Materials and methods
Search strategy
Guidelines of the Preferred Reporting Items for Systematic
Reviews and Meta-analysis (PRISMA) were considered in the
current review. Data were searched in PubMed/MEDLINE,
Scopus, Web of Science, and Cochrane library from inception
up to 27 August 2022 for all relevant published articles. The
search was applied using the following MESH and non-MESH
terms: (“green tea” OR “green tea extract” OR “catechin”
OR “catechins” OR “Camellia sinensis” OR “Thea sinensis”)
AND (Intervention OR “Intervention Study” OR “Intervention
Studies” OR “controlled trial” OR randomized OR randomized
OR random OR randomly OR placebo OR “clinical trial” OR
Trial OR “randomized controlled trial” OR “randomized clinical
trial” OR RCT OR blinded OR “double blind” OR “double
blinded” OR trial OR “clinical trial” OR trials OR “Pragmatic
Clinical Trial” OR “Cross-Over Studies” OR “Cross-Over” OR
“Cross-Over Study” OR parallel OR “parallel study” OR “parallel
trial”) (Supplementary File 1). No restriction was considered on
time and language of publications. Reference lists of the related
papers were also manually checked to prevent missing any
pertinent papers. In addition, duplicate citations were removed
after including all searched articles in the Endnote software.
Inclusion criteria and exclusion criteria
The inclusion criteria for the present review are listed as
follows: (a) randomized clinical trials (RCT) (either parallel
or cross-over design), (b) investigations on adult population
(age18y), (c) studies that administered any types of green
tea supplement, (d) clinical trials with at least one week’s of
the follow-up period, and (e) articles that provided sufficient
information on the baseline and final levels of cardiovascular
risk factors or represented required information for calculation
of those effect sizes. In the case of more than one published
article for one dataset, we included the most complete one.
If there were clinical studies with an extra intervention
group, we considered them as two separate investigations. The
following criteria were also considered to exclude studies: (a)
experimental, (b) those studies with a cohort, cross-sectional,
and case-control design, (c) review articles, (d) ecological
investigations, (e) clinical trials with no random allocation and
no control group, and (f) investigations carried out on children
and adolescents.
Data extraction
Data extraction including author’s name, publication year
and the country where the study was performed, participants’
health condition, age, sex, body mass index (BMI), study
design (parallel/cross-over), number of contributors in each
study group, dose, and duration of prune administration,
post-intervention mean and standard deviation (SD) of
cardiovascular risk factors in both prune and control groups,
post-intervention mean (SD) changes in cardiovascular risk
factors in both study groups, and confounders adjusted in the
analysis was completed by two researchers independently. If
standard errors (SEs) or interquartile ranges were reported, we
converted them to SDs. In addition, a chief researcher settled
any controversies.
Quality assessment
We systematically evaluated the bias in the included trials
by using the Cochrane Collaboration’s tool risk of bias criteria
(26). Two independent investigators assessed the quality details
of the studies in seven domains including random sequence
generation, allocation concealment, reporting bias, performance
bias, detection bias, attrition bias, and other sources of bias based
on the Cochrane Handbook for Systematic Reviews. To assess
each domain, the terms “Low”, “High”, or “Unclear” was applied
(Table 2).
Statistical analysis
The overall effect sizes were computed as mean differences
and SDs of glycemic markers and CRP between prune and
control groups. All data were inserted as means ± SD. It should
be noted that in studies where findings have been reported
as SEs and interquartile ranges, means ± SD was calculated
by statistical computations. The effect sizes were indicated
as standardized mean difference (SMD) and 95% confidence
interval (CI). The random-effects model considering between-
study variations was chosen to acquire the overall effect sizes.
Heterogeneity between studies was evaluated by I-square (I2
)
index and I250% was assumed as considerable between-
study heterogeneity (27). Subgroup analysis was performed
to find any probable sources of heterogeneity based on the
predefined variables including duration of supplementation
(≥ 12 vs.12 weeks), the dose of GTE (≥ 1,000
vs.1,000 mg/d), sex (male, female, and both), baseline TG
(≥ 150 vs.150 mg/dl), TC (≥ 200 vs.200 mg/dl), LDL
(≥ 100 vs.100 mg/dl), HDL (≥ 50 vs.50 mg/dl), FBS
(≥ 100 vs.100 mg/dl), and HbA1c (≥ 6.5 vs.6.5%),
past medical history of type 2 diabetes mellitus (T2DM; Non-
T2DM patients and T2DM patients), and baseline values of BMI
(normal, overweight, and obese), DBP (≥ 80 vs.80 mmHg)
and SBP (≥ 130 vs.130 mmHg). Fractional polynomial
modeling was applied to detect the non-linear effects of green tea
dosage (g/d) on each variab