Original Paper

Ann Nutr Metab 2008;53:612

DOI: 10.1159/000152868

Received: August 28, 2007

Accepted after revision: May 29, 2008
Published online: September 5, 2008

Effects of Dietary Onion (Allium cepa L.)

in a High-Fat Diet StreptozotocinInduced Diabetes Rodent Model
M. Shahidul Islam a, b Haymie Choi a Du Toit Loots b
a
Department of Food and Nutrition, Seoul National University, Seoul, South Korea; b Department of Nutrition,
School of Physiology, Nutrition and Consumer Science, North-West University, Potchefstroom, South Africa

Key Words
Type 2 diabetes Onion Allium cepa L. High-fat diet Rats

Abstract
Background/Aims: The present study was conducted to investigate the effects of two dietary doses of freeze-dried onion powder on diabetes-related symptoms in a high-fat (HF)
diet streptozotocin (STZ)-induced diabetes rat model. Methods: Five-week-old male Sprague-Dawley rats were fed a HF
diet for 2 weeks and then randomly divided into 4 groups as
follows: HF control (HFC), diabetic control (DBC), onion low
(ONL; 0.5%) and onion high (ONH; 2.0%). Diabetes was induced by an intraperitoneal injection of STZ (40 mg/kg body
weight) in all groups except the HFC group. Results: After 4
weeks on the experimental diets, fasting blood glucose levels for both onion-fed groups were higher than in the DBC
and HFC groups, albeit only significantly so (p ! 0.05) in the
ONL group. Serum insulin concentrations and insulin resistance were dose-dependently increased (however, not significantly so) in the onion-fed groups compared to the DBC
group. Pancreatic -cell function and liver glycogen concentrations were nonsignificantly higher in the DBC and ONH
groups compared to the ONL group. Additionally, the ONH
group had significantly higher lipid concentrations (except
for high-density lipoprotein cholesterol) compared to all
other groups. The ONL group showed a similar hyperlipid-

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emic trend, however to a lesser extent, with only triglycerides significantly differing from those of the DBC and HFC
groups. Conclusion: The results suggest that the HF onion
diet may increase insulin secretion and consequently insulin
resistance in a dose-dependent manner, resulting in a worsened hyperglycemic and hyperlipidemic diabetic state. We
conclude that higher dietary fat may impair the antidiabetic effects of dietary onion intake as has been previously reported.
Copyright 2008 S. Karger AG, Basel

Introduction

Diabetes is a major threat to global public health and

is rapidly worsening, the biggest impact being on adults
of working age in developing countries. At least 177 million people worldwide have diabetes, and this figure is
likely to more than double by 2030 [1]. Type 2 diabetes
mellitus (T2DM) is the most common form of diabetes,
accounting for 9095% of all diabetic patients. T2DM is
a heterogenous disorder characterized by a progressive
decline in insulin action (insulin resistance), followed by
the inability of -cells to compensate for insulin resistance (-cell dysfunction) [2]. At present, oral therapy for
T2DM relies on insulin secretagogues such as glibenclamide [3] and insulin sensitizers such as thiazolidinediM. Shahidul Islam, PhD
Department of Nutrition
Faculty of Health Sciences, North-West University
Potchefstroom 2520 (South Africa)
Tel. +27 18 299 2466, Fax +27 18 299 2464, E-Mail sislam1974@yahoo.com

Table 1. Composition of control and experimental diets (%)

Ingredients

Control

ONL

ONH

Corn starch
Sucrose
Casein
Lard
Soybean oil
Cellulose
Vitamin mix
Mineral mix
L-Methionine
Onion powder

