[Show abstract][Hide abstract] ABSTRACT: Background
Chromium (Cr) is commonly used as a complementary medicine for diabetes mellitus. Several studies suggest that Cr intakes may improve glucose metabolism and decrease oxidative stress. Therefore, we aimed to assess the effects of chromium histidinate (CrHis) supplementation using a range of reliable biomarkers of oxidative damage and histopathological changes in rats with diabetic retinopathy.Methods
Diabetes was induced with streptozotocin [(STZ), 55 mg/kg] by intraperitoneal injection in male Long-Evans rats. Three weeks after STZ injection, rats were divided into four groups, namely, untreated normal controls, normal rats receiving CrHis (110 ¿g/kg/day); untreated diabetics and diabetics treated with CrHis (110 ¿g/kg/day) orally for 12 weeks.ResultsIn the untreated diabetic group, levels of serum glucose, glycosylated haemoglobin (HbA1c), total cholesterol (TC) and retina malondialdehyde (MDA) were significantly increased, while expressions of retina insulin, and glucose transporter 1 (GLUT 1) and glucose transporter 3 (GLUT3) and level of serum insulin were decreased. CrHis supplementation was found to reduce the levels of glucose, HbA1c, total cholesterol and MDA and to improve the GLUT1, GLUT3 and insulin expressions in STZ-induced diabetic rats. CrHis prevents the changes in the expressions of GLUT1, GLUT3 and insulin and the level of MDA in the retina tissue, confirming the protective effect of CrHis supplementation against the retinopathy caused by STZ. Histopathologic findings suggest that the CrHis-treated diabetic group had normal retinal tissue appearance compared with the untreated diabetic group.Conclusions
These results verify that CrHis has critical beneficial effects against retinal complications. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of CrHis against diabetic complications, these preliminary experimental findings demonstrate that CrHis exhibits antidiabetic effects in a rat model of diabetic retinopathy by regulating the glucose metabolism and suppressing retinal tissue damage.
Full-text · Article · Feb 2015 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential.
Male Sprague-Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15 U/kg, i.p., n=56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8μg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot.
Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAM's, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic.
In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis has protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters.
[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P < 0·05), but serum insulin concentrations increased (P < 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P < 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P < 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P < 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.
Full-text · Article · Dec 2012 · The British journal of nutrition
[Show abstract][Hide abstract] ABSTRACT: 1. This experiment was conducted to evaluate the effects of supplemental chromium histidinate (CrHis) on performance and expressions of hepatic nuclear factors kappaB, an enhancer (NF-κB) and an inhibitor (IκBα) of activated B cells in heat-stressed Japanese quail (Coturnix coturnix japonica). 2. A total of 180, 10-d-old Japanese quail were allocated randomly into 6 groups in a 2 × 3 factorial arrangement. Birds were reared either at 22°C for 24 h/d (thermoneutral, TN) or 34°C for 8 h/d (heat stress, HS) for 32 d and fed on one of three diets supplemented with 0, 400 or 800 µg of CrHis per kg of diet. Each group consisted of 10 cages, each containing three quail. Data (performance variables and hepatic NF-κB and IκBα) were analysed using 2-way ANOVA. 3. Heat stress caused reductions in cumulative feed intake (FI) by 5·7%, weight gain (WG) by 13·0%, final body weight (FBW) by 10·3%, carcase weight by 12·6% and carcase efficiency by 2·3% and an increase in feed conversion ratio (FCR, feed consumed, g:weight gained, g) by 8·4%. As supplemental CrHis level increased up to 800 µg/kg, there were linear increases in cumulative FI (from 602 to 609 g), WG (from 134 to 138 g), FBW (from 167 to 171 g), cold carcase weight (from 110 to 114 g) and cold carcase efficiency (from 65·5 to 66·4%) and a decrease in FE (from 4·51 to 4·42). The environmental temperature by CrHis level interaction effect on performance parameters was insignificant. Hepatic NF-κB p65 concentration was higher and hepatic IκBα concentration was lower in quail exposed to HS than in quail kept at TN temperature. Increasing supplemental CrHis level linearly inhibited hepatic NF-κB p65 expression from 134·4 to 105·3% and linearly enhanced hepatic IκBα expression from 73·4 to 99·6%. The decrease in hepatic NF-κB expression and the increase in hepatic IκB expression were more notable in the TN environment than in the HS environment. 4. In conclusion, heat stress depressed performance variables and augmented lipid peroxidation and supplemental CrHis alleviated oxidative stress through modulating expressions of stress-related hepatic nuclear transcription factors (NF-κB and IκBα).
