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Research & Reviews: Journal of Computational Biology
ISSN: 2319-3433 (Online), ISSN: 2349-3720 (Print)
Volume 8, Issue 1
www.stmjournals.com
Anti-hyperglycaemic Effect of Psidium guajava Extracts in
Diabetes Mellitus: Systematic Review and Meta-analysis
Gebrekidan Gebregzabher Asfeha1, Birhane Alem Berihu2,*
1Department of Clinical Biochemistry, Division of Biomedical Sciences, School of medicine, College
of Health Sciences, Mekelle University, Mekelle, Ethiopia
2Department of Anatomy, Division of Biomedical Sciences, School of medicine, College of Health
Sciences, Mekelle University, Mekelle, Ethiopia
Abstract
Introduction: Psidium guajava belonging to family Myrtaceae is traditionally used plant for
the treatment of diabetes in many countries of the world. This systematic review was designed
to determine level of evidence of on the anti-hyperglycaemic effect of Psidium guajava extracts
from experimental trials. Methods: An electronic literature search from the database inception
was performed since December 2014 with specified terms and defined outcome. We included
only experimental study designs using Psidium guajava extract as anti-hyperglycaemic effect.
Two reviewers independently extracted data and rated the risk of bias of each included trial. A
Standard Mean difference with 95% confidence interval was an effective measure for the
outcome. The statistical analysis was done using Review Manager 5.3. Results: Studies
included in the present systematic review and meta-analysis suggests that following the
treatment of diabetic albino rats with the Psidium guajava extract showed a significant
reduction in blood glucose at all dose level of the extract p = 0.00001). This analysis showed
very promising effect of guava extract on in diabetes mellitus in terms of significance when
compared to the individual studies. Conclusion: The results of the present review have shown
the significant antidiabetic activities of extracts of Psidium guajava in experimental rats.
Although a number of included studies regarding the current topic are limited, the available
evidence is sufficient to support the anti-hyperglycaemic effect of the extract on diabetes
mellitus. Further investigations involving humans designed with attention to duration of the
blood glucose assessment are needed. Study on understanding of the mechanisms of the
antidiabetic effect Psidium guajava is also recommended.
Keywords: Diabetes mellitus, Blood glucose level, hyperglycemia, hypoglycaemia, Psidium
guajava extract.
*Author for Corresponding E-mail: birhane.visionary27@gmail.com
INTRODUCTION
Diabetes mellitus is a syndrome of metabolic
disorders that have hyperglycemia and glucose
intolerance as their hallmark. This disease is
usually due to a combination of hereditary and
environmental causes in which the blood sugar
(glucose) levels are abnormally high
(hyperglycemia) because either the body does
not produce enough insulin or the insulin so
produced cannot be used by the body [1, 2]. The
prevalence of diabetes mellitus (DM) cases has
been increasing worldwide in recent years. In
2000 the World Health Organization estimated
a total of 171 million (2.8%) people with DM
from the global population, and this figure has
been projected to increase to 366 million
(4.4%) by 2030 [3].
Although diabetes mellitus is considered
mostly as incurable disease, there has been a lot
of therapy to lower blood glucose levels, by
adjusting diet, physical exercise, counselling,
and medications associated with hyperglycemia
such as a sulfonylurea class of drugs, glinid,
biguanide, alpha-glucosidase inhibitor, a
thiazolidinedione. However, modern medicines
are often negative side effects such as the
occurrence of hyperinsulinemia (excess insulin
levels in the blood) and finally low blood
glucose levels (hypoglycaemia), weight loss,
Anti-hyperglycaemic Effect of Psidium guajava Extracts in Diabetes Gebrekidan Gebregzabher Asfeha
RRJoCB (2019) 1-9 © STM Journals 2019. All Rights Reserved Page 2
increased blood cholesterol levels, light nausea,
loss of appetite, diarrhoea, indigestion, and can
occur even more severe insulin resistance [4].
In the last few years there has been an
exponential growth in the field of herbal
medicine and these drugs are gaining popularity
both in developing and developed countries
because of their natural origin and less side
effects [5].
