Chromium

Identification

Summary

Chromium is an ingredient found in a variety of supplements and vitamins.

Brand Names

Nicomide

Generic Name

Chromium

DrugBank Accession Number

DB11136

Background

Chromium is a transition element with the chemical symbol Cr and atomic number 24 that belongs to Group 6 of the periodic table. It is used in various chemical, industrial and manufacturing applications such as wood preservation and metallurgy. The uses of chromium compounds depend on the valency of chromium, where trivalent Cr (III) compounds are used for dietary Cr supplementation and hexavalent Cr (VI) compounds are used as corrosion inhibitors in commercial settings and are known to be human carcinogens ⁵. Humans can be exposed to chromium via ingestion, inhalation, and dermal or ocular exposure ⁶. Trivalent chromium (Cr(III)) ion is considered to be an essential dietary trace element as it is involved in metabolism of blood glucose, regulation of insulin resistance and metabolism of lipids. Clinical trials and other studies suggest the evidence of chromium intake improving glucose tolerance in patients with Type I and II diabetes, however its clinical application in the standard management of type II diabetes mellitus is not established. Chromium deficiency has been associated with a diabetic-like state, impaired growth, decreased fertility and increased risk of cardiovascular diseases ^1,2,5.

According to the National Institute of Health, the daily dietary reference intake (DRI) of chromium for adult male and non-pregnant female are 35 μg and 25 μg, respectively ⁷. Chromium picolinate capsules may be used as nutritional adjuvant in patients with or at risk of type 2 diabetes mellitus (T2DM) to improve blood sugar metabolism and stabilize the levels of serum cholesterol. Chromium chloride is available as an intravenous injection for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN) ^Label.

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 51.9961
Monoisotopic: 51.940511904
Chemical Formula: Cr

Synonyms

Biochrome
Chrom
Chromium, elemental
Cromo
Dinakrome

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Pharmacology

Indication

Indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN), to maintain chromium serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms ^Label.

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Associated Therapies

Mineral supplementation therapy

Contraindications & Blackbox Warnings

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Pharmacodynamics

Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity ². In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency ^Label.

Mechanism of action

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules ³. Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol 2-kinase (PI3K). PI3K activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter-4 (Glut4)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake ³. Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI3-kinase and Akt.

Under insulin-resistant conditions, chromium also promotes GLUT-4 transporter translocation that is independent of activity of IR, IRS-1, PI3-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein ³. As a result, intracellular GLUT-4 transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells ⁸. Chromium attenuates the activity of PTP-1B in vitro, which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling ³. Transient upregulation of AMPK by chromium also leads to increased glucose uptake ³.

Target	Actions	Organism
UCytochrome b5	substrate	Humans

Absorption

Chromium compounds are both absorbed by the lung and the gastrointestinal tract. Oral absorption of chromium compounds in humans can range between 0.5% and 10%, with the hexavalent (VI) chromium more easily absorbed than the trivalent (III) form ⁵. Absorption of chromium from the intestinal tract is low, ranging from less than 0.4% to 2.5% of the amount consumed ⁷. Vitamin C and the vitamin B niacin is reported to enhance chromium absorption ⁷.

Most hexavalent Cr (VI) undergoes partial intragastric reduction to Cr (III) upon absorption, which is an action mainly mediated by sulfhydryl groups of amino acids ⁵. Cr (VI) readily penetrates cell membranes and chromium can be found in both erythrocytes and plasma after gastrointestinal absorption of Cr (IV). In comparison, the presence of chromium is limited to the plasma as Cr (III) displays poor cell membrane penetration ⁵. Once transported through the cell membrane, Cr (VI) is rapidly reduced to Cr (III), which subsequently binds to macromolecules or conjugate with proteins. Cr (III) may be bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF).

Volume of distribution

Absorbed chromium is distributed to all tissues of the body and its distribution in the body depends on the species, age, and chemical form ⁸. Circulating Cr (III) following oral or parenteral administration of different compounds can be taken up by tissues and accumulates in the liver, kidney, spleen, soft tissue, and bone ⁷.

Protein binding

In the blood, 95% of chromium (III) is bound to large molecular mass proteins, such as transferrin, while a small proportion associates with low molecular mass oligopeptides ⁶. Serum chromium is bound to transferrin in the beta globulin fraction ^Label.

Metabolism

The metabolism of Cr (VI) involves reduction by small molecules and enzyme systems to generate Cr (III) and reactive intermediates. During this process, free radicals can be generated, which is thought to induce damage of cellular components and cause toxicity of chromium ⁶. The metabolites bind to cellular constituents ⁵.