37.7
10.0
20.0
20.0
2.0
5.0
1.0
4.0
0.3
0.0

37.2
10.0
20.0
20.0
2.0
5.0
1.0
4.0
0.3
0.5

35.7
10.0
20.0
20.0
2.0
5.0
1.0
4.0
0.3
2.0

100.0

100.0

100.0

Total

one [4]. Recently, there has been a growing interest in

alternative therapies, including the use of plant foods, to
treat this disease [5].
Onion (Allium cepa L.), a rich source of organosulfur
compounds, is widely used in cooking and as a common
spice all over the world. Most of the sulfur compounds
present in onion are in the form of cysteine derivatives,
e.g. S-allyl cysteine sulfoxide. These are degraded during
extraction by the enzyme allinase into a variety of volatile
compounds including thiosulfonates and polysulfides
[6]. These compounds are reported to have several beneficial effects on health, such as preventing tumors and
cancers [7, 8], cardiovascular diseases [9], hypercholesterolemia [10, 11], hypertension [12] and diabetes [13, 14].
Apart from characterizing these plants, a number of
studies have focused on the ability of onion to ameliorate
diabetes, with many of them reporting both hypoglycemic and hypolipidemic effects in animal models of chemically induced non-insulin-dependent diabetes [6, 11, 15,
16]. Complementary to these, a human-based study
showed that 20 g of fresh onion, 3 times daily for 2 weeks,
was effective in reducing hyperglycemia in well-controlled diabetic patients when consumed in combination
with a low-fat diet (68% of energy from carbohydrates,
12% of energy from protein and 20% of energy from fat)
[17]. In the same study, however, it was determined that
the onion intervention had no antidiabetic effects when
consumed in combination with a moderate-fat-content
diet (50% of energy from carbohydrates, 20% of energy
from protein and 30% of energy from fat) [17]. From these
results it seems that the fat content of diet is an important
factor which needs to be considered when aiming to ameliorate diabetes-related symptoms using onion in the diet.
Moreover, to our knowledge, no dose response study of
Effects of Dietary Onion on Diabetes

onion in combination with a high-fat (HF) diet has been

performed to date.
In the present study, we investigated the effects of a
lower (0.5% of total diet) and higher (2.0% of total diet)
dietary dose of onion powder in a rodent model of HF
diet streptozotocin (STZ)-induced T2DM.

Materials and Methods

Preparation and Characterization of Onion Powder
Fresh white onions (A. cepa L.) were purchased from the local
market, peeled and diced before freeze-drying. The lyophilized
onion was finely ground. Characterization of the onion powder
was performed as described by Teyssier et al. [18], with minor
changes, using headspace analyses on a gas chromatograph mass
spectrometer (GC-MS). Briefly, 1 g of lyophilized onion powder
was mixed with 5 ml of distilled water in a 10-ml Vacutainer tube.
Triplicate headspace analyses were performed at room temperature for a period of 6 h, using a solid-phase microextraction polyacrylate fiber of 85 m, and transferred to the GC-MS [18]. GCMS analyses were carried out on an Agilent 6890 GC ported to a
5973 Mass Selective detector (Aglient Technologies, Santa Clara,
Calif., USA). An ion source temperature of 200 C and electron
energy of 70 eV were used. The GC was equipped with an SE-30
capillary column (Chemetrix, USA), a split/splitless injection
piece (200 C) and a direct GC-MS coupling (250 C). Helium
(1 ml/min) was used as a carrier gas. The oven temperature was
programmed to increase from 70 to 250 C at a rate of 8 C/min.
Identification of the sulfur compounds was accomplished by
comparing the retention times and the mass spectra with those of
previously injected standards (Sigma, St. Louis, Mo., USA).
Animals
The diabetic model used in this study was developed by feeding rats a HF diet in order to induce insulin resistance in combination with a low dose of intraperitoneal STZ, resulting in partial
-cell dysfunction and lowered insulin secretion. This model is
widely used for investigating the type 2 diabetic state due to the
fact that it is a non-insulin-dependent model, with insulin resistance, hyperglycemia and abnormal lipid profiles [1921].
Five-week-old male Sprague-Dawley rats weighing 120140 g
were purchased from Orient Charles River Technology (Seoul,
South Korea). The animals were housed in pairs in polycarbonated
cages, in a room with ambient humidity and temperature and a 12hour light/dark cycle. After free access to a HF diet (table 1) and
drinking water for 2 weeks, the animals were divided into 4 groups
of 8 animals as follows: HF control (HFC), diabetic control (DBC),
onion low (ONL) and onion high (ONH), where low and high
indicate the addition of lyophilized onion powder to the animals
diets such that the concentrations of onion powder in the diets
would amount to 0.5 and 2.0%, respectively. Ethical approval was
granted by the Experimental Animal Care Committee of the Institute of Laboratory Animal Resource of Seoul National University.
Induction of Diabetes
After feeding the animals a HF diet for 2 weeks, diabetes was
induced after a 12-hour fast via intraperitoneal injection (40 mg/

