The EXPLAIN Study: Exploring Plant-Based Meat Analogues for Their Impact on Health

Not Applicable

Recruiting

Conditions: Blood Pressure
Cardiometabolic Health

Interventions: Other: Standardized diet with commercially available animal meats (comparator products)
Other: Standardized diet with commercially available PBMAs (intervention products)

Registration Number: NCT06370936

Lead Sponsor: Wageningen University

Brief Summary: Plant-based diets with little to no meat are considered healthy and sustainable by the general public. The increasingly popular plant-based meat analogues (PBMAs) allow consumers to easily decrease meat intake while maintaining their dietary patterns. However, scientific knowledge on the health impact of PBMAs on humans is currently very limited.

The primary objective of this clinical trial is to evaluate if and to what extent replacing all meat products in an average Dutch diet with currently commercially available PBMAs affects the systolic blood pressure of middle-aged men and women in a 2x8 week fully dietary controlled crossover intervention study. The secondary objectives are to assess the effect of this replacement of meat products with PBMAs on cardiometabolic health, gut microbiome, intestinal health, well-being, and underlying biological mechanisms.

114 men and women with a BMI of 23-40 kg/m2, aged 45-75 years will be included in the study. Participants will follow both an 8-week completely controlled diet in which all meats are of plant-based origin (PBMAs) and an 8-week diet in which all meats are of animal origin in randomized order with a 10-week wash-out period. Before the intervention starts, the participants will be characterized to describe them on anthropometrics, glucose tolerance and insulin sensitivity, genetics, sleep patterns, and stress levels. Before the start and at the end of each 8-week dietary intervention period, several measurements, including systolic blood pressure monitoring and secondary outcome measures will be done. Additionally, systolic and diastolic blood pressure will be monitored throughout the dietary interventions and a small quantity of parameters related to the secondary objectives will be measured.

Detailed Description: Plant-based diets with little to no meat are considered healthy and sustainable by the general public. The increasingly popular plant-based meat analogues (PBMAs) allow consumers to easily decrease meat intake while maintaining their dietary patterns. PBMAs are designed to mimic the sensory and textural properties of meat and to replace animal protein with plant protein. Processing of plant-based ingredients is needed to achieve this, which potentially compromises the sustainability and health assets of PBMAs. One of the concerns with processing is that it results in relatively high salt levels in the products, which could affect the blood pressure of consumers. However, scientific knowledge on the health impact of PBMAs on humans is currently very limited. Therefore, a fully controlled dietary intervention with a standardized diet is needed to evaluate the health impact of commercially available PBMAs.

The primary objective is to evaluate if and to what extent replacing all meat products in an average Dutch diet with currently commercially available PBMAs affects the systolic blood pressure of middle-aged men and women in a 2x8 week fully dietary controlled crossover intervention study. The secondary objectives are to assess the effect of this replacement of meat products with PBMAs on cardiometabolic health, gut microbiome, and intestinal health, well-being, and underlying biological mechanisms. In addition, the investigators aim to study the relation between diet-specific responses (comparing PBMAs and meat products) and phenotype, including glucose responses and body composition.

The study compromises a randomized crossover fully controlled dietary intervention at Wageningen University which consists of 2x8 week interventions separated by a 10-week washout period. Before the intervention starts, the participants will be characterized to describe them on anthropometrics, glucose tolerance and insulin sensitivity, genetics, sleep patterns, and stress levels. Before the start and at the end of each 8-week dietary intervention period, several measurements, including systolic blood pressure monitoring and secondary outcome measures will be done. Additionally, systolic and diastolic blood pressure will be monitored throughout the dietary interventions and a small quantity of parameters related to the secondary objectives will be measured.

The study population consists of 114 men and women with a BMI of 23-40 kg/m2, aged 45-75 years, and weight stable (± \<3kg) for at least three months before inclusion. Participants will follow both an 8-week completely controlled diet in which all meats are of plant-based origin (PBMAs) and an 8-week diet in which all meats are of animal origin in randomized order with a 10-week wash-out period. Diets are fully controlled which implies that all foods and meals are provided to participants by the Human Nutrition Research Unit (HNRU) and are based on participants' habitual energy needs to maintain a stable body weight throughout the study. Except for PBMAs/meat, all other foods will be identical in both intervention diets. The composition of the diets is based on the Dutch National Food Consumption Survey. All food products provided, including the PBMAs, are commercially available.

