Check the attached “Results” section attached and then watch the YouTube video to fix it using the notes in the bottom from the professor:
Notes from the professor:
We are missing a lot of the required information here. This section should address how you identified your studies (databases, search terms, filters, etc) and reference the PRISMA diagram. It should also clearly describe the various study designs, along with their findings, in a way which references each study specifically (in-text citations would help with the organization of this). Risk of bias should be addressed. Please review the guidelines we’ve provided in the charts and rubrics from your template. Results
Chausse et al. (2014) conducted a study on the effects of intermittent fasting on enhancing
metabolic indicators. The study included 11 healthy young males with a mean BMI of 25.7. The
patients alternated days of intermittent fasting for 8 to 16 hours with days of consistent exercise
for 8 days. Unexpectedly, the reported weight reduction did not differ considerably, but the
figure below shows that fasting had an impact on metabolic biomarkers. Prior to and following
intermittent fasting, the glucose infusion rate and glucose concentrations during fasting trials
were examined.
The metabolic consequences of intermittent fasting have been investigated in four
experimental studies. Eight to 30 people of normal weight and 10 individuals who were
overweight or obese made up the modest sample sizes. Regarding these participants’ amounts of
physical activity, no information was given. Even though we doubt the therapeutic applicability
of weight reduction in 1-day research, two out of three studies found considerable weight loss.
Participants in the 22-day alternate-day fasting research lost an average of 2.5% of their body
weight (p 0.001). At least one glucocorticoid measure showed a substantial decline in three of
the investigations. The study with overweight and obese people, however, did not find this
difference and, in fact, found that a 1-day total fast had a negative impact on postprandial
glucose and insulin the following day. With conflicting outcomes, this study and another
assessed lipid levels. The postprandial TGs the day after eating were improved, according to the
1-day fasting trial. At the trial’s end point, one study found improvements in fasting TGs and
high-density lipoprotein (HDL) cholesterol but higher levels of low-density lipoprotein (LDL)
cholesterol. Inflammatory indicators significantly improved in one of two studies evaluating
inflammation.
In humans, the study found nine trials of modified fasting. Adult participants in the study,
whose sample sizes ranged from 10 to 107, were all overweight or obese. The fasting
interventions spanned in length from two to six months. Only one of the nine trials established
weekly activity targets. Overall, 7 out of 9 trials (78%) showed statistically important weight
loss, with percentages ranging from 3.2% over 12 weeks compared to the standard situation to
8.0% throughout 8 weeks in a one-arm study. In three of the six investigations, there were
significant declines in immediate insulin dosages, and there were also falls in fasted blood sugar
levels. In three out of eight investigations, the levels of circulating LDL cholesterol significantly
decreased. It’s interesting to note that both PYY (peptide tyrosine tyrosine) levels and
participants’ feelings of fullness rose. Thus, despite certain modifications in gut peptide levels
linked to hunger (such as increased ghrelin), there were net positive effects on sensations related
to lower caloric intake.
Three of the nine experiments discussed here compared simple calorie restriction with
modified fasting protocols (45, 46, and 117). According to the analysis, the weight loss plans
consisted of either a daily caloric limitation of 25% (45, 46) or 1,200–1,500 kcal (117). Weekly
activity targets were established in one of these trials. The studies revealed that intermittent
fasting causes a person’s weight to decrease more than a typical weight loss program. As such, a
typical weight loss program causes a decrease in mean loss of 5.5%, while fasting causes a mean
loss of 9.6%. According to the findings of a weight-loss trial-controlled study, fasting
intermittently resulted in a mean decrease in weight of 6.5%, which is greater than the mean
mass loss of 3.2% brought on by exercising (Eshghinia & Mohammadzadeh, 2013).
