Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts

Healthy Clinical Trial

Official title:

Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04307628
• Other study ID #: 1562149
• Status: Withdrawn
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: November 30, 2024

Study information

• Verified date: September 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 30, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Normal Weight
• Obese
• Overweight

Intervention

Other:
• Walnut
Study participants will eat 2 ounces of walnuts each day.
• Nut-Free
Study participants will not eat nuts.

Locations

Country	Name	City	State
United States	Ragle Human Nutrition Research Center	Davis	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessing the influence of walnuts on the fecal metagenome	Changes in fecal metagenomics will be assessed via Illumina sequencing	Through study completion, an average of 12 weeks
Primary	Assessing the influence of walnuts on fecal secondary bile acids	Fecal secondary bile acids will be measured by LC-QTOF/MS	Through study completion, an average of 12 weeks
Primary	Assessing the influence of walnuts on fecal short-chain fatty acids	Short-chain fatty acids in fecal matter will be measured by LC-MS/MS	Through study completion, an average of 12 weeks
Primary	Urolithins measured in plasma by UPLC/MS	Measure for changes in the levels of urolithins in separated plasma; measured in units of ug/uL. Blood will be assessed at each of the 4 study visits.	Through study completion, an average of 12 weeks
Primary	Fecal calprotectin will be measured by ELISA	Measure for changes in the levels of calprotectin in collected fecal matter; measured in units of ug/g. Feces will be assessed at each of the 4 study visits.	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on blood lipid measurements	Measure for changes in the levels of HDL and LDL in separated plasma; measured in units of mg/dL. Blood will be assessed at each of the 4 study visits	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on paraoxonase-1 (PON-1) activity	Measure for changes in PON-1 activity in separated plasma at each study of the 4 study visits. Activity will be calculated based on linear rates of hydrolysis of phenyl acetate to phenol	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on cholesterol ester transfer protein activity (CETP)	Changes in CETP activity will be measured at each of the 4 study visits. The isolated plasma will be co-incubated with donor and acceptor molecules using a commercially available assay kit.	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on hsCRP will be measured in blood	hsCRP will be measured in blood at each study visit	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on SAA will be measured in blood	SAA will be measured in blood at each study visit	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on circulating cytokines	ICAM and VCAM will be measured in blood at each study visit using a commercially available ELISA kit.	Through study completion, an average of 12 weeks
Secondary	Assessing the influence of walnuts on peripheral blood mononuclear cells (PBMC) using ex vivo stimulation assays	In-vitro: media from LPS stimulated monocytes will be used to measure gene expression and cytokines Measurement of changes in PBMC derived cytokines as a marker of inflammation at each of the 4 study visits. Assessment will be based on an increase or decrease in concentration in pg/ml.	Through study completion, an average of 12 weeks
Secondary	Dietary record analysis	Use a computer program to check for study dietary requirements. Subjects are to avoid olives and olive containing products during study protocol periods. This will be done using a subject self-recorded 3-day food record submitted to study personnel.	Through study completion, an average of 12 weeks
Secondary	Anthropometric measurements	Measure waist (cm) and hip circumference (cm) before the start of drawing blood on study day protocols.	Through study completion, an average of 12 weeks
Secondary	Measure for changes in weight	Measure weight (kg) before the start of drawing blood on study day protocols	Through study completion, an average of 12 weeks
Secondary	Measure for changes in blood pressure	Measure blood pressure (mmHg) before the start of drawing blood on study day protocols	Through study completion, an average of 12 weeks