Herbal medicines continue to play an important
role in diabetic therapy, particularly in the
developing countries where most people have
limited resources and do not have access to
modern treatment. WHO has also authenticated
the use of herbal remedies for the treatment of
diabetes mellitus. The increase in demand for
the use of plant based medicines to treat
diabetes may be due to the side effects
associated with the use of synthetic drugs such
as insulin and oral hypoglycaemic agents [6].
Psidium guajava Linn. (P. guajava) family
Myrtaceae is an important dietary plant used
traditionally for medicinal purpose around the
world. The fruit part of the guava is used
because of its food and nutritional value, but
other parts of the guava plant are used in the
traditional system due to their medicinal
properties [7]. The anti-diabetic property of
bark, leaves, fruits and peels of P. guajava has
been studied by several investigators.
The aqueous leaf extract was tested in alloxan
and STZ-induced diabetic rats. The authors
attributed the observed hypoglycaemic effect of
the extracts [8, 9, 10, 11, 12, 13]. In another
study, the anti-hyperglycaemic activity of a
stem bark extract on blood glucose levels of
normal, alloxan-induced hyperglycaemic and
normal glucose loaded rats was examined and
reported that the extract exhibited significant
hypoglycaemic activity but was devoid of
hypoglycaemic effect in normal and glucose
loaded rats [14]. Another study conducted on
the effect of guava juice in lowering blood
glucose level also showed that guava (Psidium
guajava L.) juice in 25% concentration was
effective in lowering blood glucose level [15].
On the other hand, two studies revealed
contradicting results using P. guajava raw fruit
peel and the one concluded that the Normal,
mild and severely diabetic rat models had
shown the hypoglycaemic effect of the unripe
guava fruit peel aqueous extract [16] while the
other showed the hyperglycaemic effect of P.
guajava fruit peel and suggested that the
diabetic patients should peel off the guava fruits
before consuming [17]. Unfortunately,
assessments of the anti-hyperglycaemic effect
of P. guajava have not been conducted based
on formal, systematic review and meta-
analysis. Hence, intended to conduct systematic
review and meta-analysis to determine level of
evidence of the anti-hyperglycaemic effect of
Psidium guajava extracts from experimental
trials.
METHODS
Data Sources and Search Strategy
An electronic literature search from the
database inception was performed since
December 2014 in the following databases:
MEDLINE, Cochrane Library, Pubmed,
Academic Search Complete, ScienceDirect,
Scopus, Web of Science and Google Scholar,
without year and language restrictions, using
the following key terms: Psidium guajava, or
guava; and diabetic mellitus, and blood glucose
level, or hyperglycemia, or hyperglycaemia and
control in titles or abstracts. Search strategies
were established in consultation with a
university librarian. Two reviewers (GG and
BA) independently conducted the database
searches.
Selection Criteria
We independently inspected the search results
by reading the titles and abstracts. We retrieved
each potentially relevant publication located in
the search, and assessed it for inclusion,
subsequently examining the reference lists of
eligible studies and relevant review articles. We
specified inclusion and exclusion criteria and
defined an outcome in this meta-analysis study.
We included only experimental study designs
on rats using P. guajava as anti-hyperglycaemic
effect, in which control condition involved only
distilled water, including doses of an active
standard.
Data Extraction
Research & Reviews: Journal of Computational Biology
Volume 8, Issue 1
ISSN: 2319-3433 (Online), ISSN: 2349-3720 (Print)
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Both reviewers (GG and BA) independently
extracted data and rated the risk of bias of each
included trial. Any disagreements regarding
study inclusion between two reviewers were
resolved through discussion. The following
were recorded from each trial where available:
intervention characteristics (guava dose,
control condition, additional treatments);
participant characteristics (gender, age,
weight); study characteristics (Author,
publication year); outcomes (time of outcome
assessment, unit of outcome assessment);
evaluation of each domain of the Cochrane risk
of bias assessment tool (sequence generation,
allocation concealment, blinding, incomplete
outcome data, selective outcome reporting)
[18]. The outcome was blood glucose levels,
defined as decreased or increased, as measured
after certain days of induced diabetic
development.