References
Chausse, B., Solon, C., Caldeira da Silva, C. C., Masselli dos Reis, I. G., ManchadoGobatto, F. B., Gobatto, C. A., … & Kowaltowski, A. J. (2014). Intermittent fasting
induces hypothalamic modifications resulting in low feeding efficiency, low body
mass and overeating. Endocrinology, 155(7), 24562466.https://academic.oup.com/endo/article/155/7/2456/2423365
Eshghinia, S., & Mohammadzadeh, F. (2013). The effects of modified alternate-day fasting
diet on weight loss and CAD risk factors in overweight and obese women. Journal of
Diabetes & Metabolic Disorders, 12, 1-4. 10.
https://link.springer.com/article/10.1186/2251-6581-12-4
Fann, D. Y. W., Santro, T., Manzanero, S., Widiapradja, A., Cheng, Y. L., Lee, S. Y., … &
Arumugam, T. V. (2014). Intermittent fasting attenuates inflammasome activity in
ischemic stroke. Experimental neurology, 257, 114-119. 10.
https://www.sciencedirect.com/science/article/abs/pii/S0014488614001198
Intermittent Fasting for Improving Metabolic Biomarkers: A Systematic Review
By:
Rawan Taha
ARIZONA STATE UNIVERSITY
JUNE 2023
CHAPTER I
INTRODUCTION
Metabolic syndrome in general and obesity specifically are increasingly common health
challenges in the general population. Metabolic syndrome includes conditions such as obesity,
hypertension, type 2 diabetes, and dyslipidemia and these are risk factors for cardiovascular
disease, the leading cause of death globally (Aleksandrova et al., 2018). The rates of conditions
identified under the metabolic syndrome are generally high in the population and this presents a
major challenge to public health. People with metabolic syndrome and those at risk can be
identified using metabolic biomarkers, inflammation indicators detected even in people who
have not developed the health condition yet (Aleksandrova et al., 2018). Addressing metabolic
biomarkers in preventative efforts can help reduce the rates of the syndrome and associated
health complications.
The research problem identified is the high rates of obesity and other metabolic conditions in
the United States. As of 2020, 42.4% of Americans were obese (Hales et al., 2020). Additionally,
49.64% had hypertension with many more undiagnosed cases (Chobufo et al., 2020). Type 2
diabetes mellitus rates are on the rise and so are rates of dyslipidemia. These conditions
contributing to the leading cause of death are increasingly common in the United States public
and an urgent solution is needed to address the public health problem. Dietary changes are
universal approaches to reducing metabolic biomarkers and this research revolves around the
question of intermittent fasting.
Reduction of metabolic biomarkers in people at risk of developing metabolic syndrome has
been studied by numerous researchers and several have focused specifically on intermittent
fasting. Kunduraci and Ozbek (2019) evaluated the effect of intermittent fasting among adults in
Turkey. They compared the 16:8 (16 hours of fasting and eight hour window for eating) with
continuous energy restriction programs and found that both approaches were effective in
reducing metabolic biomarkers (Kunduraci & Ozbek, 2019). Similarly, Rynders et al. (2019)
found that people who took intermittent fasting experienced a similar weight loss result as those
who undertook continuous energy restrictions. The main difference was that Rynders et al.
(2019) conducted systematic review of the literature. From these research articles, intermittent
fasting presents the same efficacy as continuous energy restriction diets. The studies also
establish the safety of intermittent fasting.
Elsewhere, Cho et al. (2019) found that people who used intermittent fasting achieved a
higher level of weight loss than those who used regular diets or continuous diet restrictions.
Their research was also a systematic review hence collating many research findings from
different studies. Findings from the study by Zouhal et al. (2020) also support these findings. The
researchers found that compared to people who did not practice intermittent fasting during
Ramadhan, those who engaged in intermittent fasting experienced a higher rate of weight loss
and a decrease in interleukin and tumor-necrosis factor (Zouhal et al., 2020). These findings
further extend the current research to outline the potential inflammatory pathways for metabolic
biomarkers associated with not only obesity but also cancer. The findings that intermittent
fasting can reduce metabolic biomarkers and contribute to weight loss have also been
corroborated in a Polish study involving older women 65 years and older (Domaszewski et al.,
2020). The researchers compared the intermittent fasting 16:8 method with the maintenance of
previous feeding habits and concluded that the former was superior in weight loss and reduction
of body fat percentage (Domaszewski et al., 2020). From these studies, it is seen that intermittent
fasting may be superior to usual diets and continuous energy restriction in weight loss and
management of some metabolic biomarkers.
Other studies have focused on intermittent fasting combined with other interventions and 12hour fasting. Jamshed et al. (2022) evaluated the effectiveness of 12:12 intermittent fasting and
found that it resulted in a reduction in weight loss but not body fat. The study was conducted
with obese adults in Birmingham, Alabama. Hottenrott et al. (2020) combined intermittent
fasting with exercise and alkaline supplements. In both intermittent fasting and control groups,
alkaline supplements were associated with better performance running. The intermittent fasting
group was more effective in weight reduction (Hottenrott et al., 2020). These findings align with
other research findings on intermittent fasting and obesity.
