J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 10, October 2026, pages 687-703

Efficacy of Melatonin in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis

↓ Figure 3. Forest plot comparing total cholesterol, LDL, HDL, and triglycerides between the melatonin and control groups. HDL: high-density lipoprotein; LDL: low-density lipoprotein.

↓ Figure 4. Forest plot showing changes in liver enzymes including ALT, AST, GGT, and ALP between melatonin and control groups. ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase.

↓ Figure 5. Forest plot comparing FBS, BP, weight, and waist circumference between melatonin and control groups. BP: blood pressure; FBS: fast blood sugar.

↓ **Table 1.** Baseline Characteristics of Intervention and Control Groups in the Included Studies
Author, year (Ref)	Design	Population/diagnosis of steatosis	Number of analyzed (Mel/Ctrl)	Mean age, years (Mel/Ctrl)	Male, n (%) (Mel/Ctrl)	Melatonin regimen	Comparator (type)	Duration	Weight, kg (Mel/Ctrl)	BMI, kg/m² (Mel/Ctrl)
Values are mean ± SD unless stated. AIH: autoimmune hepatitis; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CAP: controlled attenuation parameter; Ctrl: control arm; GGT: gamma-glutamyl transferase; HBV: hepatitis B virus; HCV: hepatitis C virus; Mel: melatonin arm; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; NR: not reported; PBC/PSC: primary biliary/sclerosing cholangitis; RCT: randomized controlled trial; ULN: upper limit of normal.
Bahrami, 2020 [3]	RCT, double-blind, parallel	NAFLD; ultrasound (steatosis ≥ grade 1) + ALT > 30 (M)/> 19 (F) U/L	24/21	44.0 ± 9.62/37.71 ± 11.31	17 (71)/14 (67)	6 mg (2 × 3 mg) orally, 1 h before bedtime	Starch placebo, matched shape/color (placebo)	12 weeks	85.45 ± 11.4/95.47 ± 16.2	29.46 ± 3.6/32.59 ± 6.1
Celinski, 2014 [4]	RCT, open-label, three-arm (melatonin and Essentiale-only arms used)	NAFLD confirmed by liver biopsy (simple steatosis 17, NASH 6 per arm)	23/23	36.16 ± 5.77/29.33 ± 9.58	8 (35)/12 (52)	2 × 5 mg/day orally + Essentiale forte 3 × 300 mg/day	Essentiale forte alone, no placebo (no melatonin)	14 months	NR/NR	NR/NR
Esmaeili, 2021 [19]	RCT, double-blind, two-period crossover	Chronic liver disease with pruritus (PSC, PBC, cirrhosis, AIH, HBV/HCV); steatosis not assessed	40 (crossover; 18 melatonin-first/22 placebo-first)	41.5 ± 12.08/49.73 ± 12.89 (by sequence)	11 (61)/11 (50) (by sequence)	10 mg (2 × 5 mg pearls) at night	Placebo pearls of identical shape, size, color and odor (placebo)	2 weeks per period, 2-week washout	NR/NR	NR/NR
Cichoz-Lach, 2010 [13]	Non-randomized controlled trial (allocation not described), three-arm	NASH confirmed by liver biopsy	15/15	NR/NR (all patients: women 22–46 years, men 26–58 years)	NR/NR (27/45 men overall)	2 × 5 mg/day orally + Essentiale forte 3 × daily	Placebo + Essentiale forte (placebo); (tryptophan arm not used)	4 weeks	NR/NR	NR/NR
Gonciarz, 2010 [14]	RCT (2:1 random allocation reported in the 2012 extension paper), placebo-controlled	NASH confirmed by liver biopsy; ALT/AST elevated	30/12	41.5 ± 4.0/40.8 ± 3.6 (from Ref [15])	18 (60)/8 (67) (from ref 15)	2 × 5 mg/day orally (09:00 and 21:00) + diet and walking program	Placebo twice daily + same lifestyle program (placebo)	12 weeks	82.5 ± 3.4/81.1 ± 3.7 (from ref 15)	NR/NR
Gonciarz, 2012 [15]	RCT (2:1 random allocation), placebo-controlled; extension of ref 14 in the same 42 patients	NASH confirmed by liver biopsy	30/12	41.5 ± 4.0/40.8 ± 3.6	18 (60)/8 (67)	2 × 5 mg/day orally (09:00 and 21:00) + diet and walking program	Placebo twice daily + same lifestyle program (placebo)	24 weeks (+ 12-week off-treatment follow-up)	82.5 ± 3.4/81.1 ± 3.7	NR/NR
Pakravan, 2017 [11]	RCT, double-blind, parallel	NAFLD by clinical and pathological findings; ultrasound grading (mild/moderate/severe)	49/48	42.5 ± 10.1/40.6 ± 9.8	33 (69)/27 (56)	One tablet orally twice daily (dose in mg not stated; abstract states “thrice daily for 3 months”)	Placebo tablets manufactured identically (placebo)	6 weeks (abstract states 3 months)	85.1 ± 13.5/86.9 ± 13.7	NR/NR
Chojnacki, 2017 [18]	RCT (allocation method not described), placebo-controlled	Hyperlipidemia on statins with ≥ 2-fold elevated aminotransferases; BMI > 30 excluded; steatosis not assessed	30/30	NR/NR (all patients 47–65 years)	NR/NR (19/60 men overall)	2 × 5 mg/day orally (07:00 and 21:00) + statin 20 mg/day + 1,600-kcal diet	Placebo at the same dose and times + same statin and diet (placebo)	6 months	NR / NR	NR/NR (≤ 30 by design)
Mohammadi, 2022 [12]	RCT, double-blind, four-arm (melatonin and placebo arms used)	NAFLD by ultrasonography + elevated ALT/AST; diabetes excluded	35/35	47.5 ± 13.02/44.4 ± 2.07	16 (46)/22 (63)	10 mg once daily at night + two placebos + same diet and activity program	Three placebos daily + same diet and activity program (placebo)	24 weeks	74.89 ± 11.88/89.44 ± 11.23	27.6 ± 3.8/28.05 ± 4.27
Mojtahedi, 2023 [17]	RCT, double-blind, four-arm (melatonin and placebo arms used)	NAFLD by transient elastography (FibroScan) with CAP steatosis S1–S3 and elevated ALT; diabetes and metabolic syndrome excluded	30/30	43.66 ± 11.01/43.12 ± 10.87	12 (40)/12 (40)	10 mg once daily orally + 500-kcal-deficit weight-loss diet	Placebo, pre-packaged and encoded, indistinguishable + same diet (placebo)	3 months	88.54 ± 15.06/93.05 ± 10.33	31.39 ± 2.82/32.57 ± 2.55
Gonciarz, 2013 [16]	Non-randomized before–after study in NASH patients with an untreated lean healthy reference group (no MASLD control arm)	NASH by liver biopsy within 12 months, overweight (BMI 25–30), aminotransferases/GGT > 1.5 × ULN; reference group: 15 lean healthy subjects	16/15 (healthy, untreated)	42.1 ± 3.4/40.5 ± 3.8	11 (69)/7 (47)	2 × 5 mg/day orally (09:00 and 21:00)	Untreated healthy subjects (no treatment; not a MASLD control arm)	28 days	NR/NR	28.6 ± 1.9/23.1 ± 1.1

