Dietary phytate, zinc and hidden zinc deficiency.

Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20µg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency.

Human zinc deficiency: discovery to initial translation.

Ananda S Prasad first suspected zinc deficiency in 1958 after he, at the request of James A Halsted, evaluated a patient with severe iron deficiency. In addition to iron deficiency, the patient appeared ∼10 y old and was severely stunted and prepubertal, though his chronological and bone age were much older. He also had hepatosplenomegaly and ate clay. The condition was not rare in that 11 cases were reported. In 1961 Prasad joined the Vanderbilt Nutrition Group led by William J. Darby at the US Naval Medical Research Unit-3, Cairo, Egypt. Prasad et al. studied 40 males similar to the index case. Contrasts with the index case included no clay eating and infection with schistosomiasis and hookworm. Zinc kinetics confirmed the zinc deficiency. Endocrine studies showed hypopituitarism. Treatment with zinc and an omnivorous diet was more efficacious for growth than no treatment, diet alone, or iron and diet. Later, Halsted et al. confirmed these findings in stunted Iranian farmers. The key role of diet in the illness became evident when Prasad found 16 severely stunted farmers from 2 oases who were not infected with schistosomiasis or hookworm. Later, Reinhold et al., in Halsted's group, reported that phytate and other indigestible zinc-binding ligands in unleavened bread prepared from high-extraction wheat flour suppress zinc absorption.

Subclinical zinc deficiency impairs human brain function.

Experiments in other species showed zinc essential for brain growth and function. Six randomized controlled comparative treatment experiments in Chinese and Mexican-American low-income children, aged 6-9 years, middle-income US adolescents, middle-income US premenopausal women and middle income US men, found that subclinical zinc deficiency changes brain function. Simultaneous treatment with a broad mixture of other micronutrients and/or an adequate omnivorous diet appeared to enhance the efficacy of zinc.

The origin and evolution of the Grand Forks Human Nutrition Research Center, 1970-90.

In the early 1960s William E. Cornatzer, MD, PhD suggested the need for increased USDA research concerning human nutrition and creation of the Grand Forks Human Nutrition Laboratory (later the Grand Forks Human Nutrition Research Center). He shared ideas with Senator Milton R. Young of North Dakota who requested that the Agricultural Research Service (ARS) prepare a proposal for such a program. In 1963 Senator Young submitted the proposal that included construction of regional centers to the U.S. Senate. The Grand Forks Human Nutrition Laboratory began operation in 1970. The attentions of Senator Young, Representative/Senator Mark Andrews, and Senator Quentin Burdick concerning the budgetary and construction needs facilitated development of the Center from its inception through 1990. Success of the enterprise rests on the creativity, industry, and other qualities of the Center's scientists and support staff, and collaborators at cooperating institutions. Their work resulted in a greater understanding of trace element nutrition and it role in human health.

Zinc deficiency in Mexican American children: influence of zinc and other micronutrients on T cells, cytokines, and antiinflammatory plasma proteins.

BACKGROUND: The Third National Health and Nutrition Examination Survey suggested some Mexican American children are at risk of zinc deficiency. OBJECTIVE: We measured the effects of zinc and micronutrients or of micronutrients alone on indexes of cell-mediated immunity and antiinflammatory plasma proteins. DESIGN: Subjects (n = 54) aged 6-7 y were randomly assigned and treated in double-blind fashion in equal numbers with 20 mg Zn (as sulfate) and micronutrients or with micronutrients alone 5 d/wk for 10 wk. RESULTS: Before treatment the mean +/- SD plasma zinc was 14.9 +/- 1.7 micromol/dL and the range was within the reference; hair zinc was 1.78 +/- 0.52 micromol/g and 41.6% were < or =1.68 micromol/g; serum ferritin was 25.7 +/- 18.6 microg/L and 50.0% were < or =20 microg/L. The zinc and micronutrients treatment increased the lymphocyte ratios of CD4(+) to CD8(+) and of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased the ex vivo generation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), decreased the generation of interleukin-10 (IL-10), and increased plasma interleukin-1 receptor antagonist (sIL-1ra) and soluble tumor necrosis factor receptor 1 (sTNF-R1). Micronutrients alone increased the ratio of CD4(+) to CD8(+) but not of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased IFN-gamma but had no effect on IL-2 or IL-10, and increased sIL-1ra but not sTNF-R1. Efficacy of zinc and micronutrients was greater than micronutrients alone for all indexes except the ratio of CD4(+) to CD8(+), which was affected similarly. CONCLUSIONS: Before treatment, concentrations of hair zinc in 41.6% of subjects and serum ferritin in 50% were consistent with the presence of zinc deficiency. The greater efficacy of the zinc and micronutrients treatment compared with micronutrients alone supports this interpretation.

Possible roles of zinc nutriture in the fetal origins of disease.

Risk of diseases of metabolism such as atherosclerosis and adult onset diabetes mellitus is increased by fetal malnutrition. Deficiencies of micronutrients essential for methylation are believed to contribute to the phenomenon in part through epigenetic abnormalities. Zinc is one of the nutrients essential for the epigenome. Because the worldwide prevalence of zinc deficiency is at least 20%, fetal zinc deficiency is common. We suggest fetal zinc deficiency contributes to the pathogenesis of metabolic diseases in adults. In support of our thesis, research in experimental models and humans established the essentiality of zinc at all stages of intrauterine and infant life. Experiments in rodents and/or non-human primates found that fetal and/or suckling zinc deficiency impairs neuropsychological functions of progeny and that the effects persist in spite of nutritional rehabilitation. In addition, maternal zinc deficiency in mice is reported to impair immunity of progeny; effects persist in spite of nutritional rehabilitation into the next generation. We suspect that zinc deficiency is a far greater human health problem than is generally recognized.