Ann Nutr Metab 2008;53:612

kg body weight) of STZ (Sigma) dissolved in citrate buffer (pH

4.5). Only buffer was injected into the HFC group. One week after
STZ injection, nonfasting blood glucose (NFBG) of all animals
was checked by a portable glucometer (Accu-Chek Active, Roche
Diagnostics Ltd., Mannheim, Germany) from blood collected
from the tail vein. Animals were considered diabetic with NFBG
values of 6300 mg/dl. The animals with blood glucose !300 mg/
dl were excluded from the study.
Diets and Feeding
The detailed compositions of the various diets are given in
table 1. The onion-containing experimental diets were prepared
by replacing equal amounts of corn starch in the control diet with
lyophilized onion powder. Animals were allowed to feed ad libitum on the allocated diets for a 4-week period after confirmation
of diabetes (1 week after the STZ injection). During this period,
dietary intake was monitored daily and body weight weekly.
Intraperitoneal Glucose Tolerance Test
In the last week of the experiment, an intraperitoneal glucose
tolerance test was performed in each animal. Animals were fasted
overnight prior to receiving an intraperitoneal injection of glucose (2 g/kg body weight). Glucose concentrations were subsequently measured in blood collected from the tail vein 0 (just before injection), 30, 60, 90 and 120 min after the glucose injection.
Blood Sampling and Liver Collection
At the end of the experimental period, fasted animals were
sacrificed by decapitation, and blood and livers were collected for
further analysis. Approximately 0.5 ml of whole blood from each
animal was collected in heparinized microtubes and immediately preserved at 4 C for subsequent analysis of glycated hemoglobin (HbA1c). The remaining blood was collected in 15-ml Falcon
tubes and centrifuged at 3,000 rpm for 15 min. The separated serum was collected and preserved at 80 C until further analysis.
Collected livers were trimmed, washed with cold saline, wiped
with filter paper, weighed, snap frozen in liquid nitrogen and preserved at 80 C until further analysis.
Analytical Methods
Blood glucose concentrations were measured by a glucose oxidoperoxidase method using a portable glucometer (Accu-Chek
Active, Roche Diagnostics). Serum insulin concentrations were
analyzed by using an ultrasensitive rat insulin ELISA kit (lot
No. 14154, Mercodia AB, Uppsala, Sweden) in a multi-well plate
ELISA reader (Biorad-680, Biorad Ltd., Hercules, Calif., USA).
Homeostatic model assessment (HOMA) was used to assess
longitudinal changes in insulin resistance (HOMA-IR) and pancreatic -cell function (HOMA-) in order to examine the natural history of diabetes during the experimental period. The following equations were used to calculate the HOMA-IR index [22]
and HOMA- index [23], respectively: HOMA-IR = (FBG in
mmol/l ! fasting serum insulin in U/l)/22.5; HOMA- = (20 !
fasting serum insulin in U/l)/(FBG in mmol/l 3.5).
The following conversion factors were used: blood glucose 1
mmol/l = 18 mg/dl; serum insulin 1 U/l = 7.174 pmol/l.
Blood HbA1c was extracted from heparinized blood using a
chromatographic cation-exchange disposable column after hemolysis, and the concentration was measured photometrically as

Ann Nutr Metab 2008;53:612

Table 2. Sulfur compounds identified via headspace analysis of

lyophilized onion powder using a GC-MS
Name of compound

Percentage of
total sulfur
compounds

Percentage of
total volatile
compounds

2,4-Dimethylthiophene
3,4-Dimethylthiophene
Propenyl methyl disulfide
Dimethyl trisulfide
Dipropyl disulfide
Propenyl propyl disulfide
Methyl propyl trisulfide
1,4-Dimethyl tetrasulfide
Dipropyl trisulfide
3,5-Diethyl-1,2,4-thiolane

0.3780.05
3.5780.47
11.5280.54
21.0780.56
19.2381.40
20.5480.55
9.3681.03
3.5980.70
5.6080.42
4.9580.35

0.1280.01
0.2780.07
1.3280.32
3.1480.90
1.8580.18
2.1380.17
1.0580.25
0.3980.19
0.6280.13
0.6080.16

described by the manufacturers instructions (HbA1c kit, lot No.

