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A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving.

BACKGROUND: : In a small pilot trial, patients with atypical depression demonstrated significant positive therapeutic response to chromium picolinate. This finding is of interest because of the demonstrated link between depression, decreased insulin sensitivity, and subsequent diabetes and chromium picolinate's insulin enhancing effect. METHODS: : In this double-blind, multicenter, 8-week replication study, 113 adult outpatients with atypical depression were randomized 2:1 to receive 600 mug/day of elemental chromium, as provided by chromium picolinate (CrPic), or placebo. Primary efficacy measures were the 29-item Hamilton Depression Rating Scale (HAM-D-29) and the Clinical Global Impressions Improvement Scale (CGI-I). RESULTS: : Of the 113 randomized patients, 110 (70 CrPic, 40 placebo) constituted the intent-to-treat (ITT) population (i.e., received at least one dose of study medication and completed at least one efficacy evaluation) and 75 (50 CrPic, 25 placebo) were evaluable (i.e., took at least 80% of study drug with no significant protocol deviations). In the evaluable population, mean age was 46 years, 69% were female, 81% were Caucasian, and mean body mass index (BMI) was 29.7. There was no significant difference between the CrPic and placebo groups in both the ITT and evaluable populations on the primary efficacy measures, with both groups showing significant improvement from baseline on total HAM-D-29 scores during the course of treatment (p < 0.0001). However, in the evaluable population, the CrPic group showed significant improvements from baseline compared with the placebo group on 4 HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and diurnal variation of feelings. A supplemental analysis of data from the subset of 41 patients in the ITT population with high carbohydrate craving (26 CrPic, 15 placebo; mean BMI = 31.1) showed that the CrPic patients had significantly greater response on total HAM-D-29 scores than the placebo group (65% vs. 33%; p < 0.05) as well as significantly greater improvements on the following HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and genital symptoms (e.g., level of libido). Chromium treatment was well-tolerated. LIMITATIONS: : The study did not include a placebo run-in period, did not require minimum duration or severity of depression, and enrolled patients with major depression, dysthymia, or depression NOS. CONCLUSIONS: : In a population of adults with atypical depression, most of whom were overweight or obese, CrPic produced improvement on the following HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and diurnal variation of feelings. In a subpopulation of patients with high carbohydrate craving, overall HAM-D-29 scores improved significantly in patients treated with CrPic compared with placebo. The results of this study suggest that the main effect of chromium was on carbohydrate craving and appetite regulation in depressed patients and that 600 mug of elemental chromium may be beneficial for patients with atypical depression who also have severe carbohydrate craving. Further studies are needed to evaluate chromium in depressed patients specifically selected for symptoms of increased appetite and carbohydrate craving as well as to determine whether a higher dose of chromium would have an effect on mood.

Adult↗

Effect of chromium picolinate on modified forced swimming test in diabetic rats: involvement of serotonergic pathways and potassium channels.

Depression occurs frequently in patients with diabetes mellitus. Chromium picolinate, an essential trace element is recommended for diabetes and also has been reported to benefit depression, but its mechanism is still debated. To investigate the mechanism, we studied its effects on serum insulin, serum glucose and on modified forced swimming test, a behavioural paradigm for depression in rats. The study involving co-administration of sub-active doses of glimepiride, a K(+) channel blocker and chromium picolinate on blood glucose levels and modified forced swimming test was also performed to probe any role of K(+) channels in its antidiabetic and antidepressants effects. Streptozotocin (55 mg/kg, intraperitoneally) was injected in rats to induce diabetes (Type 1). After a week, chromium picolinate (8 microg/ml in drinking water) was administered for 4 weeks. Normal rats received similar drug treatment. The sub-active doses of chromium picolinate (4 microg/ml in drinking water) and glimeperide (2.5 mg/kg, orally) were co-administered and their effects on modified forced swimming test and on glucose levels were measured. Chromium picolinate (8 microg/ml in drinking water) produced hypoglycaemia in diabetic and normal rats. It had no effects on the streptozotocin-induced reduction in insulin levels. Chromium picolinate (8 microg/ml in drinking water) increased swimming with subsequent decrease in immobility. The sub-active doses of chromium picolinate and glimeperide showed significant additive effects in modified forced swimming test and reduction in serum glucose concentrations, though statistically insignificant. In conclusion chromium picolinate shows antidepressant action on modified forced swimming test affecting only swimming that suggests serotonergic pathways involvement. The additive effects on swimming in modified forced swimming test and reduction in serum glucose levels shows involvement of K(+) channels in antidiabetic and antidepressant actions of chromium picolinate.

