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PubMed1998

Chromium picolinate modulates rat vascular smooth muscle cell intracellular calcium metabolism.

We have previously shown that insulin attenuates vasoconstriction, accelerates both vascular relaxation and [Ca2+]i recovery from pressor agonist-induced Ca2+ loads, and stimulates Ca2+-ATPase gene expression in rat and human vascular smooth muscle cells (VSMC). Moreover, these functions are impaired in VSMC from both insulin resistant and insulinopenic rats, suggesting that hypertension in insulin resistant states may result, in part, from impaired insulin-regulation of VSMC Ca2+ transport. Accordingly, we have now evaluated the effect of improving cellular insulin sensitivity with chromium picolinate (CrPic) on regulation of VSMC Ca2+ transport. Cultured VSMC from rats were grown from passage to confluence in the presence or absence of 1 micromol/L CrPic, maintained in a quiescent medium for 24 h and incubated with or without insulin (10(-8) mol/L) for the final 2 h. Cells were then harvested and RNA and protein extracted for Northern and Western blot analysis, respectively. Insulin caused a significant stimulation of plasmalemmal Ca2+-ATPase mRNA and protein (P < 0.05). A comparable stimulation of the mRNA and protein levels was caused by CrPic in the absence of insulin (P < 0.05), while the CrPic + insulin treatment caused a greater percentage stimulation of the Ca2+-ATPase mRNA level than either separate treatment (P < 0.05). Fluorometric analysis of the rate of [Ca2+]i recovery following stimulation with arginine vasopressin support these findings: insulin caused an 83% increase, CrPic caused a 35% increase and insulin + CrPic caused a 133% increase in [Ca2+]i recovery rate. These data suggest that CrPic may be an effective modality to reduce VSMC [Ca2+]i loads and thereby reduce peripheral vascular resistance in insulin resistant states.

Animals↗
PubMed2002

Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

Administration, Oral↗
PubMed2006

Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

Animals↗
PubMed1984

Picolinic acid in acrodermatitis enteropathica: evidence for a disorder of tryptophan metabolism.

Three children with acrodermatitis enteropathica (AE) were treated with oral zinc dipicolinate (zinc-PA). The daily dose of zinc required to prevent exacerbations, when administered as the dipicolinate complex, was one-third the minimum amount of zinc required as the sulfate salt. The concentration of picolinic acid in the plasma of asymptomatic children with AE was significantly less than that of normal children. However, oral treatment with PA alone was ineffective. The plasma of the three AE children contained a measurable quantity of kynurenine which was undetectable in plasma from normal children. Absorption of an oral zinc load was normal. The results support the hypothesis that the genetic defect in AE is in the tryptophan pathway, although the role of PA in zinc metabolism remains to be defined.

Acrodermatitis↗
PubMed2004

Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFNgamma.

Treatment of mouse macrophages with picolinic acid (PA) and gamma-interferon (IFNgamma) led to the restriction of Mycobacterium avium proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or H(2)O(2) failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. N-Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome-endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFNgamma depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.

Animals↗
PubMed2007

Synergistic effects of conjugated linoleic acid and chromium picolinate improve vascular function and renal pathophysiology in the insulin-resistant JCR:LA-cp rat.

AIMS: Conjugated linoleic acid (CLA) is a natural constituent of dairy products, specific isomers of which have recently been found to have insulin sensitizing and possible antiobesity actions. Chromium is a micronutrient which, as the picolinate (CrP), has been shown to increase insulin sensitivity in animal models, including the JCR:LA-cp rat. We tested the hypothesis that these agents may have beneficial synergistic effects on the micro- and macrovasculopathy associated with hyperinsulinaemia and early type 2 diabetes. METHODS: Insulin-resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from 4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels, aortic vascular function, renal function and glomerular sclerosis were assessed. RESULTS: CLA administration reduced food intake, body weight and fasting insulin in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats treated with both CLA and CrP. Aortic hypercontractility was reduced and the relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was increased in CrP-treated rats. Striking reductions were also observed in the level of urinary albumin and the severity of glomerular sclerosis in rats treated specifically with CLA. CONCLUSIONS: CLA and CrP have beneficial effects ameliorating several of the pathophysiologic features of an insulin-resistant rat model. These supplements may be useful adjuncts in the management of patients with the metabolic syndrome and warrant further study.

