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TABLE 1 Dietary Reference Intakes for Chromium by Life Stage Group DRI values (mg/day) AIa ULb males females Life stage group 0 through 6 mo 0.2 0.2 7 through 12 mo 5.5 5.5 1 through 3 y 11 11 4 through 8 y 15 15 9 through 13 y 25 21 14 through 18 y 35 24 19 through 30 y 35 25 31 through 50 y 35 25 51 through 70 y 30 20 > 70 y 30 20 Pregnancy £ 18 y 29 19 through 50 y 30 Lactation £ 18 y 44 19 through 50 y 45 aAI = Adequate Intake. bUL = Tolerable Upper Intake Level. Data were insufficient to set a UL. In the absence of a UL, extra caution may be warranted in consuming levels above the recommended intake.

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PART III: CHROMIUM 297 CHROMIUM C hromium potentiates the action of insulin and may improve glucose tolerance. The form of chromium found in foods is trivalent chromium, or chromium III, which is the form discussed in this chapter. Since data were insufficient to set an Estimated Average Requirement (EAR) and thus calculate a Recommended Dietary Allowance (RDA) for chromium, an Adequate Intake (AI) was instead developed. Data were insufficient to set a Tolerable Upper Intake Level (UL). The AIs for chromium are based on esti- mated intakes of chromium derived from the average amount of chromium/ 1,000 kcal of balanced diets and average energy intake. DRI values are listed by life stage group in Table 1. Rich sources of chromium include cereals, particularly some high-bran cereals. Whole grains have more chromium than do refined grains. Some beers and wines are also high in chromium. The clinical signs and symptoms of defi- ciency include impaired plasma glucose utilization and an increased need for insulin. Few serious adverse effects have been associated with excess intake of chromium from foods. CHROMIUM AND THE BODY Function The form of chromium found in foods is trivalent chromium, or chromium III, which is the form discussed in this chapter. (Another form, hexavalent chro- mium, or chromium VI, is found in the environment as a chemical by-product and has been shown to be carcinogenic when inhaled.) Dietary chromium potentiates the action of insulin. Early studies identified chromium as the element that restores glucose tolerance in rats. A number of studies have demonstrated beneficial effects of chromium on circulating glu- cose, insulin, and lipids, although the potential mechanisms of action are still being investigated. Progress in the field has been limited by the difficulty in producing chromium deficiency in animals and also by the lack of a simple, widely accepted method for identifying subjects who are chromium depleted and, thus, who would be expected to respond to chromium supplementation.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 298 Absorption, Metabolism, Storage, and Excretion Chromium absorption by the body is generally low, with absorption estimates ranging from 0.4 to 2.5 percent. Some studies suggest that chromium absorp- tion increases with exercise, but further research is necessary. Chromium is stored in the liver, spleen, soft tissue, and bone. Most absorbed chromium is excreted rapidly in the urine, and most unabsorbed chromium is excreted in the feces. DETERMINING DRIS Determining Requirements Since data were insufficient to set an EAR and thus calculate an RDA for chro- mium, an AI was instead developed. The AIs for chromium are based on esti- mated intakes of chromium derived from the average amount of chromium/ 1,000 kcal of balanced diets and average energy intake taken from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). Criteria for Determining Chromium Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Average chromium intake from human milk 7 through 12 mo Average chromium intake from human milk and complementary foods 1 through 18 y Extrapolation from adult AI 19 through > 70 y Average chromium intake based on the chromium content of foods/1,000 kcal and average energy intakea Pregnancy £ 18 y Extrapolation from adolescent female AI based on body weight 19 through 50 y Extrapolation from adult female AI based on body weight Lactation £ 18 y Adolescent female intake plus average amount of chromium secreted in human milk 19 through 50 y Adult female intake plus average amount of chromium secreted in human milk a The average chromium content in well-balanced diets was determined to be 13.4 mg/1,000 kcal, and the average energy intake for adults was obtained from NHANES III.

