Bio-Chromium Mechanism of Action

Pharmacology: Pharmacodynamics: The exact biological function of chromium has not been fully determined. Chromium is believed to potentiate the action of insulin by influencing its interaction with insulin receptors [A-6384, A-6385, A-7579, B-9256]. Insulin is primarily responsible for regulation of glucose metabolism, but also has a role in lipid metabolism due to the relationship between hyperglycaemia, hyperinsulinaemia,and hypertriglyceridaemia [A-3848, A-7579, B-9256]. Other physiological functions have been attributed to chromium (e.g., a role in thyroid function and protein metabolism), though the mechanism by which chromium acts and the biological significance are uncertain [A-5875]. However, a recent review concluded that animal and cell-based trials indicated that "chromium potentiates the actions of insulin, augments the insulin signaling pathway, blunts the negative-regulators of insulin signaling, enhances AMPK activity, up-regulating cellular glucose uptake, and attenuates oxidative stress" [A-9386].
Pharmacokinetics: Absorption of chromium is low (< ~ 2.5% [B-9256]) and falls as the amount of chromium ingested increases [A-5875]. Organic chromium is better absorbed than inorganic chromium, though its efficacy of absorption remains low [A-3911, A-6744]. Chromium is absorbed in the intestine by passive uptake and probably also by active uptake [A-5875]. Chromium is excreted primarily via urine, with small amounts lost in hair, sweat, and, in the case of organic chromium compounds, via bile [A-5875, B-9256]. Studies in diabetics have found doses of organic chromium (chromium in brewer's yeast) several times smaller than those of inorganic chromium (as chromium chloride) to result in comparable increases in chromium level in blood, hair, and erythrocytes [A-229, A-6744], and indeed in a scientific opinion from 2012, EFSA reported that ChromoPrecise was potentially up to 10 times more bioavailable than chromium chloride [EFSA Opnion].
General information: Chromium intake and body chromium status: Due to the uncertainty about how chromium deficiency in humans manifests itself, the actual requirement for chromium is not known. The recommended daily intake for chromium in most countries is in the range 50 - 200 μg [B-1714]. Analyses of diets in Scandinavian, the USA, United Kingdom, and New Zealand suggest that chromium intake is typically in the range 30 - 40μg/day [A-3, A-4710, A-5875]. Refining foods usually depletes them of chromium, and foods high in simple sugars are not only low in chromium, but also promote chromium loss [B-9256]. Assessing chromium status is difficult, as blood or tissue levels are not considered reliable markers. This situation also means that it is presently unclear whether any beneficial effect of chromium supplementation is simply due to correcting marginal deficiency or is due to a pharmacological effect of supra-physiological doses.
Forms of chromium in the body and in supplements: In the first studies of the biological role of chromium, brewer's yeast was found to reverse an impaired response to increased blood glucose level in chromium-depleted rats [A-6384]. Subsequent studies suggested that chromium, of which brewer's yeast is a rich source, was responsible for this effect. The chromium-containing substance in brewer's yeast that was considered responsible for the beneficial effect on glucose metabolism was named Glucose Tolerance Factor (GTF). GTF has been proposed to contain chromium, nicotinic acid, and the amino acids glycine, cysteine, and glutamic acid, though a molecule with such a structure and capable of reversing insulin resistance has not been isolated or synthesised [A-5875, A-6384], however, a recent study reported progress in the identification of the molecule [A-9389].
Early studies using brewer's yeast [A-227, A-229, A-6980, A-6984, A-6985], and subsequent studies using specific strains of chromium-enriched yeast [A-5939, A-6752, A-6986] found beneficial effects on glucose metabolism. The forms of chromium present in these yeasts are not known, but are presumed to be organic compounds. It is also unclear if such compounds are directly responsible for the improvements in glucose metabolism seen (i.e. they are a glucose tolerance factor), or if they are simply a source of chromium that can be utilised in processes that regulate glucose metabolism. An in vitro study using adipocytes isolated chromium-depleted rats found that yeast GTF did not have intrinsic activity (i.e. a direct interaction with insulin or insulin receptors), but rather was acting as a source of chromium [A-6384]. The same function was also attributed to chromium picolinate (a chromium compound found in supplements but not in the body) [A-6384]. Thus, diet and chromium supplements appear to function as a source of chromium that can be incorporated into biologically active chromium molecules, one candidate being the so-called low-molecular-weight chromium-binding substance (LMWCr), also known as cromodulin [A-6384, A-6385].
