THE EFFECT OF GINGER (Zingiber officianale) EXTRACT OF PESANGGRAHAN
VILLAGE OF BATU CITY TO THE LEVEL OF VOMITTING, BLOOD NATRIUM
LEVELS, AND URINE KETON IN HYPEREMESIS GRAVIDARUM PATIENTS
I Wayan Agung Indrawan, Sutrisno, Edza Akelei Ryantifa
Department of Obstetric and Gynecology, Faculty of Medicine, Brawijaya University, Malang, Indonesia/RSUD
dr. Saiful Anwar Malang
ABSTRAK
Latar belakang: Hiperemesis gravidarum adalah kondisi
mual dan muntah yang berat pada wanita hamil dan
dapat mengakibatkan dehidrasi dan ketonuria. Hal
tersebut berpotensi mengancam nyawa yang dapat
terjadi sampai 1,5% kehamilan. Jahe merupakan tanaman
obat yang aman dikonsumsi untuk mengurangi mual dan
muntah dalam kehamilan dengan senyawa terbanyak
yaitu zingiberene sekitar 35-53%.
Metode: Penelitian ini merupakan penelitian
eksperimental untuk mengetahui efek pemberian ekstrak
jahe pada pasien hiperemesis gravidarum terhadap
tingkat keparahan muntah, kadar elektrolit serum dan
ketosis pada pasien tersebut. Terdapat 3 kelompok
perlakuan dan 1 kelompok kontrol dimana kelompok
perlakuan pertama adalah kelompok pasien hiperemesis
gravidarum yang diberikan ekstrak jahe 250 mg dan
Metoklorpramid 10 mg, kelompok perlakuan kedua
adalah kelompok pasien hiperemesis gravidarum yang
diberikan ekstrak jahe 500 mg dan Metoklorpramid 10
mg, sedangkan kelompok perlakuan ketiga adalah
kelompok pasien hiperemesis gravidarum yang diberikan
ekstrak jahe 1000 mg dan Metoklorpramid 10 mg.
Kelompok kontrol adalah kelompok pasien hiperemesis
gravidarum yang diberikan Metoklorpramid 10 mg saja.
Terapi diberikan adalah selama 3 hari, selanjutnya
dilakukan pengecekan terhadap frekuensi dan tingkat
keparahan mual, hasil pemeriksaan elektrolit serum dan
adanya ketosis pada pasien tersebut melalui
pemeriksaan keton urin.
Hasil: Tidak ada perbedaan yang bermakna rerata Na(+)
sebelum dan setelah perlakuan pada kelompok
pemberian metoklorpramid 10 mg (132.08±3.03 vs
132.50±3.00; p=0.054), ekstrak jahe 250 mg dan
metoklorpramid 10 mg (130.42±2.39 vs 130.67±2.19;
p=0.191), dan ekstrak jahe 500 mg dan metoklorpramid
10 mg (130.75±2.26 vs 131.50±2.20; p=0.491). Terdapat
perbedaan bermakna keton urin sebelum dan setelah
perlakuan pada seluruh kelompok perlakuan (p<0,05).
Pemberian ekstrak jahe 1000 mg dan metoklorpramid 10
mg mampu menurunkan 100% tingkat keparahan
muntah (p=0.000).
Kesimpulan: Ekstrak jahe dengan dosis 1000 mg efektif
menstabilkan profil serum elektrolit (p=0.000),
menurunkan keton urin (p=0.002), dan menurunkan
tingkat keparahan muntah (p=0.000)
Kata kunci: ekstak jahe, rerata Na(+), keton urin, tingkat
keparahan munta
ABSTRACT
Background: Hyperemesis gravidarum is a condition of
severe nausea and vomiting in pregnant women and can
result in dehydration and ketonuria. It is potentially life
threatening that can occur up to 1.5% of pregnancies.
Ginger is a medicinal plant that is safe to consume to
reduce nausea and vomiting in pregnancy with the most
compounds, zingiberene is around 35-53%.
Method: This study was an experimental study to
determine the effect of ginger extract on hyperemesis
gravidarum patients on the severity of vomiting, serum
electrolyte levels and ketosis in these patients. There
were 3 treatment groups and 1 control group. The first
treatment group was the hyperemesis gravidarum group
given 250 mg ginger extract and Metochlorpramid 10 mg,
the second treatment group was the hyperemesis
gravidarum group given 500 mg ginger extract and
Metoclorpramid 10 mg, while the third treatment group
was the hyperemesis gravidarum group given 1000 mg
ginger extract and Metochlorpramid 10 mg. The control
group was a group of hyperemesis gravidarum patients
who was given Metochlorpramid only 10 mg. Therapy is
given for 3 days, then those patients were checked the
frequency and severity of nausea, the results of serum
electrolyte examination and the presence of ketosis in
these patients through urine ketone examination.
