Noella A. Bryden

Elevated Intakes of Supplemental Chromium Improve Glucose and Insulin Variables in Individuals With Type 2 Diabetes

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 μmol (100 μg) Cr as chromium picolinate two times per day, or 3) 9.6 μmol (500 μg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 pg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 ± 0.2%; 3.85 pmol Cr, 7.5 ± 0.2%; 19.2 pmol Cr, 6.6 ± 0.1%). Fasting glucose was lower in the 19.2-μmol group after 2 and 4 months (4-month values: placebo, 8.8 ± 0.3 mmol/1; 19.2 μmol Cr, 7.1 ± 0.2 mmol/1). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 μmol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 ± 0.4 mmol/1; 19.2 μmol Cr, 10.5 ± 0.2 mmol/1). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 μmol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Lack of toxicity of chromium chloride and chromium picolinate in rats.

OBJECTIVE To evaluate the safety of chromium (Cr) as a nutrient supplement. Several recent studies have reported beneficial effects of supplemental Cr at levels higher than the upper limit of the suggested intake for Cr. Trivalent Cr is considered relatively nontoxic but some recent unconfirmed studies have questioned its toxicity. We evaluated the toxicity of Cr chloride and a more bioavailable form of trivalent Cr, Cr tripicolinate. METHODS Harlan Sprague Dawley rats (4 weeks of age) were fed a stock diet to which was added 0, 5, 25, 50 or 100 mg of Cr per kg of diet as chloride or picolinate. Fasting blood samples were taken at 11 and 17 weeks and animals sacrificed at 24 weeks of age. Lack of toxicity was demonstrated by blood and histological measurements. Chromium incorporation into tissues was determined by graphite furnace atomic absorption. RESULTS There were no statistically significant differences in body weight, organ weights or blood variables among all the groups tested at 11, 17 and 24 weeks. Blood variables measured were glucose, cholesterol, triglycerides, blood urea nitrogen, lactic acid dehydrogenase, transaminases, total protein and creatinine. Histological evaluation of the liver and kidney of control and animals fed 100 mg/kg Cr as Cr chloride or picolinate also did not show any detectable differences. Liver and kidney Cr concentrations increased linearly for both the Cr chloride and picolinate fed animals. CONCLUSIONS These data demonstrate a lack of toxicity of trivalent Cr, at levels that are on a per kg basis, several thousand times the upper limit of the estimated safe and adequate daily dietary intake for humans. Animals consuming the picolinate supplemented diets had several-fold higher Cr concentrations in both the liver and kidney than those fed Cr chloride.

Dietary Chromium Intake Freely Chosen Diets, Institutional Diets, and Individual Foods

Chromium content of 22 daily diets, designed by nutritionists to be well-balanced, ranged from 8.4 to 23.7 μg/1000 cal with a mean ±SEM chromium content of 13.4±1.1 μg/1000 cal. Most dairy products are low in chromium and provide <0.6μg/serving. Meats, poultry, and fish are also low in chromium, providing 2 μg of chromium or less per serving. Chromium contents of grain products, fruits, and vegetables vary widely, with some foods providing >20 μg/serving. In summary, chromium content of individual foods varies, and is dependent upon chromium introduced in the growing, transport, processing, and fortification of the food. Even well-balanced diets may contain suboptimal levels of dietary chromium.

Dietary chromium effects on tissue chromium concentrations and chromium absorption in rats

Chromium (Cr) absorption is low (<1%) and there is a need to find Cr compounds that are absorbed better than inorganic Cr salts. Therefore, the incorporation of nine different chromium (Cr) compounds on tissue Cr concentration of 6-week male Wistar rats was investigated. Chromium compounds tested were Cr chloride (Cr chloride), Cr acetate (Cr acetate), Cr potassium sulfate (CrAlum), Cr trihistidine (Cr histidine), Cr triglycine (Cr glycine), Cr trinicotinic acid (CrNA), Cr dinicotinic acid dihistidine (CrNA-HIS), Cr tripicolinic acid (Cr picolinate), and Cr dinicotinic acid diglycine cysteine glutamic acid (CrNA-AA). Complexes were fed to weanling rats for 3 weeks at 5,000 ng of Cr/g of diet. Basal control diet was a cornstarch-based diet containing 30 ng Cr/g. Chromium incorporation into the kidney was greatest for CrNA-AA complex (850 ng/g dry wt) followed by CrAlum (407 ng/g), Cr acetate (397), CrNA-HIS (394), Cr picolinate (368), Cr glycine (343), Cr nicotinate (166), Cr chloride (74), CrHIS (49), and control (23 ng/g). Chromium concentration of the liver was greatest for the Cr picolinate compound (50 ng/g) followed by CrNA-AA and Cr acetate. Liver Cr concentrations of remaining complexes were not significantly different from those of the control animals that received no added Cr. Chromium concentrations were significantly greater in the kidney than those for the liver, spleen, heart, lungs, and gastrocnemius muscle. Supplemental Cr did not affect tissue zinc and copper but did alter tissue iron concentrations. Absorption of radioactive forms of Cr did not explain the differences in tissue Cr concentrations. Chromium absorption after 4 hours and retention after 24 hours were not significantly different for the forms of Cr tested. These data demonstrate that Cr concentrations are greatest in the kidney and that the form of dietary Cr significantly affects tissue Cr concentrations. Absorption of Cr does not correlate with tissue Cr concentrations and blood Cr is not in equilibrium with tissue Cr stores.

