MA;
** Center for International Health and Development, Boston University School of Public Health, Boston, MA;
Section of Nutrition, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO;
Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania;
Tropical Diseases Research Centre, Ndola, Zambia;
¶ Malaria Consortium, Accra, Ghana; and
Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Medford, MA
2To whom correspondence should be addressed. E-mail: dhamer{at}bu.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • malaria • zinc • Plasmodium falciparum • child • acute phase response • C-reactive protein
The relation between plasma micronutrient concentrations and the extent of the body’s acute phase response is an important factor in the design and conduct of studies in the field of human nutrition. Two micronutrients for which this relation has been of particular interest are vitamin A and zinc. Blood concentrations of vitamin A are depressed during the acute phase response (1–5), and it is debatable whether these changes are related to vitamin A redistribution throughout the body, increased exogenous loss (6,7), and/or increased metabolic needs (8). Because clinical signs of vitamin A deficiency can occur among women (9) and children (5) with decreased retinol concentrations and elevated acute phase response markers, it seems incorrect to ascribe these low blood levels to merely a physiologic response to infectious or inflammatory stress.
Similar, although fewer, data have been described for the relation between zinc blood concentrations and the acute phase response. Most experimentally induced infections in animals and humans show a decrease in plasma zinc concentrations (10), with more severe infections leading to a more significant decrease. Extensive experimental work has demonstrated that hepatic metallothionein is involved in the response to stress. Metallothionein can be induced by infusion of dexamethasone or other glucocorticoids, endotoxin, or cytokines (11–13). Increases in metallothionein and metallothionein mRNA are correlated with increased hepatic zinc and a corresponding reduction of circulating zinc.
Some animal models of infection, however, have shown an increase in plasma zinc with infectious/inflammatory stresses (14,15), and the results of clinical studies have not been consistent. Plasma zinc concentration was not significantly affected by common intercurrent infections such as diarrhea and respiratory tract infection in 3 community-based studies in preschool- and school-age children (16).
Acute malaria infections, especially those due to Plasmodium falciparum, are notable for very high fevers and a severe acute phase protein response (17,18). Previous studies have linked low circulating levels of vitamins A and E with the acute phase response of malaria (19,20). However, the impact of the acute phase response on blood zinc concentrations in the setting of acute malaria has not been reported. Using data from a clinical trial of zinc supplementation in children with acute malaria (21), we sought to evaluate the relation between plasma zinc concentration and the acute phase response in subjects enrolled in this trial. In addition, we were able to evaluate the response of blood zinc concentration to oral zinc supplementation.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
37.5°C) and 2000/µL asexual forms of P. falciparum in a thick blood smear were randomly assigned either zinc (20 mg/d for children <12 mo and 40 mg/d for children aged 12–60 mo) or placebo for the first 3 d of the study. Clinical and parasitologic outcomes were noted at 3, 7, 14, and 28 d. Exclusion criteria included hemoglobin < 70 g/L; severe malaria as defined by the presence of any of the following: cerebral malaria, severe anemia, renal failure, pulmonary edema, hypoglycemia, shock, spontaneous bleeding, repeated convulsions (22); nonfalciparum or mixed Plasmodium infections; concurrent severe infections (i.e., lower respiratory infection, acute otitis media, pyelonephritis, typhoid fever, bloody diarrhea, meningitis, or measles); severe dehydration; malnutrition as defined by the Wellcome criteria (23) (i.e., marasmus, kwashiorkor, or marasmic kwashiorkor); inability to tolerate oral medications or fluids; chronic illness (including tuberculosis, AIDS, severe congenital anomalies, sickle cell disease); and prior participation in this trial.
In accordance with national treatment guidelines at the time of the trial, chloroquine (10 mg/kg on d 0, 10 mg/kg on d 1, and 5 mg/kg on d 2) was given as first-line treatment for malaria. Treatment failure was defined as the presence of axillary temperature 37.5°C and parasitemia > 25% of the baseline level at 72 h. Parasitologic failure was defined as parasitemia > 25% of the baseline level with resolution of fever (i.e., temperature < 37.5°C at 72 h). If either a treatment or a parasitologic failure occurred, subjects were changed to a standard dose of either amodiaquine or sulfadoxine pyrimethamine as second-line antimalarial therapy. All subjects received standard medical care for any concurrent illnesses that were present at baseline or developed during the study. This included appropriate antimicrobial therapy for acute respiratory infections, dysentery, and other treatable infections.