Result: There was no difference in mean of Na(+) before
and after treatment in the group given Metochlorpramid
10 mg (132.08 ± 3.03 vs. 132.50 ± 3.00; p = 0.054), 250
mg ginger extract and Metochlorpramid 10 mg (130.42 ±
2.39 vs. 130.67 ± 2.19; p = 0.191), and 500 mg ginger
extract and Metochlorpramid 10 mg (130.75 ± 2.26 vs
131.50 ± 2.20; p = 0.491). There was a significant
difference in mean of Na(+) before and after treatment in
the group given 1000 mg ginger extract and
Metochlorpramid 10 mg (121.83 ± 4.28 vs 131.50 ± 2.20;
p = 0.000). There were significant differences in urine
ketones before and after treatment in all treatment
groups (p <0.05). Giving 1000 mg ginger extract and
Metochlorpramid 10 mg can reduce 100% vomiting
severity (p = 0.000).
Conclution: Ginger extract with a dose of 1000 mg
effectively stabilized the serum electrolyte profile (p =
0.000), decreased urine ketone (p = 0.002), and reduced
the severity of vomiting (p = 0.000).
Key word: ginger extract, mean of Na(+), urine ketone,
severity of vomiting
 INTRODUCTION
Nausea and vomiting are common
experiences in pregnancy, affecting 70–80% of
all pregnant women. Women with severe
nausea and vomiting during pregnancy may
have hyperemesis gravidarum (HG), an entity
distinct term from nausea and vomiting of
pregnancy (NVP), which if left untreated may
lead to significant risk and fetal morbidity
(Noel dan Sumona, 2011). Nausea and
vomiting occur in up to 80% of normal
pregnancies. Hyperemesis gravidarum,
resulting in dehydration and ketonuria, is a
more severe, disabling and potentially life-
threatening condition affecting up to 1.5% of
pregnancies. Treatment is supportive with
intravenous rehydration, antiemetics and
correction of vitamin deficiency to minimize
complications. There are good safety data to
support the use of antihistamines,
phenothiazines and metoclopramide in
hyperemesis gravidarum. On the other hand, the
use of complementary medicine such as ginger,
can relieve NPV symptoms and have been
introduced by current researchers. Prevention
of complications of hyperemesis gravidarum is
recommended, due to its serious complications,
including Wernicke encephalopathy, osmotic
demyelination syndrome and
thromboembolism (Bottomley dan Bourne,
2009).
Hyperemesis gravidarum is severe
nausea and vomiting during pregnancy that
causes fluid and electrolytes (especially Na+)
imbalances, nutritional deficiencies and weight
loss. Hyperemesis gravidarum is the most
common reason of early pregnancy hospital
admission and second common reason after
preterm labor of all pregnancies. Despite
popular use of the term “morning sickness”
NVP persists throughout the day in the majority
of affected women and has been found to be
limited to the morning in less than 2% of
women. It often begins within weeks of missing
menses and thus is caricatured across most
cultures as the initial sign of pregnancy.
Ginger is a powerful herbal medicine
which acts pharmacologically and thus has
specific indications, contraindications,
precautions and side-effects, the most notable
of which is an anticoagulant action. Midwives
and other professionals advising women in
early pregnancy about strategies for coping
with NVP should be aware of the risks and
benefits of ginger in order to provide
comprehensive and safe information to
expectant mothers. (Tiran, 2011). However,
ginger as a therapeutic agent should not be
thought of as a nutritional aid either; Ginger is
a powerful herb that deserves recognition from
other active pharmacological ingredients
(Tiran, 2011). Among all medicinal plants
cultivated in Batu, ginger is the most widely
planted plant, which is around 9,390 plants per
quarter in 2011 (Aditiyas et al., 2014).
Moreover, good ginger growth conditions,
location, and soil contour in Batu is highly
supporting a good ginger quality growth, it is
expected that ginger extract (zingiberene) from
Batu city possess an effect on vomiting in
hyperemesis gravidarum.
METHOD
We employed an experimental study
with post test only control group design from
November 2018 to January 2019. Study
population was all pregnant woman with
hyperemesis gravidarum at RSSA Malang,
RSUD dr. Iskak Tulungagung, RSUD
Gambiran Kediri, RSUD Ngudi Waluya
Wlingi, RSI Aisyiyah Pandaan, and RSI
Masyithoh Bangil. We enroll twelve women for
each study groups.