The total study duration for a participant will be a little over \>6 months, including the 10-week washout. The total time that needs to be invested by participants in this study with visits and at-home measurements is 72 hours. Participants are restricted for a total of 16 weeks in their eating habits since they need to follow a fully standardized diet. Subjects will have their blood pressure measured at the HNRU and additionally will have to measure their blood pressure at home. In addition, subjects have to wear continuous glucose and physical activity monitors twice during the study for a total of approximately 28 days. During the characterization period, participants will visit the HNRU once or twice depending on participant preference. For the measurements before and at the end of each dietary intervention period, participants visit the HNRU three times per intervention period (one extra visit after for the HFMM), so six times total. Additionally, during the dietary intervention, participants will visit the Human Research Unit twice a week during dinner time.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 114

Inclusion Criteria

BMI of 23-40 kg/m2
Age 45-75 years
Willing to consume both meat and PBMAs
Stable body weight (lost/gained ± <3 kg over the last 3 months prior to inclusion)

Exclusion Criteria

Diseases or prior surgeries affecting the stomach, liver, kidneys or intestines (allowed i.e. appendectomy)
Food allergies, intolerances (including lactose/gluten intolerance) for products used in the study design, and/or dietary restrictions interfering with the study (including special diets, vegetarians, and eating disorders)
Cardiovascular diseases (e.g. heart failure. But hypertension up to 160 mmHg is allowed for inclusion as indicated by the research physician) or cancer (e.g. non-invasive skin cancer allowed)
Anemia defined as Hb concentrations <8.5 mmol/L for men and <7.5 mmol/L for women
Diagnosed with type 1 or type 2 diabetes
Blood pressure >160 mmHg*
Major mental disorders
Drug-treated thyroid diseases (well-substituted hypothyroidism is allowed for inclusion)
Diseases with a life expectation shorter than 5 years
Regular use of/receiving medication interfering with research outcomes (as judged by research physician), such as the use of glucose-lowering drugs, insulin, use of medication that impacts gastric emptying, use of antipsychotics
Starting or changing blood pressure medication type or dose during the study. (Continuation of blood pressure medication usage is allowed during the study)
Use of anti-biotics over the last 3 months before the study start
Dietary habits interfering with study design (vegan/vegetarian, ketogenic diet, etc.)
Intention to change the intensity of exercise during the study period;
Intention to lose weight during the study period
Current smokers (including use of e-cigarettes)
Use of soft and/or hard drugs (cannabis included)
Abuse of alcohol (alcohol consumption defined as >14 glasses (women) or >21 glasses (men) of alcoholic beverages per week)
Use of strong vitamins or other dietary supplements (e.g. iron- or B12-supplements, pre- or probiotics) expected to interfere with the study outcomes.
Donated blood within 2 months prior to the screening
Inability to comply with the study diet
Being pregnant or lactating or planning to become pregnant
Unable/unwilling to download a research application on the mobile phone
Inability to understand study information and/or communicate with staff
Inability/unwillingness to comply with staff instructions
Displaying misbehavior towards other participants/staff
Participation in another study that involves an intervention within two months prior to the intervention
Working or doing a thesis/internship at the Division of Human Nutrition and Health or the Laboratory of Microbiology of Wageningen University.

[*Participants with a screening systolic blood pressure >140 mmHg - ≤160 mmHg need written permission for participation without having (medical) treatment for the study period granted by their general practitioner after assessment of their cardiovascular risk. Participants within this screening range who cannot hand over written clearance from their general practitioner will be excluded from participation. Participants whose blood pressure has measured >140 mmHg (systolic) or >90 mmHg (diastolic) one or more times during the study, will receive a letter for referral to the general practitioner.]

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PBMAs then Animal meats	Standardized diet with commercially available animal meats (comparator products)	For the first treatment period of 8 weeks, participants receive a standardized diet with a variety of PBMAs, after a 10-week washout period this is followed by a standardized diet with a variety of meat products for the second treatment period.
Animal meats then PBMAs	Standardized diet with commercially available PBMAs (intervention products)	For the first treatment period of 8 weeks, participants receive a standardized diet with a variety of meat products, after a 10-week washout period this is followed by a standardized diet with a variety of PBMAs for the second treatment period.
Animal meats then PBMAs	Standardized diet with commercially available animal meats (comparator products)	For the first treatment period of 8 weeks, participants receive a standardized diet with a variety of meat products, after a 10-week washout period this is followed by a standardized diet with a variety of PBMAs for the second treatment period.
PBMAs then Animal meats	Standardized diet with commercially available PBMAs (intervention products)	For the first treatment period of 8 weeks, participants receive a standardized diet with a variety of PBMAs, after a 10-week washout period this is followed by a standardized diet with a variety of meat products for the second treatment period.

Primary Outcome Measures

Name	Time	Method
Systolic blood pressure	12 times during the trial, 6 times per 8-week intervention (1 time before intervention period, then biweekly measurements, and 1 measurements in week 8 of 8-week intervention)	Systolic blood pressure as measured with in-clinic blood pressure measurements