Ethical approval of the study was obtained from the institutional review boards at each site and the Harvard School of Public Health. Written informed consent was obtained from the parent or guardian of each subject.
Laboratory methods. Blood for plasma zinc measurement was taken on d 0 before the administration of the study drug and then at 72 h before the last dose of zinc or placebo was given. Samples were obtained just before meals. Venous blood was drawn with zinc-free syringes and placed into heparinized zinc-free tubes. Blood was immediately centrifuged and plasma was transferred into zinc-free tubes with a plastic zinc-free pipet and frozen at –20°C. Plasma zinc was assayed by atomic absorption spectrophotometry at the Pediatric Nutrition Laboratory at the University of Colorado Health Sciences Center (24). Plasma C-reactive protein (CRP)4 was measured via immunoturbidimetric assay (Roche Diagnostics). Due to logistical constraints, we analyzed plasma zinc and CRP concentrations from 3 of the 5 sites (Ghana, Tanzania, and Zambia).
Data analysis. We used SAS software, version 8.2 (SAS Institute), for statistical analysis. Univariate correlates of baseline plasma zinc were compared using Pearson correlation coefficients. Baseline characteristics were compared using logistic regression for categorical variables using PROC LOGISTIC and ANOVA for continuous variables using PROC ANOVA allowing for adjustment of multiple comparisons, using the Scheffé test (25). Mantel-Haenszel relative risks for the differences in zinc deficiency were calculated using PROC FREQ.
Predictors of baseline plasma zinc were modeled using a generalized linear model using PROC REG. Variables eligible for inclusion into the model were admission CRP, treatment group, site, age in months, anthropometric measurements (weight for age Z-score (WAZ), height for age Z-score (HAZ), weight for height Z-score (WHZ), mean upper arm circumference), treatment failure, presence of other illness, parasitemia, and admission temperature. Each variable (or group in the case of indicator variables) was entered into the model sequentially and then removed, and the one with the largest F value was retained. This continued until all the variables with a P value 
0.05 were retained in the model. At this point, 2-way interaction terms were entered into the model using the same criteria. None of the 2-way interactions had a P value 0.05 to be retained in the model.
In order to model the predictors for change in plasma zinc from admission to 72 h, we used a regression model with the change in plasma zinc from admission to 72 h as the baseline using PROC REG. We included admission plasma zinc as one of the predictors to account for the differences in plasma zinc at baseline. The details of this model construction were similar to those described above. Variables eligible for inclusion into the model were admission CRP, the change in CRP from admission to 72 h, treatment group, site, age in months, treatment failure, presence of other illness, anthropometric measurements (WAZ, HAZ, WHZ, mean upper arm circumference), admission parasitemia, admission temperature, and change in parasitemia from admission to 72 h.
All variables included in the final models were determined to be independent by assessing colinearity with the Eigen value (25).
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
|
|
|
Multivariate analysis of predictors of admission plasma zinc (Table 2) showed that admission CRP, parasite density, and site were the most important predictors. Variables not selected for inclusion in the model included age, breastfeeding status, temperature, and anthropometric measures. The model shows that for every increment in CRP levels by 1.0 mg/L, plasma zinc was 1.0 µmol/L lower. In addition, for every 10,000 U increase in parasite density, plasma zinc was 0.08 µmol/L lower. Both CRP and parasite density were, therefore, independently associated with plasma zinc concentration at admission.
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Previous studies that examined the relation between zinc status and infectious illnesses generally concluded that despite a high incidence of acute infections among children in developing countries, plasma zinc concentrations were still reasonable indicators of zinc status. Infections in these studies were variously defined as clinically apparent infections such as diarrhea, dermatitis, and respiratory and other infections, as well as clinically silent infections based on elevations in serum CRP and/or white blood cell count. In 3 cross-sectional community-based studies among ambulatory children in poor countries, mean differences in plasma zinc concentration between infected and noninfected children were 0 µmol/L (0 µg/dL) in Zimbabwe, 0.6 to 0.8 µmol/L (3.9 to 5.2 µg/dL) in Peru, and 0.6 µmol/L (3.9 µg/dL) in Guatemala (16).
