Carnitine and Liver Mitochondria Fatty Acid Processing

Effects of Carnitine Supplementation on Liver Mitochondria Fatty Acid Processing

This double-blind, placebo-controlled randomized trial will assess whether 14 days of oral carnitine supplementation modifies mitochondrial fatty acid processing in healthy young adults.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2; Insulin Resistance
• Intervention / Treatment: Dietary supplement: L-Carnitine; Dietary supplement: Placebo

Detailed Description

This project will use stable isotope techniques and magnetic resonance spectroscopy (MRS) to take a first step toward clarifying how the benefit of oral carnitine supplementation depends on basal mitochondrial fatty acid processing (MFAP) and MFAP modification, with a specific focus on the liver. Approximately 24 healthy young individuals will be enrolled, with 20 expected to complete. Before and after 14 days of oral carnitine supplementation or placebo, MFAP will be measured using measures of acetyl-carnitine concentration (from long-TE proton MRS) and de novo lipogenesis (DNL, from analysis of blood metabolites following 13C-labeled acetate infusion and high-fructose drink challenge). The MFAP measures will be collected before and after loading participants with a high-fructose drink. Fructose is solely metabolized by the liver.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 20-40 years
• BMI of 24.5-35.5 kg/m2
• Willingness to eat a prescribed diet of standard meals for a total of six days
• Willingness to undergo carnitine or placebo supplementation for two weeks
• Willingness to undergo study procedures including blood draws, MRS, C13 acetate infusion, DXA, muscle biopsy, and consumption of a sugary drink over the course of 6 hours

Exclusion Criteria:

• Unstable weight in the last 3 months (gain or loss >7 lb (3.2 kg)
• Significant changes in the diet or level of physical activity within the past month
• Clinical history of diabetes or cancer
• Clinically diagnosed heart, kidney, lung, thyroid, liver disease or abnormal liver enzymes that are, in the opinion of the investigator, clinically significant and represent a problem for study inclusion
• Screening fasting glucose > 125 mg/dL
• Screening blood pressure >140 systolic or >90 diastolic
• Use of certain prescribed medications at the discretion of the MI
• Smoking or use of tobacco products in the last 6 months
• Pregnancy or breastfeeding
• Clinically diagnosed neuropsychiatric conditions
• Diets that deviate extremely from the typical western diet in terms of increased meat intake are excluded, at the discretion of the MI.
• Known aversion to or refusal to drink sugary beverages
• Taking any over the counter drugs that alter the intestinal tract, at the discretion of the MI (for example, anti-cholinergic drugs and erythromycin)
• Have taken carnitine supplements regularly in the past 3 months
• Unwilling to discontinue use of dietary supplements containing significant amounts of carnitine or abstain from use one week prior to trial, at the discretion of the MI
• Women who have undergone partial hysterectomy with intact ovarian function
• Standard contra-indications to MRS, including non-removable metallic or electronic implants, claustrophobia or other fear of confinement, or inability to tolerate loud scanner noise
• Calf does not fit into the MRI coil, at the discretion of the PI
• Refusal to allow use of anonymized versions of collected data for research after this study is over

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Carnitine; 500 mg of L-carnitine to be taken 3 times a day 15 minutes before meals for 14 days.	Dietary supplement: L-Carnitine; 500 mg tablets of L-Carnitine taken 3 times daily before meals.
PLACEBO_COMPARATOR: Placebo; 500 mg of placebo to be taken 3 times a day 15 minutes before meals for 14 days.	Dietary supplement: Placebo; 500 mg tablets of L-Carnitine taken 3 times daily before meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver mitochondrial fatty acid processing	Change from baseline in liver mitochondrial fatty acid processing during high-fructose drink challenge	Day 18

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Collaborators: University of Tennessee; Touro University
• Investigators: Principal Investigator: Owen Carmichael, Ph.D., Pennington Biomedical Research Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2017
• Primary Completion (ACTUAL): May 11, 2018
• Study Completion (ACTUAL): May 11, 2018

Study Registration Dates

• First Submitted: June 16, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (ACTUAL): June 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: PBRC 2016-076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized blood assay results, MRI data, and other de-identified clinical lab data will be shared with other researchers beginning 6 months after study completion. It may be obtained through a written request to the PI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No