Cardiovascular DiseasesNCT05637866
SRMA of the Effect of Soy Milk vs Cow's Milk on Cardiometabolic Outcomes
An observational study of Cardiovascular Diseases and Lipid Disorder, run by University of Toronto at 1 site in Canada.
Trial summary
Dairy consumption has shown associations with decreased incidence of cardiometabolic diseases. With the growing interest in plant-based eating, and the mounting evidence for the cardiovascular benefits of plant forward diets, national dietary guidelines have pivoted away from promoting exclusive daily dairy… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Lipid Disorder, Metabolic Disease
- What is being tested?
- Soy milk
- How many people
- 1 participants
- Where
- 1 siteCanada
- Study dates
- 1 Oct 2022to 1 Oct 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults with or without cardiovascular risk factors
Who may be able to join
- Randomized controlled trials
- Soy milk intervention
- Cow's milk comparator
- Intervention duration ≥ 3 weeks
- Data for at least 1 outcome
Who cannot join
- Non-human studies
- Observational studies
- Acute single-bolus feeding studies
- Participants < 18 years of age
- Multimodal interventions
- Lack of suitable comparator
- Intervention duration < 3 weeks
- No viable outcome data
Trial locations and contacts
1 site in 1 country.
Canada1 site
Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
Toronto, Ontario, M5C 2T2
About this study
Official title: Effect of Soy Milk for Cow's Milk on Intermediate Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Dairy consumption has shown associations with decreased incidence of cardiometabolic diseases. With the growing interest in plant-based eating, and the mounting evidence for the cardiovascular benefits of plant forward diets, national dietary guidelines have pivoted away from promoting exclusive daily dairy consumption. Soymilk is the most nutritionally comparable non-dairy plant-based alternative to cow's milk. Although the DGA, Health Canada, and various pediatric associations recognize fortified soymilk as the only non-dairy alternative equivalent to cow's milk and it can carry an approved health claim for coronary heart disease risk reduction based on the soy protein that it contains, soymilk is classified by the NOVA classification as an ultra-processed food (the opposite of the classification of cow's milk as an unprocessed or minimally processed food). To be an acceptable iso-sweet alternative to cow's milk, soymilk is also often sweetened with sucrose, which is designated as an added sugar, whereas the lactose that sweetens cow's milk is not (despite lactose in cow's milk being present in quantities that are double that of sucrose in soymilk products designed to be iso-sweet analogues of cow's milk). With near universal recommendations from major public health authorities to reduce the intake of both ultra-processed foods and added sugars and the FDA proposing to update its "healthy" claim criteria to limit added sugars, the role of soymilk as a "healthy" non-dairy alternative to cow's milk is in serious question. The effect of soy protein on other cardiometabolic outcomes is also unclear. To address this question and better inform health claims and guideline development, the investigators will conduct a systematic review and meta-analysis of randomized controlled trials of the effect of soy protein as soy milk, in substitution for cow's milk, on various intermediate cardiometabolic mediators.
Read the detailed description
RATIONALE. Soymilk and other processed soy products are at an important crossroads. Although the DGA, Health Canada, and various pediatric associations recognize fortified soymilk as the only non-dairy plant milk alternative equivalent to cow's milk and it can carry an approved health claim for coronary heart disease risk reduction based on the soy protein that it contains, soymilk is classified by the NOVA classification as an ultra-processed food (the opposite of the classification of cow's milk as an unprocessed or minimally processed food). To be an acceptable iso-sweet alternative to cow's milk, soymilk is also often sweetened with sucrose, which is designated as an added sugar, whereas the lactose that sweetens cow's milk is not (despite lactose in cow's milk being present in quantities that are double that of sucrose in soymilk products designed to be iso-sweet analogues of cow's milk). With near universal recommendations from major public health authorities to reduce the intake of both ultra-processed foods and added sugars and the FDA updating its "healthy" claim criteria to limit added sugars, the role of soymilk as a "healthy" non-dairy alternative to cow's milk is in serious question.
OBJECTIVES. The objective is to conduct a systematic review and meta-analysis of randomized controlled trials to assess the effect of soymilk in substitution for cow's milk and its modification by added sugars (sweetened versus unsweetened) on established cardiometabolic risk factors of clinical and public health importance and assess the certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system.
DESIGN. The systematic review and meta-analyses will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA).
DATA SOURCES. Medline, Embase, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by manual searches of references of included studies.
STUDY SELECTION. Randomized controlled trials of ≥3-weeks assessing the effect of soy milk in substitution for cow's milk on cardiometabolic risk factors will be included.
DATA EXTRACTION. Two or more investigators will independently extract relevant data. Authors will be contacted for additional information and any missing data will be computed/imputed using standard formulae.
RISK OF BIAS. Two or more investigators will independently assess risk of bias using the Cochrane Risk of Bias Tool 2. All disagreements will be resolved by consensus.
OUTCOMES. Outcomes will include changes in established markers of (1) adiposity (body weight, BMI, body fat, waist circumference, abdominal fat); (2) glycemic control (HbA1c, fasting plasma glucose (FPG), fasting plasma insulin (FPI), plasma glucose area under the curve (AUC), and 2h plasma glucose (2hPG)); (3) blood lipids (LDL-cholesterol, non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides); (4) blood pressure (systolic blood pressure and diastolic blood pressure); (5) non-alcoholic fatty liver disease (NAFLD) (intrahepatocellular lipids (IHCL), alanine transaminase (ALT), aspartate aminotransferase (AST), and fatty liver index (FLI)); (6) inflammation (C-reactive protein (CRP)); (7) renal function and structure (creatinine, creatinine clearance (CrCl), glomerular filtration rate (GFR), estimated GFR (eGFR), albuminuria, albumin-to-creatinine ratio (ACR)); and (8) and uric acid.
DATA SYNTHESIS. Data will be pooled using the Generic Inverse Variance method for each outcome. As one of our primary research questions relates to the role of added sugars as a mediator in any observed differences between soy milk and cow's milk, we will stratify results by the presence of added sugars in soy milk (sweetened versus unsweetened) and assess effect modification by this variable on pooled estimates. 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. Fixed-effects models will only be used where there is <5 included studies. Paired analyses will be applied for crossover design trials. Heterogeneity will be assessed (Cochran Q statistic) and quantified (I2 statistic). Sources of heterogeneity will be explored (if there are >=10 trial comparisons) by sensitivity analyses and a priori subgroup analyses (dose, comparator, follow-up, baseline levels, design, age, health status, funding and risk of bias). Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. Publication bias will be assessed (if there are >=10 trial comparisons) by inspection of funnel plots and the Egger and Begg tests. Adjustment for evidence of funnel plot asymmetry or small study effects will be conducted by the Duval and Tweedie trim-and-fill method.
GRADE ASSESSMENT. To assess the certainty of the evidence, the investigators will use the GRADE system, an evidence-based grading system adopted by >100 organizations (http://www.gradeworkinggroup.org/). It grades the evidence as high, moderate, low or very low quality based on the study design and a series of downgrades (risk of bias, imprecision, inconsistency, indirectness, publication bias) and upgrades (large magnitude of the effect, dose-response gradient, and attenuation by confounding). The investigators will follow the GRADE handbook (https://gdt.gradepro.org/app/handbook/ handbook.html) and use the GRADEpro GDT (gradepro.org) software.
ADD-ON SYNTHESIS (LACTOSE VERSUS ADDED SUGARS) To interrogate the question of the role of added sugars as a mediator of any observed effects of sweetened soymilk, we will conduct a sub-synthesis (a separate systematic review and meta-analysis of RCTs) of the effect of lactose (which is not considered an added sugar) versus added sugars (sucrose, HFCS, or fructose) irrespective of matrix (all comparisons with a matched matrix will be included). We will follow the same protocol and analysis plan as that for the main analysis.
KNOWLEDGE TRANSLATION PLAN. The investigators will follow the Ottawa model of Research for knowledge translation. The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact journals. Target audiences will include public health and clinical communities with an interest in nutrition and cardiometabolic diseases. Feedback will be incorporated and used to improve public health messages and key areas for future research will be defined. The PIs will network among opinion leaders to increase awareness and participate directly in the development of future guidelines.
