Johri Amer M, Hétu Marie-France, Heyland Daren K, Herr Julia E, Korol Jennifer, Froese Shawna, Norman Patrick A, Day Andrew G, Matangi Murray F, Michos Erin D, LaHaye Stephen A, Saunders Fraser W, Spence J David
Department of Medicine, Cardiovascular Imaging Network at Queen's University, Kingston, ON, Canada.
Department of Medicine, Queen's University, 76 Stuart Street, KGH FAPC 3, Kingston, ON, K7L 2V7, Canada.
Nutr Metab (Lond). 2022 Apr 2;19(1):26. doi: 10.1186/s12986-022-00661-9.
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 mm 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.
ClinicalTrials.gov, NCT02117661, Registered April 21, 2014, https://clinicaltrials.gov/ct2/show/NCT02117661 .
左旋肉碱（L-C）是一种普遍存在的营养补充剂，已被研究作为心血管疾病的潜在治疗方法，但其对人类动脉粥样硬化的影响尚不清楚。临床研究表明，它能改善一些心血管危险因素，而其他研究则显示促动脉粥样硬化的氧化三甲胺血浆水平升高。主要目的是确定L-C治疗是否会导致代谢综合征（MetS）参与者的颈动脉总斑块体积（TPV）进展或消退。
这是一项2期前瞻性双盲随机安慰剂对照双中心试验。MetS被定义为≥3/5项心脏危险因素：腰围增加；甘油三酯升高；高密度脂蛋白胆固醇降低；血压升高；血糖或糖化血红蛋白升高；或正在接受治疗。基线TPV≥50mm的参与者被随机分为安慰剂组或每日服用2g L-C组，为期6个月。
主要结局是6个月内TPV的变化百分比。在157名参与者中（L-C组n = 76，安慰剂组n = 81），两组之间的TPV变化没有差异。L-C组的颈动脉粥样硬化狭窄增加幅度比安慰剂组大9.3%（p = 0.02）。L-C组的总胆固醇和低密度脂蛋白胆固醇水平升高幅度更大。
尽管服用L-C的MetS参与者在6个月内颈动脉总斑块体积没有变化，但颈动脉斑块狭窄出现了令人担忧的进展。L-C在MetS中的潜在危害及其与促动脉粥样硬化代谢物的关联，引发了人们对其作为潜在治疗方法进一步使用以及作为营养补充剂广泛可得性的担忧。
ClinicalTrials.gov，NCT02117661，2014年4月21日注册，https://clinicaltrials.gov/ct2/show/NCT02117661 。