Bio-Chromium contains chromium in the form of chromium-enriched yeast, produced by culturing a specific strain of baker's Yeast (Saccharomyces cerevisiae) in a growth medium enriched with chromium. As the yeast grows, it absorbs inorganic chmium from the medium and converts the vast majority to organic chromium compounds. At the end of the culture period, the yeast is collected and inactivated by heat treatment. The growth medium is standardised and the culture process tightly controlled so that batches consistently meet quality requirements. The standardised chromium-enriched yeast manufactured by Pharma Nord is called ChromoPrecise.
Blood glucose control and the role of chromium: Blood glucose level is primarily controlled by the hormone insulin, which is excreted by the pancreas when blood glucose rises and broken down in the liver when blood glucose falls. In this way, blood glucose is normally held within an optimal range, and adverse effects associated with hyperglycaemia and hypoglycaemia (high and low blood glucose) are avoided. Control of blood sugar can be impaired if chromium status is inadequate, even when insulin is present in normal amounts or in excess [A-5875]. Evidence to support the role of chromium in the correct functioning of insulin is provided by reports of severe symptoms of diabetes in patients on total parenteral nutrition that did not include chromium [A-6749]. Administration of large amounts of exogenous insulin proved ineffective, whereas supplementation with chromium reduced diabetic symptoms to such an extent that treatment with exogenous insulin was no longer necessary. Chromium is thought to act by potentiating the efficacy of insulin, i.e. it has no direct role in blood glucose control, but rather enhances the action of insulin [A-5875, A-6382, A-6384, A-6385]. It has been proposed that chromium binds to a molecule called chromodulin, also known as low-molecular-weight chromium binding substance (LMWCr) [A-6382, A-6384, A-6385]. Once activated by the binding of chromium, chromodulin increases the insulin receptors activity and causes greater signaling activity and greater glucose transporter activity, in the presence of insulin, and possibly downregulates proteins involved in insulin resistance [A-9386].
Research: Animal and human studies have used various forms of chromium: earlier studies tended to use chromium chloride and brewer's yeast, while later studies have used chromium-enriched yeast, chromium picolinate, and other organic chromium compounds. As these forms of chromium do not appear to have intrinsic activity, but rather serve as a source of chromium, data for each form may be considered applicable to chromium in general. This assumes that chromium is absorbed and metabolised equally efficiently from the various forms. It has been suggested that the absorption and metabolism of chromium picolinate differs from that of other forms of chromium, and that chromium picolinate might also be harmful [A-5612, A-6198, A-6384]. Although the safety of chromium picolinate has been questioned [A-5358, A-5359, A-5875], clinical trials suggest that chromium picolinate is generally safe [A-6741, A-6815].
Insulin resistance: Resistance to the action of insulin (i.e. reduced insulin efficacy) precedes the development of diabetes, perhaps by several years. The first detectable sign of insulin resistance is a rise in blood insulin concentration [A-6749], as the body attempts to overcome reduced insulin efficacy by increasing the quantity secreted. Despite increased insulin production, control of blood glucose may be gradually lost, resulting in elevated fasting and post-meal blood glucose levels. Low dietary intake of chromium has been suggested to be associated with impaired glucose tolerance and fasting hyperglycaemia [A-3840]. It has been proposed that increased chromium intake may ensure optimum insulin efficacy, and so improve glycaemic control [A-442, A-3845, A-6749].
There are few recent studies on non-diabetic subjects, using organic forms of chromium, which are more readily absorbed, and as such information about the effect on prediabetic insulin resistance is inadequate.
A 2002 meta-analysis [A-6741] of controlled trials did not find a beneficial effect of chromium on blood glucose and insulin concentrations in non-diabetic subjects, though only two studies involving subjects with impaired glucose tolerance [A-6752, A-6955] were included. A subsequent study in which subjects with impaired glucose tolerance received 400 μg/d chromium (as chromium picolinate) twice daily or placebo for 3 months found no improvements in blood glucose, insulin or lipids [A-7537].
Overall, it is unclear if chromium supplementation has a beneficial effect on glycaemic control in subjects with insulin resistance. But Hua and colleague stipulate that is likely that chromium might augment insulin signaling in pre-diabetic subjects [A-9386].
As chromium supplementation is safe, persons with insulin resistance may try taking ~ 100 - 200 μg/d chromium for 2 - 3 months.
Diabetic hyperglycaemia: Type 1 diabetes mellitus: Type 1 diabetics have been found to absorb approximately twice as much ingested chromium, but also to excrete more than twice as much chromium, as healthy subjects [A-6749]. Some type 1 diabetics have also been found to have low levels of chromium in their tissues and hair, which may reflect marginal chromium status. It has been proposed that metabolic control mechanisms in type 1 diabetic attempt to compensate for a deficit of chromium by increasing absorption, but that the absorbed chromium is not effectively retained [A-6749]. Several small studies and case reports have described beneficial effects of chromium supplementation (e.g. reduced insulin requirement, decrease in glycosylated haemoglobin) in persons with type 1 diabetes [A-6749]. This might be explained by the fact that chromium potentiates the action of exogenous (injected) insulin in the same way as proposed for insulin produced by the body.
In one controlled study that included 21 type 1 diabetics, 4 months of chromium supplementation had no effect on fasting and post-prandial blood glucose or insulin levels or insulin requirements [A-229]. However, it may be relevant that the subjects received 150 μg chromium as chromium chloride or a brewer's yeast preparation that only provided 6 μg chromium. In an open study that included 48 type 1 diabetics, supplementation with 200 μg chromium (as chromium picolinate) for 10 days resulted in a positive response (i.e. improved rate of glucose disposal in an insulin sensitivity test) in 71% of the subjects [A-6765]. It was reported that these "responders" could reduce their insulin dose by 30% and experienced lesser variation in blood glucose level.
Type 2 diabetes mellitus is characterised by reduced insulin efficacy that results in decreased insulin-mediated glucose uptake and, consequently, fasting and post-meal hyperglycaemia - even in the presence of elevated blood insulin level. Blood chromium level has been found to be lower, and urinary chromium excretion higher, in type 2 diabetics compared to matched controls [A-5855, A-6397]. It has been proposed that low chromium intake may contribute to the development of insulin resistance and to type 2 diabetes, and that the condition itself may worsen chromium status due to impairment of kidney function. Kidney tubular reabsorption of filtered chromium is efficient (80 - 95% [A-5875]), but can be expected to fall with kidney damage. Chromium supplementation has been proposed as a measure to reduce the risk or extent of hyperglycaemia in type 2 diabetics. Reducing insulin resistance in type 2 diabetic may allow the introduction of hypoglycaemic agents and/or insulin therapy to be postponed.
The largest study of chromium supplementation and diabetic hyperglycaemia to date involved 833 Chinese type 2 diabetics taking 500 μg/d chromium (as chromium picolinate) for up to 10 months [A-6403]. Despite an open design and no control group, the study is considered worthy of mention due to its size and findings. All the participants took hypoglycaemic medicine and/or insulin, though possible changes to medication during the study are not mentioned. Both fasting and post-prandial blood glucose had decreased significantly after 1 month's supplementation, and remained stable over the following 2 - 10 months. Improved blood glucose control was seen in > 90% of subjects. After the first month, improvements in symptoms of excessive thirst, excessive urination, and fatigue were reported by ~ 86% of subjects. Similar effects reported by men and women.
A study in which 36 obese persons with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 17 weeks found a significant change in fasting blood glucose in favour of the chromium group, and a tendency for a greater decrease in fasting insulin in the chromium group compared to the placebo group (- 16.2% vs. - 9.5%) [A-7603]. Other measures of glycaemic control did not show any treatment-dependent changes. See Product specific research as follows for further details. A later study from the same group also found significant reductions in fasting plasma glucose and glycated hemoglobin after 8 weeks of supplementation [A-9220].