Full-text · Article · Dec 2012 · British Poultry Science
[Show abstract][Hide abstract] ABSTRACT: The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n = 45) and diabetic (n = 45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8 μg elemental chromium (Cr) per day for 12 weeks. Diabetes was induced by streptozotocin injection (40 mg/kg i.p., for 2 weeks) and maintained by high-fat feeding (40 %). Diabetes was associated with increases in cerebral NF-κB and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-κB and 4-HNE protein adducts and to increase levels of IκBα and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-κB p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-κB expression and increasing Nrf2 expression in the brain of diabetic rats.
Full-text · Article · Jul 2012 · Biological trace element research
[Show abstract][Hide abstract] ABSTRACT: Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney.
Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis.
The increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats.
Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.
[Show abstract][Hide abstract] ABSTRACT: Chromium picolinate (CrPic) has shown both antidepressant and antidiabetic properties. In this study, the effects of CrPic on serotonergic properties and carbohydrate metabolism in diabetic rats were evaluated. Sixty male Sprague-Dawley rats were divided into four groups. (1) The control group received only standard diet (8 % fat). (2) The CrPic group was fed standard diet and CrPic (80 μg CrPic per kilogram body mass (b.m.)/day), for 10 weeks (microgram/kilogram b.m./day). (3) The HFD/STZ group fed a high-fat diet (HFD, 40 % fat) for 2 weeks and then received streptozotocin (STZ, 40 mg/kg, i.p.) (i.v.) HFD-STZ-CrPic group treated as the previous group and then were administered CrPic. CrPic administration to HFD/STZ-treated rats increased brain chromium levels and improved all measurements of carbohydrate metabolism and serotonergic properties (P < 0.001). CrPic also significantly increased levels of insulin, tryptophan, and serotonin (P < 0.001) in the serum and brain, and decreased cortisol levels in the serum (P < 0.01). Except chromium levels, no significant effect of CrPic supplementation was detected on the overall measured parameters in the control group. CrPic administration was well tolerated without any adverse events. The results support the use of CrPic supplementation which improves serotonergic properties of brain in diabetes.
Full-text · Article · Mar 2012 · Biological trace element research
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate the effects of whey protein (WP) and chromium picolinate (CrPic) on body composition
and metabolic status in rats fed a high-fat diet (HFD). Male Wistar rats (n = 10/group, 8 weeks old) were divided into three groups. The control group was fed a HFD (300 g fat/kg diet). The other two
groups were fed the HFD plus 320 g whey protein isolate/kg diet (HFD + WP) with or without 80 mcg CrPic/kg body wt/day (HFD
+ WP + CrPic). After six weeks, rats were fasted, blood samples were drawn, and visceral and subcutaneous fat pads were removed
and weighed. Daily food intake was not affected by treatment. Rats fed HFD exhibited significant increases in body weight,
body fat and metabolic risk factors (p ≤ 0.05). Rats fed the HFD + WP showed a significant decrease in body weight, serum glucose and blood lipids, and a significant
increase in insulin levels (p ≤ 0.05). Rats fed the HFD + WP + CrPic had the lowest levels in total visceral fat, triglycerides, total cholesterol and
free fatty acids, and the highest insulin levels (p ≤ 0.05). Tissue concentrations of chromium (Cr) increased with CrPic supplementation (p < 0.001). The results of this study support the use of WP and CrPic supplementation to improve body composition and metabolic
syndrome risk factors.
Full-text · Article · Dec 2009 · Mediterranean Journal of Nutrition and Metabolism
[Show abstract][Hide abstract] ABSTRACT: Chromium picolinate (CrPic) is used as a dietary supplement and has beneficial effects in reducing diabetes risk factors. The present study evaluated the cytogenetic effects of CrPic in bone marrow cells of Sprague-Dawley rats (5 animals/sex/group). Test animals were dosed orally with 33, 250 or 2000 mg/kg of CrPic, which corresponded to doses of 4.1, 30.8 and 246 mg/kg of chromium. The lowest dose of CrPic, 33 mg/kg is estimated to be the human equivalent for a 50 kg person (200 mcg Cr). The animals were dosed once, and sacrificed either 18 or 42 hours (h) later. The mitotic index was determined for each rat. Metaphase cells (50 or 100/rats) were examined for interstitial deletions, chromatid and chromosome gap, breaks or other anomalies. The average percentage of damaged cells at 18 h in vehicle treated males and females were 1.2% and 0.6%, respectively. The mean values at 18 h for doses of 33, 250 and 2000 mg/kg, were 0.4%, 0.8%, 0.4% for males and 0.6%, 0.2% and 0.6% for females, respectively. At 42 h, the mean values for vehicle treated males and females were 0.4% and 0.2%, respectively. For doses of 33, 250 and 2000 mg/kg at 42 h the average percent damage was 14%, 0.8% and 0.4% for males and 0.2%, 0.2% and 0.0% for females, respectively. None of these values were statistically increased compared to the vehicle controls. The positive control Cyclophosphamide (CPM) induced a significant increase in chromosomal damage at 18 h averaging 30% in males and 37% in females, respectively (p<0.001). In the current study CrPic did not induce chromosomal damage in bone marrow cells at single doses of 33, 250 and 2000 mg/kg of body weight and thus there was no indication of any toxicity of CrPic.
