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Chromium


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Summary

  • Chromium (Cr0) is an ubiquitous trace metal. The predominant chromium form in the body is trivalent chromium (Cr3+), which may play a role in normal insulin function. (More information)
  • Trivalent chromium has been proposed to be the cofactor for an oligopeptide called chromodulin. Chromodulin may be able to potentiate the action of insulin, hence improving tissue sensitivity to insulin and facilitating glucose transport into cells. (More information)
  • Potential chromium deficiency cases have been associated with symptoms resembling diabetes mellitus: impaired glucose tolerance and increased insulin requirements. (More information)
  • The lack of an accurate measure of chromium nutritional status prevents the identification of individuals who may be susceptible to chromium deficiency. In 2001, the US Institute of Medicine set the adequate intake (AI) of chromium at 20-35 mcg/day for adults. (More information)
  • Randomized controlled trials have failed to provide any evidence of benefits of chromium supplementation in the prevention or treatment of impaired glucose tolerance and type 2 diabetes mellitus. (More information)
  • A well-balanced diet that includes fruit, vegetables, meat, fish, and grains should easily cover dietary needs of chromium. (More information)
  • Few adverse events have been reported with chromium supplementation. (More information)

Chromium was first discovered in the 1797. The most stable oxidation state of chromium in biological systems is trivalent chromium (Cr3+), which forms relatively inert complexes with proteins and nucleic acids (1). The essentiality of trivalent chromium is questioned, and its presumed function in the body remains poorly understood. Another common and stable form of chromium in the environment is hexavalent chromium (Cr6+). Hexavalent chromium is derived from trivalent chromium by heating at alkaline pH and is used as a source of chromium for industrial purposes. Hexavalent chromium is highly toxic and is classified as a human carcinogen when inhaled (2). In the acidic environment of the stomach, hexavalent chromium can be readily reduced to trivalent chromium by reducing substances present in food, which limits the ingestion of hexavalent chromium (3-5).

Function

Trivalent chromium has been proposed to be the cofactor for a biologically active molecule that could enhance the effects of insulin on target tissues. Insulin is secreted by specialized cells in the pancreas in response to increased blood glucose levels, such as after a meal. Insulin binds to insulin receptors on the surface of cells, activating the receptors and stimulating glucose uptake by cells. Through its interaction with insulin receptors, insulin provides cells with glucose for energy and helps maintain blood glucose within a narrow range of concentrations. In addition to its effects on carbohydrate (glucose) metabolism, insulin also influences the metabolism of fat and protein (6). Together, a decreased response to insulin or decreased insulin sensitivity in peripheral tissues (adipose tissue, muscle, and liver) and a progressive defect in insulin secretion may result in impaired glucose tolerance, frequently leading to overt type 2 diabetes mellitus. The body initially increases the secretion of insulin by specialized pancreatic cells to overcome the decrease in insulin sensitivity. However, the pancreas eventually fails to produce enough insulin to maintain normal blood glucose concentrations. Individuals with type 2 diabetes are at increased risk for cardiovascular disease (7); see also the article in the Research Newsletter for more information on diabetes.

Possible mechanism of action

The precise structure of the biologically active form of chromium is not known. The current model postulates that trivalent chromium might be the cofactor of a low-molecular-weight chromium-binding substance known as LMWCr or chromodulin (8). Chromodulin is thought to enhance the cascade of signaling events induced by the binding of insulin to extracellular alpha-subunit of the insulin receptor (IR). Upon insulin binding, the tyrosine kinase domain of the intracellular beta-subunit of the IR becomes activated and causes the phosphorylation of tyrosine residues in the beta-subunit itself. Subsequently, IR activation triggers a series of rapid phosphorylation reactions that activate many downstream effectors, eventually resulting in an increase in glucose uptake and storage (8).

