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Although calcium (Ca) supplementation increases bone density, the increase is small and the effect on bone strength and fracture risk is uncertain. To investigate if bone mass, morphology, and biomechanical properties are affected by deficient to copious dietary Ca concentrations, the long bones (tibia and femur) of growing female Sprague-Dawley rats (8/group) were assessed after 13 wk of consuming 1, 2, 3, 4, 5, 6, or 7 g Ca/kg of a modified AIN-93G diet. Dietary phosphorous (P) and vitamin D remained constant at recommended concentrations. The assessment included mineralization, density, biomechanical properties of breaking by a 3-point flexure test, and morphological properties by microcomputed topography scanning of trabecular bone of the proximal tibia metaphysis. Dietary treatment did not affect food intake, weight gain, renal and muscle Ca concentrations, and bone hydroxyproline. All bone parameters measured were significantly impaired by Ca deficiency in rats fed the diet containing 1 g Ca/kg. Modest impairments occurred with some parameters (bone density, biomechanical bending moment, modulus of elasticity, and stress) in rats fed 2 g Ca/kg, but all parameters stabilized between 2 and 3 g/kg diet, with no differences between 3 and 7 g/kg. The results suggest that a threshold response in bone Ca retention or bone mass at ~2.5 g Ca/kg diet is associated with similar threshold responses in bone breaking strength and related biomechanics as well as trabecular structural properties. There was no evidence of a relative P deficiency or of improved or impaired bone strength and structure as Ca intakes increased beyond those needed to maximize bone density.

Commercial elemental iron powders (electrolytic and reduced iron), as well as heme iron supplements, were tested for efficacy in improving the iron status of women. In a randomized, double-blind trial, 51 women with moderate to low iron stores received daily for 12 wk: 1) placebo, 2) 5 mg iron as heme iron or 50 mg iron as 3) electrolytic iron, 4) reduced iron, or 5) FeS[O.sub.4]. Treatments were provided in 2 capsules (heme carrier) and 3 wheat rolls (other iron sources). Differences in iron status, food nonheme iron absorption, and fecal properties were evaluated. Body iron, assessed from the serum transferrin receptor:ferritin ratio, increased significantly more in subjects administered FeS[O.sub.4] (127 [+ or -] 29 mg; mean [+ or -] SEM) and electrolytic (115 [+ or -] 37 mg), but not the reduced (74 [+ or -] 32 mg) or heme (65 [+ or -] 26 mg) iron forms, compared with those given placebo (2 [+ or -] 19 mg). Based on body iron determinations, retention of the added iron was estimated as 3.0, 2.7, 1.8, and 15.5%, in the 4 iron-treated groups, respectively. Iron treatments did not affect food iron absorption. The 50 mg/d iron treatments increased fecal iron and free radical-generating capacity in vitro, but did not affect fecal water cytotoxicity. In subjects administered FeS[O.sub.4], fecal water content was increased slightly but significantly more than in the placebo group. In conclusion, electrolytic iron was ~86% as efficacious as FeS[O.sub.4] for improving body iron, but the power of this study was insufficient to detect any efficacy of the reduced or heme iron within 12 wk. With modification, this methodology of testing higher levels of food fortification for several weeks in healthy women with low iron stores has the potential for economically assessing the efficiency of iron compounds to improve iron status.

Despite extensive use, information on the bioavailability of elemental iron powders to humans, as influenced by dose and other dietary constituents, is limited. Three experiments were conducted to assess the absorption of electrolytic iron powder relative to FeS[O.sub.4], as affected by iron dose and by ascorbic or phytic acid. Iron absorption by 56 volunteers was measured from a farina cereal breakfast radiolabeled with [sup.59]FES[O.sub.4] or an electrolytic [sup.55]Fe powder irradiated by neutron activation. Absorption was determined from whole-body counting ([sup.59]Fe) and blood isotope incorporation 2 wk later. Absorption of iron from the irradiated electrolytic powder was 5-15% that of FeS[O.sub.4]. Ascorbic acid (~160 mg) enhanced iron absorption from FeS[O.sub.4] by almost 4-fold but only doubled absorption from electrolytic iron (P for interaction < 0.01 ). Phytic acid from wheat bran inhibited iron absorption from FeS[O.sub.4] and electrolytic iron by 73 and 50%, respectively (P for interaction, NS). Compared with 3 mg, a 20-mg dose reduced fractional absorption from FeS[O.sub.4], but not electrolytic iron (P for interaction < 0.0001). Despite a much higher bioavailability (50% relative to FeS[O.sub.4]) of this same electrolytic iron when tested previously in a pig model, the bioavailability of the irradiated electrolytic iron was poor in humans. The diminished influence of ascorbic acid on the absorption of less soluble iron sources such as elemental iron powders may be an important consideration when choosing iron fortificants.

Foods are fortified with elemental forms of iron to reduce iron deficiency. However, the nutritional efficacy of current, commercially produced elemental iron powders has not been verified. We determined the bioavailability of six commercial elemental iron powders and examined how physicochemistry influences bioavailability. Relative biological value (RBV) of the iron powders was determined using a hemoglobin repletion/slope ratio method, treating iron-deficient rats with repletion diets fortified with graded quantities of iron powders, bakery-grade ferrous sulfate or no added iron. Iron powders were assessed physicochemically by measuring iron solubility in hydrochloric acid at pH 1.0 and 1.7, surface area by nitrogen gas adsorption and surface microstructure by electron microscopy. Bioavailability from the iron powders, based on absolute iron intake, was significantly less than from [FeSO.sub.4] (100%; P < 0.05) with the following rank order: Carbonyl (64%; Ferronyl, U.S.) > Electrolytic (54%; A-131, U.S.) > Electrolytic (46%; Electrolytic Iron, India) > H-Reduced (42%; AC-325, U.S.) > Reduced (24%; ATOMET 95SP, Canada) > CO-Reduced (21%; RSl-325, Sweden). Solubility testing of the iron powders resulted in different relative rankings and better RBV predictability with increasing time at pH 1.7 ([R.sup.2] = 0.65 at 150 min). The prediction was improved with less time and lower pH ([R.sup.2] = 0.82, pH 1.0 at 30 min). Surface area, ranging from 90 to 370 [m.sup.2]/kg, was also highly predictive of RBV ([R.sup.2] = 0.80). Bioavailability of iron powders is less than bakery-grade ferrous sulfate and varies up to three times among different commercial forms. Solubility at pH 1.0 and surface area were predictive of iron bioavailability in rats. KEY WORDS: * iron absorption * elemental iron powder * food fortification * iron bioavailability * hemoglobin repletion * rats

Calcium balance is decreased by an increased intake of purified proteins, although the effects of common dietary sources of protein (like meat) on calcium economy remain controversial. We compared the effects of several weeks of controlled high and low meat diets on body calcium retention, using sensitive radiotracer and whole body scintillation counting methodology. Healthy postmenopausal women (n = 15) consumed diets with similar calcium content (~600 mg), but either low or high in meat (12 vs. 20% of energy as protein) for 8 wk each, in a randomized crossover design. After 4 wk of equilibration of each diet, calcium retention was measured by extrinsically labeling the 2-d menu with [sup.47]Ca, followed by whole body scintillation counting for 28 d. Urinary and blood indicators of bone metabolism were also determined for each diet. Calcium retention was not different during the high and low meat dietary periods (d 28, mean [+ or -] pooled SD: 17.1 and 15.6%, [+ or -] 0.6%, respectively; P = 0.09). An initially higher renal acid excretion in subjects consuming the high meat compared with the low meat diet decreased significantly with time. The diets did not affect urinary calcium loss or indicators of bone metabolism. In conclusion, under controlled conditions, a high meat compared with a low meat diet for 8 wk did not affect calcium retention or biomarkers of bone metabolism in healthy postmenopausal women. Calcium retention is not reduced when subjects consume a high protein diet from common dietary sources such as meat. J. Nutr. 133: 1020-1026, 2003. KEY WORDS: * calcium * meat protein * postmenopausal * osteoporosis * renal acid

With reduced intake of meat and increased intake of phytate-containing legumes and whole grains, movement toward plant-based diets reduces dietary iron and zinc absorption. Although vegetarians have lower iron stores, adverse health effects of lower iron and zinc absorption have not been demonstrated with varied, plant-based diets consumed in developed countries. Improved assessment methods and monitoring are needed to detect and prevent possible iron and zinc deficiency with plant-based diets. Key Words: phytate-containing legumes, whole grains, plant-based diet, iron, zinc

