The Role of Branched-Chain Amino Acids and Serotonin Antagonists in the Prevention and Treatment of Cancer Cachexia

  • Alessandro Laviano
  • Antonia Cascino
  • Michael M. Meguid
  • Isabella Preziosa
  • Filippo Rossi Fanelli


Cachexia is pervasive among patients suffering from chronic diseases, including cancer, liver cirrhosis and chronic renal failure. The development of cachexia dramatically impacts on the clinical course of the underlying disease, by increasing morbidity and mortality, and impinging on patients’ quality of life. Also, weight loss influences outcome by increasing drug-induced toxicity and impeding completion of the therapeutic schedule. Particularly in cancer patients, weight loss is a reliable predictor for toxicity from treatment and shorter survival [1].


Cancer Cachexia Brain Serotonin Serotonin Antagonist Plasma Tryptophan BCAA Supplementation 
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  1. 1.
    Ross PJ, Ashley S, Norton A et al (2004) Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer 90:1905–1911PubMedCrossRefGoogle Scholar
  2. 2.
    Laviano A, Meguid MM, Rossi Fanelli F (2003) Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 4:686–694PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz MW, Woods SC, Porte DJr et al (2000) Central nervous system control of food intake. Nature 404:661–671PubMedGoogle Scholar
  4. 4.
    Giorgetti M, Tecott LH (2004) Contributions of 5-HT2C receptors to multiple actions of central serotonin systems. Eur J Pharmacol 488:1–9PubMedCrossRefGoogle Scholar
  5. 5.
    Havel PJ, Larsen PJ, Cameron JL (2000) Neuroendocrinology. In: Conn PM, Freeman ME (eds) Physiology and medicine. Humana Press, Totowa,pp 335–352Google Scholar
  6. 6.
    Heisler LK, Cowley MA, Tecott LH et al (2002) Activation of central melanocortin pathways by fenfluramine. Science 297:609–611PubMedCrossRefGoogle Scholar
  7. 7.
    Ohliger-Frerking P, Horowitz JM, Horwitz BA (2002) Enhanced adrenergic excitation of serotonergic dorsal raphe neurons in genetically obese rats. Neurosci Lett 332:107–110PubMedCrossRefGoogle Scholar
  8. 8.
    Bray GA (2000) Reciprocal relation of food intake and sympathetic activity: experimental observations and clinical implications. Int J Obes Relat Metab Disord 24(Suppl 2):S8–S17PubMedGoogle Scholar
  9. 9.
    Inui A (1999) Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Res 59:4493–4501PubMedGoogle Scholar
  10. 10.
    Diksic M, Young SN (2001) Study of the brain serotonergic system with labelled alpha-methyl-Ltryptophan. J Neurochem 78:1185–1200PubMedCrossRefGoogle Scholar
  11. 11.
    Rossi Fanelli F, Cangiano C, Ceci F et al (1986) Plasma tryptophan and anorexia in human cancer. Eur J Cancer Clin Oncol 22:89–95PubMedCrossRefGoogle Scholar
  12. 12.
    Cangiano C, Cascino A, Ceci F et al (1990) Plasma and CSF tryptophan in cancer anorexia. J Neural Transm (Gen Sect) 81:225–233CrossRefGoogle Scholar
  13. 13.
    Cangiano C, Testa U, Muscaritoli M et al (1994) Cytokines, tryptophan and anorexia in cancer patients before and after surgical tumor ablation. Anticancer Res 14:1451–1456PubMedGoogle Scholar
  14. 14.
    Laviano A, Cangiano C, Preziosa I et al (1997) Plasma tryptophan levels and anorexia in liver cirrhosis. Int J Eating Disord 21:181–186CrossRefGoogle Scholar
  15. 15.
    Aguilera A, Selgas R, Codoceo R et al (2000) Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis. Perit Dial Int 20:810–816PubMedGoogle Scholar
  16. 16.
    Cangiano C, Laviano A, Meguid MM et al (1996) Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst 88:550–552PubMedCrossRefGoogle Scholar
  17. 17.
    Hiroshige K, Sonta T, Suda T et al (2001) Oral supplementation of branched-chain amino acids improves nutritional status in elderly patients on chronic haemodialysis. Neprhol Dial Transplant 16:1856–1862CrossRefGoogle Scholar
