Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.

Diabetes, 46(11):1786-91 1997 Nov

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 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) 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 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2%; 3.85 micromol Cr, 7.5 +/- 0.2%; 19.2 micromol Cr, 6.6 +/- 0.1%). Fasting glucose was lower in the 19.2-micromol group after 2 and 4 months (4-month values: placebo, 8.8 +/- 0.3 mmol/l; 19.2 micromol Cr, 7.1 +/- 0.2 mmol/l). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 micromol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 +/- 0.4 mmo/l; 19.2 micromol Cr, 10.5 +/- 0.2 mmol/l). 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 micromol/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.

The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes.

Metabolism, 41(7):768-71 1992 Jul

Seventy-six patients with established atherosclerotic disease were treated daily with either 250 micrograms of chromium orally as chromium chloride or a placebo for a period of 7 to 16 months (mean, 11.1 months). Serum chromium increased from 2.69 +/- 0.09 to 12.12 +/- 0.77 nmol/L (mean +/- SE, P less than .005). Serum triglycerides were lower (1.68 +/- 0.11 and 2.10 +/- 0.14 nmol/L, respectively; P less than .02) in the chromium-treated patients than in the patients who received placebo, and serum high-density lipoprotein (HDL) increased (from 0.94 +/- 0.05 to 1.14 +/- 0.07 mmol/L, P less than .005) in the patients who received chromium. There was no change in serum cholesterol or blood glucose during the study.

Hypocholesterolemic effects of nicotinic acid and chromium supplementation.

J Fam Pract, 18(6):603-6 1988 Dec

During the course of a study of the hypoglycemic effects of nicotinic acid and chromium on humans, two hypercholesterolemic subjects were found to experience clinically significant decreases in serum cholesterol levels. These subjects have now been followed for one year. The first subject had a cholesterol level of 10.33 mmol/L (399 mg/dL). Daily supplementation for four weeks with 100 mg of nicotinic acid (niacin) and 200 micrograms of chromium chloride led to a decrease in serum cholesterol to 8.86 mmol/L (342 mg/dL). Further supplementation for four months led to a further decrease in serum cholesterol to 7.25 mmol/L (280 mg/dL). The second subject had a cholesterol level of 8.73 mmol/L (337 mg/dL). Four weeks of supplementation lowered the level to 6.73 mmol/L (260 mg/dL). When supplementation was discontinued, the cholesterol level rose slightly. When supplementation was reinstituted, the cholesterol level decreased to 6.68 mmol/L (258 mg/dL).

Chromium in human nutrition: a review [see comments]

J Nutr, 1993 Apr, 123(4): 626-33

This review summarizes the results of 15 controlled studies supplementing defined Cr(III) compounds to subjects with impaired glucose tolerance. Three of these (3-4 mumol Cr/d for > 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research. The development and validation of a procedure to diagnose chromium status is the second challenge. Such a test would allow the assessment of incidence and severity of deficiency in the population and the selection of deficiency in the population and the selection of chromium-responsive individuals. The third challenge is the definition of chromium's mode of action on parameters of lipid metabolism that have been reported from some studies but not others. Future research along these lines might establish whether chromium deficiency is a factor in the much discussed Syndrome X of insulin resistance.

Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly subjects

Diabetes, 1980 Nov, 29(11): 919-25

Twenty-four volunteers, mean age 78, including eight mildly non-insulin- dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium- poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.

Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. A randomized, controlled trial [see comments]

