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Chromium: Is It Essential and Is It Safe?

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Michael Eskin at University of Manitoba
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ISSN: 2376-1318
Vitamins & Minerals
Eskin, Vitam Miner 2016, 5:1
http://dx.doi.org/10.4172/2376-1318.1000e144
Editorial Open Access
Volume 5 • Issue 1 • 1000e144
Vitam Miner
ISSN: 2376-1318 VMS, an open access journal
Chromium: Is It Essential and Is It Safe?
Michael Eskin NA*
Department of Human Nutritional Sciences, University of Manitoba, Canada
*Corresponding author: Michael Eskin NA, Department of Human Nutritional
Sciences, University of Manitoba, Canada, Tel: 2044748078; Fax: 2044747592;
E-mail: Michael.Eskin@umanitoba.ca
Received March 10, 2016; Accepted March 11, 2016; Published March 18, 2016
Citation: Eskin NAM (2016) Chromium: Is It Essential and Is It Safe?. Vitam Miner
5: e144. doi:10.4172/2376-1318.1000e144
Copyright: © 2016 Eskin NAM. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Elemental chromium (Cr) was discovered in crocoite, a mineral
with a deep-orange red color, by Vaquelin in 1798 [1]. Schwartz and
Mertz [2] in 1959 were the rst to report Cr was an essential element
in rats while in 1977 Jeejebhoy et al. [3] showed it was essential in
humans. Many research studies were conducted with Cr over the years
[4] but the main focus was its relationship with diabetes mellitus [5].
While the evidence supporting an anti-diabetic role for Cr appeared
strong it was still far from denitive [6]. e two main forms of
chromium are the trivalent CrIII (chromium III) and the hexavalent
form CrVI (chromium VI). Of these, CrIII is the most stable oxidation
state found in living organisms but unable to cross cell wall membranes
easily [7]. Complexing with certain organic ligands such as picolinic
acid, however, allowed CrIII to be readily absorbed by cell membranes
[8]. A recent paper by Doddigarta and co-workers [9] showed that
male Wistar rats fed a high carbohydrate diet supplemented with
chromium picolinate (CrPlc) and melatonin, given individually or in
combination, prevented the development of insulin resistance and type
2 diabetes. A series of studies by Anderson’s group in the 1990’s [10-12]
used a low-Cr diet when feeding rats 55% sucrose, 15% lard, 25% casein
plus vitamins, and minerals. A close examination of these studies by
Bona et al. [13] questioned whether such diets were low in chromium
as based on their calculations the rats were provided with 10 times
higher levels of Cr per kg body weight than recommended for humans.
According to National Academy of Science an adequate intake (AI)
for chromium is 35 µg/day for men and 25 µg/day for women [14].
Using carefully controlled metal-free conditions (including plastic
cages); Bona et al. [13] fed male Zucker lean rats over 6 months an
AIN-93 G diet supplemented with 200 µg and 1000 µg Cr/kg. None
of the diets, including those supplemented with Cr, had any eect on
body composition, glucose metabolism or insulin sensitivity. ese
results raised serious concerns as to whether CrIII was actually essential.
A review of previous papers by Yoshida et al. [15] also questioned
whether Cr was an essential trace element. e amount of Cr provided
to experimental animals far exceeded the daily human intake of 20-
80 µg/day and was closer to a pharmacological dose. Based on these
results they also questioned whether Cr was indeed an essential trace
element. Aer an extensive of the literature, the European Food Safety
Authority determined that Cr should no longer be considered essential
for humans or animals [16].