A study in which 53 obese persons with poorly controlled type 2 diabetes (HbA_1c > 8% and insulin requirement > 50 units/d) were randomised to 500 or 1000 μg/d chromium (as chromium picolinate), or placebo, for 6 months did not find any treatment-dependent changes in glycated haemoglobin (HbA_1C) or total daily dose of insulin [A-7655]. A subsequent study, by the same group, in which 57 persons with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 6 months did not find any treatment-dependent changes in fasting plasma glucose, glycated haemoglobin (HbA_1C), or insulin sensitivity (HOMA-IR) [A-7750]. Glycated haemoglobin in the normal range, but fasting glucose was elevated, giving the potential for this parameter to be improved with chromium supplementation.
Wang et al. (2007) examined 73 subjects with type 2 diabetes in an attempt to identify which metabolic and clinical characteristics may determine an individual's response to chromium supplementation [A-8031]. Data for glycated haemoglobin, oral glucose tolerance tests, body weight, body fat mass, and insulin sensitivity. were obtained at baseline. The subjects were then randomised to 1000 μg chromium (as chromium picolinate) or placebo for 6 months. The response rate to treatment (defined as an increase in insulin sensitivity) was 63% in the chromium group compared to 30% in the control group. The only parameter found to be significantly associated with the clinical response to chromium was whole-body insulin-mediated glucose disposal. While insulin resistance was found to be the major factor determining response to chromium supplementation, it only accounted for 40% of the response. The authors suggest that genetic factors may make a major contribution to the remaining 60% unexplained variance in response to chromium supplementation. Chromium status, which was not evaluated, was another.
In a follow-up study [A-9285], where 137 subjects with type 2 diabetes where examined and their response to chromium supplementation evaluated, the researchers found that a subgroup of responders (defined as individuals who was supplemented and had an increase in insulin sensitivity of 10% or more) consisting of 46% of the supplemented individuals, had statistically greater improvements in insulin sensitivity, fasting blood glucose and glycated hemoglobin. However, these parameters where all significantly worse in the responders group at baseline, and the marked improvements actually only achieved the baseline levels of the study cohort as a whole.
It is unclear which factors determine whether an individual will benefit from chromium supplementation, as a means of reducing hyperglycemia, but it evidence suggests that especially individuals with greater elevations in fasting blood sugar and HbAc as well as more reduced insulin sensitivity might benefit more than individuals with more normal values.
Overall, it remains unclear which persons with diabetic hyperglycaemia might benefit from chromium supplementation. As chromium supplementation is safe, persons with diabetes may try taking ~ 100 - 200 μg/d chromium for 2 - 3 months. Higher doses may be taken under the supervision of a physician. Persons using diabetes medicines are recommended to monitor their blood sugar (glucose) level upon starting to take chromium, as dose adjustment may be required.
Gestational and steroid-induced hyperglycaemia: Changes to maternal glucose metabolism during pregnancy in order to maintain the supply of glucose to the developing foetus (essentially mild insulin resistance) can progress to gestational diabetes in some cases [A-6749, A-6956]. A small trial in which 30 women with gestational diabetes were given 0, 4, or 8 μg/kg/d chromium (as chromium picolinate) for 8 weeks found improved glucose tolerance, lowered hyperglycaemia, and a small reduction in glycosylated haemoglobin, with a greater effect at the higher dose [A-6956]. However, cross sectional studies have failed to find a correlation between plasma Chromium levels and gestational diabetes [A-7537, A-9384].
Glucocorticoid (steroid) administration can lead to insulin resistance [A-6749, A-6956]. In an open study, 50 patients with uncontrolled steroid-induced diabetes (not responding satisfactorily to hypoglycaemic drugs and/or insulin, and with fasting blood glucose > 13.9 mmol/l) were given 200 μg chromium (as chromium picolinate) 3 times daily for 2 weeks [A-6957]. Before starting chromium supplementation, hypoglycaemic agents were reduced by 50%. Fasting and 2-h post-meal blood glucose were reduced to under 8.3 and 10.0 mmol/l, respectively, in 47 patients.