Ann Intern Med, 1991 Dec 15, 115(12): 917-24

OBJECTIVE: To determine the efficacy of glucose tolerance factor (GTF)- chromium for increasing serum levels of high-density lipoprotein (HDL) cholesterol in patients taking beta-blockers. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Mixed primary and referral-based outpatient clinic at a university-affiliated VA Medical Center. PATIENTS: Referred sample of 72 men receiving beta-blockers, mainly for hypertension. Sixty-three patients (88%) completed the study. INTERVENTIONS: Current medications, including beta-blockers, were continued. During the 8-week treatment phase, patients in the chromium group received a total daily dose of 600 micrograms of biologically active chromium divided into three equal doses; control patients received a placebo of identical appearance and taste. MEASUREMENTS: Serum levels of total cholesterol and HDL cholesterol were measured. MAIN RESULTS: Mean baseline levels of HDL and total cholesterol (+/- SD) were 0.93 +/- 0.28 mmol/L and 6.0 +/- 1.0 mmol/L (36 +/- 11.1 mg/dL and 232 +/- 38.5 mg/dL), respectively. The difference between groups in adjusted mean change in HDL cholesterol levels, accounting for baseline HDL cholesterol levels, age, weight change, and baseline total cholesterol levels, was 0.15 mmol/L (5.8 mg/dL) (P = 0.01) with a 95% Cl showing that the treatment effect was greater than +0.04 mmol/L (+1.4 mg/dL). Mean total cholesterol, triglycerides and body weight did not change significantly during treatment for either group. Compliance as measured by pill count was 85%, and few side effects were reported. Two months after the end of treatment, the between-group difference in adjusted mean change from baseline to end of post-treatment follow-up was -0.003 mmol/L (-0.1 mg/dL). CONCLUSION: Two months of chromium supplementation resulted in a clinically useful increase in HDL cholesterol levels in men taking beta-blockers.

Trivalent chromium and the diabetes prevention program.

Med Hypotheses, 49(1):47-9 1997 Jul

The Diabetes Prevention Program is a new, 150 million dollar, NIH-sponsored study designed to determine whether non-insulin-dependent diabetes mellitus can be prevented or delayed in persons with impaired glucose tolerance. Four thousand subjects will be randomly assigned to one of four study groups and followed for 4.5 years. Study groups include intensive lifestyle intervention with diet and exercise; metformin (Glucophage) or troglitazone (an investigational drug) with standard diet and exercise; and a control group. Insulin resistance is an important pathogenic factor in impaired glucose tolerance. Trivalent chromium, a dietary supplement that potentiates the action of insulin, was not included in the program. Like metformin and troglitazone, trivalent chromium decreases insulin resistance and has an acceptable side-effect profile; furthermore, it is available at a fraction of their cost. Trivalent chromium should have been included in the Diabetes Prevention Program; it is unfortunate that it was omitted.

Chromium and other insulin sensitizers may enhance glucagon secretion: implications for hypoglycemia and weight control.

Med Hypotheses, 46(2):77-80 1996 Feb

Increased pancreatic beta-cell secretory activity usually is associated with decreased alpha-cell activity; stimulated beta-cells release gamma-aminobutyric acid, which hyperpolarizes alpha-cells, inhibiting glucagon release. Thus, insulin secretion and glucagon secretion are usually inversely coupled. This suggests that chromium and other insulin-sensitizing modalities, by down-regulating beta-cell activity, may increase glucagon secretion. Such an effect might play a role in the documented therapeutic activity of supplemental chromium and biguanides in reactive hypoglycemia, and might also be of benefit to dieters.

Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy--preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline.

Med Hypotheses, 50(5):435-49 1998 May

Impaired microcirculatory perfusion appears to be crucial to the pathogenesis of both neuropathy and retinopathy in diabetics. This in turn reflects a hyperglycemically mediated perturbation of vascular endothelial function that entails overactivation of protein kinase C, reduced availability of nitric oxide, increased production of superoxide and endothelin, impaired insulin function, diminished synthesis of prostacyclin/PGE1, and increased activation and endothelial adherence of leukocytes. These dysfunctions may be addressed with a supplementation program that includes high-dose antioxidants, fish oil, gamma-linolenic acid, chromium, arginine, carnitine, and ginkgolides. Pharmaceuticals likely to be of benefit in this regard include pentoxifylline, probucol, replacement estrogens, and inhibitors of angiotensin converting enzyme and aldose reductase.

Neurologic symptoms due to possible chromium deficiency in long-term parenteral nutrition that closely mimic metronidazole-induced syndromes.