The current research outlines the importance of intermittent fasting but is still deficient. Most
of the research focuses entirely on body fat and weight as key biomarkers. Research on other
biomarkers is scarce. Moreover, in most of the research articles reviewed, the studies were either
short-lived or had a small and non-generalizable sample. Some studies were either limited to
women or men which makes them hard to generalize to the public. Also, little research has been
conducted on other metabolic biomarkers such as blood pressure, glucose, and cholesterol.
Therefore, a gap exists in the research on intermittent fasting and its effectiveness in controlling
metabolic biomarkers. Filling this gap presents an opportunity to determine the efficacy of
intermittent fasting in reducing the rates of metabolic syndrome and conditions in the general
public.
Purpose of Study
The purpose of this study will be to determine the effectiveness of the intermittent fasting
16:8 method on decreasing metabolic biomarkers in overweight and obese individuals. The
research will determine whether intermittent fasting can reduce the risk of metabolic syndrome
in people who are already identified as overweight or obese.
Research Aims and Hypotheses
Aim: To determine the effectiveness of the intermittent fasting 16:8 method in reducing
metabolic biomarkers in overweight people.
Null Hypothesis: Compared to the maintenance of usual dietary habits intermittent fasting is not
associated with a significant change in metabolic biomarkers in overweight people.
Alternative Hypothesis: Intermittent fasting reduces metabolic biomarkers in overweight
people.
Definitions
Intermittent fasting: A dietary habit where the individual avoids any food intake for 16
hours per day and has an 8-hour window to eat (Cho et al., 2019).
Metabolic biomarkers: Biological indicators of inflammation that include waist circumference,
blood glucose, blood pressure, triglycerides, and cholesterol levels (Aleksandrova et al., 2018)
Overweight people: People who have a body mass index (BMI) of 25- 29.5 kg/m2
Delimitations and Limitations
The study will be limited to healthy members of the public who have not been diagnosed
with any chronic or terminal illness. It will also be limited to people aged between 18 and 65
years old (adults excluding older adults) with a BMI of 25 and above. The study will be limited
to people living in an urban center in the United States and those who can provide informed
consent and be available for follow-up. The main limitation of the study is that it may not be
generalized to other cities or countries due to the possible unique dietary habits of people in this
one city.
CHAPTER II
EVIDENCE ANALYSIS
A review of the literature on Intermittent Fasting for Improving Metabolic Biomarkers is
presented in the following evidence analysis tables. The quality of each study was assessed
along with the type of study, the demographics of the participants, the interventions, and major
research findings. In addition, each table delineates the strengths and limitations of each study.
The table was divided into subsections of the author, study design, participant details,
methodology, findings, and strengths and limitations.
Author and
Study
Participant
Method Details
Findings
Strengths and
location
Design
Details
Methods in your
Include all
limitations
Include first
Randomized
Number,
own words –
appropriate
Consider
author last
Control,
gender, age,
length of study,
outcomes, p-
population size,
name,
Experimenta
other identifiers
exact
values for
study design,
location (U.S,
l, Cross-
intervention
each and if it
participants,
Italy etc.) and
Sectional,
details, what
reached
length of study
include a
Cohort.
were they
statistical
etc.
superscript
Do not use
looking to
significance
citation
other
measure.
number.
systematic
reviews or
metaanalyses.
Jamshed, H.,
Randomized
Adults aged 25
Conducted
Among the 59
One strength of
Steger, F. L.,
clinical trial
to 75 years with
between August
completers, it
the study is that
Bryan, D. R.,
obesity and who
2018 and April
was discovered it collected
Richman, J. S.,
received weight- 2020
that eTRE+ER
firsthand
Warriner, A.
loss treatment
14-week study
was more
information
H., Hanick, C.
through the
Intervention
effective for
regarding the
entailed giving
losing body fat
experience of
J., & Peterson,
Weight Loss
participants
and trunk fat
the participants
C. M. (2022)
Medicine Clinic
weight loss
than CON+ER. regarding
We screened
treatment mainly
obesity and
656 people and
energy restriction
overweight.
enrolled 90
and it was
participants
randomized to
The limitations
eTRE plus ER
of the study is
and the control
short duration,
group for 8 hours
use of self-report
and more than 12
to assess patient
hours
condition.
respectively.
