Journal Reading 2

Zingiber officinale and oxidative stress in patients with ulcerative

colitis : A randomized, placebo-controlled, clinical trial
Mehrnaz Nikkhah-Bodaghia, Iradj Malekib, Shahram Agahc, Azita Hekmatdoosta

Marzuki
C175201004
PPDS ILMU GIZI
KLINIK

Pembimbing/ Penilai 1 : Prof. dr. Veni Hadju, M.Sc,Ph.D, SpGK

Penilai 2 : dr. Nurbaya Syam, M.Kes, Sp.GK (K)
Penilai 3 : dr. Marniar, M.Kes, Sp.GK (K)
 ABSTRACT

Objectives : Oxidative stress plays an essential role in ulcerative colitis (UC)

initiation and severity. We aimed to investigate the effect of ginger as a well-
known antioxidant agent on the quality of life, disease activity index and
oxidative stress in patients with UC.

Methods : Forty six patients with active mild to moderate UC randomly assigned to
consume 2000 mg/day dried ginger powder in 4 capsules or similar placebo capsules for 12
weeks. Disease activity index, quality of life and some oxidative stress factors were
measured before, at the middle and at the end of the intervention through valid and reliable
questionnaires and blood sampling.
 ABSTRACT
Results : Ginger reduced Malondialdehyde (MDA) significantly after 6 weeks (p = 0.003) and
12 weeks (p < 0.001) of intervention, where as it did not affect serum total anti-oxidant
capacity (TAC). The scores of severity of disease activity at 12th week was significantly
improved in ginger group in comparison to placebo (p = 0.017). More over, ginger increased
patients quality of life significantly at 12th week (p = 0.039).

Conclusion : Our data indicate that ginger supplementation can improve treatment of patients
with UC. Further clinical trials with different dosages and duration of ginger or its standard
extract supplementation are needed to obtain firm conclusion.
INTRODUCTION
 INTRODUCTION
Ulcerative colitis (UC), as one of Reactive Oxygen
the two major forms of Species metabolites in-jures
flammatory bowel disease (IBD).
in- theintestinal
of integritymucosa, and delay
recovery of them.

Chronic inflammatory disorder Medical therapy of UC including anti-

with frequent relapses inflammatory and immune
remissions. and sup-pressants
are often reported
to induce some side effects.

It seems that oxidative stress

Zingiber officinale root as an anti-
plays pivotalrole in
oxidative agent with known
a UC and
beneficial effects.
relapses.
initiation occurrence of
MATERIAL
AND
METHODS
 TRIAL DESIGN AND PARTICIPANTS

This study was a prospective, Patients more than 18 years Pregnant/lactating women, Participants visited three
randomized, double-blind, old, free of cancer or other as well as those consuming times during the study period
placebo- controlled trial (NO. inflammatory, autoimmune, some medications such as (at the first (T1), middle
IRCT201703164010N17). infectious and intestinal antihistamines, anti coa (T2)and end (T3) of study).
Through convenience diseases were included. gulants, calcium channel
sampling method. antagonists, NSAIDs or oral
contraceptive drugs.
 INTERVENTION
Patients who agreed to participate were randomly assigned to re- ceive either ginger (containing 500
mg dried ginger powder) or placebo capsules (maltodexterin powder). Ginger powder was made by
drying and milling the fresh edible ginger from the same farm. Randomization was conducted using the
random number table. Patients were re- commended to have 4 capsules (2000 mg) during a day along
with their meals (two capsules with breakfast, and two capsules with dinner) for 12 weeks.We asked
participants not to change their usual dietary habits and physical activity during intervention. Capsules
needed for the first and second 6 weeks of intervention were delivered to participants at the first and
second visits respectively.

Before beginning of the study, the medicine cans were coded as A or B by someone other than the re-
searchers so that the researchers did not know which kind of capsules received by each group. At
each visit, anthropometric data including weight (with light clothes to the nearest 0.1 kg), height
(without shoes to the nearest 0.5 cm), and BMI (weight (kg)/height (m2) were measured.
 INTERVENTION
Furthermore, four questionnaires were filled out by an ex-pert interviewer including "general
questionnaire" requesting general information about age, sex, duration of the disease, smoking
history, current medications, etc; "Inflammatory Bowel Disease Questionnaire-9 (IBDQ-9)"24,25
assessing UC patient’s quality of life, "Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ)"26
determining disease activity index of UC patients andfinally,3-day dietary recalls of 2 weekdays and 1
weekend day assessing patients dietary intake of en-ergy, macro/ micronutrients. For assessing the
differences between serum oxidative stress factors, before, at the middle and after inter-vention, we
collected 10cc of 12–14 h fasted blood samples, poured into heparinized laboratory tubes and
immediately centrifuged. Separated plasma was kept in −80 °C freezer for further examinations.

