The Role of Enzyme Supplementation

in Functional Dyspepsia Patients

LIANDA SIREGAR
RS KANKER DHARMAIS
DEVISI GASTROENTEROLOGI-HEPATOLOGI
Topik Bahasan
• Diagnosa Functional Dispepsia (FD) Rome IV

• Patofisiologi Functional Dispepsia dan

Pengobatan / treatment Failure FD

• Peran enzim pada FD

Topik Bahasan
• Diagnosa Functional Dispepsia (FD) Rome IV

• Patofisiologi Functional Dispepsia dan

Pengobatan / treatment Failure FD

• Peran enzim pada FD

 Kelainan Gasrointestinal Fungsional – Rome
IV

Stanghellini V. et.al. Digestive Disease; 2018

Functional Gastrointestinal Disorders (FGID) – ROME IV

• Jepretan L Jepretan Layar 2020-12-15 pukul 23.20.53 ayar 2020-12-15

pukul 23.20.53
The Classification of Dyspepsia.

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

Prevalence of underlying pathology identified at upper GI
endoscopy in patients with dyspepsia (adapted from Ford
and colleagues 20)
Prevalence of underlying pathology identified at upper
GI endoscopy in patients with dyspepsia (adapted from
Ford and colleagues20

72,5% kasus ditemukan

Hasil endoskopi adalah normal
Prevalensi Dispepsia Fungsional : berdasarkan kriteria
Rome III

Ford A.C, et.al. The Lancet; 2020

The Classification of Dyspepsia.

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

Ford A.C, et.al. The Lancet; 2020
The Classification of Dyspepsia.

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

Subtipe Dispepsia Fungsional: berdasarkan kriteria Rome IV
Sindrom Distres Postprandial Sindrom Nyeri Epigastrium

1. Rasa penuh yang tidak nyaman postprandial, terjadi 1. Nyeri atau sensasi terbakar pada epigastrium dengan
setelah makan dengan porsi biasa beberapa kali tingkat keparahan sedang, minimal satu kali dalam
dalam seminggu. DAN/ATAU seminggu. DAN
2. Rasa kenyang lebih awal sehingga makanan tidak 2. Nyeri intermiten. DAN
dapat menghabiskan makanan porsi biasa, minimal 3. Tidak tergeneralisasi atau terlokalisasi pada abdomen
beberapa kali dalam seminggu lain atau dada. DAN
4. Tidak membaik dengan defekasi atau flatus. DAN
5. Tidak memenuhi kriteria gangguan kandung empedu dan
sfingter Oddi

Kriteria Pendukung Kriteria Pendukung

3. Perut bagian atas kembung, mual postprandial, atau
sendawa berlebihan.
4. Dapat disertai Sindrom nyeri epigastrium
6. Nyeri seperti sensasi terbakar tanpa disertai nyeri pada
retrosternal
7. Nyeri yang diperberat dan diperingan Ketika menelan
makanan yang terjadi ketika puasa
8. Dapat disertai sindrom distes postprandial

Ford A.C, et.al. The Lancet; 2020

Gambaran klinis Dispepsia Fungsional

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1

Topik Bahasan
• Diagnosa Functional Dispepsia (FD) Rome IV

• Patofisiologi Functional Dispepsia dan

Pengobatan / treatment Failure FD

• Peran enzim pada FD

Motilitas Gaster

Motilitas Distal Gaster

Silbernagl. Color Atlas of Physiology; 2003

Vander et al. Human Physiology: The Mechanism of Body Function;2001
Gangguan pada Dispepsia Fungsional

Ford A.C, et.al. The Lancet; 2020

Putative mechanisms of functional dyspepsia symptoms at
the macroscopic and microscopic level

Enck P et al. Nature review ,2017

Manajemen Dispepsia Fungsional
Pasien dengan
Dispepsia Fungsional

H.Pylori positif H.Pylori negatif

Tidak respon
Eradikasi H.pylori PPI

Respon Respon
Tidak respon

Respon
Sukses TCA
Respon
Respon
Tidak respon

Pertimbangan
Prokinetik
psikoterapi

Moayyedi M. et.al. AJG; 2018

Manajemen Dispepsia

Alarm Symptomps :
• Onset usia > 55 tahun
• Perdarahan Saluran Cerna yang nyata
• Disfagia atau odinofagia
• Muntah persisten
• Berat badan turun
• Riwayat keluarga dengan kanker gaster
atau esofagus
• Teraba massa pada abdomen atau
epigastrium atau adenopati abdominal
• Anemia defisiensi besi
Ford A.C, et.al. The Lancet; 2020
Enck P, et.al. Naure Review; 2017
The Classification of Dyspepsia.

