Metabolic Effects of Betaine Supplementation

Bedside to Bench and Back: Cardiometabolic Effects of Betaine Supplementation

Betaine is important in cellular metabolic pathways. Few epidemiologic studies link betaine levels to diabetes and cardiovascular disease. Small human studies suggest benefit for non-alcoholic liver disease. In this study we will determine if administration of betaine improves metabolic measures, liver fat and/or endothelial function in humans with glucose intolerance who are overweight.

Study Overview

• Status: Completed
• Conditions: Obesity; Dysglycemia
• Intervention / Treatment: Drug: Betaine; Drug: Placebo

Detailed Description

This study is a single site, prospective, randomized (1:1), double masked, placebo controlled trial to assess metabolic effects of betaine compared to placebo on glycemia and insulin sensitivity, liver fat and endothelial function.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center and Brigham and Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) Men and women aged 21-65 years old;
• 2) Dysglycemia/prediabetes is defined as impaired fasting glucose (≥100 mg/dl), impaired glucose tolerance (2 hour post 75 g oral glucose load 140-200 mg/dl) or HbA1c 5.7-6.5%);
• 3) overweight to grade 3 obesity (BMI 25 to 45 kg/m2).

Exclusion Criteria:

• 1) cystathionine beta-synthase (CBS deficiency);
• 2) Presence of liver disease other than NAFLD;
• 3) Use of medications causing steatosis;
• 4) Known alcohol consumption ≥ 2 drink per day;
• 5) Use of medications known to cause insulin resistance;
• 6) Use of weight loss drugs (or program) within 3 months of screening;
• 7) Treatment with any experimental drug within the past 6 months;
• 8) Subjects must be willing to abstain from use of phosphodiesterase type 5 (PDE-5) inhibitors;
• 9) Pregnancy or lactation, and women of child bearing potential must use adequate contraception;
• 10) Surgery within 30 days of screening;
• 11) Heart disease defined as New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months;
• 12) Uncontrolled hypertension;
• 13) eGFR <60; 14) History of acquired immune deficiency syndrome;
• 15) History of malignancy within 5 years;
• 16) Hemoglobin <12 g/dL (males), <10 g/dL (females);
• 17) Triglycerides (TG) >500 mg/dL;
• 18) Poor mental function or any other reason to expect patient difficulty in complying with study requirements;
• 19) Metal clips or implants that preclude magnetic resonance imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo administered orally in divided doses over 3 months
Active Comparator: Betaine	Drug: Betaine; Betaine or placebo administered orally in divided doses over 12 weeks; Other Names: trimethyl glycine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting and 2 Hour Glucose Levels, Comparing Baseline and 12 Weeks.	Glucose levels were analyzed in the fasting state and two hours after glucose load, comparing baseline to 12 weeks.	baseline and 12 weeks
Change in Glucose AUC at 12 Weeks From Baseline (Glucose Tolerance)	Glucose tolerance was assessed by oral glucose tolerance, assessed using the change from baseline for fasting and 2 hour glucose, and change in Glucose AUC at 12 weeks from baseline was measured.	baseline and 12 weeks
Hepatic Fat, Change From Baseline	Intrahepatic triglyceride levels were assessed by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (Siemens 3T TIM Skyra, software version VD13; Siemens, Erlangen, Germany).	baseline and 12 weeks
Endothelial Function	Brachial artery reactivity to flow and nitroglycerin stimuli, assessed as percent change from baseline	baseline and 12 weeks
Insulin Sensitivity	Euglycemic hyperinsulinemic clamp at baseline and at end of study (12 weeks) for assessment of: glucose disposal (M) at low (25 mU/m2/min) and high (180 mU/m2/min) insulin infusion rates, reported as raw data; measurement of endogenous glucose production at basal and low insulin infusion (25 mU/m2/min), reported as change from measures at baseline of individual study days	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center
• Collaborators: American Diabetes Association

Publications and helpful links

General Publications

• Grizales AM, Patti ME, Lin AP, Beckman JA, Sahni VA, Cloutier E, Fowler KM, Dreyfuss JM, Pan H, Kozuka C, Lee A, Basu R, Pober DM, Gerszten RE, Goldfine AB. Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3038-3049. doi: 10.1210/jc.2018-00507.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: September 16, 2013
• First Submitted That Met QC Criteria: September 20, 2013
• First Posted (Estimate): September 25, 2013

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Obesity; Glucose Intolerance
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Glycine Agents; Glycine; Betaine
• Other Study ID Numbers: 2013P001265; 7-13-CE-17 (Other Grant/Funding Number: American Diabetes Association 7-13-CE-17)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No