Saskatoon Berry on Metabolism and Gut Microbiota in Healthy Subjects

Pilot Study on the Effects of Saskatoon Berry on Glucose Metabolism, Insulin Resistance and Gut Microbiota in Healthy Human Subjects

Diabetes becomes epidemic in worldwide countries. Nine out of ten diabetic patients are type 2 diabetes (T2D). T2D is characterized by insulin resistance and obesity. Uncontrolled diabetes leads to serious consequences including heart attack, stroke, chronic renal failure, liver failure, blindness and low limb amputation. Most of hypoglycemic medications have side effects. Natural foods or nutraceuticals with hypoglycemic potential are expected to provide a safer management for diabetic patients. Saskatoon berry is a popular fruit in Canadian Prairie and Northern states in USA. Our recent studies demonstrated Saskatoon berry powder (SBp) attenuated hyperglycemia, hyperlipidemia, insulin resistance, inflammation, liver steatosis and gut dysbiosis in diet-induced insulin resistant mice, a model for T2D. The results in antidiabetic activities of SBp have been supported by other groups in high fat fed rats. The combination of findings suggest that Saskatoon berry is good candidate of prebiotic functional food as a supplemental remedy for reducing insulin resistance, metabolic syndrome and preventing or managing T2D. The effect of Saskatoon berry and its products on metabolic disorders have not been studied in human subjects. We propose to examine the effect of oral administration of freeze-dried Saskatoon berry on glucose metabolism, insulin resistance and gut microbiota in healthy adults in a pilot trial.

Study Overview

• Status: Recruiting
• Conditions: Nutritional and Metabolic Diseases
• Intervention / Treatment: Dietary supplement: Saskatoon berry

Detailed Description

Subject recruitment: Healthy subjects (males and females, 18-75 years of age) in Winnipeg, who are voluntarily signing an informed consent approved by Research Ethics Board in University of Manitoba, will be eligible to the study. Exclusion criteria include: 1) candidates have a history of myocardial infarction, stroke, hypertension, diabetes, hyperlipidemia, chronic kidney disease; 2) participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a month.

Dietary product: Freeze dried Saskatoon berry have been obtained from Prairie Berries Inc. The berries were freshly frozen and no any supplementation was added to the dried berry. The product has been processed by certified facilities and the batch of dried berry has passed pathogen analysis.

Regimen: Participants (n=20) will orally administrate 30 g/day of freeze dried Saskatoon berry during breakfast for 10 weeks.

Scheduled visits:

Visit 1: Consent and enrollment. A questionnaire for domestic questionnaire including dietary intake and physical activity will be filled. Measurements of body weight, height and blood pressure will be taken during the visit.

Visit 2 (<1 week from the visit 1 and before the start of berry administration): 75 g oral glucose tolerance test (OGTT) after an overnight fasting. Insulin, liver enzymes (alanine transaminase or ALT, aspartate transaminase or AST), creatinine, lipid profile and inflammation markers (e. x. tumor necrosis factor-alpha or TNF-alpha) will be measured as baseline.

Participants will be provided with sealed packages of dried Saskatoon berry and instruction of the administration. Insulin and lipid profile will be tested in blood samples withdrawn at fast glucose for OGTT.

Visit 3 (at 5 weeks after the start of administration of Saskatoon berry): Participants will be asked to provide feedback on general well-being and the intake of Saskatoon berry. Body weight, blood pressure and heart rate will be measured and recorded.

Visit 4 (at 10 weeks after the start of the dietary regimen): Participants will be asked to collect stool sample with the collection kit within 1 week before the visit and bring it to the visit. They will also be asked to have an overnight fasting the night before visit. They will receive an OGTT. Blood samples for insulin, liver enzymes, creatinine, lipid profile and inflammation markers will be collected from each participant. During the visit, body weight, blood pressure and heart rate of participants will be taken. Questionnaires on participants' dietary intake, physical activity and feedback to the study will be completed.