488AA, Biosystems, Costa Brava, Barcelona, Spain). Serum lipid
profiles (total cholesterol, high-density lipoprotein cholesterol,
low-density lipoprotein (LDL) cholesterol and triglycerides) were
determined photometrically using commercial kits purchased
from ACE Chemicals Ltd. (Seoul, South Korea). Liver glycogen
levels were measured by a phenol-sulfuric acid method as described by Lo et al. [24].
Statistical Analysis
All data are presented as the mean 8 SD of 68 animals. Data
were analyzed by a statistical software package (Statview, version
5.0, SAS Institute, St. Louis, Mo., USA) using the Tukey-Kramer
multiple-range post hoc test. Data were considered significantly
different with p values !0.05.

Results

The sulfur compounds detected in the freeze-dried

onion powder via GC-MS analysis and their corresponding amounts are presented in table 2. The sulfur compounds constituted 11.49% of all the volatile compounds
detected via headspace analysis. The major sulfur compounds identified were dimethyl trisulfide (21.07 8
0.56% of all sulfur compounds), propenyl propyl disulfide (20.54 8 0.55%), dipropyl disulfide (19.23 8 1.40%),
propenyl methyl disulfide (11.52 8 0.54%) and methyl
propyl trisulfide (9.36 8 1.03%).
During the 4-week feeding of the allocated diets, food
intake was significantly (p ! 0.05) higher and body weight
gain was significantly lower in the DBC, ONL and ONH
groups (with no significant differences between these
groups) compared to the HFC group (table 3). FBG values
were higher in both the ONL and ONH groups compared
Islam /Choi /Loots

Table 3. Food intake, body weight, FBG, serum insulin, HOMA-IR index, HOMA- index and blood HbA1c levels for the HFC, DBC,

ONL and ONH groups at the end of the experimental period

Food intake/rat/day, g
Body weight, g
FBG, mg/dl
Serum insulin, pmol/l
HOMA-IR index
HOMA- index
Blood HbA1c, %

HFC

DBC

ONL

ONH

19.4181.15a
466.74848.80a
113.13824.42a
295.69885.69a
11.7684.95b
352.208169.52a
5.1880.46a

22.4682.94b
330.76857.08b
181.71860.13a, c
61.83827.31b
3.5981.27a
40.50841.60b
7.7881.51b

23.8680.36b
324.46821.28b
286.148112.29b
98.71828.02b
9.6784.71a, b
27.44815.35b
8.2180.63b

23.9683.47b
351.98836.89b
240.208148.3b, c
126.84868.02b
10.1187.64a, b
89.548105.96b
7.7581.08b

Values represent the mean 8 SD of 68 animals. ac p < 0.05: values with different letters within a row are significantly different
from each other (Tukey-Kramer multiple-range post hoc test).

Table 4. Liver weight, relative liver weight and liver glycogen levels in HFC, DBC, ONL and ONH groups at the end of the experimen-

tal period

Liver weight, g
Relative liver weight, %
Liver glycogen, mg/g tissue

HFC

DBC

ONL

ONH

13.3482.13
2.8580.21a
3.1581.58a

12.8181.74
3.9180.40b
20.086.65b

13.0781.00
4.0380.23b
14.1485.07c

14.5682.07
4.1380.34b
18.0882.98b

Values represent the mean 8 SD of 68 animals. Relative liver weight = (liver weight/body weight) ! 100. ac p < 0.05: values with
different letters within a row are significantly different from each other (Tukey-Kramer multiple-range post hoc test).

