The Potential Therapeutic Effect of Melatonin in Gastro-esophageal Reflux Disease

Tharwat S Kandil; Amany A Mousa; Ahmed A El-Gendy; Amr M Abbas

BMC Gastroenterol. 2010;10:7

Abstract and Introduction

Abstract

Background: Gastro-Esophageal Reflux Disease (GERD) defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor) which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury. Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models. The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy.
Methods: 36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks) Each group consisted of 9 persons. Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin.
Results: Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole. Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone.
Conclusion: The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD. It is an effective line of treatment in relieving epigastric pain and heartburn. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use.

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Abstract and Introduction
Background
Methods
Results
Discussion
Conclusion
References

Table 1. Comparison of control subjects and patients pretreated with melatonin, omeprazole and both (n = 9)
	control	Pretreatment with melatonin	Pretreatment with omeprazole	Pretreatment with melatonin and omeprazole
Symptoms:
1-Heart burn:
Yes	0	7	7	8
Duration(months)		1.3 ± 0.4	1.2 ± 0.3	1.4 ± 0.4
2-Epigastric pain:
Yes	0	6	6	6
Duration(months)		1.4 ± 0.5	1.3 ± 0.4	1.3 ± 0.4
A)LES Study:
1-LES pressure(mmHg)	22.8 ± 1.3	10 ± 1.58^a	10.5 ± 2.86^a	10.3 ± 1.68^a
2-Residual pressure (mmHg)	0.4 ± 0.01	0.012 ± 0.52^a	0.1 ± 0.064^a	0.012 ± 0.44^a
3-Relaxation duration (seconds)	5.0 ± 0.1	6.8 ± 0.12^a	6.5 ± 2.74^a	6.8 ± 0.16^a
4-Relaxation %	100 ± 0.00	86 ± 0.87^a	87.2 ± 0.17^a	85 ± 1.58^a
C) PH (at 5 cm above the LES):	7.8 ± 0.4	2.3 ± 0.36^a	2.1 ± 0.38^a	1.98 ± 0.37^a
D) BAO (mmol/h)	2.6 ± 0.6	24.7 ± 0.5^a	25.1 ± 0.6^a	24.9 ± 0.7^a
E) Serum Gastrin(pg/ml)	41.8 ± 7.1	22.1 ± 4.2^a	21.5 ± 4.6^a	21.9 ± 4.7^a
D) Melatonin level at day time (pg/ml):	36.1 ± 2.3	18.2 ± 5.54^a	18.5 ± 3.75^a	18.3 ± 3.8^a

a: p < 0.05 relative to control

Table 2. Effects of melatonin on patients with GERD group II (n = 9)
	Pretreatment with melatonin	4 weeks Post treatment with melatonin	8 weeks Post treatment with melatonin
Symptoms:
1-Heart burn:
Yes	7	3 (57.1%)	0 (100%)
Duration(months)	1.3 ± 0.4
2-Epigastric pain:
Yes	6	3 (50%)	1 (83%)
Duration(months)	1.4 ± 0.5
B)LES Study:
1-LES pressure(mmHg)	10 ± 1.58	14.5 ± 1.58^a	20.2 ± 1.56 ^ab
2-Residual pressure (mmHg)	0.012 ± 0.52	0.2 ± 0.016	0.32 ± 0.013^a
3-Relaxation duration (seconds)	6.8 ± 0.12	5.9 ± 0.16 ^a	5.3 ± 0.12 ^a
4-Relaxation %	86 ± 0.87	90 ± 0.86 ^a	100 ± 0.00 ^ab
C) PH (at 5 cm above the LES):	2.3 ± 0.36	5.2 ± 0.5 ^a	6.7 ± 0.65 ^ab
D) BAO (mmol/h)	24.7 ± 0.5	20.1 ± 0.4 ^a	16.6 ± 0.6 ^ab
E) Serum Gastrin(pg/ml)	22.1 ± 3.2	27.2 ± 2.3 ^a	32.3 ± 2.1 ^ab
D) Melatonin level at day time (pg/ml):	18.2 ± 5.54	28.26 ± 2.26 ^a	34.5 ± 2.35 ^ab

a: p < 0.05 relative to pretreatment with melatonin
b: p < 0.05 relative to 4 weeks post treatment with melatonin

