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Objective: The purpose of this study was to measure effects of chromium (Cr) and copper (Cu) depletion on lymphocyte reactivity to mitogens in diabetes-prone BHE/cdb rats., Methods: A 2 x 2 factorial research design was used, and 40 BHE/cdb rats were fed with Cr- and/or Cu-depleted diets or adequate Cr and/or Cu diets for 21 wk. Cr and Cu concentrations in diets and mineral concentrations of tissues of BHE/cdb rats were measured by using flame and graphite furnace atomic absorption spectrometry. Three glucose tolerance tests were performed to monitor the development of diabetes or glucose intolerance at weeks 12, 18, and 21. Splenocytes (2 x 10(6)) were incubated with phytohemagglutinin-l (PHA-L), concanavalin A (ConA), and lipopolysaccharides (LPSs), respectively, for 72 h. Four hours before the end of the incubation, splenocytes were pulsed with 3H-thymidine. The 3H-thymidine uptake by lymphocytes was used to calculate a stimulation index., Results: According to glucose tolerance tests, these rats did not develop diabetes or impaired glucose tolerance throughout the study. Average Cr concentrations were 0.98 to 1.03 mg Cr/kg of diet in adequate Cr diets and 8.2 to 14 micrograms Cr/kg of diet in Cr-depletion diets. Average Cu concentrations were 3.6 to 6.4 mg Cu/kg of diet in adequate Cu diets and 1.1 to 1.3 mg Cu/kg of diet in Cu-depletion diets. Organ weights did not differ significantly among treatment groups at the end of the study. Cr or Cu depletion significantly affected iron, zinc, and magnesium concentrations in the liver. A significant interactive effect of Cr and Cu was observed on lymphocyte proliferation with PHA-L stimulation at 25 micrograms/mL (P < 0.006). However, there were no significant effects of dietary treatment on lymphocyte proliferation with 10 micrograms/mL of PHA-L, ConA, or LPS stimulations., Conclusions: When Cr and Cu were adequate in the diets, there was an enhanced effect of Cu or Cr on lymphocyte proliferation. However, when Cr was depleted in the diet, there was a suppressive effect of Cu on lymphocyte proliferation. This result indicates that adequate amounts of Cr and Cu in the diet support the immune system.

The purpose of this study was to analyse effects of chromium and/or copper supplementation on immune function in hypercholesterolaemic postmenopausal women. A 2 x 2 factorial research design was used and 40 subjects were supplemented with 0.394 g lactose, 200 microg Cr, 3.0 mg Cu, or 200 microg Cr and 3.0 mg Cu/d for 12 weeks. A significant interactive effect of Cr and Cu supplementation on lymphocyte proliferation was observed with ConA 50 microg/ml stimulation. After 12 weeks of supplementation, ConA-stimulated (50 microg/ml) lymphocyte proliferation was significantly lower when Cu was added to the Cr supplementation group. Moreover, ConA-stimulated (100 microg/ml) lymphocyte proliferation was significantly lower in the Cu supplementation group compared to the Cr supplementation group after 12 weeks of supplementation. These results suggest that Cu blocks enhancement of lymphocyte proliferation by Cr supplementation and that Cu supplementation has potential suppressive effects on the immune function in these subjects.