JPEN J Parenter Enteral Nutr, 50(5):123-7 1996 Mar-Apr

BACKGROUND: We previously described a patient on home parenteral nutrition (HPN) who developed glucose intolerance and neuropathy that only responded to an infusion of chromium. A patient on HPN who had neuropathy and glucose intolerance was studied. He was also on metronidazole, which could have caused the neuropathy, but the symptoms and signs persisted. METHODS: Baseline clinical examination, nerve conduction studies, serum vitamin and trace element levels, and glucose tolerance were measured. Then, 250 micrograms of trivalent chromium as the chloride salt was infused daily for 2 weeks. The above studies were repeated. RESULTS: The patient at baseline had peripheral neuropathy of the axonal type and was glucose intolerant. Serum chromium was raised in this patient above the reference range. Despite raised serum levels, the infusion of chromium resulted in clinical remission that was marked 4 days after starting the infusion. Normalization of nerve conduction also occurred within 3 weeks of the initial study. CONCLUSIONS: Neuropathy and glucose intolerance may occur despite increased serum chromium levels and respond to chromium infusion. The previous use of drugs such as metronidazole should not exclude chromium as a potential treatment for neuropathy in HPN patients.

Effects of chromium supplementation on fasting insulin levels and lipid parameters in healthy, non-obese young subjects.

Diabetes Res Clin Pract, 28(3):179-84 1995 Jun

Trivalent chromium is an essential trace element for normal carbohydrate metabolism and insulin sensitivity. Because of this biological activity, chromium supplementation has been studied as a potential therapy of insulin resistant states and dyslipidemias, and has been promoted as a health aid to the general population. To determine if there is a risk of subclinical chromium deficiency in young, otherwise healthy adults, we evaluated the effect of chromium supplementation, versus placebo, on insulin levels and serum lipids in a double-blind, randomized trial in 26 young adults (mean age 36 years). Fasting levels of glucose, immunoreactive insulin (IRI), and lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) were measured before and after 90 days of daily supplementation with a chromium (III)-nicotinate preparation, containing 220 micrograms elemental chromium, or placebo. There were no statistically significant differences in the percentage change of fasting glucose, IRI or lipids between the chromium (n = 15) and placebo (n = 11) groups after 90 days of supplementation. However, those individuals within the chromium group with initial fasting IRI levels greater than 35 pmol/l had a significant decrease in IRI level after supplementation (P < 0.03) despite no significant changes in serum lipids. These subjects may benefit from chromium supplementation by improving insulin sensitivity and cardiovascular risk over time. (<0.03) despite no significant changes in serum lipids. These subjects may benefit from chromium supplementation by improving insulin sensitivity and cardiovascular risk over time.

Nutritional factors influencing the glucose/insulin system: chromium.

J Am Coll Nutr, 28(3):404-10 1997 Oct

Chromium (Cr) improves the glucose/insulin system in subjects with hypoglycemia, hyperglycemia, diabetes and hyperlipemia with no detectable effects on control subjects. Chromium improves insulin binding, insulin receptor number, insulin internalization, beta cell sensitivity and insulin receptor enzymes with overall increases in insulin sensitivity. There have been several studies involving Cr supplementation of subjects with NIDDM and/or lipemia and most have reported beneficial effects of Cr on the glucose/insulin system. In a recent study, Chinese subjects with NIDDM were divided into three groups of 60 subjects and supplemented with placebo, 100 or 500 micrograms of Cr as chromium picolinate 2 times per day for 4 months. Improvements in the glucose/insulin system were highly significant in the subjects receiving 500 micrograms twice per day with less or no significant improvements in the subjects receiving 100 micrograms twice per day after 2 and 4 months. In summary, Cr is involved in the control of the glucose/insulin system and the amount, and likely form of chromium, are critical when evaluating the role of chromium in this system.

Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets.

Am J Clin Nutr, 54(5):909-16 1991 Nov

The effects of low-chromium diets containing chromium in the lowest quartile of normal intake on glucose tolerance and related variables in 11 females and 6 male subjects were evaluated. Subjects with glucose concentration greater than 5.56 mmol/L but less than 11.1 mmol/L 90 min after an oral-glucose challenge were designated as the hyperglycemic group and the remainder, the control group. Glucose tolerance and circulating insulin and glucagon of the hyperglycemic group all improved during chromium supplementation (200 micrograms/d) whereas those of the control group were unchanged. Glucose and insulin concentrations 60 min after the oral-glucose challenge and the sum of the 0-90 min and 0-240 min glucose values were all significantly lower after chromium supplementation in the hyperglycemic group. These data demonstrate that consumption of diets in the lowest 25% of normal chromium intake lead to detrimental effects on glucose tolerance, insulin, and glucagon in subjects with mildly impaired glucose tolerance.