Statistical Analysis
A Standard Mean difference (SMD) with 95%
confidence interval (CI) was an effect measure
used for the outcome. A weighted mean
difference (WMD) with 95% CI was used to
synthesize the status of blood glucose level.
The outcome was measured by mg/dl of the
mean combined by using SMDs with 95% CIs.
The data synthesis was done with an intention
to treat basis. Because the results obtained from
a fixed effect model of data synthesis might be
more generalized, the random effect model was
used throughout the review for calculating
WMDs, and SMDs [19].
The inconsistency of data was examined by
looking at the graphical display of the results
and also by using an I-squared (I2). As
recommended, an I2 of 75% or more indicates
high inconsistency of data. To test the
robustness of the results, relative to features of
the studies, a sensitivity analysis was performed
to examine results by including and excluding
of included studies. The statistical analysis was
performed by the use of Review Manager 5.3
(Cochrane Collaboration, Oxford, England).
RESULTS
Description of Studies
Out of the total of 403 studies, we identified
eleven eligible experimental studies and eight
of them [8, 9, 10, 11, 12, 14, 15, 16] were used
for Meta-analysis (Figure 1). Details of the
search are shown in Figure 1 and characteristics
of the studies are shown in Tables 1. Three of
the eleven studies were excluded, one was
experimental but no appropriate data related to
blood glucose level [13] and two experimental
studies used P. guajava fruit peel and showed
no effect [16] and a hyperglycemia in treated
groups [17].
The eight eligible trials included a total of 98
rats; of these 49 (50%) had been randomly
assigned to receive different doses of guava leaf
and fruit extracts and 49 (50%) to a control
condition. Oral doses of guajava leaf, fruit or
root extracts were administered diabetic rats;
whereas the control conditions used only
distilled water (Table 1).
Before the experimental drug session, all
participants had equivalent treatment within
each trial; however, between the trials the
guava extract dose preparation was varied.
Each trial used clearly defined, standardized
methods to assess outcomes on the status of
blood glucose level. Continuous outcome data
of the seven studies were in mg/dl but in one
study, it was in mmol/L (Table 1).
Effect of P. guajava Extracts on Blood
Glucose Level
The pooled SMD on a decrease in blood
glucose level between the guava treated and
control groups was -6.80 (95% CI, -9.71, -3.89;
p = 0.00001), see Figure 2. Among the eight
studies, 42 of 49 (86%) P. guajava treated
groups showed significant decreases, but none
of the control groups showed any decrement.
Heterogeneity of the between-experimental
treatment outcome was considerable in the
comparisons (I2 = 86%, for all p <0.00001 for
the χ2 test). To perform sensitivity analysis, we
tried to remove the poorer trials in which the
quality of methodological design was not as
high as in most recent studies.
Anti-hyperglycaemic Effect of Psidium guajava Extracts in Diabetes Gebrekidan Gebregzabher Asfeha
RRJoCB (2019) 1-9 © STM Journals 2019. All Rights Reserved Page 4
Fig. 1: The process of study selection according to the PRISMA flow diagram
Table 1: Characteristics of the Included Studies.
Author
Study design
Subjects
Types of
Intervention
Measurement
of an Outcome
Study Findings
H. M.
Mukhtar et
al. 2006
Experimental
Wistar rats
(180–200 g) of
either sex
Standard drug,
Gliclazide at an
oral dose of 25
mg/kg and
Ethanol extract
at an oral dose of
250 mg/kg.