Cho, Y.,
Randomized
No participants
The method
The findings
One limitation
Hong, N.,
controlled
were involved
entailed selecting
show that after
is that the
Kim, K. W.,
trials and
because it was a
articles with
fasting for 12
studies used
Cho, S. J.,
controlled
secondary
periodic fasting,
hours lipolysis
were diverse,
Lee, M., Lee,
clinical trials
literature
periodic data, and
starts in the fat
which makes it
analysis
modified fating
tissues.
to have a broad
and evaluating the Skipping
scope that is not
trend in these
breakfast is
narrowed.
articles.
associated with
Y. H., & Lee,
B. W. (2019)
increased
stress.
Chobufo, M.
Cross-
5000 persons in
The methods
D., Gayam, V., sectional
15 counties per
entails conducting show that
that blood
Soluny, J.,
year.
a NHANES by
education level
pressure
the CDC. The
determined
readings were
Rahman, E.
study design
The findings
One strength is
U., Enoru, S.,
records helped to
one’s level of
done at the same
Foryoung, J.
get systolic and
hypertension.
time. One
B., & Nfor, T.
diastolic blood
Increasing age,
limitation is that
(2020)
pressure readings
obesity, being
two years’ time
of participants.
a man, and
period is very
those with
small or
diabetes were
studying
at risk of
changes in
hypertension.
habits.
Randomized
group of 45
The interventions
The findings
One limitation
Control
women over 60
entailed assessing
showed that
of the study is
years
and tracking the
the body mass
that it entailed
M., Pakosz, P.,
participants’ body
of the
few participants,
Bączkowicz,
composition and
experimental
which cannot
D., &
BMI. It also
group reduced
help in drawing
Sadowska-
entailed
by 2 kg.
reputable and
Krępa, E.
measuring the
Skeletal body
reliable findings.
(2020)
mental state and
mass did not
ankle-branchial
change
index.
significantly.
Domaszewski,
P., Konieczny,
Hales, C. M.,
Cross-
Adults aged 20
1999-2000
The study
One strength of
Carroll, M. D.,
sectional
and over
through 2015-
identified a
the study is the
2016
significantly
use of bulk
Ogden, C. L.
increasing
historical data.
(2020)
trend in obesity
Fryar, C. D., & study design
One limitation is
reliance on
historical data,
whose
authenticity and
reliability cannot
be determined
Aleksandrova,
Information is Both adults and
The time of the
The study
One strength is
K.,
from
children with
study is not
identified the
that the research
Mozaffarian,
secondary
obesity
specified as most
role of
is broad and
D., & Pischon,
sources
information is
biomarkers in
comparative.
from secondary
obesity related
One weakness is
sources
cases and their
that most of the
association in
information used
cardiometaboli
is not firsthand.
T. (2018).
c diseases.
Hottenrott, K.,
Clinical trials
80 overweight
All participants
The study
The advantages
Werner, T.,
subjects of age
were tested for 12
determined the
of this study are;
Hottenrott, L.,
45.5 ± 7.8 years
weeks
combined
It took a short
Meyer, T. P.,
effects of IF,
reasonable time
& Vormann, J.
exercise
and the data was
(2020).
training and
first hand hence
alkaline
very accurate.
supplementatio
n in
overweight
participants on
body
composition
and running
performance
Kunduraci, Y.
Randomized
Metabolic
E., & Ozbek,
controlled
H. (2020).
trial
12 weeks .
The study
One limitation is
syndrome
found out that
the study was on
patients, aged
technique used
metabolic
18–65 years in
to achieve
syndrome
Istanbul Turkey
energy
patients hence
restriction, in
hot giving
either
accurate data to
intermittent or
be used for
continuous,
healthy people.
alleviates the
metabolic
syndrome
biomarkers
activated by
weight loss.
Rynders, C.
Randomized
A., Thomas, E. trials
A., Zaman, A.,
Pan, Z.,
Catenacci, V.
A., &
11 adults with
overweight or
obesity (BMI ≥
25 kg/m2)
8 weeks
The available
one limitation of
evidence
this research is
indicates that
that it uses few
Intermient
participants.
