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

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Journal of Trace Elements in Medicine and Biology


journal homepage: www.elsevier.de/jtemb

CLINICAL STUDIES

Beneficial effect of chromium supplementation on glucose, HbA1 C and lipid


variables in individuals with newly onset type-2 diabetes
Shilpi Sharma a , Rajendra Prasad Agrawal b,∗ , Maya Choudhary a , Shreyans Jain b ,
Shekhar Goyal b , Vivek Agarwal b
a
College of Home Science, MPUA&T, Udaipur, Rajasthan, India
b
Diabetes Care & Research Centre, S.P. Medical College, Bikaner, Rajasthan, India

a r t i c l e i n f o a b s t r a c t

Article history: Project: Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. It
Received 8 July 2010 influences glucose metabolism by potentiating the action as taking part in insulin signal amplification
Accepted 30 March 2011 mechanism. A placebo-controlled single blind, prospective study was carried out to investigate the effect
of chromium supplementation on blood glucose, HbA1 C and lipid profile in newly onset patients with
Keywords: type-2 diabetes.
Chromium
Procedure: Total 40 newly onset type-2 diabetics were selected and after 1 month stabilization further
Type 2 diabetes
randomly divided into two groups viz. study group and placebo group. The study group received 9 g
Glycaemic control
brewer’s yeast (42 ␮g Cr) daily and the other placebo group received yeast devoid of chromium for 3
months. Subjects were instructed not to change their normal eating and living habits. Fasting blood
glucose, HbA1 C 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). HbA1 C values
improved significantly from 9.51 ± 0.26% to 6.86 ± 0.28%; p < 0.001 indicating better glycaemic control. In
experimental group total cholesterol, TG and LDL levels were also significantly reduced from 199.66 ± 3.11
to 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 control
and lipid variables in subjects with newly onset type-2 diabetes.
© 2011 Elsevier GmbH. All rights reserved.

Introduction Trivalent chromium, the form found in food and dietary supple-
ment is believed to be safe [5]. The DRI (daily reference intake) of
Trivalent chromium is considered as an essential element chromium for adult is between 20 and 35 ␮g/day depending on age
for insulin function and glucose disposal in mammalian nutri- and gender. In general, oral intake of chromium has a low level of
tion. Even 50 years ago the element chromium was proposed toxicity partially due to its very poor absorption [6].
to be an essential element for mammals with a role in main- Acute and sub acute syndromes of chromium deficiency have
taining proper carbohydrate and lipid metabolism [1]. Chromium been reported in patients receiving total parenteral nutrition [7,8].
is one of the most studied supplements and a majority of the Such a chromium deficit was proposed as a contributing factor
trials found a positive effect of chromium on fasting plasma glu- in some cases of maturity-onset diabetes and atherosclerotic dis-
cose [2]. There is growing evidence that chromium may facilitate ease [9,10]. Considerable variations are seen in concentration of
insulin signaling and chromium supplementation therefore may chromium of different food groups. Therefore, chromium intakes
improve systemic insulin sensitivity [3]. Spectroscopic and crystal- cannot be predicted from databases. Chromium repletion after
lographic investigations carried out to understand molecular basis experimental dietary depletion improved glycaemic status [11].
of chromium insulin interaction emphasized role of chromium in Much smaller quantities of chromium are required in vivo to restore
glucose metabolism [4]. normal glucose level. In the presence of Cr, in a biologically active
form, much lower levels of insulin are required, however, Cr is con-
sidered as a nutrient despite a therapeutic agent and therefore
∗ Corresponding author at: 2, Adarsh Colony, Bikaner - 334003, Rajasthan, India. seems beneficial for those whose problems are due to subopti-
Tel.: +91 151 2202431; fax: +91 151 2202131. mal intake of Cr [12]. Results from the trials support the view that
E-mail address: drrpagrawal@yahoo.co.in (R.P. Agrawal). chromium supplementation in patients with type 1, type 2, gesta-

0946-672X/$ – see front matter © 2011 Elsevier GmbH. All rights reserved.
doi:10.1016/j.jtemb.2011.03.003
150 S. Sharma et al. / Journal of Trace Elements in Medicine and Biology 25 (2011) 149–153

Table 1
Baseline 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 <0.6
W/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 <0.05