In addition to the controversy surrounding the essential status of
Cr, the safety of Cr has also become an important issue. Of the two forms
of Cr, the hexavalent form, CrVI, has long been known to be toxic and
cancinogenic. In the 19th century, Scottish workers handling hexavalent
chromium were found to develop nose cancers [17]. Later reports in
Germany in the 1930’s reported a high incidence of lung cancer in
workers exposed to this form chromium which clearly established CrVI
as a signicant occupational hazard [18]. e toxicity of CrVI gained
notoriety in the book and subsequent movie Erin Brockovitch, released
in 2000, that it was a major contaminant in the drinking water of the
town of Hinckley in California responsible for a cluster of illnesses
and cancers. A later study by Kirpnick-sohol and co-workers in 2006
[19] reported that the both the contaminant CrVI and nutritional
supplement CrIII caused large scale and irreversible genome damage
in yeast and mice when ingested in drinking water. A recent study in
Australia by Wu and co-workers [20] raised concerns regarding the
safety of nutritional supplements containing CrIII. Such supplements
are widely consumed for treating such metabolic disorders as insulin
resistance, type 2 diabetes and also as muscle development agents.
Using a combination of X-ray uorescence microscopy (XFM) and
X-ray absorption near edge structure (XANES) studies, Wu et al. [20]
found that CrIII injected into mice fat cells (adipocytes) was oxidized into
the carcinogenic forms of chromium, CrVI and CrV. e long -latency
time of Cr-induced cancers in humans makes it dicult to extrapolate
from animal studies to humans. However, these researchers strongly
recommended epidemiological studies be conducted to determine
the cancer risk of CrIII supplements. Based on the scientic data, there
is clear evidence for removing chromium as an essential element for
humans and animals. In addition, the ability of CrIII to be converted
to the toxic form of CrVI requires new regulations to protect the public
from exposure to Cr.
References
1. Baceloux DG (1999) Chromium. J Toxicol Clin Toxicol 37: 173-194.
2. Schwartz K, Mertz Z (1959) Chromium (III) and glucose tolerance factor Arch
Biochem Biophys. 85: 292-295.
3. Jeejebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A
(1977) Chromium deciency, glucose intolerance and neuropathy reversed
by chromium supplementation in a patient receiving long-term total parenteral
nutrition. Am J Clin Nutr 30: 531-538.
4. Rabinowitz MB, Gonick HC, Levine SR, Davidson MR (1983) Clinical trial of
chromium and yeast supplements on carbohydrate and lipid metabolism in
diabetic men. Biological Trace Element Research 5: 449-466.
5. Pechova A, Pavlata L (2007) Chromium as an essential nutrient: a review.
Veterinarni Medicina 52: 1-18.
6. Vincent JB (2004) Recent advances in the nutritional biochemistry of trivalent
chromium. Proc Nutr Soc 63: 41-47.
7. Mertz W (1992) Chromium: History and nutritional importance. Biol Trace Elem
Res 32: 3-8.
8. Stearns DM, Siviera SM, Wolf KK, Luke AM (2002) Chromium (III) tris(picolinate)
is mutagenic at the hypoxanthine (guanine) phosphoribosyltransfrase locuis in
Chinese hamster ovary cells. Mutation Research 513: 133-142.
9. Doddigarta Z, Ahmad J, Parwez I (2016) Effect of chromium picolinate and
melatonin either in single or in a combination in high carbohydrate diet-fed male
Wistar rats. Biofactors 42: 106-114.
10. Stifer JS, Law JS, Polansky MM, Bhathena SJ, Anderson RA (1995) Chromium
improves insulin response to glucose in rats. Metabolism 44: 1314-1320.
11. Anderson Ra, Bryden NA, Polansky MM , Reiser S (1990) Urinary chromium
excretion and insulinogenic properties of carbohydrates. The American Journal
of Clinical Nutrition 51: 864-868.
12. Stifer JS, Polansky MM, Anderson RA (1998) Dietary chromium decreases
insulin resistance in rats fed a high fat, mineral imbalanced diet. Metabolism
47: 396-400.
