Received: 31 December 2018 Revised: 18 September 2019 Accepted: 24 October 2019

DOI: 10.1002/ptr.6547

REVIEW

Effect of the herbal medicines in obesity and metabolic

syndrome: A systematic review and meta‐analysis of
clinical trials

Moloud Payab1 | Shirin Hasani‐Ranjbar1 | Nazila Shahbal3 | Mostafa Qorbani2,4 |

Azadeh Aletaha5 | Hamed Haghi‐Aminjan6 | Akbar Soltani5 | Fatemeh Khatami7 |

Shekoufeh Nikfar8 | Shokoufeh Hassani9 | Mohammad Abdollahi9 | Bagher Larijani2

1
Obesity and Eating Habits Research Center,
Endocrinology and Metabolism Molecular‐ Obesity is a medical situation in which excess body fat has gathered because of
Cellular Sciences Institute, Tehran University
imbalance between energy intake and energy expenditure. In spite of the fact that
of Medical Sciences, Tehran, Iran
2
Endocrinology and Metabolism Research the variety of studies are available for obesity treatment and management, its
Center, Endocrinology and Metabolism Clinical “globesity” still remains a big challenge all over the world. The current systematic
Sciences Institute, Tehran University of
Medical Sciences, Tehran, Iran review and meta‐analysis aimed to evaluate the efficacy, safety, and mechanisms of
3
Non‐Communicable Diseases Research effective herbal medicines in the management and treatment of obesity and meta-
Center, Endocrinology and Metabolism
bolic syndrome in human. We systematically searched all relevant clinical trials via
Population Sciences Institute, Tehran
University of Medical Sciences, Tehran, Iran Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects
4
Non‐communicable Diseases Research of raw or refined products derived from plants or parts of plants on obesity and met-
Center, Alborz University of Medical Sciences,
Karaj, Iran
abolic syndrome in overweight and obesity adult subjects. All studies conducted by
5
Evidence Based Medicine Research Center, the end of May 2019 were considered in the systematic review. Data were extracted
Endocrinology and Metabolism Clinical independently by two experts. The quality assessment was assessed using Consoli-
Sciences Institute, Tehran University of
medical Sciences, Tehran, Iran dated Standards of Reporting Trials checklist. The main outcomes were anthropomet-
6
Pharmaceutical Science Research Center, ric indices and metabolic syndrome components. Pooled effect of herbal medicines
Ardabil University of Medical Sciences, Ardabil,
on obesity and metabolic syndrome were presented as standardized mean difference
Iran
7
Chronic Diseases Research Center, (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were
Endocrinology and Metabolism Population included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella
Sciences Institute, Tehran University of
Medical Sciences, Tehran, Iran sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredi-
8
Department of Pharmacoeconomics and ents were found to be effective in the management of obesity and metabolic syn-
Pharmaceutical Administration, Faculty of
drome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to
Pharmacy, and Evidence‐based Evaluation of
Cost‐Effectiveness and Clinical Outcomes reduce appetite.
Group, Pharmaceutical Science Research
Meta‐analysis showed that intake of green tea resulted in a significant improvement
Center (PSRC), The Institute of Pharmaceutical
Sciences (TIPS), Tehran University of Medical in weight ([SMD]: −0.75 [−1.18, −0.319]), body mass index ([SMD]: −1.2 [−1.82,
Sciences, Tehran, Iran
−0.57]), waist circumference ([SMD]: −1.71 [−2.66, −0.77]), hip circumference
9
Toxicology and Diseases Group (TDG),
Pharmaceutical Science Research Center
([SMD]: −0.42 [−1.02, −0.19]), and total cholesterol, ([SMD]: −0.43 [−0.77, −0.09]).
(PSRC), The Institute of Pharmaceutical In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement
Sciences (TIPS), and Department of Toxicology

Abbreviations: BMI, body mass index; BF%, body fat percent; EC, epicatechine; EGCG, epigallocatechine gallate; FBS, fasting blood sugar; FFM, fat‐free mass; FM, fat mass; GLP‐1, glucagon‐like
peptide‐1; HC, hip circumference; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; RCT, randomized controlled trial; TC, total cholesterol; TG, triglyceride; WC, waist circumference;
WHR, waist to hip ratio

Phytotherapy Research. 2019;1–20. wileyonlinelibrary.com/journal/ptr © 2019 John Wiley & Sons, Ltd. 1
2 PAYAB ET AL.

and Pharmacology, Faculty of Pharmacy,

Tehran University of Medical Sciences, Tehran, in weight ([SMD]: −0.88, 95 % CI: [−1.13, −0.63]) and triglyceride ([SMD]: −1.67, 95 %
Iran
CI: [−2.54, −0.79]), respectively. High quality trials are still needed to firmly establish
Correspondence the clinical efficacy of the plants in obesity and metabolic syndrome.
Shirin Hasani‐Ranjbar, Obesity and Eating
Habits Research Center, Endocrinology and
K E Y W OR D S
Metabolism Molecular‐Cellular Sciences
Institute, Tehran University of Medical herbal medicines, meta‐analysis, metabolic syndrome, systematic review, obesity, randomized
Sciences, Tehran, Iran. controlled trial
Email: [email protected]
Mohammad Abdollahi, Toxicology and
Diseases Group (TDG), Pharmaceutical Science
Research Center (PSRC), The Institute of
Pharmaceutical Sciences (TIPS), and
Department of Toxicology and Pharmacology,
Faculty of Pharmacy, Tehran University of
Medical Sciences, Tehran, Iran.
Email: [email protected]

Funding information
National Institute for Medical Research
Development, Grant/Award Number: 957973

1 | I N T RO D U CT I O N adverse reactions. Despite large investments in research to develop

effective drugs for obesity, only a few drugs have been approved.
Obesity is a metabolic disorder in which abnormal or excessive body For this reason, patients and researchers are looking for complemen-
fat accumulates as a result of the imbalance between energy intake tary and alternative treatment methods such as the use of medicinal
and energy expenditure (Hasani‐Ranjbar, Jouyandeh, & Abdollahi, plants and their products for the treatment of obesity (Hasani‐Ranjbar
2013). Today, the prevalence of obesity is pervasively increasing et al., 2009; Hasani‐Ranjbar et al., 2013; Rucker et al., 2007). It has
worldwide, and it is predicted to rise even more because of changing appeared that a wide variety of herbs, including their extracts or active
lifestyle (Hasani‐Ranjbar, Nayebi, Larijani, & Abdollahi, 2009; Rucker, components, isolated from plants, can be used for metabolic syndrome
Padwal, Li, Curioni, & Lau, 2007). The World Health Organization even in specific nanoformulated pharmaceutical forms.
reported a prevalence of overweight and obesity in adults of 39% Herbal medicines and their products can reduce weight through
(1.9 billion) and 13% (650 million) in 2016, respectively (Afshin et al., five mechanisms as follows: appetite suppressant and reduced energy
2017; Apovian et al., 2015). intake, stimulation of thermogenesis and metabolic promoters,
Obesity is usually connected with poor quality of life, and it not inhibiting the activity of pancreatic lipase and reducing fat absorption,
only increases the risk of many diseases, including hypertension, dys- increasing lipolysis, and decreasing lipogenesis (Apovian et al., 2015;
lipidemia, type 2 diabetes mellitus, osteoarthritis, kidney disease, sleep Kazemipoor et al., 2015).
disorders, and some cancers, but also can cause premature death However, there are still conflicting opinions regarding the efficacy
(Afshin et al., 2017; El‐Sayed Moustafa & Froguel, 2013; Kazemipoor of such treatments due to insufficient evidence supporting their effec-
et al., 2015; Payab et al., 2018). In spite of the fact that the variety tiveness and safety. For these reasons, attention is drawn to
of studies are available for obesity treatment and management, its conducting rigorous clinical trials to evaluate scientific evidence
“globesity” still remains a big challenge all over the world (Esteghamati, regarding the effectiveness of herbal medicines.
Mazaheri, Rad, & Noshad, 2015). This systematic review focuses on the potential role of herbal med-
The pathophysiology of obesity is very complicated involving in icines in the treatment of obesity and summarizes the scientific
several interaction of different genetic, environmental, and behavioral evidence.
elements (El‐Sayed Moustafa & Froguel, 2013; Hoebel, Malan, & de Some systematic reviews conducted earlier have evaluated the
ridder, 2012). Among these factors, environmental factors (e.g., sed- efficacy of herbal medicine to treat obesity and metabolic syndrome
entary lifestyle (computer games and watching television) and nutri- (Esteghamati et al., 2015; Hasani‐Ranjbar et al., 2009; Hasani‐Ranjbar
tional disorders like consumption of high‐calorie foods and diets are et al., 2013). Due to burden imposed by obesity in the recent years, a
most putative causes of obesity (Payab et al., 2015; Payab et al., need was really felt for conducting new systematic reviews on the
2016). topic of obesity with a focus on randomized clinical trials although
Besides weight loss diet, exercise, and behavioral changes, using the number of high‐quality trials are not yet enough (Colalto, 2018;
anti‐obesity drugs have been reputed as a weight loss strategy in Izzo, Hoon‐kim, Radhakrishnan, & Williamson, 2016). By conducting
overweight and obese individuals. Currently, synthetic chemical drugs the present systematic review studies, we try to provide the highest
are used for the treatment of obesity that impose high cost and level of evidence on the efficacy, safety, and mechanisms of effective
PAYAB ET AL. 3