These findings were noted to be in contrast with animal and adult data that showed a significant reduction in plasma zinc with acute inflammatory stresses (10,26). Our results, which are more consistent with this previous literature, are likely due in part to the severe nature of the acute phase response seen in malaria, as opposed to that observed among children with more mild infectious illnesses. By definition, subjects were only included in our study if they presented with fever and evidence of malaria parasitemia. The CRP concentration (mean ± SD) at admission was 71 ± 2 mg/L in our cohort, which is substantially higher than that of other studies: 9.8 ± 17 mg/L in Peru (27), and 14 of 303 with CRP > 50 mg/L in Zimbabwe (28). Other studies in which CRP was measured to evaluate the role of the acute phase response in micronutrient status have reported concentrations ranging from 3 to 12 mg/L in 90 children in Papua New Guinea (29), 0.4 to 1.6 mg/L among preschool Indonesian children (5), and 3 mg/L in pregnant Nepali women (9).
Our findings extend recent data on plasma zinc concentrations in children with intercurrent illnesses by specifically addressing the role of acute malaria in affecting this indicator of zinc nutritional status. Among children in Nepal presenting with acute diarrhea, plasma zinc was lower in children with dysentery, fever, and elevated CRP concentrations (30). In addition, hydration status, serum albumin, and the presence of hemolysis were also correlated with plasma zinc concentration. Wieringa et al. (31) reported that among Indonesian infants (mean age 10.1 mo), 15% had elevated concentrations of CRP (defined as >10 mg/L). Plasma zinc concentration was 15.5 ± 4.8 µmol/L in those without evidence of an acute phase response versus 13.8 ± 4.7 µmol/L (90.3 ± 30.8 µg/dL) in those with elevated CRP (P < 0.01). The incidence of low plasma zinc (defined as <10.7 µmol/L) was 33.3% in those with elevated CRP and 11% in those with normal CRP and 
-1-acid glycoprotein. In contrast, our study showed a high prevalence of low plasma zinc (defined as <9.2 µmol/L, a more strict criterion) of 70% at baseline and 30–41% at 72 h.
In children living in malaria endemic regions, elevated CRP concentrations are common. In rural children from Ghana, mean CRP concentrations were 7 to 8 mg/L (32). Hurt et al. found a median concentration of 6 mg/L among >600 rural Tanzanian children, with a median value of 23.6 mg/L in those with temperature > 37.4°C on presentation (33). They also found a correlation (r = 0.24, P < 0.0001) between CRP and malaria parasite density on peripheral blood smear. Only a few studies have examined the relation between zinc status and malaria. Pregnant Malawian women with a high prevalence of malaria infection were found to have low plasma and hair zinc levels, but there was no relation between plasma zinc and CRP levels (34). Malaria prevalence was associated with hair but not plasma zinc in this cohort (35).
Plasma zinc concentrations are an imperfect measure of zinc nutritional status. Plasma zinc represents only a fraction of total body zinc, and alternative measures of zinc status such as platelet, lymphocyte, or tissue zinc are not well-suited for large field trials in developing countries (36). Measurement of metallothionein levels is a potentially more sensitive alternative to plasma zinc for the assessment of zinc status. Metallothionein production is induced by available zinc (37,38). Marginal zinc intake in a small human study was associated with a 64% reduction in metallothionein mRNA concentrations, whereas there was no change in plasma zinc levels (39). Both human and animal studies have demonstrated that production of metallothionein mRNA and metallothionein significantly increased after dietary zinc supplementation (37,39,40). A zinc supplementation study showed that total RNA extracted from dried blood spots exhibited a change in MT mRNA comparable to that of purified monocytes and peripheral blood mononuclear cells (41). Dried blood spot collection offers the advantages of convenience and feasibility in field sampling situations. Consequently, metallothionein merits further investigation as a possible alternative measure of zinc status in field studies.