Adiponectin↗
PubMed1977

Relaxation of isolated aorta of the rabbit by picolinic acids.

1 When the isolated thoracic aorta of the rabbit was contracted with prostaglandin F2alpha, 5-alkylpicolinic acids produced dose-dependent relaxations. 2 Picolinic acid, 2,5-pyridinedicarboxylic acid and 5-acetylpicolinic acid which do not have the 5-alkyl residue failed to relax blood vessels. 3 The vascular relaxation was dependent on the number of carbon atoms in the 5-alkyl compounds. 4 Relaxations which occurred with 5-alkylpicolinic acids were not affected by pretreatment with either propranolol or atropine. 5 It is concluded that the 5-alkyl residue is necessary for the vascular relaxation with 5-alkylpicolinic acid and that it was not produced by stimulation of beta-adrenoceptors or cholinoceptors but rather through an activation of the basic process.

Aminophylline↗
PubMed1992

Effects of chromium picolinate on beginning weight training students.

Changes in body weight (BW), a sum of three body circumferences (sigma C), a sum of three skinfolds (sigma SF), and the one-repetition maximum (1RM) for the squat (SQ) and bench press (BP) were examined in 59 college-age students (37 males [M], 22 females [F]) over a 12-week weight lifting program. Using a double-blind protocol, half of the students were given 200 micrograms/day chromium (Cr) in the form of chromium picolinate (CrPic) while the other half received a placebo (P). Therefore four groups were randomly formed: F-CrPic (n = 12), F-P (n = 10), M-CrPic (n = 18), and M-P (n = 19). All groups had significant increases in sigma C and significant decreases in sigma SF. No treatment effects were seen for the strength measurements, although the males experienced greater absolute increases. The only significant treatment effect found was due to the F-CrPic group gaining more BW (p = 0.0048) than the other three groups. It was concluded that CrPic supplementation had a greater effect on the females than on the males.

Adult↗
PubMed2004

Resistive training and chromium picolinate: effects on inositols and liver and kidney functions in older adults.

This study assessed the effects of resistive training (RT) with or without chromium picolinate (Cr-pic) supplementation on the 24-h urinary excretions of myo-inositol, D-chiro-inositol, and pinitol, as well as clinical indices of kidney and liver functions. Thirty-two nondiabetic subjects, age 62 +/- 4 y, performed RT twice weekly for 12 wk and consumed either 924 ug Cr/d as Cr-pic (n = 17) or a placebo (n = 15). Whole-body strength increased in all subjects by 20 % and urinary chromium excretion increased 47-fold in the Cr-pic group. Urinary myo-inositol, D-chiro-inositol, and pinitol were not changed with RT or influenced by Cr-pic. Serum indices of kidney and liver functions were within clinically normal ranges at baseline and the end of the study. These results suggest that RT did not influence the urinary excretions of inositols. High dose Cr-pic did not influence the urinary excretion of inositols and the selected indices of kidney and liver functions in conjunction with RT.

Area Under Curve↗
PubMed1993

Protective effect of picolinic acid on mice intracerebrally infected with lethal doses of Candida albicans.

We have studied the effects of picolinic acid (PLA), a product of tryptophan degradation, on mouse susceptibility to intracerebral infection with Candida albicans. We show that intraperitoneal administration of PLA significantly enhances the median survival time of mice inoculated with the lethal challenge. Furthermore, intracerebral administration of this agent induces a protective state against the local lethal infection, the phenomenon depending upon the administration schedule and doses of PLA employed. According to survival data, yeast growth in the brain as well as yeast colonization of the kidneys are drastically reduced in PLA-treated mice compared with those for untreated controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA levels specific for tumor necrosis factor and interleukin 1 are augmented and induced, respectively, after inoculation of PLA. These results indicate that PLA has a protective effect likely involving elicitation of a cytokine response in vivo against fungal infections.