Chromium (Cr) depletion may exacerbate hyperglycemia and negative outcomes of pregnancy in the streptozotocin (STZ) diabetic pregnant rat model through the regulation of the insulin-like growth factor (IGF) system. To test this hypothesis, 40 female rats, all fed a low Cr diet (i.e., 70 microgram Cr/kg diet ) from 21 d of age, were randomly assigned one of four treatments, applied on Day 1 of pregnancy, in a 2 x 2 factorial design: 1) very low Cr diet (40 microgram Cr/kg diet) + citrate buffer injection, 2) very low Cr diet + STZ injection (30 mg STZ/kg body wt in citrate buffer), 3) adequate Cr diet (2 mg Cr [from added CrK(SO4)2]/kg diet) + citrate buffer injectionand 4) adequate Cr diet + STZ injection. Blood and tissues were collected on Day 20 of pregnancy. Chromium depletion increased (P < 0.05) urinary hydroxyproline excretion, 22-kDa IGF binding protein (IGFBP) concentration and litter size but decreased (P < 0. 05) placental wt, percentage of protein per fetus, and fetal IGF-I and -II concentrations. Chromium had no effect (P > 0.10) on maternal hormones, 32-kDa IGFBP, glucose, or placental and fetal hydroxyproline concentrations. Diabetes decreased (P < 0.05) maternal wt gain, embryonic survival, litter size, mean pup wt and maternal insulin concentrations, increased (P < 0.05) maternal blood glucose, IGF-I concentrations and maternal hydroxyproline excretion but did not affect fetal concentrations of hormones, IGFBP, glucose or hydroxyproline. Interaction between chromium and diabetes tended (P < 0.10) to affect maternal IGF-II concentrations, but had no effect on other maternal or fetal variables. In conclusion, maternal chromium depletion did not exacerbate hyperglycemia or pregnancy outcome in STZ-induced diabetic rats, but may negatively affect fetal protein content by decreasing fetal IGF-II concentrations. Diabetes may negatively affect fetal growth through its effect on maternal glucose, insulin and IGF-I.

Drug-nutrient interactions affecting chromium were investigated in this study. Rats were injected with indomethacin to reduce endogenous prostaglandin synthesis and dosed with prostaglandin analogues or prostacyclin. Effects on absorption, tissue distribution and urinary excretion of 51Cr from 51CrCl3 were evaluated using a 2 x 4 factorial experimental design. Forty-eight adult male rats were food deprived for 12 h and then injected intraperitoneally with indomethacin (5 mg/kg body wt) or placebo. Thirty minutes later, rats were intubated and dosed with one of four treatments: a prostaglandin E1 analogue (misoprostol) at 50 microg/kg body wt; a prostaglandin E2 analogue (16,16-dimethylprostaglandin E2) at 7.5 microg/kg body wt; prostacyclin at 20 microg/kg body wt; or control (7.64 mmol/L Tween-80 suspended in 0.15 mol/L NaCl containing 0.48 mol/L ethanol). Immediately after intubation, rats were dosed with 3.7 mBq of 51CrCl3 by micropipette. Blood was collected from the tail at intervals after 51Cr dosing. Six hours after dosing, 51Cr rats were exsanguinated by cardiac puncture. Indomethacin, an inhibitor of prostaglandin synthesis, significantly increased (P < 0.05) 51Cr in blood at all time periods tested except at 15 min. In tissues, indomethacin significantly increased 51Cr retention. Urinary 51Cr excretion at 6 h was higher (P < 0.05) in indomethacin-pretreated rats than in control rats. Administration of indomethacin, which blocks prostaglandin synthesis, enhanced 51Cr absorption, whereas dosing with 16,16-dimethylprostaglandin E2 decreased 51Cr absorption.

The 10th edition (1989) of the Recommended Dietary Allowances provided estimated safe and adequate daily dietary intakes (ESADDI) for chromium and fluoride and summarized the substantial evidence for boron essentiality in animals. New endpoints, approaches and paradigms to use to formulate dietary guidance for these elements were reviewed by a discussion group that met as part of a national workshop. Deliberations of the group are summarized to facilitate future discussions on dietary guidance for these elements. The category, "provisional RDA" was recommended to replace the current ESADDI category because of the ambiguities associated with the ESADDI. A provisional RDA would be defined for a dietary substance that meets one of two sets of criteria: class 1, clear evidence of essentiality but uncertain or limited quantitative data or endpoints to define dietary requirements; and class 2, strong evidence of essentiality, and clear nutritional benefit based on reasonably certain quantitative data, but lack of clear information on function or endpoints to use for deficiency dietary requirements. A summary of background information and possible approaches for assigning provisional RDAs for boron, chromium and fluoride is presented.