Regarding the effect of trivalent chromium on insulin signaling, an early model (see diagram) suggested that the binding of insulin to the IR could stimulate the movement of chromium into the cell and result in the binding of chromium to apochromodulin, a form of chromodulin that lacks chromium (9, 10). Chromodulin could then bind to the IR and upregulate insulin signaling molecules, ultimately increasing the translocation of glucose transporters (GLUT-4) from cytosolic vesicles to the cell membrane (11-13). Some, but not all, studies conducted in cell-based and animal models of insulin resistance and diabetes have found that chromium inhibits the activity of protein tyrosine phosphatase-1B (PTP-1B) and other negative regulators of insulin signaling, suggesting that chromium might improve insulin sensitivity under insulin-resistant conditions (reviewed in 8). A recent study in diabetic mice also suggested that chromium may reduce insulin clearance and enhance insulin signaling by inhibiting the proteolysis (degradation) of insulin and some downstream effectors (14). Additional mechanisms that may underlie the effect of chromium on insulin sensitivity, such as the reduction of markers of oxidative stress and inflammation known to contribute to insulin resistance, are under investigation (reviewed in 8, 10).

Nutrient interactions

Iron

Chromium competes for one of the binding sites on the iron transport protein, transferrin. However, supplementation of older men with 925 mcg/day of chromium for 12 weeks did not significantly affect measures of iron nutritional status (15). A study of younger men found an insignificant decrease in transferrin saturation with iron after supplementation of 200 mcg/day of chromium for eight weeks, but no long-term studies have addressed this issue (16). In a 12-week, randomized controlled trial, supplementation with chromium picolinate (200 mcg/day) did not affect iron nutritional status in premenopausal women when compared to picolinic acid or placebo (17). Iron overload in hereditary hemochromatosis may interfere with chromium transport by competing for transferrin binding. It has been hypothesized that decreased chromium transport might contribute to the pathogenesis of diabetes mellitus in patients with hereditary hemochromatosis (3).

Vitamin C

Chromium uptake is enhanced in animals when given at the same time as vitamin C (5). In a study of three women, administration of 100 mg of vitamin C together with 1 mg of chromium resulted in higher plasma levels of chromium than 1 mg of chromium without vitamin C (3).

Carbohydrates

Compared to diets rich in complex carbohydrates (e.g., whole grains), diets high in simple sugars (e.g., sucrose) result in increased urinary chromium excretion in adults. This effect may be related to increased insulin secretion in response to the consumption of simple sugars compared to complex carbohydrates (3).

Deficiency

Potential cases of chromium deficiency have been described in a few patients on long-term intravenous feeding (parenteral nutrition) who did not receive supplemental chromium in their intravenous solutions. The subjects developed abnormal glucose utilization and increased insulin requirements that responded to chromium supplementation (18). However, because intravenous solutions provide chromium at doses well above dietary levels, it has been suggested that chromium might produce biological effects only at pharmacological doses (10). Because chromium appeared to enhance the action of insulin and chromium deficiency has been proposed to result in impaired glucose tolerance, chromium insufficiency has been hypothesized to be a contributing factor to the development of type 2 diabetes (3, 19). However, evidence for this is ambiguous at best.

Urinary chromium loss was reportedly increased by endurance exercise in male runners, suggesting that chromium needs may be greater in individuals who exercise regularly (20). In one study, weightlifting (resistive exercise) was found to increase urinary excretion of chromium in older men. However, chromium absorption also increased, leading to little or no net loss of chromium as a result of resistive exercise (21).

At present, research on the effects of potentially inadequate chromium intake and risk factors for chromium insufficiency is limited by the lack of analytical tools to determine chromium nutritional status (3, 5). Moreover, the absence of animal models for chromium deficiency makes it difficult to study possible biochemical, physiological, and functional abnormalities associated with inadequate intakes of chromium (22).

The Adequate Intake (AI)

Because there was not enough information to set an estimated average requirement (EAR), the Food and Nutrition Board (FNB) of the US Institute of Medicine (IOM) established an adequate intake (AI) based on the chromium content in healthy diets (3).