herbal medicines in the management and treatment of obesity and Herbal medicine involving mixed or single herbs and their active ingre-
metabolic syndrome in randomized clinical trials (RCTs). dients were included. The comparison interventions included herbal
medicine compared with no treatment, herbal medicine compared
with placebo, herbal medicine compared with only exercise, herbal
2 | METHODS medicine compared with synthetic medicine.

This systematic review protocol was registered in the International

Prospective Register of Systematic Reviews (Registration number: 2.2.4 | Types of outcome measures
CRD42016049753). Also, the protocol of this systematic review has
been already published (Payab et al., 2018). The primary outcome is expected to be an improvement in the body
weight, BMI, waist circumference, waist‐to‐hip ratio (WHR), body fat
(weight or mass of visceral adipose tissue, fat mass, or percent), and
2.1 | Search strategy and data collection appetite. Secondary outcome is estimated to be improvement in the
levels of cholesterol (total, low‐density lipoprotein [LDL], high‐
All studies on herbal medicines and their active ingredients used in the
density lipoprotein [HDL]), blood pressure, triglyceride, and blood
treatment of obesity and metabolic syndrome were searched and
glucose.
reviewed. For this purpose, the databases, including PubMed, Scopus,
Web of Science, and the Cochrane, were used. All search details are
described in the protocol article (all studies conducted by the end of 2.2.5 | Data extraction and quality assessment
May 2019 were considered in the systematic review).
References of relevant review and systematic review articles were Data were extracted independently from included trials by two
reviewed to increase coverage of included articles and ensure litera- authors according to a predefined data extraction sheet. The extracted
ture saturation. At least three emails with logical intervals (about 2 data included (a) general information (author, title, publication year,
weeks) were sent to the corresponding author of the article in order journal, randomization, blinding, and location), (b) participants (sample
to eliminate the limitations of nonaccess to full text. size, BMI range, and age), (c) intervention (type and name of plant,
parts of plants [e.g., leaves, stems, buds, flowers, and roots], active
ingredient [If noted] and duration), (d) control (no treatment, placebo
2.2 | Inclusion criteria
therapy), and (e) outcomes (reported outcomes, adverse events,
follow‐up time, and mechanism).
2.2.1 | Types of studies
The quality assessment in the included studies were assessed inde-

The total of applicable clinical trials (including double and single blind pendently by two blind authors using Consolidated Standards of

and data from parallel group‐designed or crossover designed) that Reporting Trials (CONSORT) checklist adapted for the herbal medicine

examine the effectiveness of herbal medicines for the treatment of (CONSORT Herbal Medicinal Interventions checklist; Gagnier et al.,

obesity and metabolic syndrome were recruited. All studies were inde- 2006). Each item is scored 1 in the checklist if is included in the corre-

pendently screened by the review authors based on their titles and sponding. At the end, scores were collected, and the total score for

abstracts. The full text of articles potentially suitable for the review each article was given. In total, each article could score up to 34

were obtained to assess relevance based on the inclusion/exclusion points.

criteria. Any disagreements in the assessment of data were resolved by dis-

cussion between the two authors, and consultation was made with a
third reviewer if there are any discrepancies. The whole process of
2.2.2 | Types of participants
study selection is summarized in the Preferred Reporting Items for
Systematic Reviews and Meta‐Analyses flow diagram (Figure 1).
Those studies evaluating the general adult human population (≥18
years) conducted on overweight or obese individuals (body mass index
[BMI] ≥ 25) or those with metabolic syndrome (based on Adult Treat- 2.2.6 | Statistical analysis
ment Panel III and International Diabetes Federation criteria) were
included in this study. As well, those studies having populations The effect of herbal medicine on obesity and metabolic syndrome was
restricted to specific diseases, conditions, or metabolic disorders were assessed using the standardized mean difference (SMD), also known
excluded. as Cohen's d. The SMD was calculated using the means difference
(endpoint from baseline) and standard deviations (SD) of the two
2.2.3 | Types of interventions groups (treatment and placebo) using the following formula as follows:
SMD = mean difference in intervention group − mean difference in
Definition of herbal medicines in this study is “entirely raw or refined placebo group/pooled SD
products derived from plants or parts of plants (e.g., flowers, leaves, Pooled SD = √ [(SD in intervention group) 2
+ (SD in placebo
2
buds, stems, roots, or tubers) used for the treatment of diseases.” group) /2].
4 PAYAB ET AL.

FIGURE 1 Flow chart for study identification and selection [Colour figure can be viewed at wileyonlinelibrary.com]

Q‐test and I2 were used for assessing heterogeneity among the 2.3 | Ethics and dissemination
studies. We used random‐effects model when the Q‐statistic for het-
erogeneity was significant at the level of 0.1 (Hozo, Djulbegovic, & In this study, ethical approval is not essential because the data that
Hozo, 2005). In other cases, the fixed‐effects model was used used are not subjects and the results discussed through peer‐reviewed
(Dersimonian & Laird, 1986). The degree of heterogeneity was quanti- publications.
fied using I2 statistics. I2 values of 25%, 50%, and 75% were consid-
ered to correspond to low, medium, and high levels of
heterogeneity, respectively. Random or fixed effects meta‐analysis 3 | RESULTS
was used to estimate pooled SMD and 95% confidence interval (CI).
The forest plot was used to present the pooled SMD and its 95 % 3.1 | Description of included studies
CI schematically (Supporting Information 1). Publication bias was
assessed using Egger's tests and the results of Egger's test were con- Figure 1 presents the flow chart of search process and the selection
sidered statistically significant at p < 0.1. The meta‐analysis was per- of study. Following a search on PubMed (n = 2,724), Scopus (n =
formed for plants with at least three articles on their effects on 8,672), Web of Science (n = 3,345), and the Cochrane (n = 2,314)
obesity and metabolic syndrome. Among all studies that evaluated databases, 12,001 relevant articles were identified. After the initial
the effect of herbal medicine on the obesity and metabolic syndrome, search and reading the title and abstracts of the article, 594 articles
green tea, Nigella sativa, C. fimbriata, G. cambogia, Irvingia gabonensis, were reviewed. Finally, 279 articles were entered into this study,
and Phaseolus vulgaris entered in the meta‐analysis. The statistical and the full texts of the articles were reviewed. The characteristics
analysis was carried out using StatsDirect 3.1.22. A p value ≤ .05 of included clinical trials and the reasons for exclusions are summa-
was considered statistically significant. rized in Table S3.
PAYAB ET AL. 5

