Obesity Clinical Trial
Official title:
Effect of Substituting Vegetable Protein for Animal-Protein on Cardiometabolic Risk: A Series of Systematic Reviews and Meta-Analyses of Controlled Feeding Trials to Provide Evidence-Based Guidance for Nutrition Guidelines Development
Vegetarian diets have been associated with a reduced risk of preventable diseases such as type 2 diabetes and cardiovascular disease. These effects may be mediated through direct or indirect pathways. Although the high intakes of nuts, legumes, dietary fibre, whole grains, and unsaturated plant oils have each individually been associated with lower risk of type 2 diabetes and cardiovascular disease, so too has the displacement of red meats, processed meats, and saturated animal fats. One of the most important considerations in moving from animal-based diets to more plant-based diets is the replacement of animal proteins (e.g. meat, fish, dairy, eggs) with vegetable proteins (e.g. legumes, nuts, and seeds). It is unclear whether this particular replacement alone results in advantages for metabolic and cardiovascular health. 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 effect of plant-based protein in exchange for animal protein on blood lipids, glycemic control, blood pressure, body weight, uric acid, markers of non-alcoholic fatty liver disease (NAFLD), and kidney function and injury. The systematic review process allows the combining of the results from many small studies in order to arrive at a pooled estimate, similar to a weighted average, of the true effect. The investigators will be able to explore whether the effects of replacing animal-based protein for plant-based protein hold true across different sexes, age groups, and background disease states and whether the effect depends on the protein source, dose, or background diet. The findings of this proposed knowledge synthesis will help improve the health of Canadians through informing recommendations for the general public, as well as those at risk of heart disease and diabetes.
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), and (7)
kidney function and injury.
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]), and (7) kidney injury and function
(creatinine, urea, creatine clearance, estimated glomerular filtration rate [eGFR],
albumin-to-creatine ratio [ACR], albuminuria, proteinuria).
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 longterm 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.
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Time Perspective: Prospective
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