Distribution, function and physiological role of melatonin in the lower gut

Table 1 Localization of melatonin membrane receptors in the ileum and the colon of rodents

	MT1	MT2	MT3
Ileum	+	+	+
Colon	+	+	+
Mucosa	+	No data	No data
Muscularis mucosae		+ (i); + (c)
Submucosa		+ (i); + (c)
Muscularis propria		+ (c)

MT: Melatonin receptor; i: Ileum; c: Colon.

Table 2 Clinical trials using melatonin in patients with irritable bowel syndrome

Authors	n	Study design	Dose	Conclusion
Lu et al[110]	17	Randomized, crossover placebo-controlled (8 wk)1	3 mg/od	CTT did not change significantly in IBS patients with melatonin treatment
Saha et al[109]	18	Randomized, placebo-controlled (8 wk)1	3 mg/od	Significant symptomatic benefit on bowel symptoms, extracolonic symptoms, and quality of life
Lu et al[108]	17	Randomized, crossover placebo-controlled (8 wk)1	3 mg/od	Significant symptomatic benefit on IBS scores, anxiety, well-being, and depression scores
Song et al[107]	40	Randomized, placebo-controlled (2 wk)1	3 mg/od	Significantly attenuated abdominal pain and reduced rectal pain

¹Treatment duration; od: Once daily; CTT: Colonic transit time; IBS: Irritable bowel syndrome.

Table 3 Case reports of melatonin self administration in patients with ulcerative colitis and Crohn’s disease

Authors	Age, gender,disease	Treatment	Dose	Result
Maldonado et al[113]	56, male, UC	Added melatonin to the otherwise unchanged drug treatment (salazosulfapyridine, corticosteroids)	3 mg/od	Two months later, the patient started to experience the symptoms of active UC, including bloody diarrhea
Jan et al[111] Mann[112]	47, male, UC	Added melatonin to an existing medication of mesalamine due to ongoing bloody diarrhea	3 mg/od	Symptoms resolved fast (2–3 d) and the beneficial effect was long lasting
Calvo et al[114]	35, female, CD	After becoming pregnant, the patient interrupted the treatment with melatonin, corticoids and salazosulfapyridine and symptoms of CD emerged again	3 mg/od	Recurrence of diarrhea and abdominal cramps within 4 d

od: Once daily; UC: Ulcerative colitis; CD: Crohn’s disease.

Table 4 Clinical trials using melatonin in patients with colorectal cancer

Authors	n	Disease	Study design	Dose	Results and conclusion
Lissoni et al[140]	18	Rectal cancer	Randomized to melatonin, melatonin + 5-methoxytryptamine or melatonin + IL-2, 5 wk	20 mg/od	Melatonin had no effect on radiation-induced lymphocytopenia
Lissoni[133]	152	CRC	Randomized to oxaliplatin/5-Fu or CPT-11/FS/5-Fu with or without melatonin	20 mg/od	Melatonin significantly reduced the occurrence of cachexia, thrombocytopenia, neurotoxicity and asthenia
Persson et al[139]	8	CRC	Randomized to fish oil or melatonin (4 wk) followed by 4 wk fish oil with melatonin	18 mg/od	Melatonin had no effect on serological inflammation markers
Cerea et al[135]	30	CRC	Randomized to CPT-11 or CPT-11 plus melatonin 9 wk	20 mg/od	Disease-control higher in CPT-11 + melatonin group
Lissoni et al[120]	7	CRC	Daily melatonin for at least 2 mo	20 mg/od	Melatonin may control tumor growth by reducing VEGF secretion
Lissoni et al[134]	25	CRC	Randomized to 5-Fu/FS or 5-Fu/FS + melatonin. 5 cycles of 28 d	20 mg/od	Melatonin reduces toxicity and increases efficacy of 5-Fu/FS chemotherapy
Lissoni et al[138]	8	CRC	Randomized to melatonin or melatonin + Aloe vera tincture until progression	20 mg/od	Melatonin + Aloe vera stabilized disease and increased survival in end-stage patients
Barni et al[137]	50	CRC	Randomized to BSC or BSC combined with low-dose IL-2 + melatonin 4 wk	40 mg/od	Low-dose IL-2 + melatonin induced tumor regression and prolonged survival in second-line treatment
Lissoni et al[136]	19	CRC	Randomized to IL-2 or IL-2 + melatonin 4 wk	40 mg/od	Melatonin enhanced the activity of IL-2, induced tumour regression, prolonged progression-free survival and overall survival

CRC: Colorectal cancer; od: Once daily; BSC: Best supportive care; VEGF: Vascular endothelial growth factor.