C

Bv

SSa

b

a

ARA

KCTG

I

ftttitciilog

T

0d

Journal of Trace Elements in Medicine and Biology 25 (2011) 149– 153

Contents lists available at ScienceDirect

Journal of Trace Elements in Medicine and Biology

j ourna l homepage: www.elsev ier .de / j temb

LINICAL STUDIES

eneficial effect of chromium supplementation on glucose, HbA1C and lipidariables in individuals with newly onset type-2 diabetes

hilpi Sharmaa, Rajendra Prasad Agrawalb,∗, Maya Choudharya, Shreyans Jainb,hekhar Goyalb, Vivek Agarwalb

College of Home Science, MPUA&T, Udaipur, Rajasthan, IndiaDiabetes Care & Research Centre, S.P. Medical College, Bikaner, Rajasthan, India

r t i c l e i n f o

rticle history:eceived 8 July 2010ccepted 30 March 2011

eywords:hromiumype 2 diabeteslycaemic control

a b s t r a c t

Project: Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. Itinfluences glucose metabolism by potentiating the action as taking part in insulin signal amplificationmechanism. A placebo-controlled single blind, prospective study was carried out to investigate the effectof chromium supplementation on blood glucose, HbA1C and lipid profile in newly onset patients withtype-2 diabetes.Procedure: Total 40 newly onset type-2 diabetics were selected and after 1 month stabilization furtherrandomly divided into two groups viz. study group and placebo group. The study group received 9 gbrewer’s yeast (42 �g Cr) daily and the other placebo group received yeast devoid of chromium for 3months. Subjects were instructed not to change their normal eating and living habits. Fasting bloodglucose, HbA1C and lipid profile were analyzed at beginning and completion of the study.Results: Results revealed that fasting blood glucose level significantly reduced in the subjects consum-ing yeast supplemented with chromium (197.65 ± 6.68 to 103.68 ± 6.64 mg/dL; p < 0.001). HbA1C values

improved significantly from 9.51 ± 0.26% to 6.86 ± 0.28%; p < 0.001 indicating better glycaemic control. Inexperimental group total cholesterol, TG and LDL levels were also significantly reduced from 199.66 ± 3.11to 189.26 ± 3.01 mg/dL; p < 0.02, 144.94 ± 8.31 to 126.01 ± 8.26; p < 0.05 and 119.19 ± 1.71 to 99.58 ± 1.10;p < 0.001 respectively.Conclusions: These data demonstrate beneficial effect of chromium supplementation on glycaemic controland lipid variables in subjects with newly onset type-2 diabetes.

ntroduction

Trivalent chromium is considered as an essential elementor insulin function and glucose disposal in mammalian nutri-ion. Even 50 years ago the element chromium was proposedo be an essential element for mammals with a role in main-aining proper carbohydrate and lipid metabolism [1]. Chromiums one of the most studied supplements and a majority of therials found a positive effect of chromium on fasting plasma glu-ose [2]. There is growing evidence that chromium may facilitatensulin signaling and chromium supplementation therefore maymprove systemic insulin sensitivity [3]. Spectroscopic and crystal-

ographic investigations carried out to understand molecular basisf chromium insulin interaction emphasized role of chromium inlucose metabolism [4].

∗ Corresponding author at: 2, Adarsh Colony, Bikaner - 334003, Rajasthan, India.el.: +91 151 2202431; fax: +91 151 2202131.

E-mail address: drrpagrawal@yahoo.co.in (R.P. Agrawal).

946-672X/$ – see front matter © 2011 Elsevier GmbH. All rights reserved.oi:10.1016/j.jtemb.2011.03.003

© 2011 Elsevier GmbH. All rights reserved.

Trivalent chromium, the form found in food and dietary supple-ment is believed to be safe [5]. The DRI (daily reference intake) ofchromium for adult is between 20 and 35 �g/day depending on ageand gender. In general, oral intake of chromium has a low level oftoxicity partially due to its very poor absorption [6].