to the DBC group; however, this difference was only significant in the ONL group compared to the DBC and
HFC groups. Although not significant, differences in
FBG were observed between the HFC and DBC and DBC
and ONH groups by the end of the experimental period,
with progressively higher values recorded for each of
these groups (table 3). Interestingly, the ONL group
showed significantly higher FBG values compared to
both the DBC and HFC groups, as well as higher values
compared to the ONH group (although nonsignificant).
Serum insulin concentrations were dose-dependently increased in the ONL and ONH groups compared to the
DBC group, with no significant differences observed between these groups (table 3). In line with this, better cell functions (HOMA- index) were observed in the
DBC and ONH groups compared to the ONL group.
However, despite these progressive increases in insulin
secretion by the onion-fed rats, insulin resistance
(HOMA-IR index) was similarly increased in the onionfed groups compared to the DBC group, although not significantly so. The concentrations of HbA1c were signifi-

cantly higher in the DBC, ONL and ONH groups compared to the HFC group, with no significant difference
observed between the DBC, ONL and ONH groups (table 3). These values also correspond well to the FBG levels
in each group.
The results of the intraperitoneal glucose tolerance
test are shown in figure 1. Blood glucose concentrations
0 min after glucose injection were significantly higher in
the ONL group compared to the DBC group. However,
no significant difference was found between the DBC and
ONH groups. No significant differences in blood glucose
concentrations were observed among the DBC, ONL and
ONH groups at the later time points of blood collection.
Data for the liver weight, relative liver weight (calculated as a percentage of body weight) and liver glycogen
levels are presented in table 4. Relative liver weight was
significantly higher in the DBC, ONL and ONH groups
compared to the HFC group, with no significant difference observed among the DBC, ONL and ONH groups.
Liver glycogen concentrations were significantly higher in
the DBC and ONH groups compared to the ONL group.

Effects of Dietary Onion on Diabetes

Ann Nutr Metab 2008;53:612

600

150

HFC

200
100

b
bc

ac
HFC

DBC

ONL

100

a a

b
a

75

a a
a a

50
ab

a
b ab

ONH
0

0
0

30

60
Time (min)

90

120

Fig. 1. Intraperitoneal glucose tolerance test in HFC, DBC, ONL

and ONH groups. Individual data points represent the mean 8
SD of 68 animals. ac p ! 0.05: values with different letters at each
time period are significantly different from each other (TukeyKramer multiple-range post hoc test).

Figure 2 shows the serum lipid concentrations at the

end of the experimental period. Serum total cholesterol
and LDL cholesterol were significantly higher in the
ONH group compared to other groups. Serum triglycerides were significantly higher in both onion-fed groups
compared to the DBC and HFC groups, with the ONH
group additionally showing significantly higher triglycerides compared to the ONL group. An overall dose-dependent hyperlipidemic effect of onion was observed in
this experiment.

Discussion

A number of studies to date have investigated the antidiabetic effects of various forms of onion, including
aqueous onion extracts [6, 16], dietary onion [11, 15, 25]
and isolated or synthesized active compounds in onion
[13, 14, 26]. These studies all report significant antihyperglycemic and antihyperlipidemic effects of these onion
interventions in alloxan- or STZ-induced diabetic rats.
However, these studies were performed using rats fed on
a diet containing normal levels of fat, and the diabetic
model used did not show insulin resistance. In the present study, we investigated the effects of two dietary dosages (0.5 and 2.0%) of freeze-dried onion powder in a rat
10

25

ONH

400
300

ONL

125

Serum lipid (mg/dl)

Blood glucose (mg/dl)

500

DBC

Ann Nutr Metab 2008;53:612

Total
cholesterol

HDL
cholesterol

LDL
cholesterol

Triglycerides

Fig. 2. Serum lipid profiles in HFC, DBC, ONL and ONH groups

at the end of the experimental period. Data bars represent the

mean 8 SD of 68 animals. HDL = High-density lipoprotein.
ac p ! 0.05: bars with different letters for each parameter are significantly different from one another (Tukey-Kramer multiplerange post hoc test).

model of HF diet (inducing insulin resistance) low-doseSTZ-induced T2DM.

