Sustainable Diets and Cardiometabolic Health

Official title

PLANETDIET: Sustainable Diets and Cardiometabolic Health: a Multi-omics Approach in a Randomized Controlled Trial (RCT)

Overview

This study aims to investigate the effects of sustainable diets on traditional and novel cardiometabolic risk factors. The primary objective is: • To test the effects of a sustainable diet on traditional cardiometabolic risk factors, specifically, a metabolic health score. The secondary objectives are: * To test the effects of sustainable diets on blood lipids, inflammatory markers, glucose markers, and anthropometric and body composition markers. * To test the effect of sustainable diets on circulating metabolomic profiles. * To test the effects of sustainable diets on circulating proteomic profiles. Participants will receive dietary interventions of a sustainable health diet, namely the PHD diet (Planetary Health Diet), an ovo-lacto-vegetarian diet, or a habitual diet following general recommendations for a healthy diet without advice on consumption of animal products. The three-arm parallel RCT will involve adults (45-70 years old) at cardiovascular risk. The primary hypothesis is that targeted interventions to adopt sustainable diets will have beneficial effects on cardiometabolic biomarkers, metabolomic, and proteomic profiles, compared to the habitual diet in individuals at cardiovascular risk.

Detailed description

Background: To promote sustainable diets for planetary and human health, the EAT-Lancet Commission called for a global dietary transformation by 2050, advocating a dietary pattern shift to align food systems with environmental sustainability and human health. The Planetary Health Diet (PHD) promotes a plant-based approach, emphasizing the consumption of whole grains, fruits, vegetables, nuts, and legumes, and limited amounts of seafood and poultry, while discouraging excessive intake of red and processed meat, added sugar, refined grains, and starchy vegetables. Despite the promotion of the popular EAT-Lancet diet, there is no Randomized Controlled Trial (RCT) evaluating the impact of this pattern on established and novel cardiometabolic biomarkers. The trial design addresses the recognized lack of RCTs evaluating changes in multi-omic profiles by adhering to different dietary interventions; the lack of RCTs on sustainable diets that consider environmental aspects; and overcome limitations of potential reverse causation and other biases from observational studies.

Investigation plan: Participants will be randomized to receive advice on changes in the overall dietary pattern from specialized dietitians. Participants in the PHD diet group will be guided to follow the EAT-Lancet recommendations adapted to be nutritionally adequate and culturally acceptable in Denmark (a high-quality plant-based diet with a low allowance of intake of eggs, dairy, chicken, and fish, but strictly avoiding red and processed meat). Participants in the vegetarian diet group will be advised to adhere to a stricter plant-based diet with an intake of eggs and dairy but avoiding chicken, fish, and red and processed meat, and no recommendations on food quantity or the environment. The two interventions will be compared with the control group, where participants will follow their habitual diet without specific advice on the consumption of animal products. The present RCT is not a weight loss trial, thus no total calorie restriction will be advised, and physical activity will not be promoted. A maximum alcohol consumption limited to 100 grams/week for men and women drinkers will be allowed.

Dietary considerations: The comparisons will allow us to address the unanswered question of whether the inclusion of moderate amounts of animal-based products in the context of a climate-friendly diet is superior to a stricter vegetarian diet. Vegan diets were not considered because of the difficulty in adherence in European settings and the potential for micronutrient deficiencies. The higher between-group contrast, considering both health and environmental impact is expected to be found for PHD vs control group.

The study will include an information meeting, screening visit, baseline visit, two visits during the intervention (1 month and 3 months), and a final visit at 6 months. Additionally, two group visits (at 2 and 4 months) will be conducted. Outcome parameters (a metabolic health score and its components) will be measured using blood samples obtained at baseline, 3 months, and final visit. Urine samples will be collected for the research biobank at the baseline, 1 month, 3 months, and final visit. Fecal samples will be collected at baseline and the final visit. Participants will wear continuous glucose monitors (CGM) for 10 days at baseline and at the end of follow-up.