↓ Table 1. Baseline Characteristics of Intervention and Control Groups in the Included Studies

Author, year (Ref)

Design

Population/diagnosis of steatosis

Number of analyzed (Mel/Ctrl)

Mean age, years (Mel/Ctrl)

Male, n (%) (Mel/Ctrl)

Melatonin regimen

Comparator (type)

Duration

Weight, kg (Mel/Ctrl)

BMI, kg/m² (Mel/Ctrl)

Values are mean ± SD unless stated. AIH: autoimmune hepatitis; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CAP: controlled attenuation parameter; Ctrl: control arm; GGT: gamma-glutamyl transferase; HBV: hepatitis B virus; HCV: hepatitis C virus; Mel: melatonin arm; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; NR: not reported; PBC/PSC: primary biliary/sclerosing cholangitis; RCT: randomized controlled trial; ULN: upper limit of normal.

Bahrami, 2020 [3]

RCT, double-blind, parallel

NAFLD; ultrasound (steatosis ≥ grade 1) + ALT > 30 (M)/> 19 (F) U/L

24/21

44.0 ± 9.62/37.71 ± 11.31

17 (71)/14 (67)

6 mg (2 × 3 mg) orally, 1 h before bedtime

Starch placebo, matched shape/color (placebo)

12 weeks

85.45 ± 11.4/95.47 ± 16.2

29.46 ± 3.6/32.59 ± 6.1

Celinski, 2014 [4]

RCT, open-label, three-arm (melatonin and Essentiale-only arms used)

NAFLD confirmed by liver biopsy (simple steatosis 17, NASH 6 per arm)

23/23

36.16 ± 5.77/29.33 ± 9.58

8 (35)/12 (52)

2 × 5 mg/day orally + Essentiale forte 3 × 300 mg/day

Essentiale forte alone, no placebo (no melatonin)

14 months

NR/NR

Esmaeili, 2021 [19]

RCT, double-blind, two-period crossover

Chronic liver disease with pruritus (PSC, PBC, cirrhosis, AIH, HBV/HCV); steatosis not assessed