Acute and sub acute syndromes of chromium deficiency havebeen reported in patients receiving total parenteral nutrition [7,8].Such a chromium deficit was proposed as a contributing factorin some cases of maturity-onset diabetes and atherosclerotic dis-ease [9,10]. Considerable variations are seen in concentration ofchromium of different food groups. Therefore, chromium intakescannot be predicted from databases. Chromium repletion afterexperimental dietary depletion improved glycaemic status [11].Much smaller quantities of chromium are required in vivo to restorenormal glucose level. In the presence of Cr, in a biologically activeform, much lower levels of insulin are required, however, Cr is con-

sidered as a nutrient despite a therapeutic agent and thereforeseems beneficial for those whose problems are due to subopti-mal intake of Cr [12]. Results from the trials support the view thatchromium supplementation in patients with type 1, type 2, gesta-

150 S. Sharma et al. / Journal of Trace Elements in Medicine and Biology 25 (2011) 149– 153

Table 1Baseline characteristics of study groups.

Variables Control Experimental t p

Mean ± SE CV Mean ± SE CV

BMI (kg/m2) 26.12 ± 0.87 16.28 25.09 ± 1.92 37.38 0.49 <0.6W/H ratio 0.92 ± 0.01 05.43 0.93 ± 0.01 05.43 1.00 <0.4

BP (mmHg) Systolic 138.5 ± 4.65 16.41 161.5 ± 5 15.13 3.37 <0.05Diastolic 87.5 ± 2.46 13.73 91.5 ± 3.47 18.53 0.94 <0.4

Mean blood glucose (mg/dL) 226.17 ± 18.36 39.69 197.65 ± 6.68 16.53 1.43 <0.2HbA1c (%) 9.30 ± 0.22 11.51 9.51 ± 0.26 15.40 0.61 <0.6

Lipid profile (mg/dL) Cholesterol 189.19 ± 2.11 05.45 199.66 ± 3.11 07.61 2.79 <0.02Triglyceride 128.99 ± 3.60 13.65 144.94 ± 8.31 28.03 1.76 <0.1

08.89 48.91 ± 1.93 19.30 1.28 <0.408.25 119.19 ± 1.71 07.01 0.81 <0.512.61 30.29 ± 1.59 25.68 1.13 <0.4

tii

olpm

M

4rjedn

othsjAcsptfdv

mdabbAeS

mat‘

Table 2Mean ± SE values of nutrient intake by diabetic patients.

Nutrient Prior After

Energy (kcal) 2004.50 ± 30.10 2014.63 ± 29.59Protein (g) 68.8 ± 0.86 67.90 ± 1.1Total fat (g) 50.20 ± 1.19 50.28 ± 1.13Visible 25.98 ± 0.63 25.18 ± 0.60Invisible 24.21 ± 0.73 25.10 ± 0.67Carbohydrates (g) 330.47 ± 7.12 326.07 ± 4.65Fiber (g) 12.41 ± 0.38 13.36 ± 0.42Calcium (mg) 651.91 ± 7.42 624.75 ± 13.99Iron (mg) 27.56 ± 0.47 27.63 ± 0.49Thiamin (mg) 1.34 ± 0.13 1.15 ± 0.02Riboflavin (mg) 1.14 ± 0.02 1.42 ± 0.02Niacin (mg) 15.42 ± 0.24 14.91 ± 0.30Carotene (�g) 2268.51 ± 98.44 2479.91 ± 43.59

mean glycosylated hemoglobin of the experimental group alsoreduced significantly from the value of 9.51 ± 0.26% to 6.86 ± 0.28%(p < 0.001) (Table 3 and Fig. 1).

p<0.001

1

2

3

4

5

6

7

8

9

10

Hb

A1c

%

Before

After

HDL 51.65 ± 0.94

LDL 121.34 ± 2.05

VLDL 28.31 ± 0.73

ional or steroid-induced diabetes can improve both glucose andnsulin metabolism [13]. On the other hand some studies deniedmportance of Cr in treatment of type 2 diabetes [14,15].

