Glycemic Index/Saturated Fatty Acid Diet and Hepatic Fat

The Effect of a Low Compared to a High Glycemic Index/Saturated Fatty Acid Diet on Hepatic Fat

Excessive fat in the liver is associated with impairments in metabolic health. Reducing the amount of carbohydrates and fat both have been shown to reduce liver fat. However, not only the amount fats and carbohydrates, but also their quality have been shown to influence liver fat. Diets high in saturated fatty acids (SFA) and diets with a high glycemic index (GI) have been shown to increase liver fat content. However, available data from human dietary intervention studies is limited and these studies did not reflect a realistic diet. In the present study a combination of low GI/SFA on the one hand and high GI/SFA on the other hand is used to reflect realistically a healthy and an unhealthy diet as they are actually consumed by the Dutch population.

The primary objective of this study is to investigate whether a two-week low compared to high GI/SFA diet reduces liver fat content. In addition, it will be investigated whether a two- week low compared to high GI/SFA diet reduces DNL, lowers the 24-hour glycemic response, lowers hepatic glycogen content, increases hepatic fat oxidation and changes hepatic lipid composition. Furthermore, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon the low and high GI/SFA diets.

Study Overview

• Status: Completed
• Conditions: Obesity; Diet, Healthy; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Behavioral: High GI/SFA diet; Behavioral: Low GI/SFA diet

Detailed Description

Rationale:

Excessive fat in the liver is associated with impairments in metabolic health. Reducing the amount of carbohydrates and fat both have been shown to reduce liver fat. However, not only the amount fats and carbohydrates, but also their quality have been shown to influence liver fat. Diets high in saturated fatty acids (SFA) and diets with a high glycemic index (GI) have been shown to increase liver fat content. However, available data from human dietary intervention studies is limited and these studies did not reflect a realistic diet. Here the investigators want to combine low GI/SFA on the one hand and high GI/SFA on the other hand to reflect realistically a healthy and an unhealthy diet as they are actually consumed by the Dutch population. It is hypothesized that such a low compared to a high GI/SFA diet reduces liver fat content and possibly liver fat composition. Furthermore, underlying pathways involved in mediating those changes in liver fat are largely unknown. Hepatic lipid storage can originate from several metabolic pathways, including de novo lipogenesis (DNL) or decreased hepatic fat oxidation. Based on current literature the investigators hypothesize that with the diets chosen here, both DNL (by differences in GI) and fat oxidation (by differences in fat composition) will be involved in causing changes in liver fat.

Objective:

The primary objective of this study is to investigate whether a two-week low compared to high GI/SFA diet reduces liver fat content. In addition, it will be investigated whether a two- week low compared to high GI/SFA diet reduces DNL, lowers the 24-hour glycemic response, lowers hepatic glycogen content, increases hepatic fat oxidation and changes hepatic lipid composition. Furthermore, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon the low and high GI/SFA diets.

Study design:

This is a randomized cross-over study comparing the effects of a high GI/SFA compared to a low GI/SFA diet.

Study population:

Up to seventeen healthy overweight/obese males and postmenopausal females, aged between 45-75 years and BMI between 27-38 kg/m2 will participate in the study (minimally 13 volunteers need to finish the study).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 ER
    • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Caucasian
• Male or postmenopausal female
• Aged 45-75 years at start of the study
• Body mass index (BMI) 27 - 38 kg/m2
• Stable dietary habits (no weight loss or gain >3kg in the past 3 months) Sedentary lifestyle (not more than 2 hours of sports per week)
• TG between 1.0 and 4.0 mmol/L

Exclusion Criteria:

• Type 2 diabetes
• Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's or dependent physician's opinion interfere with the study
• Contra-indication for MRI (which can be found in appendix II)
• Alcohol consumption of >2 servings per day
• Smoking
• Use of medication known to interfere with the safety of study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High GI/SFA diet; Subjects will adhere to a two-week high GI and high SFA diet. Crossover design, randomly assigned to start with either high GI/SFA or low GI/SFA. 4 week washout between the two diets.	Behavioral: High GI/SFA diet; Subject will adhere to a 2 week high GI/SFA diet.
Experimental: Low GI/SFA diet; Subjects will adhere to a two-week low GI and low SFA diet. Crossover design, randomly assigned to start with either high GI/SFA or low GI/SFA. 4 week washout between the two diets.	Behavioral: Low GI/SFA diet; Subject will adhere to a 2 week low GI/SFA diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic fat content	Expressed as a percentage, measured by 1H-MRS	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic De Novo Lipogenesis	Percentage of palmitate in VLDL-TG originating from DNL	20 hours
Hepatic fat composition (%SFA, MUFA, PUFA)	Measured by 1H-MRS	20 minutes
Hepatic glycogen content	Measured by 13C-MRS	20 minutes

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Unilever R&D
• Investigators: Principal Investigator: Vera Schrauwen-Hinderling, PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): March 23, 2021
• Study Completion (Actual): March 23, 2021

Study Registration Dates

• First Submitted: August 1, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 14, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Diet; NAFLD; Glycemic index
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NL69685.068.19

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