Data synthesis and statistical analysis:
A meta-analysis was performed using mean differences (MDs) and their
standard deviations (SDs) for CRP (mg/l), or these values were computed
using the data were extracted from included articles. Based on Cochrane
Handbook (40) the mean change from
baseline in the CRP concentrations and its SD for both intervention and
comparison groups were used to compute the effect size. Hozo method
(41) was used to estimate mean of CRP
concentrations if median or range was reported. Moreover, SDs were
computed by multiplying standard errors (SEs) by square root of the
sample size in studies which reported SEs. The summary of the overall
effects and heterogeneity was estimated by using the DerSimonian and
Laird random effects model (42), if a
heterogeneity test was statistically significant. Statistical
heterogeneity of intervention effects was measured using Cochran’s Q
test and I-squared statistic. Heterogeneity was considered substantial
if p-value for the Cochran’s Q test was ≤0.10 or value of the I-squared
statistic was ≥50% (43).
Subgroup analyses was performed to explore sources of heterogeneity
which included soy isoflavones dosage or soy isoflavones plus soy
protein dosage, study design, intervention duration, mean of baseline
CRP concentration, health status of participants, sample size,
geographical region, age of participants, body mass index (BMI), quality
assessment of articles and year of study publication. Meta-regression
was used to examine the impact of moderator variables on MDs and compute
adjusted effect of soy isoflavones dosage and soy isoflavones plus soy
protein dosage on MDs after controlling for other variables. Visual
inspection of Begg’s funnel plot, Begg’s rank correlation, and Eggar’s
weighted regression tests were employed to evaluate the presence of
publication bias in the meta-analysis
(44, 45).
Sensitivity analysis was conducted using the leave-one out method to
specify the effect of each study on the overall effect size. Ninety-five
percent confidence intervals were provided for all calculated effect
sizes. All analyses were conducted using STATA 15 software (Stata Corp,
Collage Station, TX).