Gut Microbiota-dependent Health Impacts of Haskap Berries (HIH)

PARTNERSHIP: Elucidating Gut Microbiota-dependent Health Impacts of Haskap Berries to Inform Agricultural Production Practices That Will Maximize Bioactive Potential

Polyphenol-rich Haskap berries (Haskap) have untapped therapeutic potential to improve human health, and agricultural producers in northern U.S. states are poised to increase production if consumer demand increases. A critical knowledge gap is that little is known about the interactions between gut microbes and Haskap polyphenols to produce bioactive metabolites linked to downstream health impacts. Additionally, little is known about which Haskap varieties and harvest timing yield the greatest bioactive potential. This study aims to address these gaps by investigating the interaction of bioactive components in Haskap with gut microbiota and the resultant gut and serum metabolites, inflammation, and metabolic health, and then couple this with analysis of berries from different Haskap varieties and harvest times.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Microbial Colonization; Metabolic Disease
• Intervention / Treatment: Dietary supplement: Placebo comparator; Dietary supplement: Haskap berry smoothie

Detailed Description

The long-term goal of this project is to form a partnership linking the health impacts of Haskap varieties and management practices that maximize health-promoting compounds to benefit both consumers and producers. Specific objectives of this study are to determine 1) the impact of Haskap on the gut microbiome and metabolome, 2) how gut microbiome composition and production of bioactive metabolites from Haskap impacts health and inflammation biomarkers, and 3) which Haskap varieties and growing practices increase production of health-promoting compounds.

To accomplish this, a four-armed, randomized, triple-blind, placebo controlled clinical trial of Haskap versus placebo for two separate groups with distinctly low and high metabolic syndrome status will be completed. Participants will be assessed for health biometrics, fat oxidation, gut microbiome composition, inflammation, and both the gut and serum metabolome before and after 8 weeks of intervention. Haskap fruit from twenty varieties will primarily come from the randomized block design field trial and fruit will be harvested at four stages of fruit maturity, then analyzed for polyphenol content. This part of the study will be replicated over three growing seasons.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mary P Miles, PhD; Phone Number: 406-994-6678; Email: mmiles@montana.edu
• Study Contact Backup: Name: Zachary T Miller, PhD; Phone Number: (406) 961-3025; Email: zachariah.miller@montana.edu

Study Locations

• United States
  • Montana
    • Bozeman, Montana, United States, 59717
      • Recruiting
      • Montana State University
      • Contact: Mary P Miles, PhD; Phone Number: 406-994-6678; Email: mmiles@montana.edu
      • Contact: Brian Bothner, PhD; Phone Number: 1-406-994-5270; Email: bbothner@montana.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Metabolically Healthy Group:

All of the following:

• Waist circumference: men ≤ 40, women ≤ 35 inches
• Systolic blood pressure: ≤ 130 mmHg
• Diastolic blood pressure: ≤ 85 mmHg
• Fasting glucose: ≤ 100 mg·dl-1
• Fasting triglycerides: ≤ 150 mg·dl-1
• HDL: men > 40, women > 50 mg·dl-1

Inclusion Criteria for Metabolically Unhealthy Group:

Required:

- Waist circumference: men ≥ 40, women ≥ 35 inches

AND ≥ 1 of the following:

• Systolic blood pressure: > 130 mmHg
• Diastolic blood pressure: > 85 mmHg
• Fasting glucose: > 100 mg·dl-1
• Fasting triglycerides: > 150 mg·dl-1
• HDL: men ≤ 40, women ≤ 50 mg·dl-1

Exclusion Criteria:

