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August 2004

LE Magazine August 2004

Chromium and parenteral nutrition.
Studies involving patients on total parenteral nutrition (TPN) led to conclusive documentation of the essential role of Cr in human nutrition. These patients developed severe diabetic symptoms including glucose intolerance, weight loss, impaired energy utilization, and nerve and brain disorders that were refractory to insulin. After addition of Cr to TPN fluids, diabetic symptoms were alleviated, and exogenous insulin was no longer required. Cr intake by healthy subjects consuming average Westernized diets is suboptimal; if these subjects experience severe physical trauma or other forms of stress, Cr status may be overtly compromised. Recommendations for daily Cr supplementation of 10-20 micrograms for patients on short-term TPN (< or = 1-3 mos) appear to be adequate. Stable patients on long-term TPN may receive ample Cr from that present in TPN fluids. Because of the variable nature of contaminating Cr, Cr intake and losses of TPN patients should be monitored.

Nutrition. 1995 Jan-Feb;11(1 Suppl):83-6

Effect of chromium supplementation on glucose tolerance and lipid profile.
OBJECTIVES: To investigate chromium status of the adult population in the western region of Saudi Arabia and the possibility of using serum chromium status measurement as indicator of this status. METHODS: The effect of chromium supplement on glucose tolerance and lipid profile was studied in 44 normal, free living adults. 200mg chromium/day as CrCL3 or a placebo was given in a double blind cross-over study, with 8 weeks experimental periods. Fasting, 1 hour and 2 hour post glucose challenge (75 g of glucose) glucose, serum fructosamine, total cholesterol, high-density lipoprotein-cholesterol, triglycerides, chromium and dietary intakes were estimated at the beginning and the end of each stage. RESULTS: Mean serum chromium increased significantly after supplement (P<.001) indicating proper absorption of the element. Supplement did not effect the total cholesterol, however, the mean high-density lipoprotein-cholesterol level was significantly increased (P<.001), the mean triglycerides levels significantly decreased (P<.001), and the mean fructosamine level significantly decreased (P<.05). In addition, chromium supplement effected 1 hour and 2 hour post glucose challenge glucose levels in subgroups of subjects with 2 hour glucose level > 10% above or below fasting level and significantly differing to it (P<.05 in both cases), by decreasing or increasing them significantly (P<.05 in all cases) so that the 2 hour mean became not significantly different to the fasting mean. Since no significant changes in weight, dietary intake or habits were found, and placebo had no effect, all noted biochemical changes were attributed to chromium. CONCLUSION: Improved glucose control, and lipid profile following chromium supplement suggests the presence of low chromium status in the studied population. However, serum chromium could not be recommended for use as an indicator of chromium status as subjects with widely varying levels responded favorably to the chromium supplement.

Saudi Med J. 2000 Jan;21(1):45-50

Beneficial effects of chromium in people with type 2 diabetes, and urinary chromium response to glucose load as a possible indicator of status.
No reliable method for the estimation of chromium (Cr) status is available yet. The aim of this study is to investigate the possibility of using urinary Cr response to glucose load as an indicator of Cr status. Seventy-eight non-insulin-dependent diabetes mellitus patients, were divided randomly into two groups and given Cr supplements as brewer's yeast and CrCl3 sequentially with placebo in between, in a double-blind, crossover design of four stages, each lasting 8 wk. At the beginning and end of each stage, subjects were weighed, their dietary data and drug dosage recorded, and blood and urine samples collected for analysis of glucose and urinary chromium (fasting and 2 h post-75-g glucose load) and fructosamine. The mean urinary Cr after the glucose load was significantly higher than the fasting mean at zero time (p<0.01). However, only 52 of the patients showed an obvious increase; the others showed a slight decrease or no change. Both supplements caused a significant increase in the means of urinary Cr and a significant decrease in the means of glucose and fructosamine. Only those subjects responding to Cr supplement by improved glucose control showed an increase in post-glucose-load urinary Cr over fasting level, after the supplement but not at zero time. Therefore, it was concluded that urinary Cr response to glucose load could be used as an indicator of Cr status.