We have shown that among children with acute malaria infection, plasma zinc concentrations are very low and are inversely correlated with CRP, as well as other measures of disease severity such as body temperature and parasite density in peripheral blood. Although part of the depression in plasma zinc concentration is likely related to the redistribution of zinc in the acute phase response, zinc supplementation was effective at improving this measure of zinc status, even when CRP and time were taken into account. Thus children with acute malaria and low plasma zinc concentrations may still be at risk of zinc deficiency, and ascribing this depression solely to the acute phase response seems unwarranted. We suggest that low plasma zinc levels be interpreted with concurrent measures of the acute phase response such as CRP, when available, especially among children with moderate to severe infectious illnesses. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for the resolution of this hypozincemia.
|
FOOTNOTES |
|---|
3 The ZAP study group is composed of Fernando Sempértegui, Bertha Estrella, Franklin R. Toapanta, Darwin S. Torres, and Dheyanira E. Calahorrano (Ecuador); Emmanuel Addo-Yobo, Paul Arthur (deceased), and Sam Newton (Ghana); Mloka Hubert and Cyprian S. Makwaya (Tanzania); Freddie Ssengooba, Joseph Konde-Lule, and Emmanuel Mukisa (Uganda); and Modest Mulenga, Thomas Sukwa, and John Tshiula (Zambia).
4 Abbreviations used: CRP, C-reactive protein; HAZ, height for age Z-score; WAZ, weight for age Z-score; WHZ, weight for height Z-score.
Manuscript received 24 September 2004. Initial review completed 4 November 2004. Revision accepted 29 December 2004.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Scrimshaw, N., Taylor, C. & Gordon, J. (1968) Interaction of nutrition and infection 1968 World Health Organization Geneva.
2. Ruz, M., Solomons, N. W., Mejia, L. A. & Chew, F. (1995) Alteration of circulating micronutrients with overt and occult infections in anaemic Guatemalan preschool children. Int. J. Food. Sci. Nutr. 46:257-265.[Medline]
3. Duggan, C., Colin, A. A., Agil, A., Higgins, L. & Rifai, N. (1996) Vitamin A status in acute exacerbations of cystic fibrosis. Am. J. Clin. Nutr. 64:635-639.
4. Stephensen, C. & Gildengorin, G. (2000) Serum retinol, the acute phase response, and the apparent misclassification of vitamin A status in the third National Health and Nutrition Examination Survey. Am. J. Clin. Nutr. 72:1170-1178.
5. Semba, R., Muilal, , West, K., Natadisastra, G., Eisinger, W., Lan, Y. & Sommer, A. (2000) Hyporetinolemia and acute phase proteins in children with and without xerophthalmia. Am. J. Clin. Nutr. 72:146-153.
6. Stephensen, C., Alvarez, J., Kohatsu, J., Hardmeier, R., Kennedy, J. J. & Gammon, R. (1994) Vitamin A is excreted in the urine during acute infection. Am. J. Clin. Nutr. 60:388-392.
7. Alvarez, J. O., Salazar-Lindo, E., Kohatsu, J., Miranda, P. & Stephensen, C. B. (1995) Urinary excretion of retinol in children with acute diarrhea. Am. J. Clin. Nutr. 61:1273-1276.
8. Stephensen, C. (2000) When does hyporetinolemia mean vitamin A deficiency?. Am. J. Clin. Nutr. 72:1-2.
9. Christian, P., Schulze, K., Stoltzfus, R. J. & West, K. P., Jr (1998) Hyporetinolemia, illness symptoms, and acute phase protein response in pregnant women with and without night blindness. Am. J. Clin. Nutr. 67:1237-1243.[Abstract]
10. Milanino, R., Marrella, M., Gasperini, R., Pasqualicchio, M. & Velo, G. (1993) Copper and zinc body levels in inflammation: an overview of the data obtained from animal and human studies. Agents Actions 39:195-209.[Medline]
11. Cousins, R. J., Dunn, M. A., Leinart, A. S., Yedinak, K. C. & DiSilvestro, R. A. (1986) Coordinate regulation of zinc metabolism and metallothionein gene expression in rats. Am. J. Physiol. 251:E688-E694.
