Clinical trial NCT03020186: Effects of Green-MED Diet Via the Gut-fat-brain Axis
Official title: Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Abdominal Obesity Metabolic Syndrome
Lead sponsor: Ben-Gurion University of the Negev
Sponsor class: OTHER
Collaborators: name: Harvard School of Public Health (HSPH)
name: University of Leipzig
First posted: 2017-01-13
Enrollment: 294
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Abdominal fat
timeFrame: 18 months
measure: Hepatic fat
timeFrame: 18 months
measure: Obesity
timeFrame: 6, 14, 18 months
Secondary outcomes:
measure: Brain anatomy
timeFrame: 18 months
measure: Cognitive function-MRI
timeFrame: 18 months
measure: Cognitive function
timeFrame: 18 months
measure: Cardiac state
timeFrame: 18 months
measure: Cardiac state
timeFrame: 18 months
measure: Endothelial dysfunction
timeFrame: 18 months
measure: Lipid profile
timeFrame: 6 , 14 and 18 months
measure: Glycemic control
timeFrame: 6 , 14 and 18 months
measure: Inflammatory state
timeFrame: 6 , 14 and 18 months
measure: Metabolomic
timeFrame: 18 months
measure: Metabolomic
timeFrame: 18 months
measure: Liver function (blood biomarkers)
timeFrame: 6 and 18 months
measure: Genetic signature
timeFrame: baseline
measure: Epigenetics
timeFrame: 18 months
measure: Epigenetics
timeFrame: 18 months
measure: Well being
timeFrame: 18 months
measure: Fecal microbiota profile
timeFrame: 6, 14, 18 months
measure: 24h- continuous glucose levels
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Dimona
country: Israel
facility: Nuclear research center Negev
Study officials:
affiliation: Ben-Gurion University of the Negev
name: Iris Shai, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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