Diastolic 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 <0.2
HbA1 c (%) 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 <0.02
Triglyceride 128.99 ± 3.60 13.65 144.94 ± 8.31 28.03 1.76 <0.1
HDL 51.65 ± 0.94 08.89 48.91 ± 1.93 19.30 1.28 <0.4
LDL 121.34 ± 2.05 08.25 119.19 ± 1.71 07.01 0.81 <0.5
VLDL 28.31 ± 0.73 12.61 30.29 ± 1.59 25.68 1.13 <0.4

tional or steroid-induced diabetes can improve both glucose and Table 2


Mean ± SE values of nutrient intake by diabetic patients.
insulin metabolism [13]. On the other hand some studies denied
importance of Cr in treatment of type 2 diabetes [14,15]. Nutrient Prior After
This present investigation was undertaken to measure the effect Energy (kcal) 2004.50 ± 30.10 2014.63 ± 29.59
of a chromium-rich brewer’s yeast on glucose tolerance, HbA1 C and Protein (g) 68.8 ± 0.86 67.90 ± 1.1
lipid levels of newly onset type 2 diabetes so that role of Cr sup- Total fat (g) 50.20 ± 1.19 50.28 ± 1.13
plementation could be figured out with reference to glycaemia in Visible 25.98 ± 0.63 25.18 ± 0.60
Invisible 24.21 ± 0.73 25.10 ± 0.67
man.
Carbohydrates (g) 330.47 ± 7.12 326.07 ± 4.65
Fiber (g) 12.41 ± 0.38 13.36 ± 0.42
Calcium (mg) 651.91 ± 7.42 624.75 ± 13.99
Iron (mg) 27.56 ± 0.47 27.63 ± 0.49
Thiamin (mg) 1.34 ± 0.13 1.15 ± 0.02
Riboflavin (mg) 1.14 ± 0.02 1.42 ± 0.02
Materials and methods Niacin (mg) 15.42 ± 0.24 14.91 ± 0.30
Carotene (␮g) 2268.51 ± 98.44 2479.91 ± 43.59
From the out patient of diabetic clinic of PBM Hospital, Bikaner Vitamin C (mg) 67.80 ± 1.90 66.96 ± 1.70
40 newly onset type 2 diabetic subjects were randomly selected a
No significant differences between the groups for any of the nutrient variables.
ranging from 35 to 67 years. As this was a single blind study sub-
jects were blinded. Medical and dietary records were screened to
exclude diabetic persons with a history of liver, kidney, intestinal Results
disorders or gout and those presently taking brewer’s yeast or other
nutrient supplements containing chromium. Baseline characteristics of both the groups were well matched
Approval from institutional ethical committee was also except for systolic blood pressure and cholesterol (Table 1). The
obtained prior to the study. After explaining the procedure and values of total calorie, fat, carbohydrate, protein, micronutrient
theme of the study, informed written consent was taken before intake before and after the study have been shown in Table 2.
hand. The subjects were randomly assigned into one of the two The magnitude of the effect of organic chromium supplementa-
supplementation groups: brewer’s yeast and placebo. Twenty sub- tion on fasting blood glucose and glycosylated hemoglobin has
jects received 9 g brewer’s yeast capsules (Twin Laboratory Inc. been also compared in placebo and study group in Table 3. After
American Fork, OTAH, U.S.A.). Another 20 subjects received placebo supplementation with chromium rich yeast, the mean fasting
capsules similar in colour and texture with that of yeast cap- blood glucose level of the subjects showed a significant decrease
sules. The brewer’s yeast content was 9 g (42 ␮g Cr) of yeast from 197.65 ± 6.68 mg/dL to 103.68 ± 6.64 mg/dL (p < 0.001). The
powder filled in 9 gelatinized capsules. Patients were asked to mean glycosylated hemoglobin of the experimental group also
take 9 capsules in a day, 3 capsules after each meal i.e. break- reduced significantly from the value of 9.51 ± 0.26% to 6.86 ± 0.28%
fast, lunch and dinner with either milk or water for 3 months (p < 0.001) (Table 3 and Fig. 1).
daily. Each subject received 1-month supply of capsules at a
visit.
Anthropometric and biochemical data were recorded. Body 10
mass index (BMI) and waist hip ratio were calculated using stan- 9
p<0.001
dard methods. Blood glucose estimation was done before breakfast 8
and twice in a week by glucometer provided to the patients. At the 7
HbA1c %

beginning and completion of the study lipid profile was analyzed 6


by using complete chemistry autoanalyzer (Ark Diagnostic Pvt. Ltd., Before
5
After
Andheri (E), Mumbai) and glycosylated hemoglobin (HbA1c) by 4
employing ion exchange chromatography technique (Roche, Basel, 3
Switzerland). 2
Statistical analysis of data was performed using arithmetic 1
mean, standard error and least square analysis. The least square
0
analysis was carried out by using SPSS version 10.0. To find out sta- Control Experimental
tistical difference between means within the group, student paired
‘t’ test was performed. Fig. 1. Comparison of HbA1 c in experimental and control groups.
S. Sharma et al. / Journal of Trace Elements in Medicine and Biology 25 (2011) 149–153 151

