Turkish Journal of Medical Sciences Turk J Med Sci

(2020) 50: 354-359

http://journals.tubitak.gov.tr/medical/
© TÜBİTAK
Research Article doi:10.3906/sag-1907-82

Efficacy of Hijamat (wet cupping therapy) in Iranian patients with nonalcoholic fatty
liver disease: a controlled clinical trial
1,2 1, 3
Homayoon BASHIRI , Arezoo BOZORGOMID *, Vahid SHOJAEIMOTLAGH 
1
Infectious Diseases Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
2
Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
3
Department of Medical Surgical Nursing, Khoy University of Medical Sciences, Khoy, Iran

Received: 11.07.2019 Accepted/Published Online: 24.01.2020 Final Version: 09.04.2020

Background/aim: Nonalcoholic fatty liver disease (NAFLD) is known to be the most prevalent chronic liver disease all over the world.
The incidence of this disease has dramatically increased during the last decade. Studies have shown a strong relationship between the
level of ferritin and the severity of NAFLD. The objective of the present study was to assess the effect of adding Hijamat, as an iron
reducing procedure, to standard lifestyle modification on the improvement of insulin resistance and liver enzymes in patients with
NAFLD.
Materials and methods: One hundred and twenty NAFLD patients participated in a randomized, controlled, single-blind trial design of
study. The control group received counselling for nutrition and physical activity for a period of 6 months. The treatment group received
the above items plus Hijamat for 3 times during 1 month. Ultrasound images of liver, HOMA-IR, and laboratory data including ALT,
AST were assessed pre- and postintervention.
Results: At the end of the study, a significant decrease was demonstrated in the serum level of HOMA-IR (–1.30 ± 0.88 vs –.02 ± 0.47,
P < 0.001) and serum levels of ALT (–6.50 ± 4.92 vs –2.38 ± 3.92, P < 0.001) and AST (–2.78 ± 4.29 vs –1.30 ± 2.33, P = 0.021) in the
Hijamat group were compared to the control group. Ultrasound images of the liver improved in 23.3% of the patients in the Hijamat
group, while the rate of improvement in the control group was 10% (P = 0.050). Hijamat therapy was safe and tolerable in this trial.
Conclusions: Hijamat resulted in a relative improvement in fatty liver severity and improved HOMA-IR and liver enzymes more than
lifestyle modification alone in patients with NAFLD.

Key words: Nonalcoholic fatty liver disease, wet cupping, Hijamat, ALT, AST

1. Introduction the liver, eventually leading to NAFLD [4]. According to

Nonalcoholic fatty liver disease (NAFLD) represents various studies, high levels of serum ferritin, as a standard
a spectrum of diseases ranging from steatosis to marker of iron storage are associated with an increase in
steatohepatitis, fibrosis, cirrhosis and even hepatocellular free radicals and induce insulin resistance in myocytes,
carcinoma which is characterized by lipid accumulation adipose tissue [5].
within hepatocytes [1]. The incidence of NAFLD has Wet cupping therapy or Hijamat is one of the oldest
been increasing during the last 3 decades, reaching medical techniques in Asia, the Middle East and Europe. It is
6%–35% in the adult population worldwide [2]. One widely referred to Iranian traditional medicine documents
of the most important reasons for this high prevalence for prevention and treatment of various disorders [6].
is the globalization of sedentary lifestyle and modern In this procedure, causative pathological substances are
dietary habits together with increased prevalence of excreted from the interstitial fluid and blood in the skin
central (abdominal) obesity, type 2 diabetes mellitus, capillary network after sucking and scarification steps
dyslipidaemia and metabolic syndrome [3]. [7]. A few studies have suggested that removal of iron by
Although the molecular mechanisms involved in phlebotomy leads to improved insulin resistance and liver
the pathogenesis of NAFLD are still poorly understood, enzymes in NAFLD patients with normal serum ferritin
insulin resistance contributes to increased delivery of free and transferrin levels [8,9]. Unlike Hijamat, one of the
fatty acids to the liver and overproduction of lipids in superficial veins of the body is cut with a scalpel and some
* Correspondence: Arezoobozorgomid@yahoo.com
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This work is licensed under a Creative Commons Attribution 4.0 International License.
 BASHIRI et al. / Turk J Med Sci