This present investigation was undertaken to measure the effectf a chromium-rich brewer’s yeast on glucose tolerance, HbA1C andipid levels of newly onset type 2 diabetes so that role of Cr sup-lementation could be figured out with reference to glycaemia inan.

aterials and methods

From the out patient of diabetic clinic of PBM Hospital, Bikaner0 newly onset type 2 diabetic subjects were randomly selectedanging from 35 to 67 years. As this was a single blind study sub-ects were blinded. Medical and dietary records were screened toxclude diabetic persons with a history of liver, kidney, intestinalisorders or gout and those presently taking brewer’s yeast or otherutrient supplements containing chromium.

Approval from institutional ethical committee was alsobtained prior to the study. After explaining the procedure andheme of the study, informed written consent was taken beforeand. The subjects were randomly assigned into one of the twoupplementation groups: brewer’s yeast and placebo. Twenty sub-ects received 9 g brewer’s yeast capsules (Twin Laboratory Inc.merican Fork, OTAH, U.S.A.). Another 20 subjects received placeboapsules similar in colour and texture with that of yeast cap-ules. The brewer’s yeast content was 9 g (42 �g Cr) of yeastowder filled in 9 gelatinized capsules. Patients were asked toake 9 capsules in a day, 3 capsules after each meal i.e. break-ast, lunch and dinner with either milk or water for 3 monthsaily. Each subject received 1-month supply of capsules at aisit.

Anthropometric and biochemical data were recorded. Bodyass index (BMI) and waist hip ratio were calculated using stan-

ard methods. Blood glucose estimation was done before breakfastnd twice in a week by glucometer provided to the patients. At theeginning and completion of the study lipid profile was analyzedy using complete chemistry autoanalyzer (Ark Diagnostic Pvt. Ltd.,ndheri (E), Mumbai) and glycosylated hemoglobin (HbA1c) bymploying ion exchange chromatography technique (Roche, Basel,witzerland).

Statistical analysis of data was performed using arithmetic

ean, standard error and least square analysis. The least square

nalysis was carried out by using SPSS version 10.0. To find out sta-istical difference between means within the group, student pairedt’ test was performed.

Vitamin C (mg) 67.80 ± 1.90 66.96 ± 1.70

aNo significant differences between the groups for any of the nutrient variables.

Results

Baseline characteristics of both the groups were well matchedexcept for systolic blood pressure and cholesterol (Table 1). Thevalues of total calorie, fat, carbohydrate, protein, micronutrientintake before and after the study have been shown in Table 2.The magnitude of the effect of organic chromium supplementa-tion on fasting blood glucose and glycosylated hemoglobin hasbeen also compared in placebo and study group in Table 3. Aftersupplementation with chromium rich yeast, the mean fastingblood glucose level of the subjects showed a significant decreasefrom 197.65 ± 6.68 mg/dL to 103.68 ± 6.64 mg/dL (p < 0.001). The

0ExperimentalControl

Fig. 1. Comparison of HbA1c in experimental and control groups.

S. Sharma et al. / Journal of Trace Elements in Medicine and Biology 25 (2011) 149– 153 151

Tab

le

3C

omp

arat

ive

effe

ct

of

chro

miu

m

on

dif

fere

nt

par

amet

ers.

Var

iabl

es

Con

trol

Exp

erim

enta

l

Bef

ore

Aft

ert

pB

efor

eA

fter

tp

Mea

n

±

SE

CV

Mea

n

±

SE

CV

Mea

n

±

SE

CV

Mea

n

±

SE

CV

BM

I (kg

/m2)

26.1

2±

0.87

16.2

728

.17

±

191

33.1

2

.98

<.04

25.0

9±

1.92

37.3

824

.46

±

0.34

6.79

0.31

<0.8

W/H

rati

o0.

92±

0.01

5.43

0.92

±

0.01

5.43

––

0.93

±

0.01

5.43

0.92

±

0.01

5.43

1.00

<0.4

BP

(mm

Hg)

Syst

olic

138.

5±

4.65

16.4

113

0.5

±

5.29

19.8

1

1.13

<.04

161.

