Journal Pre-proof

Melatonin supplementation and anthropometric indicators of obesity:

a systematic review and meta-analysis

Felipe Mendes Delpino , Lı́lian Munhoz Figueiredo

PII: S0899-9007(21)00261-6
DOI: https://doi.org/10.1016/j.nut.2021.111399
Reference: NUT 111399

To appear in: Nutrition

Received date: 25 March 2021

Revised date: 1 June 2021
Accepted date: 14 June 2021

Please cite this article as: Felipe Mendes Delpino , Lı́lian Munhoz Figueiredo , Melatonin supple-
mentation and anthropometric indicators of obesity: a systematic review and meta-analysis, Nutrition
(2021), doi: https://doi.org/10.1016/j.nut.2021.111399

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 1

Highlights
 Compared to placebo, supplementation with melatonin reduced body weight

 The results were better in studies that used doses of < 8 mg daily

 Melatonin was not effective in reducing BMI and waist circumference compared
to placebo

 More studies are needed, with greater heterogeneity, so that melatonin can be
recommended to help in the treatment of obesity
 2

Melatonin supplementation and anthropometric indicators of obesity: a systematic

review and meta-analysis

Felipe Mendes Delpino1,2*

Lílian Munhoz Figueiredo2

1
Postgraduate Program in Nursing, Federal University of Pelotas, Rio Grande do Sul,

Brazil

2
Faculty of Nursing, Federal University of Pelotas.

*CORRESPONDING AUTHOR: Felipe Mendes Delpino, Department of Nursing in

Public Health, Federal University of Pelotas, Gomes Carneiro, 01, Pelotas – RS, Brazil,

T: +53 3284-4006. E-mail: fmdsocial@outlook.com

Acknowledgements

All authors contributed to data interpretation and reviewed, edited and approved

the final manuscript.

Declaration of interest statement

The authors declare no conflict of interest.

Funding: None
 3

ABSTRACT

Objective: According to in vivo and in vitro studies, melatonin appears as a potential

supplement for obesity reduction. This study aimed to review the literature on

randomized clinical trials that evaluated the effects of melatonin supplementation on

anthropometric indicators of obesity in humans.

Research Methods & Procedures: We conducted a systematic review with meta-

analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science,

Cochrane, and Embase. We included studies that evaluated melatonin supplementation's

effects, compared to placebo, on anthropometric measures, including body weight,

BMI, and waist circumference, in people aged 18 and over. This systematic review and

meta-analysis were registered on PROSPERO: CRD42021241079.

Results: Twenty-three studies were included, of which eleven showed significant

results from melatonin supplementation on weight loss, BMI, or waist circumference,

compared to placebo. In the meta-analysis, melatonin supplementation significantly

reduced body weight [SMD: -0.48; 95% CI: -0.94, -0.02; p = <0.01; I2 = 92%]. Results

for BMI and waist circumference were null. The I2 tests were significant for the

analyses with significant results.

Conclusion: Our results demonstrated that melatonin supplementation was responsible

for significantly reducing body weight. More studies are needed until melatonin can be

recommended for weight loss.

Keywords: melatonin, weight loss, BMI, waist circumference, obesity

 4

Introduction

Obesity is a chronic condition that may lead to several diseases, such as diabetes,

coronary heart disease, and osteoarthritis [1]. Several factors may cause obesity,

including energy intake over energy needs, low physical activity, sedentariness, and

genetics [2]. Despite a temporary pause in 2009-2012, in the United States, the

prevalence of obesity is rising [3]. There is an estimate that by 2030 more than 50% of

the population will be obese, of which approximately 11% will be severely obese in the

United States [4]. This increase in obesity is responsible for costs that can exceed 549

billion dollars in two decades [4]. Globally, obesity rates increased in all ages and both

sexes, regardless of geographic location, ethnicity, or socioeconomic status [5].

Moreover, over the past three and half decades, obesity prevalence doubled worldwide,

resulting in around 11% of men and 15% of women with obesity in 2014 [6].