Citation: Eskin NAM (2016) Chromium: Is It Essential and Is It Safe?. Vitam Miner 5: e144. doi:10.4172/2376-1318.1000e144
Page 2 of 2
Volume 5 • Issue 1 • 1000e144
Vitam Miner
ISSN: 2376-1318 VMS, an open access journal
13. DiBona KR, Love S, Rhodes NR, McAdory D, Sinha SH, et al. (2011) Chromium
is not an essential trace element for mammals: Effects of a “low-chromium”
diet. J Biol Inorg Chem 16: 381-390.
14. National Research Council (2002) Dietary reference intakes for vitamin A,
arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum,
nickel, silicon, vanadium, and zinc. National Academies Press (US).
15. Yoshida M (2012) Is chromium an essential trace element in human nutrition?
Nihon Eiseigaku Zasshi 67: 485-491.
16. Carlo Agostoni, Roberto Berni Canani, Susan Fairweather-Tait, Marina
Heinonen, Hannu Korhonen, et al. (2014) Scientic opinion on dietary reference
values for chromium. EFSA J 12: 3845-3870.
17. Cohen MD, Kargacin B, Klein CB, Costa M (1993) Mechanisms of chromium
carcinogenicity and toxicity. Crit Rev Toxicol 23: 255-281.
18. Teleky LO (1936) Krebs bei chromarbeitern. Dtsch med Wochenschr 62: 1353.
19. Kirpnick-Sobol Z, Reliene R, Schiestl RH (2006) Carcinogenic Cr(VI) and the
nutritional supplement Cr(III) induce DNA deletions in yeast and mice. Cancer
Res 66: 3480-3484.
20. Wu LE, Levinu A, Harris HH, Cai Z, Lai C, et al. (2016) Carcinogenic chromium
(VI) compounds formed by intracellular oxidation of chromium ()iii) dietary
supplements by adipocytes. Angew Chem Int Ed Engl 128: 1774-1777.
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Citation: Eskin NAM (2016) Chromium: Is It Essential and Is It Safe?. Vitam
Miner 5: e144. doi:10.4172/2376-1318.1000e144
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... Cr (VI) is recognized as a toxic element to the human body because it is permeable to the cell membrane system, whereas Cr (III) is less toxic and impermeable to the cell membrane barrier. However, it is readily absorbed along with other organic ligands such as picolinic acid by the cell membrane barrier [1]. Cr (III) is used as a dietary supplement because it is present in most food such as egg yolks, grains, cereals, coffee, nuts, green beans, broccoli, meat, and brewer's yeast [2]. ...
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Based on research, several scientific publications proposed dietary trivalent chromium as an attractive alternative for the prevention of hyperglycemia in people at high risk of type 2 diabetes mellitus (T2DM). The objective of the study is to determine the influence of chromium on the reaction of glucose and insulin in individuals with type 2 diabetes and healthy subjects. The study was based on several clinical reports of randomized clinical trials (RCTs). Available RCTs that were issued before December 2020 were routinely looked for in PubMed/Medline, Scopus, Web of Sciences, Google Scholar, and Cochrane Library. Keywords, such as “chromium” OR “chromium supplements” OR “chromium picolinate” in combination with “type 2 diabetes” were also checked in English. The results of these clinical studies support the view that chromium can improve both insulin and glucose metabolism in patients with T2DM, especially in the form of dietary supplements (chromium picolinate). However, insufficient data are available to create a conclusive hypothesis that nutritional supplements of chromium could be useful for the treatment of T2DM, and thus there is no need to endorse a general prescription for the management of diabetes using these supplements. Chromium supplements have minimal usefulness based on the lower impact of established evidence, and there is no reason for promoting their use for glycemic control in patients with existing T2DM. Well-designed, high-quality, broad, and long-term trials are required to improve the current data and ensure the protection and efficacy of drugs.