5±

5

15.1

314

1.5

±

5.33

18.4

2

2.73

<0.0

2*

Dia

stol

ic

87.5

±

2.46

13.7

3

89.5

±

2.87

15.6

7

.53

<.06

91.5

±

3.47

18.5

9

89.5

±

2.87

15.6

7

0.44

<0.8

Mea

n

bloo

d

glu

cose

(mg/

dL)

226.

17±

18.3

6

39.6

924

6.31

±

5.81

11.5

7

1.05

<.04

197.

65±

6.68

16.5

210

3.68

± 6.

64

31.3

2

10.0

1

<0.0

01**

HbA

1c

(%)

9.30

±

0.22

11.5

18.

71±

0.20

8.45

2.03

<.01

9.51

±

0.26

16.4

0

6.86

± 0.

28

19.9

7

7.16

<0.0

01**

Lip

id

pro

file

(mg/

dL)

Ch

oles

tero

l18

9.19

±

2.11

5.45

185.

26±

8.6

22.6

9

.44

<.08

199.

66

±

3.11

7.61

189.

26

±

3.01

7.77

2.41

<0.0

2*

Trig

lyce

rid

e12

8.99

±

3.60

13.6

512

9.33

±

3.06

11.5

7

.12

<.09

144.

94±

8.31

28.0

312

6.01

±

8.26

32.0

5

2.12

<0.0

5*

HD

L51

.65

±

0.94

8.89

49.6

4

±

3.98

39.2

0

.51

<.06

48.9

1

±

1.93

19.3

0

50.6

9

±

1.02

9.82

0.81

<0.5

LDL

121.

34±

2.05

8.25

111.

23±

8.78

38.5

9

1.12

<.04

119.

19±

1.71

7.01

99.5

8

±

1.10

5.40

9.66

<0.0

01**

VLD

L28

.31

±

0.73

12.6

1

26.9

8

±

0.63

11.4

1

1.46

<.02

30.2

9

±

1.59

25.6

9 27

.66

±

1.58

24.4

0

1.17

<0.4

*p

<

0.05

.**

p

<

0.00

1.

p<0.05

p<0.05 p<0.001

-25

-20

-15

-10

-5

0

5

Lip

id P

rofi

le (

mg

/dl)

CholesterolTriglycerideHDLLDLVLDL

Fig. 2. Changes in lipid profile in experimental group.

The effect of chromium intervention on lipid profile is shownin Table 3 and Fig. 2. In the yeast group, a significant decline incholesterol for �10 mg/dL was observed. The similar trend emergedfor triglyceride and LDL levels. Mean triglyceride and LDL levelsreduced significantly from 144.94 ± 8.31 to 126.01 ± 8.26 mg/dLand 119.19 ± 1.71 to 99.58 ± 1.10 mg/dL respectively. The meanHDL values increased from 48.91 ± 1.93 to 50.69 ± 1.02 mg/dL at thecompletion of the study. Reduction was also observed in VLDL levelin chromium group from 30.29 ± 1.59 to 27.66 ± 1.58 mg/dL, how-ever, changes in HDL and VLDL were not statistically significant.In placebo group none of these parameters changed significantlyduring study period except for LDL and VLDL.

Discussion and conclusion

In present study, beneficial effect of chromium supplementationwas observed regarding fasting blood glucose and HbA1C. Systolicblood pressure also improved significantly while the same trendwas observed for lipid profile as it reflected in improved values ofcholesterol, triglyceride and LDL.

