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

American Journal of Clinical Nutrition

Volumn 93, Issue 4, 2011, Pages 799-808

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

^a UNIVERSITY OF CATANIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMMONIA; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; FUROSEMIDE; INSULIN; LACTULOSE; LEVACECARNINE; PLACEBO;

ABDOMINAL PAIN; ADULT; AGED; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG TOLERABILITY; DRUG URINE LEVEL; DYSTHYMIA; ELECTROENCEPHALOGRAPHY; FATIGUE; FEMALE; HEPATIC ENCEPHALOPATHY; HUMAN; LABORATORY TEST; LIVER FUNCTION; MAJOR CLINICAL STUDY; MALE; NEUROPHYSIOLOGICAL RECRUITMENT; PHYSICAL ACTIVITY; RANDOMIZED CONTROLLED TRIAL;

ACETYLCARNITINE; ADULT; AGED; AMMONIA; DOUBLE-BLIND METHOD; FATIGUE; FEMALE; HEPATIC ENCEPHALOPATHY; HUMANS; MALE; MEMORY; MENTAL FATIGUE; MIDDLE AGED; PHYSICAL ENDURANCE; SEVERITY OF ILLNESS INDEX; VITAMIN B COMPLEX; WALKING;

EID: 79953174586     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.110.007393     Document Type: Article

References (63)

