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

Amer M. JohriMarie-France HétuDaren K. HeylandJulia E. HerrJennifer KorolShawna FroesePatrick A. NormanAndrew G. DayMurray F. MatangiErin D. MichosStephen A. LaHayeFraser W. Saunders & J. David Spence 

Nutrition & Metabolism volume 19, Article number: 26 (2022) Cite this article



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).


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.


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.


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:, NCT02117661, Registered April 21, 2014,

figure 2
Quantification of carotid arterial plaque acquired by three-dimensional ultrasound.
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