Biol Trace Elem Res. 2002 Feb;85(2):97-109

Antioxidant effects of chromium supplementation with type 2 diabetes mellitus and euglycemic subjects.
To determine the effects of chromium (Cr) supplementations on oxidative stress of type 2 diabetes and euglycemic (EU) subjects, adult having HbA(1C) values of <6.0% (EU), 6.8-8.5% (mildly hyperglycemic, MH), and >8.5% (severely hyperglycemic, SH) were supplemented for 6 months with 1000 microg/day of Cr (as Cr yeast) or with a placebo. In the beginning, the levels of the plasma Cr in the MH and SH groups were 25-30% lower than those of the EU subjects. The values of thiobarbituric acid reactive substances (TBARS) and total antioxidative status (TAS) of the MH and SH groups were significantly higher than those of the EU ones. Following supplementations, the levels of plasma TBARS in the Cr groups of MH and SH groups were significantly decreased (the inverse was found in the EU) and showed no significant changes in the placebo group. The levels of plasma TAS in the Cr groups of EU and MH were significantly decreased (the inverse was found in the SH) and showed no significant changes in the placebo group. No significant difference was found in the antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities during supplementations. These data suggest that Cr supplementation was an effective treatment strategy to minimize increased oxidative stress in type 2 diabetes mellitus patients whose HbA(1C) level was >8.5%, and the Cr in EU groups might act as a prooxidant.

J Agric Food Chem. 2004 Mar 10;52(5):1385-9

Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls.
This study aimed to compare the trace element status of patients with type 2 diabetes (n = 53) with those of nondiabetic healthy controls (n = 50). The concentrations of seven trace elements were determined in the whole blood, blood plasma, erythrocytes, and lymphocytes of the study subjects. Vanadium and iron levels in lymphocytes were significantly higher in diabetic patients as compared to controls (p < 0.05 for iron and p < 0.01 for vanadium). In contrast, lower manganese (p < 0.01) and selenium (p < 0.01) concentrations were detected in lymphocytes derived from patients with type 2 diabetes versus healthy subjects. Furthermore, significantly lower chromium levels (p < 0.05) were found in the plasma of diabetic individuals as compared to controls. Trace element concentrations were not dependent on the degree of glucose control as determined by correlation analysis between HBA1c versus metal levels in the four blood fractions. In summary, this study primarily demonstrated that trace element levels in lymphocytes of patients with type 2 diabetes could deviate significantly from controls, whereas, in general, no considerable differences could be found when comparing the other fractions between both patient groups. Therefore, it seems reasonable to analyze metal levels in leukocytes to determine trace element status in patients with type 2 diabetes and perhaps in other diseases.

Biol Trace Elem Res. 2001 Mar;79(3):205-19

Chromium and insulin resistance.
Since as early as the 50s of the last century, it has been known that chromium is essential for normal glucose metabolism. Too little chromium in the diet may lead to insulin resistance. However, there is still no standard against which chromium deficiency can be established. Nevertheless, chromium supplements are becoming increasingly popular. Various systematic reviews have been unable to demonstrate any effects of chromium on glycaemic regulation (possibly due partly to the low dosages used), but there is a slight reduction in body weight averaging 1 kg. In a double-blind randomised placebo-controlled trial in a Chinese population with type-2 diabetes mellitus, supplementation with 1000 micrograms of chromium led to a fall in the glycosylated haemoglobin level (HbA1c) by 2%. Toxic effects of chromium are seldom seen; recently, however, the safety of one of the dosage forms of chromium, chromium picolinate, has been questioned. One should be aware that individual patients with type-2 diabetes mellitus may have an increased risk of hypoglycaemic episodes when taking chromium supplements as self-medication.

Ned Tijdschr Geneeskd. 2004 Jan 31;148(5):217-20

The effects of LDL reduction and HDL augmentation on physiologic and inflammatory markers.
Cholesterol plays an important role in atherogenesis. Oxidized low-density lipoprotein cholesterol is harmful to arteries whereas high-density lipoprotein cholesterol appears to have beneficial properties on vascular function. There is increasing evidence that inflammation is also involved in the atherogenic process. Inflammation accelerates atherosclerosis and promotes thrombogenesis, and inflammatory biomarkers have been correlated with cardiovascular risk. There is now evidence that lowering low-density lipoprotein and raising high-density lipoprotein cholesterol have beneficial effects on inflammation that might contribute to the reduction in clinical cardiovascular events with currently available lipid-altering therapies. New therapeutic strategies are being designed to inhibit specific aspects of the inflammatory system that contribute to the initiation and progression of atherosclerosis.

