A predictive approach to nutrient criteria.

Violation of a water quality standard triggers the need for a total maximum daily load (TMDL); this should result in actions that improve water quality, but sometimes at significant cost. If the standard is well-conceived, a designated-use statement characterizes societal values, and a criterion provides a measurable surrogate for designated use. This latter provision means that scientists measure the criterion and view violations of the criterion as equivalent to noncompliance with the designated use. However, if a criterion is not a good indicator of designated use, it is apt to result in misallocation of the limited resources for water quality improvement through the TMDL process. This concern provides the basis for our assessment of the national nutrient criteria strategy recently proposed by the U.S. EPA. We acquired data sets for four case studies (Lake Washington, Neuse River Estuary, San Francisco Bay, and Lake Mendota) and then used expert elicitation to quantify designated-use attainment for each case. Applying structural equation modeling, we identified good water quality criteria as the best predictors of the designated use elicited response variable. Further, we used the model to relate the level (concentration) of each criterion to the probability of compliance with the designated use; this provides decision-makers with an estimate of risk associated with the criterion level, facilitating the selection of appropriate water quality criteria.

Magnesium deficiency in the rat: effects of fructose, boron and copper.

Magnesium (Mg) participates in many biochemical reactions which involve a variety of other nutrients. To elucidate some nutrient interactions, fructose (FR) and starch (ST) were compared as carbohydrate sources, and boron (B) and copper (Cu) were added to low-Mg diets for young male rats. Lack of Mg always caused characteristic deficiency symptoms. FR resembled Mg deficiency in effects on body, liver, and kidney weights and on plasma cholesterol level, but did not affect serum Mg or calcium (Ca). FR effects apparently were not mediated by changes in plasma Mg and Ca concentrations and were not prevented by adding Cu. B appeared to lessen effects of a low-Mg diet on body growth, serum cholesterol, and ash concentration in bone, but exacerbated deficiency symptoms, without affecting the concentration of Mg or Ca in serum. Results suggest that increased FR intake and marginal B might adversely affect individuals whose Mg status is suboptimal.

The effects of dietary boric acid on bone strength in rats.

The effects of dietary boron (B) (from boric acid [BA]) on bone strength were evaluated using male F344 rats. B was administered by dietary admixture of BA to NIH-07 feed at concentrations of 200, 1000, 3000, and 9000 ppm. The latter two levels were found in previous studies to be reproductively toxic to both males and the developing fetus. The first two levels are below and just at, respectively, the levels for producing fetal malformations, and are below the dose required to produce male reproductive toxicity. Resistance to destructive testing was measured on femora, tibiae, and lumbar vertebrae. Although femur and tibia resistance to bending force were not affected by any amount of dietary B, vertebral resistance to a crushing force was increased by approximately 10%, at all dose levels (200-9000 ppm). These data show that even levels of BA that are not reproductively toxic can affect the strength of the axial skeleton in rats.

Adding zinc reduces bone strength of rats fed a low-calcium diet.

This experiment examined skeletal effects of moderate zinc (Zn) supplementation of a low-calcium diet. Male weanling rats were fed experimental diets for about 4 wk. One diet was adequate (control), whereas two others were calcium-deficient, but otherwise adequate. One of the low-calcium (Ca) diets was supplemented with Zn. Dimensions, weight, mineral content, and mechanical properties of femurs were measured. Ca deficiency reduced bone mineral content and strength markedly. Adding Zn to the low-Ca diet further reduced bone strength and elasticity, compared with the unsupplemented low-Ca diet. When the Ca intake is low, possible benefits of Zn supplements should be weighted against risk of deterioration of mechanical properties of bone.

The effects of dietary boron on bone strength in rats.