blood is removed from the body in phlebotomy [10]. Most least 20 min, 3 times per week) as a routine treatment.
people usually prefer Hijamat to phlebotomy because it After 4 months, the treatment group received Hijamat
is easier and causes less pain. In light of the cumulative for 3 times during 1 month (0 days, 14 days, and 28 days)
evidence for the association between serum ferritin and [11]. Hijamat was performed using sterile disposable cups
NAFLD, this study was conducted to evaluate the role of at 5 points: both scapulas, both lumbar regions and vertex.
Hijamat therapy in the improvement of liver enzymes and Disposable cups were placed on these points and negative
HOMA-IR in patients with NAFLD. pressure was applied by a cupping pump. The cups were
removed after about 2–3 min. Then, 26-gauge disposable
2. Materials and methods lancets were used for scarification to a depth of 2 mm at
2.1. Study design sites of cups. Vacuum pumping was repeated for the second
The study was a randomized, single-blind (observer-blind) time and 3–5 cm3 of a bloody excretion was removed per
trial and the duration of the study was 6 months. The study cupping site. The sites were then covered with sterile pads.
design is depicted in Figure. The patients were randomly 2.2. Study participants
divided to the treatment and control groups using the Subjects were selected from those adults aged 18 years
stratified blocked randomization method with a computer. or above consecutively referred to the Gastroenterology
All NAFLD cases initially received counselling to reduce and Hepatology Clinic of the Imam Reza Therapeutic
the intake of carbohydrate, red meat, fried foods, sugars, Educational Hospital (Kermanshah, Iran) with a
and fat and increase fibre intake and physical exercise (at diagnosis of NAFLD. This hospital is the largest centre

Assessment of eligibillity (n= 131)

Excluded (n=11)
Not meeting inclusion criteria(n=9)
Declined to participate (n=2)

Randomized (n=120)

Allocated to control (n=60)

Allcocated to intervention (n=60)
lifestyle modification
lifestyle modification and Hijamat

Assessment at 1th month Assessment at 1th month

Assessment at 6th month Assessment at 6th month

Lost to follow- up Lost to follow- up
(give to reasons) (n=0) (give to reasons) (n=0)

Analyzed (n=60) Analyzed (60)

Figure. Flow chart of the allocation, follow-up, and analysis of this clinical trial.

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among referral centres in Kermanshah Province, west of used for within-group comparisons. Categorical variables
Iran. A diagnosis of NAFLD was made according to the were compared using chi-square test. The P < 0.05 was
clinical evidence, liver enzymes and ultrasonography considered as statistically significant.
criteria. All subjects provided informed written consent
for the study. The patients with viral hepatitis B and/or 3. Results
C infection, jaundice, autoimmune hepatitis, Wilson’s As shown in Figure, 11 of 131 assessed patients with
disease, α-1-antitrypsin deficiency, type 1 or secondary NAFLD were excluded from the study for various reasons.
forms of diabetes, celiac disease, alcohol consumption, A total of 120 patients (61 males, 59 females) with mean
corticosteroids consumption and kidney disorders as well age of 39.46 ± 8.38 were assessed in this study. The patients
as pregnant or lactating women were excluded from the were randomly divided into 2 groups, including 60 patients
study. Demographic data such as age, sex and medical in the treatment group and 60 subjects in the control
history were gathered from patient interviews during group. The mean age of the subjects in the treatment and
screening. control group was 38.38 and 40.53 years, respectively (P =
2.3. Sample size 0.161). There were 30 female participants in the treatment
There were no similar studies to help us with the study and 29 in the control group. (P = 0.855). There were no
sample size. It has been recommended that around 60 statistical differences between groups for other baseline
patients are a reasonable sample size for a pilot study to characteristics (P > 0.05), so the groups were comparable.
investigate the treatment effects [12]. Thus, we decided to The patients’ characteristics are described in Table 1.
recruit at least 60 patients in each group as a convenience A paired t‑test showed that after 6 months of Hijamat,
sample. mean ALT, AST and HOMA-IR decreased significantly
from baseline (P < 0.001). In the control group, all
2.4. Biochemical assessment
variables after study were significantly decreased compare
Blood samples were collected from participants after a
to the baseline except for HOMA-IR (P = 0.724) (Table 2).
12-h overnight fast before and after the intervention. After
According to the data shown in Table 3, significant
serum separation, the samples were labelled and stored
improvements were observed in HOMA-IR and serum
at –70 °C until analysis. Enzymatic activities of alanine
levels of ALT and AST in the treatment group compared
aminotransferase (ALT) and aspartate aminotransferase
to the control group after the intervention (P < 0.05).
(AST) were measured with the Hitachi 902 autoanalyzer
Hijamat was safe and tolerable in this trial and there
(Japan) using Pars Azmoon (Iran) analytical kits.
were no reports of any side effects. The ultrasonographic
Laboratory reference ranges for ALT and AST were 5-41
findings of the liver improved significantly in the case
IU/L and 5-37 IU/L, respectively. Insulin resistance was
group compared to the control group (P < 0.001). The
determined using the homeostasis model assessment
fatty liver grade improved in 23.3% of the subjects in the
(HOMA-IR) by the following formula: fasting insulin (µu/
Hijamat group, while the rate of improvement was 10% in
mL) × fasting glucose (mmoL/dL)/405.
the control group (Table 4).
2.5. Ultrasound imaging of the liver
Ultrasound images of each participant were also evaluated 4. Discussion
before and after the intervention. Hepatic steatosis was This study was conducted to investigate whether or not
graded as 0 (no fat accumulation), 1 (minimal increase Hijamat therapy is effective in the improvement of liver
in echogenicity along with normal appearance of the enzymes and histology in patients with NAFLD. To the
diaphragm and portal vein wall), 2 (moderate increase in best of our knowledge, this study is the first published
echogenicity along with slightly impaired visualization of clinical trial of the effect of a combination of Hijamat and
the portal vein wall and diaphragm), and 3 (severe increase lifestyle modification on liver enzymes and HOMA-IR
in echogenicity along with poor or no visualization of the in patients with NAFLD. Therefore, considering the low
diaphragm, portal vein wall and the posterior portion of number of research articles, we are only able to discuss
the right hepatic lobe) [13]. the hypothetical mechanisms of Hijamat that may provide
2.6. Statistical analysis clues to the research question.
The SPSS software was used for statistical analysis version 16 The results showed a significant improvement in
(SPSS Inc., Chicago, IL, USA). The Kolmogorov–Smirnov the serum levels of ALT and AST in the Hijamat group
test was applied to evaluate the normal distribution of the versus controls. Evidence suggests an association between
data in each group. Continuous variables are presented as increased serum ferritin and ALT levels [14]. Increased
mean ± standard deviation (SD). Independent-samples ferritin and body iron stores can lead to advanced fibrosis
t-test or Mann–Whitney U test was used for between- in patients with NAFLD [15]. Studies have shown that
group comparisons as appropriate and paired t-test was iron chelation therapy and Hijamat could be beneficial