<0.001**
<0.001**

<0.001**
<0.02*

<0.02*
<0.05*
<0.8
<0.4

<0.8

<0.5

<0.4
p
0

0.31

2.73
0.44

7.16

2.41
2.12
0.81
9.66
1.17
10.01
1.00

Lipid Profile (mg/dl)


t
-5
Cholesterol
6.79 Triglyceride
5.43

18.42
15.67

31.32
19.97

7.77

9.82
32.05

5.40
24.40
CV

-10 HDL
p<0.05 LDL
VLDL
141.5 ± 5.33
89.5 ± 2.87

103.68 ± 6.64

8.26

1.58
24.46 ± 0.34

6.86 ± 0.28

3.01

1.02
1.10
0.92 ± 0.01

-15
Mean ± SE

±
±
±
±
±
189.26
126.01
50.69
99.58
27.66
After

-20

p<0.05 p<0.001

-25
37.38
5.43

15.13
18.59

16.52
16.40

7.61
28.03
19.30
7.01
25.69
CV

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


25.09 ± 1.92

91.5 ± 3.47

197.65 ± 6.68

3.11
8.31
1.93
1.71
1.59
9.51 ± 0.26
0.93 ± 0.01
Experimental

The effect of chromium intervention on lipid profile is shown


161.5 ± 5
Mean ± SE

in Table 3 and Fig. 2. In the yeast group, a significant decline in


±
±
±
±
±
199.66
144.94
48.91
119.19
30.29

cholesterol for 10 mg/dL was observed. The similar trend emerged
Before

for triglyceride and LDL levels. Mean triglyceride and LDL levels
reduced significantly from 144.94 ± 8.31 to 126.01 ± 8.26 mg/dL
and 119.19 ± 1.71 to 99.58 ± 1.10 mg/dL respectively. The mean
<.04

<.04
<.06

<.04
<.01

<.08
<.09
<.06
<.04
<.02

HDL values increased from 48.91 ± 1.93 to 50.69 ± 1.02 mg/dL at the

p

completion of the study. Reduction was also observed in VLDL level


in chromium group from 30.29 ± 1.59 to 27.66 ± 1.58 mg/dL, how-
.98

1.13
.53

.44
.12
.51
1.12
1.46
1.05
2.03

ever, changes in HDL and VLDL were not statistically significant.



t

In placebo group none of these parameters changed significantly


during study period except for LDL and VLDL.
33.12
5.43

19.81
15.67

11.57
8.45

22.69
11.57

38.59
11.41
39.20
CV

Discussion and conclusion


130.5 ± 5.29
89.5 ± 2.87

246.31 ± 5.81

3.98
8.78
3.06

0.63
0.92 ± 0.01

8.71 ± 0.20
28.17 ± 191

8.6

In present study, beneficial effect of chromium supplementation


Mean ± SE

±
±
±
±
±

was observed regarding fasting blood glucose and HbA1 C. Systolic


185.26
129.33
49.64
111.23
26.98

blood pressure also improved significantly while the same trend


After

was observed for lipid profile as it reflected in improved values of


cholesterol, triglyceride and LDL.
Average individual becomes chromium deficit with age.
Chromium deficiency is strongly associated with many aspects of
16.27
5.43

16.41
13.73

39.69
11.51

5.45
13.65
8.89
8.25
12.61

metabolic syndrome including insulin resistance and type 2 dia-


CV

betes. Cr supplementation alone and combination of Cr together


with vitamin C and E were found very effective for improvement of
226.17 ± 18.36

glucose metabolism in type 2 diabetes [16]. Oral Cr (D-phe) treat-


138.5 ± 4.65
87.5 ± 2.46

2.11
26.12 ± 0.87

9.30 ± 0.22

3.60
0.94
2.05
0.73
0.92 ± 0.01

ment was reported to reduce glucose intolerance, insulin resistance


Mean ± SE

±
±
±
±
±
Comparative effect of chromium on different parameters.

and hepatic ER stress in obese, insulin resistant mice [17]. In one


Control

189.19
128.99
51.65
121.34
28.31
Before

previously conducted study Cr yeast decreased the fasting blood


glucose and LDL level in streptozotocin induced diabetic rats [18].
These results are in accordance with the outcomes of the present
study. Cr yeast supplementation was considered to have poten-
Triglyceride
Cholesterol
Diastolic

tial to improve carbohydrate and lipid metabolism amongst human


Systolic

VLDL

patients featuring type 2 diabetes mellitus [19]. In vitro study find-


HDL
LDL

ings showed that chromium picolinate (Cr pic) may improve insulin
Mean blood glucose (mg/dL)

sensitivity by enhancing intracellular insulin receptor. Treatment


with Cr pic for 10 weeks significantly ameliorated changes in
metabolic risk factors including favourable changes in histopathol-
Lipid profile (mg/dL)

ogy of the liver, kidney and pancreas suggesting its potential role in
the management of diabetes [20]. Intake of milk powder contain-
BMI (kg/m2 )

