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Garlic Antidiabetic

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GARLIC (ALLIUM SATIVUM) SUPPLEMENTATION WITH STANDARD

ANTIDIABETIC AGENT PROVIDES BETTER DIABETIC CONTROL


IN TYPE 2 DIABETES PATIENTS
RIZWAN ASHRAF1, RAFEEQ ALAM KHAN1 AND IMRAN ASHRAF2

Department of Pharmacology, Faculty of Pharmacy, University of Karachi, Pakistan


2
Department of Geriatric Medicine, Kings Hospital, London, UK

ABSTRACT
Garlic has been used safely since ancient times as both food and medicine in human populations, but studies of
its efficacy in the management of diabetes have yielded conflicting results. This study has evaluated the
potential hypoglycemic effects of garlic in type 2 diabetic patients. The study was conducted in diagnosed type
2 diabetic patients (n=60) with fasting blood sugar level above 126 mg/dl to evaluate the effects of adding garlic
tablets with standard antidiabetic therapy on blood sugar. Patients were divided randomly into 2 groups. Group
1 (n=30) was given tablet Garlic (KWAI) 300 mg thrice daily + Metformin 500 mg twice daily and Group 2
(n=30) was given Placebo+Metformin 500 mg twice daily respectively for 24 weeks. Serum lipids and fasting
blood glucose were measured at week 0, 12 and week 24.
Group1 showed significant reduction in fasting blood sugar at week 24 with a percentage decrease of (-3.12
percent) (P = <0.005) as compared to group 2 (0.59 percent). At the end of week 24, GR1 group also showed
considerable decrease in mean total cholesterol (6.2 mg/dl, -2.82%, P=<0.005), LDL-C (-3 mg/dl, 2.18%
P=<0.005), triglycerides (-5.2 mg/dl, 3.12%, P<0.005) while HDL cholesterol was significantly increased (2.36
mg/dl, 6.72%, P<0.005) as compared to GR2 group. Combination of garlic with typical antidiabetic remedy has
shown to improve glycemic control in addition to antihyperlipidemic activity. Garlic may be a good addition in
the management of patients with diabetes and hyperlipidemia.
Keywords: Allium sativum, blood glucose, diabetes, garlic.

INTRODUCTION
The pervasiveness of type 2 diabetes mellitus (T2DM) is
rising globally almost approaching epidemic proportions
(Zimmet et al., 2001). According to WHO, the incidence
of diabetes was 4.0% in 1995 which by the year 2025 is
estimated to mount to 5.4%. This will lead to raise in the
number of diabetic patients from 135 million in 1995 to
300 million in 2025. Greater increase will be in
developing countries where the number of patients
afflicted with diabetes will rise to about 170% from 84
million to 228 million as compared to the developed
countries where the number of patients will go up 42%,
from 51 million to 72 million (King et al., 1998). In
Pakistan, no of patients afflicted with diabetes are
estimated to increase from 4.3 million in 1995 to 14.5
million in 2025. It is expected that more than 75% of
diabetic populace will be from developing countries by
the year 2025 (Shera et al., 2007).
In patients with T2DM, a common pharmacological
treatment approach is less well accepted. Usually
treatment started with an oral antidiabetic agent but due to
the progressive character of the illness, patients ultimately
need one or more supplementary antidiabetic agents
(DeFronzo, 1999). Selection of particular drug depends
upon on individual patient status and the presence of other
*Corresponding author: e-mail: drriz72@yahoo.com
Pak. J. Pharm. Sci., Vol.24, No.4, October 2011, pp.565-570

cardiovascular risk factors like dyslipidemia


hypertension (Nathan DM et al., 2009).

and

Owing to the worldwide rise in the incidence and


socioeconomic burden of diabetes, it is quite important to
discover pharmacological preparation that not only
provide good glycemic control but also proved to be safe
and cost effective. The utilization of natural substances
has increased for various diseases amongst general public
over last few years not only because of their easy
availability without prescription, cost and appointment to
the health care professionals, but also owing to the belief
that natural substances has less adverse effects as
compared to synthetic medicines. Numerous natural
substances have been investigated for their potential
antidiabetic effects (Fujita et al., 2001; Park et al., 2006;
Youn et al., 2004). Garlic is one of such natural
substances which have been considered for long time to
provide protective effects on various cardiovascular
disease risk factors (Steiner et al., 2001). Although blood
glucose lowering effect of different garlic preparations
has been comprehensively reported in animal models of
diabetes (Anwar et al., 2003; Duncan, 1999; Liu et al.,
2005; Liu et al., 2006), studies reporting hypoglycemic
effects of garlic in humans are scarce and conflicting
(Bordia et al., 1998; Jain et al., 1993; Zhang et al., 2001).
Keeping in mind the lack of scientific evidence regarding
hypoglycemic effects of garlic from human studies and
inconsistent data from animal studies and increasing

565

Garlic (Allium sativum) supplementation


prevalence of diabetes mellitus worldwide and growing
curiosity in natural remedies, we designed a study to
substantiate the blood glucose lowering potential of garlic
in type 2 diabetic patients.