Route of elimination

Absorbed chromium is excreted mainly in the urine, accounting for 80% of total excretion of chromium; small amounts are lost in hair, perspiration and bile ⁵. Chromium is excreted primarily in the urine by glomerular filtration or bound to a low molecular-weight organic transporter ⁸.

Half-life

The elimination half-life of hexavalent chromium is 15 to 41 hours ⁵.

Clearance

Excretion of chromium is via the kidneys ranges from 3 to 50 μg/day ^Label. The 24-hour urinary excretion rates for normal human subjects are reported to be 0.22 μg/day ⁸.

Adverse Effects

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Toxicity

Oral LD50 for Cr (VI) is 135 - 175 mg/kg in mouse and 46 - 113 mg/kg in rat ⁵. Oral LD50 for Cr (III) in rat is >2000 mg/kg ⁵. LD50 of chromium (III) oxide in rats is reported to be > 5g/kg ⁶. Other LD50 values reported for rats include: 3.5 g/kg (CI 3.19-3.79 g/kg) for chromium sulphate; 11.3 g/kg for chromium (III) acetate; 3.3 g/kg for chromium nitrate; and 1.5 g/kg for chromium nitrate nonahydrate ⁶.

Acute overdose of chromium is rare and seriously detrimental effects of hexavalent chromium are primarily the result of chronic low-level exposure ⁵. In case of overdose with minimal toxicity following acute ingestion, treatment should be symptomatic and supportive ⁵. There is no known antidote for chromium toxicity.

Hexavalent chromium is a Class A carcinogen by the inhalation route of exposure and Class D by the oral route ⁵. The oral lethal dose in humans has been estimated to be 1-3 g of Cr (VI); oral toxicity most likely involves gastrointestinal bleeding rather than systemic toxicity ⁵. Chronic exposure may cause damage to the following organs: kidneys, lungs, liver, upper respiratory tract ^MSDS. Soluble chromium VI compounds are human carcinogens. Hexavalent chromium compounds were mutagenic in bacteria assays and caused chromosome aberrations in mammalian cells. There have been associations of increased frequencies of chromosome aberrations in lymphocytes from chromate production workers ⁴. In human cells in vitro, Cr (VI) caused chromosomal aberrations, sister chromatid exchanges and oxidative DNA damage ⁵.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Chromium which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Chromium which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Chromium which could result in a higher serum level.
Acetaminophen	Acetaminophen may decrease the excretion rate of Chromium which could result in a higher serum level.
Acetazolamide	Acetazolamide may increase the excretion rate of Chromium which could result in a lower serum level and potentially a reduction in efficacy.

Food Interactions

Administer vitamin supplements. Niacin (from food or supplements) may increase the absorption of chromium.
Take with foods containing vitamin C. Vitamin C may increase the absorption of chromium.

Products

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Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Accelerator	Tablet	150 mcg	Oral	Health 4 All Products Limited.	Not applicable	Not applicable
Bio-chrome	Capsule	200 mcg / cap	Oral	SantÉ Naturelle (Ag) LtÉe	2000-06-28	2002-06-18
Chelated Chromium 200 Mcg	Tablet	200 mcg / tab	Oral	Wn Pharmaceuticals Ltd.	1998-06-26	2008-07-17
Chelated Chromium Capsules	Capsule	100 mcg / cap	Oral	Albion	1996-09-06	2002-07-12
Chelated Chromium Gtf 500mcg Tab	Tablet	500 mcg	Oral	Gahler Enterprises Ltd.	1987-12-31	2009-09-28

