Modulation of Insulin Sensitivity by Betaine Upregulation of FGF21

People with poor insulin sensitivity do not respond normally to elevations in blood sugar. This may increase their risk of developing diabetes in the future. The purpose of this research study is to determine if the nutrient betaine, found in beets, spinach and wheat products, can enhance the production of fetal growth factor 21 (FGF21), a molecule that is believed to promote insulin sensitivity.

Study Overview

• Status: Completed
• Conditions: Insulin Sensitivity
• Intervention / Treatment: Dietary supplement: Betaine; Dietary supplement: Dextrose

Detailed Description

AIM: To determine if betaine is a modulator of FGF21 in humans. Low plasma betaine is associated with an increased risk of metabolic syndrome, but the mechanisms modulating this correlation are poorly delineated. Betaine bioavailability in humans is determined by dietary intake and genetic polymorphisms that influence betaine metabolism. Therefore, moderating betaine levels could be particularly beneficial for some individuals. FGF21 is elevated in response to insulin insensitivity and is under active investigation as a therapeutic modality. The mechanisms of action of FGF21 and betaine on insulin sensitivity in humans are incompletely understood. This study tests the hypothesis that betaine induces FGF21 secretion and insulin sensitizing actions in humans by measuring plasma FGF21, betaine, choline (betaine precursor), glucose, insulin and adiponectin in response to betaine supplementation over a 24 hour time course in 20 healthy, lean individuals. This pilot nutrition intervention will provide key preliminary evidence for understanding whether and how betaine exerts metabolic benefit in humans and will inform a future study to investigate the novel betaine-FGF21-insulin sensitivity axis in a larger cohort.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Kannapolis, North Carolina, United States, 28081
      • UNC Nutrition Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• Able/willing to consume study meals
• Non-smoker
• BMI in normal range (18-24.9)

Exclusion Criteria:

• Use of chronic medications
• Abnormal physical examination or chronic illness
• Use of drugs or medications known to alter choline/betaine metabolism
• Consumption of more than 2 oz of alcohol/day or 24 oz wine/day
• Use of choline/betaine-containing dietary supplements during the previous 3 months
• Diagnosed with Cystathionine Beta-Synthase (CBS) Deficiency
• Pregnant or breastfeeding
• Known hypersensitivity to betaine
• Current substance abuse or addiction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Betaine; 6 gram dose of betaine delivered in encapsulated form	Dietary supplement: Betaine; 6 gram one-time dose of betaine delivered in encapsulated form with an unsweetened beverage
PLACEBO_COMPARATOR: Dextrose; 6 gram dose of dextrose delivered in encapsulated form	Dietary supplement: Dextrose; 6 gram one-time dose of dextrose delivered in encapsulated form with an unsweetened beverage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma Fetal Growth Factor 21 (FGF21) concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement
Plasma choline concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement
Plasma betaine concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement
Plasma glucose concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement
Plasma insulin concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement
Plasma adiponectin concentration	0, 0.5, 1, 2, 4, 8, and 24 hours post- betaine or placebo supplement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Typical dietary intake	Assessed via questionnaire	During day 2 of the first 3 day phase
Typical exercise habits	Assessed via questionnaire	During day 2 of the first 3 day phase

Collaborators and Investigators

• Sponsor: UNC Nutrition Research Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (ESTIMATE): April 21, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): August 12, 2014
• Last Update Submitted That Met QC Criteria: August 11, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Betaine
• Other Study ID Numbers: 13-2548