12. Lehman-McKeeman, L. D., Andrews, G. K. & Klaassen, C. D. (1988) Induction of hepatic metallothioneins determined at isoprotein and messenger RNA levels in glucocorticoid-treated rats. Biochem. J. 249:429-433.[Medline]
13. Schroeder, J. J. & Cousins, R. J. (1990) Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Proc. Natl. Acad. Sci. U.S.A. 87:3137-3141.
14. Fisher, G. L. (1977) Effects of disease on serum copper and zinc values in the beagle. Am. J. Vet. Res. 38:935-940.[Medline]
15. Feldman, B. F., Keen, C. L., Kaneko, J. J. & Farver, T. B. (1981) Anemia of inflammatory disease in the dog: measurement of hepatic superoxide dismutase, hepatic nonheme iron, copper, zinc, and ceruloplasmin and serum iron, copper, and zinc. Am. J. Vet. Res. 42:1114-1117.[Medline]
16. Brown, K. H. (1998) Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am. J. Clin. Nutr. 68:425S-429S.[Abstract]
17. Gillespie, S. H., Dow, C., Raynes, J. G., Behrens, R. H., Chiodini, P. L. & McAdam, K. P. (1991) Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria. J. Clin. Pathol. 44:228-231.
18. Hurt, N., Smith, T., Tanner, M., Mwankusye, S., Bordmann, G., Weiss, N. A. & Teuscher, T. (1994) Evaluation of C-reactive protein and haptoglobin as malaria episode markers in an area of high transmission in Africa. Trans. R. Soc. Trop. Med. Hyg. 88:182-186.[Medline]
19. Das, B. S., Thurnham, D. I. & Das, D. B. (1996) Plasma alpha-tocopherol, retinol, and carotenoids in children with falciparum malaria. Am. J. Clin. Nutr. 64:94-100.
20. Thurnham, D. I. & Singkamani, R. (1991) The acute phase response and vitamin A status in malaria. Trans. R. Soc. Trop. Med. Hyg. 85:194-199.[Medline]
21. The Zinc Against Plasmodium Study Group (2002) Effect of zinc on the treatment of Plasmodium falciparum malaria in children: a randomized controlled trial. Am. J. Clin. Nutr. 76:805-812.
22. World Health Organization Division of Control of Tropical Diseases (1990) Severe and complicated malaria. Trans. R. Soc. Trop. Med. Hyg. 84(suppl.):1-65.
23. Anonymous, (1970) Classification of infantile malnutrition. Lancet 2:302-303.
24. Smith, J., Butrimovitz, G. & Purdy, W. (1979) Direct measurement of Zn in plasma by atomic absorption spectroscopy. Clin. Chem. 25:1487-1491.
25. Kleinbaum, D., Kupper, L. & Muller, K. (1988) Applied Regression Analysis and Other Multivariable Methods 2nd ed. 1988 PWS-Kent Publishing Company Boston, MA.
26. Beisel, W. (1977) Zinc metabolism in infection. Brewer, G. Prasad, A. eds. Zinc Metabolism: Current Aspects in Health and Disease 1977 A. R. Liss New York, NY. .
27. Brown, K., Lanata, C., Yuen, M., Peerson, J., Butron, B. & Lonnerdal, B. (1993) Potential magnitude of the misclassification of a population’s trace element status due to infection: example from a survey of young Peruvian children. Am. J. Clin. Nutr. 58:549-554.
28. Friis, H., Ndhlovu, P., Kaondera, K., Sandstrom, B., Michaelsen, K. F., Vennervald, B. J. & Christensen, N. O. (1996) Serum concentration of micronutrients in relation to schistosomiasis and indicators of infection: a cross-sectional study among rural Zimbabwean schoolchildren. Eur. J. Clin. Nutr. 50:386-391.[Medline]
29. Rosales, F. J., Topping, J. D., Smith, J. E., Shankar, A. H. & Ross, A. C. (2000) Relation of serum retinol to acute phase proteins and malarial morbidity in Papua New Guinea children. Am. J. Clin. Nutr. 71:1582-1588.
30. Strand, T. A., Adhikari, R. K., Chandyo, R. K., Sharma, P. R. & Sommerfelt, H. (2004) Predictors of plasma zinc concentrations in children with acute diarrhea. Am. J. Clin. Nutr. 79:451-456.