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PART III: CHROMIUM 299 The UL The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse effects for almost all people. Data were insufficient to set a UL for chromium. No adverse effects have been con- vincingly associated with excess intake from food or supplements, but this does not mean that there is no potential for adverse effects resulting from high in- takes. Since data were limited, caution may be warranted. DIETARY SOURCES Foods Chromium is widely distributed throughout the food supply, but many foods contribute less than 1–2 mg per serving. Determining the chromium content of foods requires rigorous contamination control because standard methods of sample preparation contribute substantial amounts of chromium to the foods being analyzed. In addition, the chromium content of individual foods widely varies and may be influenced by geochemical factors. Consequently, dietary chromium intakes cannot be determined using any existing databases. The chromium content of foods may increase or decrease with processing. Refined grains have been shown to have less chromium than whole grains; conversely, acidic foods have been shown to gain chromium content during processing that involves the use of stainless steel containers or utensils. Cereals tend to be a significant contributor of chromium to diets. High- bran cereals are generally, but not always, high in chromium. Most dairy prod- ucts are low in chromium and provide less than 0.6 mg per serving. Meats, poultry, and fish generally contribute 1–2 mg per serving, but processed meats are higher in chromium and may acquire it from exogenous sources. Chro- mium concentrations of fruits and vegetables highly vary. Some brands of beer and some French wines, particularly red wines, are high in chromium. Wines have not been analyzed for chromium in the United States. Dietary Supplements According to U.S. data from the 1986 National Health Interview Survey (NHIS), 8 percent of adults consumed supplements that contained chromium. Based on data from NHANES III, the median supplemental intake of chromium was 23 mg/day for those who took supplements, an amount similar to the average di- etary chromium intake.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 300 Bioavailability Most chromium compounds are soluble at the pH of the stomach, but less soluble hydroxides may form as pH is increased. The environment of the gas- trointestinal tract and ligands provided by food and supplements are important for mineral absorption. Several dietary factors may affect the bioavailability of chromium (see “Dietary Interactions”). Dietary Interactions There is evidence that chromium may interact with certain other nutrients and dietary substances (see Table 2). TABLE 2 Potential Interactions with Other Dietary Substances Substance Potential Interaction Notes SUBSTANCES THAT AFFECT CHROMIUM Vitamin C Vitamin C may enhance the In one study, plasma chromium concentrations in three absorption of chromium. women were consistently higher when they were given 1 mg chromium as CrCl3 with 100 mg ascorbic acid than when given chromium without ascorbic acid. Simple Diets high in simple sugars Urinary chromium excretion was found to be related to sugars (35 percent of total kcal) may the insulinogenic properties of carbohydrates. increase urinary excretion of chromium. Phytate Phytate may decrease In rats, phytate at high levels had adverse effects on chromium absorption. chromium absorption, but lower levels of phytate did not have detrimental effects on chromium status. Medications Antacids and other drugs When rats were dosed with physiological doses of that alter stomach acidity or chromium and prostaglandin inhibitors, such as gastrointestinal prostaglandins aspirin, chromium levels in the blood, tissues, and may affect chromium urine markedly increased. Medications, such as absorption. antacids, reduced chromium absorption and retention.

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PART III: CHROMIUM 301 INADEQUATE INTAKE AND DEFICIENCY Chromium deficiency has been reported in three patients who did not receive supplemental chromium in their total parenteral nutrition (TPN) solutions. Their clinical signs and symptoms included unexplained weight loss, peripheral neu- ropathy, impaired plasma glucose removal, increased insulin requirements, el- evated plasma free fatty acids, and low respiratory quotient. Because chromium is known to potentiate the action of insulin and be- cause these chromium-deficient TPN patients were observed to have impaired glucose utilization and increased insulin requirements, it has been hypothesized that poor chromium status contributes to the incidence of impaired glucose tolerance and Type II diabetes (prevalence of impaired glucose tolerance was 15.8 percent in adults aged 40 to 74 years in NHANES III). However, address- ing this hypothesis is difficult because of the current lack of information about the variability in dietary chromium intakes and because there is not a simple, widely acceptable method that identifies potential study subjects with poor chromium status. EXCESS INTAKE Ingested chromium has a low level of toxicity that is partially due to its very poor absorption. Although no adverse effects have been convincingly associ- ated with the excess intake of chromium from food or supplements, this does not mean that the potential for adverse effects does not exist. Because data on the adverse effects of chromium intake were limited, caution may be warranted. Special Considerations Individuals susceptible to adverse effects: Data suggest that people with preex- isting renal and liver disease may be particularly susceptible to the adverse effects of excess chromium. These individuals should be particularly careful to limit their chromium intake.

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PART III: CHROMIUM 303 KEY POINTS FOR CHROMIUM Chromium potentiates the action of insulin and may improve 3 glucose tolerance. Since data were insufficient to set an EAR and thus calculate 3 an RDA for chromium, an AI was instead developed. The AIs for chromium are based on estimated intakes of 3 chromium derived from the average amount of chromium/1,000 kcal of balanced diets and average energy intake. Data were insufficient to set a UL. 3 Although no adverse effects have been convincingly 3 associated with the excess intake of chromium from food or supplements, this does not mean that the potential for adverse effects does not exist. The form of chromium found in the diet is trivalent chromium, 3 or chromium III. Another form, hexavalent chromium, or chromium VI, is found in the environment as a chemical by- product and has been shown to be carcinogenic when inhaled. Dietary chromium intakes cannot be determined using any 3 existing databases. Rich sources of chromium include cereals, particularly all-bran 3 cereals. Whole grains have more chromium than do refined grains. Because chromium is known to potentiate the action of insulin 3 and because some chromium-deficient TPN patients have been observed to have impaired glucose utilization and increased insulin requirements, it has been hypothesized that poor chromium status contributes to the incidence of impaired glucose tolerance and Type II diabetes. The potential relationship between chromium and Type II diabetes remains under study. Ingested chromium has a low level of toxicity that is partially 3 due to its very poor absorption. Data suggest that people with preexisting renal and liver 3 disease may be particularly susceptible to the adverse effects of excess chromium.