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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
294
\*\*\*\*Sub-study from all 3 main arms: Autologous fecal microbiota supplement intervention derived from the time of maximal weight loss: At the 6-month time period, the time of anticipated greatest weight reduction, participants's feces samples will be processed to capsulized inocula. Samples will be frozen within 2 hours and will be kept at -80c pending analysis. Participants will be randomized to receive either research capsules or identical placebo capsules between 8 and 14 months time period. Placebo capsules will consist of a combination of powdered cocoa and vegetable gelatin in normal saline/glycerol and will be identical in appearance to research capsules.
Nuclear research center Negev
Dimona, Israel
Abdominal fat
Changes in visceral fat (MRI)
Time frame: 18 months
Hepatic fat
Changes in hepatic fat (MRI)
Time frame: 18 months
Obesity
Changes in body weight and waist circumference
Time frame: 6, 14, 18 months
Brain anatomy
Changes in hippocampus volume, diffusion Tensor Imaging (MRI)
Time frame: 18 months
Cognitive function-MRI
Changes in resting state connectivity (MRI, sub-study)
Time frame: 18 months
Cognitive function
cognitive tests
Time frame: 18 months
Cardiac state
Changes in cardiac anatomy (MRI, substudy)
Time frame: 18 months
Cardiac state
Changes in cardiac function (MRI, substudy)
Time frame: 18 months
Endothelial dysfunction
Changes endothelial function (ECG)
Time frame: 18 months
Lipid profile
Changes in lipid biomarkers (blood draw)
Time frame: 6 , 14 and 18 months
Glycemic control
Changes in glycemic biomarkers (blood draw)
Time frame: 6 , 14 and 18 months
Inflammatory state
Changes in inflammatory biomarkers (blood draw)
Time frame: 6 , 14 and 18 months
Metabolomic
Changes in sub-lipids (blood draw)
Time frame: 18 months
Metabolomic
Changes in sub-proteins ( blood draw)
Time frame: 18 months
Liver function (blood biomarkers)
Changes in liver function biomarkers (blood draw)
Time frame: 6 and 18 months
Genetic signature
SNPs associated with fat distribution and visceral fat
Time frame: baseline
Epigenetics
changes in mRNAs
Time frame: 18 months
Epigenetics
changes in genes' methylation
Time frame: 18 months
Well being
assessed by questionnaire
Time frame: 18 months
Fecal microbiota profile
Diversity Index as a key measure
Time frame: 6, 14, 18 months
24h- continuous glucose levels
24h dynamics of glucose using continuous glucose monitor. substudy
Time frame: 2 weeks
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