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

The Classification of Dyspepsia.

overlapped

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

 The Classification of Dyspepsia.

Therapy
overlapped
Resistant

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

Review Artikel : Pilihan Terapi pada Dispepsia Fungsional

Masuy et al.Aliment Pharmacol Ther. 2019;49:1134–1172

Summary of evidence for efficacy of treatment approaches for functional dyspepsia

Ford A.C, et.al. The Lancet; 2020

Topik Bahasan
• Diagnosa Functional Dispepsia (FD) Rome IV

• Patofisiologi Functional Dispepsia dan

Pengobatan / treatment Failure FD

• Peran enzim pada FD

Dietary Nutrients and Their Fates in the Gastrointestinal Tract
Products Sites of
Nutrient Enzymes
Generated Digestion
α-Amylase, disaccharidases, Saliva, intestinal
Starch, glycogen Glucose
oligosaccharidases lumen, brush border

Maltose Glucose Glucoamylase, sucrase

Sucrose Sucrase Brush border

Glucose + fructose
Glucose + galactose
Lactose Amino acids, Lactase
dipeptides,
tripeptides Pepsin, pancreatic enzymes, brush border Stomach, intestinal
Proteins
enzymes lumen, brush border
Fatty acids, 2-
Triglycerides Pancreatic lipase Intestinal lumen
monoacylglycerol

Nucleic acids Nucleosides, bases DNAses, RNAses Intestinal lumen

Only very limited

Fiber”: cellulose, lignin, Acetate, propionate,
fermentation by colon
hemicelluloses lactate, H2, CH4, CO2
bacteria
Peran Enzim Pencernaan
Organ yang Memproduksi Enzim Pencernaan

Tripsin, Kimotripsin,
Pankreas Karboksipeptidase, Lipase,
Amilase

Glucoamilase, Sukrase,
Small Intestine Isomaltase, Laktase

Metabolisme Lemak
Peran Enzim Pencernaan

Metabolisme Karbohidrat Metabolisme Protein

Silbernagl. Color Atlas of Physiology; 2003
Penyebab defisiensi dan Inadekuat Enzim Pencernaan

Gangguan Sekresi Habitual/drug

Pilihan Diet Usia

Swami OC et al. Int J Basic Clin Pharmacol; 2017

Penyebab defisiensi dan Inadekuat Enzim Pencernaan

Gangguan Sekresi Habitual/drug

Pilihan Diet Usia

Swami OC et al. Int J Basic Clin Pharmacol; 2017

 The Use of Digestive Enzymes in Specific Digestive Disorders

Pancreatic Insufficiency Lactose Intolerance

Casein and Gluten Intolerance Celiac Disease

Microbial Control Colon Health

Gangguan Sekresi
Disfungsi organ Defisiensi Nutrisi Pembedahan
pencernaan Gastrointestinal

Mucosal Disease

Swami OC et al. Int J Basic Clin Pharmacol; 2017

Infusiensi Pankreas Eksokrin

Lipase Lipid Muncul gejala :

• Rasa penuh
Protease Protein • Nyeri
Nutrient
• Kembung
Amilase Karbohidrat • Mual
 Penyebab Infusiensi Pankreas Eksokrin

Hilangnya Fungsi Pankreas Postcibal Asynchromy Penurunan Sekresi walaupun

• Pankreatitis kronik • Reseksi gaster Parenkim Pankreas Baik
• Fibrosis kistik • Short bowel syndrome • Obstruksi ductus pancreas (tumor
• Tumor pankreas • Crohn’s disease, papilla)
diabetes melitus • Penurunan stimulasi endogen
• Reseksi pankreas
(penyakit celiac, crohn’s disease,
diabetes melitus)
• Short bowel syndrome
• Inaktivasi intravascular (Zollinger
Keller J.et.al.Gut; 2005 Ellison Syndrome,
tetrahydrolipstatin)
 The Classification of Dyspepsia.