Inclusion and Exclusion Criteria
Inclusion criteria
Pregnant woman with nausea and
vomitus from early pregnancy up to 16 weeks
with dehydration, electrolyte imbalance (low
blood sodium), and ketosis.
Exclusion criteria
Pregnant woman with nausea and
vomitus with gestational age > 16 weeks
without dehydration, electrolyte imbalance
(low blood sodium), and ketosis
Ginger extract treatment
The ginger extract capsule was given in
three different dosage: 250 mg, 500 mg, and
1000 mg. Ginger extract treatment was co-
administered with anti-emetic drug,
metoclopramide 10 mg which was definitive
treatment for hyperemesis gravidarum. Both
treatments were given three times a day at
breakfast (7-9 am), lunch (11 am-1 pm) and
dinner (7-9 pm) for three days.
 Blood sodium and urinary ketones Table 2 found no statistical differences of
Serum electrolyte levels (sodium, urine ketone level between pre and post
potassium, and chloride) examination was treatment of metoclopramide 10 mg + ginger
carried out with an electrolyte analyzer using extract 250 mg (p=0.014). Similar results were
the Ion Selective Electrode (ISE) method. Urine also found in metoclopramide 10 mg+ginger
ketone examination was carried out using urine extract 1000 mg (p=0.002<α). Therefore,
analyzer with similar principle with electrolyte metoclopramide 10 mg + ginger extract 1000
analyzer. mg could decrease urine ketones of pregnant
women with hyperemesis gravidarum.
Data Analysis This result showed that ginger extract
Data were analyzed statistically using with dosage of 250 mg, 500 mg, and 1000 mg
SPSS 23 software program. Shapiro-Wilk test could affect urine ketones of pregnant women
was used to assess data distribution according with hyperemesis gravidarum.
to p-value and significance level of α = 0.05.
Data comparison before and after treatment DISCUSSION
were carried out to determine ginger extract
treatment effect. Comparison of multiple Vomiting reflexes protect the body
groups was done using One Way Anova test. against ingested toxins from food that is not
detected by the vision, smell, or taste. Irritation
Before or distension of the gastrointestinal tract may
After p-
Groups Mean ± SD
Mean ± SD value
also induce nausea and vomiting; distension of
the duodenum, specifically, a strong stimulus.
Metc 10 mg 132.08±3.03 132.50±3.00 0.054 The most implicated factor is human chorionic
Metc 10mg+ginger 130.42±2.39 130.67±2.19 0.191 gonadotropin (hCG). This link between hCG
ext 250mg and NVP is based largely on the temporal
Metc 10mg+ginger 130.75±2.26 131.50±2.20 0.491 relationship between the peak of NVP and the
ext 500mg peak of hCG production, both of which occur
Metc10mg+ginger 121.83±4.28 131.50±2.20 0.000 between 12- and 14-weeks gestation. In
ext 1000mg addition, nausea and vomiting are often worse
in pregnant women with conditions associated
with elevated hCG levels such as molar
Table 1 found no statistical differences of pregnancies, multiple gestations, and Down’s
blood sodium level between pre (132.08±3.03) syndrome (Lee dan Saha, 2009; Davis, 2004).
and post (132.50±3.00) treatment of Higher urinary hCG and serum hCG levels have
metoclopramide 10 mg (p=0.054>α), also been found in women with NVP compared
metoclopramide 10 mg + ginger extract 250 mg to those who are asymptomatic (Lee dan Saha,
(p=0.191> α), metoclopramide 10 mg + ginger 2009).
extract 500 mg (p=0.491> α). This result In relation to its antiemetic properties,
showed that ginger extract with dosage of 250 ginger (and its constituents) acts peripherally,
and 500 mg were unable to affect blood sodium within the gastrointestinal tract, by increasing
level pregnant women with hyperemesis the gastric tone and motility due to anti-
gravidarum. However, there was a significant cholinenergic and anti-serotonergic actions. It
difference between metoclopramide 10 mg + is also reported to increase gastric emptying.
ginger extract 1000 mg (p=0.000< α). This combination of functions explains the
widely accepted ability of ginger to relieve
Groups
Negative Positive
Ties
p- symptoms of functional gastrointestinal
Ranks Ranks value disorders, such as dyspepsia, abdominal pain,
Metc 10 mg 10 0 2 0.02
and nausea, which is often associated with
Metc 10mg+ginger 6 0 6 0.014
decreased gastric motility. (Lete dan Allué,
ext 250mg
2016; Hu et al., 2011).