This study was designed to examine the interactions among dietary iron (Fe), copper (Cu), and zinc (Zn) and their effects on Fe status and oxidative stress in female rats. In a three-factor central composite response surface design, rats were assigned to 15 groups and fed modified AIN-93G basal diets with varying amounts of Fe and Zn (7.0, 15.5, 45.8, 135.6, or 300 [[micro]gram]/g diet) and Cu (0.5, 1.1, 3.2, 9.2, or 20 [[micro]gram]/g diet) for 6 wk. Variations in hemoglobin, hematocrit, and serum ferritin were mainly related to dietary Fe. Liver nonheme Fe was directly affected by dietary Fe and was slightly attenuated by interactions between Cu and Zn, and Zn and Fe. Serum ceruloplasmin activity was primarily determined by an interaction between Cu and Zn with substantial moderation by the quadratic effect of dietary Cu. Liver and heart total superoxide dismutase (SOD) and Cu/Zn SOD activities were directly affected by dietary Cu. Dietary Fe was the only significant, yet weak, predictor of liver thiobarbituric acid reactive substances (TBARS) and vitamin E content and serum triacylglycerols. Variability in serum Cu was mostly determined by the interaction between Cu and Fe, with modification from the quadratic effect of dietary Cu. Serum Zn varied with dietary Zn with a small negative influence from the interaction between Cu and Fe. In summary, Fe status was minimally influenced by dietary Zn or Cu, and Fe intakes 10-fold greater than required did not induce overt oxidative stress in female rats. In addition, measures of antioxidant capacity were primarily influenced by dietary Cu and were optimal at moderate intakes of this micronutrient. KEY WORDS: * iron * copper * zinc * oxidative stress * response surface * female rats

In addition to determining the amounts of isolated nutrients required for physiological function and homeostatic control, setting Recommended Dietary Allowances requires a consideration of nutrient bioavailability from foods in common diets. Bioavailability algorithms, or mathematical models to estimate nutrient bioavailability from different diets, have great appeal to help establish recommended intakes and identify beneficial dietary modifications. Accurate algorithms are difficult to develop because of the chemical complexity of the food supply and the numerous interactions that affect the bioavailability of mineral elements. A combination of reductionist and holistic approaches is necessary to identify the effects of isolated dietary components, and then to evaluate these effects in the complicated matrix of a whole diet. The most extensive development of bioavailability algorithms for mineral nutrients has been for iron, and understanding the strengths and weaknesses of the iron algorithms may help in development of algorithms for other inorganic nutrients such as zinc. Examples are provided to indicate the possible revision of iron bioavailability algorithms, the difficulty of verifying the iron bioavailability algorithms with iron status indices, and the possible development of zinc bioavailability algorithms. Bioavailability must be considered in the context of the biological control of mineral absorption, utilization and excretion, which may outweigh the importance of mineral bioavailability from diets in affluent countries with a varied and abundant food supply. While bioavailability algorithms may be helpful in estimating the effects of dietary changes or recommendations, and in improving diets of populations with a high incidence of deficiency of the mineral, they are not as yet sufficiently developed and validated for setting quantitative recommendations for 'bioavailable' mineral intake. J. Nutr. 126: 2345S-2353S, 1996. INDEXING KEY WORDS: * iron * zinc * absorption * bioavailability algorithms

The effect of dietary protein on zinc requirement and zinc bone deposition in growing rats was investigated. It was shown that high levels of dietary protein increased the dietary requirement for zinc, reduced feed intake and growth in zinc-deficient rats, and increased zinc deposition on bones in rats with adequate dietary zinc. High protein diets also decreased the organic matrix of bone while increasing zinc deposition. This indicates that excess dietary protein results in a metabolic disorder rather than an enhancement of the zinc's bioavailability.

A category of compounds called nutraceuticals has been proposed as a new regulatory category separate from current US Food and Drug Administration (FDA) regulations for food or drugs. The Nutraceutical […]

Edited by Donald B. McCormick, Dennis M. Bier, and Robert J. Cousins, Palo Alto, Calif.: Annual Reviews; 2000. Hardcover. Pp 745. ISBN: 0-8243-2820-5 The latest volume of this series builds [...]

Should commercial multivitamin supplements be recommended for all adults? Recent papers in the Journal of the American Medical Association (JAMA) reviewed the scientific literature on vitamin supplementation (1) and recommended [...]

Should overnutrition rather than undernutrition be the principle iron-related concern in modern industrialized countries? This multiauthored work attempts, with mixed success, to implicate iron in infection, aging, cardiovascular disease, cancer, [...]

This is a collection of multiauthored papers presented at the Ninth Annual Bristol-Myers Squibb/Mead Johnson Symposium on Nutrition Research, held September 11 to 13, 1989, in England. The contributors have [...]