Hypoglycaemia: Two studies have examine the effect of chromium on hypoglycaemia. Supplementation of 8 women with symptoms of reactive hypoglycaemia with 200 μg/d chromium (as chromium chloride) or placebo for 3 months significantly reduced the extent of hypoglycaemia following an oral glucose test [A-442]. Improvements in symptoms of hypoglycaemia, such as trembling, sweating, and blurred vision were also reported. In an open, uncontrolled study, supplementation of 20 subjects with symptomatic hypoglycaemia with 125 μg/d chromium (as chromium-enriched yeast) for 3 months reduced hypoglycaemia following an oral glucose challenge in half the individuals [A-148] (see Product specific research for further details).
Blood lipid profile: Adverse changes to lipid metabolism are associated with insulin resistance and diabetes [A-3848, B-5535]. It has been suggested that hyperinsulinaemia due to insulin resistance leads to increased plasma triglycerides and reduced plasma HDL-cholesterol [A-3848], both of which are associated with an increased risk of atherosclerosis [A-59, A-3847, A-4948]. Many of the studies of the effect of chromium on glucose metabolism in healthy subjects and persons with insulin resistance or diabetes also examined blood lipids (total cholesterol, HDL- and LDL-cholesterol, triglycerides). The results have been inconsistent, with some studies finding improvements in at least one or more parameter (e.g. A-3210, A-3503, A-3847, A-4948, A-6744, A-6973,) while others have found no significant improvement in the measured parameters (e.g. A-233, A-442, A-6752, A-6778, A-6973, A-6977, A-6981, A-6988). The inconsistent response may reflect differences in the subjects' chromium status and/or the design of the various studies. Most studies have used chromium picolinate. One study using chromium yeast found no improvements in serum total cholesterol, HDL-cholesterol, or free fatty acids[A-6752].
A study in which 36 obese persons with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 17 weeks did not find any treatment-dependent changes in fasting blood lipids (total-, LDL-, and HDL-cholesterol, triglycerides, and apolipoproteins A-1 & B. [A-7603]. The subjects' baseline total cholesterol (5.6 mmol/l) was in the normal range, which may have limited the potential of the study to detect any beneficial effects of chromium supplementation on blood lipids. See Product specific research for further details.
A study in which 53 obese persons with poorly controlled type 2 diabetes (HbA_1c > 8% and insulin requirement > 50 units/d) were randomised to 500 or 1000 μg/d chromium (as chromium picolinate), or placebo, for 6 months [A-7655], in a post-hoc analysis of the relationship between increase in blood chromium concentration and the various blood lipid parameters, found weak, but statistically significant relationships (decreases) for total- and LDL- cholesterol, and the total-to-HDL cholesterol ratio, and the tendency for a relationship with triglycerides.
A subsequent study, by the same group in which 57 overweight persons with type 2 diabetes were randomised to 400 μg/d chromium (as Bio-Chromium), or placebo, for 6 months did not find any treatment-dependent changes in fasting blood lipids (total-, LDL-, and HDL-cholesterol, and triglycerides) [A-7750]. However, the baseline values for the parameters were well within the normal range (e.g. total cholesterol was ~4.5 mmol/l), limiting the potential of the study to detect any beneficial effects of chromium supplementation.
In a recent meta-analysis [A-9383], which included 15 studies, among others the 3 mentioned previously, the authors found that chromium supplementation had no effect on total cholesterol, significantly lowered triglycerides, had no significant effect on LDL-C but increased HDL-C.
Overall, it is unclear if chromium supplementation has a beneficial effect on blood lipid profile, though improvements seen in some studies suggest that optimal chromium status is desirable, and that the effect might be more pronounced in individuals with worse baseline levels.
Overweight and body composition: Due to the role of insulin in the regulation of glucose and lipid metabolism, chromium supplementation may aid weight control and have beneficial effects on body composition. The proposed beneficial effect of chromium on glucose metabolism may also reduce a tendency for hypoglycaemia that can lead to a craving for sweet, often calorie-rich, foods.
In a recent Cochrane review, in which the effect of chromium supplementation on overweight over a range of doses from 200 μg/d to 1000 μg/d was evaluated in a total of 622 subject from 9 trials, they found that chromium supplementation, compared to placebo resulted in a weightloss of 1,1 kg. However they found the evidence to be of low quality and did not find a dose-dependant effect [A-9382].