Energy
Restrictions
Melanson, E.
paradigms
L. (2019).
cause equal
weight
reduction when
compared to
Continuous
Energy
Restrictions,
with no
changes in
weight or body
fat loss across
groups being
observed in 9
out of 11
studies
assessed.
Zouhal, H.,
Experimental
28 males with
Bagheri, R.,
method
obesity
30 days
The results of
One advantage
this study show of this study is
Ashtary-
that fasting
that it was
Larky, D.,
during
carried out
Wong, A.,
Ramadan
during a time
Triki, R.,
reduced
when fasting
Hackney, A.
systemic
was mandatory
C., &
inflammatory
hence increasing
Abderrahman,
biomarkers in
data accuracy.
A. B. (2020).
obese males
and there was
no detrimental
effects on the
indicators of
liver and renal
function.
Ogden, C. L.,
National
9120
Between 2003-
According to
The advantage
participants
2012 (10 years)
the
of this article is
Kit, B. K., &
study, there
that it used large
Flegal, K. M.
have been no
amount of data
(2014)
significant
Carroll, M. D., survey.
changes in
hence being
obesity
more accurate.
prevalence in
youth or adults
between 20032004 and
2011-2012.
Obesity
prevalence
remains high
and thus it is
important to
continue
surveillance.
Ravussin, E.,
Clinical trial
Meal-timing
One limitation
interventions
of this study is
Poggiogalle,
facilitate
that it took a
E., Hsia, D. S.,
weight loss
very short time
& Peterson, C.
primarily by
hence may be
M. (2019).
decreasing
inaccurate.
Beyl, R. A.,
11 overweight
4 days
adults
appetite rather
than by
increasing
energy
expenditure
Harvey, J.,
Randomized
Study 1; 44
6 months and 4
Howell, A.,
Clinical trials
women on
months
Morris, J., &
Intermittent
Energy
According to
this study,
intermittent
dieting could
be an effective
way to achieve
One limitation
about this study
is that it requires
Harvie, M.
Restrictions for
(2018).
6 months
Study 2; 72
women on two
weight loss
without having
to worry about
calorie
compensation.
more time for
The study
concluded that
High-calorie
breakfasts are
advantageous
and may be a
practical
substitute for
managing
obesity and
metabolic
syndrome at
dinnertime.
The advantage
From the
The advantage
credible results.
types of
Intermitent
Energy
Restrictions for
4 months
Jakubowicz,
Randomized
Overweight and
D., Barnea,
experiments
obese women
M., Wainstein,
(BMI 32.4 ± 1.8
J., & Froy, O.
kg/m2) with
(2013
metabolic
12 weeks
syndrome
85 obese women 12 months
of this study is
that it specific
on the research
population
hence its
findings are
useful for that
population.
Viegener, B.
Randomized
J., Renjilian,
controlled
study, the
about this study
D. A.,
trials
group that did
is that it
McKelvey, W.
intermittent
compares two
F., Schein, R.
fasting lost
populations over
L., Perri, M.
weight faster
different lengths
G., & Nezu, A.
than those that
of time.
M. (1990).
did regular
treatment.
Acosta-
Controlled
8-week-old male 2 weeks
From the
One limitation is
Rodríguez, V.
experiment
mice
study,
the time
A., de Groot,
concentrating
allocated was
M. H., Rijo-
their food
little hence can
Ferreira, F.,
intake and
be led to
Green, C. B.,
suddenly
inconclusive
& Takahashi,
boosting their
results.
J. S. (2017
wheel-running
activity during
the rest period,
mice under
Caloric
Restriction
self-imposed a
temporal
component,
exposing
previously
unappreciated
linkages
between
feeding,
metabolism,
and behavior.
Hoddy, K. K.,
Random trials 74 obese people
Gibbons, C.,
between the age
Kroeger, C.
of 25-65 years.
M.,
8weeks
These results
imply that the
effectiveness
of an 8-week
ADF regimen
One limitation
about this study
is that it is
Trepanowski,
J. F.,
Barnosky, A.,
Bhutani, S., …
& Varady, K.
