Background: Vegetarian diets have been associated with a reduced risk of preventable
cardiometabolic diseases such as type 2 diabetes and cardiovascular disease. It is
unclear whether the replacement of animal protein with vegetable protein has
cardiometabolic advantages.
Objectives: To improve evidence-based guidance for dietary guidelines and health claims
development, we propose to conduct a series of systematic reviews and meta-analyses of
the effects of plant-based protein in replacement for animal protein on cardiometabolic
risk factors including: (1) blood lipids, (2) glycemic control, (3) blood pressure, (4)
body weight, (5) uric acid, (6) markers of non-alcoholic fatty liver disease (NAFLD), (7)
kidney function and injury, and (8) CRP as an inflammation marker.
Design: The planning and conduct of the proposed meta-analyses will follow the Cochrane
handbook for systematic reviews of interventions. The reporting will follow the Preferred
Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials
will be searched using appropriate search terms.
Study selection: Long term (≥ 3 weeks), randomized, controlled trials that investigate
the effect of exchange of plant proteins for animal proteins on the outcomes previously
mentioned in humans will be included. Studies that have an acute feeding design, are not
randomized, or lack a suitable control will not be included. Both isocaloric and
non-isocaloric studies will be included.
Data extraction: Independent investigators (≥2) will extract information about study
design, sample size, subject characteristics, pulse form, dose, follow-up, and the
composition of the background diets. Mean±SEM values will be extracted for all outcomes.
Standard computations and imputations will be used to derive missing variance data. Risk
of bias and study quality will be assessed using the Cochrane Risk of Bias Tool and the
Heyland Methodological Quality Score (MQS), respectively.
Outcomes: The proposed syntheses will each assess a set of outcomes related to a
different area of cardiometabolic risk: (1) blood lipids (established therapeutic targets
for the prevention of cardiovascular disease - LDL-C, apo-B, non-HDL-C), (2) glycemic
control (glycated blood proteins, fasting glucose and insulin, and Homeostasis model
assessment of insulin resistance [HOMA-IR]), (3) body weight, (4) uric acid, (5) blood
pressure (systolic BP and diastolic BP), (6) markers of NAFLD (imaging and spectroscopy
endpoints of liver fat and biomarkers of hepatocellular injury [transaminases]), (7)
kidney injury and function (creatinine, urea, creatine clearance, estimated glomerular
filtration rate [eGFR], albumin-to-creatine ratio [ACR], albuminuria, proteinuria) and
(8) inflammation marker (CRP).
Data synthesis: Separate pooled analyses will be conducted for each area of
cardiometabolic control using the Generic Inverse Variance method. Random-effects models
will be used even in the absence of statistically significant between-study
heterogeneity, as they yield more conservative summary effect estimates in the presence
of residual heterogeneity. Exceptions will be made for the use of fixed-effects models
where there is <5 included trials irrespective of heterogeneity or small trials are being
pooled with larger more precise trials in the absence of statistically significant
heterogeneity. Paired analyses will be applied to all crossover trials. Heterogeneity
will be tested by Cochran's Q statistic and quantified by the I2 statistic. Sources of
heterogeneity will be explored by sensitivity and subgroup analyses. A priori subgroup
analyses will include study design, dose, vegetable protein type, animal protein
comparator, follow-up, baseline values, and study quality. Significant unexplained
heterogeneity will be investigated by additional post hoc subgroup analyses (e.g. age,
sex, level of feeding control [metabolic, supplemented, dietary advice], washout in
crossover trials, energy balance of the background diet, composition of the background
diet [total % energy from fat, carbohydrate, protein], change in cholesterol intake,
change in glycemic index, etc.). Meta-regression analyses will assess the significance of
subgroups analyses. Publication bias will be investigated by the inspection of funnel
plots and application of Egger's and Begg's tests.
Knowledge translation plan: Results will be disseminated through traditional means such
as interactive presentations at local, national, and international scientific meetings
and publication in high impact factor journals. Innovative means such as webcasts with
e-mail feedback mechanisms will also be used. Knowledge Users will act as knowledge
brokers networking among opinion leaders and different adopter groups to increase
awareness at each stage. Four Knowledge Users will also participate directly as members
of nutrition guidelines committees. Target adopters will include the clinical practice,
public health, industry, research communities, and patient groups. Feedback will be
incorporated and used to guide analyses and improve key messages at each stage.
Significance: The proposed project will demonstrate that the improvement in long term
health measures. This demonstration will aid in knowledge translation related to the
effects of plant proteins on cardiometabolic risk, kidney disease management, and
metabolic syndrome, strengthening the evidence-base for dietary recommendations and
health claims and improving health outcomes through informing healthcare providers and
patients, stimulating industry innovation, and guiding future research.