A small controlled study in which over-weight African-American women on a modest diet were given 200 μg/d chromium (as chromium picolinate) 3 times daily for 8 weeks found a significant loss of fat and a sparing of muscle [A-6658]. In contrast, a controlled study in which 44 moderately obese women following an exercise plan were given 400 μg chromium (as chromium picolinate) for 12 weeks found no effect on body weight or body composition [A-6778]. Other studies, some involving exercise, have not found a beneficial effect on body composition [A-5939, A-6955, A-6958, A-6959, A-6962, A-6972].
A well-controlled study involving women fed nutritionally balanced diets with controlled energy intake did not find supplementation with 200 μg/d chromium (as chromium picolinate) or placebo for 12 weeks to result in any differences in body weight or body fat [A-8033]. These findings suggest that chromium supplementation in it self does not reduce bodyweight, under energy controlled circumstances.
In a pilot study from 2013 [A-9381] it was found that chromium supplementation numerically reduced binge-eating episodes and a sensitivity analysis showed that the the 2 supplementation groups lost weight compared to placebo. The authors state that the small sample size caused a limited statistical power.
Similarly in a study from [A-9380] chromium supplementation, 1000 μg/d, had a beneficial effect on hunger levels, food intake under ad libitum conditions, feed cravings and resulted in a tendency towards weight loss compared to placebo. Based on a confirmatory study in rats, the authors speculate that chromiums effects might be partially caused by a direct effect on the brain.
Oxidative stress in diabetics: A controlled study in which 23 euglycaemic, 20 mildly hyperglycaemic, and 21 severely hyperglycaemic subjects were given 1000 μg/d chromium (as chromium-enriched yeast) or placebo for 6 months found evidence for a reduction in oxidative stress in the diabetic subjects, but an increase in the non-diabetic subjects [A-7102].
A study in which 36 obese persons with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 17 weeks found whole blood glutathione peroxidase activity and erythrocyte reduced glutathione to have increased slightly in the chromium group and decreased in the placebo group, resulting in a significant change in favour of the chromium group [A-7603]. Plasma total antioxidative capacity, plasma malondialdehyde, and erythrocyte superoxide dismutase did not show any treatment-dependent changes.
Product specific research: Clausen (1988) - Biol. Trace Elem. Res: 17 : 229-236 (A-148): In an open, uncontrolled study, 20 subjects with symptoms of hypoglycaemia were given 125 μg/d chromium as Bio-Chromium chromium-enriched yeast for 3 months [A-148]. An oral glucose test made one month after supplementation ended found the negative part of the glucose curve (i.e. that part of the curve under the normal fasting glucose level) to be reduced in 11 subjects (69%), unchanged in 2 subjects, and increased in 3 subjects compared to the baseline level. In response to a questionnaire, 7 patients (47%) reported a reduced sensitivity to cold following chromium supplementation, with sensitivity to cold disappearing totally in 2 subjects. Improvements in symptoms such as trembling hands, emotional instability, and disorientation were also reported.
Gaede P, et al (2003) N Engl J Med 348 383-93 (A-6888): The Steno-2 Study, compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.
Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin, 2 daily Bio-Antioxidant and 1 Bio-Chromium.
The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79).
In conclusion, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.