1. Wilkinson DJ, Smeeton NJ, Watt PW. Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol 2010;91:200-19.
2. Prakash R, Mullen KD. Medscape. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010;7:515-25.
3. Banister EW, Cameron BJ. Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med 1990;11:S129-42.
4. Malaguarnera M, Pistone G, Astuto M, et al. L-Carnitine in the treatment of mild or moderate hepatic encephalopathy. Dig Dis 2003;21:271-5. (Pubitemid 37323484)
5. Malaguarnera M, Pistone G, Astuto M, et al. Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo- controlled trial. Dig Dis Sci 2006;51:2242-7.
6. Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr 2008;46:181-90. (Pubitemid 351215559)
7. Malaguarnera M, Cammalleri L, Gargante MP, Vacante M, Colonna V, Motta M. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86:1738-44. (Pubitemid 350232191)
8. Fritz IB, Yue KT. Long-chain carnitine acyltransferase and the role of acylcarnitine derivatives in the catalytic increase of fatty acid oxidation induced by carnitine. J Lipid Res 1963;4:279-88.
9. Morris AJ, Carey EM. Postnatal changes in the concentration of carnitine and acylcarnitines in the rat brain. Brain Res 1983;284:381-4. (Pubitemid 13046065)
10. Bremer J. Carnitine-metabolism and functions. Physiol Rev 1983;63:1420-80.
11. Gatti R, De Palo CB, Spinella P, De Palo EF. Free carnitine and acetyl carnitine plasma levels and their relationship with body muscular mass in athletes. Amino Acids 1998;14:361-9. (Pubitemid 28349826)
12. Rao KV, Mawal YR, Qureshi IA. Progressive decrease of cerebral cytochrome C oxidase activity in sparse-fur mice: role of acetyl-L-carnitine in restoring the ammonia-induced cerebral energy depletion. Neurosci Lett 1997;224:83-6. (Pubitemid 27122176)
13. Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J 1992;6:3379-86. (Pubitemid 23007103)
14. Nałecz KA, Miecz D, Berezowski V, Cecchelli R. Carnitine: transport and physiological functions in the brain. Mol Aspects Med 2004;25:551-67. (Pubitemid 39195076)
15. Alessio HM. Exercise-induced oxidative stress. Med Sci Sports Exerc 1993;25:218-24. (Pubitemid 23061983)
16. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925-6.
17. Conn HO, Leevy CM, Vlahcevic ZR, et al. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 1977;72:573-83. (Pubitemid 8097592)
18. Conn HO. Trail making and number connection tests in the assessment of mental state in portal systemic encephalopathy. Am J Dig Dis 1977;22:541-50. (Pubitemid 8116254)
19. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
20. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46:1121-3.
21. Wessely S, Powell R. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry 1989;52:940-8. (Pubitemid 19220165)
22. Blair SN, Haskell WL, Ho P, et al. Assessment of habitual physical activity by a seven-day recall in a community survey and controlled experiments. Am J Epidemiol 1985;122:794-804. (Pubitemid 16207346)
23. Harada ND, Chiu V, Stewart AL. Mobility-related function in older adults: assessment with a 6-minute walk test. Arch Phys Med Rehabil 1999;80:837-41. (Pubitemid 29320983)
24. Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85-94.
25. Van Der Rijt CC, Schalm SW, De Groot GH, De Vlieger M. Objective measurement of hepatic encephalopathy by means of automated EEG analysis. Electroencephalogr Clin Neurophysiol 1984;57:423-6. (Pubitemid 14134766)
26. Opolon P, Rapin JR, Huguet C, et al. Hepatic failure coma (HFC) treated by polyacrylonitrile membrane (Pam) hemodialysis (Hd). Trans Am Soc Artif Intern Organs 1976;22:701-10.
27. Pugh RN, Murray-Lyon LM, Dawson JL, Petroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646-9.
28. Da Fonseca-Wollheim F. Direct determination of plasma ammonia without deproteinization. An improved enzymic determination of ammonia, II (author's transl). Z Klin Chem Klin Biochem 1973;11:426-31.
29. Babij P, Matthews SM, Rennie MJ. Changes in blood ammonia, lactate and amino acids in relation to workload during bicycle ergometer exercise in man. Eur J Appl Physiol Occup Physiol 1983;50:405-11. (Pubitemid 13118286)
30. Rhodes VA, Watson PM, Hanson BM. Patients' descriptions of the influence of tiredness and weakness on self-care abilities. Cancer Nurs 1988;11:186-94.
31. Ferreira LF, Reid MB. Muscle-derived ROS and thiol regulation in muscle fatigue. J Appl Physiol 2008;104:853-60.
32. Fitts RH. The cross-bridge cycle and skeletal muscle fatigue. J Appl Physiol 2008;104:551-8. (Pubitemid 351231501)
33. Noakes TD, Calbet JA, Boushel R, et al. Central regulation of skeletal muscle recruitment explains the reduced maximal cardiac output during exercise in hypoxia. Am J Physiol Regul Integr Comp Physiol 2004;287:R996-9.
34. Gleeson M. Interleukins and exercise. J Physiol 2000;529:1.
35. Robson-Ansley PJ, de Milander L, Collins M, Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 2004;29:411-8. (Pubitemid 39107948)
36. Carmichael MD, Davis JM, Murphy EA, et al. Role of brain IL-1beta on fatigue after exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol 2006;291:R1344-8.
37. Meeusen R. Exercise and the brain: insight in new therapeutic modalities. Ann Transplant 2005;10:49-51.
38. Amann M, Dempsey JA. Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance. J Physiol 2008;586:161-73.
39. Karlic H, Lohninger A. Supplementation of L-carnitine in athletes: does it make sense? Nutrition 2004;20:709-15.
40. Stephens FB, Constantin-Teodosiu D, Greenhaff PL. New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol 2007;581:431-44. (Pubitemid 46831747)
41. Constantin-Teodosiu D, Howell S, Greenhaff PL. Carnitine metabolism in human muscle fiber types during submaximal dynamic exercise. J Appl Physiol 1996;80:1061-4. (Pubitemid 26087274)
42. Carlin JI, Harris RC, Cederblad G, Constantin-Teodosiu D, Snow DH, Hultman E. Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse. J Appl Physiol 1990;69:42-5. (Pubitemid 20230940)
43. Constantin-Teodosiu D, Carlin JI, Cederblad G, Harris RC, Hultman E. Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise. Acta Physiol Scand 1991;143:367-72.
44. Cooper AJ, Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev 1987;67:440-519. (Pubitemid 17063608)
45. Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci 2008;53:3018-25.
46. Malaguarnera M, Pistone G, Rampello E, Leotta C, Scarpello L, Rampello L. Effects of L-carnitine in patients with hepatic encephalopathy. World J Gastroenterol 2005;11:7197-202. (Pubitemid 43154020)
47. Olde Damink SW, Jalan R, Dejong CH. Interorgan ammonia trafficking in liver disease. Metab Brain Dis 2009;24:169-81.
48. Lockwood AH. Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis 2004;19:345-9. (Pubitemid 39361192)
49. Jones EA. Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab Brain Dis 2002;17:275-81. (Pubitemid 36204757)
50. Rovira A, Córdoba J, Raguer N, Alonso J. Magnetic resonance imaging measurement of brain edema in patients with liver disease: resolution after transplantation. Curr Opin Neurol 2002;15:731-7. (Pubitemid 35471683)
51. Ahboucha S, Butterworth RF. Pathophysiology of hepatic encephalopathy: a new look at GABA from the molecular standpoint. Metab Brain Dis 2004;19:331-43. (Pubitemid 39361191)
52. Vaquero J, Butterworth RF. The brain glutamate system in liver failure. J Neurochem 2006;98:661-9. (Pubitemid 44051268)
53. Lozeva-Thomas V. Serotonin brain circuits with a focus on hepatic encephalopathy. Metab Brain Dis 2004;19:413-20. (Pubitemid 39361197)
54. Hassinger TD, Atkinson PB, Strecker GJ, et al. Evidence for glutamate-mediated activation of hippocampal neurons by glial calcium waves. J Neurobiol 1995;28:159-70.
55. Girard G, Butterworth RF. Effect of portacaval anastomosis on glutamine synthetase activities in liver, brain, and skeletal muscle. Dig Dis Sci 1992;37:1121-6.
56. Olde Damink SW, Dejong CH, Deutz NE, et al. Kidney plays a major role in ammonia homeostasis after portasystemic shunting in patients with cirrhosis. Am J Physiol Gastrointest Liver Physiol 2006;291:G189-94.
57. Neri S, Pistone G, Saraceno B, Pennisi G, Luca S, Malaguarnera M. L-carnitine decreases severity and type of fatigue induced by interferon-alpha in the treatment of patients with hepatitis C. Neuropsychobiology 2003;47:94-7. (Pubitemid 36469847)
58. Pistone G, Marino A, Leotta C, Dell'Arte S, Finocchiaro G, Malaguarnera M. Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue. Drugs Aging 2003;20:761-7. (Pubitemid 36995252)
59. Malaguarnera M, Di Mauro A, Gargante PM, Rampello L. L-carnitine reduces severity of physical and mental fatigue and improves daily activities in the elderly. South Med J 2006;99:315-6.
60. Imperato A, Ramacci MT, Angelucci L. Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats. Neurosci Lett 1989;107:251-5.
61. Melanson EL, Knoll JR, Bell ML, et al. Commercially available pedometers: considerations for accurate step counting. Prev Med 2004;39:361-8. (Pubitemid 38842444)
62. Lichtman SW, Pisarska K, Berman ER, et al. Discrepancy between self-reported and actual caloric intake and exercise in obese subjects. N Engl J Med 1992;327:1893-8. (Pubitemid 23006963)
63. Bajaj JS, Hafeezullah M, Zadvornova Y, et al. The effect of fatigue on driving skills in patients with hepatic encephalopathy. Am J Gastroenterol 2009;104:898-905.