Adequate Intake (AI) for Chromium

Life Stage  Age  Males (mcg/day)  Females (mcg/day) 
Infants  0-6 months  0.2 0.2
Infants  7-12 months  5.5 5.5
Children  1-3 years  11 11
Children  4-8 years  15 15
Children  9-13 years  25 21
Adolescents  14-18 years  35 24
Adults  19-50 years  35 25
Adults  51 years and older  30 20
Pregnancy  18 years and younger  - 29
Pregnancy  19 years and older - 30
Breast-feeding  18 years and younger  - 44
Breast-feeding  19 years and older - 45

 

The case of trivalent chromium essentiality has been questioned in both animals and humans in the last decades, and the European Food Safety Authority — which provides dietary guidelines for the EU community — recently concluded that requirements for chromium could not be established (22). The IOM is not currently reconsidering the AIs for chromium.

Disease Prevention

Impaired glucose tolerance and type 2 diabetes mellitus

Early controlled studies in subjects with impaired glucose tolerance have reported that chromium supplementation improved some measure of glucose utilization or had beneficial effects on blood lipid profiles (23). Impaired glucose tolerance refers to a prediabetic state and is currently defined by the presence of impaired fasting glucose (fasting plasma glucose concentration of 110-125 mg/dL) and impaired glucose tolerance status (plasma glucose concentration of 140-199 mg/dL during a two-hour challenge test with a 75-g oral glucose load) (24). Impaired glucose tolerance is associated with modest increases in risk of cardiovascular disease, as well as other traditional microvascular complications of diabetes (25). Current estimates suggest that up to 70% of individuals with impaired glucose tolerance may eventually develop type 2 diabetes (26).

In a recent randomized, double-blind, placebo-controlled study in 56 subjects at risk of type 2 diabetes, six months of daily chromium picolinate supplementation (500 mcg or 1,000 mcg) had no effect on glucose and insulin concentrations, insulin sensitivity, and blood lipid profiles (27). Another randomized, placebo-controlled trial in 31 non-diabetic individuals reported a great variability in serum and urinary chromium concentrations in response to a daily supplementation with 1,000 mcg of chromium picolinate for 16 weeks. Also, in the chromium-supplemented group, participants with higher vs. lower serum chromium concentrations (>3.1 mcg/L vs. ≤3.1 mcg/L) exhibited a decline in insulin sensitivity that could not be explained by expression changes in the genes involved in insulin signaling (28). Additionally, a meta-analysis of nine randomized clinical trials published between 1992 and 2010 reported that chromium at doses of 200-1,000 mcg/day for 8-16 weeks had no effect on fasting glucose concentrations in 309 non-diabetic individuals (29). Although evidence is lacking to support chromium supplementation, there is a need for an accurate measure of chromium nutritional status to identify the individuals who might be deficient and thus most likely to benefit from chromium supplementation (29).

Cardiovascular disease

Impaired glucose tolerance and type 2 diabetes are associated with adverse changes in lipid profiles and increased risk of cardiovascular disease. Studies examining the effects of chromium supplementation on lipid profiles have given inconsistent results. While some studies have observed reductions in serum total cholesterol, LDL-cholesterol, and triglyceride levels or increases in HDL-cholesterol levels, others have observed no effect. Such mixed responses of lipid and lipoprotein levels to chromium supplementation may reflect differences in chromium nutritional status. It is possible that only individuals with insufficient dietary intake of chromium will experience beneficial effects on lipid profiles after chromium supplementation (4, 5, 30).