Supplements for weight loss are easily found in the market [7]. Consumers are looking

for products that are effective and safe for weight loss. A study showed that the terms

most commonly found in weight loss products are natural, with 92% of labels, miracle /

extraordinary, 77%, and scientific, with 31% [8]. Also, some of these products promise

weight loss of up to 1 kg per day [8]. However, most of them fail to show significant

effects in the treatment of obesity, such as resveratrol [9], vitamin D [10], and omega-3

[11].

Melatonin supplementation appears as a potential for obesity reduction. A review found

evidence that melatonin may play a role in modulating white adipose tissue and

increasing brown adipose tissue volume and activity, reducing adiposity [12]. A study

with adult male zebrafish demonstrated that melatonin supplementation exerts anti-

obesity protective effects, inducing weight loss [13]. Also, in rats, melatonin
 5

supplementation reduced mean weight gain [14]. However, for humans, a meta-analysis

from 2017 found no evidence from melatonin supplementation on body weight [15].

Despite the lack of melatonin results on body weight, there is new evidence from recent

clinical trials showing a significant reduction from melatonin supplementation in body

weight and BMI [16–19]. Thus, a new meta-analysis is necessary to evaluate the

possible benefits of melatonin supplementation in treating obesity.

Considering the new body of evidence and the potential of melatonin in the treatment of

obesity, this study aimed to review the literature on randomized clinical trials that

evaluated the effects of melatonin supplementation on anthropometric indicators of

obesity in humans.

Methods

We conducted a systematic review and meta-analysis about the effects of

supplementation with melatonin and body weight, BMI, and waist circumference in

humans. The Preferred Reporting Items for Systematic Reviews and Meta-analyzes

(PRISMA) recommendations were followed [20]. We also registered in the

International Prospective Registry for Systematic Reviews (PROSPERO)

(CRD42021241079).

Inclusion criteria

We included studies that evaluated melatonin supplementation's effects, compared to

placebo, on anthropometric measures, including body weight, BMI, and waist

circumference, in people aged 18 and over.

 6

Exclusion criteria

We excluded observational studies, studies with animals, and non-randomized clinical

trials.

Search strategy

Table 1 shows the PICOS strategy (Population, Intervention, Comparison, Outcomes,

Study design) in which we utilized to determine the article's eligibility. We performed

the searches in the following databases (Pubmed, LILACS, Scielo, Scopus, Web of

Science, Cochrane, and Embase) until March 2021. No data or language restrictions

were applied. Two groups of keywords were used to find the articles selected using the

Medical Subject Headings (MeSH). In the first, terms for melatonin were used:

"melatonin." In the second, we used terms for anthropometric indicators of obesity:

"body composition," "body compositions," "fat mass," "weight reduction," "weight

losses," "body weight," "weight loss," "waist circumference," "BMI," and "obesity." We

utilized the Boolean operators "OR" and "AND" within or between groups, respectively.

Study selection

Two reviewers (FMD and LMF) conducted the process of study selection. First, we

screened titles, followed by abstracts and full texts. The disagreements were solved by

consensus. References were revised for possible additional articles.

Risk of bias

We used the Cochrane tool to assess the risk of bias across the studies [21]. We

assessed the risk of bias independently (FMD and LMF), and disagreements were

solved by consensus. The scale items refer to questions about 1- random sequence
 7

generation (selection bias); 2- allocation concealment (selection bias); 3- blinding of

patients and personnel (performance bias); 4- blinding of outcome assessment

(detection bias); 5- incomplete outcome data (attrition bias); 6- selective reporting

(reporting bias); 7- other bias, (other potential bias, not included in the domains

described above). For the last item, we considered it as high risk if studies combined

melatonin with other substances when it was impossible to detect specific results from

melatonin. We utilized the Review Manager 5.4 software to perform the Cochrane

scale. We utilized a funnel plot and Egger’s tests to determine publication bias, for the

analyses with more than ten studies, through the package dmetar on RStudio.

Meta-analysis

In the quantitative analyses, we included studies that provided mean with standard

deviation (SD), before and after the intervention, on body weight, BMI, and waist

circumference. For studies with no information, we calculated the mean change through

the following equation: SD change = square root [(SD baseline2 + SD final2) - (2×R×

SDbaseline x SDfinal)] [22]. For studies that reported standard error (SEM), we calculated

the standard deviation using the following formula: SD = SEM x square root (n), in

which n is the number of subjects in each group. Results are presented as the

standardized mean difference (SMD) and 95% confidence intervals (95%CI). The

Higgins I2 statistic estimated the heterogeneity between studies. We considered the

heterogeneity statistically significant if I2> 50% and p-value <0.05 [23]. We also

applied the DerSimonian and Laird random-effects model to pool the SMDs. We

performed the meta-analyses on RStudio through package Meta. The level of

significance was set at 5%. We conducted stratified analyses by doses, < 8mg daily and

> 10 mg daily, and by intervention time, < 8 weeks and > 10 weeks. Moreover, we
 8

conducted a sensitivity analysis excluding studies that combined melatonin with other

substances and those that are not double-blind.

Results

Studies characteristics

Figure 1 presents the study selection flowchart. After excluding duplicates, we

found 435 titles. In the title reading, we selected 79 abstracts. The process of full-text

reading resulted in 30 articles, from which 17 studies were selected based on inclusion

and exclusion criteria. We also found six additional studies in other sources, including

reading references from studies and Google Scholar, totaling 23 studies in the present

review.

The main characteristics and results of the included studies are shown in table 2.

Most studies (n=16) were published between 2016 and 2020 [16–18,24–36]. Twelve

studies were carried out in Iran [17,25–29,33–38], followed by four in Poland

[16,24,39,40], two in Brazil [32,41], one in Mexico [42], one in the United States [43],

one in Denmark [30], one in Italy [31], and one in Iraq [18]. The sample size ranged

from 25 [41] to 119 individuals [32]. Eight studies were only with women

[16,18,25,26,30,31,38,40]. The melatonin doses ranged from 3 [30–33,37,41] to 10 mg

daily [18,24,26,28,29,34,35,39]. Intervention time ranged from three [41] to 48 weeks

[30]. Three studies combined melatonin with other substances [18,31,40]. Three studies

were conducted with overweight or obese individuals [24,38,40].

Main findings
 9

Eleven studies showed significant results from melatonin supplementation on

weight loss, BMI, or waist circumference, compared to placebo [16–

18,27,30,32,36,37,39,40,42]. From the eight studies with women, four (50%) found

significant results in weight loss, BMI, or waist circumference [16,18,30,40].

Meta-analysis

Figure 2 shows the results from the meta-analysis for body weight, BMI, and

waist circumference. The analysis included 533 individuals in the intervention group

and 532 in the control group for body weight. Results showed that supplementation with

melatonin significantly reduced body weight when compared to placebo [SMD: -0.48;

CI95%: -0.94, -0.02; p = < 0.01; I2 = 92%]. For BMI, from 442 individuals in the

intervention group and 435 in the control, results were null [SMD: -0.31; CI95%: -0.63,

0.0; p = < 0.01; I2 = 80%]. For waist circumference, from 307 individuals in the

intervention group and 300 in the control, results were also null [SMD: -0.18; CI95%: -

0.60, 0.23; p = < 0.01; I2 = 83%].

Figure 3 presents the meta-analysis for body weight stratified by doses and

intervention time. In the studies that utilized 8 mg or less per day, melatonin reduced

body weight compared to placebo [SMD: -0.76; CI95%: -1.45, -0.08; p = < 0.01; I2 =

94%]. For 10 mg or more daily, results were not significant [SMD: 0.03; CI95%: -0.18,

0.24; p = 0.96; I2 = 0%]. When stratified by intervention time, results were not

significant for studies with a duration from up to eight weeks [SMD: -0.80; CI95%: -

2.01, 0.41; p = < 0.01; I2 = 96%] and those longer than 10 weeks [SMD: -0.30; CI95%:

-0.66, 0.06; p = < 0.01; I2 = 82%].

Results of melatonin supplementation on BMI stratified by doses and

intervention time are shown in figure 4. For studies with doses of up to 8 mg daily,
 10

results were not significant [SMD: -0.46; CI95%: -0.93, 0.01; p = < 0.01; I2 = 86%].

The same occurred for studies that used doses of 10 or more mg per day [SMD: -0.03;

CI95%: -0.27, 0.20; p = 0.58; I2 = 0%]. After stratification by intervention time, the

results remained not significant for studies with a low duration [SMD: -0.40; 95% CI: -

1.17, 0.37; p = < 0.01; I2 = 89%] and longer duration [SMD: -0.30; 95% CI: -0.60, 0.00;

p = < 0.01; I2 = 69%].

Figure 5 shows the meta-analysis for waist circumference stratified by doses and

intervention time. Results were not significant for < 8 mg daily [SMD: -0.32; 95% CI: -

0.88, 0.23; p = < 0.01; I2 = 87%] and > 10 mg daily [SMD: 0.14; 95% CI: -0.26, 0.54; p

= 0.23; I2 = 31%]. The same occurred in the stratification for studies with an

intervention time of up to eight weeks [SMD: -0.15; 95% CI: -1.02, 0.72; p = < 0.01; I2

= 89%] and ten or more weeks [SMD: -0.26; 95% CI: -0.59, 0.07; p = 0.05; I2 = 55%].

Figure 6 shows the sensitivity analyses in which we excluded the studies that

combined melatonin with other substances and those that are not double-blind. The

results remained significant for body weight [SMD: -0.49; CI95%: -0.98, -0.01; p = <

0.01; I2 = 92%]. For BMI, the results were not significant [SMD: -0.19; CI95%: -0.52,

0.13; p = < 0.01; I2 = 78%], as well as for waist circumference [SMD: -0.14; CI95%: -

0.67, 0.40; p = < 0.01; I2 = 87%].

Risk of bias

Around 21% of the items were classified as unclear or high risk of bias. Two

studies had four or more of the seven items classified as unclear or high risk of bias

[31,39]. The item with more studies classified as unclear or high risk of bias was the

item 2 (Allocation concealment) with 12 studies [16–19,24,29,31,33,36,39–41],

followed by item 1 (Random sequence generation) with eight studies [16–18,31,36,39–

 11

41]. Three studies showed a high risk of bias in item seven because they combined

melatonin wither other substances [18,31,40]. All items had at least one study classified

as unclear or high risk of bias.

Figure 8 shows the funnel plot assessing the publication bias for melatonin

effects on body weight, BMI, and waist circumference. Egger´s test showed no

significant asymmetry for body weight (p = 0.60) and waist circumference (p = 0.374).

However, for BMI, Egger´s test showed an asymmetry (p = 0.048).

Discussion

Our main objective was to evaluate the effects of melatonin supplementation

compared to placebo on anthropometric indicators of obesity, such as body weight,

BMI, and waist circumference. To the best of our knowledge, we are the first meta-

analysis that showed significant melatonin results in reducing body weight. For this

measure, we found a reduction by 0.48 kg in the general analysis and 0.76 kg in the

studies that utilized < 8 mg of melatonin daily. A previous meta-analysis from 2017 that

included six unique studies and a total of 244 patients found null results for body weight

[15]. Another meta-analysis with six studies and 338 individuals included was unable to

demonstrate significant effects of melatonin supplementation on body weight compared

to placebo [44]. We included 16 studies and more than 1065 individuals between the

intervention and control groups, which can explain the difference between the results.

Our results were similar to the previous meta-analyses for BMI and waist circumference

and did not show statistical significance.

 12

Melatonin seems to be a safe supplement. Previous review studies about

melatonin security showed that its use generally has favorable safety [45,46]. According

to a review on the safety of exogenous melatonin, even at high doses melatonin is safe

in the short term. Mild adverse effects can occur, such as dizziness, headache, nausea

and drowsiness, with no reports of serious adverse effects [45]. In another review, with

37 randomized clinical trials, few adverse events were found, generally mild to

moderate [47]. Studies from long term, 12 months, demonstrated that melatonin has no

severe side effects [48]. However, previous reviews suggest studies with longer

durations to prove the long-term safety of melatonin and should be avoided in pregnant

and breast-feeding women [45,47].

The mechanisms that can help with weight loss through melatonin

supplementation are complex and not fully understood. In animals, melatonin treatment

may reduce brain damage induced by leptin deficiency-dependent obesity [49]. In mice,

melatonin supplementation prevented the deleterious effects caused by an excessive

intake of a high-fat diet, which can be a potential in the metabolic and inflammatory

disorders that obesity can cause [50]. Also, melatonin supplementation prevented body

mass gain through a decreased lipogenesis rate and increased lipolytic capacity in white

adipocytes [50]. Melatonin supplementation may also improve obesity-induced

adipokine changes by regulating inflammatory infiltration [51]. Furthermore, in mice,

melatonin may prevent obesity by serving as a probiotic agent to reverse dysbiosis of

the intestinal microbiota [52].

In mice, melatonin may present an anti-obesity effect acting to prevent the

progression of pro-inflammatory markers in the epididymal adipose tissue in

conjunction with a reduction in adiposity [53]. There is evidence that melatonin may
 13

protect against maternal obesity-associated oxidative stress and meiotic defects in

oocytes [54]. A review study showed that oral supplementation with melatonin in obese

female mice ameliorates maternal obesity-induced defective phenotypes in oocytes

through the SIRT3-SOD2-dependent mechanism [54]. Melatonin plays a role in

physiological functions in the body. It may be promising to prevent and treat obesity,

according to a review about melatonin and kidney injury in obese and diabetic

conditions [55]. Moreover, in a study with twenty-eight male Wistar rats, it was

identified that plasma melatonin levels were decreased in obese rats with periodontitis

compared with controls [56]. However, our results still do not support melatonin to be

managed to treat obesity. The reduction in weight loss was significant but modest, and

the other measures had no significant effects, reinforcing the need for further studies.

The heterogeneity test, I2, was significant for the analyses with significant

results. This heterogeneity can be explained by the variations in the duration, type of

sample, and dosage of melatonin between studies. Although Egger's test showed no

asymmetry for body weight, our results should be interpreted with caution. Future

studies are needed to prove the results from melatonin supplementation, especially in

BMI and waist circumference. We recommend that subsequent studies use doses of less

than 8 mg daily with intervention time over at least four weeks. Moreover, our

Cochrane scale showed a high number of studies with an unclear or high risk of bias in

essential items from the methodology, especially those related to the random sequence

of randomization and allocation of participants.

This review has several strengths. First, we included seven databases to find all

studies on the subject. Second, our meta-analyses included a large number of

individuals, reaching more than a thousand for body weight and more than double that
 14

compared to the previous meta-analyses. Third, we conducted a sensitivity analysis,

bias scale, and Egger´s test to identify any bias that could influence the results.

However, we understand that we are not free from limitations. We consider a limitation

because studies published in the gray literature, such as theses, dissertations, and

abstracts of congresses, were not included. We also do not consider the control for diet

or exercise that some studies may have done. However, we chose not to consider diet or

exercise since our objective was to identify melatonin effects without considering these

behavioral factors. Finally, we not included studies with children and adolescents due to

the low number of publications with this population. We chose not to include it in the

analyses since children and adolescents may have different responses to melatonin

supplementation than adults, leading to possible bias in the results.

In conclusion, our results showed that supplementation with melatonin reduced

body weight when compared to placebo. However, our results were not significant for

BMI and waist circumference. The present results should be interpreted with caution,

and more studies are needed until melatonin can be recommended for treating obesity.

Declaration of interests

The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
 15

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 21

Table 1. PICOS criteria for inclusion and exclusion of studies

Inclusion criteria Exclusion criteria

Participants Studies with humans of all ages Studies that were not with humans

Any melatonin supplementation dose Studies without melatonin

Intervention
supplementation
Placebo or usual care; any other None
Comparison nonpharmacological interventions or
pharmacological interventions
Anthropometric indicators of obesity: Studies that did not evaluated
Outcomes body weight, waist circumference, and anthropometric indicators of obesity
BMI parameters
Randomized clinical trials with adults Observational design studies, studies that
aged 18 and over were not carried out on humans, and
Study type
clinical trials that were not randomized
(without control group)
Language No limit
Year of publication No limit
 22

Table 2. Detailed description of each study included in the systematic review

Identification Location Sample Duration Study design Melatonin doses Main results
Age
in weeks

25 individuals with chronic 64 years in the

Randomized 3 mg daily or There were no significant differences
Nunes et al., 2008 Brazil obstructive pulmonary intervention group 3
double-blind placebo between groups in the BMI
disease and 67 in the control

Mean age of 42 years

The intervention group showed a
Gonciarz et al., 42 individuals with in the intervention 10 mg daily or
Poland 24 Randomized significant weight loss compared to
2012 nonalcoholic steatohepatitis group and 41 in the placebo
the placebo
control

Mean age of 31 years

Romo-Nava et al., 44 individuals with bipolar in the intervention Randomized 5 mg daily or The intervention group showed less
Mexico 8
2013 disorder or schizophrenia group and 29 in the double-blind placebo weight gain than the control group
control

Mean age of 63 years

There were no significant differences
United 39 individuals with in the intervention Randomized 8 mg daily or
Goyal et al., 2014 10 in anthropometric measurements
States metabolic syndrome group and 58 in the double-blind placebo
between groups
control

Modabbernia et al., 36 individuals with Randomized 3 mg daily or

Iran Mean age of 33 years 8 Less increase in BMI and waist
2014 schizophrenia double-blind placebo
circumference in the intervention
 23

group

Mean age of 58 years 5 mg daily +

The intervention group showed a
Chojnacki et al., 64 overweight in the intervention fluoxetine or
Poland 24 Randomized significant reduction in BMI,
2015 postmenopausal women group and 56 in the placebo +
compared to the placebo
control fluoxetine

Mean age of 34 years

There were no significant differences
Mesri Alamdari et in the intervention Randomized 6 mg daily or
Iran 44 obese women 6 in anthropometric measurements
al., 2015 group and 35 in the double-blind placebo
between groups
control

The intervention group showed a

Mean age of 62 years
reduction in fat mass and an increase
in the intervention Randomized 1 mg, 3 mg daily
Amstrup et al., 2016 Denmark 81 postmenopausal women 48 in lean mass. However, there were no
group and 63 in the double-blind or placebo
significant differences in body weight
control
or BMI

3 mg daily + There were no significant differences

D’Anna et al., 2016 Italy 40 women with amenorrhea Mean age of 49 years 24 Randomized myo-inositol or in anthropometric measurements
myo-inositol between groups

119 individuals with The intervention group showed a

Goncalves et al., Randomized 3 mg daily or
Brazil migraine with or without Mean age of 37 years 4 significant weight loss compared to
2016 double-blind placebo
aura the placebo

Agahi et al., 2017 Iran 100 individuals that were Mean age of 37 years 8
Randomized 3 mg daily or There were no significant results in the
treated with the second-
 24

generation antipsychotics for double-blind placebo intervention group

the first time

Mean age of 43 years

100 individuals with There were no significant differences
Pakravan et al., in the intervention Randomized 10 mg daily or
Iran nonalcoholic fatty liver 12 in anthropometric measurements
2017 group and 41 in the double-blind placebo
disease between groups
control

Mean age of 68 years

There were no significant differences
60 diabetic patients with in the intervention Randomized 10 mg daily or
Raygan et al., 2017 Iran 12 in anthropometric measurements
cardiovascular disease group and 65 in the double-blind placebo
between groups
control

The intervention group showed a

Rezvanfar et al., 66 individuals with type 2 Randomized 6 mg daily or
Iran Mean age of 52 years 12 significant weight loss compared to
2017 diabetes double-blind placebo
the placebo

Mean age of 38 years

There were no significant differences
Szewczyk-Golec et in the intervention 10 mg daily or
Poland 30 obesity individuals 4 Randomized in anthropometric measurements
al., 2017 group and 36 in the placebo
between groups
control

Mean age of 57 years

Compared to placebo, the BMI
Chojnacki et al., in the intervention Randomized 8 mg daily or
Poland 60 postmenopausal women 48 reduced significantly in the
2018 group and 56 in the double-blind placebo
intervention group
control