SIGNIFICANCE. Both proposed projects will aid in knowledge translation related to the role of soy milk as a "healthy" non-dairy alternative to cow's milk, strengthening the evidence-base for guidelines development in the U.S., Canada, Europe, and beyond and improving health outcomes, by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.
- Conditions
- Cardiovascular Diseases, Lipid Disorder, Metabolic Disease, Non-Alcoholic Fatty Liver Disease
- Being tested
- Soy milk
- Keywords
- Cholesterol, triglycerides, apolipoprotein B, hemoglobin A1c, fasting plasma glucose, fasting plasma insulin, 2hr plasma glucose, body weight, body mass index, body fat, waist circumference, blood pressure, adiposity, fatty liver, NAFLD, CRP, Inflammation, HDL-C, LDL-C, Non-HDL-c
- Medical subject headings
- Cardiovascular Diseases, Lipid Metabolism Disorders, Metabolic Diseases, Non-alcoholic Fatty Liver Disease, Body Weight, Obesity, Fatty Liver, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Soy milkOther
Soya milk or soymilk, a plant-based beverage that can be sweetened or unsweetened.
| Study group | Role | What they receive |
|---|---|---|
| Soy Milk | Soy milk beverage Receives: Other: Soy milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood lipids - LDL-Cholesterol (LDL-C)
LDL-C mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Blood lipids - HDL-Cholesterol (HDL-C)
HDL-C mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Blood lipids - Triglycerides (TG)
TG mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Blood lipids - non-HDL-Cholesterol (Non HDL-C)
Non-HDL-C mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Blood lipids - Apolipoprotein B (ApoB)
ApoB mean difference and 95% CIs in g/L
Measured: Immediately after the intervention
Glycemic control - Hemoglobin A1c (HbA1c)
HbA1c mean difference and 95% CIs in %
Measured: Immediately after the intervention
Glycemic control - fasting plasma glucose (FPG)
FPG mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Glycemic control - fasting plasma insulin (FPI)
FPI mean difference and 95% CIs in mmol/L
Measured: Immediately after the intervention
Glycemic control - glucose tolerance - plasma glucose area under the curve (AUC)
AUC mean difference and 95% CIs in mmol x min/l
Measured: Immediately after the intervention
Glycemic control - glucose tolerance - 2h plasma glucose (2h-PG)
2h plasma glucose (2h-PG) during a 75g oral glucose tolerance test (OGTT) in mmol/L
Measured: Immediately after the intervention
Adiposity - Body weight
Body weight mean difference and 95% CIs in kg
Measured: Immediately after the intervention
Adiposity - Body mass index (BMI)
BMI mean difference and 95% CIs in kg/m2
Measured: Immediately after the intervention
Adiposity - Body fat
Body fat mean difference and 95% CIs in %
Measured: Immediately after the intervention
Adiposity - Waist circumference
Waist circumference mean difference and 95% CIs in cm
Measured: Immediately after the intervention
Blood pressure - systolic blood pressure (SBP)
SBP mean difference and 95% CIs in mmHg
Measured: Immediately after the intervention
Blood pressure - diastolic blood pressure (DBP)
DBP mean difference and 95% CIs in mmHg
Measured: Immediately after the intervention
Markers of non-alcoholic fatty liver disease (NAFLD) - Intrahepatocellular lipids (IHCL)
IHCL mean difference and 95% CIs in %
Measured: Up to 20 years
Markers of non-alcoholic fatty liver disease (NAFLD) - alanine transaminase (ALT)
ALT mean difference and 95% CIs in U/L
Measured: Immediately after the intervention
Markers of non-alcoholic fatty liver disease (NAFLD) - aspartate aminotransferase (AST)
AST mean difference and 95% CIs in U/L
Measured: Immediately after the intervention
Markers of non-alcoholic fatty liver disease (NAFLD) - fatty liver index (FLI)
FLI mean difference and 95% CIs
Measured: Immediately after the intervention
Markers of inflammation - C-reactive protein (CRP)
CRP mean difference and 95% CIs in mg/dL
Measured: Immediately after the intervention
Renal function and structure - creatinine
Creatinine mean difference and 95% CIs in mcmol/L
Measured: Immediately after the intervention
Renal function and structure - creatinine clearance (CrCl)
CrCl mean difference and 95% CIs in mL/min
Measured: Immediately after the intervention
Renal function and structure - glomerular filtration rate (GFR)
GFR mean difference and 95% CIs in ml/min/1.73 m2
Measured: Immediately after the intervention
Renal function and structure - estimated GFR (eGFR)
eGFR mean difference and 95% CIs in ml/min/1.73 m2
Measured: Immediately after the intervention