All randomized and nonrandomized clinical trials and before–after mg/day; Ross, 2011, Ngondi, Oben, & Minka, 2005), C. fimbriata
studies were entered. The comparison interventions included (a) com- (with dose of 1,000 mg/day; Kuriyan et al., 2007, Astell, Mathai,
parison between herbal medicine and no treatment, (b) comparison Mcainch, Stathis, & Su, 2013, Arora et al., 2015), respectively
between herbal medicine and placebo, (c) comparison between herbal (Table 1).
medicine and only exercise, and (d) comparison between herbal medi- Among the studies, the most effective plants on the weight loss
cine and synthetic medicine. Some studies have examined single plant are green tea (with effective dose of 6,000 mg/day for green tea
and some combination of plants. and 400–800 mg/day for catechins), P. vulgaris (with effective dose
Most countries that have studied herbal medicine for obesity treat- of 1,000 mg/day), G. cambogia (with effective dose of 2,400
ment are the United States, Korea, Japan, Iran, China, Italy, Australia, mg/day), N. sativa (with effective dose of 3,000 mg/day), puerh tea
and India. (with effective dose of 1,000 mg/day), I. gabonensis (with effective
dose of 300 mg/day), C. fimbriata (with effective dose of 1,000
mg/day), respectively. Other plants that have been affected by weight
3.2 | Quality of included studies
loss and BMI include cumin (with doses of 100 and 3,000 mg/day;
Zare, Heshmati, Fallahzadeh, & Nadjarzadeh, 2014, Taghizadeh,
Quality of included studies was assessed using the CONSORT scor-
Memarzadeh, Asemi, & Esmaillzadeh, 2015), flaxseed (with doses of
ing. Each item is scored 1 in the checklist if is included in the corre-
sponding. At the end, scores were collected, and the total score for 2,500 and 6,000 mg/day; Saxena & Katare, 2014, Cassani, Fassini,

each article was given. In total, each article could score up to 34 Silvah, Lima, & Marchini, 2015), Hibiscus sabdariffa (with effective
dose of 75 mg/day; Kuriyan, Kumar, Rajendran, & Kurpad, 2010,
points. The average CONSORT score was 23.78 ± 3.51. Scoring of
Chang, Peng, Yeh, Kao, & Wang, 2014), rosehip (with dose of 100
articles was not for the inclusion and/or exclusion purposes but
rather for assessing the quality of the studies. The item of “eligibility mg/day; Nagatomo et al., 2015, Andersson, Berger, Hogberg,
Landin‐olsson, & Holm, 2012), Lycium Barbarum (with doses of 30,
criteria for participants and the settings and locations where the
60, and 120 ml/day; Amagase & Nance, 2011, Amagase & Nance,
data were collected” had the highest score and the items of “charac-
teristics of the herbal product” had the lowest one. 2008), cinnamon (with doses of 550 and 2,000 mg/day; Vafa et al.,
2012, Akilen, Tsiami, Devendra, & Robinson, 2010), and so forth, as
detailed in Table S3.
4 | OUTCOMES Among all the examined plants, green tea has the most evidence. In
the studies, the extract of this plant and its active ingredients, includ-
ing caffeine, gallocatechine, epigallocatechine, catechins, epicatechine,
4.1 | Effect of herbal medicines on anthropometric
indices epigallocatechine gallate (EGCG), gallocatechine gallate, and
epicatechine gallate, have been used (Lee, Kim, & Kim, 2009;
4.1.1 | Body weight Mielgo‐Ayuso et al., 2014; Nagao et al., 2007; Wang et al., 2010).

In the first place, noteworthy reduction in body weight and BMI was
observed in herbs, including green tea (green tea with doses of 300, 4.1.2 | Waist and hip circumference
400, 870, 928, 1,000, 1,500, and 6,000 mg/day and catechins with
doses of 150, 300, 458, 468, 886, and 1,200 mg/day; Janssens, Some studies have also reported additional effects on reduced waist
Hursel, & Westerterp‐plantenga, 2015, Hsu et al., 2008, Basu and hip circumference in addition to weight. There was a significant
et al., 2010, Vieira Senger, Schwanke, Gomes, & Valle Gottlieb, decrease in waist circumference (WC) and hip circumference (HC) in
2012, Wang et al., 2010, Di Pierro, Menghi, Barreca, Lucarelli, & relation to the intake of green tea (green tea with doses of 300,
Calandrelli, 2009, Tsai, Chiu, Yang, Ouyang, & Yen, 2009, Nagao, 400, 870, 928, 1,000, and 6,000 mg/day and catechins with doses
Hase, & Tokimitsu, 2007, Mielgo‐Ayuso et al., 2014, Diepvens, of 150, 300, 458, 468, 886, and 1,200 mg/day; Basu, Fu, et al.,
Kovacs, Vogels, & Westerterp‐Plantenga, 2006, Chantre & Lairon, 2010, Vieira Senger et al., 2012, Hsu et al., 2008, Nagao et al., 2007,
2002, Chen, Liu, Chiu, & Hsu, 2016), P. vulgaris (with doses of 445, Tsai et al., 2009, Wang et al., 2010), P. vulgaris (with doses of 445,
1,000, and 3,000 mg/day; Chantre & Lairon, 2002, Hartman et al., 1000, and 3,000 mg/day; Perricone, 2010, Celleno et al., 2007,
2011, Celleno, Tolaini, D'amore, Perricone, & Preuss, 2007, Udani, Hartman et al., 2011), N. sativa (with doses of 1,500, 1,600, 2,000,
Hardy, & Madsen, 2004), G. cambogia (with doses of 1,667, 2,400, and 3,000 mg/day; Mahdavi et al., 2015, Qidwai, Hamza, Qureshi, &
and 3,000 mg/day (equivalent 1,000, 1,200, and 1,500 mg Gilani, 2009), I. gabonensis (with doses of 150, 300, and 3,150
hydroxycitric acid; Hayamizu et al., 2003, Mattes & Bormann, mg/day; Ngondi et al., 2005, Ross, 2011), and C. imbriata (with dose
2000, Heymsfield et al., 1998), N. sativa (with doses of 1,500, of 1,000 mg/day; Arora et al., 2015, Astell et al., 2013, Kuriyan
1,600, 2,000, and 3,000 mg/day; Mahdavi, Namazi, Alizadeh, & et al., 2007), respectively.
Farajnia, 2015), puerh tea (with dose of 1,000 mg/day; Mahdavi Green tea (Diepvens et al., 2006), N. sativa (Mahdavi et al., 2015),
et al., 2015, Kubota et al., 2011, Yang et al., 2014, Fujita & C. fimbriata (Arora et al., 2015; Astell et al., 2013), and H. sabdariffa
Yamagami, 2008), I. gabonensis (with doses of 150, 300, and 3,150 (Chang et al., 2014) decreased the WHR.
6 PAYAB ET AL.

TABLE 1 Herbal agents for obesity and metabolic syndrome. Dosage, duration, and therapeutic effects

No. Name Dose Duration Outcome

1 Green tea (Camellia sinensis; 12) a

Green tea: 300, 400, 870, 928, 1,000, and 8–12 Weight ↓ SBP, DBP ↓
6,000 mg/day weeks
Catechins: 150, 300, 458, 468, 886, and BMI ↓ TG ↑
1,200 mg/day WC ↓ TC ↓
HC ↓ LDL ↓
WHR ↔ HDL ↑
FBS ↓
FM ↓
FFM ↑
BF% ↓
2 Phaseolus vulgaris (5) 445, 1,000, and 3,000 mg/day 4–12 weeks Weight ↓ SBP, DBP ↓
BMI ↓ TG ↓
WC ↓ TC ↓
HC ↓ LDL ↓
WHR ↔ HDL ↓
FM ↓ FBS ↓
FFM ↓
3 Garcinia cambogia (Garcinia gummi‐ 1,667, 2,400, and 3,000 mg/day (1,000, 12–16 weeks Weight ↓ TG ↓
gutta; 5) 1,200, and 1,500 mg hydroxycitric acid) BMI ↔ TC ↓
WC ↔ LDL ↓
HC ↔ HDL ↑
WHR ↔
FM ↓
4 Nigella sativa (5) 1500, 1600, 2000, 3000 mg/day 6–8 weeks Weight ↓ SBP, DBP ↔
BMI ↔ TG ↓
WC ↓ TC ↓
HC↔ LDL ↓
WHR ↓ HDL ↑
FBS ↓
5 Puerh Tea (4) 1000 mg/day 12 weeks Weight ↓ TG ↓
BMI ↓ TC ↓
LDL ↓
HDL ↑
FBS ↓
6 Irvingia gabonensis (3) 150, 300, 3150 mg/day 4–10 weeks Weight ↓ TG ↓
WC ↓ TC ↓
BF% ↓ LDL ↓
FBS ↓
7 Caralluma Fimbriata (3) 1000 mg/day 8–12 weeks Weight ↓ SBP, DBP ↑
BMI ↔ TG ↔
WC ↓ TC ↔
HC ↔ LDL ↔
WHR ↔ HDL ↔
FBS ↔
8 Hibiscus Sabdariffa (3) 75, 500, 1000 mg/day 4–12 weeks Weight ↓ TG ↓
BMI ↓ TC ↓
WC ↓ LDL ↓
WHR ↓ HDL ↔
BF% ↓ FBS ↓

Abbreviations: BF%, body fat percent; BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; FFM, fat‐free mass; FM, fat mass; HC,
hip circumference; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; WC,
waist circumference; WHR, waist to hip ratio.
a
Number of studies.