Health claims

Increases muscle mass

Claims that chromium supplementation increases lean body mass and decreases body fat are based on the relationship between chromium and insulin action (see Function). In addition to regulating glucose metabolism, insulin is known to affect fat and protein metabolism (6). At least 12 placebo-controlled studies have compared the effect of chromium supplementation (172-1,000 mcg/day of chromium as chromium picolinate) with or without an exercise program on lean body mass and measures of body fat (reviewed in 31). In general, the studies that used the most sensitive and accurate methods of measuring body fat and lean mass (dual energy x-ray absorbtiometry or DEXA and hydrodensitometry or underwater weighing) did not find a beneficial effect of chromium supplementation on body composition (4, 30).

Promotes weight loss

Controlled studies of chromium supplementation have demonstrated little if any beneficial effect on weight or fat loss, and claims of weight loss in humans appear to be exaggerated. In 1996, the US Federal Trade Commission (FTC) ruled that there was no scientific basis for claims that chromium picolinate could promote weight loss and fat loss in humans (32). Recently, a meta-analysis of 11 randomized, double-blind, placebo-controlled trials in 866 overweight or obese subjects found a significant 0.50-kilogram (1.10-pound) reduction in body weight with supplemental chromium (most exclusively in the form of chromium picolinate) at doses between 137 mcg/day and 1,000 mcg/day for 8-24 weeks (33). However, such a small change did not reach a clinically significant weight loss of ≥5% of the initial body weight (34). Recent reports have suggested that supplemental chromium may reduce food craving and intake in overweight or obese women (35, 36). Yet, current available data remain insufficient to support the use of chromium supplements in weight-loss strategies (37).

Disease Treatment

Type 2 diabetes mellitus

Type 2 diabetes mellitus is characterized by chronic hyperglycemia (elevated blood glucose concentration) and insulin resistance. Because resistance to insulin is usually associated with a compensatory rise in insulin secretion, circulating insulin concentrations in type 2 diabetic subjects may be higher than in healthy individuals. Yet, the resistance of peripheral tissues (especially liver and skeletal muscle) to insulin also implies that the physiological effects of insulin are reduced.

Since cell culture and rodent models of diabetes have implicated chromium in the regulation of insulin sensitivity and blood glucose levels, the relationship between chromium nutritional status and type 2 diabetes mellitus has generated considerable scientific interest. Early reports observed that individuals with overt type 2 diabetes for over two years had higher rates of urinary chromium loss than healthy individuals (38). Small, well-designed studies of chromium supplementation in individuals with type 2 diabetes showed no improvement in blood glucose control, although they provided some evidence of reduced insulin concentrations and improved blood lipid profiles (39). In 1997, the results of a placebo-controlled trial conducted in China indicated that chromium supplementation might be beneficial in the treatment of type 2 diabetes (40). One hundred and eighty participants were randomized to receive either a placebo or chromium supplements in the form of chromium picolinate at either 200 mcg/day or 1,000 mcg/day. After four months of treatment, fasting blood glucose concentrations were found to be 15% to 19% lower in those who took 1,000 mcg/day of chromium compared to those who took the placebo. Yet, blood glucose concentrations in those taking 200 mcg/day of chromium did not differ significantly from those who took placebo. Chromium picolinate at either 200 mcg/day or 1,000 mcg/day was also associated with reduced insulin concentrations compared to placebo. The level of glycated hemoglobin A1c (HbA1c), a measure of glycemic control, was also significantly reduced in both chromium-supplemented groups. However, a number of limitations made it difficult to extrapolate the results to the US population (41). Besides, the study was excluded from recent meta-analyses of randomized controlled trials due to insufficient data quality (29, 42).

A recent meta-analysis of seven randomized, placebo-controlled studies indicated that chromium intake of at least 250 mcg/day for no less than three months significantly reduced fasting glucose concentrations in diabetic subjects but had no effect on the levels of HbA1c (42). Another meta-analysis of nine randomized controlled trials, including a total of 440 participants with diabetes, failed to find a significant reduction in fasting glucose concentrations with chromium monotherapy (200-1,000 mcg/day) (29). However, large-scale randomized controlled trials of chromium supplementation are needed to demonstrate if chromium is effective in the treatment of type 2 diabetes mellitus. Additionally, recent suggestions have been made that greater doses of chromium may be required to observe beneficial effects of chromium supplementation (10).

