Oral acetyl-l-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study

Malaguarnera, Michele; Vacante, Marco; Giordano, Maria; Pennisi, Giovanni; Bella, Rita; Rampello, Liborio; Malaguarnera, Mariano; Volti, Giovanni Li; Galvano, Fabio

doi:10.3945/ajcn.110.007393

Cited by 83 publications

(56 citation statements)

References 63 publications

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“…The present data showed that L-carnitine reinforced the mitochondrial β-oxidation and the activity of the key ROS-scavenging antioxidant enzymes such as Sod2 and CAT without an increase in oxidative stress. In addition, L-carnitine has recently been shown to exhibit ammonia reduction in hepatic encephalopathy patients and improvement of fatigue, which reflects the wide pharmacological effects of L-carnitine on hepatic and muscular mitochondrial function recovery [24]. We were not able to demonstrate such effects of L-carnitine in our model, as we did not examine plasma ammonia levels or physical scores that reflect hepatic encephalopathy and related effects.…”

Section: Discussionmentioning

confidence: 90%

L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway

et al. 2014

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Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% α-tocopherol (α-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis.ConclusionL-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial β-oxidation and redox system.

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Section: Discussionmentioning

confidence: 90%

L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway

et al. 2014

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“…Several reports have already cited the NH3-lowering effects of carnitine in cirrhosis (8,15,16), and levocarnitine is being adopted as a new therapeutic option for cases of cirrhosis accompanied by refractory hepatic encephalopathy that prove resistant to synthetic disaccharides and rifaximin. Carnitine is also used to treat hyperammonemia when using valproic acid and antimicrobials containing a pivoxil group (17).…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma

Iwasa

Sugimoto

Ishihara

et al. 2015

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Summary Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. l-Carnitine is a vitamin-like substance and several reports have described the usefulness of l-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (l-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine1BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine1BCAA and BCAAalone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/ or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb.

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“…Calibration was obtained using hydrogen peroxide (0.2–20 mmol/L). [32,33] The limit of detection for this assay is approximately 0.25 nmol/L.…”

Section: Methodsmentioning

confidence: 99%

Immunological reaction and oxidative stress after light or heavy polypropylene mesh implantation in inguinal hernioplasty

et al. 2016

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The relationship between mesh weight and host tissue reaction has, so far, not been fully investigated. Lightweight meshes (LWM) are thought to give less inflammatory response compared with heavyweight meshes (HWM). The present study is a randomized, controlled, double-blind clinical trial performed in 61 patients who underwent an elective inguinal hernioplasty. The primary outcome of the study was to investigate the relationship between total amount of prosthetic material (polypropylene), immunological reaction, and oxidative stress. The study was double-blinded. Sixty-one patients were recruited for the study and randomly assigned to 2 groups (groups A and B). Levels of inflammation markers (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) and oxidative stress markers (reduced glutathione [GSH] and lipid hydroperoxides [LOOH]) were determined preoperatively and after undergoing inguinal hernioplasty (after 6, 72, and 288 hours), respectively, with LWM and HWM. There was no significant difference in IL-6 levels between HWM and LWM (P = 0.3, 0.7, 0.8 after 6, 72, and 288 hours, respectively). A statistically significant difference was found after 72 hours for TNF-α (P = 0.01), for GSH after 6 hours (P < 0.01), and after 6 and 72 hours for LOOH (P = 0.05, 0.01, respectively). Oxidative stress occurred at earlier time points and was pore accentuated HWM versus LWM and prodromal to TNF-α increase.Also, in randomized clinical trial, the use of LWM gives advantages in terms of less inflammatory response when compared with HWM. Moreover, there is a significant higher oxidative stress after implantation of HWM. The intensity of oxidative stress seems to be strongly related to the amount of implanted polypropylene. (Trial registration number: NCT01090284).

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Oral acetyl-l-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study

Abstract: Patients with HE treated with ALC showed a decrease in the severity of both mental and physical fatigue and an increase in physical activity. This trial was registered at clinicaltrials.gov as NCT01223742.

Cited by 83 publications

References 63 publications

L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway

L-Carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway

Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma

Immunological reaction and oxidative stress after light or heavy polypropylene mesh implantation in inguinal hernioplasty

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