Average individual becomes chromium deficit with age.Chromium deficiency is strongly associated with many aspects ofmetabolic syndrome including insulin resistance and type 2 dia-betes. Cr supplementation alone and combination of Cr togetherwith vitamin C and E were found very effective for improvement ofglucose metabolism in type 2 diabetes [16]. Oral Cr (D-phe) treat-ment was reported to reduce glucose intolerance, insulin resistanceand hepatic ER stress in obese, insulin resistant mice [17]. In onepreviously conducted study Cr yeast decreased the fasting bloodglucose and LDL level in streptozotocin induced diabetic rats [18].These results are in accordance with the outcomes of the presentstudy. Cr yeast supplementation was considered to have poten-tial to improve carbohydrate and lipid metabolism amongst humanpatients featuring type 2 diabetes mellitus [19]. In vitro study find-ings showed that chromium picolinate (Cr pic) may improve insulinsensitivity by enhancing intracellular insulin receptor. Treatmentwith Cr pic for 10 weeks significantly ameliorated changes inmetabolic risk factors including favourable changes in histopathol-ogy of the liver, kidney and pancreas suggesting its potential role inthe management of diabetes [20]. Intake of milk powder contain-

ing 400 �g/day of chromium for 16 weeks in subjects with type 2diabetes mellitus resulted in lowering of FPG, fasting insulin andimprovement of metabolic control in male patients [21]. Researchadvocated that supplementation of well controlled type 2 diabetes

1 ts in M

wbclpapm

rpaicpwssohdc[psstaa

dediwsgstnrefssmawoirtGds

sfommd[oli

[

[

[

52 S. Sharma et al. / Journal of Trace Elemen

ith Cr enriched yeast is safe and can result in improvements inlood glucose variables and oxidation stress [22]. Brewer’s yeasthromium supplementation provided better control of glucose andipid variables while decreasing drug dosage in type 2 diabetesatients [23]. Chromium appeared to be a safe supplement andsserted to have a role as adjunctive therapy when chemistry andharmacology, efficiency and safety of trivalent chromium in treat-ent of type 2 diabetes was evaluated [24].Several researchers indicated towards the similar outcomes

egarding potential of Cr supplementation in type 2 diabeticatients [25,26] while some have made its role in diabetes debat-ble. Few studies disclaimed beneficial effect of Cr supplementationn diabetes [14,15,27]. In a double blind randomized placeboontrolled trial in Chinese population with type 2 diabetes, sup-lementation with 1000 �g of Cr led to a fall in HbA1C by 2% [28]hile with 400 �g of Cr no improvement was observed in another

tudy by the same researcher [15]. An earlier researcher foundimilar observations previously concluding that beneficial effectsf chromium in individuals with diabetes were observed at levelsigher than the upper limit of the estimated safe and adequate dailyietary intake [29]. In a study, six different commercial trivalenthromium compounds were compared for their metabolic effects30]. Only three enhanced insulin sensitivity (NBC, chelavite andicolinate), however all tested compounds seemed safe. In a recenttudy, 1000 �g/day dose of Cr Pic could not change the insulinensitivity index statistically but increased acute insulin responseo glucose [31]. The variations observed in various studies werettributed to duration of study, form of Cr used, the extent of obesitynd glucose intolerance of the subjects [32].

The effect of chromium in in vitro, and probably in in vivo,epends on the presence of endogenous or exogenous insulin. Noffect has been demonstrated in in vitro systems that did not eitherepend on or contain insulin [33]. Chromium deficiency causes an

mpaired response to added insulin in rat epididymal fat tissue andhen glucose uptake or glucose oxidation or utilization for lipid

ynthesis was measured, the dose–effect curve was flat. This sug-ests cell transport, the first step of the sugar metabolism, as a majorite of action for chromium. Overall, chromium has been postulatedo act by one or more of the following ways; (A) increase in theumber of insulin receptors, (B) increased binding of insulin to itseceptor and (C) increased activation of the receptor in the pres-nce of insulin [34]. Thus chromium is one of the “master” nutrientor controlling blood sugar in diabetic population, may be respon-ible to reduce myocellular lipids and enhance insulin sensitivity inubjects with type 2 diabetes. It suggested that modulation of lipidetabolism by Cr in peripheral tissues may represent a novel mech-

nism of action [35]. In previous chromium supplemented study, itas demonstrated that in rats chromium enhances the movement

f glucose into tissues at the same time chromium deficiency causesmpaired glucose uptake and insulin resistance [36]. These can beestored to normal by repletion of chromium. Other studies reporthat plasma glucose of genetically diabetic mice improves afterTF supplementation [37,38]. Rats fed with a hypercholesterolemiciet for 35 days were protected from hypercholesterolemia whenupplemented with chromium [39].