Insulin potentiating factor and chromium content of selected foods and spices

An unidentified factor that potentiates the action of insulin in glucose metabolism was investigated in selected foods and spices. Chromium content of these foods and spices was also determined. Foods and spices were extracted with 0.1N NH4OH (1∶20, w/v) and the supernatants assayed for insulin potentiation activity in the rat epididymal fat cell assay (see ref.6). Among the selected foods, tuna fish, peanut butter, and vanilla ice cream had some insulin potentiating activity. Among the spices, apple pie spice, cinnamon, cloves, bay leaves, and turmeric potentiated insulin activity more than three-fold. Chromium concentration of foods ranged from 1 to 145 ng/g, and spices ranged from 4 to 1818 ng/g. Insulin potentiating activity of foods and spices did not correlate with total chromium. Spices are generally used for flavor and taste in food preparations, but cinnamon, cloves, bay leaves, and turmeric may have an additional role in glucose metabolism.

Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables

Seventy-six normal, free-living subjects were given supplements of 200 micrograms chromium (Cr) in the form of chromic chloride or a placebo in a double-blind crossover study with 3-month experimental periods. Twenty of the 76 subjects had serum glucose concentrations greater than or equal to 100 mg/dL 90 minutes after a glucose challenge (1 g glucose per kilogram of body weight). Chromium supplementation significantly decreased (P less than 0.05) the 90-minute glucose concentration of these subjects from 135 +/- 9 to 116 +/- 11 mg/dL; fasting glucose concentrations also decreased significantly. The 90-minute serum glucose levels of the 35 subjects with glucose concentrations less than the fasting serum glucose level were increased significantly by Cr supplementation, from 71 +/- 1 to 81 +/- 4 mg/dL. Fasting and 90-minute serum glucose concentrations of the remaining subjects who displayed 90-minute glucose concentrations greater than fasting levels but less than 100 mg/dL were not affected by Cr supplementation. In this study, immunoreactive serum insulin concentration, body weight, lipids, and other selected clinical variables did not change significantly during Cr supplementation. These data demonstrate that Cr supplementation decreases the serum glucose levels of subjects with 90-minute glucose concentrations greater than or equal to 100 mg/dL following a glucose challenge, increases serum glucose levels of subjects with 90-minute glucose concentrations less than fasting levels, and has no effect on the serum glucose levels of subjects with 90-minute glucose values similar to but greater than fasting levels.

Effect of Exercise (Running) on Serum Glucose, Insulin, Glucagon, and Chromium Excretion

Chromium is involved in normal glucose metabolism. To test whether chromium is also associated with the exercise-induced increases in glucose utilization, urinary chromium excretion, serum glucose, insulin, and glucagon of nine male runners (23–46 yr) were evaluated. Blood samples were taken prior to, immediately following, and 2 h after a strenuous 6-mile run. Urine samples were also taken at these times, and total daily urine collections were made the day of the run and the following day. Mean serum glucose for all runners immediately after running was 185 ± 19 mg/dl compared with 90 ± 1 mg/dl (mean ± SE) prior to running. Mean serum glucagon immediately after running was significantly elevated compared with that observed prior to or 2 h after running; serum insulin levels were not altered significantly. Mean urinary chromium concentration was increased nearly five-fold 2 h after running; similar results were obtained when chromium concentration was expressed per mg of creatinine. Total daily urinary Cr excretion was approximately two times higher the day of running compared with the following nonrun day. Daily urinary excretion of sodium, potassium, and calcium were measured to determine if exercise had a general nonspecific effect on renal function; daily urinary excretion of these was not changed by exercise. These data demonstrate that accompanying the exercise-induced changes associated with increased glucose utilization, there is a significant increase in chromium excretion.