Table 3. Effects of omeprazole on patients with GERD Group III (n = 9)
	Pretreatment with omeprazole	4 weeks Post treatment with omeprazole	8 weeks Post treatment with omeprazole
A) Symptoms:
1-Heart burn:
Yes	7	2 (71.4%)	0 (100%)
Duration(months)	1.2 ± 0.3
2-Epigastric pain:
Yes	6	2	0
Duration(months)	1.3 ± 0.4	(66.7%)	(100%)
B)LES Study:
1-LES pressure(mmHg)	10.5 ± 2.86	10.4 ± 4.05	10.5 ± 2.85
2-Residual pressure (mmHg)	0.1 ± 0.064	0.2 ± 0.15	0.1 ± 0.07
3-Relaxation duration (seconds)	6.5 ± 2.74	6.3 ± 2.7	6.3 ± 2.65
4-Relaxation %	87.2 ± 0.17	87.3 ± 0.25	87.1 ± 0.1
C) PH (at 5 cm above the LES):	2.1 ± 0.38	5.9 ± 0.48^a	7.2 ± 0.32^ab
D) BAO (mmol/h)	25.1 ± 0.6	17.2 ± 0.7^a	11.5 ± 0.6^ab
E) Serum Gastrin (pg/ml)	21.5 ± 4.6	32.1 ± 2.1^a	35.9 ± 1.8^ab
D) Melatonin level at day time (pg/ml):	18.5 ± 3.75	19.2 ± 3.47	17.9 ± 3.72

a: p < 0.05 relative to pretreatment with melatonin
b: p < 0.05 relative to 4 weeks Post treatment with melatonin

Table 4. Effects of melatonin and omeprazole on patients with GERD group IV (n = 9)
	Pretreatment with melatonin and omeprazole	4 weeks Post treatment with melatonin and omeprazole	Post 8 weeks treatment with melatonin and omeprazole
A) Symptoms:
1-Heart burn:
Yes	8	1(87.5%)	0 (100%)
Duration(months)	1.4 ± 0.4
2-Epigastric pain:
Yes	6	1(83.3%)	0 (100%)
ration(months)	1.3 ± 0.4
B) LES Study:
1-LES pressure(mmHg)	10.3 ± 1.68	14.5 ± 1.26^a	20.5 ± 1.22^ab
2-Residual pressure (mmHg)	0.012 ± 0.44	0.21 ± 0.016	0.33 ± 0.016^a
3-Relaxation duration (seconds)	6.8 ± 0.16	5.8 ± 0.13^a	5.2 ± 0.12^a
4-Relaxation %	85 ± 1.58	90 ± 1.23^a	100 ± 0.00^ab
C) PH (at 5 cm above the LES):	1.98 ± 0.37	6.1 ± 0.55^a	7.5 ± 0.31^ab
D) BAO (mmol/h)	24.9 ± 0.7	15.8 ± 0.9^a	10.2 ± 0.9^ab
E) Serum Gastrin (pg/ml)	21.9 ± 4.7	33.6 ± 2.7^a	36.8 ± 2.1^ab
D) Melatonin level at day time (pg/ml):	18.3 ± 3.8	28.83 ± 1.82^a	34.5 ± 2.35^ab

a: p < 0.05 relative to pretreatment with melatonin
b: p < 0.05 relative to 4 weeks Post treatment with melatonin