40 (crossover; 18 melatonin-first/22 placebo-first)

41.5 ± 12.08/49.73 ± 12.89 (by sequence)

11 (61)/11 (50) (by sequence)

10 mg (2 × 5 mg pearls) at night

Placebo pearls of identical shape, size, color and odor (placebo)

2 weeks per period, 2-week washout

NR/NR

Cichoz-Lach, 2010 [13]

Non-randomized controlled trial (allocation not described), three-arm

NASH confirmed by liver biopsy

15/15

NR/NR (all patients: women 22–46 years, men 26–58 years)

NR/NR (27/45 men overall)

2 × 5 mg/day orally + Essentiale forte 3 × daily

Placebo + Essentiale forte (placebo); (tryptophan arm not used)

4 weeks

NR/NR

Gonciarz, 2010 [14]

RCT (2:1 random allocation reported in the 2012 extension paper), placebo-controlled

NASH confirmed by liver biopsy; ALT/AST elevated

30/12

41.5 ± 4.0/40.8 ± 3.6 (from Ref [15])

18 (60)/8 (67) (from ref 15)

2 × 5 mg/day orally (09:00 and 21:00) + diet and walking program

Placebo twice daily + same lifestyle program (placebo)

12 weeks

82.5 ± 3.4/81.1 ± 3.7 (from ref 15)

NR/NR

Gonciarz, 2012 [15]

RCT (2:1 random allocation), placebo-controlled; extension of ref 14 in the same 42 patients

NASH confirmed by liver biopsy

30/12

41.5 ± 4.0/40.8 ± 3.6

18 (60)/8 (67)

2 × 5 mg/day orally (09:00 and 21:00) + diet and walking program

Placebo twice daily + same lifestyle program (placebo)

24 weeks (+ 12-week off-treatment follow-up)

82.5 ± 3.4/81.1 ± 3.7

NR/NR

Pakravan, 2017 [11]

RCT, double-blind, parallel

NAFLD by clinical and pathological findings; ultrasound grading (mild/moderate/severe)

49/48

42.5 ± 10.1/40.6 ± 9.8

33 (69)/27 (56)

One tablet orally twice daily (dose in mg not stated; abstract states “thrice daily for 3 months”)

Placebo tablets manufactured identically (placebo)

6 weeks (abstract states 3 months)

85.1 ± 13.5/86.9 ± 13.7

NR/NR

Chojnacki, 2017 [18]

RCT (allocation method not described), placebo-controlled

Hyperlipidemia on statins with ≥ 2-fold elevated aminotransferases; BMI > 30 excluded; steatosis not assessed

30/30

NR/NR (all patients 47–65 years)

NR/NR (19/60 men overall)

2 × 5 mg/day orally (07:00 and 21:00) + statin 20 mg/day + 1,600-kcal diet

Placebo at the same dose and times + same statin and diet (placebo)

6 months

NR / NR

NR/NR (≤ 30 by design)

Mohammadi, 2022 [12]

RCT, double-blind, four-arm (melatonin and placebo arms used)

NAFLD by ultrasonography + elevated ALT/AST; diabetes excluded

35/35

47.5 ± 13.02/44.4 ± 2.07

16 (46)/22 (63)

10 mg once daily at night + two placebos + same diet and activity program

Three placebos daily + same diet and activity program (placebo)

24 weeks

74.89 ± 11.88/89.44 ± 11.23

27.6 ± 3.8/28.05 ± 4.27

Mojtahedi, 2023 [17]

RCT, double-blind, four-arm (melatonin and placebo arms used)

NAFLD by transient elastography (FibroScan) with CAP steatosis S1–S3 and elevated ALT; diabetes and metabolic syndrome excluded

30/30

43.66 ± 11.01/43.12 ± 10.87

12 (40)/12 (40)

10 mg once daily orally + 500-kcal-deficit weight-loss diet

Placebo, pre-packaged and encoded, indistinguishable + same diet (placebo)

3 months

88.54 ± 15.06/93.05 ± 10.33

31.39 ± 2.82/32.57 ± 2.55

Gonciarz, 2013 [16]

Non-randomized before–after study in NASH patients with an untreated lean healthy reference group (no MASLD control arm)

NASH by liver biopsy within 12 months, overweight (BMI 25–30), aminotransferases/GGT > 1.5 × ULN; reference group: 15 lean healthy subjects

16/15 (healthy, untreated)

42.1 ± 3.4/40.5 ± 3.8

11 (69)/7 (47)

2 × 5 mg/day orally (09:00 and 21:00)

Untreated healthy subjects (no treatment; not a MASLD control arm)

28 days

NR/NR

28.6 ± 1.9/23.1 ± 1.1