Resistant to overlapped
treatment

CJ Black, LA Houghton et al.Ther Adv Gastroenterol 2018,vol.11:1-17

Overlapped condition
certain populations of EPS are resistant for the treatment using anti-
acid therapy or prokinetics are considered as the involvement with
several other overlapped diseases.
We have also reported that almost 40% of FD patients with
abnormalities of pancreatic enzyme was determined as early chronic
pancreatitis (ECP) using endosonography .
Our results suggest that the measurement of early phase of gastric
emptying may be a useful tool to distinguish ECP patients from FD
patients. Gastric emptying is partly regulated by ghrelin and glucagon-
like peptide 1 (GLP-1) production. Further studies will be needed to
clarify whether the inflammation in gastrointestinal tract affect ghrelin
and GLP-1 production, respectively.
Penyebab defisiensi dan Inadekuat Enzim Pencernaan

Gangguan Sekresi Habitual/drug

Pilihan Diet Usia

Swami OC et al. Int J Basic Clin Pharmacol; 2017

 Usia Perubahan fungsi pankreas terkait usia

Gambaran Makroskopik dan Mikroskopik

Lohr. J.M. et.al. Journal of Internal Medicine; 2018

Penyebab defisiensi dan Inadekuat Enzim Pencernaan

Gangguan Sekresi Habitual/drug

Pilihan Diet Usia

Swami OC et al. Int J Basic Clin Pharmacol; 2017

Drug induced malabsorption
Drug induced malabsorption
Drug induced malabsorption
Penyebab defisiensi dan Inadekuat Enzim Pencernaan

Gangguan Sekresi Habitual/drug

Pilihan Diet Usia

Swami OC et al. Int J Basic Clin Pharmacol; 2017

Feinle-Bisset, C. & Azpiroz, F. Nat. Rev. Gastroenterol. Hepatol. 10, 150–157 (2013)
Makanan yang Menginduksi Dispepsia Fungsional

Enck P, et.al. Nature Review; 2017

Makanan yang Menyebabkan Gejala Dispepsia
Gejala Jenis makanan

Rasa penuh Daging merah, pisang, roti, kue, pasta, sosis,

gorengan, kacang, mayones, susu, coklat,
telur, permen, bawang, dan jeruk

Kembung Minuman berkarbonasi, bawang, kacang-

kacangan, pisang dan susu,

Nyeri epigastrium dan/atau Kopi, keju, bawang, merica, susu, coklat dan
sesasi terbakar nanas

Bisset C F.et.al Nat.Rev.Gastroenterol.Hepatol;2013

Peran Pilihan Diet pada Dispepsia Fungsional

Pesce M. et.al. World J Gastroenterol; 2020

Role of specific foods and their contribution to
functional dyspepsia symptoms
Role of specific foods and their contribution to functional
dyspepsia symptoms
Comparison of different therapies for the treatment of functional dyspepsia

