Effects of Carnosine In Patients With Peripheral Arterial Disease Patients

Summary

The purpose of this study is to determine whether carnosine (a food ingredient found in chicken and red meat) supplementation (2 g) for 6 months in participants with non-claudication and claudication peripheral arterial disease (PAD) improves walking ability. Previous studies with heart failure patients have shown that carnosine supplementation increases walking capacity in these patients.

Timeline

Start

2025-05-20

Primary completion

2028-10-01

Completion

2028-10-01

Publications

• Background de Courten B, Jakubova M, de Courten MP, Kukurova IJ, Vallova S, Krumpolec P, Valkovic L, Kurdiova T, Garzon D, Barbaresi S, Teede HJ, Derave W, Krssak M, Aldini G, Ukropec J, Ukropcova B. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial. Obesity (Silver Spring). 2016 May;24(5):1027-34. doi: 10.1002/oby.21434. Epub 2016 Apr 4.
• Background Vincent KA, Shyu KG, Luo Y, Magner M, Tio RA, Jiang C, Goldberg MA, Akita GY, Gregory RJ, Isner JM. Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor. Circulation. 2000 Oct 31;102(18):2255-61. doi: 10.1161/01.cir.102.18.2255.
• Background Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation. 1995 Mar 1;91(5):1472-9. doi: 10.1161/01.cir.91.5.1472.
• Background Waeckel L, Mallat Z, Potteaux S, Combadiere C, Clergue M, Duriez M, Bao L, Gerard C, Rollins BJ, Tedgui A, Levy BI, Silvestre JS. Impairment in postischemic neovascularization in mice lacking the CXC chemokine receptor 3. Circ Res. 2005 Mar 18;96(5):576-82. doi: 10.1161/01.RES.0000159389.55544.20. Epub 2005 Feb 17.
• Background Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003 Jun 23;161(6):1163-77. doi: 10.1083/jcb.200302047. Epub 2003 Jun 16.
• Background Creager MA, Olin JW, Belch JJ, Moneta GL, Henry TD, Rajagopalan S, Annex BH, Hiatt WR. Effect of hypoxia-inducible factor-1alpha gene therapy on walking performance in patients with intermittent claudication. Circulation. 2011 Oct 18;124(16):1765-73. doi: 10.1161/CIRCULATIONAHA.110.009407. Epub 2011 Sep 26.
• Background Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993 Dec 15;82(12):3610-5.
• Background Silvestre JS, Mallat Z, Tedgui A, Levy BI. Post-ischaemic neovascularization and inflammation. Cardiovasc Res. 2008 May 1;78(2):242-9. doi: 10.1093/cvr/cvn027. Epub 2008 Feb 5.
• Background Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005 Mar;45(3):321-5. doi: 10.1161/01.HYP.0000154789.28695.ea. Epub 2005 Jan 17.
• Background Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999 Jul 15;18(14):3964-72. doi: 10.1093/emboj/18.14.3964.
• Background Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996 Sep;16(9):4604-13. doi: 10.1128/MCB.16.9.4604.
• Background Ziello JE, Jovin IS, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med. 2007 Jun;80(2):51-60.
• Background Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004 Sep 3;95(5):449-58. doi: 10.1161/01.RES.0000141145.78900.44.
• Background Serrano Hernando FJ, Martin Conejero A. [Peripheral artery disease: pathophysiology, diagnosis and treatment]. Rev Esp Cardiol. 2007 Sep;60(9):969-82. doi: 10.1157/13109651. Spanish.
• Background Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7. doi: 10.1177/08830738020170111501.
• Background Hobson RM, Saunders B, Ball G, Harris RC, Sale C. Effects of beta-alanine supplementation on exercise performance: a meta-analysis. Amino Acids. 2012 Jul;43(1):25-37. doi: 10.1007/s00726-011-1200-z. Epub 2012 Jan 24.
• Background Parkhouse WS, McKenzie DC, Hochachka PW, Ovalle WK. Buffering capacity of deproteinized human vastus lateralis muscle. J Appl Physiol (1985). 1985 Jan;58(1):14-7. doi: 10.1152/jappl.1985.58.1.14.
• Background Beebe HG, Dawson DL, Cutler BS, Herd JA, Strandness DE Jr, Bortey EB, Forbes WP. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med. 1999 Sep 27;159(17):2041-50. doi: 10.1001/archinte.159.17.2041.
• Background Harwood AE, Smith GE, Cayton T, Broadbent E, Chetter IC. A Systematic Review of the Uptake and Adherence Rates to Supervised Exercise Programs in Patients with Intermittent Claudication. Ann Vasc Surg. 2016 Jul;34:280-9. doi: 10.1016/j.avsg.2016.02.009. Epub 2016 Apr 25.
• Background Treat-Jacobson D, McDermott MM, Bronas UG, Campia U, Collins TC, Criqui MH, Gardner AW, Hiatt WR, Regensteiner JG, Rich K; American Heart Association Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Council on Cardiovascular and Stroke Nursing. Optimal Exercise Programs for Patients With Peripheral Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019 Jan 22;139(4):e10-e33. doi: 10.1161/CIR.0000000000000623. No abstract available.
