Malnutrition: trials and triumphs.

Severe malnutrition is uncommon but often fatal, particularly in very young infants or when oedema is present. Another major contributor to mortality is undiagnosed infection. Three pilot studies have recently been performed in severely malnourished patients in therapeutic feeding centres in sub-Saharan Africa. In each, a practical management problem was addressed and a potential solution tested. Three conclusions were reached: young breastfeeding infants were best managed using a supplemented suckling technique; routine antibiotics from admission reduced mortality; and in adults with oedematous malnutrition, therapeutic diets with a lower-than-usual protein:energy ratio were effective in reducing mortality and permitting catch-up weight gain.

Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence.

The S-100 Ca2+ binding protein, calprotectin, isolated from neutrophil lysates, has been reported to exhibit zinc reversible biostatic activity in vitro. We verified these findings with C. albicans and investigated whether the growth inhibition resulted from zinc deprivation due to chelation by calprotectin. Calprotectin concentrations of 250 micrograms/ml significantly inhibited the growth of C. albicans. This was reversed by supplementing culture medium with 10 microM ZnSO4. Incubation of calprotectin in culture medium for 24 h prior to inoculation significantly reduced the minimum inhibitory concentration. When this latter medium was ultrafiltered to remove the calprotectin and then inoculated with C. albicans, significant growth inhibition was still present: again it was reversed by zinc. These findings implicate zinc chelation as a novel, potentially important host defence function of an abundant neutrophil protein.

Effect of zinc on lean tissue synthesis during recovery from malnutrition.

During recovery from severe wasting, malnourished children gain weight at greatly accelerated rates. To determine if additional zinc added to their basal therapeutic diets increased the retention of lean tissue and stimulated protein metabolism, we studied three groups of children taking either the basal diet alone or the basal diet supplemented with either 76 mumol (5 mg) or 153 mumol (10 mg) Zn/kg diet. The zinc-supplemented children gained similar weight and consumed the same amount of diet as the unsupplemented children. Zinc supplementation resulted in a greater net absorption of nitrogen and a higher rate of protein turnover, as estimated from urinary ammonia 15N enrichment after oral [15N]glycine. We conclude that additional zinc affected the composition of newly synthesized tissue and intermediary nitrogen metabolism.

Effect of zinc supplementation on the dietary intake, rate of weight gain, and energy cost of tissue deposition in children recovering from severe malnutrition.

Children recovering from severe malnutrition on a milk based diet have low plasma zinc concentrations: children recovering on a soya based diet have much lower plasma zinc concentrations, lower rates of weight gain, and higher energy costs of tissue deposition. However, they do not demonstrate the clinical features of anorexia, diarrhea, and skin lesions usually associated with zinc deficiency. We therefore supplemented 16 children with zinc acetate on the basis that a therapeutic response to zinc constitutes the best evidence of a preexisting zinc deficiency. Fourteen of the 16 children had an immediate and definite increase in their rate of weight gain with zinc supplementation. This was associated with a decrease in the energy cost of tissue deposition, regrowth of the thymus, and activation of the sodium pump. We conclude that the children were indeed zinc deficient. We suggest that the anorexia of zinc deficiency is related to an inability to metabolize nitrogen in the zinc deficient state, and that our children did not show an appetitive response because of the relatively low protein content of the diets we used. Based on the premise that the abnormalities seen in our children may have been secondary to mild zinc deficiency, we suggest that limitation of lean tissue synthesis, with resultant obesity, and a propensity to infection are the major features of a mild zinc deficiency. Children undergoing a period of "catch up" weight gain or growth should have supplemental zinc, particularly if they have had diarrhea or if the use of a soya based formula is contemplated.

Leucocyte sodium transport and dietary zinc in protein energy malnutrition.

Zinc supplementation of children who were just completing a period of rapid "catch-up" growth during recovery from severe malnutrition was found to stimulate sodium transport in their leucocytes. These results suggest that zinc status should be studied in the large number of serious illnesses, now known or thought to be associated with impaired sodium transport.

Zinc and immunocompetence in protein-energy malnutrition.

Malnourished children have thymic atrophy which is reversed by zinc supplementation. To see if their defect in cell-mediated immunity was also associated with zinc deficiency ten children were skin-tested with Candida antigen on both arms. One test site was covered with local zinc sulphate and the other with placebo ointment. There was a highly significant increase in the typical delayed-hypersensitivity reaction at the site covered with zinc. The magnitude of the difference between the supplemented and unsupplemented arms correlated negatively with the plasma-zinc concentration. These data show that zinc deficiency is a cause of the immunoincompetence seen in malnutrition. The normal reactions of the zinc-supplemented side indicate that, of the many nutritional deficits of malnourished children, zinc deficiency specifically impairs the cell-mediated immune system. Local skin-testing with and without zinc may provide a measure of zinc status. Local application of zinc may enhance the reliability of tests to diagnose diseases such as tuberculosis in malnourished patients.

Effect of zinc on thymus of recently malnourished children.

Zinc-deficient animals and children have thymic atrophy and an increased susceptibility to infections. Children with protein-energy malnutrition similarly have thymic atrophy, zinc deficiency, and increased susceptibility to infections. 8 children, recently malnourished, who were supplemented with zinc, showed an increase in thymic size as judged radiographically. It is suggested that zinc deficiency may play a part in the thymic atrophy and infections associated with malnutrition.