Racek et al. (2006) Biol. Trace Elem. Res . 109 : 215-230 (A-7603): 36 persons (27 women, 9 men) with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 17 weeks. The subjects had a mean age of 61 years and a mean BMI of 34. The subjects' diabetes was generally well-controlled (baseline glycated haemoglobin (HbA_1C)of 7.4%): in 29 cases by diet alone, while the remaining subjects used oral anti-hypoglycaemia medication. Chromium supplementation significantly increased blood (serum) chromium level relative to placebo, though in none of the subjects did it exceed the upper reference limit of 0.5 μg/l. Fasting blood glucose increased in the control group and decreased in the chromium group, resulting in a significant change in favour of the chromium group. Serum levels of glycated haemoglobin (HbA_1C), glycated protein, and fasting insulin did not differ significantly between the treatment groups, though there appeared to be a tendency for a greater decrease in fasting insulin in the chromium group compared to the placebo group (-16.2% vs. -9.5%). There were no treatment-dependent changes in fasting blood lipids (total-, LDL-, and HDL- cholesterol, triglycerides, and apolipoproteins A-1 & B. There was a tendency for a greater decrease in body weight in the chromium group compared to the placebo group (- 1.3 kg vs. - 0.3 kg). The authors noted that the upper normal or only marginally elevated values for a number of the parameters reflecting glycaemic control and lipid metabolism may have limited the potential of the study to detect any beneficial effects of chromium supplementation. With respect to markers of oxidative stress, whole blood glutathione peroxidase activity and erythrocyte reduced glutathione both increased slightly in the chromium group and decreased in the placebo group, resulting in a significant change in favour of the chromium group. Plasma total antioxidative capacity, plasma malondialdehyde, and erythrocyte superoxide dismutase did not show any treatment-dependent changes. No subjects withdrew from the study due to adverse effects. No undesirable changes to any of the 15 laboratory parameters reflecting glucose and lipid homeostasis or oxidative stress were observed in the chromium group compared to the placebo group.
Kleefstra et al. (2007) - Diabetes Care 30 (5) 1092 - 1096 (A-7750): 57 persons (22 women, 35 men) with type 2 diabetes were randomised to 200 μg/d chromium (as Bio-Chromium) twice daily, or placebo, for 6 months. The subjects had a mean age of 67 years and a mean BMI of 30. The subjects' diabetes was generally well-controlled (baseline glycated haemoglobin (HbA_1C) of 7.1%) with oral anti-hypoglycaemia medication. 1 subject in each treatment group withdrew from the study due to mild gastrointestinal adverse effects, and a further subject in the chromium group was lost to follow-up due to a cerebrovascular accident. No treatment-dependent differences in any of the parameters measured were observed (glycated haemoglobin (HbA_1C), fasting plasma glucose, insulin sensitivity (HOMA-IR), blood lipids (total-, LDL-, and HDL cholesterol, triglycerides), BMI, body fat, and blood pressure. The upper normal or only marginally elevated values for a number of the parameters reflecting glycaemic control (excluding fasting glucose which was markedly elevated) and lipid metabolism may have limited the potential of the study to detect any beneficial effects of chromium supplementation. The authors noted that as the chromium status of the participants was not assessed, they may have studies persons with a relatively normal chromium status.
Krol E, et al. (2010): Biol Trace Elem Res, DOI 10.1007/s12011-010-8917-5(A-8928).
The aim of this clinical study was to evaluate the efficacy of Cr yeast supplementation on body mass, carbohydrate, lipids and mineral indices in type 2 diabetic patients. Twenty adult type 2 diabetic subjects (11 males and 9 females aged 37-63) were supplemented with Cr brewer's yeast in dosages of 500 μg Cr/person/day or placebo for 8 weeks in a double-blind, placebo-controlled crossover design. It was found that supplemental Cr did not affect body mass, blood lipid profile, resistin levels, and the serum and hair Zn, Fe, and Cu levels, but increased serum Cr (by 116%) and hair Cr (by 20.6%) concentrations and improved some blood carbohydrate indices (significant increase in the β cell function index by 18.8%) in type 2 diabetic patients. In conclusion, Cr yeast has a weak hypoglycemic potential, but does not affect body mass, blood biochemical profile, and microelement levels in type 2 diabetic subjects.
Muzik P, et al. (2011): Chromium supplementation in diabetic dogs and cats; EJCAP (Veterinari Lekar) 21 (1); 62-67 (A-9138).
The article provides an overview of diabetes in dogs and cats in general and details the importance of chromium action in the therapy of diabetic patients. In the final section, results of chromium supplementation in 17 diabetic dogs are described. The levels of glycaemia of all animals initially treated with insulin only are statistically compared to glycaemic levels after adding bioactive chromium to the therapy. A statistically significant positive effect of chromium supplementation to diabetic dogs treated with insulin is documented. The decrease of glucose level may be explained by elevated insulin activity or as reduction of insulin resistance, mediated by means of chromium supplementation.