No preview · Article · Apr 2008 · Toxicology in Vitro
[Show abstract][Hide abstract] ABSTRACT: Chromium supplements are widely used as an alternative remedy for type 2 diabetes mellitus (T2DM). In vitro study findings show that chromium picolinate (CrPic) may improve insulin sensitivity by enhancing intracellular insulin receptor. In this study, we evaluated the metabolic effects of CrPic in a rat model of T2DM. Male Sprague-Dawley rats (n = 45, 8 weeks old) were divided into 3 groups. The controls (group I) received a standard diet (12% of calories as fat); group II received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg; HFD/STZ) on day 14; group III rats were given group II diets with the addition of 80 microg CrPic per kilogram body weight per day. The addition of CrPic in the group III treatment lowered glucose by an average of 63% (P < .001), total cholesterol by 9.7% (P < .001), and triglycerides by 6.6% (P < .001) compared with group II treatment. Compared with group II, CrPic treatment also lowered free fatty acid levels by 24% (P < .001), blood urea by 33% (P < .05), and creatinine level by 25% (P < .01), and reduced the severity of glomerular sclerosis (P < .0001). Histopathologic findings suggest that the CrPic-treated group had normal renal tubular appearance compared with the HFD/STZ-treated group. Normal appearance of hepatocytes was observed in the CrPic-treated group. These results showed that CrPic has marked beneficial effects against microvascular complications. In conclusion, HFD/STZ rats provide a novel animal model for T2DM. Further treatment with CrPic for 10 weeks significantly ameliorated changes in metabolic risk factors including favorable changes in histopathology of the liver, kidney, and pancreas, suggesting its potential role in the management of diabetes.
[Show abstract][Hide abstract] ABSTRACT: The atherogenic index of plasma (AIP), defined as logarithm [log] of the ratio of plasma concentration of triglycerides to high-density lipoprotein (HDL) cholesterol, has recently been proposed as a predictive marker for plasma atherogenicity and is positively correlated with cardiovascular disease risk. The nutrient combination of chromium picolinate and biotin (CPB) has been previously shown to reduce insulin resistance and hyperglycemia in patients with type 2 diabetes (T2DM).
Thirty-six moderately obese subjects with T2DM and with impaired glycemic control were randomized to receive CPB or placebo in addition to their oral hyperglycemic agents for 4 weeks. Measurements of blood lipids (including ratio of triglycerides to HDL cholesterol), fructosamine, glucose, and insulin were taken at baseline and after 4 weeks.
At the final visit, the active group had a significantly lower AIP compared to the placebo group (P < 0.05). A significant difference in triglyceride level (P < 0.02) and the ratio of low-density lipoprotein (LDL) to HDL cholesterol (P < 0.05) was also observed between the groups at the final visit. In the active group, the changes in urinary chromium levels were inversely correlated with the change in AIP (P < 0.05). Urinary chromium levels were significantly increased in the CPB group. In the CPB group, glucose levels decreased at 1 hour and 2 hours and glucose area under the curve and fructosamine level were significantly decreased. Ratios of total to HDL cholesterol, LDL to HDL cholesterol, and non-HDL to HDL cholesterol were significantly decreased between the treatments at final visit. No significant adverse events were observed in the CPB or placebo groups.
These results suggest that the combination of chromium picolinate and biotin may be a valuable nutritional adjuvant therapy to reduce AIP and correlated CVD risk factors in people with T2DM.