The major bioactive components in onions are sulfur
compounds, e.g. S-allyl cysteine sulfoxide, S-methyl cysteine sulfoxide, diallyl trisulfide, dimethyl trisulfide, propenyl propyl disulfide, dipropyl disulfide, propenyl methyl disulfide, methyl propyl trisulfide and dipropyl trisulfides, to name only a few. Many of these compounds have
been shown to have antidiabetic as well as insulinotropic
activity in experimental animals [13, 14, 2629]. This
may explain the dose-dependent improvement in -cell
functions (HOMA-) and consequently increased insulin secretion seen in our study. However, due to the fact
that the model used was already sensitive to developing
insulin resistance (HOMA-IR) due to the HF diet, the increased insulin secretion induced by the inclusion of onion in the diet only worsened this parameter, consequently resulting in increased FBG, HbA1c and liver glycogen
levels. The slightly reduced FBG seen in the ONH group
compared to the ONL group can be explained by the
comparatively higher level of insulin secretion in the
ONH group, with insulin resistance similar to that of the
ONL group. Similarly, the HbA1c values correspond to
the FBG values, supporting this explanation.
At first glance, one would expect the liver glycogen
levels to correspond to FBG and HbA1c; however, in the
Islam /Choi /Loots

ONH group, glycogen levels were seen to be increased

despite lowered FBG and HbA1c compared to the ONL
group. Abnormal hepatic glucose metabolism is a wellknown complication associated with T2DM. Several enzymes may be involved, but the best described in this regard are hepatic glucokinase and glucose-6-phosphatase
[30, 31]. Previous studies have reported that altered hepatic glucokinase and glucose-6-phosphatase activities
result in the abnormal hepatic glycogen synthesis associated with the diabetic condition [32, 33]. These studies
also report that intervention with antidiabetic plant extracts or synthesized organic compounds further influence these enzymes, increasing liver glycogen synthesis
and in turn lowering FBG levels [30, 31]. However, the
dose administered is an important factor in initiating
these effects, with lower doses showing no effects.
The sulfur compounds found in onions are also known
to influence hepatic enzyme activity [13]. This may explain the altered liver glycogen secretions seen in our
study, with activation or inhibition of certain enzymes at
certain onion dosages. However, as it was not the aim of
this study to investigate the effects of onion on the enzyme systems involved in glycogen metabolism, we can
only speculate on the possible mechanism underlying
this effect.
Apart from the fact that the HF onion diets were not
able to correct the abnormal hyperglycemia, they additionally worsened the hyperlipidemia in a dose-dependent manner due to the increased insulin resistance in
these groups. It is already well known that insulin resistance results in increased free fatty acid release from adipose tissue and uptake by the liver, consequently resulting in the hyperlipidemia associated with T2DM [34].

Additionally, onion is also thought to increase the absorption of LDL, increase the endogenous production of
LDL and lower LDL uptake by peripheral tissues when
administered in conjunction with an HF diet [35].
Previous studies have shown dietary onion to be effective in reducing hyperglycemia [13] and hyperlipidemia
[13, 36] when fed in combination with a diet containing
normal levels of fat. However, it has also been shown that
dietary fat is an important factor influencing FBG, serum
insulin and serum lipid concentrations in both diabetic
humans and experimental animals [37]. Confirming this,
in a human-based study, it was found that although the
consumption of 3 ! 20 g of fresh onion per day for 2
weeks by diabetic patients positively changed both FBG
and serum lipid concentrations when it was consumed
together with a low-fat diet (68% of energy from carbohydrates, 12% of energy from protein and 20% of energy
from fat), the opposite was shown to be true when it was
taken in combination with a moderate-fat-containing
diet (50% of energy from carbohydrates, 20% of energy
from protein and 30% of energy from fat) [17]. The results
of our study further support this, suggesting that neither
a lower (0.5%) nor a higher (2.0%) dietary dose of onion
is beneficial for alleviating the diabetic condition when
given in combination with an HF diet and may even further worsen the situation.

Acknowledgement
This study was supported by a grant from the Korean Health
21 R&D Project, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG1-CH12-0002).

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