To the best of our knowledge, this is the first clinical study to examine the antioxidant activity in CAD patients after oral LC supplementation (1000 mg/d). In this clinical trial, we have demonstrated that LC administered at a dose of 1000 mg/d for 12 weeks significantly reduced the oxidative stress and increased the antioxidant enzymes activities in patients with CAD. After 12 weeks of LC supplementation at a dose of 1000 mg/d can reduce the level of MDA by 7% and increase the activities of CAT by 16%, SOD by 47%, and GPx by 12%. Decreased RBCs antioxidative enzymes may accelerate the development of atherosclerosis . Increased RBCs antioxidant enzymes activities can provide a protection against oxidative damage to the endothelial cells . In the present study, there was a significant positive correlation between the levels of LC and antioxidant enzymes activities after supplementation. LC was found to be an effective antioxidant agent in cardiovascular disease models and prevent endothelial dysfunction through its antioxidant property [8, 21, 22]. As a result, it seems clear that LC has a protective effect against CAD, which could be ascribed to its antioxidant capacity.
Gülçin et al.  have reported that LC might be a good antioxidant. LC has an effect on free radicals (such as 1, 1-diphenyl-2-picryl-hydrazyl radical, superoxide anion radical, hydrogen peroxide) scavenging. LC might interfere with the reactive oxygen species formation and chelate the metal ferrous ions . In the LC molecule, the carbonyl group can stabilize the free radicals formed on α-carbon with conjugation, and it protects plasma components against the toxic action of reactive oxygen species and reactive nitrogen species [8, 9]. In addition, LC is also an essential cofactor of carnitine palmitoyltransferase 1 (CPT1), which allows fatty acid transport into mitochondria and the incorporation of long chain fatty acids into the β-oxidation cycle to obtain acetyl-CoA [23–25], and these substances enter the tricarboxylic acid (TCA) cycle to synthesize adenosine triphosphate (ATP). At this step of ATP synthesis, a large amount of oxygen is consumed, and the oxygen is reduced to water at the end of the TCA cycle. Then, oxygen concentration decreases and reactive oxygen species formation is also reduced [8, 26]. We suggest that LC could be acting as a buffer for excessive acetyl groups in mitochondria, decreasing mitochondrial superoxide production during hypoxia or substrate excess, especially in the ischemic tissues.
During recent decades, much evidence has been acquired that support a clear association between oxidative stress and atherosclerotic plaque evolution [2, 3, 27–30].Oxidative stress might play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases, and antioxidant therapy might prove beneficial in combating these problems [3, 27]. Administering LC at a higher dose (≥2000 mg) has shown a cardio-protective effect and reduced the death rate from CAD . However, the Ministry of Health and Welfare in Taiwan recommends a daily dietary intake of no more than 2000 mg of LC. As a result, we tested a dose of 1000 mg/d in CAD patients and expected that the dose of LC (1000 mg/d) could be a dietary supplement for daily use. Based on the results of this study, we suggest that LC might be a useful dietary supplement for CAD to protect against excessive oxidative stress.
Regarding the safety of LC supplementation, Singh and Aslam  indicated that there are some side effects, such as mild nausea and vomiting after LC supplement at a dose of 2000 mg/d, but in three divided doses, supplementation might not cause any side effects. In the present study, we administered LC to CAD patients at a dose of 1000 mg/d in two divided doses (500 mg/b.i.d), and there were no clinically significant changes in the subjects’ vital signs, serum chemical values, or hematological values (such as blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, or glutamic pyruvate transaminase); additionally there were no serious adverse events, no complaints of myalgia or muscle weakness, no withdrawals due to adverse events, and no cardiovascular event or death report during and the end of the study. Therefore, we suggest that a dose of 1000 mg/d is safe for CAD patients.
Recent work has suggested that dietary LC might accelerate atherosclerosis via gut microbiota metabolites, complicating the role of LC supplementation in health . We considered that the need for LC supplementation in CAD patients might be dependent on the status of LC in the body. Thus, LC is considered a “conditionally essential nutrient. Animals and human studies have shown that the content of LC was low in acute myocardial infarction and chronic heart failure [33, 34]. A recent invited commentary in Mayo Clinic Proceedings clarifies that there is no good reason to suspect that, within the dose range used clinically, LC would promote atherosclerosis or otherwise compromise cardiovascular health. To the contrary, there is ample reason to conclude that carnitine is protective for vascular health . As a result, it should be recommended that CAD patients with lower levels of LC and higher oxidative stress take LC supplements to increase their LC status and anti-oxidation capacity.
There are some limitations of the present study that should be mentioned. First, the number of participants was small, although we did recruit more subjects than expected. Second, this study was designed using daily LC supplements for 3 months only. Larger and longer intervention studies are needed to understand and establish the beneficial effects of a high dose of LC in patients with CAD. Further study is also needed to measure more mechanistic parameters and more direct indicators of oxidative damage, such as nitrotyrosine, myeloperoxidase (MPO), or oxidized low density lipoprotein (ox LDL) levels to understand the antioxidative mechanism of LC in CAD patients.