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Serotonin and Cancer Anorexia: Myths or Facts?

Department of Clinical Medicine, University La Sapienza, Rome, Italy
Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY

To the Editor:

In their excellent paper, Davis et al¹ review the relevant clinical issue of cancer-associated anorexia. Although the paper is very informative, detailed, and updated, we felt that the statement questioning the possible role of brain serotonin in the pathogenesis of human cancer anorexia, "there is no evidence to confirm the central neurohumoral changes associated with [human] anorexia",¹ could be misleading, and that a clarification was needed.

In humans, brain serotonergic activity cannot be easily measured in vivo, and therefore is inferred by CSF levels of tryptophan, the precursor of serotonin. In anorectic cancer patients, plasma and CSF concentrations of tryptophan in particular are increased when compared with controls and nonanorectic cancer patients.^2,3 Also, after tumor removal, plasma tryptophan normalizes and food intake improves.⁴ The involvement of brain serotonin in cancer anorexia is also supported by data linking this monoamine with the anorexia characterizing other chronic diseases. In uremic patients, the presence of anorexia is associated with low circulating levels of branched-chain amino acids,⁵ which compete with tryptophan for brain entry, therefore suggesting increased brain tryptophan levels.⁶ Similarly, increased plasma tryptophan levels have been associated with the presence of anorexia in patients with liver cirrhosis.⁷ Finally, the therapeutic approach specifically designed to reduce brain tryptophan entry and serotonin synthesis, that is, administration of branched-chain amino acids, has been shown effective to improve anorexia not only in cancer patients,⁸ but in uremic and cirrhotic patients as well.^5,9

We acknowledge that evidence we reported in the preceding paragraph reported could be considered circumstantial. However, we believe that their consistency demonstrated across different clinical settings indicates that serotonin is an important player in experimental and human anorexia.

Authors' Disclosures of Potential Conflicts of Interest

The following authors or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Research Funding: F. Rossi Fanelli, Ross Products Division of Abbott Laboratories. For a detailed description of these categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section of Information for Contributors found in the front of every issue.

REFERENCES

1. Davis MP, Dreicer R, Walsh D, et al: Appetite and cancer-associated anorexia: A review. J Clin Oncol 22:1510-1517, 2004[Abstract/Free Full Text]

2. Rossi Fanelli F, Cangiano C, Ceci F, et al: Plasma tryptophan and anorexia in human cancer. Eur J Cancer Clin Oncol 22:89-95, 1986[CrossRef][Medline]

3. Cangiano C, Cascino A, Ceci F, et al: Plasma and CSF tryptophan in cancer anorexia. J Neural Transm Gen Sect 81:225-233, 1990[CrossRef][Medline]

4. Cangiano C, Testa U, Muscaritoli M, et al: Cytokines, tryptophan and anorexia in cancer patients before and after surgical tumor ablation. Anticancer Res 14:1451-1456, 1994[Medline]

5. Hiroshige K, Sonta T, Suda T, et al: Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. Nephrol Dial Transplant 16:1856-1862, 2001[Abstract/Free Full Text]

6. Aguilera A, Selgas R, Codoceo R, et al: Uremic anorexia: A consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis. Perit Dial Int 20:810-816, 2000[Abstract/Free Full Text]

7. Laviano A, Cangiano C, Preziosa I, et al: Plasma tryptophan and anorexia in liver cirrhosis. Int J Eat Disord 21:181-186, 1997[CrossRef][Medline]

8. Cangiano C, Laviano A, Meguid MM, et al: Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst 88:550-552, 1996[Free Full Text]

9. Marchesini G, Bianchi G, Merli M, et al: Nutritional supplementation with brached-chain amino acids in advanced cirrhosis: A double-blind, randomized trial. Gastroenterology 124:1792-1801, 2003[CrossRef][Medline]

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