Adverse events of treatment were monitored during visits as well as follow up phone calls at third and
ninth weeks. During intervention, participants with disease relapse leading to hospitalization or patients
who did not want to continue the study protocol were excluded. Adherence to treatment was evaluated
by counting the number of pills remaining in medicine can at the second and third visits. If > 10% of
capsules were remained, the patient was excluded from the study.
RESULTS
s
 MEASUREMENTS
Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as indicators of oxidative
stress status, were determined using ELISA. We analyzed dietary intake values of energy and
nutrients through modified Nutritionist 4 using national food composition tables. We rated IBDQ-9 to
evaluate each participant´s quality of life. IBDQ questionnaire is the most utilized questionnaire for
evaluating the quality of life in patients with IBD in clinical and epidemiological stu-dies, regarding due
to its high validity, reliability, sensitivity and in-tercultural adaptation.

Our questionnaire had 9 questions about patient´s emotional and social challenges such as the levels
of sa-tisfaction or happiness in personal life, patient's energy, feeling of sickness, feeling tired, cancel
or delay a scheduled task as well as bowel habits such as gas excretion, flatulence, stool frequency
and cramps during past two weeks. Each question has 7 items and each item has its own
corresponding score; so each question covers points 1 to 7. The total score of questionnaire can be
from 9 to 63. The higher score re-flects the better quality of life of patient.
 MEASUREMENTS
Evidence have shown that IBDQ score is significantly correlated with clinical and colonoscopy results.
We also rated SCCAIQ to evaluate each participant´s disease activity. This questionnaire score
correlates closely to laboratory data and is reported to be a reliable tool for initial assessment of UC
out-patients.This questionnaire has multiple items with total score be-tween 0–19; which higher scores
reflect more severity of UC symptoms during past week.
PRIMARY

The primary outcome measure was a significant

reduction in SCCAIQ score.

SECONDARY OUTCOMES
Secondary outcome measures were IBDQ-9 score,
serum concentration of MDA, and TAC.
STATISTICAL ANALYSIS
Estimation of sample size for this study was based on detection
of 4 score difference in mean SCCAIQ score with power of 80%
(β = 20%).12 In this study, the calculated sample size for each
group was 21 patients. Due to the potential loss of samples, 25
patients in each group were considered.

We applied SPSS 19 for the statistical analysis. The collected

data normality distribution was assessed by Shapiro-Wilks test.
We used chi-square test in order to compare the qualitative
confounding variables and independent t-test in order to
compare the variable means between ginger and control groups.
We assumed p value < 0.05 as sta-tistically significant.
DISCUSSION
 DISCUSSION
To our knowledge, this is the first clinical trial that has investigated the effects of ginger on oxidative
stress in patients with UC. Our results have shown that consumption of 2 g/day dried ginger powder
for 90 days can improve some aspects of oxidative stress and disease activity. It seems that this
dosage and duration of supplementation was too low to induce significant improvement in patients with
UC. Ginger sup- plementation reduced MDA significantly; however, it could not affect TAC. Thus, it
could significantly decrease the total score of SCCAIQ, and IBDQ; however, the difference with
placebo did not reach to a significant point for IBDQ.

Ginger restored parameters of the redox state of the colonic mucosa through improving colonic
enzymatic and non-enzymatic defense sys-tems to the extent that approaches the normal values. In
addition, antioxidant properties of ginger have been reported in clinical trials of other diseases with
oxidative stress condition such astype 2 diabetes and Tuberculosis. Our study confirmed the results of
these studies in patients with UC. However, serum MDA improved more than TAC in our study, which
might be due to relatively short duration and low dosage of supplementation.
 DISCUSSION
some advantages; it was the first randomized, double blind, placebo controlled, clinical trial evaluated
the effects of ginger on oxidative stress in UC patients, all known covariates were controlled during
study, and study outcomes were measured every 6 weeks that have shown the trend of study outcome
measurements.