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
24 Multivitamins + Minerals	Chromium (20 mcg) + Ascorbic acid (150 mg) + Beta carotene (10000 unit) + Biotin (25 mcg) + Calcium (130 mg) + Cholecalciferol (400 unit) + Choline bitartrate (25 mg) + Copper (1 mg) + Cyanocobalamin (25 mcg) + Ferrous fumarate (15 mg) + Folic acid (.8 mg) + Inositol (25 mg) + Magnesium (65 mg) + Manganese (2 mg) + Molybdenum (20 mcg) + Niacin (25 mg) + Calcium pantothenate (25 mg) + Potassium (15 mg) + Potassium Iodide (.1 mg) + Pyridoxine hydrochloride (25 mg) + Racemethionine (25 mg) + Riboflavin (25 mg) + Selenium (20 mcg) + Thiamine hydrochloride (25 mg) + Vanadium (20 mcg) + Vitamin A palmitate (5000 unit) + Vitamin E (50 unit) + Zinc (10 mg)	Tablet	Oral	Stanley Pharmaceuticals, A Division Of Vita Health Products Inc.	1997-04-30	2002-07-31
50 Plus Multiple Vitamins & Minerals	Chromium (10 mcg) + Ascorbic acid (90 mg) + Biotin (45 mcg) + Calcium (200 mg) + Cholecalciferol (400 unit) + Copper (2 mg) + Cyanocobalamin (25 mcg) + Folic acid (0.4 mg) + Magnesium (100 mg) + Manganese (5 mg) + Molybdenum (25 mcg) + Nicotinamide (40 mg) + Pantothenic acid (10 mg) + Potassium Iodide (0.15 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin (3.2 mg) + Selenium (25 mcg) + Thiamine mononitrate (2.25 mg) + Vanadium (10 mcg) + Vitamin A palmitate (6000 unit) + Zinc (15 mg)	Tablet	Oral	Gfr Pharma Ltd.	2002-10-20	2004-06-15
A.M. Formula	Chromium (133.3 mcg) + Vanadium (25 mcg)	Tablet	Oral	Abundance Naturally Ltd	1998-06-05	1999-08-06
Aces Caplet	Chromium (25 mcg) + Beta carotene (15000 unit) + Calcium ascorbate (350 mg) + Selenium (100 mcg) + Vitamin E (200 unit) + Zinc (25 mg)	Tablet	Oral	Nu Life Nutrition Ltd.	1997-08-15	2005-03-15
Aces Tab	Chromium (25 mcg) + Calcium ascorbate (350 mg) + Cholecalciferol (200 unit) + Selenium (100 mcg) + Vitamin A (5000 unit) + Vitamin E (200 unit) + Zinc (25 mg)	Tablet	Oral	Nu Life Nutrition Ltd.	1987-12-31	2005-03-15

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Keylosa	Chromium (35 ug/1) + Ascorbic acid (120 mg/1) + Calcium carbonate (200 mg/1) + Cholecalciferol (20 ug/1) + Cyanocobalamin (8 ug/1) + Ferrous fumarate (27 mg/1) + Folic acid (1000 ug/1) + Magnesium oxide (200 mg/1) + Manganese sulfate (23 mg/1) + Molybdenum (45 ug/1) + Nicotinamide (20 mg/1) + Pyridoxine (20 mg/1) + Riboflavin (3.4 mg/1) + Selenium (55 ug/1) + Thiamine mononitrate (3 mg/1) + Vitamin A (1500 ug/1) + Vitamin E (30 mg/1) + Zinc oxide (25 mg/1)	Capsule, coated	Oral	Novian Pharmaceuticals	2023-10-06	Not applicable
Lipovite	Chromium (1 mg/1mL) + Choline (1 mg/1mL) + Citrulline (1 mg/1mL) + Dexpanthenol (1 mg/1mL) + Inositol (1 mg/1mL) + Levocarnitine (1 mg/1mL) + Lidocaine (1 mg/1mL) + Mecobalamin (1 mg/1mL) + Methionine sulfoximine (1 mg/1mL) + Nicotinamide (1 mg/1mL) + Pyridoxine (1 mg/1mL) + Riboflavin (1 mg/1mL) + Thiamine chloride (1 mg/1mL)	Injection	Intramuscular	Perdido Key Health And Wellness Inc	2015-11-23	Not applicable
Nicomide	Chromium (100 ug/1) + Cupric oxide (2 mg/1) + Folic acid (500 ug/1) + Nicotinamide (750 mg/1) + Selenium (50 ug/1) + Zinc glycinate (27 mg/1)	Tablet	Oral	Avion Pharmaceuticals, Llc	2014-12-08	Not applicable
Nicotinamide	Chromium (100 ug/1) + Copper (2 mg/1) + Folic acid (850 ug/1) + Nicotinamide (750 mg/1) + Selenium (50 ug/1) + Zinc (27 mg/1)	Tablet	Oral	Acella Pharmaceuticals, LLC	2021-05-25	Not applicable
Strovite Forte Caplet	Chromium (50 ug/1) + Ascorbic acid (500 mg/1) + Biotin (0.15 mg/1) + Copper (3 mg/1) + Cyanocobalamin (50 ug/1) + Folic acid (1 mg/1) + Iron (10 mg/1) + Magnesium (50 mg/1) + Molybdenum (20 ug/1) + Niacin (100 mg/1) + Pantothenic acid (25 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Riboflavin (20 mg/1) + Selenium (50 ug/1) + Thiamine mononitrate (20 mg/1) + Vitamin A (4000 [iU]/1) + Vitamin D (400 [iU]/1) + Vitamin E (60 [iU]/1) + Zinc (15 mg/1)	Tablet, coated	Oral	Exeltis Usa, Inc.	1996-10-01	2023-01-13