Animals↗

Chromium concentrations in serum, blood clot and urine from patients following total hip arthroplasty.

Chromium released from implant alloys may be incorporated into organometallic complexes as Cr3+ [Cr(III)] or CR6+[Cr(VI)]. Since Cr(VI) is far more biologically active than Cr(III), there is considerable interest in identifying the valence state that predominates in corrosion products, either in vitro or in vivo. It is known that erythrocytes display a unidirectional uptake of Cr(VI) while effectively excluding Cr(III). Thus it was felt that a study of the chromium content of blood clot, in comparison to chromium concentrations in serum and urine, could shed light on the valency question. Fourteen patients who received conventional polymethylmethacrylate cemented cobalt-chromium alloy/ultra high molecular weight polyethylene total hip replacements as well as seven control patients who underwent orthopaedic procedures without implantation were studied. Blood and urine specimens were obtained preoperatively, post-operatively and, for total hip patients, at routine early follow up. Chromium content was determined by electrothermal atomic absorption spectroscopy. A significant post-operative rise in serum chromium content was observed for total hip replacement patients, as previously reported, but not for control patients. Unexpected day-to-day variations in clot chromium content, without significant increases, were also observed. Longer time studies are required to determine chromium valence states in corrosion products in this model.

Adult↗

Chromium picolinate increases membrane fluidity and rate of insulin internalization.

The effects of chromium chloride, chromium nicotinate, and chromium picolinate on insulin internalization in cultured rat skeletal muscle cells was examined. Insulin internalization was markedly increased in cells cultured in a medium that contained chromium picolinate and the increased internalization rate was accompanied by a marked increase in the uptake of both glucose and leucine. The effect was specific for chromium picolinate since neither zinc picolinate nor any of the other forms of chromium tested was effective. The increased insulin internalization rate may result from an increase in membrane fluidity since chromium picolinate and to a lesser extent, chromium nicotinate, increased the membrane fluidity of synthetic liposomal membranes.

Animals↗

A comparison of the insulin-sensitive transport of chromium in healthy and model diabetic rats.

In response to insulin, chromium(III) is moved from the blood to the tissues where it is ultimately lost in the urine, apparently as the oligopeptide chromodulin; this transfer of chromium is mediated by the protein transferrin. To examine the effects of type 1 and type 2 diabetes on the transport of chromium, the fate of chromium from intravenously introduced (51)Cr(2)-labelled transferrin was monitored after 2 h in healthy and diabetic model rats; the effects of insulin on the transport of chromium in these groups were also examined. Diabetic rats had greater urinary chromium loss, greater movement of chromium from the blood to the tissues, most notably to the skeletal muscle, and an alteration of the distribution of chromium in the blood plasma.

Animals↗

Kinetics of an intratracheally administered chromium catalyst in rats.

Chromium-based catalysts are used for the synthesis of polyethylene, but little is known about the hazard and biomonitoring possibilities of this type of chromium for workers who may be occupationally exposed to such compounds. Therefore, the bioavailability and toxicokinetics of chromium were studied in male Wistar rats after a single intratracheal instillation (2 ml/kg body weight) of various doses (1, 5, or 25 mg/kg body weight) of the catalyst (approximately 1% chromium bound to an amorphous silica matrix), either before (CAT-Cr[III]) or after (CAT-Cr[VI]) heat treatment. The results were compared with those of equivalent amounts of two chromium salts (CrCl(3) and K(2) Cr(2) O (7). Each dose group was composed of three rats. The concentration of chromium was determined by atomic absorption spectrometry in urine (collected daily for 7 d) and in plasma, erythrocytes, lung, and liver tissue obtained 2 d (only highest concentration) and 7 d after dosing. On d 2, a significant increase in lung weight was found in the animals treated with the highest dose of the hexavalent Cr products. On d 7, on the basis of body weights, lung weights, and lung histology, there was no overt toxicity, except after the highest dose of CAT-Cr(VI). The elimination of all forms of chromium was apparently monoexponential, with calculated half-life elimination times in urine of 4-11 h for Cr(III) (CAT-Cr[III] and CrCl3 ) and 8-21 h for Cr(VI) (CAT-Cr[VI] and K(2) Cr(2) O(7). On d 2, the erythro-cytes Cr concentrations were significantly higher for the hexavalent Cr products than for the trivalent Cr products. After 7 d, the erythrocytes Cr concentrations were significantly increased above control values (3 microg/L) only in rats treated with the 2 highest doses of Cr( VI) compounds (12 and 64 microg/L for K(2) Cr(2) O(7), and 14 and 79 microg/L for CAT-Cr[VI]). The present study shows that intratracheally instilled Cr(VI) and Cr(III) have different toxicokinetic profiles and that the Cr(VI) catalyst has the same bioavailability and excretion kinetics as a water-soluble Cr(VI) salt. Exposure to chromium compounds could be monitored by measuring Cr concen-trations in urine (shortly after exposure) and in erythrocytes (also at later time points after high Cr[VI] exposure).

