Zinc deficiency assessment

Hotz, C. and Brown, K. (2004). International Zinc Nutrition Consultative Group (IZiNCG) technical document 1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr. Bull. 25(1, Suppl 2), S94-S203. 

In addition to the classical symptoms of zinc deficiency mentioned above, the following unusual conditions have been reported liver and spleen enlargement, abnormal dark adaptation and abnormalities of taste. Several laboratory procedures for diagnosing zinc deficiency are available. Measurement of zinc levels in plasma is useful in certain cases. Levels of zinc in the red cells and hair may be used for assessment of body zinc status. More accurate and useful parameters are neutrophil zinc determination and quantitative assay of alkaline phosphatase activity in neutrophils. Determination of zinc in 24 h urine may help diagnose deficiency if sickle cell disease, chronic renal disease and liver cirrhosis are ruled out. A metabolic balance study may clearly distinguish zinc-deficient subjects. 

Interesting research assessing the influence of select nutrients on apo A-I expression has been published (reviewed in Mooradian et al.36). Among some of the nutrients associated with decreased expression of the apo A-I gene in cell culture or animal models are polyunsaturated fatty acids, trans-fatty acids, omega-3 fatty acids, glucose, antioxidant vitamins, and zinc deficiency. In contrast, monounsaturated fatty acids, soy proteins, alcohol, and copper deficiency are associated with increased expression of the human apo A-I gene. 

Zinc complexes with hydroxypyranones, for example, maltol or kojic acid, have been known for many years. These, and analogous complexes with hydroxypyridinones, have been assessed as zinc supplements in cases of severe zinc deficiency, and more recently as potential insulin mimics. 

Zinc deficiency in humans is difficult to diagnose because a suitable functional test, or a test for zinc reservoirs, has been lacking, Milne et ai. (1987) documented that a variety of zinc-requiring enzymes of the red blood cell seem to resist the effects of dietary zinc deficiency, but demonstrated that liver alcohol dehydrogenase may be sensitive to the deficiency. The activity of this enzyme was assessed by a functional test — the ethanol tolerance test. The ethanol tolerance test would be expected to be influenced by factors unrelated to zinc status, such as the state of Induchon of the ethanol oxidizing system, and hence may not be the functional test of choice for assessing zinc status. 

The influence on metals such as copper and zinc may be difficult to assess, since penicillamine not only increases the excretion but also the absorption of these metals (140). A zinc deficiency syndrome, with skin lesions, alopecia, granulocytopenia, and eye damage, has been described in association with penicillamine (141). 

In one of our first experiments, five week old A/J females were fed diet supplemented with adequate (61 yg/g) or deficient (0.6 yg/g) amounts of dietary zinc. A restricted group received a diet containing adequate zinc (61 yg/g) but were limited to the average amount of diet consumed the previous day by the zinc deficient mice as a control for inanition. On day 24 all of the mice were injected with 1 x 10 sheep red blood cells (SRBC). Four days later the response to the SRBCs was assessed using a modification of the Jerne plaque assay (Fraker and Leucke, 1977 Leucke et al., 1978). 

The prevalence of marginal zinc deficiency in human populations is unknown because of the lack of a good means of assessing zinc status. Measurement of plasma zinc is straightforward, but it does not serve as a reliable indicator of zinc status. Plasma zinc is a quantitatively minor pool that can be easily influenced by minor shifts in tissue zinc. Plasma concentrations do not fall with decreasing dietary intake, except at very low intakes. Plasma zinc can also be affected by factors unrelated to zinc status (e.g., time of day, stress, and infection). Cellular components of blood can be assayed, but erythrocyte concentrations of zinc are maintained in deficient states and variable results have been found with leucocytes. Hair zinc concentrations may reflect available zinc but will also depend on the rate of hair growth. 

Trace elements Provide standard parenteral trace element preparation (containing zinc, copper, manganese, chromium, and selenium) daily in PN Assess patient for any possible adjustments needed (e.g., delete copper and manganese from PN if the patient has evidence of severe cholestasis, supplemental zinc and selenium for any Gl or fistula losses) or potential deficiencies... 

The total content of the major elements in soil is of little practical significance since only a tiny, soluble fraction is available for absorption by plant roots (West, 1981 Tinker, 1986). To some extent this is less true for trace elements and micronutrients where for example, analyses of total copper or zinc can be used to assess the likelihood of plant deficiencies or toxicities. Nonetheless, for an element to be bioavailable it has to be relatively soluble. 

This is documented by the discovery of essential functions for the "new trace elements in the past seven years (I) and by the increasing knowledge of marginal or pronoimced deficiencies in humans of such elements as iron (2), zinc (3), chromium (4), and perhaps copper (5) and selenium (6), Although some of these deficiencies occur only in special age and sex groups or under unusual conditions, their existence has aroused public and scientific concern for the exact definition of human trace element needs and for the assessment of trace element nutritional status. These two major challenges for human trace element research cannot be met without proper analytical support. I will attempt to describe the present status of trace element analysis as it relates to nutrition research and to point out some new concepts that might well influence the future direction of trace element analysis. 

Risk assessments are conducted under a far different set of guidelines. One of the first efforts to establish an upper limit for zinc intake was proposed by the Environmental Protection Agency (EPA) in the United States during their development of a reference dose for zinc. The reference dose, or RfD, is the level of substance intake that can be sustained for a lifetime without ill-effect. In setting an RfD the toxicologist tends to take a cautious approach. Copper and iron deficiency are known to be induced by high levels of zinc administration for example, a daily intake of 50 mg/day of supplemental zinc has been reported to produce modest inhibition of a red blood cell enzyme called superoxide dismutase. Whether or not this is a toxic effect remains a matter of conjecture to this day (8, 9). However, toxicologists, in the interest of public health, have tended to interpret this as a potentially adverse effect and 50 mg per day of supplemental zinc intake has become a point of reference for toxicity . 

At every step in the chain from soils to man, the essential mineral elements interact with other elements, and these Interactions may profoundly affect the availability of essential elements or the amount of the essential element required for normal growth or metabolic function. For example, a high level of sulfate in the soil may depress the uptake of selenium by plants, and cause the people that eat the plants to suffer from selenium deficiency. The availability of zinc may be depressed if the diet is high in calcium. These and other interactions must be considered in assessing whether a given soil will supply plants with needed nutrients, and, in turn, whether plants will supply the people that consume them with needed nutrients. 

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