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Table 1. Baseline characteristics and biochemical parameters of control and Hijamat groups.

Variables Control group (n = 60) Hijamat group (n = 60) P-value

Age, years 40.53 ± 7.32 38.38 ± 9.26 0.161a
Gender, female (%) 29 (48.33) 30 (50) 0.855b
ALT, IU/L 46.30 ± 4.26 45.88 ± 4.39 0.883c
AST, IU/L 45.46 ± 5.25 44.33 ± 4.79 0.220a
HOMA-IR 2.23 ± 0.62 3.19 ± 0.65 0.630c
Sonography (%)
Grade I 26 (43.3) 31 (51.7) 0.364b
Grade II 34 (56.7) 28 (46.7)
Grade III - 1 (1.7)

Values are expressed as mean ± SD

a
Independent sample t-test
b
Chi-square test
c
Mann–Whitney U test

Table 2. Comparison between baseline laboratory parameters and after 6 months of intervention.

Variables Control group Hijamat group

Baseline After 6 months P-value Baseline After 6 months P-value

ALT, IU/L 46.30 ± 4.26 43.91 ± 3.70 <0.001 45.88 ± 4.39 39.38 ± 4.22 <0.001
AST, IU/L 45.46 ± 5.25 44.17 ± 5.74 <0.001 44.33 ± 4.79 41.55 ± 4.43 <0.001
HOMA-IR 2.23 ± 0.62 2.21 ± 0.71 0.724 3.19 ± 0.65 1.89 ± 0.52 <0.001

Data are Mean ±SD.

P values calculated by paired sample t-test

Table 3. Comparison of mean changes in studied variables of 120 patients with

nonalcoholic fatty liver disease.

Variables Control group Hijamat group P-value

Change in ALT, IU/L –2.38 ± 3.92 –6.50 ± 4.92 <0.001
Change in AST, IU/L –1.30 ± 2.33 –2.78 ± 4.29 0.021
Change in HOMA-IR –.02 ± 0.47 –1.30 ± 0.88 <0.001

Data are mean ± SD.

