Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome

Authors

Amer M. Johri, Queen's University, School of Medicine
Marie France Hétu, Queen's University, School of Medicine
Daren K. Heyland, Clinical Evaluation Research Unit
Julia E. Herr, Queen's University, School of Medicine
Jennifer Korol, Clinical Evaluation Research Unit
Shawna Froese, Clinical Evaluation Research Unit
Patrick A. Norman, Kingston Health Sciences Centre
Andrew G. Day, Kingston Health Sciences Centre
Murray F. Matangi, Kingston Heart Clinic
Erin D. Michos, Johns Hopkins School of Medicine
Stephen A. LaHaye, Queen's University, School of Medicine
Fraser W. Saunders, Kingston Health Sciences Centre
J. David Spence, Western UniversityFollow

Document Type

Article

Publication Date

12-1-2022

Journal

Nutrition and Metabolism

Volume

19

Issue

1

URL with Digital Object Identifier

10.1186/s12986-022-00661-9

Abstract

Background: L-carnitine (L-C), a ubiquitous nutritional supplement, has been investigated as a potential therapy for cardiovascular disease, but its effects on human atherosclerosis are unknown. Clinical studies suggest improvement of some cardiovascular risk factors, whereas others show increased plasma levels of pro-atherogenic trimethylamine N-oxide. The primary aim was to determine whether L-C therapy led to progression or regression of carotid total plaque volume (TPV) in participants with metabolic syndrome (MetS). Methods: This was a phase 2, prospective, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined as ≥ 3/5 cardiac risk factors: elevated waist circumference; elevated triglycerides; reduced HDL-cholesterol; elevated blood pressure; elevated glucose or HbA1c; or on treatment. Participants with a baseline TPV ≥ 50 mm3 were randomized to placebo or 2 g L-C daily for 6 months. Results: The primary outcome was the percent change in TPV over 6 months. In 157 participants (L-C N = 76, placebo N = 81), no difference in TPV change between arms was found. The L-C group had a greater increase in carotid atherosclerotic stenosis of 9.3% (p = 0.02) than the placebo group. There was a greater increase in total cholesterol and LDL-C levels in the L-C arm. Conclusions: Though total carotid plaque volume did not change in MetS participants taking L-C over 6-months, there was a concerning progression of carotid plaque stenosis. The potential harm of L-C in MetS and its association with pro-atherogenic metabolites raises concerns for its further use as a potential therapy and its widespread availability as a nutritional supplement. Trial registration: ClinicalTrials.gov, NCT02117661, Registered April 21, 2014, https://clinicaltrials.gov/ct2/show/NCT02117661.