A. (2016).
Julia, C.,
Cohort study
Péneau, S.,
46435 people
10 years
above 18 years
for weight loss
may be
influenced by
the absence of
a
compensatory
rise in hunger
along with an
increase in
fullness
sensations.
population
From the
One strength of
study, when
this research is
specific
Andreeva, V.
loosing weight, that it takes a
A., Méjean,
it is essential to long time, hence
C., Fezeu, L.,
maintain a
being more
Galan, P., &
dietary
accurate.
Hercberg, S.
balance.
(2014).
Horne, B. D.,
A systemic
Both male and
Literature from
There are few
Limitations of
Muhlestein, J.
review of
female
2015
literature
this research is
B., &
public
sources on the
that it is not
Anderson, J.
literature on
randomized
conclusive.
L. (2015).
randomized
clinical trials
clinical trials
hence need for
more research
Carter, S.,
Randomized
137 men and
Clifton, P. M.,
noninferiority
women with
type 2 diabetes, this research is
type 2 diabetes
intermittent
that it has
calorie
updated
& Keogh, J. B. trial
(2018
12 months
In patients with One strength of
restriction is
supporting
comparable to
evidence which
continuous
makes it valid.
energy
restriction in
terms of
effectiveness in
lowering
HbA1c.
CH III
METHODS
This systematic review was conducted based on the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) standards, which guides in the selection of
articles for use in information extraction. PRISMA helped in assessing, locating, and
incorporating the information that is available into the report. It is worth noting that the PICO
approach that entails the use of population, intervention, comparison, and outcome of treatment
intervention. The PICO approach helped to develop a model as outlined in the table below. The
study was used to determine the impact of intermittent fasting of about 12 to 16 hours could help
the obese and overweight to manage their weight. The impact of the intervention was traced
across several articles, which showed the impact of intermittent fasting on the metabolic activity
rate. The rate of effectiveness of intermittent fasting was evaluated among obese and overweight
individuals that participated in the studies. It is worth noting that the studies that were only
included were those that were obese or overweight with a BMI of 25 or above.
Throughout this systematic review, the flow diagram of PRISMA located below,
determined the guidelines and workflow that was used to analyze and review each piece of
literature. The flow diagram also contains information about how each piece of literature was
incorporated into this review in terms of locating, assessing, and appropriateness. Research
studies that fell under the categories of either meta-analyses or systematic reviews were used to
find material or data that was capable of meeting the criteria of inclusion. However, metaanalyses and systematic reviews were not included in finding necessary data or information for
inclusion and were excluded from this review.
The core search terms used in the systematic review include “obese”, “obesity”,
“intermittent fasting”, “dieting,” fasting and many others. The major databases that were used
include PubMed, Google Scholar, and the Cumulative Index to Nursing and Allied Health
Literature (CINAHL).
The research articles that were used in this review had to meet the standards in The
Academy of Nutrition and Dietetics (AND) Quality Criteria Checklist for Primary Articles. For
studies that passed the checklist, the studies were incorporated into the Academy of Nutrition
and Dietetics (AND) Evidence Analysis Table (Chapter 2). The tables outlined each research
study and summarized the outcomes. It is worth noting that the tables provided a methodical
arrangement of each research study by outlining the author(s), year of publication, sample
characteristics, treatment and control groups, intervention/exposure examined, results, and
strengths and limitations.
PICO Inclusion Criteria
PICO
Potential Search Terms
Population:
Those with obesity and overweight (of BMI 25 or above)
Intervention:
Intermittent fasting for 8-16 hours.
Comparison (you may not
have):
Those not fasting but following a hypocaloric diet
Outcome(s):
Reduced body weight and BMI.
Search Terms Used for Systematic Review and Evidence Analysis
Database
Date of search
Search String
Filters Used
Numb
er of
result
s
Numb
er of
result
s after
remov
ing
duplic
ates
After
reviewin
g for
quality,
articles
kept
PubMed
4-June-23
“overweight”,
“obese” and
intermittent fasting
5 years, clinical
trial, randomized
controlled trial
36
34
21
Google
Scholar
5-June-23
“overweight”,
“obese” and
intermittent fasting
5 years, clinical
trial, randomized
controlled trial
22,700
11,470
15
CINAHL
15-June-23
“overweight”,
“obese” and
intermittent fasting
5 years, clinical
trial, randomized
controlled trial
97
80
9
Methods
PRISMA 2009 Flow Diagram
Records identified through
database searching
(n = )
Additional records identified
through other sources
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