4.1.3 | Body fat (FFM). Also, significant decrease was seen in FM and BF% by green
tea (green tea with dose of 6,000 mg/day and catechins with doses of
In addition, some studies have recognized the effectiveness of herbal 458, 468, and 886 mg/day; Tsai et al., 2009, Wang et al., 2010), I.
plants on body fat percent (BF%), fat mass (FM), and fat‐free mass gabonensis (with dose of 300 mg/day; Ngondi et al., 2005), H. sabdariffa
PAYAB ET AL. 7

(with dose of 75 mg/day; Chang et al., 2014), Phaseolus Vulgaris (with 4.2 | Effect of herbal medicines on food intake
dose of 445 mg/day; Celleno et al., 2007, Perricone, 2010), G. cambogia
(with doses of 2,400 and 3,000 mg/day [equivalent 1,200 and 1,500 mg Besides, a significant decrease in appetite and increase in hunger was
hydroxycitric acid]; Heymsfield et al., 1998, Vasques et al., 2014), seen by P. vulgaris (with dose of 100 mg/day; Spadafranca et al., 2013),
Ecklonia cava (with doses of 72 and 144 mg/day; Shin, Kim, Park, Lee, C. fimbriata (with dose of 1,000 mg/day; Kuriyan et al., 2007), spinach
& Hwang, 2012), cumin (with dose of 3,000 mg/day; Zare et al., 2014), (with dose of 5,000 mg/day; Rebello et al., 2015, Stenblom, Egecioglu,
Coleus forskolii (with dose of 250 mg/day; Loftus, Astell, Mathai, & Su, Landin‐olsson, & Erlanson‐albertsson, 2015), flaxseed (with dose of
2015), Sorghum tea (with dose of 1,000 ml/day) (Yokomichi, 2015), 2,500 mg/day; Ibrugger, Kristensen, Mikkelsen, & Astrup, 2012), fenu-
Gynostemma pentaphyllum (with dose of 450 mg/day; Park et al., greek (with dose of 8,000 mg/day; Mathern, Raatz, Thomas, & Slavin,
2014), and cinnamon (with dose of 550 mg/day; Vafa et al., 2012). 2009), G. cambogia (with dose of 1,000 mg/day; Mayer et al., 2014,
There was a significant increase in FFM with green tea (green tea Preuss et al., 2004), green coffee (Roshan, Nikpayam, Sedaghat, &
with dose of 6,000 mg/day and catechins with doses of 458, 468, Sohrab, 2018), and the combination simplicifolia, asiatica, Taraxacum
and 886 mg/day; Nagao et al., 2007, Wang et al., 2010), G. ambogia officinale, Cynara Scolymus, Paullina Sorbilis, Alga Klamath (Rondanelli,
(with dose of 3,000 mg/day [equivalent 1500 mg hydroxycitric acid]; Klersy, Iadarola, Monteferrario, & Opizzi, 2009), and a combination
Vasques et al., 2014), aloe vera (with dose of 588 mg/day; Choi, of G. cambogia and Amorphophallus konjac (Vasques et al., 2008;
Kim, Son, Oh, & Cho, 2013), cocoa (with dose of 1.4 g/day; Ibero‐ Figure 2). Some other articles have shown that Gundelia tournefortii
Baraibar et al., 2014), and rapeseed (with dose of 3,500 mg/day; (Hajizadeh‐Sharafabad, Alizadeh, Mohammadzadeh, Alizadeh‐Salteh,
Baxheinrich, Stratmann, Lee‐barkey, Tschoepe, & Wahrburg, 2012). & Kheirouri, 2016), Coleus forskohlii (Loftus et al., 2015), N. sativa
The names of all herbs with substantial effects on FM and FFM are (Mahdavi et al., 2015), Garcinia atroviridis (Roongpisuthipong,
described in details in Table S5. Kantawan, & Roongpisuthipong, 2007), C. fimbriata (Kuriyan et al.,

FIGURE 2 Potential mechanisms of herbal medicine for obesityHerbal medicines and their products that can reduce weight through five
mechanisms as follows: appetite suppressant and reduced energy intake, stimulation of thermogenesis and metabolic promoters, inhibiting the
activity of pancreatic lipase and reducing of fat absorption, as well as increasing lipolysis and decreasing lipogenesis [Colour figure can be viewed
at wileyonlinelibrary.com]
8 PAYAB ET AL.

2007), a combination of ephedra and caffeine (Hackman et al., 2006) 4.5 | Effect of herbal medicines on lipid profile
as well as a combination of walnut and flaxseed (Wu et al., 2010) sig-
nificantly reduces energy intake (Figure 2). 4.5.1 | Triglyceride

First, the most effective plants on the triglyceride (TG) was seen by N.
4.3 Effect of herbal medicines on energy
| sativa (with effective dose of 1,000 mg/day; Mahdavi et al., 2015), H.
expenditure sabdariffa (with effective dose of 75 mg/day; Asgary, Soltani, Zolghadr,
Keshvari, & Sarrafzadegan, 2016), puerh tea (Chu et al., 2011), I.
Additionally, a remarkable increase in energy expenditure was seen by gabonensis (with effective dose of 300 mg/day; Ross, 2011), chia (with
Kaempferia parviflora (with dose of 100 mg/day; Matsushita et al., dose of 35 g/day; Tavares Toscano, Tavares Toscano, Leite Tavares, da
2015), Aframomum melegueta (with dose of 30 mg/day; Sugita et al., Oliveira Silva, & Silva, 2014), P. vulgaris (with effective dose of 1,000
2014), oolong tea (with dose of 5,000 mg/day; Komatsu et al., mg/day; Hartman et al., 2011), flaxseed (Cassani et al., 2015; Saxena
2003), and green tea, a combination of tyrosine, green tea and caf- & Katare, 2014), G. cambogia (with effective dose of 2,400 mg/day;
feine (Belza, Toubro, & Astrup, 2009), and a combination of Camellia Vasques et al., 2014), cinnamon (with doses of 550 and 3,000
sinensis, Capsicum Annum Oleoresin, Fucus vesiculosus, Allium sativa, mg/day; Vafa et al., 2012, Gupta Jain, Puri, Misra, Gulati, & Mani,
mint essential oil, and Piper nigrum (Rondanelli et al., 2013; Figure 2). 2017), pomegranate (with dose of 1,000 mg/day; Hosseini,
Saedisomeolia, Wood, Yaseri, & Tavasoli, 2016), pistachio (with dose
of 53 g/day; Li et al., 2010), soybean (with dose of 2,000 mg/day; Choi
4.4 | Effect of herbal medicines on hormones et al., 2014), a combination of S. indicus and G. mangostana (Stern,
Peerson, Mishra, Mathukumalli, & Konda, 2013), and a combination
Further, some literatures have pinpointed the effect of herbs on hor-
of Aralia Mandshurica and Engelhardtia chrysolepis (Abidov et al.,
mones as described below.
2006). Other plants that have been affected by decreased TG are
detailed in Table S6.