Curr Opin Cardiol. 2003 Jul;18(4):295-300

New perspectives on the use of niacin in the treatment of lipid disorders.
Therapy with niacin (nicotinic acid) is unique in that it improves all lipoprotein abnormalities. It significantly reduces low-density lipoprotein cholesterol, triglyceride, and lipoprotein(a) levels, while increasing high-density lipoprotein cholesterol levels. This makes niacin ideal for treating a wide variety of lipid disorders, including the metabolic syndrome, diabetes mellitus, isolated low high-density lipoprotein cholesterol, and hypertriglyceridemia. Niacin-induced changes in serum lipid levels produce significant improvements in both coronary artery disease and clinical outcomes. Niacin is currently available in 3 formulations (immediate release, extended release, and long acting), which differ significantly with respect to their safety and efficacy profiles. Immediate-release niacin is generally taken 3 times a day and is associated with adverse flushing, gastrointestinal symptoms, and elevations in blood glucose levels. Long-acting niacin can be taken once daily and is associated with significantly reduced flushing, but its metabolism increases the risk of hepatotoxic effects. Extended-release niacin, also given once daily, has an absorption rate intermediate between the other formulations and is associated with fewer flushing and gastrointestinal symptoms without increasing hepatotoxic risk.

Arch Intern Med. 2004 Apr 12;164(7):697-705

Niacin for dyslipidemia: considerations in product selection.
The efficacy and safety profiles of various forms of niacin for treating dyslipidemia are described. Niacin is well recognized for treating dyslipidemia in adults and has been shown to be effective in reducing coronary events. It has a broad range of effects on serum lipids and lipoproteins, including lowering total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides. Niacin is the most effective lipid-modifying drug for raising high-density-lipoprotein (HDL) cholesterol levels and has been shown to lower Lp(a) lipoprotein. Niacin reduces triglycerides and very-low-density-lipoprotein and LDL cholesterol synthesis, primarily by decreasing fatty acid mobilization from adipose tissue. Niacin appears to raise HDL cholesterol by reducing hepatic apolipoprotein A-l clearance and enhancing reverse cholesterol transport. Niacin is metabolized through a conjugation or nicotinamide pathway. Standard immediate-release niacin is metabolized primarily through the conjugation pathway, which results in a high frequency of flushing. Long-acting niacin is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Extended-release niacin has a more balanced metabolism and causes fewer of both types of adverse effects. Improved serum lipid levels during niacin therapy have been associated with clinical and angiographic evidence of reduced coronary artery disease, especially when combined with statins. Niacin is particularly useful for managing high triglyceride and low HDL cholesterol levels as well as the lipid abnormalities associated with metabolic syndrome, including those commonly encountered in patients with diabetes. Several niacin products are available with significant differences in their safety and efficacy profiles. Health care providers must consider the differences between agents when recommending niacin for dyslipidemia treatment.

Am J Health Syst Pharm. 2003 May 15;60(10):995-1005

Vanadate improves cardiac function and myocardial energy metabolism in diabetic rat hearts.
Vanadium mimicking the metabolic effects of insulin is known to decrease serum glucose levels and to influence glucose metabolism in diabetes mellitus. However, it is unclear whether vanadium ameliorates the metabolic disorder in diabetic hearts causing myocardial dysfunction. The purpose of this study was to assess the effects of vanadium on cardiac performance and energy metabolism in diabetic rat hearts. Four groups of Wistar rats were studied: untreated control rats (group C, n = 8). vanadate-treated rats (group V, n = 10), untreated diabetic rats (group DM, n = 9) induced by streptozotocin. and vanadate-treated diabetic rats (group DMV, n = 8). Vanadate-treated rats drank a 1.5 mM sodium orthovanadate (Na3VO4) solution during a 4 week diabetic condition. Hearts were perfused with Krebs-Henseleit buffer after the diabetic duration. After the maximum left ventricular dP/dt and cardiac efficiency were calculated, the myocardial contents of ATP and creatine phosphate (P-Cr) and myocardial energy metabolism were assessed by cytosolic phosphorylation potential. Peak positive and negative dP/dt, and cardiac efficiency decreased significantly in group DM compared with group C, while there were no significant differences between groups C and DMV. The myocardial contents of ATP (micromol/g wet heart) and P-Cr (micromol/g wet heart), and cytosolic phosphorylation potential (M(-1)) increased from 2.72 +/- 0.46. 1.45 +/- 0.58. and 3,530 +/- 1,220 in group DM to 3.88 +/- 0.76, 3.81 +/- 1.36, and 11,200 +/- 2,400 in group DMV, respectively. It is concluded that vanadium restored the production of high energy phosphates in the myocardium and improved myocardial dysfunction by regulating metabolic processes in diabetic rat hearts.

Jpn Heart J. 2003 Sep;44(5):745-57