After 10 days,
blood glucose
levels are
presented as
means ± SEM of
mg/dl
A consistent
significant
reduction in blood
glucose levels was
observed
Deepthi R,
et al. 2012
Experimental
Wistar rats
(150–200 g)
Dry leaf extract
(500 mg/kg),
Fresh leaf extract
(500 mg/kg) of
P. guajava
Serum glucose
levels were
estimated and
expressed as
Mean ± S.E.M of
mg/dl
The hydro
alcoholic extract
of fresh leaves of
Psidium guajava
produced a very
significant
Research & Reviews: Journal of Computational Biology
Volume 8, Issue 1
ISSN: 2319-3433 (Online), ISSN: 2349-3720 (Print)
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reduction in blood
glucose levels
H. M.
Mukhtar et
al. 2004
Experimental
Male Wistar rats
(160–200 g)
Standard anti-
diabetic drug
Gliclazide at an
oral dose of 25
mg/kg.
Ethanol extract
at a dose of 250
mg/kg;
After 10 days,
the blood
glucose levels
were determined.
Data were
expressed Mean
± SEM of mg/dl
Psidium guajava
leaves possess
statistically
significant
hypoglycaemic
activity
Prashant K
et al. 2009
Experimental
6–8 wk old,
healthy, male
albino
Wistar rats, of
body weight
150–200 g.
45 mg/kg wt.
streptozotocin
250 mg/kg of the
reference drug
tolbutamide.
300, 400 and 500
mg/kg of extract
powder
suspended in
dist. Water
The blood
glucose level
was measured
and expressed as
mean ± SD of
mg/dl
The daily
treatment with 400
mg/kg of the
extract for 21 days
brought FBG
significantly
down.
Kateregga
JN et al.
2014
Experimental
30 Wistar albino
rats of either sex
weighing
between 80 and
120 g.
120 mg/kg of
Alloxan
monohydrate.
Psidium guajava
ethanolic leaf
extract of 800
mg/kg
Glibenclamide at
a dose of 50
mg/kg.
Blood was
obtained and
blood glucose
level was
expressed as
means ± SEM of
mg/dl
The ethanolic
extract of P.
guajava leaves
demonstrated anti-
hyperglycaemic
activity and is safe
to use.
Santosh M
et al. 2015
Experimental
Male Wister rats
weighting
(180±10) g
Alloxan
tetrahydrate (100
mg/kg i.p.).
Ethanolic
extracts of P.
guajava leave
(EEPGL) at 750
mg/kg.
Blood glucose
level of samples
was expressed as
Mean ± SEM of
mmol/L.
Results exhibited
the significant
antidiabetic
activities of
ethanolic extracts
of P. guajava
leave in Wister
rats.
Abdol H et
al. 2012
Experimental
Male Wistar
rats, weighing
180–250 g,
divided into 5
groups (10 rats
in each)
Alloxan
1g/l of an
aqueous ethanol
P. Guava leaf
extract
10 days after
diabetes,
Glucose level
expressed as
mean ± S.E.M.
of mg/dl in every
week
Psidium guava
administration can
decrease blood
glucose levels
Vini V et al.
2012
Experimental
Male sex mice
(Mus musculus)
weighing 20–30
grams and 2–3
months old.
Metformin HCl;
Guava juice:
100%, 50%, and
25%
100% Guava
juice increases
while 50% and
25% Guava
juices decrease
blood glucose
levels expressed
as Mean ± SDM
of mg/dl
The consumption
guava juice
provides a more
significant
reduction in blood
glucose than that
in control group.
Shakeera
BM et al.
2013
Experimental
Male albino rats
of 6–8 weeks
age, weighing
150–180 g.
Alloxan
monohydrate
150 mg/kg
Leaf extract of P.
guajava (500
mg/kg body
weight).
Values were
expressed as
means ± S.D.
No value for
blood glucose
level
Anti–
hyperglycaemic
potential of the
extract of P.
guajava leaf
provided a new
therapeutic avenue
against diabetes.
Anti-hyperglycaemic Effect of Psidium guajava Extracts in Diabetes Gebrekidan Gebregzabher Asfeha
RRJoCB (2019) 1-9 © STM Journals 2019. All Rights Reserved Page 6
P.K. Rai et
al. 2007
Experimental
Female adult
albino Wistar
rats (210–250 g)
of
approximately
same age group
Streptozotocin
(STZ, 45 mg/kg
bw) in 0.1 M
citrate buffer.