A significant improvement in blood glucose level of diabeticubjects was observed after chromium rich yeast supplementationor 3 months in present study. On the other hand, no change wasbserved in placebo group in this respect. The findings of a studyanifested that mean levels of plasma chromium were approxi-ately 33% lower and urine values almost 100% higher in 93 type 2

iabetes patients compared to a group of healthy control subjects

40]. These investigators also noted that in the early years of onsetf type 2 diabetes, plasma chromium values were inversely corre-ated with plasma glucose. Several investigators reported a markedmprovement in glucose disposal or insulin output in men after

[

[

edicine and Biology 25 (2011) 149– 153

chromium supplementation. A correlation was reported betweendecreased serum cholesterol level and improved glucose tolerancein 27 normal and hyperglycemic women, aged 40–75 years sup-plemented with a chromium rich brewer’s yeast extract [41]. Inanother study 24 volunteers with mean age 78, including 8 mildlytype 2 diabetes subjects, who were randomly allocated to one of thetwo groups and were fed (daily for 8 weeks) 9 g of either brewer’syeast or chromium poor torula yeast, a significant improvementwas observed in the experimental group [42]. These observationsalong with the results of the present study suggested that in invitro studies chromium must be supplied in the form of complexwith certain ligands, which may enhance its absorption, activityand tissue retention.

The present study documents significant improvement intriglycerides and LDL in yeast supplemented group. Other work-ers also reported improvement in serum triglyceride and totallipid levels as a result of chromium supplementation [43,44]. Astudy was conducted on 14 diabetic patients and found that 30 g ofbrewer’s yeast (50 �g of chromium for 8 weeks daily) was highlyeffective in reducing cholesterol and triglyceride levels as well asincreased high-density lipoprotein cholesterol [45]. Similarly theeffect of brewer’s yeast supplementation on human serum lipidswas assessed [46]. A group of 19 hyperlipidemic adults consumed10 g chromium rich brewer’s yeast (48 �g daily) for 8 weeks. Thetotal circulating serum cholesterol decreased by a modest amountin this group after supplementation. These findings indicate thatchromium rich brewer’s yeast is active in in vitro system andimproves the blood lipid concentrations when given in physiolog-ical active form.

In summary, the addition of organic chromium supplementsresult in improved glycemic control. The reduction in HbA1C andmean blood glucose reflect the ability of chromium to maintaineuglycemia. Moreover, the decrease in triglyceride and LDL suggestadditional benefits in terms of reducing the risk of complication inpatients with newly onset type-2 diabetics.

Thus, this study has demonstrated that chromium supplementa-tion is an effective regimen for newly onset type-2 diabetic patientsand may provide possible positive effect on other coronary riskfactors associated.

References

[1] Vincent JB. Chromium: celebrating 50 years as an essential element? DaltonTrans 2010;39(16):3787–94.

[2] Bartlett HE, Eperjesi F. Nutritional supplementation for type 2 diabetes: a sys-tematic review. Ophthalmic Physiol Opt 2008;28(l):503–23.

[3] Hummel M, Standl E, Schnell O. Chromium in metabolic and cardiovasculardisease. Horn Metab Res 2007;39(10):743–51.

[4] Sreekanth R, Pattabhi V, Rajan SS. Molecular basis of chromium insulin inter-actions. Biochem Biophys Res Commun 2008;369:725–9.

[5] Extracted from a Program Announcement from the National Institute ofDiabetes and Digestive and Kidney Diseases. National Center for Com-plementary and Alternative Medicine, Office of Dietary Supplements,http://grants.nih.gov/grants/guide [PA number: PA-01-114, release date: July2, 2001].

[6] Dave S, MS, RD/LD, CDE, Chromium and diabetes management; April 2008,www.healthcastle.com.

[7] Jeejeebhoy KN. The role of chromium in nutrition and therapeutics and as apotential toxin. Nutr Rev 1999;57:329–35.