31. Wieringa, F. T., Dijkhuizen, M. A., West, C. E., Northrop-Clewes, C. A. & Muhilal, (2002) Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J. Nutr. 132:3061-3066.
32. Filteau, S., Morris, S., Raynes, J., Arthur, P., Ross, D., Kirkwood, B., Tomkins, A. & Gyapong, J. (1995) Vitamin A supplementation, morbidity, and serum acute-phase proteins in young Ghanaian children. Am. J. Clin. Nutr. 62:434-438.
33. Hurt, N., Smith, T., Teuscher, T. & Tanner, M. (1994) Do high levels of C-reactive protein in Tanzanian children indicate malaria morbidity?. Clin. Diagn. Lab. Immunol. 1:437-444.
34. Huddle, J. M., Gibson, R. S. & Cullinan, T. R. (1998) Is zinc a limiting nutrient in the diets of rural pregnant Malawian women?. Br. J. Nutr. 79:257-265.[Medline]
35. Gibson, R. S. & Huddle, J. M. (1998) Suboptimal zinc status in pregnant Malawian women: its association with low intakes of poorly available zinc, frequent reproductive cycling, and malaria. Am. J. Clin. Nutr. 67:702-709.[Abstract]
36. Krebs, N. F., Hambidge, K. M., Westcott, J. E., Miller, L. V., Sian, L., Bell, M. & Grunwald, G. (2003) Exchangeable zinc pool size in infants is related to key variables of zinc homeostasis. J. Nutr. 133:1498S-1501S.
37. Davis, S. R. & Cousins, R. J. (2000) Metallothionein expression in animals: a physiological perspective on function. J. Nutr. 130:1085-1088.
38. Maret, W. (2000) The function of zinc metallothionein: a link between cellular zinc and redox state. J. Nutr. 130:1455S-1458S.
39. Allan, A. K., Hawksworth, G. M., Woodhouse, L. R., Sutherland, B., King, J. C. & Beattie, J. H. (2000) Lymphocyte metallothionein mRNA responds to marginal zinc intake in human volunteers [erratum appears in Br. J. Nutr. (2001) 85: 247]. Br. J. Nutr. 84:747-756.[Medline]
40. Sullivan, V. K., Burnett, F. R. & Cousins, R. J. (1998) Metallothionein expression is increased in monocytes and erythrocytes of young men during zinc supplementation. J. Nutr. 128:707-713.
41. Cao, J. & Cousins, R. J. (2000) Metallothionein mRNA in monocytes and peripheral blood mononuclear cells and in cells from dried blood spots increases after zinc supplementation of men. J. Nutr. 130:2180-2187.
This article has been cited by other articles:
|
|
 |
|
  C. A. Lin, M. J. Manary, K. Maleta, A. Briend, and P. Ashorn An Energy-Dense Complementary Food Is Associated with a Modest Increase in Weight Gain When Compared with a Fortified Porridge in Malawian Children Aged 6-18 Months J. Nutr., March 1, 2008; 138(3): 593 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Romieu, F. Castro-Giner, N. Kunzli, and J. Sunyer Air pollution, oxidative stress and dietary supplementation: a review Eur. Respir. J., January 1, 2008; 31(1): 179 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N Meydani, J. B Barnett, G. E Dallal, B. C Fine, P. F Jacques, L. S Leka, and D. H Hamer Serum zinc and pneumonia in nursing home elderly Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1167 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Hodkinson, M. Kelly, H. D. Alexander, I. Bradbury, P. J. Robson, M. P. Bonham, J. M. O'Connor, C. Coudray, J. J. Strain, and J. M. W. Wallace Effect of Zinc Supplementation on the Immune Status of Healthy Older Individuals Aged 55-70 Years: The ZENITH Study J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2007; 62(6): 598 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kongsbak, M. A. Wahed, H. Friis, and S. H. Thilsted Acute Phase Protein Levels, T. trichiura, and Maternal Education Are Predictors of Serum Zinc in a Cross-Sectional Study in Bangladeshi Children J. Nutr., August 1, 2006; 136(8): 2262 - 2268. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