Animals↗

Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics.

A placebo-controlled double-blind cross-over study was carried out to assess the effect of chromium supplementation (200 micrograms trivalent chromium daily for 6 wk) on glucose tolerance, insulin response, long-term diabetic control, and serum lipids in 10 noninsulin-dependent diabetics aged 37 to 68 yr. After chromium supplementation 24-h urinary chromium excretion showed a 9-fold increase indicating a positive chromium balance in the subjects. There was no significant difference between chromium supplementation and placebo periods in glucose tolerance and in fasting or 2-h postglucose serum insulin levels but the 1-h postglucose serum insulin level was slightly lower on chromium supplementation than on the placebo (55 +/- 9.0 versus 64 +/- 11; p less than 0.01, paired t test). Serum total cholesterol and triglycerides and their high-density, low-density, and very low-density lipoprotein subfractions showed no change after chromium supplementation as compared to the placebo period.

Adult↗

Increased chromium uptake in polymorphonuclear leukocytes from burned patients.

Following thermal injury neutrophil function is severely impaired and thought to be hypometabolic; however, the host is considered to be hypermetabolic. To further investigate the metabolism and the function of neutrophils following thermal injury, neutrophil migration and chromium uptake were studied using radio-labelled neutrophils. Random and directed migration were found to be significantly reduced compared to control values. Neutrophil lysozyme content was also reduced in these burn cells while serum lysozyme from the same patients was significantly elevated over control values. These data suggest lysozyme is released by the neutrophil into the circulatory system. The influx of chromium in cells from burned patients was much greater than the influx in normal cells used in studies for chemotaxis. Influx of chromium over time and over varying concentrations of chromium was linear (r2 = 0.90) in cells from burned patients and normals. Cells from burned patients, however, took up more chromium than normals. Influx velocity of chromium was also determined and found to be greater in burn cells than normal cells. Since it has been shown that chromium influx is an energy-dependent reaction it is suggested that cellular energy stores are being depleted by the influx of chromium. Whether this is a response to an intracellular deficit or uncoupling of metabolic pathways is not known at this time.

Adult↗

Pro-oxidative vs antioxidative properties of ascorbic acid in chromium(VI)-induced damage: an in vivo and in vitro approach.

The effect of antioxidant ascorbic acid (vitamin C) pretreatment on chromium(VI)-induced damage was investigated using the yeast Saccharomyces cerevisiae as a model organism. The objective of this study was to pretreat yeast cells with the antioxidant ascorbic acid in an effort to increase cell tolerance against reactive chromium intermediates and reactive oxygen species formed during chromium(VI) reduction. Intracellular oxidation was estimated using the fluorescence indicators dihidro-2,7-dichlorofluorescein, dihydroethidium and dihydrorhodamine 123. The role of ascorbic acid pretreatment on chromium(VI) toxicity was determined by measuring mitotic gene conversion, reverse mutations, 8-OHdG, hydroxyl radical, superoxide anion and chromium(V) formation. The chromium content in the biomass was determined by flame atomic absorption spectrometry. In the absence of chromium, ascorbic acid effectively protected the cells against endogenous reactive oxygen species formed during normal cellular metabolism. In vitro measurements employing EPR and the results of supercoiled DNA cleavage revealed that the pro-oxidative action of ascorbic acid during Cr(VI) reduction was concentration-dependent and that harmful hydroxyl radical and Cr(V) had formed following Cr(VI) reduction. However, the in vivo results highlighted the important role of increased cytosol reduction capacity related to modification of Cr(V) formation, increased chromium accumulation, better scavenging ability of superoxide anions and hydrogen peroxide, and consequently decreased cytotoxicity and genotoxicity in ascorbic acid pretreated cells. Ascorbic acid influenced Cr(VI) toxicity both as a reducing agent, by decreasing Cr(V) persistence, and as an antioxidant, by decreasing intracellular superoxide anion and hydrogen peroxide formation and by quenching free radicals formed during Cr(VI) to Cr(III) reduction. Increased 8-OHdG and decreased reduced glutathione in ascorbic acid-treated cells might induce an endogenous antioxidant defense system and thus increase cell tolerance against subsequent Cr-induced stress.