Association between zinc pool sizes and iron stores in premenopausal women without anaemia.

The simultaneous occurrence of Zn and Fe deficiencies in man has been known since the discovery of human Zn deficiency. However, it is not established that low Fe stores per se or Fe-deficiency anaemia infer low Zn status. Therefore our objective was to identify relationships between Zn and Fe status in premenopausal women without anaemia. We also examined the contribution of food frequencies and blood loss to Zn and Fe status. The subjects were thirty-three apparently healthy premenopausal women without anaemia, who were not taking dietary supplements containing Zn or Fe or oral contraceptives. Main outcomes were Zn kinetic parameters based on the three-compartment mammillary model and serum ferritin (SF) concentration; contributing factors were the frequency of consumption of specific foods and menorrhagia. Lower SF was significantly associated with smaller sizes of Zn pools. The breakpoint in the relationship between SF and the lesser peripheral Zn pool was found to be 21.0 microg SF/l. SF also correlated positively with frequency of beef consumption and negatively with bleeding through menstrual pads (BTMP). Similar to SF, the Zn pool sizes correlated positively with frequency of beef consumption, and negatively with BTMP. In summary, Zn pool sizes and Fe stores were highly correlated in premenopausal women. SF concentrations < 20 microg/l suggest an increased likelihood of low Zn status.

Renal and gastrointestinal potassium excretion in humans: new insight based on new data and review and analysis of published studies.

OBJECTIVES: Little is known about the relationship between the renal and gastrointestinal excretion of potassium in humans. This information is important in light of strong associations of potassium intake with hypertension and occlusive stroke. METHODS: We determined the relationship between fecal and urinary excretion of potassium under both fixed and variable potassium intakes using our unpublished archival data and published data of others. Twenty-five subjects were evaluated. RESULTS: On a fixed, low oral potassium intake (61.2 +/- 4.7 mmol/day; mean +/- SD), there was an inverse relationship between fecal and urinary potassium excretion (r = -0.66, p = 0.040). In studies in which potassium intake varied between 61-135 mmol/day, fecal and urinary potassium excretions were positively correlated (r = 0.58, p = 0.024). Considerable within-and-between-subject variation was observed in the relationship between fecal and urinary potassium excretion. CONCLUSIONS: Inter-individual variation in fecal potassium excretion may arise from both variation in dietary potassium intake and intrinsic individual differences in the renal versus gastrointestinal handling of potassium.

Zinc requirements and the risks and benefits of zinc supplementation.

The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.

Origins of the Interdepartmental Committee on Nutrition for National Defense, and a brief note concerning its demise.

The Interdepartmental Committee on Nutrition for National Defense was established in 1955 after malnutrition was found common among troops of the Republic of Korea and of the Republic of China (Taiwan). The initial purpose was identification of nutrition problems among military personnel (later, and among civilians) of countries of "special interest." Surveys measured status, assisted with the establishment of nutrition resources, and facilitated investigator learning and research. A major initial accomplishment was the preparation of a manual of procedures, which evolved into the 1963 Manual for Nutrition Surveys. The first 3 surveys, conducted in 1956, were of the armies of Iran, Pakistan, and Korea. They identified poor nutrition status in some troops, provided a basis for improving rations, and confirmed the effectiveness of the methodology. These surveys were followed by surveys of 30 additional countries that in nearly all instances included civilians and provided a basis for programs and the institutions for improvement of nutrition. On August 1, 1967, the program was reorganized and the Nutrition Program, CDC, based at NIH, was created. This occurred in response to the 1967 Partnership for Health Amendments "to make a comprehensive survey of the incidence and location of serious hunger and malnutrition, and health problems incident thereto, in the United States and to report these conditions to the Congress." The Ten State Nutrition Survey was done in response. Findings of malnutrition, especially in populations of low-income states were politically unwelcome in some quarters. Consequently the program was redirected, and, according to 2 observers, the survey findings were suppressed.

Association between plasma zinc concentration and zinc kinetic parameters in premenopausal women.

The objective of this study was to measure relationships between plasma zinc (Zn) concentrations and Zn kinetic parameters and to measure relationships of Zn status with taste acuity, food frequency, and hair Zn in humans. The subjects were 33 premenopausal women not taking oral contraceptives and dietary supplements containing iron and Zn. Main outcomes were plasma Zn concentrations, Zn kinetic parameters based on the three-compartment mammillary model using 67Zn as a tracer, electrical taste detection thresholds, and food frequencies. Lower plasma Zn was significantly (P < 0.01) associated with smaller sizes of the central and the lesser peripheral Zn pools, faster disappearance of tracer from plasma, and higher transfer rate constants from the lesser peripheral pool to the central pool and from the central pool to the greater peripheral pool. The break points in the plasma Zn-Zn kinetics relationship were found between 9.94 and 11.5 micromol/l plasma Zn. Smaller size of the lesser peripheral pool was associated with lower frequency of beef consumption and higher frequency of bran breakfast cereal consumption. Hypozincemic women with plasma Zn <10.7 micromol/l or 700 ng/ml had decreased thresholds of electrical stimulation for gustatory nerves. Our results based on Zn kinetics support the conventional cutoff value of plasma Zn (10.7 micromol/l or 700 ng/ml) between normal and low Zn status.