4.4.1 | Glucagon‐like peptide‐1

4.5.2 | Total cholesterol, low‐density lipoprotein, and
A significant increase in the secretion of Glucagon‐like peptide‐1 high‐density lipoprotein
(GLP‐1) was seen by a combination of C. sinensis, Capsicum Annum
Oleoresin, F. vesiculosus, A. sativa, mint essential oil, P. nigrum Second, a significant decrease in total cholesterol (TC) was seen as a
(Rondanelli et al., 2013), combination of Lippia citriodora and H. result of intaking green tea (with effective dose of 6,000 mg/day; Tsai
sabdariffa (Boix‐Castejon et al., 2018), and green plant membranes et al., 2009), N. sativa (with effective dose of 3,000 mg/day; Latiff,
(chlorophyll and thylakoid; Montelius et al., 2014; Figure 2). Parhizkar, Dollah, & Hassan, 2014), H. sabdariffa (with effective dose
of 75 mg/day; Kuriyan et al., 2010), I. gabonensis (with effective dose
of 300 mg/day; Ngondi et al., 2005, Ross, 2011), flaxseed (with dose
4.4.2 | Adiponectin
of 2,500 mg/day;Cassani et al., 2015 , Saxena & Katare, 2014), G.
cambogia (with effective dose of 2,400 mg/day; Hayamizu et al.,
A significant increase in the secretion of adiponectin was seen by
2003), puerh tea (with effective dose of 1,000 mg/day; Chu et al.,
green tea (Chen et al., 2016; Hsu et al., 2008), I. gabonensis (Ngondi,
2011), E. cava (with doses of 72 and 144 mg/day; Shin et al., 2012),
Etoundi, Nyangono, Mbofung, & OBEN, 2009), sea buckthorn
cinnamon (with dose of 3,000 mg/day; Gupta Jain et al., 2017), rice
(Lehtonen et al., 2011) Salba‐chia (Salvia hispanica L.; Vuksan et al.,
bran (with doses of 30–50 mg/day; Hongu et al., 2014; Ito,
2017), a combination of Sphaeranthus indicus and Garcinia mangostana
Nakashima, & Matsuoka, 2015), a combination of S. indicus and G.
(Stern, Peerson, Mishra, Mathukumalli, & Konda, 2013), the combina-
mangostana (Stern, Peerson, Mishra, Mathukumalli, & Konda, 2013),
tion Dolichos Biflorus and Piper betle (Sengupta et al., 2012), and a
a combination of Cissus quadrangularis and I. gabonensis (Oben,
combination of C. sinensis, Capsicum Annum Oleoresin, F. vesiculosus,
Ngondi, Momo, Agbor, & Sobgui, 2008), and a combination of P.
A. sativa, mint essential oil, and P. nigrum (Rondanelli et al., 2013;
vulgaris and Ceratonia siliqua (Birketvedt, Travis, Langbakk, &
Figure 2).
Florholmen, 2002). Other plants that have been affected by decreased
TC are detailed in Table S6.
4.4.3 | Leptin A significant decrease in LDL was seen by green tea (with effective
dose of 6,000 mg/day; Tsai et al., 2009), N. sativa (with effective dose
A significant decrease in the secretion of leptin was seen by I. of 3,000 mg/day; Latiff et al., 2014), H. sabdariffa (with effective dose
gabonensis (Ngondi et al., 2009; Ross, 2011), P. vulgaris (Hartman of 75 mg/day; Kuriyan et al., 2010), puerh tea (with effective dose of
et al., 2011), G. ambogia (Preuss et al., 2004), rapeseed oil (Baxheinrich 1,000 mg/day; Chu et al., 2011), I. gabonensis (with effective dose of
et al., 2012), and a combination of ephedra and caffeine (Hackman 300 mg/day; Ngondi et al., 2005, Ross, 2011), flaxseed (Cassani
et al., 2006; Figure 2). et al., 2015, Saxena & Katare, 2014), G. cambogia (with effective dose
PAYAB ET AL. 9

of 2,400 mg/day; Hayamizu et al., 2003), E. cava (Shin et al., 2012), 4.7.1 | C‐reactive protein
hops (Morimoto‐Kobayashi et al., 2016), rice bran (Hongu et al.,
2014, Ito et al., 2015), rapeseed (Baxheinrich et al., 2012), strawberries A significant decrease in concentration of C‐reactive protein was seen
(Basu et al., 2010), a combination of C. quadrangularis and I. gabonensis by I. gabonensis (Ngondi et al., 2009), pomegranate (Hosseini et al.,
(Oben et al., 2008), and a combination of ma huang and kola nut 2016), Palmaria palmata (Allsopp et al., 2016), puerh tea (Chu et al.,
(Coffey, Steiner, Baker, & Allison, 2004). Other plants that have been 2011; Yang et al., 2014), Opuntia ficus‐indica (Godard et al., 2010), car-
affected by decreased LDL are detailed in Table S6. damom (Kazemi et al., 2017), Salba‐chia (S. hispanica L.; Vuksan et al.,
An increase in HDL was seen by green tea (Tsai et al., 2009), N. 2017), and the combination red orange, grapefruit, sweet orange, and
sativa (Latiff et al., 2014), E. cava (Shin et al., 2012), G. cambogia guarana (Dallas et al., 2014; Figure 2).
(Hayamizu et al., 2003), puerh tea (Chu et al., 2011), pomegranate
(Hosseini et al., 2016), cinnamon (with dose of 3,000 mg/day; Gupta 4.7.2 | Tumor necrosis factor alpha
Jain et al., 2017), yerba mate (Balsan et al., 2019), brown rice (Bui
et al., 2014), Artemisia princeps pampanini (Cho et al., 2012), and a Puerh tea decreased concentration of tumor necrosis factor alpha (Chu
combination of ma huang and kola nut (Coffey et al., 2004). Other et al., 2011; Figure 2).
plants that have been affected by decreased LDL are detailed in
Table S6. 4.7.3 | Interleukin 6

Puerh tea (Chu et al., 2011) and pomegranate (Hosseini et al., 2016)
4.6 | Effect of herbal medicines on glycemic indices decreased the concentration of interleukin 6 (Figure 2).

The most effective plants on the fasting blood glocuse (FBS) was seen
4.8 | Meta‐analysis
by green tea (with doses of 150 and 1,000 mg/day; Diepvens et al.,
2006, Vieira Senger et al., 2012), H. sabdariffa (with dose of 1,000
Overall decreased of weight and BMI were −0.75 (95% CI: −1.18,
mg/day; Kuriyan et al., 2010), puerh tea (with dose of 10 g/day; Chu
−0.319) and −1.2 (95% CI: −1.82, −0.57) more in green tea than that
et al., 2011), I. gabonensis (with doses of 150 and 300 mg/day; Ngondi
in control group (Table 2). There was high significant heterogeneity
et al., 2005, Ross, 2011), P. vulgaris (with dose of 250 mg/day;
between included studies (I2 = 94.3%, I2 = 95.9%). In nine studies,
Hartman et al., 2011), N. sativa (with dose of 1,600 mg/day; Latiff
pooled mean difference for effects of green tea on WC and HC com-
et al., 2014), chia (Nieman et al., 2009), E. cava (with doses of 72
pared with the placebo group was −1.71 (95% CI: −2.66, −0.77) and
and 144 mg/day; Shin et al., 2012), cinnamon (with doses of 550
−0.42 (95% CI: −1.02, −0.19) with high heterogeneity (I2 = 97.1%
and 3, 000 mg/day; Vafa et al., 2012, Gupta Jain et al., 2017), carob
and I2 = 93.3%), respectively (Table 2). Eight clinical trials reported
(with dose of 4.45 g/day; Banuls et al., 2016), brown rice (Bui et al.,
the effect of green tea on BF%. A pooled mean difference was found
2014), a combination of ephedra and caffeine (Hackman et al.,
to be significant (−1.96, CI: 95%: −3.28, −0.65).
2006), a combination of C. quadrangularis and I. gabonensis, a combina-
In three studies, SMD for effect of P. vulgaris on weight compared
tion of coptidis, mori, and Puerariae lobatae (Gao et al., 2013), and a
with the placebo group was −0.88 (95% CI: −1.13, −0.63) with high
combination of S. indicus and G. mangostana (Stern, Peerson, Mishra,
heterogeneity (I2 = 90.7%).
Mathukumalli, & Konda, 2013). Other plants that have been affected
All of eight articles on green tea or placebo groups investigated TG,
by decreased FBS are detailed in Table S6.
TC, LDL, and HDL as the outcome at baseline and follow‐up. Overall
A significant decrease in hemoglobin A1c was seen by H. sabdariffa
decrease of TC was −0.43 (95% CI: −0.77, −0.09). Green tea did not
(Asgary et al., 2016), Citrus aurantium (Haller, Benowitz, & Jacob,
significantly improve the lipid profiles such as TG (SMD: −0.2, 95%
2005), Gynostemma pentaphyllum (Park et al., 2014), sea buckthorn
CI: −0.52, 0.12) and HDL (SMD: 0.18, 95% CI: −0.01, 0.36).
(Lehtonen et al., 2011), bilberries (Lehtonen et al., 2011), Ilex
Meta‐analyses suggested that intake of N. sativa resulted in a sta-
paraguariensis (Kim, Oh, Kim, Chae, & Chae, 2015), a combination of
tistically significant improvement in TG (SMD: −1.67, 95 % CI: −2.54,
P. vulgaris and C. siliqua (Birketvedt et al., 2002), and a combination
−0.79).
of grape seeds and pine bark (LaRiccia, Farrar, Sammel, & Gallo, 2008).
Three clinical trials reported the effect of I. gabonensis on weight. A
In two studies, on two plants, chia (Nieman et al., 2009) and Rhus
pooled mean difference was found to be significant (−0.66, CI: 95%:
coriaria L. (Ardalani et al., 2016), it has been shown that they can
−0.96, −0.36).
increase the level of insulin secretion (Figure 2).

4.9 | Publication bias

4.7 | Effect of herbal medicines on inflammatory
factors Publication bias was estimated by Egger's test. The results of
Egger's test confirmed that there was no publication bias among the
Some papers have concurred on the effect of herbs on inflammatory studies investigated the effect of green tea on weight (coefficient =
factors that includes the following. −1.76, p = .364), HC (coefficient = −2.48, p = .652), WHR (coefficient
10 PAYAB ET AL.

TABLE 2 Meta‐analysis of effects of herbal medicine on obesity and metabolic syndrome

Heterogeneity assessment
Number
Name Variable of Study Pooled SMD (95% CI) Model I‐squared (I2; %) Heterogeneity chi‐squared

Green tea (Camellia sinensis) Weight 16 −0.75 (−1.18, −0.319)* Random 94.3 261.08
BMI 14 −1.2 (−1.82, −0.57)* Random 95.9 315.05
WC 9 −1.71 (−2.66, −0.77)* Random 97.1 276.31
HC 8 −0.42 (−1.02, −0.19)* Random 93.3 105.15
WHR 4 −0.11 (−0.34, 0.12) Fixed 0.0 2.62
TG 8 −0.2 (−0.52, 0.12) Fixed 63.5 19.16
TC 8 −0.43 (−0.77, −0.09)* Fixed 66.6 20.98
LDL 8 −0.21 (−0.4, −0.03)* Fixed 40.2 11.7
HDL 8 0.18 (−0.01, 0.36) Fixed 0.5 7.04
FBS 6 0.16 (−0.08, 0.39) Fixed 0.0 2.22
SBP 6 −0.17 (−0.3, 0.01) Fixed 16.3 5.97
DBP 6 −0.85 (−1.7, 0.01) Random 92.6 53.75
FM 6 −0.4 (−0.56, −0.24)* Fixed 76.4 21.16
BF% 8 −1.96 (−3.28, −0.65)* Random 97.3 221.41
FFM 4 0.07 (−0.15, 0.29) Fixed 0.0 0.09
Nigella sativa BMI 3 −0.001 (−0.24, 0.24) Fixed 0.0 0.75
TG 4 −1.67 (−2.54, −0.79)* Random 90.3 30.82
TC 4 −0.43 (−1.28, 0.42) Random 91.7 36.14
LDL 4 −0.86 (−1.7, −0.03)* Random 91.1 33.68
HDL 3 −1.04 (−2.7, 0.63) Random 96.5 57.57
SBP 3 −0.34 (−0.59, −0.1)* Fixed 52.1 4.17
Caralluma fimbriata Weight 3 0.02 (−0.3, 0.32) Fixed 0.0 0.03
BMI 3 −0.06 (−0.36, 0.24) Fixed 0.0 0.38
WC 3 −0.1 (−0.4, 0.19) Fixed 0.0 0.31
HC 3 −0.01 (−0.31, 0.29) Fixed 0.0 0.03
Garcinia cambogia Weight 5 0.13 (−0.09, 0.34) Fixed 5.3 4.22
Irvingia gabonensis Weight 3 −0.66 (−0.96, −0.36)* Fixed 0.0 1.33
Phaseolus vulgaris Weight 3 −0.88 (−1.13, −0.63)* Random 90.7 21.58

Abbreviations: BF%, body fat percent; BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; FFM, fat‐free mass; FM, fat mass; HC,
hip circumference; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; WC,
waist circumference; WHR, waist to hip ratio.
*p ≤ .05 is considered as significant.

= −9.81, p = .136), TG (coefficient = −2.98, p = .322), LDL (coefficient = In a study that examined turmeric in the treatment of metabolic
−1.5, p = .468), HDL (coefficient = 0.8, p = .689), FBS (coefficient = syndrome, adverse effects such as nausea and dyspepsia were
9.38, p = .639), systolic blood pressure (coefficient = −0.45, p = .72), reported (Amin, Islam, Anila, & Gilani, 2015). Other undesired effects
diastolic blood pressure (coefficient = −0.45, p = .72), body free mass such as abdominal distention, flatulence, and epigastric pain were also
(coefficient = 1.07, p = .722), and FFM (coefficient = −0.22, p = .6). seen during the first week of the consumption of H. sabdariffa
Also, no significant publication bias was observed about the effect (Kuriyan et al., 2010).
of N. sativa on BMI (coefficient = 4.31, p = .462), TC (coefficient = Also, some adverse effects such as headache, nausea, gastrointes-
12.99, p = .171), LDL (coefficient = 12.99, p = .171), and systolic blood tinal irritation, plus back, leg, ankle, and joint pain were associated with
pressure (coefficient = 7.61, p = .655). the combination use of S. indicus and G. mangostana (Stern, Peerson,
In three studies, there was no publication bias among the effect of Mishra, Sadasiva Rao, & Rajeswari, 2013).
C. fimbriata on weight (coefficient = 0.39, p = .426), BMI (coefficient = The consumption of 3 and 9 mg dihydrocapsiate per day resulted
−1.69, p = .171), and HC (coefficient = 0.27, p = .605). in dry mouth cases 44% and 66% of subjects, respectively (Galgani &
The results of Egger's test confirmed that there was no publication Ravussin, 2010).
bias among the studies investigated the effect of G. cambogia (coefficient Adverse effects of headache and nausea were reported in
= −0.95, p = .814) and P. vulgaris (coefficient = −4.05, p = .867) on weight. a study that examined the effectiveness of combination of
C. sinensis, Cassia obtusifolia, and Sophora japonica (Lenon et al.,
4.10 | Adverse effects 2012).
The use of I. gabonensis was associated with headache (n = 5), sleep
Overall, there were no serious adverse effects reported by the studies difficulty (n = 6), and intestinal flatulence (n = 6) in subjects (Ngondi
conducted on herbal medicine. et al., 2009).
PAYAB ET AL. 11