Animals↗
PubMed1999

Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men.

The effects of chromium picolinate (CrPic) supplementation and resistance training (RT) on skeletal muscle size, strength, and power and whole body composition were examined in 18 men (age range 56-69 yr). The men were randomly assigned (double-blind) to groups (n = 9) that consumed either 17.8 micromol Cr/day (924 microg Cr/day) as CrPic or a low-Cr placebo for 12 wk while participating twice weekly in a high-intensity RT program. CrPic increased urinary Cr excretion approximately 50-fold (P < 0.001). RT-induced increases in muscle strength (P < 0.001) were not enhanced by CrPic. Arm-pull muscle power increased with RT at 20% (P = 0.016) but not at 40, 60, or 80% of the one repetition maximum, independent of CrPic. Knee-extension muscle power increased with RT at 20, 40, and 60% (P < 0.001) but not at 80% of one repetition maximum, and the placebo group gained more muscle power than did the CrPic group (RT by supplemental interaction, P < 0.05). Fat-free mass (P < 0.001), whole body muscle mass (P < 0.001), and vastus lateralis type II fiber area (P < 0.05) increased with RT in these body-weight-stable men, independent of CrPic. In conclusion, high-dose CrPic supplementation did not enhance muscle size, strength, or power development or lean body mass accretion in older men during a RT program, which had significant, independent effects on these measurements.

Aged↗
PubMed1995

Effect of recombinant growth hormone and chromium picolinate on cytokine production and growth performance in swine.

The effect of dietary chromium picolinate (CrP) and recombinant porcine growth hormone, somatotropin (rPST) administration on growth performance and cytokine production in Landrace-Poland China gilts was determined using a 2 by 2 treatment array. Treatments were: (1) control (basal diet), (2) CrP-supplemented diet (basal diet + 300 micrograms Cr3+/kg diet as CrP), (3) rPST (100 pg/kg body weight/day), and (4) rPST+CrP. CrP-supplemented diets were fed beginning at 20 kg body weight through 90 kg. Administration of rPST was begun at 60 kg weight and continued through 90 kg. All rPST treated pigs demonstrated improvements in growth performance versus controls. Pigs given CrP-supplemented diets showed no differences in growth performance. At 90 kg, pigs were challenged with endotoxin (lipopolysaccharide, 0.2 microgram/kg i.v.). Blood samples were collected at 0, 1, and 3 h postchallenge. Plasma IL-6 levels increased from 23 U/ml at time 0 to 1,927 U/ml at 3 h for control swine. Swine from the CrP treatment group had IL-6 levels of 8,130 U/ml at 3 h post-LPS. There were no differences in plasma IL-6 from pigs in the rPST and rPST+CrP treatment groups compared to the controls. Endotoxin challenge had no effect on either blood glucose levels or induction of TNF-alpha in any treatment group. PBMC from CrP-treated animals produced more IL-2 than peripheral blood mononuclear cells from all other groups.

Animals↗
PubMed1988

Influence of dietary picolinic acid on mineral metabolism in the rat.

Male rats were fed isonitrogenous, isocaloric diets containing different amounts of dietary zinc and picolinic acid (PA) (25, 60, 120 ppm Zn, 0, 20, 40, 60 mmol PA/kg diet) and balance collections of urine and faeces made over a 4-day period. Rats fed 25 ppm Zn were in negative Zn and Cu balance during the experiment. Faecal Zn, but not urinary Zn excretion was elevated with increasing dietary Zn supply. Urinary Zn, Cu and Mg excretion increased with increasing intakes of dietary PA, regardless of Zn intake. Tissue Zn levels were unaffected by dietary Zn or PA. It is concluded that dietary PA forms soluble complexes with metal ions which are rapidly absorbed but are then re-excreted in urine and may not be available for metabolism or incorporation into tissues.