Gestational diabetes

Few studies have examined the effects of chromium supplementation on gestational diabetes, a condition that is estimated to affect 4.6% and 9.2% of pregnant women in the US (43). The occurrence of gestational diabetes during pregnancy is associated with insufficient insulin secretion and glucose intolerance of variable severity (44). Peripheral insulin resistance usually increases in the second or third trimester of pregnancy. Because elevated maternal blood glucose concentrations can have adverse effects on the developing fetus, women with gestational diabetes are at increased risk of pregnancy complications (45). After delivery, impaired glucose tolerance generally reverts to normal glucose tolerance. However, nearly one-third of women who have had gestational diabetes develop postpartum glucose intolerance (prediabetes or type 2 diabetes) (46, 47).

An observational study in pregnant women did not find serum chromium levels to be associated with measures of glucose tolerance or insulin resistance in late pregnancy (48). However, it is not known whether measures of serum chromium levels truly reflect tissue chromium levels and chromium status during pregnancy. A more recent prospective study following 425 pregnant women also failed to find a correlation between serum chromium concentrations and incidence of gestational diabetes (49). A cross-sectional study of 90 pregnant women in southern India found that those with gestational diabetes had significantly lower serum chromium concentrations compared to gestational diabetes-free women. Given the above mixed results, it should be noted that different methods were used to measure circulating chromium concentrations in each study. Also, it is possible that nutritional chromium status may vary among ethnically distinct populations so that studies including pregnant women from different ethnic backgrounds and/or geographical areas would give different results.

In addition, there is currently insufficient evidence to evaluate the effect of supplemental chromium on gestational diabetes. Women with gestational diabetes whose diets were supplemented with 4 mcg of chromium per kilogram of body weight daily as chromium picolinate for eight weeks had decreased fasting blood glucose and insulin concentrations compared to those who took a placebo. Yet, insulin therapy rather than chromium picolinate was required to normalize severely elevated blood glucose levels (4, 50).

Sources

Food sources

The amount of chromium in food is variable and has been measured accurately in relatively few foods. Presently, there is no large database for the chromium content of food. Processed meats, whole-grain products, high-bran cereals, green beans, broccoli, nuts, and egg yolk are good sources of chromium. Foods high in simple sugars, such as sucrose and fructose, are usually low in chromium and may actually promote chromium excretion (4). Estimated average chromium intakes in the US range from 23-29 mcg/day for adult women and 39-54 mcg/day for adult men (3). The chromium content of some foods is listed in the table below and expressed in micrograms (mcg) (51). Since chromium content varies significantly between different batches of the same food, the information provided in the table below should serve only as a guide to the chromium content of food.

Food Serving Chromium (mcg)
Broccoli ½ cup 11.0
Green beans ½ cup 1.1
Potatoes (mashed) 1 cup 2.7
Grape juice 8 fl. ounces 7.5
Orange juice 8 fl. ounces 2.2
Beef 3 ounces 2.0
Turkey breast 3 ounces 1.7
Turkey ham (processed) 3 ounces 10.4
Waffle 1 (~2.5 ounces) 6.7
Bagel 1 2.5
English muffin 1 3.6
Apple w/ peel 1 medium 1.4
Banana 1 medium 1.0

 

Supplements

A recent cross-sectional survey indicated that 19% of the US population uses chromium-containing dietary supplements (i.e., single-nutrient supplements and multiple ingredient supplements), with the highest proportion of users (29%) found in adults aged over 50 years (52). Trivalent chromium is available as a supplement in several forms, including chromium chloride, chromium nicotinate, chromium picolinate, and high-chromium yeast. These are available as stand-alone supplements or in combination products. Doses typically range from 50 to 200 mcg of elemental chromium (53). Much of the research on impaired glucose tolerance and type 2 diabetes uses chromium picolinate as the source of chromium, although recent investigations suggest that its bioavailability may not be greater than that of dietary chromium (54). Some concerns have been raised over the long-term safety of chromium picolinate supplementation (see Safety).

Safety

Toxicity

Hexavalent chromium (chromium VI; Cr6+) is a recognized carcinogen. Exposure to hexavalent chromium in dust has been associated with an increased incidence of lung cancer and is known to cause inflammation of the skin (dermatitis).

In contrast, there is little evidence that trivalent chromium (chromium III; Cr3+) is toxic to humans. The toxicity from oral intakes is considered to be low because ingested chromium is poorly absorbed, and most absorbed chromium is rapidly excreted in the urine (55). Because no adverse effects have been convincingly associated with excess intake of trivalent chromium from food or supplements, the Food and Nutrition Board (FNB) of the Institute of Medicine did not set a tolerable upper intake level (UL) for chromium. Yet, despite limited evidence for adverse effects, the FNB acknowledged the possibility of a negative impact of high oral intakes of supplemental trivalent chromium on health and advised caution (3).

Chromium picolinate

Most of the concerns regarding the long-term safety of trivalent chromium supplementation arise from several studies in cell culture, suggesting trivalent chromium, especially in the form of chromium picolinate, may increase DNA damage (56-58). Presently, there is no evidence that trivalent chromium increases DNA damage in living organisms (3), and a study in 10 women taking 400 mcg/day of chromium as chromium picolinate found no evidence of increased oxidative damage to DNA as measured by antibodies to an oxidized DNA base (59).

Many studies have demonstrated the safety of daily doses of up to 1,000 mcg of chromium for several months (40, 60). However, there have been a few isolated reports of serious adverse reactions to chromium picolinate. Kidney failure was reported five months after a six-week course of 600 mcg/day of chromium in the form of chromium picolinate (61), while kidney failure and impaired liver function were reported after the use of 1,200-2,400 mcg/day of chromium in the form of chromium picolinate over a period of four to five months (62). Additionally, a 24-year old healthy male reportedly developed reversible, acute renal failure after taking chromium picolinate-containing supplements for two weeks (63). Individuals with pre-existing kidney or liver disease may be at increased risk of adverse effects and should limit supplemental chromium intake (3).

Drug interactions

Little is known about drug interactions with chromium in humans. Large doses of calcium carbonate or magnesium hydroxide-containing antacids decreased chromium absorption in rats. In contrast, non-steroidal anti-inflammatory drugs, aspirin and indomethacin, can increase chromium absorption in rats (5).

Linus Pauling Institute Recommendation

The lack of sensitive indicators of chromium nutritional status in humans makes it difficult to determine the level of chromium intake most likely to promote optimum health. Following the Linus Pauling Institute recommendation to take a multivitamin/mineral supplement containing 100% of the daily values (DV) of most nutrients will generally provide 60-120 mcg/day of chromium, well above the adequate intake of 20-25 mcg/day for adult women and 30-35 mcg/day for adult men.

Older adults (> 50 years)

Although the requirement for chromium is not known to be higher for older adults, one study found that chromium concentrations in hair, sweat, and urine decreased with age (64). Following the Linus Pauling Institute recommendation to take a multivitamin/mineral supplement containing 100% of the daily values (DV) of most nutrients should provide sufficient chromium for older adults.

Because impaired glucose tolerance and type 2 diabetes mellitus are associated with serious health problems, individuals with either condition should seek medical advice if considering the use of high-dose chromium supplementation.

References


Written in April 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in October 2014 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in October 2014 by:
John B. Vincent, Ph.D.
Professor, Department of Chemistry
The University of Alabama
Tuscaloosa, Alabama

Copyright 2001-2014  Linus Pauling Institute


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