some limitations; we could not use invasive methods such as colonoscopy and tissue biopsy to
measure the severity of the disease and the tissue oxidative stress indices because patients did not
accept to undertake colonoscopy at the end of the study. However, we used SCCAIQ, which has been
shown as an effective indicator of the severity of UC.
CONCLUSION
CONCLUSION
In conclusion this randomized, placebo controlled
trial found that 2000 mg/day ginger
supplementation can improve disease severity
index and oxidative stress in patients with active
mild to moderate UC. Further clinical trials with
different dosages and duration of ginger or its
standard extract supplementation are needed to
obtain firm con-clusion.
TERIMA
KASIH
II. Khusus
Menilai VIA (Validity, Importance, Aplicability)
PENELITIAN RANDOMIZED CONTROLLED TRIAL

UJI KLINIS
Validity
1.Apakah awal penelitian didefinisikan dengan jelas? (pertanyaan penelitian/tujuan penelitian) Ya,
stres oksidatif memainkan peran penting dalam inisiasi dan keparahan kolitis ulserativa (UC). Kami
bertujuan untuk menyelidiki effect jahe sebagai agen antioksidan terkenal pada kualitas hidup, indeks
aktivitas penyakit dan stres oksidatif pada pasien dengan UC.

2.Apakah menyatakan desain penelitian dengan jelas ? Ya, Penelitian ini merupakan percobaan
prospektif, acak, double-blind, terkontrol plasebo (NO. IRCT201703164010N17). Melalui metode
convenience sampling, pasien dengan UC ringan sampai sedang aktif direkrut dari tiga klinik
gastroenterologi di Teheran dan Sari, Iran
3.Apakah ada pembanding yang jelas? Tidak ada, karena Sepengetahuan peneliti, ini adalah fiuji
klinis pertama yang telah menyelidiki efek jahe pada stres oksidatif pada pasien dengan UCA.

4.Apakah faktor kausal dikemukakan? Ya, Meskipun efek jahe dan komponen fenoliknya pada UC
diperiksa dalam model eksperimental dan menghasilkan peningkatan stres oksidatif dan skor
mikroskopis dan makroskopik jaringan kolon, tidak ada bukti aplikasi jahe dalam percobaan
manusia. Jadi, kami melakukan uji klinis untuk menyelidiki apakah suplementasi dengan bubuk
jahe kering dapat meningkatkan respons pasien UC terhadap perawatan rutin, kualitas hidup,
indeks aktivitas penyakit, dan status oksidatif serum atau tidak.

5.Apakah kelompok-kelompok yang dibandingkan sebanding pada tahap awal atau karakteristik
kelompok yang dibandingkan ? ya, tidak ada perbedaan yang signifikan dalam karakteristik dasar
peserta pada awal penelitian dan Tidak ada perbedaan signifikan antara jumlah asupan energi,
zat gizi makro dan zat gizi mikro antara dua kelompok pada setiap waktu intervensi kecuali untuk
asupan fiber (serat), yang signifikan dikurangi selama penelitian pada kelompok control.
6.Apakah follow up dilakukan secara memadai ? Ya, . Pada setiap kunjungan, data
antropometri meliputi berat badan (dengan pakaian tipis hingga 0,1 kg terdekat), tinggi
badan (tanpa sepatu hingga 0,5 cm terdekat), dan IMT (berat badan (kg)/tinggi badan
(m2)diukur.Selain itu,recall diet 3 hari dari 2 hari kerja dan 1 hari akhir pecan dihitung
untuk menilai asupan makanan pasien energi baik makro dan atau mikronutrien. Efek
samping pengobatan dipantau selama kunjungan serta panggilan telepon tindak lanjut
pada minggu ketiga dan kesembilan.
•Metode P I C O
P
Patient : Semua pasien' diagnosis UC sebelumnya dan ditangani oleh ahli gastroenterologi menggunakan pemeriksaan histopatologi.

Population : Melalui metode convenience sampling, pasien dengan UC ringan sampai sedang aktif direkrut dari tiga klinik
gastroenterologi di Teheran dan Sari, Iran

Problem : Baru-baru ini, prevalensi UC meningkat terutama di kalangan konsumen diet barat di seluruh dunia, bahkan daerah di
mana penyakit ini sebelumnya dilaporkan jarang terjadi seperti negara-negara Afrika dan Asia. Sementara terapi medis UC
termasuk anti-inflamasi dan kekebalan sering dilaporkan menginduksi beberapa efek samping pada mata, tulang, saluran
pencernaan, hati, pankreas dan sistem kekebalan tubuh.