Table 5. Comparison of the three treated groups with GERD
	Melatonin	Omeprazole	Melatonin and Omeprazole	P value
	Melatonin	Omeprazole	Melatonin and Omeprazole	P1	P2	P3
A)Symptoms:
Heart burn:
control	0	0	0
pretreatment:
yes	7	7	8
duration (months)	1.3 ± 0.4	1.2 ± 0.3	1.4 ± 0.4
4 weeks
8 weeks	3(57.1%)	2(71.4%)	1(87.5%)
	0(100%)	0(100%)	0(100%)
Epigastric pain:
-control	0	0	0
pretreatment:
yes	6	6	6
duration (months)	1.4 ± 0.5	1.3 ± 0.4	1.3 ± 0.4
4 weeks	3(50%)	2(66.7%)	1(83.3%)
8 weeks	1(83%)	0(100%)	0(100%)
B) LES Study:				P1	P2	P3
1-LES pressure(mmHg)
control	22.8 ± 1.3	22.8 ± 1.3	22.8 ± 1.3	0.9	0.9	0.9
pretreatment:	10 ± 1.58	10.5 ± 2.86	10.3 ± 1.68	0.65	0.7	0.86
4 weeks	14.5 ± 1.58	10.4 ± 4.05	14.5 ± 1.26	0.006	0.468	0.002
8 weeks	20.2 ± 1.56	10.5 ± 2.85	20.5 ± 1.22	0.000	0.68	0.000
2-Residual pressure (mmHg)				P1	P2	P3
- control	0.4 ± 0.01	0.4 ± 0.01	0.4 ± 0.01	1.0	1.0	1.0
pretreatment:	0.012 ± 0.52	0.1 ± 0.064	0.012 ± 0.44	0.578	1.00	0.556
4 weeks	0.2 ± 0.016	0.2 ± 0.15	0.21 ± 0.016	1.00	0.198	0.198
8 weeks	0.32 ± 0.013	0.1 ± 0.07	0.33 ± 0.016	0.000	0.08	0.000
3-Relaxation duration (seconds)				P1	P2	P3
control	5.0 ± 0.1	5.0 ± 0.1	5.0 ± 0.1	1.0	1.0	1.0
pretreatment::	6.8 ± 0.12	6.5 ± 2.74	6.8 ± 0.16	0.747	1.000	0.747
4 weeks	5.9 ± 0.16	6.3 ± 2.7	5.8 ± 0.13	0.662	0.153	0.585
8 weeks	5.3 ± 0.12	6.3 ± 2.65	5.2 ± 0.12	0.747	0.102	0.059
4-Relaxation %				P1	P2	P3
control	100 ± 0.00	100 ± 0.00	100 ± 0.00	1.0	1.0	1.0
pretreatment:	86 ± 0.87	87.2 ± 0.17	85 ± 1.58	0.12	0.116	0.14
4 weeks	90 ± 0.86	87.3 ± 0.25	90 ± 1.23	0.1	1.000	0.1
8 weeks	100 ± 0.00	87.1 ± 0.1	100 ± 0.00	0.01	1.00	0.01
C) PH (at 5 cm above the LES):				P1	P2	P3
control:	7.8 ± 0.4	7.8 ± 0.4	7.8 ± 0.4	1.0	1.0	1.0
pretreatment:	2.3 ± 0.36	2.1 ± 0.38	1.98 ± 0.37	0.1	0.1	0.1
4 weeks	5.2 ± 0.5	5.9 ± 0.48	6.1 ± 0.55	0.008	0.002	0.09
8 weeks	6.7 ± 0.65	7.2 ± 0.32	7.5 ± 0.31	0.01	0.008	0.1
D) BAO(mmol/h)				P1	P2	P3
- control:	2.6 ± 0.6	2.6 ± 0.6	2.6 ± 0.6	1.0	1.0	1.0
pretreatment:	24.7 ± 0.5	25.1 ± 0.6	24.9 ± 0.7	0.1	0.1	0.1
4 weeks	20.1 ± 0.4	17.2 ± 0.7	15.8 ± 0.9	0.008	0.002	0.09
- 8 weeks	16.6 ± 0.6	11.5 ± 0.6	10.2 ± 0.9	0.01	0.008	0.1
E) Serum Gastrin(pg/ml)				P1	P2	P3
control:	41.8 ± 7.1	41.8 ± 7.1	41.8 ± 7.1	1.0	1.0	1.0
pretreatment:	22.1 ± 4.2	21.5 ± 4.6	21.9 ± 4.7	0.1	0.1	0.1
4 weeks	27.2 ± 2.3	32.1 ± 2.1	33.6 ± 2.7	0.008	0.002	0.09
- 8 weeks	32.3 ± 2.1	35.9 ± 1.8	36.8 ± 2.1	0.01	0.008	0.1
D) Melatonin level at day time (pg/ml):				P1	P2	P3
control	36.1 ± 2.3	36.1 ± 2.3	36.1 ± 2.3	1.0	1.0	1.0
pretreatment:	18.2 ± 5.54	18.5 ± 3.75	18.3 ± 3.8	0.1	0.665	0.472
4 weeks	28.26 ± 2.26	19.2 ± 3.47	28.83 ± 1.82	0.000	0.55	0.000
8 weeks	34.5 ± .35	17.9 ± 3.72	34.5 ± 2.35	0.000	1.00	0.000

P1: group III versus group II
P2: group IV versus group II
P3: group IV versus group III

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