Fruit peel extract
powder of
P.Gujava (100,
200 or 400
mg/kg bw)
Blood glucose
level expressed
as values mean ±
SD of mg/dl
Significant
hyperglycaemic
effect of P.
guajava fruit peel
extract
Fig. 2: The effect of Guava Extracts on Blood Glucose Level- Forest Plot.
After excluding these trials [11, 14, 16], our
results did not significantly change (SMD = -
4.34 (95% CI -6.59; -1.79), 𝑃 = 0.0001) and
heterogeneity became lower (I2 = 83%).
Risk of Bias
Based on the definitions from the Cochrane risk
of bias assessment tool [18], no. study was
judged to have a high risk of bias. All used
random assignment of laboratory animals;
however, most studies did not describe methods
in detail.
Publication Bias
It was difficult to determine if there was
publication bias from the funnel plot because of
the small numbers of studies (Figure 3).
DISCUSSION
This meta-analysis is the first quantitative
review of experimental studies evaluating the
effect of P. guajava extracts on blood glucose
levels. Our meta-analysis of eight studies in
diabetic rats showed that P. guajava extract
differed significantly from distilled water and
we found that administration of guajava
extracts significantly decreased blood glucose
level (SMD = -6.80 (95% CI, -9.71, -3.89; p =
0.00001). This analysis showed very promising
effect of guava extract in terms of significance
when compared to the individual studies. The
statistical significance of one study (p<0.001)
[8] was the most powerful evidence among the
studies that tried to study the anti-diabetic effect
of P. guajava which is very far from p =
0.00001 of this study.
Although, the studies included in the meta-
analysis were small, and there was significant
heterogeneity probably due to variations in
Study or Subgroup
H. M. Mukhtar et al 2006
Deepthi R et al 2012
H. M. Mukhtar et al 2004
Prashant K et al 2009
Kateregga JN et al 2014
Santosh M et al 2015
Abdol H et al 2012
Vini V et al 2012
Total (95% CI)
Heterogeneity: Tau² = 11.15; Chi² = 51.67, df = 7 (P < 0.00001); I² = 86%
Test for overall effect: Z = 4.58 (P < 0.00001)
Mean
138
86.48
95.6
255.7
100.4
129.96
118.88
105
SD
6.1492
6.0374
18.9835
6.8
23.6129
21.3321
29.8519
23.61
Total
5
5
6
6
5
5
10
7
49
Mean
356.8
189.26
354.8
326.9
465.6
522.54
442.5
140.71
SD
4.6063
4.5839
26.528
6.8
63.0571
72.8511
186.353
39.79
Total
5
5
6
6
5
5
10
7
49
Weight
1.8%
6.1%
12.2%
12.8%
14.2%
14.6%
19.2%
19.2%
100.0%
IV, Random, 95% CI
-36.38 [-56.89, -15.86]
-17.32 [-27.15, -7.49]
-10.37 [-15.56, -5.18]
-9.67 [-14.52, -4.81]
-6.93 [-11.02, -2.84]
-6.61 [-10.53, -2.69]
-2.32 [-3.51, -1.13]
-1.02 [-2.16, 0.12]
-6.80 [-9.71, -3.89]
Guava treated No guava treated Std. Mean Difference
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding of participants and personnel (performance bias)
(D) Blinding of outcome assessment (detection bias)
(E) Incomplete outcome data (attrition bias)
(F) Selective reporting (reporting bias)
(G) Other bias
+ + + + + + +
+ + + + + + +
+ + + + + + +
+ + + + + +
+ + –+ + + +
+ + + + + +
+ + + + + +
+ + + + + +
Risk of Bias
A B C D E F G
Std. Mean Difference
IV, Random, 95% CI
-50 -25 0 25 50
Favours [Guava treated] Favours [non treated]
Research & Reviews: Journal of Computational Biology
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ISSN: 2319-3433 (Online), ISSN: 2349-3720 (Print)
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guajava dose, participant characteristics, trial
duration. The analysis of heterogeneity was
done by I2 of 86%, p<0.00001.