Racek et al. (2013) Biol. Trace Elem. Res . 155(1) : 1-4 (A-9220): Chromium is required for a normal insulin function, and low levels have been linked with insulin resistance. The aim of this study was to follow the effect of chromium supplementation on fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and serum lipids in patients with type 2 diabetes mellitus (DM2) on insulin therapy. Eleven randomly selected patients with DM2 on insulin therapy were supplemented with a daily dose of 100 μg chromium yeast for the first supplementation period of 2 weeks. In the second supplementation period, the chromium dose was doubled and continued for the next 6 weeks. The third phase was a 6-week washout period. After each period, the levels of FPG and HbA1c were compared with the corresponding values at the end of the previous period. Serum triglycerides, total HDL and LDL cholesterol values after supplementation were compared with the baseline values. FPG decreased significantly after the first period of chromium supplementation (p<0.001), and a tendency to a further reduction was observed after the second supplementation period. Similarly, HbA1c decreased significantly in both periods (p<0.02 and p<0.002, respectively). Eight weeks after withdrawal of chromium supplementation, both FPG and HbA1c levels returned to their pre-intervention values. The serum lipid concentrations were not significantly influenced by chromium supplementation. Chromium supplementation could be beneficial in patients with DM2 treated with insulin, most likely due to lowered insulin resistance leading to improved glucose tolerance. This finding needs to be confirmed in a larger study.
Each tablet of Bio-Chromium contains 100 micrograms of elementary chromium. The chromium used in Bio-Chromium is organically bound meaning it is bound to natural amino acids from yeast (chromium yeast). It has an excellent bioavailability in the body ensuring that it is up to 10 times more absorbable than other approved sources of chromium. Bio-Chromium is made with a patented organic source called ChromoPrecise, which is a chromium yeast developed specifically to provide optimal bio-availability. Bio-Chromium is manufactured not only in compliance with GMP but also according to the highest pharmaceutical standards in order to ensure excellent quality and safety with exhaustive documentation.
Chromium is an essential mineral that contributes to normal metabolism of carbohydrates, lipids, and proteins. In addition, chromium supports biological processes involved in maintaining normal blood sugar levels. Inorganically bound chromium usually have a poor bioavailability in the body. The effect of a chromium supplement is determined by how effectively the nutrient is absorbed in the body.
The body's chromium reserve is around 4-6 mg. With increasing age, the concentration of chromium in various tissues may drop significantly. Snacking on something sweet may offer temporary relief because of the quick "sugar fix" that gives immediate energy, but the effect wears off soon after, leaving them where they started.
In the long run, such cravings for sugary foods may have a negative effect on body weight. With a product like Bio-Chromium, you can help your body maintain normal blood sugar levels and prevent these situations from occurring.
From GTF to chromodulin: For many years it was thought that chromium was included as part of a substance called GTF (Glucose Tolerance Factor). GTF were believed in addition to chromium to consist of the B vitamin, niacin, and the amino acids glycine, cysteine and glutamic acid. The theory of GTF was only partially supported, and the existence of a specific GTF molecule in the body has never been proven. More recent research has however revealed the existence of a unique chrome-binding molecule called chromodulin, which is slightly different from GTF, but with the same characteristics. So when we talk about chromodulin instead of GTF, it's the same benefits we are referring to.
Chromium is several things: Normally, we associate chromium with the chromium-plated fixtures in bathrooms or on motorbikes. The chromium form used for these purposes (industrial chromium) is not part of human biochemistry. We need chromium in its so-called trivalent form. Trivalent means that it is able to form three chemical bonds with other atoms (industrial chromium is hexavalent).
Scandinavian, British, and American dietary analyses show that the average chromium intake is somewhere around 30-40 μg daily. EFSA (the European Food Safety Authority) recommends a daily chromium intake of 40 μg, while the WHO considers the nutrient as safe with intakes up to 250 μg.
Blood sugar is a common term for blood levels of glucose, which is the body's energy source. The hormone insulin plays a crucial role in metabolising sugar, as insulin enables sugar to enter the cells. Chromium contributes to the process by ensuring that insulin can bind to insulin receptors in the cell membranes. The body's normal blood sugar values are between 3 and 7 mmol/l.