8-Hydroxy-2'-Deoxyguanosine↗

Chromium chloride inhibits oxidative stress and TNF-alpha secretion caused by exposure to high glucose in cultured U937 monocytes.

Chromium supplementation has been proposed to promote the action of insulin and the lowering of blood glucose levels in diabetic patients. However, the molecular mechanism by which chromium increases insulin sensitivity is not known. Using U937 monocytes as a cell culture model, this study demonstrates that chromium inhibits the secretion of TNF-alpha, a cytokine known to inhibit the sensitivity and action of insulin. U937 cells were cultured with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degrees C for 24 h. This study demonstrates that chromium supplementation prevents the increase in TNF-alpha levels and oxidative stress caused by the high levels of glucose in cultured U937 monocytic cells. Similarly, chromium supplementation prevented elevated TNF-alpha secretion and lipid peroxidation levels in H(2)O(2)-treated U937 cells. This study demonstrates for the first time that chromium supplementation inhibits TNF-alpha secretion in U937 monocytes cultured in high-glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel molecular mechanism by which chromium supplementation may increase insulin sensitivity and glycemic control in diabetic patients.

Antioxidants↗

Dietary organic chromium supplementation and its effect on the immune response of rainbow trout (Oncorhynchus mykiss).

Recently, there has been an increasing interest in the potential effect of dietary chromium on the health of fish, particularly with respect to their metabolism and growth. Information as to the role of this mineral on their immune response, is limited however, so the aim of this study was to assess the effects of dietary chromium yeast supplementation on the immune response of rainbow trout (Oncorhynchus mykiss). Juvenile rainbow trout (56 g average weight) were fed three semipurified diets containing different levels of chromium (1540, 2340 and 4110 ppb), obtained by supplementing a basal diet with 800 or 2570 ppb chromium yeast, for 6 weeks. After this, time differences in their immune response were examined. A positive influence was observed on serum lysozyme activity at this time in fish maintained on the high chromium diet. The respiratory burst of head-kidney macrophages was also examined, and statistical differences were found in the level of respiratory burst elicited by macrophages from both groups of fish fed supplemented chromium after 3 and 6 weeks of feeding (absorbance at 3 weeks: 0.118, 0.166. 0.151 and 6 weeks 0.114, 0.168, 0.151 for the 1540, 2340 and 4110 ppb groups). Macrophages of fish receiving diets supplemented with chromium also had a greater ability to phagocytose yeast after 6 weeks than the control fish (40.5, 48 and 48.5% macrophages phagocytic in the 1540, 2340 and 4110 ppb groups, respectively). The results of the study show that chromium yeast is able to modulate the immune response of rainbow trout, and this effect appears to be both dose- and time-dependent.

Animal Feed↗

Human ingestion of chromium (VI) in drinking water: pharmacokinetics following repeated exposure.

Regulatory agencies have established safe drinking water concentrations for hexavalent chromium [Cr(VI)] based in part on the presumed capability of human gastric juices to rapidly reduce Cr(VI) to nontoxic trivalent chromium [Cr(III)] prior to systemic absorption. This study examines dose-related pharmacokinetics in humans following repeated oral exposure to Cr(VI) in drinking water. In particular, we sought to examine whether plausible drinking water exposures to Cr(VI) caused a sustained increase in red blood cell chromium levels, a specific marker for systemic uptake of Cr(VI). Adult male volunteers ingested a liter (in three volumes of 333 ml, at approximate 6-hr intervals) of deionized water containing Cr(VI) concentrations ranging from 0.1 to 10.0 mg/liter. Samples of urine, plasma, and red blood cells were collected and analyzed for chromium. A dose-related increase in urinary chromium excretion was observed in all volunteers. Red blood cell and plasma chromium concentrations became elevated in certain individuals at the highest doses. The RBC chromium profiles suggest that the ingested Cr(VI) was reduced to Cr(III) before entering the bloodstream, since the chromium concentration in the RBCs dropped rapidly postexposure. These findings suggest that the human gastrointestinal tract has the capacity to reduce ingested Cr(VI) following ingestion of up to 1 liter of water containing 10.0 mg/liter of Cr(VI), which is consistent with USEPA's position that the Cr(VI) drinking water standard of 0.10 mg Cr(VI)/liter is below the reductive capacity of the stomach.