Previous studies from our laboratory found that when boric acid (BA) was administered in the diet to rats, boron levels in bone were approximately fourfold greater than serum levels. The current studies were undertaken to determine if these elevations produced adverse effects on several bone-related measures, including serum electrolyte levels, bone structure, and bone strength. Data from two studies are presented: in the first study, young adult male rats consumed a powdered diet containing 0, 3000, 4500, 6000, or 9000 ppm BA for 9 weeks. Endpoints were serum calcium, phosphorous, potassium, and chloride, as well as blood and bone boron concentrations ([B]) measured weekly during the 9-week exposure period, and at 8, 16, 24, and 32 weeks after the end of exposure. In the second study, the male and female young adult rats diet contained 0, 200, 1000, 3000, or 9000 ppm BA for 12 weeks; endpoints measured weekly were serum levels of calcium, phosphorous, and magnesium, bone [B], and bone structure (humerus) and strength (tibia, femur, and lumbar vertebrae). In treated rats, calcium was reduced in the first study but not the second. Serum phosphorous was reduced in both studies; potassium was unchanged, chloride was increased by 1%, and magnesium was reduced in all BA-exposed groups in the second study, to a maximal 19% reduction. Bone [B] was consistently increased in all treated groups, to concentrations approximately fourfold those of serum. After cessation of exposure, serum and urinary boron concentrations dropped to within control values within a week. However, even 32 weeks after the end of exposure, bone [B] remained threefold greater than controls. Male tibia and femur resistance to bending was unchanged. However, vertebral strength in compression was significantly increased by 5-10% in all dose groups (200 to 9000 ppm). The pattern was substantially similar in females. Only the humerus was examined by light microscopy and was found to be unchanged at any level of BA consumption. These data show that, despite a reduction in some serum electrolyte levels, BA consumption increased vertebral resistance to crush force, without detectably altering the microscopic structure of the humerus or the resistance of femur and tibia to a bending load. This increase in compression resistance occurred at exposure levels substantially below those that were previously reported to be reproductively toxic.

Interactions between magnesium and vitamin D: possible implications in the immune system.

Evidence clearly shows that magnesium and vitamin D [1 alpha, 25-dihydroxyvitamin D3; 1,25(OH)2D3] independently affect numerous aspects of the immune system. Although no reports of interactive effects on components of immunity have been found, there is evidence that the two nutrients interact in other biosystems, sometimes involving calcium. Furthermore, this paper identifies numerous places in common where both magnesium and vitamin D reportedly affect immune function. Fundamental sites for possible interaction within the immune system include cell transformation, regulation of the cell cycle, stabilization of nuclear DNA/chromatin, production of reactive oxygen species (ROS), and effects on enzymatic and hormonal actions. The presence of different functional, chemical forms of both of the nutrients within biological systems, and the availability of synthetic drug relatives of both to introduce into such systems, complicate interactive studies because such differing forms may not necessarily interact similarly or interact at all within the immune system or elsewhere. Regardless, there are compelling reasons to believe that examining interactions between magnesium and vitamin D within the immune system could prove rewarding, especially since the physiological statuses of both nutrients in human populations are less than optimum. Such human populations include the elderly whose immune function may be compromised.

Relation of boron to the composition and mechanical properties of bone.

A review of the experimental studies relating boron to biological effects on appendicular and axial bones in animal models suggests that numerous influences, known and unknown, affect the responsiveness of bone to dietary boron. Degrees of skeletal response to boron are modified by other nutritional variables that include calcium, magnesium, vitamin D, and fluoride. Evidence suggests that appendicular and axial bones may differ in their responses. Tests of the mechanical properties of bones may provide useful criteria for assessing the impacts of boron status on bone. These tests might resolve questions about optimal intakes of boron because mechanical properties sometimes respond to boron when composition of bones does not. Difficulty in interpreting some of the existing research arises because of the incipient state of knowledge regarding boron nutriture, to analytical problems associated with determining accurately the small quantities of boron in feed and tissues, and to technological difficulties in controlling extraneous exposure of experimental animals to boron. Yet there is considerable evidence that both compositional and functional properties of bone are affected by boron status.

In vitro autoradiographic localization of amylin binding sites in rat brain.