Chromium induced clinical improvement in symptomatic hypoglycemia.

Biol Trace Elem Res, 54(5):229-36 1988 Sep-Dec

The present study included 20 patients indicating clinical symptoms of hypoglycemia, of which 19 showed a minimal glucose level in the tolerance curve above 2.2 mmol/L (limit for glucose induced hypoglycemia). This clinical state is defined here as "symptomatic hypoglycemia. All individuals were studied for effects of a daily intake for three mo of a yeast chromium supplement (125 micrograms Cr/d). The patients were followed by means of their oral glucose tolerance curve (1 g glucose/kg body wt) and by an interrogation scheme prior to during and after chromium supplementation. During three mo of chromium supplementation, a decrease was found in the negative part of the glucose tolerance curve, i.e., the part of the curve being below the fasting level in eight patients (40%). However, one mo after treatment, 10 patients out of 13 (77%) showed decreased areas of the negative part of the glucose tolerance curve compared to the values during treatment, and 11 out of 15 (73%) showed decreases in the negative part of the curve when post-treatment data were compared to ante-treatment data. The subjective clinical effects were followed by means of a questionnaire. Subjectively, the effects of organo-chromium were especially pronounced on chilliness. Thus seven (47%) indicated improvement and two (15%) indicated that the chilliness disappeared. However, trembling, emotional instability, and disorientation symptoms improved as well.

A study of chromium in human cataractous lenses and whole blood of diabetics, senile, and normal population.

Biol Trace Elem Res, 54(5):133-8 1992 Jan-Mar

Chromium (Cr) is of known biological importance, necessary for the maintenance of normal glucose metabolism. There is a lower level of blood Cr concentrations in cases of diabetes. Diabetes carries a risk of cataract development, so the potential effects of Cr on the eye may need to be studied in more depth. The presence of this trace element in both normal and cataractous human lenses has to our knowledge not been investigated so far. The concentration of total Cr in 61 human lenses and 38 blood samples was determined by electrothermal atomic absorption spectrometry with Zeeman effect (EAASZ). Analysis of the levels of Cr in human lenses shows a significant difference between normal and diabetic populations, and an absence of difference between senile and diabetic populations.

Chromium deficiency and cardiovascular risk.

Cardiovasc Res, 18(10):591-6 1984 Oct

Recent measurements have demonstrated that plasma chromium levels in patients with coronary artery disease are very much lower than in normal subjects. A review of the literature concerning the physiological functions of chromium (or GTF) shows it to be implicated in most of the known factors of cardiovascular risk, via its effect on insulin levels and activities. Chromium deficiency leads to impaired lipid and glucide metabolism and results in high circulating insulin levels, the probable consequences of which suggest that chromium deficiency may be a primary risk factor in cardiovascular disease.

Effects of chromium and guar on sugar-induced hypertension in rats

Clin Nephrol, 1995 Sep, 44(3): 170-7

Ingestion of sugars (sucrose, fructose, glucose) by various rat strains is associated with perturbations in the glucose/insulin system and higher systolic blood pressure (SBP). The association suggests causality, because alterations in insulin metabolism have been found in essential hypertension and many experimental forms of hypertension. To test the hypothesis that sugar-induced SBP elevation is secondary to perturbed insulin metabolism, we examined in 2 experiments effects of chromium and guar, substances known to affect insulin metabolism, on SBP of Spontaneously Hypertensive Rats (SHR). In both studies, sucrose compared to starch ingestion caused significant elevation of SBP; but addition of 2 chromium nicotinate complexes and guar prevented development of sugar-induced SBP elevations. The basal, genetic hypertension of the SHR was not affected by either nutrient. An additional finding in the first study was that sugar-consuming SHR supplemented with chromium had greater BW and increased organ weight (kidney, spleen, and liver) than nonsupplemented SHR. Accordingly, we have shown that two different mechanisms known to ameliorate insulin perturbations, use of chromium and guar, prevent sugar-induced SBP elevations. Since essential hypertension may be due to insulin perturbations and high dose chromium supplementation seems nontoxic, this may prove to be a useful means to lower blood pressure (BP) in some essential hypertensives, as well as diabetic hypertensives. Soluble fiber in the form of guar is also quite effective in favorably influencing sugar-induced SBP elevations.