RESULTS

MATERIALS AND METHODS

The present study demonstrated significant reduction in


fasting blood sugar levels in group 1 (GR2=Garlic
metformin) as compared to group 2 (GR2=Placebo
metformin).

This was a 24 weeks, single-blind and placebo controlled


study. Study was done simultaneously in different
primary health care centers in Karachi, Pakistan in
cooperation with registered medical practioners. Patients
with diagnosed type 2 diabetes mellitus (n=60) were
recruited and were divided into 2 groups, each comprised
of 30 patients. Patients in group 1 (GR1) were given
garlic tablets (odor-free, commercial preparations, Kwai,
Lichtwer Pharmaceuticals, Berlin, Germany that provides
0.6% allicin) at a dose of 300 mg three times per day
while patients in group 2 (GR2) were given placebo. Both
the groups received metformin in addition to garlic and
placebo respectively at a dose of 500 mg twice daily. All
patients in the study were selected according to following
criteria.

The demographic data of the study population is shown in


table 1. The patients were male (56%) and females (40%).
The mean age was 40 years in garlic treated group and 35
years in placebo treated group (range 25-60 years) (table
1). Measurements of fasting blood glucose and lipid
profile were done at 12 week intervals i.e. at week 0,
week 12 and week 24 (table 1 and 2, figs. 1 and 2). Out of
60 patients initially enrolled in the study, fifty-four
patients completed the study protocol till week 24. One
patient in the garlic added group (GR1) reported heart
burn in the first week of study and say no to follow the
study protocol. Two patient in GR1 and three patients in
placebo group (GR2) were dropped out as they did not
come back for follow up due to unknown reasons.
Seventeen patients in GR1 and eighteen patients in GR2
were found to have concurrent dyslipidemia.

Inclusion criteria
Patients of either sex, aged between 25-70 years, with
recently diagnosed type 2 diabetes mellitus with fasting
blood sugar levels between 100 to 130 mg/dl.
Exclusion criteria
Patients having record of allergy to garlic, ischemic heart
disease, angina, impaired hepatic or renal dysfunction,
bleeding disorders and pregnant or lactating women.
The patients previous record and recent blood glucose
levels were evaluated at the time of presentation in OPD
and those having a profile that fulfilled our inclusion
criteria were counseled those who were ready to
participate and follow study protocol were enrolled after
taking informed and written consent (tables 1 and 2). All
the necessary credentials of patients, record of follow up
visits and laboratory analysis data of each patient were
documented on special proforma intended for this study.
The patients were advised to come for follow-up
fortnightly. Patients were advised to come with 12 hours
fasting for lipid profile and fasting blood sugar analysis at
week 0, week 12 and week 24 respectively. At each visit,
all patients were fully inquired about drug compliance and
side effects of drugs. Patients were motivated to keep
their nutritional plan, physical activity, and general life
style as constant as possible throughout the study period.
The patients were forbidden to take any other medication
during the study period. Statistical analysis was done with
one-way analysis of variance (ANOVA) followed by
Tukey post-hoc test. Statistical P value less than 0.05 was
considered significant.

566

Table 1: Demographic Data of GR1 and GR2 Group

Men
Women
Age (years)
Body weight (Kg)
Height (cm)
Average duration of
type 2 diabetes mellitus
Co-morbid disease

GR1
Garlic +
Metformin
17
13
40 5.04
68.2 10.45
165.2 8.81
Recently
diagnosed
None

GR2
Placebo+
Metformin
16
14
35 4.58
69.1 7.58
166.4 6.58
Recently
diagnosed
None

Table 2: Changes in Fasting Blood Glucose from week 0


to week 12 & week 24 of treatment with GR1 and GR2 in
patients with type 2 diabetes mellitus
Drugs
Fasting
Blood
Glucose

GR1
GR2

Week 0
(mg/dl )
128.3 +
0.311
(n=30)
112.9
0.542
(n=30)

Week 12
(mg/dl )
126.9
0.369*
(n=27)
111.7
0.540
(n=27)

Week 24
(mg/dl )
124.8
0.330**
(n=27)
110.2
0.520
(n=27)

GR1 = (Garlic+ Metformin), GR2 = (Placebo + Metformin)


*Significant P value <0.05 as compared to placebo
**Highly significant P value <0.005 as compared to placebo.
Values are in mean SEM
All observations were measured in mg/dl.
Figures in Parenthesis indicate number of patients.