• BMI <18 or > 40 kg/m^2
• potential allergy to Haskap or placebo ingredients
• use of anti-inflammatory, lipid lowering, glucose lowering, blood pressure, or any other medications that may interfere with study measures
• pregnant or lactating woman
• diagnosis with type 1 or type 2 diabetes or any other condition that may interfere with study measures
• smoke cigarettes
• have taken antibiotics in the past 90 days
• take supplements including pre/probiotics or "superfoods" within 30 days of starting the study
• are planning on starting a weight loss or exercise regiment change
• follow a specific diet such as low carbohydrate, vegan, and vegetarian
• consume over 5 servings of fruit/vegetables per day
• are unwilling to reduce caffeine intake to one 8 oz serving per day for the durations of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo, Metabolically Healthy; The placebo supplement will have no polyphenol content and will be carbohydrate-matched to the experimental group. A twice daily dose (10-12 hours apart) will be consumed for 8 weeks.	Dietary supplement: Placebo comparator; A smoothie with no polyphenolic content and matched in carbohydrate composition to the experimental haskap smoothie
Experimental: Haskap, Metabolically Healthy; The haskap supplement will consist of a haskap berry smoothie. A twice daily dose (10-12) hours apart will be consumed for 8 weeks.	Dietary supplement: Haskap berry smoothie; A smoothie blend of berries and water
Placebo Comparator: Placebo, Metabolically Unhealthy; The placebo supplement will have no polyphenol content and will be carbohydrate-matched to the experimental group. A twice daily dose (10-12 hours apart) will be consumed for 8 weeks.	Dietary supplement: Placebo comparator; A smoothie with no polyphenolic content and matched in carbohydrate composition to the experimental haskap smoothie
Experimental: Haskap, Metabolically Unhealthy; The haskap supplement will consist of a haskap berry smoothie. A twice daily dose (10-12) hours apart will be consumed for 8 weeks.	Dietary supplement: Haskap berry smoothie; A smoothie blend of berries and water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
16 subunit ribosomal ribonucleic acid (16S rRNA) gut microbial composition	fecal microbial composition	8 weeks
Inflammation (pg/mL)	Serum interleukin (IL) IL-1B, IL-6, IL-10, IL-17, IL-23, tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma)	8 weeks
Lipid Panel (mg/dL)	Serum triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (CHOL), glucose (GLU)	8 weeks
F2 isoprostanes	urine	8 weeks
Untargeted metabolomic analysis	Serum metabolome	8 weeks
Untargeted metabolomic analysis	Fecal metabolome	8 weeks
Exercise Induced Fat Oxidation	Measurement in g/min of fat being utilized during exercise at 40-60% of the participants estimated VO2max	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric Assessments	waist circumference (cm)	8 weeks
Anthropometric Assessments	visceral adipose (L)	8 weeks
Anthropometric Assessments	BMI (kg/m2)	8 weeks
Anthropometric Assessments	fat free mass (%)	8 weeks
Blood pressure	SBP/DBP (mmHG)	8 weeks
Acute Diet	24-hour dietary recall using the Automated Self-Administered 24-hour Dietary. Assessment Tool (ASA24). Outcome is macronutrient and micronutrient composition of food entry.	8 weeks
Habitual Diet	Habitual diet recall using Dietary History Questionnaire (DHQ) III (1 year recall). Outcome measures are healthy eating index (HEI) scores which include nine components based on adequacy (total fruit, whole fruit, total vegetables, greens and beans, whole grains, dairy, total protein foods, seafood and plant proteins, fatty acids) and four components based on moderation (refined grains, so-dium, added sugars, saturated fats). Each component is ranked 1-10 in order of increasing health. Total HEI score is reported as the sum of all components (100 possible points) with more points indicating increased health of diet.	Baseline
Estimated VO2 max	Estimation of participants VO2 max (ml/k/min) from a Fatmax test	0 weeks

Collaborators and Investigators

• Sponsor: Montana State University
• Collaborators: Montana State Agricultural Experiment Station
• Investigators: Principal Investigator: Mary P Miles, PhD, Montana State University

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Polyphenols; Gut microbial composition; Microbial metabolism; Serum metabolome
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Inflammation; Infections; Communicable Diseases; Metabolic Diseases
• Other Study ID Numbers: 2024-1417-FCR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No