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Chromium


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Although trivalent chromium is recognized as a nutritionally essential mineral, scientists are not yet certain exactly how it functions in the body. The two most common forms of chromium are trivalent chromium (III) and hexavalent chromium (VI). Chromium (III) is the principal form in foods as well as the form utilized by the body. Chromium (VI) is derived from chromium (III) by heating at alkaline pH and is used as a source of chromium for industrial purposes. It is a strong irritant and is recognized as a carcinogen when inhaled. At low levels, chromium (VI) is readily reduced to chromium (III) by reducing substances in foods and the acidic environment of the stomach, which serve to prevent the ingestion of chromium (VI) (1-3)

Function

A biologically active form of chromium participates in glucose metabolism by enhancing the effects of insulin. 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, which activates the receptors and stimulates glucose uptake by cells. Through its interaction with insulin receptors, insulin provides cells with glucose for energy and prevents blood glucose levels from becoming elevated. In addition to its effects on carbohydrate (glucose) metabolism, insulin also influences the metabolism of fat and protein. A decreased response to insulin or decreased insulin sensitivity may result in impaired glucose tolerance or type 2 diabetes, also known as non-insulin dependent diabetes mellitus (NIDDM). Type 2 diabetes is characterized by elevated blood glucose levels and insulin resistance (1); see the article in the Research Newsletter for more information on diabetes.

The precise structure of the biologically active form of chromium is not known. Recent research suggests that a low-molecular-weight chromium-binding substance (LMWCr) may enhance the response of the insulin receptor to insulin. The following is a proposed model for the effect of chromium on insulin action (diagram). First, the inactive form of the insulin receptor is converted to the active form by binding insulin. The binding of insulin by the insulin receptor stimulates the movement of chromium into the cell and results in binding of chromium to apoLMWCr, a form of the LMWCr that lacks chromium. Once it binds chromium, the LMWCr binds to the insulin receptor and enhances its tyrosine kinase activity. The ability of the LMWCr to activate the insulin receptor is dependent on its chromium content. When insulin levels drop due to normalization of blood glucose levels, the LMWCr may be released from the cell in order to terminate its effects (4). More recent studies have indicated that chromium enhances insulin action by increasing the insulin-stimulated translocation of glucose transporters to the cell membrane (5). The mechanism for the effect of chromium on insulin action is currently under investigation (5-7).

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 of chromium/day for 12 weeks did not significantly affect measures of iron nutritional status (8). A study of younger men found an insignificant decrease in transferrin saturation with iron after supplementation of 200 mcg of chromium/day for eight weeks, but no long-term studies have addressed this issue (9). Iron overload in hereditary hemochromatosis may interfere with chromium transport by competing for transferrin binding. This has led to the hypothesis that decreased chromium transport might contribute to the diabetes associated with hereditary hemochromatosis (1)

Vitamin C

Chromium uptake is enhanced in animals when given at the same time as vitamin C (3). 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 (1)

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 (1).

Deficiency

Chromium deficiency was reported in three patients on long-term intravenous feeding who did not receive supplemental chromium in their intravenous solutions. These patients developed abnormal glucose utilization and increased insulin requirements that responded to chromium supplementation. Additionally, impaired glucose tolerance in malnourished infants responded to an oral dose of chromium chloride. Because chromium appears to enhance the action of insulin and chromium deficiency has resulted in impaired glucose tolerance, chromium insufficiency has been hypothesized to be a contributing factor to the development of type 2 diabetes (1, 10).

Several studies of male runners indicated that urinary chromium loss was increased by endurance exercise, suggesting that chromium needs may be greater in individuals who exercise regularly (11). In a more recent study, resistive exercise (weight lifting) was found to increase urinary excretion of chromium in older men. However, chromium absorption was also increased, leading to little or no net loss of chromium as a result of resistive exercise (12).

At present, research on the effects of inadequate chromium intake and risk factors for chromium insufficiency are limited by the lack of sensitive and accurate tests for determining chromium nutritional status (1, 3).

The Adequate Intake (AI)

Because there was not enough information on chromium requirements to set a recommended dietary allowance (RDA), the Food and Nutrition Board set an adequate intake level (AI) based on the chromium content in normal diets (1).

