{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:23:06Z","timestamp":1788308586818,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alterations in the central nervous system in cancer patients are pivotal in determining appetite dysregulation and body weight loss (BWL). Autonomic nervous system activity was tested by measuring heart rate variability (HRV) in cancer patients presenting with anorexia. We considered inpatients with different types of cancer and investigated anorexia using their FAACT scores. HRV was evaluated by a three-channel Holter ECG. The domains of low frequencies (LF, sympathetic activity) and high frequencies (HF, parasympathetic activity) were calculated. Also, SDNN (autonomic activity) and RMSSD (parasympathetic activity) were assessed. We enrolled 56 patients with cancer and 23 controls. In cancer patients, RMSSD and SDNN were lower than in controls (p &lt; 0.001 and p = 0.009). Sympathetic activity (LF nu) was lower in cancer patients than in controls (p = 0.023), including sympathovagal balance (LF\/HF nu ratio) (p = 0.025). RMSSD was reduced in anorexic (p &lt; 0.001) and non-anorexic (p = 0.003) cancer patients compared to controls. The SDNN was lower in anorexic cancer patients than in non-anorexic cancer patients (p = 0.025), and it was lower in anorexic cancer patients than in controls (p = 0.001). LF nu was lower in anorexic cancer patients than in controls (p = 0.015), as was LF\/HF (p = 0.031). SDNN was negatively correlated with BWL in the cancer group (rho = \u22120.40; p = 0.007). Our data support the hypothesis that autonomic nervous system dysregulation exists in patients with cancer presenting with anorexia, with implications for its diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/nu15234936","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T07:40:01Z","timestamp":1701157201000},"page":"4936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Anorexia in Cancer and Its Association with Autonomic Nervous System Activity Assessed by Heart Rate Variability"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-0236","authenticated-orcid":false,"given":"Alessio","family":"Molfino","sequence":"first","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gallicchio","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Imbimbo","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Melena","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Antonini","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2015-765X","authenticated-orcid":false,"given":"Antonietta","family":"Gigante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Muscaritoli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Muscaritoli, M., Modena, A., Valerio, M., Marchetti, P., Magarotto, R., Quadrini, S., Narducci, F., Tonini, G., Grassani, T., and Cavanna, L. (2023). The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study. Cancers, 15.","DOI":"10.3390\/cancers15123206"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1016\/j.clnu.2021.02.016","article-title":"Cancer-associated anorexia: Validity and performance overtime of different appetite tools among patients at their first cancer diagnosis","volume":"40","author":"Molfino","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bossi, P., Delrio, P., Mascheroni, A., and Zanetti, M. (2021). The Spectrum of Malnutrition\/Cachexia\/Sarcopenia in Oncology According to Different Cancer Types and Settings: A Narrative Review. Nutrients, 13.","DOI":"10.3390\/nu13061980"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s12276-022-00752-w","article-title":"Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia","volume":"54","author":"Yeom","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Abraham, M., Kordatou, Z., Barriuso, J., Lamarca, A., Weaver, J.M.J., Cipriano, C., Papaxoinis, G., Backen, A., and Mansoor, W. (2019). Early recognition of anorexia through patient-generated assessment predicts survival in patients with oesophagogastric cancer. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224540"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.trecan.2022.01.004","article-title":"Emerging signaling mediators in the anorexia-cachexia syndrome of cancer","volume":"8","author":"Talbert","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/jcsm.12156","article-title":"Cancer anorexia: Hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer","volume":"8","author":"Molfino","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Olson, B., Diba, P., Korzun, T., and Marks, D.L. (2021). Neural Mechanisms of Cancer Cachexia. Cancers, 13.","DOI":"10.3390\/cancers13163990"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2165\/00007256-200333070-00004","article-title":"Heart rate monitoring: Applications and limitations","volume":"33","author":"Achten","year":"2003","journal-title":"Sports Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/psyp.12027","article-title":"The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies","volume":"50","author":"Langewitz","year":"2013","journal-title":"Psychophysiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/advances\/nmz136","article-title":"Association between Micronutrients and Heart Rate Variability: A Review of Human Studies","volume":"11","author":"Lopresti","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/ejcn.2009.35","article-title":"Body mass index is related to autonomic nervous system activity as measured by heart rate variability","volume":"63","author":"Molfino","year":"2009","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1023\/A:1016670403148","article-title":"Re-validation and shortening of the Functional Assessment of Anorexia\/Cachexia Therapy (FAACT) questionnaire","volume":"9","author":"Ribaudo","year":"2000","journal-title":"Qual. Life Res."},{"key":"ref_15","unstructured":"Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996). Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Circulation, 93, 1043\u20131065."