Acute effects on chromium, copper, zinc, and selected clinical variables in urine and serum of male runners

Nine male runners (23-46 yr) ran 6 mi near their maximal pace. Blood and urine samples were obtained prior to, immediately after, and 2 h following the run; 24-h urine collections were also taken on the run and nonrun days. Serum chromium increased significantly (P < 0.05) from 0.12 ± 0.02 (mean ± SE) to 0.17 ± 0.03 ng/mL immediately following running and remained elevated, 0.19 ± 0.03 ng/mL, after 2 h. Urinary chromium concentration was elevated several-fold 2 h following running and daily urinary chromium losses were about twofold higher on the day of the run compared to a rest day. Serum zinc was not significantly different from prerun values immediately following running, 81 ± 4 and 85 ± 4 pμg/dL, respectively, but then decreased significantly to 75 ± 4 2 h after exercise. Urinary zinc concentration was elevated more than twofold 2 h after running and total urinary losses on the day of the run were more than 1.5-fold higher than those on the nonrun day. Serum copper was not altered by exercise. Serum high density lipoprotein (HDL) cholesterol, but not total cholesterol increased significantly following running. HDL cholesterol values were similar to prerun values within 2 h of running. Serum triglycerides, phosphate, creatinine, bilirubin, uric acid, and alkaline phosphatase were also elevated immediately following running, whereas albumin, total protein, and blood urea nitrogen remained constant. These data demonstrate that accompanying the transitory changes in selected clinical indices caused by strenuous running there are alterations in chromium and zinc concentrations in serum and urine and increased specific urinary losses of these essential nutrients.

Stability and absorption of chromium and absorption of chromium histidinate complexes by humans.

Increased intake of chromium (Cr) often leads to improvements in glucose, insulin, lipids, and related variables in studies involving humans and experimental and farm animals. However, the results are often variable, depending not only on the selection of subjects but also dietary conditions and the form of supplemental Cr used. Our objective was to find a Cr supplement suitable for humans that was absorbed better than any of those available. Chromium absorption by six adult subjects, three males and three females, was determined based on the amount of Cr excreted in the urine in the initial 2 d following intake of 200 μg of Cr of the various forms of chromium tested. The absorption of the newly synthesized complexes was greatest for those containing histidine. Urinary Cr losses for six control subjects consuming 200 μg of Cr as Cr histidinate increased from basal levels of 256±48 to 3670±338 ng/d compared with 2082±201 ng for Cr picolinate, the currently most popular nutrient supplement, in the 48h following Cr consumption. Chromium histidinate complexes were stable and absorption was similar to the initial values after more than 2 yr. Mixing of some of the complexes with starch, which was postulated to improve Cr absorption, was shown to essentially block Cr absorption within 1 mo. These data demonstrate that urinary Cr losses need to be determined because stability and absorption of the Cr complexes varies widely and could be responsible for the variability in some of the Cr supplementation studies. Chromium ***DIRECT SUPPORT *** A02Q2015 00003 histidinate complexes are absorbed better than any of the Cr complexes currently available and need to be evaluated as Cr nutritional supplements.

Effects of carbohydrate loading and underwater exercise on circulating cortisol, insulin and urinary losses of chromium and zinc

SummaryThe effects of carbohydrate loading on relative stress responses of eight male subjects performing intermittent leg exercise at 80% maximum oxygen consumption during headout immersion in 25°C water were tested. Carbohydrate loading increased the number of work cycles completed, with less physical stress compared with that completed following the control diet period. Pre-exercise serum cortisol values were similar on both diets prior to exercise but following exercise control values were greater (1152, 94 vs 858, 77 nmol l−1; mean, SEM). Chromium losses, which have been shown to correlate with stress, were lower during the carbohydrate loading period, 8.6, 1.3 vs 12.4, 2.0 ng h−1, and were correlated with post-exercise serum cortisol. Urinary zinc losses were also lower during carbohydrate loading, while urinary losses of potassium, magnesium and calcium remained constant. Insulin values decreased similarly following exercise in both groups and were not altered by carbohydrate loading. These data demonstrate that carbohydrate loading increases immersion exercise output with less stress as determined by serum cortisol and urinary chromium losses.