Chromium (Cr) potentiates the effects of insulin and a role for insulin in ascorbic acid transport has been reported. Therefore, the effects of Cr and ascorbate depletion on tissue ascorbic acid and 14C distribution and excretion after a 14C ascorbate dose were investigated in guinea pigs. As utilization of dietary Cr is affected by interaction with other minerals, tissue manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) were examined. For 20 wk, 40 weanling animals were fed either a Cr-deficient (< 0.06 micrograms Cr/g diet, -Cr) or a Cr-adequate (2 micrograms Cr from CrCl3/g diet, +Cr) casein-based diet and were given 1 mg ascorbate/d (-C) or 10 mg ascorbate/d (+C) for 20 wk. Animals fed the Cr-depleted diet had decreased weight at 20 wk (p < 0.01). Six hours before necropsy, animals were dosed by micropipette with 1.8 microCi of L-[carboxyl-14C] ascorbic acid and placed in metabolic cages. Ascorbate supplementation increased Fe concentrations in most analyzed tissues, hepatic 14C, tissue ascorbate and Mn concentration in the adrenal and testes, but decreased the concentrations of Cu in the kidney and Mn in the spleen. Liver Mn concentration was higher and kidney Mn concentration was lower in +Cr animals. Interactions between Cr and ascorbic acid affected Mn concentrations in bone and brain. These results indicate that ascorbate and Cr may affect Mn distribution. Chromium supplementation decreased plasma cortisol, brain 14C and the amount of 14C expired as carbon dioxide. These findings suggest that dietary Cr may affect ascorbic acid metabolism and the metabolic response to stress.

Vanadium has been reported to affect numerous physiological processes; however, a demonstration that vanadium deficiency consistently impairs biological function is lacking. The purpose of this study was to determine if the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, is affected by dietary supplementation of vanadate and/or chronic ascorbic acid deficiency. To determine if vanadium and/or ascorbic acid affected mineral metabolism, tissue minerals also were analyzed. Weanling male guinea pigs were assigned randomly to groups of 10 in a 2 x 2 factorial design. The dietary variables were ascorbate, 0.5 or 10 mg/day, and vanadium < 0.01 microgram or 0.5 microgram/g diet as NH4VO3 in a low Cr diet containing < 0.07 microgram Cr/g diet. After 21 weeks on this diet, guinea pigs receiving more ascorbate had lower liver weight/body weight ratios and increased bone copper. Testes weight/body weight ratios, hepatic glycogen and bone copper decreased while hepatic lipids, fecal bile acids, plasma cortisol and bone calcium and magnesium were increased by vanadium supplementation. An interaction between vanadium and ascorbate affected cholesterol excretion in feces, hepatic iron, plasma cholesterol concentration and the activity of HMG CoA reductase. This study provides evidence of increased bone mineral concentrations with vanadium supplementation and of an interaction between vanadium and ascorbate which affected cholesterol metabolism.

Forty-eight male genetically obese (OB) mice (C57BL/6J-OB) and 48 lean male littermates were randomly assigned within main plots (OB or lean) to one of eight diets. Diets were low chromium or supplemented with 1 mg chromium as CrCl3 per kg. Starch, sucrose, fructose or glucose comprised 50% of the diet, which met AIN recommendations except for chromium. Experimental diets and deionized water were available ad libitum for 26 d. Mice were fasted 10 h and were intubated 2 h before killing with 15 microCi of 51CrCl3 in a 25% carbohydrate solution (2 mg carbohydrate/g body wt) of either starch, sucrose, glucose or fructose corresponding to the diet previously fed. 51Cr concentrations were significantly higher in the blood, liver, spleen, epididymal fat pad, testes and femur of animals given their carbohydrate load as starch than in animals fed sucrose, fructose or glucose. Carbohydrate had a significant effect on chromium concentrations of testes, spleen, kidney and liver with values generally being higher with the starch diet. Chromium supplementation increased bone and kidney chromium concentrations and heart and muscle glycogen. These data indicate that the source of carbohydrate can alter chromium absorption and retention.