Renal function and structure - albumin excretion rate (AER)
AER mean difference and 95% CIs in mg/L
Measured: Immediately after the intervention
Renal function and structure - albumin-to-creatinine ratio (ACR)
ACR mean difference and 95% CIs in mg/mmol creatinine
Measured: Immediately after the intervention
Uric acid
Uric acid in mcmol/L
Measured: Immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2022
- Study start1 Oct 2022
- Primary completion30 Mar 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Sievenpiper, University of Toronto
- Investigators
- John L. Sievenpiper, MD,PhD,FRCPC, Principal investigator, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05637866
- Sponsor's protocol ID
- CIHR - Soy vs cow's milk
- Status last verified
- Mar 2023
- First submitted
- 10 Nov 2022
- Last updated
- 6 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no individual data collected. However, data from all included studies will be published in the manuscript and supplementary material
Publications
Malik VS, Sun Q, van Dam RM, Rimm EB, Willett WC, Rosner B, Hu FB. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr. 2011 Sep;94(3):854-61. doi: 10.3945/ajcn.110.009621. Epub 2011 Jul 13.
PubMed 21753066Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012 Feb;95(2):283-9. doi: 10.3945/ajcn.111.022533. Epub 2011 Dec 28.
PubMed 22205311McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a review of the evidence. Nutr Metab (Lond). 2013 Jul 3;10(1):46. doi: 10.1186/1743-7075-10-46.
PubMed 23822206Erlich MN, Ghidanac D, Blanco Mejia S, Khan TA, Chiavaroli L, Zurbau A, Ayoub-Charette S, Almneni A, Messina M, Leiter LA, Bazinet RP, Jenkins DJA, Kendall CWC, Sievenpiper JL. A systematic review and meta-analysis of randomized trials of substituting soymilk for cow's milk and intermediate cardiometabolic outcomes: understanding the impact of dairy alternatives in the transition to plant-based diets on cardiometabolic health. BMC Med. 2024 Aug 22;22(1):336. doi: 10.1186/s12916-024-03524-7.
PubMed 39169353
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Soy Milk for Cow's Milk on Intermediate Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- ClinicalTrials.gov ID
- NCT05637866
- Acronym / sponsor ID
- CIHR - Soy vs cow's milk
- Conditions
- Cardiovascular Diseases, Lipid Disorder, Metabolic Disease, Non-Alcoholic Fatty Liver Disease
- Keywords
- Cholesterol, triglycerides, apolipoprotein B, hemoglobin A1c, fasting plasma glucose, fasting plasma insulin, 2hr plasma glucose, body weight
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 30 Mar 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 5 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dairy consumption has shown associations with decreased incidence of cardiometabolic diseases. With the growing interest in plant-based eating, and the mounting evidence for the cardiovascular benefits of plant forward diets, national dietary guidelines have pivoted away from promoting exclusive daily dairy consumption. Soymilk is the most nutritionally comparable non-dairy plant-based alternative to cow's milk. Although the DGA, Health Canada, and various pediatric associations recognize fortified soymilk as the only non-dairy alternative equivalent to cow's milk and it can carry an approved health claim for coronary heart disease risk reduction based on the soy protein that it contains, soymilk is classified by the NOVA classification as an ultra-processed food (the opposite of the classification of cow's milk as an unprocessed or minimally processed food). To be an acceptable iso-sweet alternative to cow's milk, soymilk is also often sweetened with sucrose, which is designated as an added sugar, whereas the lactose that sweetens cow's milk is not (despite lactose in cow's milk being present in quantities that are double that of sucrose in soymilk products designed to be iso-sweet analogues of cow's milk). With near universal recommendations from major public health authorities to reduce the intake of both ultra-processed foods and added sugars and the FDA proposing to update its "healthy" claim criteria to limit added sugars, the role of soymilk as a "healthy" non-dairy alternative to cow's milk is in serious question. The effect of soy protein on other cardiometabolic outcomes is also unclear. To address this question and better inform health claims and guideline development, the investigators will conduct a systematic review and meta-analysis of randomized controlled trials of the effect of soy protein as soy milk, in substitution for cow's milk, on various intermediate cardiometabolic mediators.