Metc 10mg+ginger 11 0 1 0.003
Calcium is necessary for blood clotting
ext 500mg
and involved in blood acid-alkaline reaction
Metc10mg+ginger 12 0 0 0.002
control. Ginger is not a good source of calcium
ext 1000mg
and potassium. This plant species is a rich
source of minerals that play an important role in
many physiological processes in the human
body. This plant species is a rich source of
minerals that play an important role in many
physiological processes in the human body. The
calcium content of ginger roots varied from
0.163 to 0.297 g kg-1 FM depending on the type
of organic substrate. In other studies, calcium
concentrations in ginger varied widely. Shirin,
Jamuna (2010) demonstrated that the average
Ca content of ginger rhizomes was 0.104 g kg-
1 FM, Tanweer et al. (2014) and Latona et al.
(2012) reported Ca content of 0.280 g kg-1 FM,
whereas in a study by Gupta, Sharma (2014) Ca
content reached 0.104 g kg-1 FM (Srinivasan,
2017).
The mineral elemental composition of
ginger root samples indicated that ginger is rich
in essential minerals like: calcium 280.0
mg/100g, Iron 279.7 mg/100g, Zinc 64.0
mg/100g, Manganese 5.90 mg/100g and
Copper 8.80 mg/100g. The essential minerals
like calcium and phosphorus are important in
extra- cellular and intra-cellular body functions
and as components responsible for the building
block of structural component in human body
(Yu et al., 2011). Minerals like Iron, even if
present in threshold level can act as anti-oxidant
and are involved in strengthening the immune
system. Whereas Zinc are known to prevent
cardiomyopathy, muscle degeneration, growth
retardation and bleeding disorder. Therefore,
the presence of these minerals in ginger root
provides bases for their use in food application.
Referring to the USDA National Nutrient
Database for standard reference and DTU
Fødevaredatabanken, raw ginger roots is a
source of potassium (415 mg/100 g). When
referring to ANSES Table Ciqual 2017, data are
very different: ginger powder is a source of
phosphorus (168 mg/100 g) and is rich
magnesium (214 mg/100 g), potassium (1320
mg/100 g), manganese (33,3 mg/100 g), zinc
(3,64 mg/100 g), iron (19,8 mg/100 g), and
niacin (9,62 mg/100 g). these differences
between nutrient database showed high
quantitative variations that could be explained
by the plant variability itself but also used
analytical method which can differ from
database to another.
Nausea and vomiting are common in
pregnancy, occurring in 70–85% of all gravid
women. Hyperemesis gravidarum is a
complication of pregnancy characterized by
extreme nausea, vomiting, and dehydration in
the first trimester. Hyperemesis gravidarum
causes uncontrolled vomiting requiring
hospitalization, severe dehydration, muscle
wasting, electrolyte imbalance, ketonuria, and
loss of more than 5% of the body weight.
Hyperemesis gravidarum occurs in 0.3–2.0% of
pregnancies, differs from the common nausea
and vomiting experienced during pregnancy,
and often requires hospitalization. Starvation is
commonly seen in patients with hyperemesis
gravidarum.
Lipolysis, the removal of fatty acid
chains from the glycerol to which they are
bound in their storage form as triglycerides, is
carried out by lipases. Fatty acids are then
broken down to acetyl-CoA by means of beta
oxidation inside the mitochondria. Under
fasting conditions, adipose tissue initiates
lipolysis and produces glycerol and free fatty
acids (FFAs). The maternal liver converts these
FFAs to glycerol and ketone to glucose, which
can cross the placenta to maintain fetal
metabolism. FFAs are required as a source of
energy for the development of the fetus and are
used for maintaining the fluidity, permeability,
and conformation of membranes; they are the
precursors of prostacyclins, prostaglandins,
thromboxanes, and leukotrienes. Therefore,
accurate measurement of plasma FFAs has
important physiological and clinical
implications. To understand and decrease the
effects of hyperemesis gravidarum-caused
dehydration, muscle wasting, electrolyte
imbalance, ketonuria and weight loss, we wish
to evaluate which FFAs are used as an energy
source in pregnant women with hyperemesis
gravidarum.
Current study found that 10 mg of
metoclopramide and 1000 mg of ginger extract
treatments were capable to reduce urine
ketones, in which all the twelve patients in the
group showed urine ketone decrement (100%).
Our result was in line with previous studies.
Therefore, it can be said that based on multiple
studies, ginger extract treatment was proved
effective.
CONCLUSION
Ginger extract with dose 1000 mg is
effective for reducing vomiting severity,
increasing sodium levels and decreasing urine
ketones.
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