Amylin is a recently discovered 37 amino acid peptide which is co-secreted from the pancreas with insulin and acts to modulate carbohydrate metabolism. Recently, high-affinity binding sites for [125I]rat amylin have been identified in the rat central nervous system. These sites also have high affinity for the structurally related peptides calcitonin gene-related peptide and salmon calcitonin. In the present study we have used in vitro autoradiography to map the distribution of these [125I]rat amylin binding sites in rat brain. High to moderate levels of binding were present in mid-caudal accumbens nucleus, fundus striati and parts of the bed nucleus of the stria terminalis and substantia inominata. This binding extended caudally into parts of the amygdalostriatal transition zone and the central and medial amygdaloid nuclei. High to moderate levels of binding also occurred in much of the hypothalamus including the medial preoptic, dorsomedial hypothalamic and medial tuberal nuclei as well as the ventrolateral subnucleus of the ventromedial hypothalamic nucleus. Other regions of high level binding included the subfornical organ, the vascular organ of the lamina terminalis, area postrema, locus coeruleus, dorsal raphe and caudal parts of the nucleus of the solitary tract. The subfornical organ, vascular organ of the lamina terminalis and area postrema, which display some of the highest binding densities, lack a patent blood-brain barrier and thus could be responsive to blood-borne amylin. In conclusion we have mapped, in detail, the distribution of amylin binding sites in rat brain. The location of binding is consistent with potential roles for these sites in appetite, fluid and electrolyte homeostasis, autonomic function and regulation of mood.

Effects of magnesium deficiency on strength, mass, and composition of rat femur.

Magnesium (Mg) participates in the normal formation and remodeling of bone. However, little is known about effects of Mg status on the biomechanical function of bone. We examined gross morphometry and composition as well as biomechanical properties of the femurs of male rats fed diets adequate or deficient in Mg. Comparison of deficient animals and controls yielded a number of differences (all significant at P < 0.05). Mg-depleted animals exhibited slow growth, inefficient food utilization, and greatly reduced concentrations of Mg in both serum and femur ash. Compared with controls, femurs from depleted animals were shorter, but wet weights, diameters, and midfemoral cross-sectional areas showed no differences. Bone length was reduced to a greater degree than could be accounted for by differences in body weights between the groups. Bones of Mg-deficient rats contained less dry matter and less ash (which contained more Ca/g) than those of controls, along with a higher percentage of moisture. Significantly reduced bone strength in depleted animals was evident from the lighter loads supported at the elastic limit (yield point) and at fracture and from decreased stresses accompanying those loads. Modulus of elasticity, however, was not affected by Mg depletion. Different yield and breaking loads were related to different body weights of groups, but stresses were reduced for deficient bones even after adjusting for body size. Our data establish abnormal biomechanical behavior of cortical bone in Mg-deficient animals and emphasize the importance of measuring such functional properties of bone in the assessment of responses to altered metabolic conditions under experimental conditions.

Salmon calcitonin binding and stimulation of cyclic AMP generation in rat skeletal muscle.

Salmon calcitonin potently competes for amylin binding sites in rat brain and has amylin-like actions upon glucose metabolism in rat muscle. We report here that [125I]-salmon calcitonin binds to rat hindlimb muscle membranes with high affinity (Kd = 0.47 pM). Binding was inhibited by rat amylin (Ki = 2 nM), rat alpha CGRP (Ki = 8 nM), rat beta CGRP (Ki = 11 nM), and rat calcitonin (Ki = 64 nM). Binding was maximal when measured in a hypotonic NaHepes buffer, and was significantly reduced in affinity when salts of Mg++, Ca++, Na+ or K+ were present. Incubation of rat hindlimb muscle membranes with salmon calcitonin at concentrations of 10 pM and above stimulated cyclic AMP generation. These results describe a skeletal muscle binding site which may mediate some of the actions of exogenous salmon calcitonin and of endogenous amylin and related peptides upon skeletal muscle fuel metabolism.

High affinity amylin binding sites in rat brain.

Amylin, a 37-amino acid peptide structurally related to calcitonin gene-related peptide, is synthesized in and released along with insulin from pancreatic beta-cells. Amylin is proposed to act as an endocrine partner to insulin, in part through actions upon skeletal muscle that promote cycling of gluconeogenic precursors to liver. We report here that binding sites with high affinity (Kd = 27 pm) for radioiodinated rat amylin are present in the nucleus accumbens region of rat brain. Competition experiments show that sites measured in nucleus accumbens membranes have high affinity for rat amylin, lower affinity for rat calcitonin gene-related peptides, and very low affinity for rat calcitonin. In contrast to rat calcitonin, salmon calcitonin has a high affinity for these sites, indicating that it shares critical binding determinants with amylin. We further tested whether salmon calcitonin shares with amylin the ability to regulate glycogen metabolism in rat skeletal muscle. Salmon calcitonin potently inhibits insulin-stimulated glucose incorporation into rat soleus muscle glycogen, suggesting that rat skeletal muscle may also contain receptor populations that have high affinity for both amylin and salmon calcitonin.