BP (mmHg)

p < 0.001.

ing 400 ␮g/day of chromium for 16 weeks in subjects with type 2


W/H ratio

HbA1 c (%)

p < 0.05.
Variables

diabetes mellitus resulted in lowering of FPG, fasting insulin and


Table 3

improvement of metabolic control in male patients [21]. Research


*

**

advocated that supplementation of well controlled type 2 diabetes


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

with Cr enriched yeast is safe and can result in improvements in chromium supplementation. A correlation was reported between
blood glucose variables and oxidation stress [22]. Brewer’s yeast decreased serum cholesterol level and improved glucose tolerance
chromium supplementation provided better control of glucose and in 27 normal and hyperglycemic women, aged 40–75 years sup-
lipid variables while decreasing drug dosage in type 2 diabetes plemented with a chromium rich brewer’s yeast extract [41]. In
patients [23]. Chromium appeared to be a safe supplement and another study 24 volunteers with mean age 78, including 8 mildly
asserted to have a role as adjunctive therapy when chemistry and type 2 diabetes subjects, who were randomly allocated to one of the
pharmacology, efficiency and safety of trivalent chromium in treat- two groups and were fed (daily for 8 weeks) 9 g of either brewer’s
ment of type 2 diabetes was evaluated [24]. yeast or chromium poor torula yeast, a significant improvement
Several researchers indicated towards the similar outcomes was observed in the experimental group [42]. These observations
regarding potential of Cr supplementation in type 2 diabetic along with the results of the present study suggested that in in
patients [25,26] while some have made its role in diabetes debat- vitro studies chromium must be supplied in the form of complex
able. Few studies disclaimed beneficial effect of Cr supplementation with certain ligands, which may enhance its absorption, activity
in diabetes [14,15,27]. In a double blind randomized placebo and tissue retention.
controlled trial in Chinese population with type 2 diabetes, sup- The present study documents significant improvement in
plementation with 1000 ␮g of Cr led to a fall in HbA1 C by 2% [28] triglycerides and LDL in yeast supplemented group. Other work-
while with 400 ␮g of Cr no improvement was observed in another ers also reported improvement in serum triglyceride and total
study by the same researcher [15]. An earlier researcher found lipid levels as a result of chromium supplementation [43,44]. A
similar observations previously concluding that beneficial effects study was conducted on 14 diabetic patients and found that 30 g of
of chromium in individuals with diabetes were observed at levels brewer’s yeast (50 ␮g of chromium for 8 weeks daily) was highly
higher than the upper limit of the estimated safe and adequate daily effective in reducing cholesterol and triglyceride levels as well as
dietary intake [29]. In a study, six different commercial trivalent increased high-density lipoprotein cholesterol [45]. Similarly the
chromium compounds were compared for their metabolic effects effect of brewer’s yeast supplementation on human serum lipids
[30]. Only three enhanced insulin sensitivity (NBC, chelavite and was assessed [46]. A group of 19 hyperlipidemic adults consumed
picolinate), however all tested compounds seemed safe. In a recent 10 g chromium rich brewer’s yeast (48 ␮g daily) for 8 weeks. The
study, 1000 ␮g/day dose of Cr Pic could not change the insulin total circulating serum cholesterol decreased by a modest amount
sensitivity index statistically but increased acute insulin response in this group after supplementation. These findings indicate that
to glucose [31]. The variations observed in various studies were chromium rich brewer’s yeast is active in in vitro system and
attributed to duration of study, form of Cr used, the extent of obesity improves the blood lipid concentrations when given in physiolog-
and glucose intolerance of the subjects [32]. ical active form.
The effect of chromium in in vitro, and probably in in vivo, In summary, the addition of organic chromium supplements
depends on the presence of endogenous or exogenous insulin. No result in improved glycemic control. The reduction in HbA1 C and
effect has been demonstrated in in vitro systems that did not either mean blood glucose reflect the ability of chromium to maintain
depend on or contain insulin [33]. Chromium deficiency causes an euglycemia. Moreover, the decrease in triglyceride and LDL suggest
impaired response to added insulin in rat epididymal fat tissue and additional benefits in terms of reducing the risk of complication in
when glucose uptake or glucose oxidation or utilization for lipid patients with newly onset type-2 diabetics.
synthesis was measured, the dose–effect curve was flat. This sug- Thus, this study has demonstrated that chromium supplementa-
gests cell transport, the first step of the sugar metabolism, as a major tion is an effective regimen for newly onset type-2 diabetic patients
site of action for chromium. Overall, chromium has been postulated and may provide possible positive effect on other coronary risk
to act by one or more of the following ways; (A) increase in the factors associated.
number of insulin receptors, (B) increased binding of insulin to its
receptor and (C) increased activation of the receptor in the pres-
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