Swami OC et al. Int J Basic Clin Pharmacol; 201

Advantages of digestive enzymes preparation over antacids

• Advantages of digestive enzymes preparation over antacids

Swami OC et al. Int J Basic Clin Pharmacol; 201

Evaluation of the Safety and Efficacy of a Multienzyme Complex
in Patients with Functional Dyspepsia: A Randomized, Double-
Blind, Placebo-Controlled Study
 Functional dyspepsia (FD) is a highly prevalent disorder having nonspecific symptoms and varied pathophysiology.
Its treatment remains a challenge as therapeutic options are limited, unsatisfactory, and elusive. Thus, safety and
efficacy of DigeZyme, a proprietary multienzyme complex (MEC), was evaluated as a dietary supplement in FD
patients. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 patients were randomly
assigned (1:1 ratio) to receive either MEC (50mg, TID; n=20) or placebo (n=20) for 60 days. Reports of adverse or
serious adverse events (AEs), abnormal results of vital signs, abnormal findings during physical examination, and
abnormal laboratory investigations were monitored closely. Efficacy measures were change in Short-Form Leeds
Dyspeps Supplementation with MEC was associated with statistically significant differences (P value ranging from .
0401 to .0033) in all efficacy parameters compared with placebo ia Questionnaire (SF-LDQ), Nepean Dyspepsia
Index-Short Form (NDI-SF), Visual Analog Scale (VAS), Clinical Global Impression Severity Rating Scale (CGI-S), and
Glasgow Dyspepsia Severity Score (GDSS) at baseline and follow-up visits on day 15, 30, and 60. Supplementation
with MEC was associated with statistically significant differences (P value ranging from .0401 to .0033) in all
efficacy parameters compared with placebo. The between-group comparison also revealed that MEC supplement
had a significantly greater effect (P<.001) versus placebo. No investigation product-related AEs were reported.
There were no clinically significant abnormalities in physical findings and no statistically
significant changes in biochemical and hematological parameters, vital signs, body weight, and
body mass index observed between the two groups at baseline and follow-up visits. MEC
supplementation represents an effective and safe alternative to manage dyspepsia symptoms
in FD patients
 JOURNAL OF MEDICINAL FOOD J Med Food 21 (11) 2018, 1120–1128 Mary Ann Liebert, Inc., and Korean Society of
Food Science and Nutrition
Evaluation of the Safety and Efficacy of a Multienzyme Complex
in Patients with Functional Dyspepsia: A Randomized, Double-
Blind, Placebo-Controlled Study
 Functional dyspepsia (FD) is a highly prevalent disorder having nonspecific symptoms and varied pathophysiology. Its treatment remains a
challenge as therapeutic options are limited, unsatisfactory, and elusive. Thus, safety and efficacy of DigeZyme, a proprietary multienzyme
complex (MEC), was evaluated as a dietary supplement in FD patients. In this randomized, double-blind, placebo-controlled, parallel-group
study, 40 patients were randomly assigned (1:1 ratio) to receive either MEC (50mg, TID; n=20) or placebo (n=20) for 60 days. Reports of
adverse or serious adverse events (AEs), abnormal results of vital signs, abnormal findings during physical examination, and abnormal
laboratory investigations were monitored closely. Efficacy measures were change in Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ),

