Investigation on the Effect of Carnitine Supplement on Gut Microbiota and TMAO Production Capacity

In this project, the investigators aim to explore the impact of dietary L-carnitine supplementation on the TMAO production capacity of gut microbiota.

Study Overview

• Status: Completed
• Conditions: Dietary Exposure
• Intervention / Treatment: Dietary supplement: L-carnitine supplementation (500 mg per tablet per day, purchased from GNC company)

Detailed Description

Recent studies have established plasma trimethylamine N-oxide (TMAO) levels as a strong, independent risk factor for cardiovascular disease. TMAO is produced by the interaction between gut microflora and ingested L-carnitine from food. Research indicates that both plasma TMAO concentration and the TMAO production capacity of gut microbiota in vegetarians are significantly lower than in omnivores, likely due to the reduced L-carnitine intake in vegetarian diets. This study aims to explore the impact of L-carnitine supplementation on the TMAO production capacity of human gut microbiota and to identify TMAO-producing bacteria within the gut microflora. The study plans to recruit both omnivore and vegetarian volunteers to undergo a one-month L-carnitine supplementation, followed by an evaluation of changes in TMAO production using an oral L-carnitine challenge test, along with gut microbiota assessment. TMAO concentration will be measured using LC-MS/MS, and gut microbiome analysis will be conducted through shotgun metagenome sequencing. Bioinformatic analysis may reveal potential TMAO-producing bacteria. Understanding the changes in TMAO production and gut microbiota composition post-L-carnitine supplementation may enhance our knowledge of the interplay between L-carnitine supplements, TMAO, and gut microflora.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy subjects aged 20 to 65 years old
• no usage of antibiotics within one month
• no use of carnitine supplement within one month

Exclusion Criteria:

• having serious GI disorder
• medical history of myasthenia gravis
• history of diabetes,
• history of hyperparathyroidism,
• history of chronic kidney disease
• history of epilepsy
• history of severe anemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-carnitine supplementation; All participants received L-carnitine supplementation (500 mg per tablet per day, provided by GNC) for one month. Oral carnitine challenge tests and fecal sampling were conducted both before and after the intervention.	Dietary supplement: L-carnitine supplementation (500 mg per tablet per day, purchased from GNC company)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMAO level	plasma and urine TMAO concentrations of oral carnitine challenge test	Before and 1 month after L-carnitine supplementation
Compositional and functional alterations of gut microbiota	The compositional and functional changes of gut microbiota will be evaluated by shotgun metagenome sequencing. Taxonomy will be calculated as relative abundance of species-level genome bins (SGBs) and specific bacteria genes will be quantified as Reads Per Kilobase per Million (RPKM).	Before and 1 month after L-carnitine supplementation

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Director: Ming-Shiang Wu, MD, PhD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Wu WK, Chen CC, Liu PY, Panyod S, Liao BY, Chen PC, Kao HL, Kuo HC, Kuo CH, Chiu THT, Chen RA, Chuang HL, Huang YT, Zou HB, Hsu CC, Chang TY, Lin CL, Ho CT, Yu HT, Sheen LY, Wu MS. Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut. 2019 Aug;68(8):1439-1449. doi: 10.1136/gutjnl-2018-317155. Epub 2018 Oct 30.

Study record dates

Study Major Dates

• Study Start: May 18, 2016
• Primary Completion (Actual): November 20, 2017
• Study Completion (Actual): October 7, 2019

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: July 17, 2016
• First Posted (Estimated): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 10, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Gut microbiota; Trimethylamine N-oxide; Oral carnitine challenge test; L-carnitine supplementation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: 201507055MINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO