L-Carnitine supplementation ameliorates serum tumor necrosis factor-alpha and matrix metalloproteinase-3 in knee osteoarthritis women
DOI:
https://doi.org/10.3329/bjp.v12i1.30417Keywords:
Knee, L-Carnitine, Clinical trial, Matrix metalloproteinase-3, Osteoarthritis, Tumor necrosis factor-alphaAbstract
Seventy-two females with mild to moderate knee osteoarthritis were included in this randomized double-blind placebo-controlled study. Patients in the intervention group (n=36) received L-carnitine supplement (750 mg/day) for two months. L-Carnitine supplementation led to decrease in serum TNF-? and MMP-3 levels significantly in comparison with the baseline (p<0.001 and p<0.001, respectively) and placebo group (p<0.001 and p=0.03, respectively). In addition, physicians global assessment of the severity of osteoarthritis decreased significantly in the L-carnitine group (p<0.001) and placebo group (p=0.012) after supplementation. At the end of the study, a significant difference was observed between the two groups for mean physicians global assessment of the severity of osteoarthritis (p<0.001), adjusted for baseline values and duration of osteoarthritis. L-Carnitine supplementation has beneficial effects in reducing inflammatory biomarkers in knee osteoarthritis patients which subsequently leads to the alleviation of disease symptoms.
Downloads
48
22 Read
5
References
Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum, 1986; 29: 1039-49.
Aktas E, Sener E, Zengin O, Uyar Gocun P, Deveci MA. Serum TNF-alpha levels: Potential use to indicate osteoarthritis progression in a mechanically induced model. Eur J Orthop Surg Traumatol. 2012; 22: 11922.
Andereya S, Streich N, Schmidt-Rohlfing B, Mumme T, Mu¨ ller-Rath R, Schneider U. Comparison of modern marker proteins in serum and synovial fluid in patients with advanced osteoarthrosis and rheumatoid arthritis. Rheumatol Int. 2006; 26: 43238.
Anonymous: Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update: American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum, 2000; 43: 1905-15.
Atik SO. Leukotriene B4 and prostaglandin E2 activity in synovial fluid in osteoarthritis. Prostaglandins Leukot Essent Fatty Acids. 1990; 39: 25354.
Bellare N, Argekar H, Bhagwat A, Situt V, Pandita N. Gluco-samine and chondroitin sulphate supplementation along with diet therapy provides better symptomatic relief in osteoarthritic patients as compared to diet therapy alone. Int J Pharm Sci Rev Res. 2014; 24: 21523.
Berenbaum F. New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther. 2008; 10 (Suppl 2): S1.
Bianchi E, Mannelli LDC, Menicacci C, Lorenzoni P, Aglianò M, Ghelardini C. Prophylactic role of acetyl-L-carnitine on knee lesions and associated pain in a rat model of osteoarthritis. Life Sci. 2014; 106: 3239.
Cetinkaya A, Bulbuloglu E, Kantarceken B, Ciralik H, Kurutas EB, Buyukbese MA, Gumusalan Y. Effects of L-carnitine on oxidant/anti-oxidant status in acetic acid-induced colitis. Dig Dis Sci. 2006; 51: 488-94.
Cho H, Walker A, Williams J, Hasty KA. Study of osteoarthritis treatment with anti-inflammatory drugs: Cyclooxygenase-2 inhibitor and steroids. Bio Med Res Int. 2015; 2015: 1-11.
Conner EM, Grisham MB. Inflammation, free radicals and anti-oxidants. Nutrition 1996; 12: 274-77.
Dean DD, Martel-Pelletier J, Pelletier JP, Howell DS, Woessner JF. Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 1989; 84: 67885.
Deng R, Su Z, Hua X, Zhang Z, Li DQ, Pflugfelder SC. Osmo-protectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells. Mol Vis. 2014; 20: 1243-52.
Derosa G, Maffioli P, Ferrari I, DAngelo A, Fogari E, Palumbo I, Randazzo S, Cicero AF. Comparison between orlistat plus L-carnitine and orlistat alone on inflammation parameters in obese diabetic patients. Fundam Clin Pharmacol. 2011; 25: 64251.
Duranay M, Akay H, Yilmaz FM, Senes M, Tekeli N, Yucel D. Effects of L-carnitine infusions on inflammatory and nutritional markers in haemodialysis patients. Nephrol Dial Transplant. 2006; 21: 3211-14.
Felson DT. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am. 2004; 42: 1-9.
Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2002; 39: 23746
Geraci A, Zatta D, Strazzabosco C, Tomasello G, Alongi G, Genovese M, Sanfilippo A, D'Arienzo M. The clinical effectiveness of glucosamine sulfate, chondroitin sulfate, hydrolyzed collagen type II, hydrolyzed hyaluronic acid and L-carnitine supplement in patients with osteoarthritis of the knee: A multicenter randomized double blind controlled clinical trial. Minerva Ortop Traumatol. 2012; 63: 917.
Garrelds IM, Elliott GR, Pruimboom WM, Zijlstra FJ, Bonta IL. Effects of carnitine and its congeners on eicosanoid discharge from rat cells: Implications for release of TNF?. Mediators Inflamm. 1993; 2: S57-62.
Garrelds IM, Elliott GR, Zijlstra FJ, Bonta IL. Effects of short-and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes. Brit J Nutr. 1994; 72: 785-93.
Hua X, Deng R, Zhang Z, Su Z, De-Quan L, Pflugfelder SC. L-Carnitine suppresses the production of pro-inflammatory cytoiknes by preventing the hyperosmolarity-induced oxidative stress in human corneal epithelial cells. IOVS 2014; 55: 3058.
Idrovo JP, Yang WL, Matsuda A, Nicastro J, Coppa GF, Wang P. Post-treatment with the combination of 5-aminoimidazole-4-carboxyamide ribonucleoside and carnitine improves renal function after ischemia/reperfusion injury. Shock 2012; 37: 3946.
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011; 7: 3342.
Koc A, Ozkan T, Karabay AZ, Sunguroglu A, Aktan F. Effect of L-carnitine on the synthesis of nitric oxide in RAW 264A7 murine macrophage cell line. Cell Biochem Funct 2011; 29: 679-85.
Kolahi S, Malek Mahdavi A, Mahdavi R, Lak S. Effect of l-carnitine supplementation on clinical symptoms in women with osteoarthritis of the knee: A randomized, double-blind, placebo-controlled trial. Eur J Integ Med. 2015; 7: 54046.
Kurutas EB, Cetinkaya A, Bulbuloglu E, Kantarceken B. Effects of anti-oxidant therapy on leukocyte myeloperoxidase and Cu/Zn-superoxide dismutase and plasma malondialdehyde levels in experimental colitis. Mediators Inflamm. 2005; 2005: 390-94.
Lee BJ, Lin JS, Lin YC, Lin PT. Anti-inflammation effects of L-carnitine supplementation (1000 mg/d) in coronary artery disease patients. Nutr J. 2014; 31: 7985.
Liu S, Wu HJ, Zhang ZQ, Chen Q, Liu B, Wu JP, Zhu L. L-Carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase. Cancer Biol Ther. 2011; 12: 125-30.
Malaguarnera M, Gargante MP, Russo C, Antic T, Vacante M, Malaguarnera M, Avitabile T, Li Volti G, Galvano F. L-Carnitine supplementation to diet: A new tool in treatment of nonalcoholic steatohepatitisa randomized and controlled clinical trial. Am J Gastroenterol. 2010; 105: 133845.
Martel-Pelletier J, McCollum R, Fujimoto N, Obata K, Cloutier JM, Pelletier JP. Excess of metalloproteinases over tissue inhibitor of metalloproteinase may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest. 1994; 70: 80715.
Massicotte F. Epidemiology of osteoarthritis. In: Understanding osteoarthritis from bench to bedside. Martel-Pelletier J, Pelletier JP (eds). Kerala, India, Research Signpost, 2011, pp 126.
Mehta K, Gala J, Bhasale S, Naik S, Modak M, Thakur H, Deo N, Miller MJ. Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: A randomized controlled trial. BMC Complement Altern Med. 2007; 7: 3446.
Moeinian M, Ghasemi-Niri SF, Mozaffari S, Abdollahi M. Synergistic effect of probiotics, butyrate and L-Carnitine in treatment of IBD. JMHI. 2013; 7: 50-53.
Pendleton A, Arden N, Dougados M, Doherty M, Bannwarth B, Bijlsma JW, Cluzeau F, Cooper C, Dieppe PA, Günther KP, Hauselmann HJ, Herrero-Beaumont G, Kaklamanis PM, Leeb B, Lequesne M, Lohmander S, Mazieres B, Mola EM, Pavelka K, Serni U, Swoboda B, Verbruggen AA, Weseloh G, Zimmermann-Gorska I. EULAR recommendations for the management of osteoarthritis: Report of task force standing committee for international clinical studies including therapeutic trials (ESCISIT). Ann Rheum Dis. 2000; 59: 936-44.
Phillips CR, Brasington RD. Osteoarthritis treatment update: Are NSAIDs still in the picture? Musculoskelet Med. 2010; 27: 6571.
Rainsford KD, Ying C, Smith F. Effects of 5-lipoxygenase inhibitors on interleukin production by human synovial tissues in organ culture: Comparison with interleukin-1-synthesis inhibitors. J Pharm Pharmacol. 1996; 48: 4652.
Setia S, Sanyal SN. Nuclear factor kappa B: A pro-inflammatory, transcription factor-mediated signalling pathway in lung carcinogenesis and its inhibition by nonsteroidal anti-inflammatory drugs. J Environ Pathol Toxicol Oncol. 2012; 31: 27-37.
Shakeri A, Tabibi H, Hedayati M. Effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia. Hemodial Int. 2010; 14: 498504.
Siomek A. NF-?B signaling pathway and free radical impact. Acta Biochim Pol. 2012; 59: 323-31.
Sowers M. Epidemiology of risk factors for osteoarthritis: Systemic factors. Curr Opin Rheumatol. 2001; 13: 44751.
Stoppoloni D, Politi L, Dalla Vedova P, Messano M, Koverech A, Scandurra R, Scotto d'Abusco A. L-Carnitine enhances extracellular matrix synthesis in human primary chondrocytes. Rheumatol Int. 2013; 33: 23992403.
Suchitra MM, Ashalatha VL, Sailaja E, Rao AM, Reddy VS, Bitla AR, Sivakumar V, Rao PV. The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl. 2011; 22: 115559.
Tastekin N, Aydogdu N, Dokmeci D, Usta U, Birtane M, Erbas H, Ture M. Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis. Pharmacol Res. 2007; 56: 30310.
Uzuner N, Kavukcu S, Yilmaz O, Ozkal S, Islekel H, Karaman O, Soylu A, Kargi A. The role of L-carnitine in treatment of a murine model of asthma. Acta Med. 2002; 56: 295-301.
Vescovo G, Ravara B, Gobbo V, Sandri M, Angelini A, Della Barbera M, Dona M, Peluso G, Calvani M, Mosconi L, Dalla Libera L. L-Carnitine: A potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol. 2002; 283: 80210.
Winter BK, Fiskum G, Galo LL. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. Br J Cancer. 1995; 72: 117379.
Wittenberg RH, Willburger RE, Kleemeyer KS, Peskar BA. In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint disease. Arthritis Rheum. 1993; 36: 1444-50.
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