• Background Treat-Jacobson D, McDermott MM, Beckman JA, Burt MA, Creager MA, Ehrman JK, Gardner AW, Mays RJ, Regensteiner JG, Salisbury DL, Schorr EN, Walsh ME; American Heart Association Council on Peripheral Vascular Disease; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Lifestyle and Cardiometabolic Health. Implementation of Supervised Exercise Therapy for Patients With Symptomatic Peripheral Artery Disease: A Science Advisory From the American Heart Association. Circulation. 2019 Sep 24;140(13):e700-e710. doi: 10.1161/CIR.0000000000000727. Epub 2019 Aug 26.
• Background McDermott MM, Guralnik JM, Tian L, Zhao L, Polonsky TS, Kibbe MR, Criqui MH, Zhang D, Conte MS, Domanchuk K, Li L, Sufit R, Leeuwenburgh C, Ferrucci L. Comparing 6-minute walk versus treadmill walking distance as outcomes in randomized trials of peripheral artery disease. J Vasc Surg. 2020 Mar;71(3):988-1001. doi: 10.1016/j.jvs.2019.05.058. Epub 2019 Dec 23.
• Background McDermott MM, Dayanidhi S, Kosmac K, Saini S, Slysz J, Leeuwenburgh C, Hartnell L, Sufit R, Ferrucci L. Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease. Circ Res. 2021 Jun 11;128(12):1851-1867. doi: 10.1161/CIRCRESAHA.121.318242. Epub 2021 Jun 10.
• Background McDermott MM, Spring B, Tian L, Treat-Jacobson D, Ferrucci L, Lloyd-Jones D, Zhao L, Polonsky T, Kibbe MR, Bazzano L, Guralnik JM, Forman DE, Rego A, Zhang D, Domanchuk K, Leeuwenburgh C, Sufit R, Smith B, Manini T, Criqui MH, Rejeski WJ. Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1266-1276. doi: 10.1001/jama.2021.2536.
• Background Money SR, Herd JA, Isaacsohn JL, Davidson M, Cutler B, Heckman J, Forbes WP. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg. 1998 Feb;27(2):267-74; discussion 274-5. doi: 10.1016/s0741-5214(98)70357-x.
• Background Dawson DL, Cutler BS, Meissner MH, Strandness DE Jr. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation. 1998 Aug 18;98(7):678-86. doi: 10.1161/01.cir.98.7.678.
• Background Girolami B, Bernardi E, Prins MH, Ten Cate JW, Hettiarachchi R, Prandoni P, Girolami A, Buller HR. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med. 1999 Feb 22;159(4):337-45. doi: 10.1001/archinte.159.4.337.
• Background Peacock JM, Keo HH, Duval S, Baumgartner I, Oldenburg NC, Jaff MR, Henry TD, Yu X, Hirsch AT. The incidence and health economic burden of ischemic amputation in Minnesota, 2005-2008. Prev Chronic Dis. 2011 Nov;8(6):A141. Epub 2011 Oct 17.
• Background Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15.
• Background Boakye AA, Zhang D, Guo L, Zheng Y, Hoetker D, Zhao J, Posa DK, Ng CK, Zheng H, Kumar A, Kumar V, Wempe MF, Bhatnagar A, Conklin DJ, Baba SP. Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization. Front Physiol. 2019 Jul 2;10:751. doi: 10.3389/fphys.2019.00751. eCollection 2019.
• Background Schon M, Just I, Krumpolec P, Blazicek P, Valkovic L, Aldini G, Tsai CL, De Courten B, Krssak M, Ukropcova B, Ukropec J. Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering. Physiol Res. 2023 Mar 8;72(1):87-97. doi: 10.33549/physiolres.934911. Epub 2022 Dec 22.
• Background Caruso J, Charles J, Unruh K, Giebel R, Learmonth L, Potter W. Ergogenic effects of beta-alanine and carnosine: proposed future research to quantify their efficacy. Nutrients. 2012 Jul;4(7):585-601. doi: 10.3390/nu4070585. Epub 2012 Jun 26.
• Background Harris RC, Stellingwerff T. Effect of beta-alanine supplementation on high-intensity exercise performance. Nestle Nutr Inst Workshop Ser. 2013;76:61-71. doi: 10.1159/000350258. Epub 2013 Jul 25.
• Background Hipkiss AR. Energy metabolism, proteotoxic stress and age-related dysfunction - protection by carnosine. Mol Aspects Med. 2011 Aug;32(4-6):267-78. doi: 10.1016/j.mam.2011.10.004. Epub 2011 Oct 15.
• Background Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T. Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem. 2003 Feb 21;278(8):6521-31. doi: 10.1074/jbc.M209764200. Epub 2002 Dec 6.
• Background Drozak J, Veiga-da-Cunha M, Vertommen D, Stroobant V, Van Schaftingen E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J Biol Chem. 2010 Mar 26;285(13):9346-9356. doi: 10.1074/jbc.M109.095505. Epub 2010 Jan 22.
• Background Lombardi C, Carubelli V, Lazzarini V, Vizzardi E, Bordonali T, Ciccarese C, Castrini AI, Dei Cas A, Nodari S, Metra M. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition. 2015 Jan;31(1):72-8. doi: 10.1016/j.nut.2014.04.021. Epub 2014 May 10.
• Background Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015 Apr 24;116(9):1509-26. doi: 10.1161/CIRCRESAHA.116.303849.
• Background Annex BH. Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol. 2013 Jul;10(7):387-96. doi: 10.1038/nrcardio.2013.70. Epub 2013 May 14.

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