Intervensi : Pasien yang setuju untuk berpartisipasi secara acak diberikan jahe (mengandung bubuk jahe kering 500mg) atau kapsul
plasebo (bubuk maltodeksterin). Pasien dianjurkan untuk minum 4 kapsul (2000mg) selama sehari bersama dengan
makanan mereka (dua kapsul dengan sarapan, dan dua kapsul dengan makan malam) selama 12 minggu. Kami meminta
peserta untuk tidak mengubah kebiasaan diet dan aktivitas fisik mereka selama intervensi. Kapsul yang dibutuhkan untuk
intervensi 6 minggu pertama dan kedua diberikan kepada peserta di kunjungan pertama dan kedua .
C
Comparison : Empat puluh enam pasien dengan UC ringan hingga sedang aktif secara
acak ditugaskan untuk mengonsumsi bubuk jahe kering 2000mg/hari dalam 4 kapsul atau
kapsul placebo (bubuk maltodeksterin) serupa selama 12 minggu.

O
Outcome : Ukuran hasil utama adalah jahe secara signifikan mengurangi skor SCCAIQ.
Ukuran hasil sekunder adalah skor IBDQ-9, konsentrasi serum MDA, dan TAC.

 IMPORTANT
Apakah outcome/hasil dipaparkan secara jelas (hasil uji statistik dengan hasil nilai P) ? Ya.
Dapat dilihat pada TABEL 2, Tidak ada perbedaan signifikan antara jumlah asupan energi,
zat gizi makro dan zat gizi mikro antara dua kelompok pada setiap waktu intervensi kecuali
untuk asupan fiber, yang signifikan menurun selama penelitian pada kelompok kontrol.
 IMPORTANT
1. Apakah outcome/hasil dipaparkan secara jelas (hasil uji statistik
dengan hasil nilai P) ? Ya. Dapat dilihat pada TABEL 2, Tidak ada
perbedaan signifikan antara jumlah asupan energi, zat gizi makro
dan zat gizi mikro antara dua kelompok pada setiap waktu
intervensi kecuali untuk asupan fiber, yang signifikan menurun
selama penelitian pada kelompok kontrol.

Pada gambar 2, meskipun dua kelompok secara statistik serupa

dalam faktor stres oksidatif, kualitas hidup, dan skor aktivitas
penyakit pada garis dasar, independen T-uji menunjukkan bahwa
MDA pada kelompok jahe signifikanfisedikit lebih rendah dari
kelompok kontrol setelah 6 minggu (p = 0,003) dan 12 minggu (p <
0,001)
Pada Tabel 3, tingkat serum MDA menurun secara signifikan terutama pada
kelompok jahe (p < 0,001). . Selama waktu studi, konsentrasi MDA signifikan jauh
lebih rendah pada kelompok jahe dibandingkan dengan kelompok plasebo (p <
0,001) dan perubahan ini tetap signifikan setelah penyesuaian untuk bobot dan
nilai dasar.
Pada Tabel 4, Skor keparahan aktivitas penyakit pada minggu ke-12 signifikan
sedikit meningkat pada kelompok jahe dibandingkan dengan plasebo (p=0,017).

1. Seberapa besarkah ketepatan estimasi outcome yang didapat dengan nilai

RR dengan nilai korelasi 95% CI? Tidak ada nilai RR dengan nilai korelasi 95 %
CI pada penelitian ini.
 APLICABILITY
1. Apakah karakteristik pasien mirip dengan subjek uji klinis yang diteliti ? Ya, terdapat pasien
yang mirip dengan subjek berdasarkan kelompok usia dan jenis kelamin sesuai kriteria inklusi
pada penelitian.

2. Apakah bukti ini akan mempunyai pengaruh yang penting secara klinis terhadap faktor
prognostik pasien kita tentang apa yang telah ditawarkan/diberikan kepada pasien kita? Ya,
hasil penelitian ini menunjukkan bahwa konsumsi 2 g/hari bubuk jahe kering selama 90 hari
dapat meningkatkan beberapa aspek stres oksidatif dan aktivitas penyakit. Akan tetapi dosis
dan durasi suplementasi ini terlalu rendah untuk menginduksi secara signifikan perbaikan pada
pasien dengan UC. Uji klinis lebih lanjut dengan dosis dan durasi yang tepat dari jahe atau
suplementasi ekstrak standarnya diperlukan untuk mendapatkan kesimpulan yang lebih akurat.

3. Apakah simpulan tentang hasil studi tersebut berguna bagi pasien dalam tatalaksana secara
keseluruhan ? ya, bahwa suplementasi jahe 2000mg/hari dapat meningkatkan indeks
keparahan penyakit dan stres oksidatif pada pasien dengan UC ringan hingga sedang aktif.
TERIMA
KASIH