P-values calculated by independent sample t-test.

in patients with mild iron overload. El-Shanshory et al. one possible mechanism for therapeutic effects of Hijamat
(2014) selected 40 thalassaemic children and divided them is the excretion of excess iron in the interstitial fluid [16].
into 2 groups: 20 subjects received iron chelation therapy Furthermore, a significantly larger improvement was
(ICT) plus Hijamat and 20 patients received iron chelation observed in the HOMA-R index in the case group versus
therapy as the control group. The authors concluded the control group. Hijamat can decrease oxidative stress
that Hijamat could significantly decrease iron overload, through decreasing the iron stores, resulting in improved
potentiate ICT and decrease oxidative stress. Therefore, insulin resistance that may lead to decreased production

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Table 4. Evaluation of fatty infiltration in liver tissue after the intervention between studied
groups.

Fatty infiltration Control group Hijamat group P-value

Frequency Percent Frequency Percent

Improved 6 10 14 23.3 0.050
Not recovered 54 90 46 76.7

P-values calculated by chi‑square test.

of liver glucose, which is one of the mechanisms for years of age and in very slim and weak or extremely obese
developing steatosis in NAFLD. Moreover, oxidative individuals [23].
stress, as a cause of NAFLD, is associated with production Although Hijamat was more effective on liver
of reactive oxygen species [17], either via peroxisomal enzymes; the benefits of lifestyle modifications are well
and mitochondrial β-oxidation of hepatic fatty acids demonstrated. Several studies have shown that permanent
or via inflammatory cell activation. This occurrence lifestyle changes induce weight loss and improve liver
leads to increased lipidperoxidation and the release of enzymes and histological outcomes in NAFLD [24,25].
proinflammatory cytokines, resulting in the impairment Several points should be considered as the strengths
of cell membrane integrity [17]. of this study such as its novelty in introducing a safe and
Several studies have evaluated the effect of Hijamat affordable therapy for improvement of liver enzymes and
on different biochemical markers and found that it was histology in patients with NAFLD. However, the study
an effective alternative therapy. For example, it has been also had several limitations like not assessing many fatty
suggested that Hijamat can effectively reduce the levels of liver biochemical markers such as oxidative stress, serum
cholesterol and LDL and prevent cardiovascular disease lipid profile and serum and liver iron levels, a short follow-
[18]. It is also worth mentioning that there is a significant up period, and lack of daily assessment of calorie intake
positive correlation between increased levels of cholesterol by patients. Also due to the nature of Hijamat, it is not
and LDL and increasing grades of fatty liver [19]. Mahaling possible to blind participants to performed intervention.
et al. found that individuals with fatty liver had increased Taken together, the results of this study implied that
levels of cholesterol, LDL, and very LDL (VLDL) and Hijamat was a safe and economic, and the complementary
decreased levels of HDL [20]. use of Hijamat plus lifestyle modification could be more
Khodadoostan et al. evaluated the effect of phlebotomy effective in reducing HOMA-IR and ALT and AST levels
on liver enzymes and histology in patients with NAFLD. and improve the fatty liver grade.
The authors concluded that phlebotomy decreased liver
cell damage and improved liver enzymes and histology [9]. Acknowledgement/Disclaimers/Conflict of interest
Another study conducted in Italy evaluated patients with The authors want to thank their colleagues in Imam Reza
nonalcoholic fatty liver disease and hyperferritinemia. The Therapeutic Educational hospital of Kermanshah, Iran
result showed a significant reduction in insulin resistance for their contribution to the patient’s diagnosis. We also
following phlebotomy in the treatment group as compared extend our thanks to clinical research development center
to the control group [21]. Nevertheless, Hijamat may be of Imam Reza Hospital for their kind advise. This study
superior to other excretory procedures such as phlebotomy. was supported by a grant from the Vice Chancellery for
Unlike phlebotomy, Hijamat rarely causes anaemia, Research and Technology, Kermanshah University of
as blood cells are not filtered through capillary pores. Medical Sciences (grant number: 89065). The authors
Moreover, it filters and clears interstitial fluids from excess declare that they have no conflict of interest.
fluids and/or soluble causative pathological substances
that were reported to be rich in iron [10]. Hijamat therapy Informed consent
is a very safe procedure when performed by trained health All the participants gave written informed consent prior to
staff. However, few studies have reported some side effects the study and this study was conducted in accordance with
for cupping therapy, such as persistent skin discoloration, the Declaration of Helsinki. The protocol was approved
bruising, scars, burns and infections [22]. Nevertheless, by the Ethics Committee of Kermanshah University of
Hijamat is contraindicated in subjects under 2 and over 60 Medical Sciences (IRCT138905154520N1).

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