A combination of dietary and host-related factors determines iron and zinc absorption, and several in vitro methods have been developed as preliminary screening tools for assessing bioavailability. An expert committee has reviewed evidence for their usefulness and reached a consensus. Dialyzability (with and without simulated digestion) gives some useful information but cannot predict the correct magnitude of response and may sometimes predict the wrong direction of response. Caco-2 cell systems (with and without simulated digestion) have been developed for iron availability, but the magnitude of different effects does not always agree with results obtained in human volunteers, and the data for zinc are too limited to draw conclusions about the validity of the method. Caco-2 methodologies vary significantly between laboratories and require experienced technicians and good quality cell culture facilities to obtain reproducible results. Algorithms can provide semi-quantitative information enabling diets to be classified as high, moderate, or low bioavailability. While in vitro methods can be used to generate ideas and develop hypotheses, they cannot be used alone for important decisions concerning food fortification policy, selection of varieties for plant breeding programs, or for new product development in the food industry. Ultimately human studies are required for such determinations.

Iron deficiency remains a major global health problem affecting an estimated 2 billion people. The World Health Organization ranked it as the seventh most important preventable risk for disease, disability, and death in 2002. Since an important factor in its causation is the poor bioavailability of iron in the cereal-based diets of many developing countries, SUSTAIN set up a Task Force, consisting of nutritional, medical, industry, and government experts to consider strategies for enhancing the absorption of fortification iron. This paper summarizes the findings of this Task Force. Detailed reviews of each strategy follow this overview. Highly soluble compounds of iron like ferrous sulfate are desirable food fortificants but cannot be used in many food vehicles because of sensory issues. Thus, potentially less well-absorbed forms of iron commonly are used in food fortification. The bioavailability of iron fortificants can, however, be enhanced with innovative ingredient technologies. Ascorbic acid, NaFeEDTA, ferrous bisglycinate, and dephytinization all enhance the absorption of fortification iron, but add to the overall costs of fortification. While all strategies cannot be recommended for all food fortification vehicles, individual strategies can be recommended for specific foods. For example, the addition of ascorbic acid is appropriate for dry blended foods such as infant foods and other dry products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. NaFeEDTA can be recommended for fortification of fish sauce and soy sauce, whereas amino acid chelates may be more useful in milk products and beverages. With further development, dephytinization may be possible for low-cost, cereal-based complementary foods in developing countries. Encapsulation of iron salts in lipid coatings, while not an iron absorption-enhancing strategy per se, can prevent soluble forms of iron from interacting undesirably with some food vehicles and hence broaden the application of some fortificants. Research relevant to each of these strategies for enhancing the bioavailability or utility of iron food fortificants is reviewed. Individual strategies are evaluated in terms of enhancing effect and stability, organoleptic qualities, cost, and regulatory issues of interest to the nutrition community, industry, and consumers. Recommendations are made on potential usages and further research needs. Effective fortification depends on the selection of technically feasible and efficacious strategies. Once suitable strategies have been identified, cost becomes very important in selecting the best approach to implement. However it is essential to calculate cost in relation to the amount of bioavailable iron delivered. An approach to the calculation of cost using a conservative estimate of the enhancing effects of the innovative technologies discussed in the supplement is given in the final section.

The avian kidney has shown a remarkable ability to maintain adequate and even normal function in the face of a mycotoxin challenge. Full evaluation of the nephrotoxicity of a substance must therefore go beyond pathological and ultrastructural documentation and include a complete functional evaluation. To date, only three nephrogenic mycotoxins, citrinin, ochratoxin A, and aflatoxin B-1 have been assessed for their ability to alter avian renal function. At non-lethal doses, citrinin appears to have acute reversible effects on the distal portion of the nephron, possibly acting to inhibit water absorption. Ochratoxin A is more potent and less acute than citrinin,but less site-specific in that both proximal and distal tubules are damaged, resulting in severe loss of both fluids and electrolytes. Aflatoxin B-1 at a dosage and duration which induced hepatotoxicity, concurrently exerted nephrogenic effects such as increased urinary calcium excretion and decreased inorganic phosphate excretion. In commercial broilers aflatoxin B-1 has been shown to decrease plasma levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D and may also decrease endogenous parathyroid hormone synthesis and the renal sensitivity to parathyroid hormone. Furthermore, exposure to aflatoxin B-1 may cause prolonged alteration in renal function such as reduced glomerular filtration rate. This review summarizes the studies which have been conducted to evaluate avian renal function during both acute and chronic exposure to these three mycotoxins.

1. Effects of diethyl maleate (DEM) mediated glutathione (GSH) depletion on hepatic and renal cortical blood flow (perfusion), plasma GSH, and portal prostacyclin (6-ketoPGF1-alpha) and thromboxane (TxB2) were determined in anaesthetized swine.2. Although DEM depleted hepatic GSH to 25% of control, plasma GSH increased 10-fold in comparison to controls. DEM caused a drop in blood pressure and renal cortical perfusion but had no effect on hepatic perfusion or portal 6-ketoPGF1-alpha or TxB2 levels.3. Possibly, the unexpected rise in plasma GSH may have inhibited prostanoid synthesis, preventing any alterations in tissue perfusion that may have occurred following tissue GSH depletion.

Glutathione (GSH) is important in detoxification and regulating cyclooxygenase activity. Since the liver has high levels of GSH, xenobiotic-induced changes in hepatic GSH could affect hepatic tissue blood perfusion (HP) via alterations in prostaglandin synthesis. In anesthetized male New Zealand rabbits, elevating GSH with GSH monoethyl ester had no affect on HP. Treatment of rabbits with diethyl maleate to deplete GSH also had no affect on HP in animals previously given GSH monoethyl ester. However, HP increased within 20 min in rabbits treated with diethyl maleate prior to GSH monoethyl ester. In another experiment, a similar rise in HP following GSH depletion was accompanied by arterial plasma 6-ketoPGF1α (the stable metabolite of prostacyclin) levels that were 4-times higher than in the controls. Plasma TxB2 (the stable metabolite of throm☐ane) also increased following diethyl maleate, but only to levels that were 25-times lower than for 6-ketoPGF1α. Since indomethacin blocked the rise in HP, as well as the increases in 6-ketoPGF1α and TxB2, these results indicate changes in HP may occur following GSH depletion as a result of increased synthesis of one or more arachidonic acid metabolites and implicate prostacyclin as a possible mediator of this phenomenon.