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In the leather industry, Cr (III) is used as a basic tanning agent. The wastewater discharged from the tannery industry contains a high concentration of chromium. Recent studies indicate the genotoxic effects especially DNA damage and oxidative stress of Cr (III) in tannery workers. Cr (III) interacts with DNA to form DNA cross-links and DNA strand breaks. It also modifies the oxidative DNA base through the Haber–Weiss reaction. The present study is based on an overview of scientific literature and previous observations regarding the effects of tannery chromium effluents on exposed workers and the population in the vicinity. This study strongly suggests for use of a non-toxic substitute of chromium to be used for the tanning process and placement of tannery industries on the outskirts of the city. In South Asian developing countries like India, Pakistan and Bangladesh where the economy is strongly dependent on leather manufacturing industries, there is a need to spread proper information regarding the harmful effects of chromium toxicity to the workforce employed in the tannery and also to the people living in the surrounding area. Workers should be provided with the required safety protections like gloves, aprons, foot/shoe covers, masks, etc. Last but most important on an immediate basis is the installation of the proper efficient waste treatment plant, so that, waste should be treated before moving out of the industry.
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Chromium (Cr) has been studied since the end of the 19 th century, when carcinogenic effects of hexavalent Cr were discovered. Essentiality of trivalent Cr was demonstrated in 1959; Cr 3+ has been studied in humans and laboratory animals since the 1970s and it is only since the 1990s that Cr has been studied as an essen-tial element in livestock animals with the same intensity. Trivalent chromium is essential to normal carbohydrate, lipid and protein metabolism. Chromium is biologically active as part of an oligopeptide – chromodulin – poten-tiating the effect of insulin by facilitating insulin binding to receptors at the cell surface. With chromium acting as a cofactor of insulin, Cr activity in the organism is parallel to insulin functions. Cr absorption is low, ranging between 0.4 and 2.0% for inorganic compounds while the availability of organic Cr is more than 10 times higher. Absorbed Cr circulates in blood bound to the β-globulin plasma fraction and is transported to tissues bound to transferrin. Absorbed Cr is excreted primarily in urine, by glomerular filtration; a small amount is excreted through perspiration, bile and in milk. The demand for Cr has been growing as a result of factors commonly referred to as stressors, especially during different forms of nutritional, metabolic and physical strain. This review describes Cr metabolism, the different biological functions of Cr and symptoms of Cr deficiency.
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Chromium is not an essential trace element for mammals: Effects of a "low-chromium" diet
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Chromium was proposed to be an essential trace element over 50 years ago and has been accepted as an essential element for over 30 years. However, the studies on which chromium's status are based are methodologically flawed. Whether chromium is an essential element has been examined for the first time in carefully controlled metal-free conditions using a series of purified diets containing various chromium contents. Male Zucker lean rats were housed in specially designed metal-free cages for 6 months and fed the AIN-93G diet with no added chromium in the mineral mix component of the diet, the standard AIN-93G diet, the standard AIN-93G diet supplemented with 200 μg Cr/kg, or the standard AIN-93G diet supplemented with 1,000 μg Cr/kg. The chromium content of the diet had no effect on body mass or food intake. Similarly, the chromium content of the diet had no effect on glucose levels in glucose tolerance or insulin tolerance tests. However, a distinct trend toward lower insulin levels under the curve after a glucose challenge was observed with increasing chromium content in the diet; rats on the supplemented AIN-93G diets had significantly lower areas (P < 0.05) than rats on the low-chromium diet. The studies reveal that a diet with as little chromium as reasonably possible had no effect on body composition, glucose metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet. Together with the results of other recent studies, these results clearly indicate that chromium can no longer be considered an essential element.
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Chromium deficiency, glucose intoerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition
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Full-text available
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A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.