  18. 18.
    Marchesini G, Bianchi G, Merli M et al (2003) Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 124:1792–1801PubMedCrossRefGoogle Scholar
  19. 19.
    Marks DL, Butler AA, Turner R et al (2003) Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 144:1513–1523PubMedCrossRefGoogle Scholar
  20. 20.
    Laviano A, Meguid MM (1996) Nutritional issues in cancer management. Nutrition 12:358–371PubMedCrossRefGoogle Scholar
  21. 21.
    Edelman MJ, Gandara DR, Meyers FJ et al (1999) Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome. Cancer 86:684–688PubMedCrossRefGoogle Scholar
  22. 22.
    Blaha V, Yang ZJ, Meguid MM et al (1998) Ventromedial nucleus of hypothalamus is related to the development of cancer-induced anorexia: in vivo microdialysis study. Acta Medica (Hradec Kralove) 41:3–11Google Scholar
  23. 23.
    Herreros R, Serrat I, Boronat A (1999) L-DOPA and cancer anorexia. Palliat Med 13:83–84PubMedCrossRefGoogle Scholar
  24. 24.
    Lozano RH, Jofre IS (2002) Novel use of L-DOPA in the treatment of anorexia and asthenia associated with cancer. Palliat Med 16:548PubMedCrossRefGoogle Scholar
  25. 25.
    Cahlin C, Gelin J, Delbro D et al (2000) Effect of cyclooxigenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cachexia related to prostanoids. Cancer Res 60:1742–1749PubMedGoogle Scholar
  26. 26.
    Lundholm K, Gelin J, Hyltander A et al (1994) Antiinflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 54:5602–5606PubMedGoogle Scholar
  27. 27.
    Squadrito F, Calapai G, Altavilla D et al (1994) Central serotoninergic system involvement in the anorexia induced by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase. Eur J Pharmacol 255:51–55PubMedCrossRefGoogle Scholar
  28. 28.
    Lugarini F, Hrupka BJ, Schwartz GJ et al (2002) A role for cyclooxygenase-2 in lipopolysaccharideinduced anorexia in rats. Am J Physiol Regul Integr Comp Physiol 283:R862–R868PubMedGoogle Scholar
  29. 29.
    Nakamura K, Li YQ, Kaneko T et al (2001) Prostaglandin E3 receptor protein in serotonin and catecholamine cell groups: a double immunofluorescence study in the rat brain. Neuroscience 103:763–775PubMedCrossRefGoogle Scholar
  30. 30.
    Gomes-Marcondes MCC, Ventrucci G, Toledo MT et al (2003) A leucine-supplemented diet improved protein content of skeletal muscle in young tumorbearing rats. Braz J Med Biol Res 36:1589–1594PubMedCrossRefGoogle Scholar
  31. 31.
    Ventrucci G, Mello MAR, Gomes-Marcondes MCC (2004) Proteasome activity is altered in muscle tissue of tumour-bearing rats fed a leucine-rich diet. Endocr Relat Cancer 11:887–895PubMedCrossRefGoogle Scholar
  32. 32.
    Smith HJ, Wyke SM, Tisdale MJ (2003) Mechanism of the attenuation of Proteolysis-Inducing Factor stimulated protein degradation in muscle by b-hydroxy-bmethylbutyrate. Cancer Res 64:8731–8735CrossRefGoogle Scholar
  33. 33.
    Paddon-Jones D, Sheffield-Moore M, Urban RJ et al (2004) Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab 89:4351–4358PubMedCrossRefGoogle Scholar
  34. 34.
    Poon RT-P, Yu W-C, Fan S-T, Wong J (2004) Longterm oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther 19:779–788PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • Alessandro Laviano
    • 1
  • Antonia Cascino
    • 1
  • Michael M. Meguid
    • 2
  • Isabella Preziosa
    • 1
  • Filippo Rossi Fanelli
    • 1
  1. 1.Department of Clinical MedicineUniversity of Rome La SapienzaRomeItaly
  2. 2.Department of SurgerySurgical Metabolism and Nutrition Laboratory, Neuroscience Programs,University Hospital, Upstate Medical UniversitySyracuseUSA

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