Administration, Oral↗

Differential sensitivity of chromium-mediated DNA interstrand crosslinks and DNA-protein crosslinks to disruption by alkali and EDTA.

Some compounds of hexavalent chromium are well-established carcinogens. Chromium enters mammalian cells in the hexavalent form and is reduced to chromium (III). Treatment of purified DNA with chromium (III) produces DNA-DNA interstrand crosslinks (DDC) which obstruct the progression of DNA polymerases in vitro. DDC were also detected in chromate-treated cultured normal human lung cells using the renaturing agarose gel electrophoresis (RAGE) assay and correlated with base-specific inhibition of DNA replication. Curiously, DDC have gone undetected in studies of cultured cells using the alkaline elution (AE) technique, whereas chromium-mediated DNA-protein crosslinks (DPC) were readily detected by AE. We tested the hypothesis that AE conditions [60 mM tetraethyl ammonium hydroxide (TEA), 20 mM EDTA, pH 12.6, for 16 h at room temperature] dissociate DDC but not DPC using chromium(III)-treated plasmid DNA and the RAGE assay. Dose-dependent chromium-induced DDC were unaffected by TEA (pH 11.8) alone or by more rigorous alkaline denaturation conditions (200 mM NaOH, pH 13.5, for 16 h). DDC were, however, completely disrupted by EDTA (pH 12.6) alone or the combination of TEA and EDTA (pH 12.6). In contrast, DPC remained largely intact under these conditions. Therefore, past AE-based studies which have failed to detect chromium-induced DDC do not prove the absence of this lesion. AE may not be suitable for detecting DDC induced by EDTA-chelatable agents such as metals.

Caustics↗

Toxic effects of chromium and its compounds.

Chromium was discovered in 1797 by Vauquelin. Numerous industrial applications raised chromium to a very important economic element. At the same time, with the development of its uses, the adverse effects of chromium compounds in human health were being defined. Trivalent chromium is an essential trace element in humans and in animals. Chromium as pure metal has no adverse effect. Little toxic effect is attributed to trivalent chromium when present in very large quantities. Both acute and chronic toxicity of chromium are mainly caused by hexavalent compounds. The most important toxic effects, after contact, inhalation, or ingestion of hexavalent chromium compounds are the following: dermatitis, allergic and eczematous skin reactions, skin and mucous membrane ulcerations, perforation of the nasal septum, allergic asthmatic reactions, bronchial carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric deficiency. Prevention of occupational risks, biological monitoring of workers, and treatment of poisoning are also reported.

Animals↗

Reduction of chromium(VI) in Chinese hamster V-79 cells.

The cellular reduction of chromate(VI) was studied by electron spin resonance spectrometry. Incubation of Chinese hamster V-79 cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complex in a manner dependent on time (30 min-2 h) and concentration (50-500 microM). Following removal of extracellular chromate, the level of chromium(V) complex decreased quickly during the first hour but more slowly for the next hour, whereas the level of chromium(III) remained unchanged, indicating that chromium(III) is the ultimate ion of this metal in cells. Alkaline elution studies demonstrated that treatment of cells with Na2CrO4 induced DNA single-strand breaks that decreased quickly and DNA-protein crosslinks that persisted for 2 h after removal of this metal. These results suggest that the cellular levels of chromium(V) and chromium(III) may be associated with the formation of DNA damage induced by chromium (VI).

Animals↗

Use of SEC-ICP-MS with a collision cell for determining the interaction of chromium with DNA extracted from metal-contaminated soils.

