Modulation of Insulin Sensitivity by Betaine Upregulation of FGF21

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Modulation of Insulin Sensitivity by Betaine Upregulation of FGF21

Conditions
-----------------
Insulin Sensitivity

Intervention / Treatment
-----------------
* Dietary Supplement: Betaine
* Dietary Supplement: Dextrose


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Betaine<br>6 gram dose of betaine delivered in encapsulated form | Dietary Supplement: Betaine<br>* 6 gram one-time dose of betaine delivered in encapsulated form with an unsweetened beverage<br>|
| Placebo Comparator: Dextrose<br>6 gram dose of dextrose delivered in encapsulated form | Dietary Supplement: Dextrose<br>* 6 gram one-time dose of dextrose delivered in encapsulated form with an unsweetened beverage<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |