The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Pakravan, Hassan; Ahmadian, Mehdi; Fani, A; Aghaee, Davood; Brumanad, Sareh; Pakzad, Bahram

doi:10.4103/2277-9175.204593

Cited by 43 publications

(22 citation statements)

References 25 publications

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“…Thus, our results are in line with a recent study that reported melatonin benefits in neonatal rat brain inflammation through an inverse miR-34a-SIRT1 relationship [60]. Moreover, this study could have translational value because the same dose of melatonin for 3 months limited NAFLD in other rodent models and also in patients [61,62,63].…”

Section: Discussionsupporting

confidence: 90%

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Stacchiotti

Grossi

García-Gómez

et al. 2019

Cells

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Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II/LC3I ratio, p62/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.

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Section: Discussionsupporting

confidence: 90%

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Stacchiotti

Grossi

García-Gómez

et al. 2019

Cells

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“…Recently, we depicted in another study that the administration of 10 mg/day melatonin for 12 weeks to diabetic people with ischemic heart disease had favorable impacts on inflammatory status and oxidative stress parameters (26). Pakravan et al (47) also found that supplementation with 10 mg/day melatonin significantly decreased CRP levels in people with non-alcoholic fatty liver disease. In a recent meta-analysis conducted by Akbari et al (48), melatonin supplementation decreased systemic inflammatory markers in patients with metabolic diseases.…”

Section: Discussionmentioning

confidence: 95%

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

et al. 2019

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Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18–40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements ( n = 28) or placebo ( n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (β −0.47; 95% CI, −0.86, −0.09; P = 0.01), serum total testosterone (β −0.11 ng/mL; 95% CI, −0.21, −0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (β −0.61 mg/L; 95% CI, −0.95, −0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (β −0.25 μmol/L; 95% CI, −0.38, −0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (β 106.07 mmol/L; 95% CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (β 81.05 μmol/L; 95% CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) ( P = 0.03) and tumor necrosis factor alpha (TNF-α) ( P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Clinical Trial Registration: www.irct.ir , identifier IRCT2017082733941N9, Available online at: https://www.irct.ir/trial/26051

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“…18 Previous studies revealed that melatonin treatment significantly decreased the severity of steatosis, immigration of inflammatory cells, hepatic cell damage and reduced serum and tissue inflammatory cytokine levels. [19][20][21] Moreover, melatonin induces T-cell proliferation and up-regulation of proinflammatory cytokines. 22,23 Prior studies demonstrated that melatonin could be involved in liver protection in a highfat diet, chemical component toxicity, biliary injuries, and eventually fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding liver enzymes, former studies indicated that treatment with melatonin may decrease liver enzyme levels. 10,21,27 In recent study on 100 biopsy-proven Groups:1 = Normal participants, 2 = mild to moderate fibrosis, 3 = sever fibrosis NAFLD cases, 12-week treatment with melatonin alleviates liver enzyme levels. 21 However,, these studies did not assess the association between melatonin level with steatosis or fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Levels in Patients with Nonalcoholic Fatty Liver Disease Compared with Healthy Individuals according to Fibrosis Level

Sohrabi

Gholami

Taheri³

et al. 2021

Middle East J Dig Dis

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BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide. Studies have shown that melatonin, as a regulatory hormone, is effective in different cell protective pathways. We aimed to compare serum melatonin levels of patients with NAFLD with different stages of fibrosis with that of healthy individuals. METHODS In this cross-sectional study patients, aged >20 years with elevated serum liver enzymes and trance abdominal sonographic diagnosis of fatty liver who met the exclusion criteria for NAFLD were included. The participants were categorized into three groups as follows: 1) severe fibrosis (fibrosis > 9.1 kPa and steatosis > 285 dbm), 2) mild-moderate fibrosis (fibrosis: 6-9.0 kPa and steatosis 240-285), and 3) normal group with fibrosis < 5.8 kPa and steatosis < 240 dbm based on Fibroscan evaluation. Five ml of fasting venous blood was taken from each patient and the control group for laboratory assessment. A questionnaire including demographic, anthropometric, laboratories (serum ALT, AST, triglyceride, total cholesterol and melatonin level), and clinical data was completed for all participants. RESULTS 97 people with a mean±SD age of 42.21 ± 11 years were enrolled. 59 (60.0%) patients were women. we observed that the melatonin levels were increased by advancing fibrosis. Based on control- attenuated parameter results the melatonin levels significantly differed between the healthy individuals and patients with severe steatosis. There was a direct association between increased melatonin levels and liver enzymes. CONCLUSION As a regulatory hormone, melatonin may directly be associated with liver cell injuries. Therefore, considered regulatory substances such as melatonin either diagnostic or therapeutic can improve the patients’ outcome.

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The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Cited by 43 publications

References 25 publications

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

Melatonin Levels in Patients with Nonalcoholic Fatty Liver Disease Compared with Healthy Individuals according to Fibrosis Level

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