In a study with Ephedra sinica consumption, adverse effects such Viechtbauer, & Westerterp‐plantenga, 2009; Onakpoya, Hung, Perry,
as palpitation, insomnia, dry mouth, and gastrointestinal symptoms Wider, & Ernst, 2011).
such as anorexia, nausea, vomiting, and constipation were observed. Some herbs and their active compounds can reduce weight
Also, with Evodia rutaecarpa, the side effects of palpitation, trem- through several mechanisms. For example, catechins in green tea
bling, dizziness, and nervousness were reported (Kim, Park, Kim, & and its derivatives can inhibit fat synthesis, increase energy expendi-
Ko, B. P., 2008). ture, and inhibit fat digestion leading to weight loss. Green tea also
Also, in another study, using G. cambogia was associated with reduces the size of the waist, body fat, blood cholesterol, and blood
adverse effects of common cold, toothache, diarrhea, and headache glucose and also increases the secretion of some hormones, such as
(Hayamizu et al., 2003). adiponectin (Moon et al., 2007; Saito, Yoneshiro, & Matsushita, 2015).
In the current study, we found that TG and LDL were significantly
reduced in subjects who received N. sativa. However, the effect of N.
5 | DISCUSSION sativa consumption on anthropometric and glycemic indices was not
significant in this meta‐analysis.
Nowadays, the use of medicinal herbs to treat obesity has attracted To the best of our knowledge, there is two other meta‐analysis
much attention. Medicinal plants have beneficial effects on the treat- studies that examined the anti‐obesity effects of N. sativa. They only
ment of patients with obesity and have demonstrated fewer side stated that most of the studies reported the beneficial effects of N.
effects than synthetic drugs. The potential mechanisms of medicinal sativa on obesity management (Mohtashami & Entezari, 2016; Namazi,
herbs for treating obesity are presented in Figure 2. A wide range of Larijani, Ayati, & Abdollahi, 2018).
preclinical and clinical studies has examined the effects of medicinal Also, the current meta‐analysis revealed that supplementation with
plants as antidiabetic, anti‐obesity, anti‐inflammatory, and antioxidant P. vulgaris can be helpful to reduce body weight. Whereas our meta‐
agents. To date, the mechanism and effect of many medicinal plants in analysis revealed a significant difference in weight loss over placebo,
the treatment of obesity and metabolic syndrome have not yet been a previous meta‐analysis of P. vulgaris showed a nonsignificant differ-
determined. Over the past decade, many advances have been made ence in weight loss between P. vulgaris and placebo groups (Udani,
in research conducted on herbs with weight‐loss properties, many of Tan, & Molina, 2018).
which have supported the effectiveness of medicinal plants in the In addition, in our meta‐analysis on controlled clinical trials showed
treatment of obesity and metabolic syndrome factors. Regarding the that consumption of I. gabonensis exerted moderate effects as a com-
fact that systematic review studies produce the highest level of evi- plementary therapy for the reduction of body weight. To the best of
dence, this study aimed to investigate the efficacy, safety and mecha- our knowledge, there is no meta‐analysis that has examined the anti‐
nisms of effective herbal medicines in the management and treatment obesity effects of I. gabonensis.
of obesity and metabolic syndrome in RCTs (Colalto, 2018; Izzo et al., Our meta‐analysis revealed that G. cambogia consumption on
2016). All plants with therapeutic effects on obesity and components weight was not significant in this study. However, other meta‐analysis
of the metabolic syndrome are summarized in Tables 3, 4, and 5 (Sup- that has examined the anti‐obesity effects of G. cambogia, reported a
plementary). The anti‐obesity effects include losses in weight, BMI, small, statistically significant difference in a weight loss of G. cambogia
waist and hip circumferences, and reduced body fat, which will be over placebo (Onakpoya, Terry, & Ernst, 2011).
discussed later. Herbs exert their anti‐obesity effects through various Weight loss could be realized through a satiety sensation mecha-
mechanisms such as appetite reduction and satiety boosting, increas- nism. The hunger and satiety feeling is regulated through the interac-
ing energy expenditure, reducing digestive absorption of fat, and tions between the nervous, endocrine, and digestive systems and the
increasing lipolysis of fat. adipose tissue (Field, Chaudhri, & Bloom, 2010; Rui, 2013). For exam-
Several clinical trials have been conducted to investigate the anti‐ ple, the ghrelin hormone is secreted through the digestive tract when
obesity properties of medicinal plants. Many herbs such as green the stomach is empty, causing a sense of hunger (Pradhan, Samson, &
tea, P. vulgaris, G. cambogia, N. sativa, puerh tea, I. gabonensis, and C. Sun, 2013; Sato et al., 2014). Leptin is another hormone affecting the
fimbriata have components to lose weight and weight control in appetite, secreted by adipocytes of adipose tissue, which induces sati-
patients with obesity. For example, the combination of E. sinica, kola ety. Leptin inhibits neuropeptide Y activity. This hormone can also
nut, and white willow bark for 3 months daily reduced body weight inhibit lipogenesis. Some studies on herbs with leptin secretion
by 1.5 kg compared with placebo (Coffey et al., 2004). decreasing properties have reported I. gabonensis, P. vulgaris, and G.
The meta‐analysis was performed on green tea, P. vulgaris, G. cambogia as having weight losing effects (Ameer, Scandiuzzi, Hasnain,
cambogia, N. sativa, I. gabonensis, and C. fimbriata. Kalbacher, & Zaidi, 2014; Mirza et al., 2011). Another herb with appe-
Our meta‐analysis revealed that green tea consumption makes a tite suppressant quality is fenugreek which is used as a flavoring in dif-
significant decrease in weight, BMI, WC, HC, FM, TC, and LDL in com- ferent countries. In one study on 18 patients with obesity, taking 8
parison with the placebo group. There were no significant improve- g/day of fenugreek increased the sensation of satiety compared with
ments in FFM, BP, FBS, HDL, and TG. Also, a meta‐analysis study on placebo (Mathern et al., 2009).
RCT studies has shown that taking green tea extract and green coffee Natural herbal compounds, such as ephedrine derived from the E.
extract significantly reduces weight compared with placebo (Hursel, sinica, also reduce appetite by activating adrenergic receptors in the
12 PAYAB ET AL.

hypothalamus. But taking this combination of compounds has severe methylglutaryl‐CoA reductase, an important enzyme in the pathway
side effects such as addiction, psychological symptoms, tachycardia, for biosynthesis of cholesterol (Law, Wald, & Rudnicka, 2003).
high blood pressure, and heart diseases (Powers, 2001) Some other herbal compounds also have the ability to lower blood
Also, dietary fibers like guar gum and pectin can induce satiety lipids by inhibiting the 3‐hydroxy‐3‐methylglutaryl‐CoA reductase
through the mechanism of gastroparesis. enzyme among which one can name puerh tea and green tea (due to
The effectiveness and mechanisms through which some herbs act EGCG; Cuccioloni et al., 2011; Zhao, Pan, Liu, & Li, 2013). Other herbs
as an anti‐obesity treatment are still controversial. Over the past that reduce cholesterol are N. sativa, H. sabdariffa, G.cambogia, I.
decade, many studies have been done on weight loss properties of gabonensis, and flaxseed.
medicinal plants. Dietary fibers such as guar gum and pectin are not broken down by
Moreover, energy expenditure could also lead to weight loss. Some digestive enzymes in humans and can reduce the amount of lipids and
herbal compounds, including capsaicin in pepper and catechins in cholesterol by binding to dietary fats (Topping, 1991). Polyphenols and
green tea, can enhance thermogenesis through brown fat tissue (Saito flavonoids (e.g., omija fruit, onion, liquoric, G. cambogia, and
et al., 2015). Other plants that can increase energy use include K. Sajabalssuk) and the fiber contained in guar gum and pectin can bind
parviflora, A. melegueta, and oolong tea. Berberine is an alkaloid com- to bile acids and inhibit enterohepatic circulation and increase fecal
pound in the Berberis plant that not only increases the expression of bile acid excretion. This mechanism reduces the level of blood choles-
uncoupling protein 1 in brown fat tissue, but also distinguishes white terol and improves lipid profiles of individuals (Racette et al., 2010.(
from brown tissue, which can contribute to the increased thermogen- Another point of interest tackled by several research is the
esis and weight loss (Zhang et al., 2014) . antihyperglycemic properties of some herbs. Chronic inflammatory
Another factor that increases energy expenditure is the 5' adeno- conditions associated with obesity, especially visceral adipose tissue,
sine monophosphate‐activated protein kinase (AMPK) enzyme. Acti- play an important role in insulin resistance and the increased blood
vating AMPK in the muscles increases cellular access to energy, glucose levels. Some herbal compounds increase insulin sensitivity
which can inhibit anabolic pathways and activate catabolic pathways and reduce blood glucose levels (Samad & Ruf, 2013).
such as fat oxidation and Adult Treatment Panel III production and Hormones like GLP‐1 and adiponectin increase insulin sensitivity.
reduce fat storage (Hardie, Ross, & Hawley, 2012). Among the plant The herbal compounds that can increase the amount of GLP‐1 secre-
compounds that can activate AMPK are resveratrol and Berberine. tion includes C. sinensis, Capsicum Annum Oleoresin, F. vesiculosus, A.
(Lee et al., 2006; Wang et al., 2015) sativa, mint essential oil, P. nigrum, which increase insulin sensitivity
Several researches have recognized fat lipolysis mechanism to be a and reduce blood glucose in a dose‐dependent manner (Canfora,
strong player in weight loss. Jocken, & Blaak, 2015; Cerf, 2013; MacDonald et al., 2002). In one
Some herbs and their active ingredients reduce weight by altering study on participants with type 2 diabetes mellitus, consuming 500
fat metabolism and increasing the oxidation of fats, as well as mg of green tea extract, three times a day, increased the level of
inhibiting the synthesis of fatty acids, such as epigallocatechin‐3‐ GLP‐1 in the blood, which enhanced insulin sensitivity in these individ-
gallate in green tea (Thielecke et al., 2010), cappinoids (Snitker et al., uals (Liu et al., 2014).
2009), and L. barbarum (Amagase & Nance, 2011). Also, various herbal Intraperitoneal injection of resveratrol into the animal model
products that contain caffeine and ephedrine could stimulate lipolysis increased the levels of GLP‐1 hormone in the blood of rats (Park
(Yun, 2010). et al., 2012). Increasing the secretion of adiponectin also enhanced
In addition, reducing fat absorption is also confirmed by several insulin sensitivity. Among herbs that could raise adiponectin secretion
research as having weight loss properties. Dietary fats contain triglyc- are green tea, I. gabonensis, sea buckthorn, S. indicus, and G.
erides, which need to be hydrolyzed to be absorbed by the intestine. mangostana.
The triglyceride hydrolysis stage is mainly carried out by the pancre- Other plants that can increase insulin secretion are chia and R.
atic lipase enzyme, which is secreted by the pancreas in the small coriaria L., fenugreek, and ginseng. However, more research is needed
intestine in response to food intake. One of the synthetic drugs that regarding the extraction of these plants (Graf, Raskin, Cefalu, &
inhibit this enzyme is Orlistat (Guerciolini, 1997). Yerba mate is a Ribnicky, 2010; Vuksan et al., 2001).
group of herbs that can inhibit the pancreatic lipase enzyme (Martins Extract of A. sativum, bitter melon and Crocus sativus in an animal
et al., 2010). model of type 2 diabetes can protect their β‐pancreatic cells. Also,
Various plant compounds, including saponins (Actiponin, Zizyphus curcumin content of turmeric, catechins in green tea, and berberine
jujube, Puerariae flos, and Tribulus), caffeine (green tea, kola nut, and can also increase the number of beta cells in animal models of type
guarana), polyphenols and flavonoids (omija fruit, onion, liquoric, G. 2 diabetes (Hosseini, Shafiee‐nick, & Ghorbani, 2015).
cambogia, and sajabalssuk) can inhibit the pancreatic lipase enzyme. Dietary fibers like guar gum and pectin can decrease glycemic
(Birari & Bhutani, 2007) index with a sense of satiety and delay in gastric emptying.
Last but not the least, lipid synthesis inhibition is another strategy To achieve the goal of covering various pathways and mechanisms,
for the treatment of obesity. Among the synthetic drugs used to it is possible to combine the herbs and their active compounds to
reduce cholesterol are statins, isolated from fungi for the first time, induce synergistic effects. Targeting multiple pathways can increase
which have the ability to inhibit the enzyme 3‐hydroxy‐3‐ the effectiveness of treatments and prevent resistance to a
PAYAB ET AL. 13