Detailed description
RATIONALE. Soymilk and other processed soy products are at an important crossroads. Although the DGA, Health Canada, and various pediatric associations recognize fortified soymilk as the only non-dairy plant milk alternative equivalent to cow's milk and it can carry an approved health claim for coronary heart disease risk reduction based on the soy protein that it contains, soymilk is classified by the NOVA classification as an ultra-processed food (the opposite of the classification of cow's milk as an unprocessed or minimally processed food). To be an acceptable iso-sweet alternative to cow's milk, soymilk is also often sweetened with sucrose, which is designated as an added sugar, whereas the lactose that sweetens cow's milk is not (despite lactose in cow's milk being present in quantities that are double that of sucrose in soymilk products designed to be iso-sweet analogues of cow's milk). With near universal recommendations from major public health authorities to reduce the intake of both ultra-processed foods and added sugars and the FDA updating its "healthy" claim criteria to limit added sugars, the role of soymilk as a "healthy" non-dairy alternative to cow's milk is in serious question.
OBJECTIVES. The objective is to conduct a systematic review and meta-analysis of randomized controlled trials to assess the effect of soymilk in substitution for cow's milk and its modification by added sugars (sweetened versus unsweetened) on established cardiometabolic risk factors of clinical and public health importance and assess the certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system.
DESIGN. The systematic review and meta-analyses will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA).
DATA SOURCES. Medline, Embase, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by manual searches of references of included studies.
STUDY SELECTION. Randomized controlled trials of ≥3-weeks assessing the effect of soy milk in substitution for cow's milk on cardiometabolic risk factors will be included.
DATA EXTRACTION. Two or more investigators will independently extract relevant data. Authors will be contacted for additional information and any missing data will be computed/imputed using standard formulae.
RISK OF BIAS. Two or more investigators will independently assess risk of bias using the Cochrane Risk of Bias Tool 2. All disagreements will be resolved by consensus.
OUTCOMES. Outcomes will include changes in established markers of (1) adiposity (body weight, BMI, body fat, waist circumference, abdominal fat); (2) glycemic control (HbA1c, fasting plasma glucose (FPG), fasting plasma insulin (FPI), plasma glucose area under the curve (AUC), and 2h plasma glucose (2hPG)); (3) blood lipids (LDL-cholesterol, non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides); (4) blood pressure (systolic blood pressure and diastolic blood pressure); (5) non-alcoholic fatty liver disease (NAFLD) (intrahepatocellular lipids (IHCL), alanine transaminase (ALT), aspartate aminotransferase (AST), and fatty liver index (FLI)); (6) inflammation (C-reactive protein (CRP)); (7) renal function and structure (creatinine, creatinine clearance (CrCl), glomerular filtration rate (GFR), estimated GFR (eGFR), albuminuria, albumin-to-creatinine ratio (ACR)); and (8) and uric acid.
DATA SYNTHESIS. Data will be pooled using the Generic Inverse Variance method for each outcome. As one of our primary research questions relates to the role of added sugars as a mediator in any observed differences between soy milk and cow's milk, we will stratify results by the presence of added sugars in soy milk (sweetened versus unsweetened) and assess effect modification by this variable on pooled estimates. 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. Fixed-effects models will only be used where there is <5 included studies. Paired analyses will be applied for crossover design trials. Heterogeneity will be assessed (Cochran Q statistic) and quantified (I2 statistic). Sources of heterogeneity will be explored (if there are >=10 trial comparisons) by sensitivity analyses and a priori subgroup analyses (dose, comparator, follow-up, baseline levels, design, age, health status, funding and risk of bias). Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. Publication bias will be assessed (if there are >=10 trial comparisons) by inspection of funnel plots and the Egger and Begg tests. Adjustment for evidence of funnel plot asymmetry or small study effects will be conducted by the Duval and Tweedie trim-and-fill method.