At the end of week 24, the changes in fasting blood


glucose levels from week 0 to week 24 were significantly
Pak. J. Pharm. Sci., Vol.24, No.4, October 2011, pp. 565-570

Rizwan Ashraf et al.


divergent between GR1 and GR2 groups (table 2 and fig.
1). The GR1 group has shown significant reduction in
mean glucose levels. The garlic treated GR1 group had a
mean fasting blood glucose of 128.3 0.311 mg/dl at
week 0 which was reduced to 126.9 0.369* mg/dl
(P<0.05) at week 12 and to 124.8 0.330** mg/dl
(P<0.005) at week 24. The percentage change in fasting
blood glucose from week 0 to week 24 in GR1 showed a
greater decreasing trend (3.12 %) (P=<0.005) as
compared to GR2 which showed a decrease of 1.78%.

% decrease in FBS

GR1
4.00%

GR2

3.12%

3.00%

1.78%

2.00%
1.00%
0.00%

Fig. 1: % change in FBS from week 0 to week 24 with


GR1 and GR2:
GR1 = Garlic + Metformin, GR2 = Placebo + Metformin
FBS= Fasting blood sugar

The changes observed in total cholesterol, HDLcholesterol, and LDL-cholesterol and triglycerides were
appreciably dissimilar when compared between GR1 and
GR2 groups (table 3 and fig. 2). The garlic treated group
had a significant reduction in mean total cholesterol as
compared to the placebo treated group. At the end of
week 24, GR1 group showed considerable decrease in
mean total cholesterol (6.2 mg/dl, -2.82%, P=<0.005),
LDLC (-3 mg/dl, 2.18 % P=<0.005), triglycerides (-5.2
mg/dl, 3.12%, P<0.005) while HDL cholesterol was
significantly increased (2.36 mg/dl, 6.72%, P<0.005) as
compared to GR2 group. The changes in lipid profile
were appeared to be duration dependent as the significant
increase in HDL was seen after 12 weeks of study.
GR1

GR2

8.00%

6.72%

6.00%
4.00%
2.00%
0.00%

-0.04%
-0.68%

-2.00%
-4.00%

-0.45%
-2.18%

-2.82%

-3.10%

TC

TG

LDL

-3.17%

HDL

Fig. 2: % changes in Lipid Profile with GR1 and GR2


from week 0 to week 24.
GR1 = Garlic + Metformin, GR2 = Placebo + Metformin
(-) indicates decrease in percentage, T. Chol. = Total Cholesterol, TG. =
Triglyceride, HDL = High

Pak. J. Pharm. Sci., Vol.24, No.4, October 2011, pp. 565-570

DISCUSSION
The present study was focused to monitor the effects of
addition of garlic to antidiabetic agent metformin on
fasting blood glucose levels in patients with type 2
diabetes mellitus; metformin was selected in this study
since it is recognized as a first-line antidiabetic agent for
the management of type 2 diabetes (Esposito et al., 2011).
It is suitable irrespective of age, body weight, severity of
hyperglycemia and provides a convenient pharmacological base for combined therapy with other
antidiabetic agents (Scarpello and Howlett, 2008).
Metformin has a lower mortality and cardiovascular risk
as compared with most insulin secreting agents such as
glimepiride, glibenclamide, glipizide, and tolbutamide in
patients with type 2 diabetes mellitus (Schramm T et al.,
2011). Another benefit of metformin is that it does not
produce hypoglycemia because it does not stimulate
insulin secretion when it is given alone in patients with
type diabetes mellitus (Wright et al., 2006). Metformin is
also renowned to facilitate modest weight loss in type 2
diabetic patients (Golay, 2008). The garlic was added to
antidiabetic agent metformin with the hypothesis that it
will not only provide better glycemic control but will also
helps in improving lipid profile which is a frequent
occurrence in patients with type 2 diabetes mellitus. The
results observed in the present study demonstrate
statistical significant decrease in fasting blood glucose
and serum lipids when compared from baseline values at
week 0 to week 12 and week 24 in garlic treated group as
compared to placebo treated group.
Our study confirms the earlier hypoglycemic effects of
garlic observed in previous preclinical trials. Numerous
trials in animal models of diabetes (Al-Qattan et al.,
2008; Eidi et al., 2006; Sheila et al., 1992; Chang et al.,
1980; Jeloder et al., 2005, Banerjee et al., 2003) has
demonstrated the blood glucose lowering as well as
antioxidant effects of garlic (Lee et al., 2009). Insulin
levels were found to be increased in diabetic rats when
given garlic oil (Devaki et al., 1992; Venmahdi et al.,
1992). Garlic was also found to be effective in preventing
adrenal hypertrophy, elevation of corticosterone and
increased blood glucose in diabetic mice (Kasuga et al.,
1999).
S-allyl cysteine sulfoxide (alliin), a sulfur
containing amino acid in garlic has been reported to have
comparative efficacy with standard antidiabetic agents
like glibenclamide and insulin in controlling
hyperglycemia in diabetic animals (Sheela et al., 1995;
Sheela et al., 1992). The changes observed in present
study are in accordance with the findings of Eidia et al.,
2006 who reported that administration of the both garlic
extract and glibenclamide tend to bring serum glucose and
insulin appreciably toward normal values.
Although many of the previous trials in animal models
showed considerable hypoglycemic effects of garlic,