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Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes
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Chromium(III) nutritional supplements are widely consumed for their purported antidiabetic activities. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure (XANES) studies have now shown that non-toxic doses of [Cr3 O(OCOEt)6 (OH2 )3 ](+) (A), a prospective antidiabetic drug that undergoes similar H2 O2 induced oxidation reactions in the blood as other Cr supplements, was also oxidized to carcinogenic Cr(VI) and Cr(V) in living cells. Single adipocytes treated with A had approximately 1 μm large Cr hotspots containing Cr(III) , Cr(V) , and Cr(VI) (primarily Cr(VI) thiolates) species. These results strongly support the hypothesis that the antidiabetic activity of Cr(III) and the carcinogenicity of Cr(VI) compounds arise from similar mechanisms involving highly reactive Cr(VI) and Cr(V) intermediates, and highlight concerns over the safety of Cr(III) nutritional supplements.
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Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet-fed male Wistar rats
Article
  • Dec 2015
  • BIOFACTORS
This study is designed to know the effects of chromium picolinate (CrPic) and melatonin (Mel) each alone and in a combination on high carbohydrate diet-fed (HCD-fed) male Wistar rats that exhibit insulin resistance (IR), hyperglycemia, and oxidative stress. Wistar rats have been categorized into five groups. Each group consisted of six male Wistar rats, control rats (group I), HCD (group II), HCD + CrPic (group III), HCD + Mel (group IV), and HCD + CrPic + Mel (group V). Insignificant differences were observed in serum levels of superoxide dismutase, nitric oxide, and zinc in group III, group IV, and group V when each group was compared with group II rats respectively. Significant differences were observed in group III, group IV, and group V when each group was compared with group II in homeostasis model assessment-estimated IR (P < 0.05, <0.0.05, <0.05), and in the levels of blood glucose (P < 0.05, <0.0.05, <0.05), total cholesterol (P < 0.05, <0.001, <0.001), triacylglycerols (<0.05, <0.001, <0.001), high density lipoprotein cholesterol (P < 0.05, <0.001, <0.001), malondialdehyde (P < 0.05, <0.05, <0.001), catalase (P <0.05, <0.05, <0.05), glutathione (P < 0.05, <0.05, <0.05), Mel (P < 0.05, <0.05, <0.001), and copper (P < 0.05, <0.05, < 0.001). In view of these results, HCD-fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving CrPic and Mel administration in alone or in a combination. © 2015 BioFactors, 2015.
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Clinical trial of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men
Article
  • Dec 1983
  • BIOL TRACE ELEM RES
Chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition has been shown to cause diabetes mellitus. Prior trials in humans indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random cross-over trial of inorganic chromium trichloride, a brewer's yeast that contained Cr as glucose-tolerance-factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 months each. Subgroups included 21 ketosis-prone, 7 ketosis-resistant non-obese, and 15 ketosis-resistant obese men. Cr levels were followed pre- and post-treatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as the change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after iv tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments.
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Is Chromium an Essential Trace Element in Human Nutrition?
Article
  • Oct 2012
  • Nihon Eiseigaku Zasshi
抄録 It has been recognized that chromium is an essential trace element associated with carbohydrate metabolism, and chromium deficiency causes an impaired glucose tolerance. Recently, however, Vincent et al. have reported that chromium is not an essential trace element. In the present report, the author evaluated the nutritional essentiality of chromium by reviewing several previous reports. In almost all previous reports, the chromium concentration in the animal feed used was higher than 0.1 μg/g, and it is difficult to consider that the experimental animals were in a low-chromium state. In addition, the amount of chromium administered to the animals for the improvement of glucose tolerance was at a pharmacological level, and corresponded to a level that far exceeded the human daily chromium intake (20 to 80 μg/day). On the other hand, recent research has clearly shown that feeding with a severely low-chromium diet (0.016 μg/g) does not impair glucose tolerance. The amount of chromium absorbed in humans estimated from chromium intake (20 to 80 μg/day), chromium absorption rate (1%), and urinary chromium excretion (<1 μg/day) is less than 1 μg/day, which is much lower than those of other essential trace elements. In addition, because there is an inconsistency between the chromium concentration in food and chromium intake, chromium intake seems to be dependent on chromium contamination during food processing and cooking. It is concluded that there is a high possibility that chromium is not an essential trace element.
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