GRADE ASSESSMENT. To assess the certainty of the evidence, the investigators will use the GRADE system, an evidence-based grading system adopted by >100 organizations (http://www.gradeworkinggroup.org/). It grades the evidence as high, moderate, low or very low quality based on the study design and a series of downgrades (risk of bias, imprecision, inconsistency, indirectness, publication bias) and upgrades (large magnitude of the effect, dose-response gradient, and attenuation by confounding). The investigators will follow the GRADE handbook (https://gdt.gradepro.org/app/handbook/ handbook.html) and use the GRADEpro GDT (gradepro.org) software.
ADD-ON SYNTHESIS (LACTOSE VERSUS ADDED SUGARS) To interrogate the question of the role of added sugars as a mediator of any observed effects of sweetened soymilk, we will conduct a sub-synthesis (a separate systematic review and meta-analysis of RCTs) of the effect of lactose (which is not considered an added sugar) versus added sugars (sucrose, HFCS, or fructose) irrespective of matrix (all comparisons with a matched matrix will be included). We will follow the same protocol and analysis plan as that for the main analysis.
KNOWLEDGE TRANSLATION PLAN. The investigators will follow the Ottawa model of Research for knowledge translation. The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact journals. Target audiences will include public health and clinical communities with an interest in nutrition and cardiometabolic diseases. Feedback will be incorporated and used to improve public health messages and key areas for future research will be defined. The PIs will network among opinion leaders to increase awareness and participate directly in the development of future guidelines.
SIGNIFICANCE. Both proposed projects will aid in knowledge translation related to the role of soy milk as a "healthy" non-dairy alternative to cow's milk, strengthening the evidence-base for guidelines development in the U.S., Canada, Europe, and beyond and improving health outcomes, by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Soy Milk | – | Other: Soy milkSoy milk beverage |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with or without cardiovascular risk factors
Key inclusion criteria (5 listed)
- Randomized controlled trials
- Soy milk intervention
- Cow's milk comparator
- Intervention duration ≥ 3 weeks
- Data for at least 1 outcome
Key exclusion criteria (8 listed)
- Non-human studies
- Observational studies
- Acute single-bolus feeding studies
- Participants < 18 years of age
- Multimodal interventions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Soy milkSoya milk or soymilk, a plant-based beverage that can be sweetened or unsweetened. | Other | Soy Milk |
Primary outcome
Blood lipids - LDL-Cholesterol (LDL-C)
Time frame: Immediately after the intervention
LDL-C mean difference and 95% CIs in mmol/L
Blood lipids - HDL-Cholesterol (HDL-C)
Time frame: Immediately after the intervention
HDL-C mean difference and 95% CIs in mmol/L
Blood lipids - Triglycerides (TG)
Time frame: Immediately after the intervention
TG mean difference and 95% CIs in mmol/L
Blood lipids - non-HDL-Cholesterol (Non HDL-C)
Time frame: Immediately after the intervention
Non-HDL-C mean difference and 95% CIs in mmol/L
Blood lipids - Apolipoprotein B (ApoB)
Time frame: Immediately after the intervention
ApoB mean difference and 95% CIs in g/L
Glycemic control - Hemoglobin A1c (HbA1c)
Time frame: Immediately after the intervention
HbA1c mean difference and 95% CIs in %
Glycemic control - fasting plasma glucose (FPG)
Time frame: Immediately after the intervention
FPG mean difference and 95% CIs in mmol/L
Glycemic control - fasting plasma insulin (FPI)
Time frame: Immediately after the intervention
FPI mean difference and 95% CIs in mmol/L
Glycemic control - glucose tolerance - plasma glucose area under the curve (AUC)
Time frame: Immediately after the intervention
AUC mean difference and 95% CIs in mmol x min/l
Glycemic control - glucose tolerance - 2h plasma glucose (2h-PG)
Time frame: Immediately after the intervention
2h plasma glucose (2h-PG) during a 75g oral glucose tolerance test (OGTT) in mmol/L
Adiposity - Body weight
Time frame: Immediately after the intervention