Secondary Outcome Measures

Name	Time	Method
Home diastolic blood pressure	Twice daily for 16 weeks total (both 8-week interventions)	Diastolic blood pressure as measured by participant at-home
Fasting blood nutritional status	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Circulating vitamins and minerals related to meat and plant-based meat intake, including important circulating vitamins such as vitamins B6, B12, and D, and minerals such as markers of iron status, zinc, magnesium, and calcium.
Interstitial glucose profile	4 weeks during trial, 2 continuous weeks per 8-week intervention	Interstitial glucose concentrations, as measured by continuous glucose monitoring.
Fecal microbiome composition	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Microbiome composition in the feces.
Fasting and postprandial circulating metabolites with a high fat mixed meal (HFMM) challenge	2 times during the trial. 1 time at the end of each 8 week-intervention.	Circulating fasting and postprandial metabolites upon a high-fat mixed meal (HFMM). At t=0, 30, 60, 90, 120, 180, and 240 minutes after the consumption of the HFMM blood is collected. This measurement is only for participants with veins suitable for a Venflon catheter.
Home systolic blood pressure	Twice daily for 16 weeks total (both 8-week interventions)	Systolic blood pressure as measured by participant at-home
Fasting blood insulin levels	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Fasting insulin concentration
Microbiome metabolites	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Microbial metabolites of interest, such as SCFAs will be measured using high-performance liquid chromatography (HPLC).
Diastolic blood pressure	12 times during the trial, 6 times per 8-week intervention (1 time before intervention period, then biweekly measurements, and 1 measurements in week 8 of 8-week intervention)	Diastolic blood pressure as measured with in-clinic blood pressure measurements
Blood immune markers	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Blood immune- and immune-metabolism markers. This includes immune-related proteins including cytokines.
Home heart rate	Twice daily for 16 weeks total (both 8-week interventions)	Heart rate as measured by participant at-home with blood pressure monitor
Fasting blood glucose levels	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Fasting glucose concentration
Fasting blood HbA1c levels	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Fasting HbA1c concentration
Blood immune cell populations	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Blood (immune) cell subpopulations. This compromises of whole blood CD45+ cell subset abundance such as abundance of T-lymphocytes and B-lymphocytes.
Physical activity	4 weeks during trial, 2 continuous weeks per 8-week intervention	Continuous physical activity levels, measured by the Actigraph accelerometer wGT3X-BT (ActiGraph, Pensacola, USA)
Gastro-intestinal transit time	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Transit time measured using the blue dye method
Self reported product-specific attitude towards meat and PBMAs	6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.	Self-reported product-specific attitude towards meat and PBMAs as measured using a questionnaire. Scores between 1-7. Low scores indicate a negative attitude toward the product, and high scores indicate a positive attitude toward the product.
Fasting blood lipid spectrum	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Metabolomic analysis to determine all circulating blood lipids, including all cholesterol types, triglycerides and free fatty acids
Fasting blood metabolite profile	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Fasting blood metabolome as determined by metabolomics.
Fasting blood proteomic profile	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Proteomic analysis of fasting blood, incorporating an O-link panel, to determine circulating blood proteins, including protein biomarkers for inflammation such as cytokines.
Fasting blood cell transcriptomic profile	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Analysis of blood cells using transcriptomics to determine the blood transcriptome.
Metabolites in 24-hour urine	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Metabolomic analysis of urine collected over 24 hours, including markers for sodium excretion, urea nitrogen excretion, kidney function and consumption of (plant-based) meat, pH, and volume of urine.
Oral microbiome composition	4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)	Microbiome composition in saliva.
Microbiome functionality	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Microbiome functionality and genetic composition is assessed using batch-fermentation.
Self-reported stool consistency and frequency	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Self-reported stool consistency and frequency by using the Bristol Stool Chart (BSC) (scores between 1-7). Low scores indicate constipation and high scores diarrhea. Scores of 3-4 indicate a 'normal' stool.
Self reported meal-specific satiety with meat and PBMAs	6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.	Self reported meal-specific satiety with meat and PBMAs measured using a questionnaire. The Visual Analogue Scale (VAS) is used for questions about satiety and Likert scale is used to assess the intensity of product attributes. Low scores indicate low liking/experience, and high scores indicate high liking/experience.
Self-reported general attitude toward meat and PBMAs	10 times during trial. 5 times per 8-week intervention (before intervention, week 1,2,4 and 8).	Self-reported general attitude toward meat and PBMAs as measured using a questionnaire. Scores between 1-7. Low scores indicate a negative general attitude and high scores indicate a positive general attitude
Self-reported gastro-intestinal symptoms	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Gastro-intestinal symptoms as measured using the GSRS questionnaire (gastro-intestinal rating scale). The GSRS contains five scales: reflux syndrome, abdominal pain, constipation syndrome, diarrhoea syndrome and indigestion syndrome. Scores between 1-7. Low scores indicated absence or mild presence of symptoms, high scores indicated heavy presence of symptoms.
Self-reported constipation	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.	Gastro-intestinal obstipation symptoms as measured using the PAC-SYM questionnaire (Patient Assessment of Constipation Symptoms). Scores between 1-4. Low scores indicated absence or mild presence of symptoms, high scores indicated heavy presence of symptoms.

Trial Locations

Locations (1): Wageningen University, Division of Human Nutrition
🇳🇱
Wageningen, Gelderland, Netherlands

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