567

Garlic (Allium sativum) supplementation


human studies are inadequate and showed conflicting
results. Some of the clinical trials on garlic showed
hypoglycemic effects in humans (Zhang et al., 2001;
Kiesewetter et al., 1991; Bordia et al., 1998; Jain et al.,
1993; Ali et al., 1995), but were done in normal healthy
individuals. The present study is unique from previous
clinical trials because hypoglycemic effects of garlic have
been observed in patients with type 2 diabetes mellitus in
combination with a standard antidiabetic agent
metformin. The present study is in accordance with a
previous clinical trial by Sobenin et al., 2008 who also
reported hypoglycemic potential of garlic in patients with
type 2 diabetes mellitus although the preparation used was
different from that used in the present study. Our study
contradicts with the study of Afkhami-Ardekani et al.,
2006 who reported that garlic has no hypoglycemic and
antilipidemic effects. The hypoglycemic effects observed
in this study are also in agreement with the earlier clinical
trial by Li et al., 2000 that reported discernible reduction
in blood sugar levels in patients with hyperglycemia.
Mahmodi et al., 2006 also reported hypoglycemic effects
of garlic similar to that found in our study. Although the
precise mechanism for hypoglycemic effects of garlic is
not apparent, however it has been proposed in some
studies that garlic acts as an insulin secretagogue. It has
also been proposed that allylepropyldisulphide or diallyle
disulphide present in garlic are responsible for
hypoglycemic effect of garlic (Jain et al., 1973; Chang et
al., 1980; Jain et al., 1974; Jain et al., 1975). Antioxidant
effects of garlic are another possible mechanism that
makes it a contender as antidiabetic agent (Queiroz et al.,
2009; Lee et al., 2009). Antioxidant effect of S-allyl
cysteine sulfoxide, isolated product from garlic, is
considered to possess antiglycation properties.
Garlic was also found to produce hypoglycemic effects by
sparing insulin inactivation from sulphydryl group
(Banerjee et al., 2002). Patients with diabetes frequently
have coexisting hyperlipidemia commonly known as
diabetic dyslipidemia that is known to increase the risk
for cardiovascular disease many fold. Patients with
diabetes commonly require combination of antidiabetic
and antilipidemic agents to prevent the patients against
morbidity associated with cardiovascular disease. We
found significant antilipidemic effects of garlic on all the
lipid parameters as compared to placebo group. The
change observed in lipid profile in the present study is in
accordance with previous clinical trials (Steiner et al.,
1996; Tohidi et al., 2000; Ashraf et al., 2005; Jabbar et
al., 2005; Kannar et al., 2001).
The proposed mechanism for antilipidemic effects of
garlic is inhibition of hydroxymethylglutaryl-CoA
reductase (HMG-CoA reductase), by allicin (Siegel et al.,
1999; Adler et al., 1997). Garlic is supposed to reduce
total cholesterol largely owing to decrease in LDL-C
levels. The present study contradicts with some previous
trials (Tanamai et al., 2004; Turner et al., 2004; Peleg et

568

al., 2003) which showed garlic to be ineffective. The most


probable reason for this contradiction may be attributed to
difference in garlic preparation, dose and duration of
study.
Although garlic was assumed safe and recommended for
many common ailments since ancient times, too much
utilization of garlic can cause problems. Garlic breath and
infrequent allergic response are predictable adverse
effects. Reports have also revealed gastrointestinal side
effects like nausea and diarrhea (Sieger et al., 1992; Desai
et al., 1990) associated with raw garlic and garlic powder
preparations. In the present study, garlic did not produce
any considerable problem in patients with type 2 diabetes
mellitus and only one patient has complained of gastric
discomfort, the possible reasons for this good tolerance
might be enteric coated, odorless garlic tablet preparation
used in this study.

CONCLUSION
The present study has demonstrated significant
hypoglycemic and hypolipidemic effects of garlic when
added with standard antidiabetic agent. Comprehensive
clinical studies are desirable to verify the effectiveness of
garlic either alone or in combination with other
antidiabetic or antihyperlipidemic agents in the treatment
and prevention of diabetes and other cardiovascular risk
factors.
Disclosure statement
The authors do not have any competing financial
interests.

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