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

 

Disease Prevention

Impaired glucose tolerance and type 2 diabetes mellitus

In 12 out of 15 controlled studies of people with impaired glucose tolerance, chromium supplementation was found to improve some measure of glucose utilization or to have beneficial effects on blood lipid profiles (13). Impaired glucose tolerance refers to a metabolic state between normal glucose regulation and overt diabetes. Commonly, blood glucose levels are higher than normal but lower than those accepted as diagnostic for diabetes. Impaired glucose tolerance is associated with increased risk for cardiovascular diseases but is not associated with the other classic complications of diabetes. About 25% to 30% of individuals with impaired glucose tolerance eventually develop type 2 diabetes (14). Generally, chromium supplementation in a variety of forms, at doses of about 200 mcg/day for two to three months, has been found to be beneficial. The reasons for the variation or lack of effect in some studies are not clear, but chromium depletion is not the only known cause of impaired glucose tolerance. Additionally, the lack of an accurate measure of chromium nutritional status prevents researchers from identifying those individuals who are most likely to benefit from chromium supplementation (3, 15). A recent meta-analysis of 15 randomized clinical trials reported that chromium had no effect on glucose or insulin concentrations in nondiabetic individuals (16).

Cardiovascular disease

Impaired glucose tolerance and type 2 diabetes are associated with adverse changes in lipid profiles and increased risk of cardiovascular diseases. Studies examining the effects of chromium supplementation on lipid profiles have been notable for their 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 inconsistent responses of lipid and lipoprotein levels to chromium supplementation may reflect differences in chromium nutritional status. It is possible that only those individuals with insufficient dietary intake of chromium will experience beneficial effects on lipid profiles after chromium supplementation (2, 3, 17).

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 affecting glucose metabolism, insulin is known to affect fat and protein metabolism. At least 12 placebo-controlled studies have compared the effect of chromium supplementation (200-1,000 mcg as chromium picolinate/day) with or without an exercise program on lean body mass and measures of body fat. In general, those studies that have 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) do not indicate a beneficial effect of chromium supplementation on body composition (2, 17).

Promotes weight loss

Controlled studies of chromium supplementation (200-400 mcg as chromium picolinate/day) have demonstrated little if any beneficial effect on weight or fat loss (18), and claims of weight loss in humans appear to be exaggerated. In 1997, the U.S. Federal Trade Commission (FTC) ruled that there is no basis for claims that chromium picolinate promotes weight loss and fat loss in humans (2, 15, 17). More recently, a meta-analysis of ten randomized, double-blind, placebo-controlled trials of chromium picolinate supplementation found that chromium picolinate was associated with a 1.1-kilogram (2.4-pound) reduction in body weight; however, such a small change may not be clinically relevant (19). Additionally, a recent study reported that chromium picolinate supplementation attenuated body weight gain in type 2 diabetic patients taking sulfonylurea drugs (20).

Disease Treatment

Type 2 diabetes mellitus

Type 2 diabetes is characterized by elevated blood glucose levels and insulin resistance. Although insulin levels in type 2 diabetics may be higher than in healthy individuals, the physiological effects of insulin are reduced. Because chromium is known to enhance the action of insulin, the relationship between chromium nutritional status and type 2 diabetes has generated considerable scientific interest. Individuals with type 2 diabetes have been found to have higher rates of urinary chromium loss than healthy individuals, especially those with diabetes of more than two years duration (21). Prior to 1997, well-designed studies of chromium supplementation in individuals with type 2 diabetes showed no improvement in blood glucose control, though they provided some evidence of reduced insulin levels and improved blood lipid profiles (22). 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 (23). One hundred eighty participants took either a placebo or chromium in the form of chromium picolinate at doses of 200 mcg/day and 1,000 mcg/day. At the end of four months, blood glucose levels were 15%-19% lower in those who took 1,000 mcg/day compared with those who took the placebo. Blood glucose levels in those taking 200 mcg/day did not differ significantly from those that took placebo. Insulin levels were lower in those who took either 200 mcg/day or 1,000 mcg/day of chromium picolinate. Glycosylated hemoglobin levels, a measure of long-term control of blood glucose, were also lower in both chromium-supplemented groups, especially in the group taking 1,000 mcg/day. Because the chromium nutritional status of the Chinese participants was not evaluated and the prevalence of obesity was much lower than is typically associated with type 2 diabetics in the U.S., extrapolation of these results to a U.S. population is difficult. There have been subsequent studies investigating the utility of chromium picolinate for the treatment of type 2 diabetes. A recent review reported that 13 of 15 clinical studies, including the study conducted in China, found chromium picolinate improved at least one measure of glycemic control in diabetic patients (24). Chromium picolinate is more bioavailable than other supplemental forms of chromium and therefore may be more efficacious. However, large-scale randomized controlled trials of chromium supplementation for type 2 diabetes are needed to determine if chromium is effective in the treatment of type 2 diabetes.

