Obesity-related Health Benefits of Apples

NCT03523403 | Completed

• 3 other identifiers: UGuelph Apple StudyUofG2014-2028REB#16JA013
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is characterized by an underlying inflammatory state in which various inflammatory signaling molecules, termed cytokines, affect metabolic processes central to type 2 diabetes and cardiovascular disease; leading causes of disability and death in Ontario. Such obesity-associated inflammation is partly due to the movement of endotoxin (i.e. lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria) from the gut microbiota to the blood, resulting in elevated blood levels of LPS (a condition termed metabolic endotoxemia) that stimulates inflammation. Digestion of a high-fat meal increases blood LPS and is subsequently associated with inflammation and metabolic impairments. However, in this context, little is known about how the consumption of bioactive-rich foods, such as whole apples, can improve impaired inflammatory and metabolic responses in overweight and obese individuals. Apples are a key commodity to study given that they are Ontario's predominant fruit crop with the apple industry valued at approximately $400 million, they require little food preparation, and they are common in the diet year-round. There are some, but limited, reports of potential apple-induced health benefits related to reductions in inflammation and improved metabolic responses in lean/healthy individuals, but work in overweight and obese individuals is especially lacking. Thus, to address the gap in our understanding of how daily apple intake may improve the health consequences of obesity, we will conduct a randomized clinical trial in which overweight and obese adults will consume three Ontario-grown Gala apples (approximately 300 g) as part of their typical diet in one sitting (i.e. acute consumption) and/or daily for six weeks (i.e. chronic consumption). The Acute Apple Consumption phase of the study will follow a randomized crossover design in which participants' rate of gastric emptying, efficacy of dietary lipid digestion and absorption, and production of inflammatory cytokines and biomarkers of metabolism will be assessed before and after consuming a high-fat meal (designed to provide 1 g fat/kg body weight) with or without three apples in one sitting. The Chronic Apple Consumption phase of the study will follow a randomized, controlled, parallel-arm design in which participants' (fasting) production of inflammatory cytokines and biomarkers of metabolism, as well as their gut microbiota profile, will be assessed before and after consuming three apples (or no apples) daily for six weeks. We hypothesize that the consumption of three whole apples in one sitting and daily for six weeks will improve these parameters in overweight and obese individuals at risk of developing chronic metabolic diseases.

Conditions

Obesity, Abdominal; Hyperlipidemias; Inflammation; Dysbiosis

Keywords

Obesity; Diet; Apples; Polyphenols; Soluble fibre; Blood lipids; Lipid digestion; Inflammation; Cytokines; Microbiota; Dysbiosis; Type 2 diabetes risk; Cardiovascular disease risk

Outcome Measures

Primary Outcomes (3)

• Plasma triglyceride levels

  Fasting, and for the Acute phase of the study only: 20, 40, 60, 80, 100, 120, 140, 160, 180, 240, 300, and 360 minutes post-prandially

• Plasma inflammatory cytokine levels

  E.g. adiponectin, leptin, IL-1B, IL-6, IL-10, TNF-a, MCP-1, MIP-1a, etc.

  Fasting, and for the Acute phase of the study only: 20, 40, 60, 80, 100, 120, 140, 160, 180, 240, 300, and 360 minutes post-prandially

• Gut microbiota profile

  16S rRNA gene sequencing to identify different microbes within fecal samples, representative of the gut microenvironment

  Immediately before and after the 6-week Chronic phase of the study

Secondary Outcomes (7)

• Fatty acid composition of chylomicron-rich fraction of blood

  For the Acute phase of the study only: fasting and 120, 240, and 360 minutes post-prandially

• Plasma ApoB48 levels

  For the Acute phase of the study only: fasting and 120, 240, and 360 minutes post-prandially

• Rate of gastric emptying

  For the Acute phase of the study only: fasting and 20, 40, 60, 80, 100, 120, 140, 160, 180, 240, 300, and 360 minutes post-prandially

• Levels of inflammatory cytokines secreted from peripheral blood mononuclear cells isolated from whole blood samples and stimulated with or without lipopolysaccharide

  Fasting, and for the Acute phase of the study only: 240 post-prandially

• Plasma lipopolysaccharide binding protein

  Fasting, and for the Acute phase of the study only: 20, 40, 60, 80, 100, 120, 140, 160, 180, 240, 300, and 360 minutes post-prandially

Study Arms (4)

Acute phase - intervention

EXPERIMENTAL

Participants will be asked to consume 3 whole apples and a high-fat meal (a mixture of commercially available whipping cream and milk, providing 1 g of fat per kg of body weight) within 30 minutes.