Body weight mean difference and 95% CIs in kg
Adiposity - Body mass index (BMI)
Time frame: Immediately after the intervention
BMI mean difference and 95% CIs in kg/m2
Adiposity - Body fat
Time frame: Immediately after the intervention
Body fat mean difference and 95% CIs in %
Adiposity - Waist circumference
Time frame: Immediately after the intervention
Waist circumference mean difference and 95% CIs in cm
Blood pressure - systolic blood pressure (SBP)
Time frame: Immediately after the intervention
SBP mean difference and 95% CIs in mmHg
Blood pressure - diastolic blood pressure (DBP)
Time frame: Immediately after the intervention
DBP mean difference and 95% CIs in mmHg
Markers of non-alcoholic fatty liver disease (NAFLD) - Intrahepatocellular lipids (IHCL)
Time frame: Up to 20 years
IHCL mean difference and 95% CIs in %
Markers of non-alcoholic fatty liver disease (NAFLD) - alanine transaminase (ALT)
Time frame: Immediately after the intervention
ALT mean difference and 95% CIs in U/L
Markers of non-alcoholic fatty liver disease (NAFLD) - aspartate aminotransferase (AST)
Time frame: Immediately after the intervention
AST mean difference and 95% CIs in U/L
Markers of non-alcoholic fatty liver disease (NAFLD) - fatty liver index (FLI)
Time frame: Immediately after the intervention
FLI mean difference and 95% CIs
Markers of inflammation - C-reactive protein (CRP)
Time frame: Immediately after the intervention
CRP mean difference and 95% CIs in mg/dL
Renal function and structure - creatinine
Time frame: Immediately after the intervention
Creatinine mean difference and 95% CIs in mcmol/L
Renal function and structure - creatinine clearance (CrCl)
Time frame: Immediately after the intervention
CrCl mean difference and 95% CIs in mL/min
Renal function and structure - glomerular filtration rate (GFR)
Time frame: Immediately after the intervention
GFR mean difference and 95% CIs in ml/min/1.73 m2
Renal function and structure - estimated GFR (eGFR)
Time frame: Immediately after the intervention
eGFR mean difference and 95% CIs in ml/min/1.73 m2
Renal function and structure - albumin excretion rate (AER)
Time frame: Immediately after the intervention
AER mean difference and 95% CIs in mg/L
Renal function and structure - albumin-to-creatinine ratio (ACR)
Time frame: Immediately after the intervention
ACR mean difference and 95% CIs in mg/mmol creatinine
Uric acid
Time frame: Immediately after the intervention
Uric acid in mcmol/L
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
- Background: PubMed 21753066Malik VS, Sun Q, van Dam RM, Rimm EB, Willett WC, Rosner B, Hu FB. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr. 2011 Sep;94(3):854-61. doi: 10.3945/ajcn.110.009621. Epub 2011 Jul 13.
- Background: PubMed 22205311Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012 Feb;95(2):283-9. doi: 10.3945/ajcn.111.022533. Epub 2011 Dec 28.
- Background: PubMed 23822206McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a review of the evidence. Nutr Metab (Lond). 2013 Jul 3;10(1):46. doi: 10.1186/1743-7075-10-46.
- Derived from this study: PubMed 39169353Erlich MN, Ghidanac D, Blanco Mejia S, Khan TA, Chiavaroli L, Zurbau A, Ayoub-Charette S, Almneni A, Messina M, Leiter LA, Bazinet RP, Jenkins DJA, Kendall CWC, Sievenpiper JL. A systematic review and meta-analysis of randomized trials of substituting soymilk for cow's milk and intermediate cardiometabolic outcomes: understanding the impact of dairy alternatives in the transition to plant-based diets on cardiometabolic health. BMC Med. 2024 Aug 22;22(1):336. doi: 10.1186/s12916-024-03524-7.
- Canada's Food GuideLink provided by the sponsor.
- Individual participant dataSharing planned: No. There is no individual data collected. However, data from all included studies will be published in the manuscript and supplementary material
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John L. Sievenpiper, MD,PhD,FRCPC principal investigator
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Lipid Disorder, run by University of Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood lipids - LDL-Cholesterol (LDL-C) (time frame: Immediately after the intervention). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05637866, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.