Gestational diabetes

Few studies have examined the effects of chromium supplementation on gestational diabetes. Gestational diabetes occurs in about 2% of pregnant women and usually appears in the second or third trimester of pregnancy. Blood glucose levels must be tightly controlled to prevent adverse effects on the developing fetus. After delivery, glucose tolerance generally reverts to normal. However, 30% to 40% of women who have had gestational diabetes develop type 2 diabetes within 5 to 10 years. 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, although serum chromium levels may not reflect tissue chromium levels (25). 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 levels compared with those who took a placebo. However, insulin therapy rather than chromium picolinate was required to normalize severely elevated blood glucose levels (2, 26).

Sources

Food sources

The amount of chromium in foods is variable and has been measured accurately in relatively few foods. Presently, there is no large database for the chromium content of foods. Processed meats, whole grain products, ready-to-eat bran cereals, green beans, broccoli, and spices are relatively rich in chromium. Foods high in simple sugars, such as sucrose and fructose, are not only low in chromium but have been found to promote chromium loss (2). Estimated average chromium intakes in the U.S. range from 23-29 mcg/day for adult women and 39-54 mcg/day for adult men (1). The chromium content of some foods is listed below in micrograms (mcg) (27). Because chromium content in different batches of the same food has been found to vary significantly, the information in the table below should serve only as a guide to the chromium content of foods.

Food Serving Chromium (mcg)
Broccoli 1/2 cup 11.0
Green beans 1/2 cup 1.1
Potatoes 1 cup, mashed 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

Chromium (III) is available as a supplement in several forms: 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 (28). Chromium nicotinate and chromium picolinate may be more bioavailable than chromium chloride (17). In much of the research on impaired glucose tolerance and type 2 diabetes, chromium picolinate was the source of chromium. However, some concerns have been raised over the long-term safety of chromium picolinate supplementation (see Safety).

Safety

Toxicity

Hexavalent chromium or chromium (VI) is a recognized carcinogen. Exposure to chromium (VI) in dust is associated with increased incidence of lung cancer and is known to cause inflammation of the skin (dermatitis). In contrast, there is little evidence that trivalent chromium or chromium (III) is toxic to humans. Because no adverse effects have been convincingly associated with excess intake of chromium (III) from food or supplements, the Food and Nutrition Board (FNB) of the Institute of Medicine did not set a tolerable upper level of intake (UL) for chromium. Because information is limited, the FNB acknowledged a potential for adverse effects of high intakes of supplemental chromium (III) and advised caution (1).

Most of the concerns regarding the long-term safety of chromium (III) supplementation arise from several studies in cell culture, suggesting chromium (III), especially in the form of chromium picolinate, may increase DNA damage (29-31). Presently, there is no evidence that chromium (III) increases DNA damage in living organisms (1), and a study in ten 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 (32).

Several studies have demonstrated the safety of daily doses of up to 1,000 mcg of chromium for several months (23, 33). 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 of chromium/day in the form of chromium picolinate (34), 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 (35). Additionally, a 24-year old healthy male reportedly developed reversible, acute renal failure after taking chromium picolinate-containing supplements for two weeks (36). Individuals with pre-existing kidney or liver disease may be at increased risk of adverse effects and should limit supplemental chromium intake (1).

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, aspirin and indomethacin (a non-steroidal anti-inflammatory drug) both increased chromium absorption in rats (3).

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/multimineral 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 level of 20 to 25 mcg/day for adult women and 30 to 35 mcg 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 (37). Following the Linus Pauling Institute recommendation to take a multivitamin/multimineral supplement containing 100% of the daily values (DV) of most nutrients should provide sufficient chromium for most older adults.

Because impaired glucose tolerance and type 2 diabetes are associated with potentially serious health problems, individuals considering high-dose chromium supplementation to treat either condition should do so in collaboration with a qualified health care provider.

References


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

Updated in September 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in September 2007 by:
Richard A. Anderson, Ph.D.
Lead Scientist
Beltsville Human Nutrition Research Center
Beltsville, Maryland

Copyright 2001-2014  Linus Pauling Institute


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The Linus Pauling Institute Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, foods, and beverages for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

The information on dietary factors and supplements, foods, and beverages contained on this Web site does not cover all possible uses, actions, precautions, side effects, and interactions. It is not intended as nutritional or medical advice for individual problems. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed.


 
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