Other: Apples

Acute phase - control

NO INTERVENTION

Participants will be asked to consume a high-fat meal (a mixture of commercially available whipping cream and milk, providing 1 g of fat per kg of body weight) within 30 minutes.

Chronic phase - intervention group

EXPERIMENTAL

Participants will be asked to consume 3 whole apples per day for 6 weeks.

Other: Apples

Chronic phase - control group

NO INTERVENTION

Participants will be asked to consume no apples per day for 6 weeks.

Interventions

Apples OTHER

3 whole Ontario-grown Gala apples

Acute phase - intervention; Chronic phase - intervention group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• BMI ≥ 25 kg/m2 and/or waist circumference ≥ 40" for males or ≥ 30" for females
• Current/prior use of acetaminophen without complications

You may not qualify if:

• Pregnant or breastfeeding females
• Fasting blood glucose ≥ 7.0 mmol/L
• Chronic diseases, including by not limited to: type 2 diabetes, cardiovascular disease, liver disease, etc.
• Gastrointestinal conditions or illnesses, including but not limited to: lactose intolerance, Celiac disease, Crohn's disease, Ulcerative Colitis, Irritable Bowel Disorder
• Inflammatory conditions or active infection
• Serious major medical condition requiring hospitalization within the last year
• Taking any prescription medications (including hormonal contraceptives) or over the counter medications prescribed by a medical professional
• Taking any natural health products or dietary supplements, other than a multivitamin low in phenolic acids
• Taking any medication or natural health product contraindicated with acetaminophen
• Allergy to acetaminophen
• Use of immunomodulating agents
• Antibiotic use within last 3 months
• Alcohol consumption of ≥ 4 drinks/sitting or ≥ 14 drinks/week
• Use of tobacco products or recreational drugs

Sponsors & Collaborators

• University of Guelph: lead
• Ontario Ministry of Agriculture, Food and Rural Affairs: collaborator
• Ontario Apple Growers: collaborator
• Agriculture and Agri-Food Canada: collaborator

Study Sites (1)

Human Nutraceutical Research Unit, University of Guelph

Guelph, Ontario, N1G 2W1, Canada

Location

Related Publications (2)

• Liddle DM , Lin X , Ward EM , Cox LC , Wright AJ , Robinson LE . Apple consumption reduces markers of postprandial inflammation following a high fat meal in overweight and obese adults: A randomized, crossover trial. Food Funct. 2021 Jul 21;12(14):6348-6362. doi: 10.1039/d1fo00392e. Epub 2021 Jun 8.

  PMID: 34105575 DERIVED

• Liddle DM, Lin X, Cox LC, Ward EM, Ansari R, Wright AJ, Robinson LE. Daily apple consumption reduces plasma and peripheral blood mononuclear cell-secreted inflammatory biomarkers in adults with overweight and obesity: a 6-week randomized, controlled, parallel-arm trial. Am J Clin Nutr. 2021 Aug 2;114(2):752-763. doi: 10.1093/ajcn/nqab094.

  PMID: 33964852 DERIVED

MeSH Terms

Conditions

Obesity, Abdominal; Hyperlipidemias; Inflammation; Dysbiosis; Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Pathologic Processes

Study Officials

• Danyelle M Liddle, MSc

  University of Guelph

  STUDY DIRECTOR

• Xinjie Lin, MSc

  University of Guelph

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: All 60 participants will participate in the Chronic phase of the study, which will follow a randomized, controlled, parallel-arm design to investigate the effects of consuming 3 apples per day for 6 weeks. 30 of those 60 participants will also participate in the Acute phase of the study, which will follow a randomized, crossover design to investigate the effects of eating 3 apples in addition to a high-fat meal in one sitting.

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: May 14, 2018
• Study Start: October 12, 2017
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: April 18, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)