Chromium

Common Name(s): Brewer's yeast , chromium chloride , chromium nicotinate , chromium picolinate

Uses

Chromium supplementation has been studied for a variety of indications, especially diabetes and weight loss, but clinical studies have shown inconsistent results. The role of supplemental chromium remains controversial.

Dosing

The currently accepted value for chromium dietary intake is 25 mcg/day for women and 35 mcg/day for men. Daily dosages used in clinical trials for periods of up to 9 months range as follows: brewer's yeast up to 400 mcg/day; chromium chloride 50 to 600 mcg/day; chromium nicotinate 200 to 800 mcg/day; chromium picolinate 60 to 1,000 mcg/day. The potential for genotoxic effects exists at higher dosages.

Contraindications

None well documented. Renal failure may be considered a relative contraindication.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Limited animal experimentation showed skeletal and neurological defects in the offspring of mice fed chromium picolinate.

Interactions

None well documented.

Adverse Reactions

Ingestion or exposure to certain forms of chromium may cause or contribute to GI irritation and ulcers, dermatitis, hemorrhage, circulatory shock, and renal tubule damage.

Toxicology

No risk of genotoxicity at low dosages over the short-term exists for chromium as a dietary supplement. However, at higher dosages, such as those used in trials evaluating the efficacy of chromium in glycemic control, concern exists for potential genotoxic effects.

The element chromium (Cr) is abundant in the earth's crust and is found in concentrations ranging from 100 to 300 ppm. 1 Industrially, it is obtained from chrome ore, among other sources. The organic form of chromium exists in a dinicotino-glutathionine complex in natural foods and is better absorbed than the inorganic form. Good dietary sources of chromium include brewer's yeast, liver, potatoes with skin, beef, fresh vegetables, and cheese. 2

History

Chromium is a steel-gray lustrous metal that is important as an additive in the manufacture of steel alloys (chrome steel, chrome-nickel steel, stainless steel) and greatly increases the durability and resistance of these metals; hence its use in metal prosthetic implants. Synthetically-produced 51 Cr is used as a tracer in various hematologic disorders and in the determination of blood volume. 3 As chromium is considered to be important for normal glucose metabolism, a number of over-the-counter products promote the use of chromium, alone or in combination with glucose tolerance factor, to improve carbohydrate utilization. The effectiveness of these products has not been established, although they represent nutritionally sound sources of chromium.

Chemistry

Chromium has an atomic weight of 51.996. The element may occur in compounds in di-, tri-, or hexavalent forms. Hexavalent chromium is the highest oxidation state of elemental chromium. Trivalent chromium is the most stable oxidation state for chromium, and it is this form that is found in common nutritional supplements, generally as the picolinate. 4 , 5 A number of naturally occurring isotopes have been identified, the most common of which is 52 Cr (approximately 84% of the isotopes). 51 Cr has a half-life of approximately 28 days. Many chromium salts are industrial hazards. 6

Uses and Pharmacology

To date, no chromium-containing biomolecules have been definitively described, and no clinical manifestation of trivalent chromium deficiency in humans has been established. 4 , 7 The argument for chromium supplementation relies on evidence from case reports of resolution of diabetic symptoms refractory to insulin via chromium added to total parenteral nutrition, and experiments in which animals deficient in chromium exhibited impaired glucose metabolism. 4 , 5 , 8 , 9

Diabetes

Chromium may influence glucose metabolism by increasing the number of insulin receptors or by binding insulin to receptors. 7 , 10 , 11 , 12 The US Food and Drug Administration concludes that, based on very limited credible evidence, chromium picolinate may reduce the risk of insulin resistance and therefore may reduce the risk of type 2 diabetes. 8 , 13

A number of systematic reviews and meta-analyses have been conducted to determine the effect of chromium on glycemic control, although large, quality trials are limited. 7 , 8 , 10 , 14 The majority of studies have found no effect on measured outcomes, with a few studies contributing to the positive observed effects. 8 , 15 Variations of preparations used in the trials and study conditions make generalization of the results difficult. 8 , 10

In patients with diabetes, chromium supplementation may produce a modest increase in glycemic control. 7 , 8 , 10 , 14 , 16 Among healthy trial participants, chromium supplementation does not have an effect on glycemic control. 7 , 8 , 10 , 17

Limited studies evaluating the effect of a combination of chromium picolinate (600 mcg/day) and biotin have shown improved glycemic control in type 2 diabetes. 18 , 19 , 20

Chromium-deficient patients may be more likely to show a positive response; however, most patients with diabetes are not chromium deficient. 7 , 10 The effects of chromium on corticosteroid-induced diabetes have been studied. 21 Chromium picolinate 1,000 mcg daily decreased the QTc interval in patients with type 2 diabetes. 11 , 22

Hyperlipidemia

Results of the limited number of quality clinical trials are equivocal. Positive results have been reported in a review of the effects of chromium picolinate in type 2 diabetes 14 and in obese participants. 13 However, a systematic review and other reviews reported no effect in type 2 diabetes. 8 , 15 , 16 Limited studies evaluating combined chromium picolinate and biotin supplementation in type 2 diabetes have shown improved lipid profiles. 19 , 20 , 23 , 24