therapeutic agent. As a matter of fact, the combination of medicinal an effective option for weight and body fat loss. The effectiveness
plants for therapeutic use calls for preclinical studies, and their effi- and the relevant mechanisms through which herbal medicine work
cacy, toxicity, and complications should be investigated thoroughly in as an anti‐obesity treatment are still controversial. The results of this
various phases. To give an instance, consuming a combination of tyro- systematic review demonstrate the effectiveness of herbal medicine
sine, green tea, and caffeine increases energy expenditure. As well, for the treatment of obesity and metabolic syndrome. According to
using up a combination of walnut and flaxseed reduces energy intake. the results of the present study on controlled clinical trials, green
Also, a combined intake of EGCG and resveratrol could increase tea, P. vulgaris, G. cambogia, N. sativa, puerh tea, I. gabonensis, and C.
energy expenditure in overweight people (Most, Goossens, Jocken, fimbriata were found to induce an acceptable anti‐obesity effect and
& Blaak, 2014). metabolic syndrome. However, there is still a need to determine a
There are many medicinal herbs that are used for long periods of good anti‐obesity drug candidate with more effect and less adverse
time, which entail adverse side effects. For example, skin rash was effect. The results of this study indicate the specific doses of each
reported in individuals consuming a herbal combination called xin‐ju‐ medicinal herbs that could be effective. In addition, these data can
xiao‐gao‐fang (rhubarb, coptis, semen cassia, and citrus aurantium; be beneficial for the pharmaceutical industry and policy makers to
Zhou et al., 2014). Cautious should be made on the dose and duration study the natural products and extracts of these plants in order to find
of in taking medicinal plants. Most of the clinical studies in this field a mixture with higher efficacy. In the future, it is recommended to
have usually been short in terms of duration, and the majority lack standardize herbal medicine intervention on obesity and metabolic
standardized design and implantation. An increasing demand is arising syndrome. On the same basis, a plethora of research and well‐
for studies investigating the efficacy and consistency of the use of designed clinical trials are needed to address these issues and to
herbs and their extracts in the treatment of obesity. So far, several assess the adverse effects associated with herbal medicines and their
unintended serious complications have been reported in literature. mechanism of action.
An example is the herb E. sinica that has shown digestive, psycholog-
ical, and cardiovascular side effects (Shekelle et al., 2003). The use of ACKNOWLEDGEMENTS
Garcinia extract is also associated with digestive complications This article was a part of a larger project, which was granted by the
(Onakpoya, Terry, & Ernst, 2011). National Institute for Medical Research Development (NIMAD, Grant
957973).

6 | STRENGTHS AND LIMITATION

AUTHOR CONT R IBUT IONS
One of the strong points of the current systematic review was that it MP participated in the study design, drafting the manuscript and had
summarized the effects of herbal medicine on different obesity indices significant role in development of the selection criteria, risk of bias
and metabolic syndrome components and inflammatory factors. RCTs assessment strategy, and data extraction criteria. SHR participated in
are assumed as the most appropriate study designs to demonstrate the study design and interpretation. NSH contributed to the develop-
casual effects, and their summarized findings could be used as useful ment of the selection criteria, the risk of bias assessment strategy, and
data. In addition, the present study was comprehensive systematic lit- data extraction criteria. MQ participated in the statistical analysis. AA
erature search, which was carried out aiming to find all relevant contributed to the development of the selection criteria, the risk of
articles. bias assessment strategy, and data extraction criteria. HH participated
This study has some limitations. First, the present systematic review in the statistical analysis. AS participated in the study design and inter-
did not include unpublished resources such as books and dissertations. pretation. FKH developed the search strategy. SHN participated in
Second, high heterogeneity was seen across studies, including differ- critical review. MA participated in the study design and interpretation.
ences in types of herbs (e.g., only herbs vs. herbs plus other composi- BL participated in critical review. All authors read, provided feedback,
tions), and participants' characteristics (e.g., gender, geographic region, and approved the final manuscript.
genetic background, and dietary habits), different definitions of out-
comes (obesity and metabolic syndrome based on different criteria). CON F L I C T S OF IN TE RE S T
Third, only English articles were included in our search.
The authors declare no conflicts of interest.

7 | CONCLUSION AND IMPLICATIONS FOR ORCID

F U T U R E R E S E A RC H Moloud Payab https://orcid.org/0000-0002-9311-8395

Mohammad Abdollahi https://orcid.org/0000-0003-0123-1209
So far, different approaches have been followed to reduce weight and
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double‐blinded, multicenter, prospective trial. The American Journal of

Chinese Medicine, 42, 1345–1356. https://doi.org/10.1142/ How to cite this article: Payab M, Hasani‐Ranjbar S, Shahbal
S0192415X14500840
N, et al. Effect of the herbal medicines in obesity and metabolic
syndrome: A systematic review and meta‐analysis of clinical
SUPPORTING INFORMATION
trials. Phytotherapy Research. 2019;1–20. https://doi.org/
Additional supporting information may be found online in the 10.1002/ptr.6547
Supporting Information section at the end of the article.