Bahrami et al., 2019 Iran Mean age of 43 years 12 Compared to placebo, the weight,
70 individuals with Randomized 6 mg daily or
BMI, and waist circumference reduced
 25

metabolic syndrome double-blind placebo significantly in the intervention group

Mean age of 29 years

There were no significant differences
56 women with Polycystic in the intervention Randomized 5 mg daily or
Jamilian et al., 2019 Iran 12 in anthropometric measurements
ovarian syndrome group and 28 in the double-blind placebo
between groups
control

There were no significant differences

58 women with polycystic Randomized 10 mg daily or
Shabani et al., 2019 Iran Mean age of 26 years 12 in anthropometric measurements
ovary syndrome double-blind placebo
between groups

Mean age of 46 years 10 mg daily +

Compared to placebo, the BMI
35 women with metabolic in the intervention Randomized metformin or
Abood et al., 2020 Iraq 12 reduced significantly in the
syndrome group and 48 years in double-blind placebo +
intervention group
the control metformin

Mean age of 44 years

Compared to placebo, the weight,
45 individuals with non- in the intervention Randomized 6 mg daily or
Bahrami et al., 2020 Iran 12 BMI, and waist circumference reduced
alcoholic fatty liver disease group and 38 in the double-blind placebo
significantly in the intervention group
control

Mean age of 64 years

10 mg daily or There were no significant differences
Daneshvar Kakhaki 60 individuals with in the intervention Randomized
Iran 12 placebo in anthropometric measurements
et al., 2020 Parkinson disease group and 66 in the double-blind
between groups
control

Iran Mean age of 66 years 12 There were no significant differences

Ostadmohammadi 60 diabetic individuals in Randomized 10 mg daily or
in the intervention in anthropometric measurements
 26

et al., 2020 hemodialysis group and 64 in the double-blind placebo between groups
control
 27

Records identified through

database searching
Identification
(n = 576)

Records after duplicates removed

(n = 435

Abstract screened
Screening

(n = 79)

Did not evaluate the outcome

studied: 8
Full-text articles assessed for
eligibility Study with children: 2
(n = 30)
Repeated study: 1

Conference Abstract: 2
Eligibility

Studies included in
qualitative synthesis Articles found in other sources
(n = 23)
(6)
Included

Studies included in quantitative

synthesis (meta-analysis)
(n = 20)

Figure 1. Flowchart of the selection of studies presented in the review

28
 29

Figure 2. Melatonin effects on body weight, BMI, and waist circumference.

 30

Figure 3. Melatonin effects on body weight stratified by doses (< 8 mg and > 10 mg
daily) and intervention time (< 8 weeks and > 10 weeks).
 31

Figure 4. Melatonin effects on BMI stratified by doses (< 8 mg and > 10 mg daily)
and intervention time (< 8 weeks and > 10 weeks).
 32

Figure 5. Melatonin effects on waist circumference stratified by doses (< 8 mg and

> 10 mg daily) and intervention time (< 8 weeks and > 10 weeks).
 33

Figure 6. Sensitivity analysis showing melatonin effects on fasting body weight,

BMI, and waist circumference.
34
35
 36

Figure 7. Cochrane risk of bias toll results for included studies.

 37

Figure 8. Funnel plot assessing the publication bias for effects of melatonin on body

weight, BMI, and waist circumference

Figure captions

Figure 1. Flowchart of the selection of studies presented in the review

Figure 2. Melatonin effects on body weight, BMI, and waist circumference.

Figure 3. Melatonin effects on body weight stratified by doses (< 8 mg and > 10 mg

daily) and intervention time (< 8 weeks and > 10 weeks).

Figure 4. Melatonin effects on BMI stratified by doses (< 8 mg and > 10 mg daily)

and intervention time (< 8 weeks and > 10 weeks).

Figure 5. Melatonin effects on waist circumference stratified by doses (< 8 mg and

> 10 mg daily) and intervention time (< 8 weeks and > 10 weeks).

Figure 6. Sensitivity analysis showing melatonin effects on fasting body weight,

BMI, and waist circumference.

Figure 7. Cochrane risk of bias toll results for included studies.

Figure 8. Funnel plot assessing the publication bias for effects of melatonin on body

weight, BMI, and waist circumference