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fpubh.2017.00258","article-title":"An Overview of Heart Rate Variability Metrics and Norms","volume":"5","author":"Shaffer","year":"2017","journal-title":"Front. Public. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14666","DOI":"10.1038\/s41598-022-18865-7","article-title":"Increased sympathetic modulation in breast cancer survivors determined by measurement of heart rate variability","volume":"12","author":"Majerova","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1200\/JCO.22.01997","article-title":"Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients with Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer","volume":"41","author":"Sandhya","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.bbi.2019.03.009","article-title":"Heart rate variability and inflammation: A meta-analysis of human studies","volume":"80","author":"Williams","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s10286-009-0019-0","article-title":"Autonomic tone and C-reactive protein: A prospective population-based study","volume":"19","author":"Singh","year":"2009","journal-title":"Clin. Auton. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1049970","DOI":"10.3389\/fonc.2022.1049970","article-title":"The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer","volume":"12","author":"Cherifi","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"712823","DOI":"10.3389\/fpsyg.2021.712823","article-title":"Can Exercise Reduce the Autonomic Dysfunction of Patients with Cancer and Its Survivors? A Systematic Review and Meta-Analysis","volume":"12","author":"Mayo","year":"2021","journal-title":"Front. Psychol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jpainsymman.2009.06.014","article-title":"The association between autonomic dysfunction and survival in male patients with advanced cancer: A preliminary report","volume":"39","author":"Fadul","year":"2010","journal-title":"J. Pain. Symptom Manag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1242\/dmm.026609","article-title":"Hypothalamic circuits regulating appetite and energy homeostasis: Pathways to obesity","volume":"10","author":"Timper","year":"2017","journal-title":"Dis. Mod. Mech."},{"key":"ref_25","first-page":"S487","article-title":"Influence of the hypothalamic paraventricular nucleus (PVN) on heart rate variability (HRV) in rat hearts via electronic lesion","volume":"26","author":"Deng","year":"2015","journal-title":"Biomed. Mater. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E1000","DOI":"10.1152\/ajpendo.90252.2008","article-title":"Neural control of the anorexia-cachexia syndrome","volume":"295","author":"Laviano","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1097\/00001756-199503270-00011","article-title":"Correlation between food intake and CSF IL-1 alpha in anorectic tumor bearing rats","volume":"6","author":"Opara","year":"1995","journal-title":"Neuroreport"},{"key":"ref_28","first-page":"R566","article-title":"Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells","volume":"275","author":"Ilyin","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_29","first-page":"40","article-title":"Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats","volume":"48","author":"Laviano","year":"2000","journal-title":"J. Investig. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1210\/en.2007-0017","article-title":"Regulation of central melanocortin signalling by interleukin-1 beta","volume":"148","author":"Scarlett","year":"2007","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cmet.2007.09.012","article-title":"Serotonin and the orchestration of energy balance","volume":"6","author":"Tecott","year":"2007","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF01245044","article-title":"Plasma and CSF tryptophan in cancer anorexia","volume":"81","author":"Cangiano","year":"1990","journal-title":"J. Neural Transm. Gen. Sect."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Molfino, A., Imbimbo, G., Amabile, M.I., Ammann, T., Lionetto, L., Salerno, G., Simmaco, M., Chiappini, M.G., and Muscaritoli, M. (2023). Fatigue in Patients on Chronic Hemodialysis: The Role of Indoleamine 2,3-Dioxygenase (IDO) Activity, Interleukin-6, and Muscularity. Nutrients, 15.","DOI":"10.3390\/nu15040876"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3346\/jkms.2010.25.8.1140","article-title":"Heart rate variability and length of survival in hospice cancer patients","volume":"25","author":"Kim","year":"2010","journal-title":"J. Korean Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/WNP.0000000000000210","article-title":"Prognostic Value of Heart Rate Variability in Patients with Cancer","volume":"32","author":"Guo","year":"2015","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jpsychores.2016.08.004","article-title":"Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis","volume":"89","author":"Zhou","year":"2016","journal-title":"J. Psychosom. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/SPC.0000000000000379","article-title":"How much does reduced food intake contribute to cancer-associated weight loss?","volume":"12","author":"Martin","year":"2018","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/s41430-018-0245-4","article-title":"Cancer-associated malnutrition","volume":"72","author":"Baracos","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100092","DOI":"10.1016\/j.esmoop.2021.100092","article-title":"Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines","volume":"6","author":"Arends","year":"2021","journal-title":"ESMO Open"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4936\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:32:07Z","timestamp":1760131927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":39,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["nu15234936"],"URL":"https:\/\/doi.org\/10.3390\/nu15234936","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]}}}