Animals↗
PubMed2005

Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice.

To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration.

Animals↗
PubMed2003

The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent.

The element chromium apparently has a role in maintaining proper carbohydrate and lipid metabolism in mammals. As this role probably involves potentiation of insulin signalling, chromium dietary supplementation has been postulated to potentially have effects on body composition, including reducing fat mass and increasing lean body mass. Because the supplement is absorbed better than dietary chromium, most studies have focused on the use of chromium picolinate [Cr(pic)(3)]. Cr(pic)(3) has been amazingly popular with the general public, especially with athletes who may have exercise-induced increased urinary chromium loss; however, its effectiveness in manifesting body composition changes has been an area of intense debate in the last decade. Additionally, claims have appeared that the supplement might give rise to deleterious effects. However, over a decade of human studies with Cr(pic)(3) indicate that the supplement has not demonstrated effects on the body composition of healthy individuals, even when taken in combination with an exercise training programme. Recent cell culture and in vivo rat studies have indicated that Cr(pic)(3) probably generates oxidative damage of DNA and lipids and is mutagenic, although the significance of these results on humans taking the supplement for prolonged periods of time is unknown and should be a focus for future investigations. Given that in vitro studies suggest that other forms of chromium used as nutritional supplements, such as chromium chloride, are unlikely to be susceptible to generating this type of oxidative damage, the use of these compounds, rather than Cr(pic)(3), would appear warranted. Potential neurological effects (both beneficial and deleterious) from Cr(pic)(3) supplementation require further study.

Animals↗
PubMed2005

New derivatives of picolinic acid and nicotinic acid with anticonvulsant activity.

Previously obtained Pic-BZA is a potent anticonvulsant with low neurotoxicity, but its half-time of action is only about 15 min. In search for equally effective anticonvulsants but with a longer time of action fourteen Pic-BZA analogs were obtained. The compounds were evaluated in the Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA, 7) appeared to be the most effective compound of the series.

Animals↗
PubMed2006

Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes.

OBJECTIVE: Chromium picolinate (CrPic) supplementation has been suggested to improve glycemia, but there are conflicting reports on efficacy. We sought to determine the effect of CrPic on insulin sensitivity, glycemic control, and body composition in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-seven subjects with type 2 diabetes were evaluated. After baseline, subjects were placed on a sulfonylurea (glipizide gastrointestinal therapeutic system 5 mg/day) with placebo for 3 months. Subjects were then randomized in a double-blind fashion to receive either the sulfonylurea plus placebo (n = 12) or the sulfonylurea plus 1,000 microg Cr as CrPic (n = 17) for 6 months. Body composition, insulin sensitivity, and glycemic control were determined at baseline, end of the 3-month single-blind placebo phase, and end of study. RESULTS: Subjects randomized to sulfonylurea/placebo, as opposed to those randomized to sulfonylurea/CrPic, had a significant increase in body weight (2.2 kg, P < 0.001 vs. 0.9 kg, P = 0.11), percent body fat (1.17%, P < 0.001 vs. 0.12%, P = 0.7), and total abdominal fat (32.5 cm(2), P < 0.05 vs. 12.2 cm(2), P < 0.10) from baseline. Subjects randomized to sulfonylurea/CrPic had significant improvements in insulin sensitivity corrected for fat-free mass (28.8, P < 0.05 vs. 15.9, P = 0.4), GHb (-1.16%, P < 0.005 vs. -0.4%, P = 0.3), and free fatty acids (-0.2 mmol/l, P < 0.001 vs. -0.12 mmol/l, P < 0.03) as opposed to sulfonylurea/placebo. CONCLUSIONS: This study demonstrates that CrPic supplementation in subjects with type 2 diabetes who are taking sulfonylurea agents significantly improves insulin sensitivity and glucose control. Further, CrPic supplementation significantly attenuated body weight gain and visceral fat accumulation compared with the placebo group.

Adipose Tissue↗