Weight loss

A meta-analysis of the effects of chromium picolinate in weight reduction found few quality trials available for inclusion. A small positive effect of chromium was found in 2 trials. A reduction of 1.1 to 1.2 kg over 10 to 13 weeks was estimated versus placebo (200 or 400 mcg chromium picolinate daily). 25 Two reviews found no effect on lean muscle mass, muscle strength, or body composition. 26 , 27 Two further studies conducted after the meta-analysis and reviews found no change in percentage of body fat or body mass index. 15 , 28

Other uses

Case reports of 8 patients have shown clinical response to chromium monotherapy for chronic refractory mood disorders. These include patients with bipolar II disorder, dysthymic disorder, and major and minor depression. 29 , 30

Limited studies in postmenopausal women suggest a role for chromium in prevention of osteoporosis. 31 , 32

Dosage

The currently accepted value for chromium dietary intake is 25 mcg/day for women and 35 mcg/day for men. 4 , 33 Daily dosages used in clinical trials for periods of up to 9 months range as follows 8 , 10 , 25 , 27 : brewer's yeast of up to 400 mcg; chromium chloride 50 to 600 mcg; chromium nicotinate 200 to 800 mcg; chromium picolinate 60 to 1,000 mcg. At the higher end of the range, the potential for genotoxic effects may outweigh potential benefits. 4 , 5

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Limited animal experimentation showed skeletal and neurological defects in the offspring of mice fed chromium picolinate. 4 , 34

Interactions

None well documented. A study conducted among patients with HIV taking antiretroviral therapy found an increased urinary excretion of chromium. A correlation between decreased serum chromium levels and metabolic abnormalities in patients infected with HIV on antiretroviral therapy was observed. 17

Adverse Reactions

Trivalent chromium compounds found in foods show little or no toxicity.

Oral ingestion of chromate salts may lead to irritation of the GI tract (eg, nausea, ulcers, vomiting), hemorrhage, and circulatory shock. Renal damage, including acute tubular necrosis, has been observed following occupational exposure to chromium. Liver necrosis is also possible. 35 , 36 Rhabdomyolysis has been reported for chromium picolinate and combination products containing chromium. 28 , 37

A case report of acute oral poisoning with hexavalent chromium (as potassium dichromate) noted ulceration in the gastric fundus as well as renal tubule toxicity, but noted normal glomerular filtration and creatine clearance. The use of large doses of parenteral ascorbic acid is controversial in the management of chromium poisoning. Experimental evidence suggests that hexavalent chromium is reduced by ascorbic acid to a less soluble form and hence, a less toxic trivalent form; however, this has not been supported with clinical evidence and may lead to worsened nephrotoxicity due to increased oxaluria. 36

Topical effects following exposure to chromium and chromates may lead to eczematous dermatitis and ulceration. Ulceration and perforation of the nasal septum have also occurred. 38 , 39

Isolated incidents of deleterious effects of chromium picolinate supplementation in humans have been reported; however, the importance of these isolated incidents is difficult to ascertain. 26

Increased levels of serum chromium have been reported for patients with chronic renal failure receiving metal-on-metal prosthetic implants, but with no negative effect on renal function. 40

Toxicology

Hexavalent chromium, having the highest oxidation state of elemental chromium, is a well-established carcinogen. 4 , 5 , 41 Trivalent chromium is the most stable oxidation state for chromium, and it is this form that is found in common nutritional supplements, generally as the picolinate. 4 , 5 Oxidation of trivalent chromium complexes within the extracellular fluid, with resultant cellular uptake of the reactive hexavalent chromium species, is the main concern with chromium supplementation. 4

A review of toxicological studies does not indicate a risk of genotoxicity at low dosages over the short-term with chromium as a dietary supplement. 4 , 5 However, at higher dosages, such as those used in trials evaluating the efficacy of chromium in glycemic control, the potential for genotoxic effects may outweigh potential benefits. 4 , 5

However, toxicological studies should be interpreted correctly, as the effects are dependent on the general chemistry of the ligand or complex being tested, as well as the treatment conditions and media used. 4 In bacterial mutagenicity assays, trivalent chromium compounds appear to be largely inactive. 5 Mixed results have been reported for short-term bioassays using cultured mammalian cells, and an increasing number of mutagenic and genotoxic effects are being published. 5 In monkeys fed hexavalent chromium for 180 days at levels common in industrial settings, resultant oxidative stress in the testes was considered to be responsible for spermatozoa toxicity. 42 Limited animal experimentation showed skeletal and neurological defects in the offspring of mice fed chromium picolinate during pregnancy or lactation. 4 , 34

Concern regarding the release of chromium from metal implants (ie, in total knee arthroplasty and hip replacements) has been studied. 40 , 43 , 44 , 45 , 46 , 47 Studies conducted for periods of up to 6 years have shown initial increases in chromium serum levels, but not in erythrocyte levels, probably as a result of corrosion of the implant surface and wear. Peak chromium levels were reported at 9 months, with a gradual decline thereafter in 1 study. 47 A gender difference was also reported in 1 study; higher levels of serum chromium were noted in women. 43 No evidence of systemic toxic effect or mutagenicity was found in patients in any of these studies, 43 , 44 , 45 , 46 , 47 including those with chronic renal failure. 40

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