Zinc deficiency in children with environmental enteropathy—development of new strategies: report from an expert workshop

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.

A murine model of diarrhea, growth impairment and metabolic disturbances withShigella flexneriinfection and the role of zinc deficiency

“…However, little is known about the mechanisms involved. 43,44 In this model, chronic infection outcomes, characterized by the persistent colonization and cytokine production findings, were observed in zinc-deficient mice exposed to S. flexneri infection. In the house chow-fed mice, there was an early biochemical response to infection including changes in energy-related pathways such as fatty acid β-oxidation, the TCA cycle, and nicotinamide metabolism.…”

Environmental enteropathy

“…Zinc deficiency decreases intestinal ion transport, and alters intestinal permeability and mucosal immune function but there is no substantial proof that zinc supplementation is able to reverse these effects [37]. On the other hand, high-dose multiple micronutrient supplementation has shown to increase small bowel absorptive surface area [38].…”

Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

“…Zinc deficiency alters immune functions [ 48 ] and is known to be a contributing factor to severe diarrhea [ 49 ]. Zinc deficiency is a major cause of childhood morbidity and mortality in low-income countries, in particular since it occurs in parallel with deficiencies of other micronutrients and animal proteins [ 49 ]. Environmental enteropathy (see below) perturbs zinc homeostasis in the gut [ 49 ].…”

“…Zinc deficiency is a major cause of childhood morbidity and mortality in low-income countries, in particular since it occurs in parallel with deficiencies of other micronutrients and animal proteins [ 49 ]. Environmental enteropathy (see below) perturbs zinc homeostasis in the gut [ 49 ]. Therefore, zinc supplementation reduces the incidence and severity of diarrhea, but is also considered to be part of a prevention strategy.…”