The potential of chromium to bind to DNA isolated directly from soil microbial communities was investigated in this study. An analytical scheme was developed to distinguish between chromium bound to DNA and its fragments or chromium contained elsewhere in an environmental DNA extract. DNA was extracted from chromium-contaminated soils and purified using DNA clean-up resins. Size-exclusion chromatography was employed due to its advantages in the separation and molecular weight approximation of large biomolecules. It was coupled with two on-line detection systems (spectrophotometric and inductively coupled plasma mass spectrometric) to study the binding of chromium to DNA or other components in a DNA extract. A collision cell was pressurized with helium to remove diatomic and polyatomic interferents resulting from the chosen mobile phase. Chromium peaks were observed in both the large and small molecular weight regions of the chromatogram; to further confirm that the environmentally extracted DNA contained Cr, the subsequently purified DNA was examined for total Cr using flow injection ICP-MS to accommodate small sample volumes. DNA samples isolated from the two soils examined contained 0.5-0.7 ppb Cr, indicating that DNA isolated directly from a chromium-contaminated soil has chromium bound to the nucleic acids.

Chromatography, Gel↗

Assessment of biological chromium among stainless steel and mild steel welders in relation to welding processes.

Air and biological monitoring were used for assessing external and internal chromium exposure among 116 stainless steel welders (SS welders) using manual metal arc (MMA), metal inert gas (MIG) and tungsten inert gas (TIG) welding processes (MMA: n = 57; MIG: n = 37; TIG: n = 22) and 30 mild steel welders (MS welders) using MMA and MIG welding processes (MMA: n = 14; MIG: n = 16). The levels of atmospheric total chromium were evaluated after personal air monitoring. The mean values for the different groups of SS welders were 201 micrograms/m3 (MMA) and 185 micrograms/m3 (MIG), 52 micrograms/m3 (TIG) and for MS welders 8.1 micrograms/m3 (MMA) and 7.3 micrograms/m3 (MIG). The curve of cumulative frequency distribution from biological monitoring among SS welders showed chromium geometric mean concentrations in whole blood of 3.6 micrograms/l (95th percentile = 19.9), in plasma of 3.3 micrograms/l (95th percentile = 21.0) and in urine samples of 6.2 micrograms/l (95th percentile = 58.0). Among MS welders, mean values in whole blood and plasma were rather more scattered (1.8 micrograms/l, 95th percentile = 9.3 and 1.3 micrograms/l, 95th percentile = 8.4, respectively) and in urine the value was 2.4 micrograms/l (95th percentile = 13.3). The analysis of variance of chromium concentrations in plasma previously showed a metal effect (F = 29.7, P < 0.001), a process effect (F = 22.2, P < 0.0001) but no metal-process interaction (F = 1.3, P = 0.25). Concerning urinary chromium concentration, the analysis of variance also showed a metal effect (F = 30, P < 0.0001), a process effect (F = 72, P < 0.0001) as well as a metal-process interaction (F = 13.2, P = 0.0004). Throughout the study we noted any significant differences between smokers and non-smokers among welders. Taking in account the relationships between chromium concentrations in whole, plasma or urine and the different welding process. MMA-SS is definitely different from other processes because the biological values are clearly higher. These higher levels are due to the very significant concentrations of total soluble chromium, mainly hexavalent chromium, in welding fumes.

Adult↗

Glucose tolerance and plasma lipid distributions in rats fed a high-sucrose, high-cholesterol, low-chromium diet.

Male Sprague-Dawley rats were fed either a low-chromium (60 to 100 micrograms per kg of diet) or chromium-supplemented (5 mg per kg of diet), high-sucrose, high-cholesterol diet from weaning until age 18 months. Rats that were pair- and meal-fed the low-chromium diet had higher one-hour postprandial plasma glucose concentrations than their supplemented partners at ages 4 and 8 months (P less than 0.05), but not at age 12 months. One-hour postgavage (250 mg glucose/100 g body wt) glucose concentrations did not differ between dietary groups at 12 months. Plasma cholesterol concentrations increased up to age 12 months, but neither they nor postprandial triglyceride concentrations differed significantly between dietary groups. Ad libitum feeding of the low-chromium and chromium-supplemented diets was initiated at age 14 months in order to determine whether there were differences due to dietary chromium content which might not be manifest on the pair-feeding regimen. Animals of both dietary groups had significant weight gain by age 16 months, but their one-hour postgavage plasma glucose concentrations did not differ significantly. Plasma cholesterol concentrations increased significantly following institution of ad libitum feedings, but neither they nor lipoprotein cholesterol or triglyceride distributions differed significantly between dietary groups. Experimental conditions, methods, and results from this study and previous studies are compared and critically examined. We suggest that other factors in addition to dietary chromium content may contribute to the differences in glucose tolerance and plasma cholesterol concentrations described in such studies and that there is a need for improved documentation of glucose intolerance and tissue chromium concentrations in this animal model.

Animals↗