Chemical Identifiers

UNII: 0R0008Q3JB
CAS number: 7440-47-3
InChI Key: VYZAMTAEIAYCRO-UHFFFAOYSA-N
InChI: InChI=1S/Cr
IUPAC Name: chromium
SMILES: [Cr]

References

General References

Wallach S: Clinical and biochemical aspects of chromium deficiency. J Am Coll Nutr. 1985;4(1):107-20. [Article]
Anderson RA: Chromium in the prevention and control of diabetes. Diabetes Metab. 2000 Feb;26(1):22-7. [Article]
Hua Y, Clark S, Ren J, Sreejayan N: Molecular mechanisms of chromium in alleviating insulin resistance. J Nutr Biochem. 2012 Apr;23(4):313-9. doi: 10.1016/j.jnutbio.2011.11.001. [Article]
CHROMIUM, ELEMENTAL - National Library of Medicine HSDB ... - Toxnet - NIH [Link]
CHROMIUM COMPOUNDS - National Library of Medicine HSDB ... - Toxnet - NIH [Link]
Chromium Toxicological Overview - Health Protection Agency - Gov.uk [Link]
Dietary Supplement Fact Sheet: Chromium [Link]
Dailymed Label: DIVISTA - chromium picolinate capsule [Link]

External Links

KEGG Compound: C06268
PubChem Compound: 23976
PubChem Substance: 347827914
ChemSpider: 22412
RxNav: 2496
ChEBI: 28073
Wikipedia: Chromium

FDA label

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MSDS

Download (49.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Unknown Status	Treatment	Hyperuricemia	1
3	Completed	Treatment	Type 2 Diabetes Mellitus	1
2	Completed	Prevention	Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Traumatic Brain Injury (TBI)	1
2	Terminated	Prevention	Obesity / Weight Gain	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	150 mcg
Injection, solution, concentrate	Intravenous
Capsule	Oral	200 mcg / cap
Tablet, film coated	Oral
Solution	Oral
Tablet	Oral	200 mcg / tab
Capsule	Oral	100 mcg / cap
Tablet	Oral	200 mcg
Tablet	Oral	0.2 mg
Tablet	Oral	500 mcg
Capsule	Oral	100 mcg
Tablet, extended release	Oral	200 mcg
Capsule	Oral	200 mcg
Tablet	Oral	100 mcg / tab
Tablet, extended release	Oral
Capsule	Oral
Capsule	Oral	10 mcg / cap
Tablet, effervescent	Oral
Capsule, coated	Oral
Injection	Intramuscular
Kit	Oral
Liquid	Intravenous
Liquid	Oral
Tablet	Oral
Tablet	Oral
Capsule	Oral
Tablet	Oral	6 mcg / tab
Tablet, coated	Oral
Powder, for solution	Oral
Powder	Oral	150 mcg / 20 g
Powder	Oral
Tablet	Oral	100 mcg

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	1900	MSDS
boiling point (°C)	2642	MSDS
water solubility	Insoluble	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.0 mg/mL	ALOGPS
logP	-1.3	ALOGPS
logP	-0.16	Chemaxon
logS	1.08	ALOGPS
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	0	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	0 Å²	Chemaxon
Rotatable Bond Count	0	Chemaxon
Refractivity	0 m³·mol^-1	Chemaxon
Polarizability	1.78 Å³	Chemaxon
Number of Rings	0	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST): Not Available
Spectra: Not Available
Chromatographic Properties: Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Cytochrome b5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Metal ion binding
Specific Function: Cytochrome b5 is a membrane bound hemoprotein which function as an electron carrier for several membrane bound oxygenases.
Gene Name: CYB5A
Uniprot ID: P00167
Uniprot Name: Cytochrome b5
Molecular Weight: 15329.985 Da

References

Jannetto PJ, Antholine WE, Myers CR: Cytochrome b(5) plays a key role in human microsomal chromium(VI) reduction. Toxicology. 2001 Feb 28;159(3):119-33. [Article]

Carriers

Details1. Serotransferrin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Transferrin receptor binding
Specific Function: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from si...
Gene Name: TF
Uniprot ID: P02787
Uniprot Name: Serotransferrin
Molecular Weight: 77063.195 Da

References

Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [Article]

Drug created at December 03, 2015 16:51 / Updated at April 19, 2024 20:55

Chromium

Identification

Structure for Chromium (DB11136)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

Carriers

References