[8] Anderson RA. Chromium and parenteral nutrition. Nutrition 1995;11:83–6.[9] Schroeder HA, Nason AP, Tipton IH. Chromium deficiency as a factor in

atherosclerosis. J Chronic Dis 1990;23:123–42.10] Hambidge KM. The clinical significance of trace element deficiencies in man.

Proc Nutr Soc 1974;33:249–55.11] Anderson RA, Polansky M, Bryden N, Canary J. Supplemental chromium effects

on glucose, insulin, glucagon, and urinary chromium losses in subjects con-suming controlled low-chromium diets. Am J Clin Nutr 1991;54:909–16.

12] Anderson RA. Chromium in the prevention and control of diabetes. Diabetes

Metab 2000;26(1):22–7.

13] Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. DiabetesCare 2004;27(11):2741–51.

14] Kleefstra N, Houweling ST, Jansman FG, Groenier KH, Gans RO, Meyboom-de Jong B, et al. Chromium treatment has no effect in patients with poorly

ts in M

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

S. Sharma et al. / Journal of Trace Elemen

controlled, insulin-treated type 2 diabetes in an obese Western popula-tion: a randomized, double-blind, placebo-controlled trial. Diabetes Care2006;29(3):521–5.

15] Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de JongB, et al. Chromium treatment has no effect in patients with type 2 diabetes ina Western population: a randomized, double-blind, placebo-controlled trial.Diabetes Care 2007;30(5):1092–6.

16] Lai MH. Antioxidant effects and insulin resistance improvement of chromiumcombined with vitamin C and e supplementation for type 2 diabetes mellitus.J Clin Biochem Nutr 2008;43(3):197–8.

17] Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J. Chromium alleviates glucoseintolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity(Silver Spring) 2008;16(6):1331–7.

18] Lai MH, Chen YY, Cheng HH. Chromium yeast supplementation improves fast-ing plasma glucose and LDL-cholesterol in streptozotocin-induced diabeticrats. Int J Vitam Nutr Res 2006;76(6):391–7.

19] Balk EM, Tatsioni A, Lichtenstein AH, Lau J, Pittas AG. Effect of chromiumsupplementation of glucose metabolism and lipids: a systematic review ofrandomized controlled trials. Diabetes Care 2007;30(9):e102.

20] Sahin K, Onderci M, Tuzcu M, Ustundag B, Cikim G, Ozercan IH, et al.Effect on chromium on carbohydrate and lipid metabolism in a rat model oftype 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. Metabolism2007;56(9):1233–40.

21] Pei D, Hsieh CH, Hung YJ, Li JC, Lee CH, Kuo SW. The influence of chromiumchloride-containing milk to glycemic control of patients with type 2 diabetesmellitus: a randomized, double-blind, placebo-controlled trial. Metabolism2006;55(7):923–7.

22] Racek J, Trefil L, Rajdl D, Mudrova V, Hunter D, Senft V. Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markersof oxidative stress in subjects with type 2 diabetes mellitus. Biol Trace Elem Res2006;109(March (3)):215–30.

23] Bahijiri SM, Mira SA, Mufti AM, Ajabnoor MA. The effects of inorganic chromiumand brewer’s yeast supplementation on glucose tolerance, serum lipid and drugdosage in individuals with type 2 diabetes. Saudi Med J 2000;21(9):831–7.

24] Ryan GJ, Wanko NS, Redman AR, Cook CB. Chromium as adjunctive treatmentfor type 2 diabetes. Ann Pharmacother 2003;37(6):876–85.

25] Yang X, Palanichamy K, Ontko AC, Rao MN, Fang CX, Ren J, et al. Anewly synthetic chromium complex-chromium (phenylalanine)3 improvesinsulin responsiveness and reduce whole body glucose tolerance. FEBS Lett2005;579(6):1458–64.

26] Keszthelyi Z, Past T, Koltai K, Szabo L, Mozsik G. Chromium (III)-ionenhances the utilization of glucose in type-2 diabetes mellitus. Orv Hetil2003;144(42):2073–6.