Fig. 3: Studies on the Hypoglycaemic Effect of Guava Extracts—Funnel Plot.
The majority of design and participant features
did not significantly alter the pooled
hypoglycaemic effects of P. guajava. In
sensitivity analysis, excluding trial with poorer
methodological quality did not bring a
significant change in the heterogeneity.
There was almost consistent evidence of benefit
from P. guajava in the treatment of diabetes.
Seven of the included studies yielded a
significant effect in the experimental rats.
According to the evaluated studies, P. guajava
extract seems to be well tolerated with rates of
adverse effects and no difference was reported
between intervention and distilled water.
Studies included in the present systematic
review and meta-analysis suggests that
following the treatment of diabetic albino rats
with the with the Psidium guajava extract
showed a considerable reduction in blood
glucose at all dose rates of the extract [9].
Comparative study on the ethanol extract of P.
guajava has shown statistically significant (p<
0.001) and considerable fall in blood glucose
levels in alloxan-induced diabetic rats as
compared with diabetic control [11]. From the
data obtained Alloxan induced diabetic rats
showed a significant reduction in blood glucose
levels (p<0.05) with both dry and fresh leaf
Psidium guajava extract, [12]. Similarly, oral
administration of the ethanol extract of Psidium
guajava led to a significant blood glucose
lowering effect in alloxan-induced
hyperglycaemic rats [14]. The results of study
by Santosh Mazumdar et al. [8] revealed the
antidiabetic activity of selected ethanolic
extracts of Psidium guajava which is
significant at positive control (p<0.01 and
p<0.001). Study by Santosh Mazumdar et al.
[8] supports most of the studies that reports
guajava leaf extract can decrease blood glucose
levels [14, 20- 23]. Treatment with freshly
prepared ethanol extract of Psidium guajava
significantly reduced blood glucose level and
lipid profile levels in diabetic albino rats and
had a similar effect in diabetic patients [13].
Though the antidiabetic activity of ethanolic
extract of Psidium guajava was diverse at
different treated doses in the studies included in
the present Meta anlysis, it supported the
Anti-hyperglycaemic Effect of Psidium guajava Extracts in Diabetes Gebrekidan Gebregzabher Asfeha
RRJoCB (2019) 1-9 © STM Journals 2019. All Rights Reserved Page 8
folklore claim on antidiabetic activity of these
plants.
CONCLUSION
Although a number of included studies
regarding the current topic is limited, the
available evidence is sufficient to support the
anti-hyperglycaemic effect of Psidium guajava
extracts in diabetes mellitus. This meta-analysis
suggests that administration of guava extracts
to diabetic patients may have significant role in
lowering blood glucose level. However,
additional trials involving humans designed
with large sample sizes and with attention to
duration of the blood glucose assessment are
needed. A better understanding of the
mechanisms of the antidiabetic effect P.
guajava and characterization of active
components should also be another aspect of
future investigation.
Abbreviations
SMD: standard mean difference; CI:
confidence interval; I2: hetrogenicity.
Competing Interests
The authors declare that they have no
competing interests.
ACKNOWLEDGEMENTS
The authors acknowledge the immense help
received from the scholars whose articles are
cited and included in references of this
manuscript. The authors are also grateful to
authors / editors / publishers of all those
articles, journals and books from where the
literature for this article has been reviewed and
discussed.
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Volume 8, Issue 1
ISSN: 2319-3433 (Online), ISSN: 2349-3720 (Print)
RRJoCB (2019) 1-9 © STM Journals 2019. All Rights Reserved Page 9
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Cite this Article
Gebrekidan Gebregzabher Asfeha, Birhane
Alem Berihu. Anti-hyperglycaemic Effect
of Psidium guajava Extracts in Diabetes
Mellitus: Systematic review and Meta-
analysis. Research & Reviews: Journal of
Computational Biology. 2019; 8(1): 1–9p.
