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Effects of Green-MED Diet Via the Gut-fat-brain Axis

Not Applicable
Completed
Conditions
Abdominal Obesity Metabolic Syndrome
Interventions
Other: Physical activity+ MED diet
Other: Physical activity+green MED diet
Other: Physical activity
Registration Number
NCT03020186
Lead Sponsor
Ben-Gurion University of the Negev
Brief Summary

Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat (green-MED diet) may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase.

Detailed Description

The investigators aim to compare the effect of green-MED diet+ physical activity (PA) vs. MED diet+ PA vs. PA on the gut-fat-brain axis and to explore the additional contribution of autologous fecal microbiota derived at the rapid weight loss phase on regain phase. Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase. The investigators will follow the participants with magnetic resonance imaging (MRI) that will include abdominal and hepatic fat, cardiac and anatomic/functional brain assessments. The investigators will perform cognitive tests and will measure changes in gut microbiota and sub-metabolomic profiling. The trial will be performed in an isolated workplace (the Nuclear Research Center) which holds an exclusive cafeteria that provides free, dietary -monitored, lunch, and an internal medical department. The exclusive nutritional profile of walnuts, with its relative high polyphenols content and unique composition, may benefit several health outcomes. Epidemiologic studies and RCTs suggest that walnuts consumption is associated with better weight status, adiposity measures and cardiometabolic state. However, some individuals avoid walnuts because they are calorie-dense, and fear that they will promote weight gain. Walnuts contain numerous well-characterized beneficial nutritional components, such as unsaturated fats, especially omega-3 fatty acids, dietary fibers, and high levels of vitamins and minerals. Among other well-recognized components, nuts are highly rich in polyphenols, mainly flavonoids. Polyphenols may potentially interact with physical activity and promote neurogenesis; a process that may significantly contribute to the brain's ageing process. Similarly, the polyphenol epigallocatechin-3-gallate (EGCG, a type of catechin found in green tea), was proposed to exert neuroprotective effects. New specific developed strain of duckweed \[Wolffia globose, "Mankai"\] , an aquatic plant, which might serve as a protein source and contains all the 9 essential and the 6 conditional amino acids. "Mankai" \[(Generally recognized as safe (GRAS)\] is a cultivated strain of Wolffia globosa, which is an aquatic plant, part of the family of plants known commonly as duckweeds. Duckweeds are very simple flowering aquatic plants, which float on or just beneath the surface of still or slow-moving bodies of water. There is a long history of the use of Wolffia species, in particular Wolffia Globosa, as food, especially in Southeast Asia: Burma, Laos and northern Thailand, where it has been used as a vegetable for many generations. The nutritional composition of "Mankai" has been determined and found to be high in protein, containing all the essential and conditionally essential amino acids, dietary fibers and several vitamins and minerals.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
294
Inclusion Criteria

age >30 years with abdominal adiposity (waist circumference: men > 102 cm, women > 88 cm) or dyslipidemia (TG>150mg/dl and HDL-c <40mg/dL for men and <50mg/dL for women)

Exclusion Criteria

Individuals who may not be able to partake in PA in the gym; TGs>400 mg/dL; serum creatinine>2 mg/dL; disturbed liver function; major illness that might require hospitalization; pregnant or lactating women; presence of active cancer, is receiving or received chemotherapy in the last three years; participation in another trial; participants who are treated with Coumadin (warfarin) - given its interaction with vitamin K and high level of this vitamin in "Mankai" green shake; pacemaker or platinum implant, because of the impossibility of MRI screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Physical activity+ MED dietPhysical activity+ MED dietOn top of the PA intervention described in Arm 1, the participants will be guided for moderate weight loss with a traditional Mediterranean (MED) diet, low in simple carbohydrates. The diet will include 1oz/day of walnuts that will be provided free of charge.
Physical activity+ green-MED dietPhysical activity+green MED dietOn top of the PA intervention described in Arm 1, the participants will guided for moderate weight loss with a MED diet, low in simple carbohydrates that will be rich in plants and polyphenols and low in processed meat. The diet will include 1oz/day of walnuts, 3-4 cups/day of green tea and \~500cc green shake/dinner based on specific strain of duckweed \[Wolffia globose, "Mankai"\], an aquatic plant, which might serve as a plant protein source. All the above will be provided free of charge.
Physical activityPhysical activityPhysical activity (PA) group will receive free gym memberships and the instruction necessary to engage in moderate-intensity physical activity, \~80% of which will have an aerobic component. The participants will get basic health promoting guideline for healthy diet .
Primary Outcome Measures
NameTimeMethod
Abdominal fat18 months

Changes in visceral fat (MRI)

Hepatic fat18 months

Changes in hepatic fat (MRI)

Obesity6, 14, 18 months

Changes in body weight and waist circumference

Secondary Outcome Measures
NameTimeMethod
Brain anatomy18 months

Changes in hippocampus volume, diffusion Tensor Imaging (MRI)

Cognitive function-MRI18 months

Changes in resting state connectivity (MRI, sub-study)

Cognitive function18 months

cognitive tests

Cardiac state18 months

Changes in cardiac function (MRI, substudy)

Endothelial dysfunction18 months

Changes endothelial function (ECG)

Lipid profile6 , 14 and 18 months

Changes in lipid biomarkers (blood draw)

Glycemic control6 , 14 and 18 months

Changes in glycemic biomarkers (blood draw)

Inflammatory state6 , 14 and 18 months

Changes in inflammatory biomarkers (blood draw)

Metabolomic18 months

Changes in sub-proteins ( blood draw)

Liver function (blood biomarkers)6 and 18 months

Changes in liver function biomarkers (blood draw)

Genetic signaturebaseline

SNPs associated with fat distribution and visceral fat

Epigenetics18 months

changes in genes' methylation

Well being18 months

assessed by questionnaire

Fecal microbiota profile6, 14, 18 months

Diversity Index as a key measure

24h- continuous glucose levels2 weeks

24h dynamics of glucose using continuous glucose monitor. substudy

Trial Locations

Locations (1)

Nuclear research center Negev

🇮🇱

Dimona, Israel

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