Melatonin is a naturally occurring hormone produced by the pineal gland that has numerous biologic effects, including antioxidant properties and potential effects on the sleep-wake cycle and immune system functions. Melatonin is available as a dietary supplement. Long-term effects of supplementation are not known. Melatonin has been studied for its effect on anorexia, depression, fatigue, sleep-wake disturbances, and cognitive impairment in people with cancer.
Effectiveness Not Established
Research Evidence Summaries
Del Fabbro, E., Dev, R., Hui, D., Palmer, L., & Bruera, E. (2013). Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: A double-blind placebo-controlled trial. Journal of Clinical Oncology, 31, 1271–1276.doi: 10.1200/JCO.2012.43.6766
To compare melatonin with placebo for impact on appetite in patients with advanced cancer
Intervention Characteristics/Basic Study Process:
Patients were randomly assigned to receive 20 mg melatonin or identical placebo daily for 28 days. Study assessments were done at baseline and at four weeks. Patients were stratified according to whether or not they were currently receiving antitumor treatment.
- The study reported on a sample of 48 patients.
- Mean patient age was 60 years, with a range of 32–86 years.
- The sample was 56% female and 44% male.
- All patients had locally recurrent or metastatic disease.
- Outpatient setting
The study was a double-blind, randomized, placebo-controlled trial.
- Edmonton Symptom Assessment Scale
- Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
- FACIT subscale questionnaire
- Toxicity questionnaire
Bioimpedance for body composition and weight
There were no significant differences between groups in symptoms or change in symptoms at four weeks. There were no differences in change in body weight or body composition. Thirty-three percent of patients were lost to follow-up.
Melatonin had no effect on appetite or other symptoms in patients with advanced cancer.
- The study had a small sample size, with less than 100 patients.
- Patient withdrawals were 10% or greater.
Findings of this study do not support the use of melatonin to improve appetite or other symptoms in patients with advanced cancer.
Yavuzsen, T., Davis, M.P., Walsh, D., LeGrand, S., & Lagman, R. (2005). Systematic review of the treatment of cancer-associated anorexia and weight loss. Journal of Clinical Oncology, 23, 8500–8511.doi: 10.1200/JCO.2005.01.8010
Studies were included in the review if they reported on
- Adult patients older than 18 years of age
- Patients with nonhematologic malignancies
- Patients with anorexia or symptoms of anorexia, such as lack of appetite, weight loss, poor performance status, and decreased quality of life.
The review involved only prospective, randomized controlled trials (RCTs; double- and single-blind or unblended and phase III trials). The quality of studies was assessed using the validated scale published by Jadad et al. (1996).
There were 55 studies reviewed that met the eligibility criteria.
Multiple RCTs have been conducted to investigate the safety and efficacy of pharmacologic agents to stimulate appetite. Only two therapeutic interventions for cancer-related anorexia demonstrated enough evidence to support their use in patients with cancer: corticosteroids and progestins. Other studies had mixed outcomes, positive results in only a single randomized trial, or were not placebo-controlled.
There is strong evidence supporting the use of progestins in patients with cancer, of which the most commonly reported drugs were MA and MPA. There was increased weight with both progestins; there was also evidence of a dose-response, but higher doses did not confer any additional benefit with regard to appetite. Metaclopromide is effective for nausea and early satiety but has not been shown to directly stimulate appetite.
The RCTs did not show sufficient evidence to justify the use of dronabinol, EPA, EPO, ghrelin, interferon, melatonin, nandrolone, NSAIDs, or pentoxyfilline in cancer-related anorexia. Cyproheptadine is a weak appetite stimulant, but side effects are limiting.
The optimal dose, start time, and duration of treatment for many appetite stimulants are still unknown. A more systematic approach to research methodology is needed. In addition, uniform outcome measures to better assess the value of various appetite stimulants are needed. These should include subjective ratings of appetite and associated symptoms (e.g., early satiety) and objective measures (e.g., food consumed, weight gain, weight loss).