No preview · Article · Apr 2007 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Dyslipidemia, often found in type 2 diabetes mellitus (T2DM) patients, plays an important role in the progression of cardiometabolic syndrome. Two essential nutrients, chromium and biotin, may maintain optimal glycemic control. The authors report here a randomized, double-blind placebo-controlled trial (N=348; chromium picolinate and biotin combination [CPB]: 226, placebo: 122; T2DM participants with hemoglobin A1c [HbA1c] >or=7%) evaluating the effects of CPB on lipid and lipoprotein levels. Participants were randomly assigned (2:1 ratio) to receive either CPB (600 microg chromium as chromium picolinate and 2 mg biotin) or a matching placebo once daily for 90 days. Statistical analyses were conducted in all eligible participants. Subsequent supplemental analyses were performed in T2DM participants with hypercholesterolemia (HC) and in those using stable doses of statins. In the primary analysis, CPB lowered HbA1c (P<.05) and glucose (P<.02) significantly compared with the placebo group. No significant changes were observed in other lipid levels. In participants with HC and T2DM, significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index were observed in the CPB group (P<.05). Significant decreases in LDL-C, total cholesterol, HbA1c , and very low-density cholesterol levels (P<.05) were observed in the CPB group taking statins. CPB treatment was well tolerated with no adverse effects, dissimilar from those associated with placebo. These data suggest that intervention with CPB improves cardiometabolic risk factors.
Full-text · Article · Feb 2007 · Journal of the CardioMetabolic Syndrome
[Show abstract][Hide abstract] ABSTRACT: Purpose – Many foods naturally contain dietary Cr, but lost during processing and cooking. Type 2 diabetes mellitus (T2DM) has been associated with poor glycemic control and low Cr status. The objectives of the current study were to evaluate the dietary Cr intake and its relationship with diabetes risk factors in moderately obese subjects with T2DM. Design/methodology/approach – Thirty-six subjects (age: 26–65 years) were recruited through local advertisements. Subjects were taking stable doses of oral antidiabetic medication(s) excluding concomitant insulin. Subjects had HbA1c =7 per cent, persistent impaired glucose control (2 hour glucose >200 mg dL-1) and at least a one-year history of T2DM. Demographic characteristics, blood pressure, body mass index (BMI), family and medical history were recorded. Three-day dietary intakes were collected and evaluated for Cr and nutrient content using Nutritionist V software. Plasma glucose, circulating insulin and lipid profile were analyzed. Homeostatic model assessment insulin resistance (IR), beta cell function (BCF) and derived ratios were calculated. Morning void urinary chromium levels were also measured. Findings – It was observed that mean dietary Cr intake of adults (30 mcg) was below the suggested recommended daily intake (RDI) of 120 mcg day-1. These estimates correspond to approximately 16.4 µg Cr per 1000 Kcals. A significant correlation was observed between dietary Cr and fasting insulin (p<0.05), total-C (p<0.05), LDL-C (p<0.01), triglycerides (p<0.05), BCF (p<0.05), TG/HDL-C ratio (p<0.01), HOMA BCF (p<0.05) and with atherogenic index in plasma (p<0.05). Originality/value – In this study, the consumption of chromium is less than the RDI. Overall the results suggest that the US diets are inadequate in the essential metal chromium. Further studies are required to explore the relationship of Cr absorption with dietary Cr intake and risk factors in T2DM.
No preview · Article · Oct 2006 · Nutrition & Food Science
[Show abstract][Hide abstract] ABSTRACT: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). Printed by Jouve, 75001 PARIS (FR) Europäisches Patentamt European Patent Office Office européen des brevets A61K 31/555 (2006.01) A61K 31/4188 (2006.01) A61P 3/06 (2006.01) A61P 7/00 (2006.01) (86) International application number:
[Show abstract][Hide abstract] ABSTRACT: Glucose control remains the cornerstone of therapeutic strategies in patients with type 2 diabetes mellitus (DM). Clinical trial data suggest that chromium picolinate (CrPic) improves insulin sensitivity, glycemic control, and improved symptomatology in diabetes while biotin favorably affects abnormalities in glucose regulation. Methods: A 12-week, open-labeled, nutrition and education program was conducted to determine the effects of a CrPic and biotin combination on glycemic control. Subjects (n = 30) with type 2 DM who had a baseline HbA1c ³ 7% and were receiving oral antidiabetic medications for at least 6 months prior to the study were eligible for enrollment. The program included supplementation with (CrPic, 300 µg of Cr, and biotin 150 µg) twice daily, promotion of blood glucose monitor use, and provision of educational information on diabetes management. Pre- and post study levels of HbA1c were measured for each subject. Results: After 12 weeks, a significant drop was noted in subjects with baseline HbA1c from 8.5% to 7.4% with a mean change of 1.1% (p < 0.01). No adverse events were reported. The subjects with medications responded significantly to the combination of CrPic and biotin. Conclusions: When used in conjunction with an educational feedback program and antidiabetic medications, the combination of CrPic and biotin (Diachrome®) is safe and effective in diabetes.
No preview · Article · Mar 2006 · Trace Elements and Electrolytes
[Show abstract][Hide abstract] ABSTRACT: : 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.
: 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).
: 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.
: 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.
: 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.
No preview · Article · Sep 2005 · Journal of Psychiatric Practice