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. 2022 Apr 2;19(1):26.
doi: 10.1186/s12986-022-00661-9.

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

Amer M Johri  1   2 , Marie-France Hétu  3 , Daren K Heyland  4 , Julia E Herr  3 , Jennifer Korol  4 , Shawna Froese  4 , Patrick A Norman  5 , Andrew G Day  5 , Murray F Matangi  6 , Erin D Michos  7 , Stephen A LaHaye  8 , Fraser W Saunders  9 , J David Spence  10
Affiliations

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

Amer M Johri et al. Nutr Metab (Lond). .

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 .

Keywords: Cardiovascular; Carotid; L-carnitine; Plaque; Ultrasound.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT participant flow diagram
Fig. 2
Fig. 2
Quantification of carotid arterial plaque acquired by three-dimensional ultrasound. Philips VPQ software was used to assess plaque in 3D. A cross section of the vessel demonstrates a percent lumen reduction (stenosis) of 36% at baseline compared to 47% at month 6
Fig. 3
Fig. 3
Forest plot of stratified sub-analysis of percent change in stenosis. Although we found significant differences in percent increase of carotid stenosis within sub-groups, no tests for treatment arm by sub-group interactions reached p < 0.05. LC, L-carnitine. N = 157
See this image and copyright information in PMC

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References

    1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC, Jr, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Circulation. 2009;120:1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644. - DOI - PubMed
    1. Alberti KG, Zimmet P, Shaw J, Group IDFETFC The metabolic syndrome–a new worldwide definition. Lancet. 2005;366:1059–1062. doi: 10.1016/S0140-6736(05)67402-8. - DOI - PubMed
    1. Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Role of carnitine in disease. Nutr Metab (Lond) 2010;7:30. doi: 10.1186/1743-7075-7-30. - DOI - PMC - PubMed
    1. Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Annu Rev Nutr. 1986;6:41–66. doi: 10.1146/annurev.nu.06.070186.000353. - DOI - PubMed
    1. Mingorance C, Rodriguez-Rodriguez R, Justo ML, Herrera MD, de Sotomayor MA. Pharmacological effects and clinical applications of propionyl-L-carnitine. Nutr Rev. 2011;69:279–290. doi: 10.1111/j.1753-4887.2011.00387.x. - DOI - PubMed

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