Clinical trial NCT04307628: Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
Official title: Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Healthy
Normal Weight
Overweight
Obese
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2020-03-13
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The researchers will investigate blood and fecal responses in qualified study participants after eating walnuts for 4 weeks compared to not eating walnuts for 4 weeks. The two dietary interventions will be separated by a 4 week washout period. The order of diets will be random; study participants will complete both interventions. Dietary modifications will be part of the study protocol.

Detailed description: The researchers hypothesize that walnut consumption will induce changes in fecal metagenome, identifiable walnut-derived bioactives (urolithins) and other microbial-derived products (short-chain fatty acids and secondary bile acids). The researchers hypothesize that walnut consumption will result in improvements to blood lipid profiles, including decreased total and LDL-cholesterol; increased HDL-related cholesterol efflux capacity and antioxidant protection; and decreased inflammatory biomarkers relative to control diet. The researchers hypothesize changes in cardiometabolic health biomarkers will be correlated with food bioactive metabolites and/or fecal metagenome. Pathway analysis will identify metabolic pathways differentially regulated by walnut-derived bioactives and walnut-responsive microbial genes.

Eligibility criteria: Inclusion Criteria:

Generally healthy men and women between 20-65 years of age and BMI range of 20.0-34.9 kg/m2 will be recruited from the Davis - Sacramento metropolitan area. Enrolled subjects must be willing to consume 2 ounces (approximately 1/2 cup) of walnuts daily and modify their diet to avoid eating walnuts and other nuts, and foods or beverages high in polyphenols (a list will be provided) during study enrollment . Adults unable to consent, individuals who are not yet adults (infants, children, teenagers), pregnant or lactating women, women planning to become pregnant in the next four months and prisoners will be specifically excluded. Screening will take place by phone interview and through in-person screening and consent, including anthropometric and biochemical assessments and health history questionnaires.

Exclusion Criteria:

* Allergy to walnuts or other nuts
* Eating more than 25 grams of fiber per day, assessed by the Block Dietary-Fruit-Vegetable-Fiber Screener©
* Taking medications or supplements known to affect metabolism or gut microbiota composition (i.e. Metformin, statins, antibiotics within the past 3 months, fiber supplements, probiotics, and others)
* Documented chronic diseases including diabetes, renal or liver disease, metabolic syndrome, active cancer, MI or stroke, history of gastric bypass or GI disease (e.g. Crohn's Disease, Irritable Bowel Disease, diverticulosis/diverticulitis,etc)
* Smoker or living with a smoker, including vaporizer and/or electronic cigarettes.
* Illicit drug use, cannabis usage, or consuming \>1 alcoholic drink/day
* Extreme dietary or exercise patterns; vegan diet.
* Recent weight fluctuations (\>10% in the last 6 months)
* Taking prescription lipid medications or supplements that may affect lipoprotein metabolism (i.e. \>1 g of fish oil/day, antioxidant supplements)
* Taking exogenous hormones (e.g. hormonal birth control)
* Poor venous access
* Unwillingness to comply with study protocols

Primary outcomes:
measure: Assessing the influence of walnuts on the fecal metagenome
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on fecal secondary bile acids
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on fecal short-chain fatty acids
timeFrame: Through study completion, an average of 12 weeks
measure: Urolithins measured in plasma by UPLC/MS
timeFrame: Through study completion, an average of 12 weeks
measure: Fecal calprotectin will be measured by ELISA
timeFrame: Through study completion, an average of 12 weeks
Secondary outcomes:
measure: Assessing the influence of walnuts on blood lipid measurements
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on paraoxonase-1 (PON-1) activity
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on cholesterol ester transfer protein activity (CETP)
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on hsCRP will be measured in blood
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on SAA will be measured in blood
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on circulating cytokines
timeFrame: Through study completion, an average of 12 weeks
measure: Assessing the influence of walnuts on peripheral blood mononuclear cells (PBMC) using ex vivo stimulation assays
timeFrame: Through study completion, an average of 12 weeks
measure: Dietary record analysis
timeFrame: Through study completion, an average of 12 weeks
measure: Anthropometric measurements
timeFrame: Through study completion, an average of 12 weeks
measure: Measure for changes in weight
timeFrame: Through study completion, an average of 12 weeks
measure: Measure for changes in blood pressure
timeFrame: Through study completion, an average of 12 weeks
Other outcomes:
Locations:
city: Davis
country: United States
facility: Ragle Human Nutrition Research Center
state: California
Study officials:
affiliation: University of California, Davis
name: Francene M Steinberg, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: