Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 65, Issue 3, Pages 289-295Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000000197
Keywords
l-carnitine; hemodialysis; TMA; TMAO; atherosclerosis
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22590904, 25282029]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [26860487, 25282029] Funding Source: KAKEN
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Objectives:Food or supplement-derived l-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral l-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue.Methods:Thirty-one HD patients with carnitine deficiency were treated with oral l-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured.Results:Oral l-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline (AGE) was positively correlated with sICAM-1 (P = 0.043) and was a sole independent determinant of sICAM-1 (R-2 = 0.133, P = 0.043).Conclusions:This study demonstrated that although oral l-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of l-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.
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