Participants will have access to a study app that will include a timeline of the study, study materials including dietary recommendations, meal planners and recipes according to the intervention group, and instructions for collecting biosamples. Participants will also use the app to respond to self-reported questionnaires. Food boxes containing targeted products for each intervention will be distributed to participants at baseline, 1 month, and 3 months.

Participants will attend two group visits (5-15 participants), where they will receive educational material, information about the science behind the trial and have the opportunity to share experiences with their peers.

Interventions

• Behavioral Dietary advice (PHD)
  It consists of a written document outlining the PHD diet recommendations. Participants will receive: 1) information about the PHD guidelines by EAT-Lancet (a high-quality plant-based diet with a low allowance of intake of eggs, dairy, chicken, and fish, but strictly avoiding red and processed meat) adapted to be nutritionally adequate and culturally accepted in Denmark, 2) a meal planner for their calorie demands (templates for 2000 kcal/day; 2500 kcal/day; and 3000 kcal/day), 3) guidance on alt
• Behavioral Dietary advice (Ovo-lacto-vegetarian diet)
  It consists of a written document outlining the ovo-lacto-vegetarian diet guidelines. Participants will receive information to adhere to a stricter plant-based diet with an intake of eggs and dairy, but avoiding chicken, fish, and red and processed meat, and guidance on alternatives for substituting meat when cooking at home or eating out. Recommendations on food quantity or on consuming local and seasonal foods will not be given to pinpoint differences in the environmental aspect between interv
• Behavioral Dietary advice (control)
  It consists of a written document outlining the general recommendations of a healthy diet (i.e. consumption of fruits and vegetables, decreasing the intake of sugar-sweetened beverages, etc.) without any specific advice on the consumption of animal products.
• Behavioral Behavioural support PHD
  This component is designed to help participants adhere to the PHD through four individual and personalized dietary visits with a dietitian. Participants will also have access to a digital recipe collection in the study app. Recipes will be tagged by meal type and by season.
• Behavioral Food boxes PHD
  Food boxes will be sent to participants' homes. PHD food boxes will include seasonal and local fruits and vegetables, whole grain products, legumes, nuts, and dairy or milk alternatives. If allergies or intolerances are identified, the food boxes will be modified to maintain safety and dietary compliance.
• Behavioral Group visits PHD
  Group visits will provide support through nutritional education, social interaction, and peer learning, all focused on the dietary behavior changes required by the intervention. PHD group visits will cover topics such as PHD principles, and the related environmental and health outcomes.
• Behavioral Behavioural support (Ovo-lacto-vegetarian diet)
  This component is designed to help participants adhere to the ovo-lacto-vegetarian through four individual and personalized dietary visits with a dietitian. Participants will also have access to a digital recipe collection in the study app. Recipes will be tagged by meal type.
• Behavioral Food boxes (Ovo-lacto-vegetarian diet)
  Food boxes will be sent to participants' homes. Ovo-lacto-vegetarian food boxes will include fruits and vegetables, whole grains, legumes, nuts, soy-based products, eggs, and cheese. Local and seasonal aspects will not be taken into consideration. If allergies or intolerances are identified, the food boxes will be modified to maintain safety and dietary compliance.
• Behavioral Group visits (Ovo-lacto-vegetarian diet)
  Group visits will provide support through nutritional education, social interaction, and peer learning, all focused on the dietary behavior changes required by the intervention. Ovo-lacto-vegetarian group visits will cover topics such as plant-based eating and nutritional adequacy.
• Behavioral Behavioral support (control)
  Participants will attend four short individual dietary visits with a dietitian, where they will review the recorded dietary data. Participants of the control group will not have access a recipe collection or meal planner.

Primary outcome measures

• Changes in metabolic health score [Time frame: Baseline, 3 and 6 months]

Secondary outcome measures (12)

• Changes in low-lipoprotein-cholesterol concentrations (LDL-c) [Time frame: Baseline, 3 and 6 months]
• Changes in high-lipoprotein-cholesterol concentration (HDL-c) [Time frame: Baseline, 3 and 6 months]
• Changes in triglycerides concentration [Time frame: Baseline, 3 and 6 months]
• Changes in Apoliprotein A1 (ApoA1) concentration [Time frame: Baseline, 3 and 6 months]
• Changes in Apoliprotein B (ApoB) concentration [Time frame: Baseline, 3 and 6 months]
• Changes in fasting glucose [Time frame: Baseline, 3 and 6 months]
• Changes in insuline [Time frame: Baseline, 3 and 6 months]
• Changes in HA1c [Time frame: Baseline, 3 and 6 months]
• Changes in continuous glucose monitor (CGM) measures [Time frame: Baseline and 6 months]
• Changes in high-sensitive C-reactive protein concentrations [Time frame: Baseline, 3 and 6 months]
• Changes in Interleukin 6 (IL-6) concentrations [Time frame: Baseline, 3 and 6 months]
• Changes in systolic blood pressure [Time frame: Baseline, 3 and 6 months]

Eligibility criteria

Inclusion criteria

• Adults (males and females) between 45 and 70 years of age at the time of inclusion.
• Participants must have at least two metabolic alterations: 1) Waist Circumference (WC) >102 cm (males) or >88 cm (females); 2) self-reported medication for blood pressure or blood pressure >130/85 mmHg; 3) self-reported prediabetes or non-fasting plasma glucose 140-199 mg/dL (prediabetes); 4) self-reported lipid-lowering medication or diagnosis of impaired blood lipids (triglycerides: ≥ 150 mg/dL; and HDL: men: < 40 mg/dL and women: < 50 mg/dL).
• Participants are not institutionalized, able to read and provide consent before participation, and willing to attend in-person visits at the study site.
• Participants should have access to a smartphone and computer, or tablet and must be internet-literate.
• Understand Danish both in writing and when spoken.

Exclusion criteria

• Participants with any serious illness or history of cancer within the past 5 years (except adequately treated localized basal cell skin cancer or in situ uterine cervical cancer).
• Diagnosed with diabetes mellitus, CVD event (myocardial infarction, revascularization procedure, or stroke), or atrial fibrillation.
• Participants with diagnosed psychiatric conditions or cognitive impairment.
• Current smokers including all kinds of nicotine-containing products.
• BMI >35 kg/m2.
• Known or suspected abuse of alcohol or recreational drugs. Regular alcohol consumption exceeding the Danish national guidelines (i.e., more than 10 standard drinks per week or more than 4 drinks on any single day) will be excluded.
• Pregnancy or planning a pregnancy in the next year.
• Not willing to consume chicken and fish or not willing to make dietary changes related to the intervention.
• Participants with multiple food allergies that could hinder adherence to the intervention.
• Any other issue that makes the project responsible (PI or medical responsible) doubt the eligibility of the volunteer.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Denmark · 1 center

• Department of Nutrition, Exercise and Sports, University of Copenhagen. Rolighedsvej 26, D — Copenhagen

Publications

• Willett W, Rockstrom J, Loken B, Springmann M, Lang T, Vermeulen S, Garnett T, Tilman D, DeClerck F, Wood A, Jonell M, Clark M, Gordon LJ, Fanzo J, Hawkes C, Zurayk R, Rivera JA, De Vries W, Majele Sibanda L, Afshin A, Chaudhary A, Herrero M, Agustina R, Branca F, Lartey A, Fan S, Crona B, Fox E, Bignet V, Troell M, Lindahl T, Singh S, Cornell SE, Srinath Reddy K, Narain S, Nishtar S, Murray CJL. PMID 30660336

Identifiers

NCT: NCT07189676 · H-25030722 · Protocol code

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