Participants will receive a $50 honorarium gift card for their participation. Sample collection and analyses: OGTT, ALT, AST, creatinine and lipid profile will be analyzed in Clinical Chemistry in Health Science Centre, Winnipeg. Inflammation mediators will be analyzed in the Dr. G. Shen's laboratory. Homeostatic model assessment-insulin resistance or homeostatic model assessment for insulin resistance (HOMA-IR) will be calculated based on fasting plasma glucose and insulin. Stool samples will be aliquoted and stored under -80°C before submission. Microbiome analysis will be conducted in Integrate Microbiome Resource at Dalhousie University.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Garry Shen, MD PhD; Phone Number: 204-789-3816; Email: garry.shen@umanitoba.ca
• Study Contact Backup: Name: Amy Hui, PhD; Phone Number: 204-780-3985; Email: amy.hui@umanitoba.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Recruiting
      • University of Manitoba
      • Contact: Garry Shen, MD PhD; Phone Number: 204-789-3816; Email: gshen@ms.umanitoba.ca
      • Contact: Amy Hui, PhD; Phone Number: 204-789-3985; Email: Amy.Hui@umanitoba.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy subjects living in Winnipeg.
2. Willingness to sign an informed consent.

Exclusion Criteria:

1. History of myocardial infarction, stroke, hypertension, diabetes, hyperlipidemia, chronic kidney disease.

2) Participants are taking hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a 1 month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm	Dietary supplement: Saskatoon berry; Freeze dried Saskatoon berry (30 g) will be orally administrated daily for 10 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose tolerance	75 g oral glucose tolerance test (2 h postprandial plasma glucose in mM/L)	Changes from baseline to 10 weeks after the start of dietary intervention
Gut microbiome	Stool will be collected for 16S rRNA gene sequencing in % of abundance	Changes from baseline to 10 weeks after the start of dietary intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile	total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol in mM/L	Onset and 10 weeks after the start of dietary intervention
C-reactive protein	C-reactive protein in mg/L	Onset and 10 weeks after the start of dietary intervention
Liver enzymes	ALT, AST in units/L	Onset and 10 weeks after the start of dietary intervention
Body mass index accord to body weight and height	Body weight in kg, heights in cm, and body mass index in kg/M^2	Onset, 5 and 10 weeks after the start of dietary intervention
Blood pressure	Systolic and diastolic blood pressure in mmHg	Onset, 5 and 10 weeks after the start of dietary intervention
Tumor necrosis factor-alpha	Tumor necrosis factor-alpha in pg/mL	Onset, 5 and 10 weeks after the start of dietary intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary intake, physical activities	3 day food intake and the type in gram, frequency in time/day and length of physical activities index in artificial score (score scale 0-3, high means more activity)	Onset and 10 weeks after the start of dietary intervention

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Diabetes Canada
• Investigators: Principal Investigator: Garry Shen, PhD, University of Manitoba

Publications and helpful links

General Publications

• Zhao R, Khafipour E, Sepehri S, Huang F, Beta T, Shen GX. Impact of Saskatoon berry powder on insulin resistance and relationship with intestinal microbiota in high fat-high sucrose diet-induced obese mice. J Nutr Biochem. 2019 Jul;69:130-138. doi: 10.1016/j.jnutbio.2019.03.023. Epub 2019 Apr 9.
• Huang F, Zhao R, Xia M, Shen GX. Impact of Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice. Microorganisms. 2020 Aug 14;8(8):1238. doi: 10.3390/microorganisms8081238.
• du Preez R, Wanyonyi S, Mouatt P, Panchal SK, Brown L. Saskatoon Berry Amelanchier alnifolia Regulates Glucose Metabolism and Improves Cardiovascular and Liver Signs of Diet-Induced Metabolic Syndrome in Rats. Nutrients. 2020 Mar 27;12(4):931. doi: 10.3390/nu12040931.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2023
• Primary Completion (Estimated): October 20, 2025
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Healthy subjects; Gut microbiota; Glucose tolerance; Saskatoon berry
• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: HS23500 (B2019:122)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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