Magnesium and immune function: recent findings.

Recent findings regarding roles for magnesium in immunocompetence confirm and extend previous knowledge of its participation in natural and adaptive immunity. The detrimental effects of severe magnesium deficiency have been confirmed. There is better comprehension of how magnesium relates to mechanisms that control cellular activities and regulate interactions among cells that affect immune functions. Insight has been gained into how magnesium status affects susceptibility to physiological disorders, such as cardiomyopathy and cancer, that are exacerbated by inflammation and by the chemical mediators of anaphylaxis. More information is needed about the impact of less severe magnesium deficiency and of supplemental magnesium on indicators of immune function. Future studies should explore interactive relationships between Mg and such nutrients as vitamin D to elucidate more completely the roles that Mg can play in optimizing immune function.

Effects of dietary magnesium and nickel on growth and bone characteristics in rats.

We examined the interaction of dietary magnesium (Mg) and nickel (Ni) on growth and, in particular, the size, composition and mechanical properties of bones in weanling rats. Male rats were fed a diet with 0.3, 1.0 or 2.0 times the recommended concentration of Mg and adequate amounts of other nutrients. After a week, groups fed the low- and high-Mg diets were subdivided and fed the same concentration of Mg plus 0 or 500 mg Ni/kg diet (from Ni chloride) for the remaining 7 weeks. Rats fed low Mg with added Ni grew slowly and had smaller femurs and vertebrae that contained less ash and withstood less force before breaking or compression than did bones of rats fed the low-Mg diet without Ni. However, the breaking stress calculated for femurs from Mg-depleted, Ni-supplemented animals was increased. Ni did not produce these effects when added to a diet high in Mg. Compared with high dietary concentrations, the low-Mg intake had little effect unless Ni was added.

A review of biointeractions of Ni and Mg. I. Enzyme, endocrine, transport, and skeletal systems.

Magnesium (Mg) and nickel (Ni) are biologically active elements in higher animals. Recent studies in vivo as well as in vitro point to interactions of Ni and Mg; non-immunological roles of these elements are reviewed here. Ni and Mg play roles in some of the same enzyme and endocrine systems, body and cell structures, and transport systems. Mg status has determined some responses to dietary Ni. Information available at this time is inadequate to permit assessment of all functions of Mg and Ni and their interactions in human populations. Evidence to date, however, warrants further investigation of the nutritional and metabolic relationships between these elements, over wide ranges of dietary intakes or exposure levels.

A review of biointeractions of Ni and Mg. II. Immune system and oncology.

Reports of interactions, in vivo and in vitro, between Ni and Mg in humoral and cellular immunity, hypersensitivity and inflammation, and in tumourigenesis are explored from a mechanistic viewpoint. Although Mg is present in much larger concentrations in normal mammalian systems than Ni, similar chemical and physical properties may allow Ni to exchange for Mg at reactive sites with damaging consequences to living organisms. Consequences of such exchanges could involve reduced immunocompetence and related carcinogenic transformation of cells. Mg status and environmental exposure to Ni are conceivable antecedents to possible biological sequelae in humans.

Anthropometric measurements of white and black southern adolescent girls.

Anthropometric measurements of 691 white and 550 black 12-, 14-, and 16-year-old girls from three income groups, residing in the southern United States, were evaluated, Heights, weights, mid-upper arm circumferences, and arm muscle areas of 14-year-old girls were significantly higher than those of 12-year-old girls and significantly lower than those of girls 16 years of age; triceps skinfolds, arm fat areas, and body mass indexes of 12-year-olds were significantly lower than those of older subjects. Blacks had significantly higher weights, body mass indexes, and arm muscle areas than whites. Black 12-year-old girls were significantly taller than white 12-year-old girls but significantly shorter than older girls of either race; white 16-year-old girls were significantly taller than blacks of that age. Body mass indexes of black 12-year-olds and white 14-year-olds were significantly higher than those of white 12-year-olds, and significantly lower than those of black 14- and 16-year-olds. Medium-income blacks and whites of all income levels had lower (usually significantly) weights, body mass indexes, mid-upper arm circumferences, arm muscle areas, and arm fat areas than low- and high-income blacks did. Anthropometric values of white, but not of black, girls were generally similar to those reported in surveys of primarily white girls.

Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females.

Response of iron, copper, and zinc status to supplementation with Zn or a combination of Zn and Fe was assessed in adult females in a 10-wk study. Group Z received 50 mg Zn/d as Zn gluconate; group F-Z received 50 mg Fe as ferrous sulfate monohydrate in addition to the Zn. For Group Z, serum ferritin, hematocrit, and erythrocyte Cu,Zn-superoxide dismutase (ESOD) were significantly lower (p less than 0.05) after 10 wk supplementation compared with pretreatment levels. Serum Zn increased (p less than 0.01) but no change occurred in serum ceruloplasmin, hemoglobin, or salivary sediment Zn with treatment. For Group F-Z ESOD decreased with treatment as did salivary sediment Zn (p less than 0.05). Serum ferritin and serum Zn increased significantly, but hemoglobin, hematocrit, and ceruloplasmin were not affected by this treatment. Supplementation with Zn poses a risk to Fe and Cu status. Inclusion of Fe with Zn ameliorates the effect on Fe but not on Cu status.

Self-esteem of adolescent girls as related to weight.

The Rosenberg Self-esteem Scale was administered to 550 14- and 16-yr.-old (+/- 6 mo.) girls. Self-esteem scores were categorized by weight and weight by height. Scores on the Quetelet Index for obesity were correlated with self-esteem scores. Mean self-esteem of the low- and middle-weight by height group was significantly higher than the mean of the high-weight by height group. In analyzing weight alone, the self-esteem of the middle-weight group was significantly higher than the self-esteem of the high-weight group. The correlation of the obesity index and self-esteem indicated that as weight increased self-esteem decreased.

Nutrients supplied by food groups in diets of teenaged girls.

Sources of nutrients were determined in diets of teenaged girls, a group generally thought to be at nutritional risk. This study of Southern adolescent girls of two races examines intakes of energy, energy-yielding nutrients, vitamins, minerals, and other components of various food groups. Effects of race, age, place of residence, and per capita income on nutrients furnished by food groups were determined from two 24-hour dietary recalls from each of 1,195 girls, aged 12, 14, or 16. Of the food groups examined, foods of low nutrient density provided the most energy, fat, and carbohydrate. The meat group provided the most protein. Dairy products, which supplied the largest amounts of six vitamins and minerals of any food group, were used less by black, rural, or older teenagers than by white, urban, or younger girls. Blacks obtained more vitamin A from vegetables and more thiamin from meat than whites. Amounts of meat, starchy, and low-nutrient-density subgroups also varied with race, age, and/or place of residence. As income increased, consumption of starches (especially breakfast cereals) and eggs decreased and that of fruit increased.

Factors related to blood pressure in a biracial adolescent female population.

Blood pressure levels, anthropometric parameters, and dietary intakes were assessed in 1981 and 1983 in a population of black (n = 236) and white (n = 296) adolescent girls, aged 14 and 16 years in 1983. The 14-year-old black girls exhibited significantly higher mean systolic and diastolic blood pressures than whites in both years. Body weight and Quetelet index were more strongly associated with blood pressure than were height and triceps skinfold thickness. Correcting blood pressures for weight, Quetelet index, 2-year changes in height, and age at menarche decreased in each case (but did not negate) the observed race differences in blood pressure. Dietary calcium and potassium intakes were inversely related to blood pressure, and a race difference in the intake of these nutrients (whites greater than blacks) was observed. Covariate adjustment for calcium, but not for potassium, decreased the magnitude of race differences in blood pressure. Family type (single-parent vs nuclear) and place of residence (urban vs nonurban) appeared to be the most important confounding variables for race differences in blood pressure, since differences largely were eliminated by controlling for these factors. Conflicting reports in the literature regarding the age range during which race differences in blood pressure become apparent may be partially attributed to the complex interrelationships among these factors and the potential influence of other genetic-environmental interactions that may also play a role in blood pressure regulation.