Supplementation with MEC was

Nepean Dyspepsia Index-Short Form (NDI-SF),

associated with statistically significant differences (P

value ranging from .0401 to .0033) in all efficacy
parameters compared with placebo
 everity Score (GDSS) at baseline and follow-up visits on day 15, 30, and 60. Supplementation with MEC was associated with statistically
significant differences (P value ranging from .0401 to .0033) in all efficacy parameters compared with placebo. The between-group
comparison also revealed that MEC supplement had a significantly greater effect (P<.001) versus placebo. No investigation product-related
AEs were reported. There were no clinically significant abnormalities in physical findings and no statistically significant
changes in biochemical and hematological parameters, vital signs, body weight, and body mass index observed
between the two groups at baseline and follow-up visits. MEC supplementation represents an effective and safe
alternative to manage dyspepsia symptoms in FD patients
 JOURNAL OF MEDICINAL FOOD J Med Food 21 (11) 2018, 1120–1128 Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
Clinical evidence of efficacy and safety of oral enzymes supplement
in Gastro Intestinal Disease  
 Ran et al. assessed patients (n=151, 18 to 75 years) diagnosed with chronic digestive
diseases presenting with two or more dyspepsia symptoms such as epigastric pain,
abdominal distension, epigastric burn, belching, diarrhea and constipation. The efficacy of
an enzyme preparation containing 24-mg enzyme extract of Aspergillus oryzae (cellulase,
protease and amylase) and 220 mg pancreatin (lipase, proteinase and amylase) given post-
meal (2 tablets), thrice a day was assessed in these patients.
 Patients recruited included functional dyspepsia, GERD, a peptic ulcer (without
complications such as bleeding, perforation, stenosis and malignancy), chronic gastritis,
partial gastrectomy, small or large intestinal resection, diverticulosis, liver cirrhosis
(without serious complications), chronic biliary disease including cholecystitis,
cholelithiasis, polyps of the gallbladder, cholecystectomy, chronic pancreatic disease
including chronic pancreatitis, chronic pancreatic insufficiency, diabetes mellitus with
dyspepsia symptoms and geriatric reduction of digestive function.
 Compared with placebo, 2 weeks of enzymatic treatment decreased the severity index of
dyspepsia symptoms significantly. The efficacy rates of enzyme preparation and the placebo
on dyspepsia were 90% and 22%, respectively (P <0.01).
(Article  in  International Journal of Basic & Clinical Pharmacology · April 2017 )
Clinical evidence of efficacy and safety of oral enzymes supplement
in Gastro Intestinal Disease  
 Ran et al. assessed patients (n=151, 18 to 75 years) diagnosed with chronic digestive diseases presenting with two or
more dyspepsia symptoms such as epigastric pain, abdominal distension, epigastric burn, belching, diarrhea and
constipation. The efficacy of an enzyme preparation containing 24-mg enzyme extract of Aspergillus oryzae (cellulase,
protease and amylase) and 220 mg pancreatin (lipase, proteinase and amylase) given post-meal (2 tablets), thrice a day
was assessed in these patients.
 Patients recruited included functional dyspepsia, GERD, a peptic ulcer (without complications such as bleeding,
perforation, stenosis and malignancy), chronic gastritis, partial gastrectomy, small or large intestinal resection,
diverticulosis, liver cirrhosis (without serious complications), chronic biliary disease including cholecystitis,
cholelithiasis, polyps of the gallbladder, cholecystectomy, chronic pancreatic disease including chronic pancreatitis,
chronic pancreatic insufficiency, diabetes mellitus with dyspepsia symptoms and geriatric reduction of digestive
function.

Compared with placebo, 2 weeks of enzymatic treatment

decreased the severity index of dyspepsia symptoms
significantly. The efficacy rates of enzyme preparation and
the placebo on dyspepsia were 90% and 22%, respectively
(P <0.01).
(Article  in  International Journal of Basic & Clinical Pharmacology · April 2017 )
 New Enzyplex
• Enzim Amilase…………………………….................................... 10.000 unit
• Enzim Protease………………………………................................ 9.000 unit
• Enzim Lipase…………………………………................................ 240 unit
• Deoxycholic Acid……………………………………………………………………. 30 mg
• Simethicone………………………………………………………………………….. 25 mg
• Vitamin B1…………………………………………………………………………….. 10 mg
• Vitamin B2…………………………………………………………………………….. 5 mg
• Vitamin B6…………………………………………………………………………….. 5 mg
• Vitamin B12………………………………………………………….. 5 mcg
• Niacinamide………………………………...................................... 10 mg
• Ca Panthotenat……………………………………………………… 5 mg
 Indikasi New Enzyplex
• Membantu proses pencernaan
• Membantu mencegah dan mengatasi gejala-gejala gangguan pencernaan seperti
rasa kembung, rasa penuh di lambung , sendawa. flatus.
• Pada keadaan dimana dibutuhkan peningkatan enzim pencernaan seperti :
Makan yang berlebihan, intoleransi terhadap makanan, salah cerna ( malabsorbsi
), gangguan pankreas, gangguan hiperasiditas lambung, lanjut usia dan lain-lain
gangguan pencernaan fungsional.
 Dosis New Enzyplex
• 1-2 tablet pada waktu makan atau sesudahnya atau menurut petunjuk dokter
Kesimpulan
• Enzim pencernaan diproduksi dan disekresi oleh system pencernaan untuk
mendegradasi lemak, protein, dan karbohidrat

• Dispepsia fungsional merupakan gangguan tersering pada gastrointestinal

• Beberapa faktor yang dapat menyebabkan inadekuat dan defisiensi enzim

pancreas seperti gangguan sekresi, habitual, pilihan diet dan usia

• Terapi suplementasi enzim memiliki peran penting pada kelainan pencernaan

seperti insufisiensi pancreas eksokrin