27] Trumbo PR, Ellwood KC. Chromium picolinate intake and risk of type 2 diabetes:an evidence-based review by the United States food and Drug administration.Nutr Rev 2006;(8):357–63.

28] Kleefstra N, Bilo HJ, Bakker SJ, Houweling ST. Chromium and insulin resistance.Ned Tijdschr Geneeskd 2004;148(5):217–20.

[

edicine and Biology 25 (2011) 149– 153 153

29] Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, et al. Elevatedintakes of supplemental chromium improve glucose and insulin variables inindividuals with type 2 diabetes. Diabetes 1997;46(11):1786–91.

30] Preuss HG, Echard B, Perricone NV, Bagchi D, Yasmin T, Stohs SJ. Comparingmetabolic effects of six different commercial trivalent chromium compounds.J Inorg Blochem 2008;102(11):1986–90.

31] Iqbal N, Cardillo S, Volger S, Bloedon LT, Anderson RA, Boston R, et al. Chromiumpicolinate does not improve key features of metabolic syndrome in obese non-diabetic adults. Metab Syndr Relat Disord 2009;7(2):143–50.

32] Anderson RA. Chromium and polyphenols from cinnamon improve insulin sen-sitivity. Proc Nutr Soc 2008;67(1):48–53.

33] Mertz W, Roginski EE, Reba RC. Biological activity and fate of I.V. Cr III in rats.Am J Physiol 1965;209:489–94.

34] Anderson RA. Chromium and insulin resistance. Nutr Res Rev2003;16(2):267–75.

35] Cefalu, et al. Characterization of the metabolic and physiologic responseto chromium supplementation in subjects with type 2 diabetes mellitus.Metabolism 2010;59(5):755–62.

36] Davis CM, April CR, Vincent JB. Synthetic multi nuclear chromium assemblyactivates insulin receptor kinase activity: functional model for low molecular-weight, chromium-binding substance. Inorg Chem 1997;36:5316–20.

37] Tuman RW, Doisy RS. Studies in the genetically diabetic mouse: effect of GTFand clofibrate (CPIB) on the diabetic syndrome. In: Hoekstra WG, Suttie JW,Ganther HE, Mertz W, editors. Trace Element Metabolism in Animals. II. Balti-more: University Park Press; 1974. p. 678–88.

38] Tuman RW, Bilbo JT, Doisy RJ. Comparison and effects of natural and syn-thetic glucose tolerance factor in normal and genetically diabetic mice. Diabetes1988;27:49–56.

39] Staub HW, Reussner G, Thiessen R. Serum cholesterol reduction by chromiumin hypercholesterolemic rats. Science 1999;166:746–7.

40] Morris BW, MacNeil S, Hardesty CA, Heller S, Burgin C, Gray TA. Chromiumhomeostasis in patients with Type II (NIDDM) diabetes. J Trace Elem Med Biol1999;13:57–61.

41] Liu VJ, Morris JS. Relative chromium responses as an indicator of chromiumstatus. Am J Clin Nutr 1998;31:972–6.

42] Offenbacher EG, Pi-Sunyer FX. Beneficial effect of chromium rich yeast on glu-cose tolerance and blood lipids in elderly subjects. Diabetes 1980;29:919–25.

43] Press RI, Geller J, Evans GW. The effect of chromium picolinate on serumcholesterol and apolipoprotein fraction in human subjects. West J Med1990;152:41–5.

44] Lee NA, Reasner CA. Beneficaial effect of chromium supplementation on serumtriglyceride levels in NIDDM. Diabetes Care 1994;17:1449–52.

45] Saner G, Yuzbasiyan V, Neyzi O, Unoj H, Saka N, Cigdem. Alteration of chromium

metabolism and effect of chromium supplementation in Turner’s syndromepatients. Am J Clin Nutr 1983;38:574–8.

46] Elwood JC, Mori RA, Puddey IB, Beiten LJ, Burke V, Morton AR, et al. Effectof high chromium brewer’s yeast on human serum lipids. J Am Coll Nutr1997;3:263–74.