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.