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Role of Enzyme Supplementation

in Management of Indigestion

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Digestion

Food processing takes place in the oral cavity to reduce


particle size and form a bolus

Gastric processing to initiate chemical and enzymatic


breakdown

Small intestinal processing to break down macromolecules


and absorb nutrients

Fermentation and elimination of water in the colon

Boland M.. J Sci Food Agric. 2016;96(7):2275-2283.

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Indigestion
Indigestion
Pain or discomfort in the upper abdomen along
with epigastric pain
Postprandial fullness

Dyspepsia/indigestion is derived Early satiety


from the Greek words ‘dys’ and Anorexia
‘pepse’ which together mean
Belching
‘difficult digestion’
Nausea and vomiting

Upper abdominal pain

Heartburn and regurgitation

Kumar A et al. J Assoc Physicians India. 2012;60(6):9-12.

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Epidemiology

The prevalence of indigestion depends upon the geographical location


and the definition of indigestion.1

The prevalence of functional dyspepsia is estimated to be around 11%


to 29% worldwide, whereas the prevalence of uninvestigated dyspepsia
is reported to vary between 7% to 45%.1

The prevalence of indigestion in India is estimated to be around 30%.2

1. Mahadeva S et al. World J Gastroenterol. 2006;12(17): 2661-2666.


2. Kumar A et al. J Assoc Physicians India. 2012;60(6):9-12.

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Prevalence of Indigestion in Asia

Country Prevalence
Turkey UD = 28.4%
Iran UD = 8.9%
India UD = 30.4%
Russia UD = 20%
China FD = 23.5%
Malaysia UD = 14.6%
Korea UD = 15.5%, FD = 8.1%
Taiwan UD = 27.8%, FD = 23.8%
Hong Kong UD = 18.4%
Singapore UD = 7.9%
Japan UD = 10%, FD = 17%
UD, uninvestigated dyspepsia; FD, functional dyspepsia; Hp, Helicobacter pylori.

Source: Ghoshal UC, et al., 2011.

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Indigestion Due to Dietary Patterns

Excessive intake of food and carbonated drinks leads to bloating.1

Overeating, consumption of spicy and fatty foods, citrus juices, carbonated beverages, caffeine
and alcohol lead to heartburn which is another important symptom of indigestion.1

Since lipids are a main trigger of indigestion symptoms such as nausea, bloating, pain, fullness,
and other related symptoms, consumption lipid-rich food products aggravate indigestion.2

In most of the Asian countries like India, spicy foods are consumed in abundance, which increases
the risk of indigestion.3

1. Schachter H. Indigestion and Heartburn.1990.


2. Khodarahmi et al. Adv Biomed Res. 2016;5:76.
3. Ghoshal UC et al. J Neurogastroenterol Motil. 2011;17(3): 235-244.

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Indigestion in Elderly

Around 40% of older patients have age-related gastrointestinal disorders

After the age of 60, problems like indigestion and other ailments of digestive
system may occur due to the following reasons:
• Slower rate of metabolism
• Susceptibility to diverticulosis
• Comorbidities like thyroid disorders and diabetes
• Use of medications
• Inactivity and overweight
• Increased sensitivity

Mylifestages: https://www.mylifestages.org/health/digestive_health/aging_and_digestion.page

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Indigestion Due to Comorbid Diabetes

 Indigestion is one of the common complication of diabetes mellitus due to


reduced GI motility, reduced pancreatic enzyme secretion1
 Indigestion due to insufficient pancreatic enzymes is found in 51% (26-74%)
of type I diabetes mellitus patients and in 32% (28-36%) of type II diabetes
mellitus patients
 The symptoms of indigestion could be of varying levels (mild to severe).

1. Demir K. Eur J Surg Sci. 2012;3(1):1-4.

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Indigestion and Gastrointestinal Surgery
80% of the patients who undergo gastric, duodenal and pancreatic
surgery experience indigestion followed by weight loss.1,2

Gastrointestinal and pancreatic surgery cause anatomical and


physiological changes that lead to indigestion.3

Thus, it is necessary to replace the lost pancreatic enzymes


sufficiently to avoid indigestion and malnutrition after
surgeries.3

Incorporating high calorie diets is the first step, which involves 6 to


8 meals distributed throughout the day.3

1. Sikkens ECM, et al. J Gastrointest Surg. 2012;16(8);1487-1492.


2. Friess H, et al. Digestion. 1993;54(suppl 2):48-53.
3. Domínguez-Muñoz JE. HPB (Oxford). 2009;11(suppl 3):3-6.

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Indigestion Due to Gastrointestinal Surgery

Absence of antro-fundic and duodeno-fundic reflexes cause a disturbance in fundus


Total/partial resections of the

relaxation.
with/without duodenal
stomach and pancreas,

This absence of fundus relaxation expels pancreatic secretion, which is neurally


stimulated.
Post duodenal resection, a reduction in CCK-mediated stimulation of pancreatic
resection

secretion takes place.


Due to the resection of distal stomach, large nutrient particles reach the jejunal
lumen.
Pancreatic resection is associated with a reduction in exocrine pancreatic secretion.
Anatomical reconstruction causes an imbalance between the gastric emptying of
nutrients and bilio-pancreatic secretion.

CCK, cholecystokinin.

1. Domínguez-Muñoz JE. HPB (Oxford). 2009;11(suppl 3):3-6.

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Lipids – a Major Trigger for Indigestion

Lipids are a major For the nutrient


trigger of They also fat to act on
indigestion modulate upper gastrointestinal
symptoms such gastrointestinal sensations and
as nausea, sensations and indigestion
bloating, pain symptoms in a symptoms, fat
and fullness dose-related hydrolysis by
during stomach fashion lipases is
distension mandatory

1. Fried M, et al. Gut. 2002;51(suppl 1):i54-i57.

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Lipids and CCK

According to various studies, fat ingestion releases CCK which plays a major role
in regulating the upper gastrointestinal function.

Gastric motility is altered due to the release of CCK, thus inhibiting gastric
emptying after meals.

By modifying the release of CCK, the postprandial gastric acid secretion is inhibited by
products of fat hydrolysis.

CCK, cholecystokinin.

Fried M, et al. Gut. 2002;51(suppl 1):i54-i57.

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Role of CCK

Fat ingestion leads to the release of CCK which regulates the upper gastrointestinal
function.

This released CCK alters gastric motility which leads to the inhibition of postprandial
gastric emptying.

The postprandial gastric acid secretion is inhibited by products of fat hydrolysis by


altering CCK release.

CCK, cholecystokinin.

Fried M, et al. Gut. 2002;51(suppl 1):i54-i57.

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Clinical Assessment of Indigestion

Physical
Medical history
examination

Upper
Laboratory
gastrointestinal
tests
endoscopy

NIH. https://www.niddk.nih.gov/health-information/digestive-diseases/indigestion-dyspepsia/diagnosis.

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Assessment of Symptoms
 Excessive intake of food and carbonated drinks
leads to bloating, thus the evaluation of dietary
history plays a vital role in the diagnosis of
indigestion and its symptoms.1
 Symptoms like bloating/flatulence and abdominal
discomfort should be treated1
 Fatty stools is another symptom which is caused
due to indigestion occurring due to pancreatic
causes, as pancreatic dysfunction causes
malabsorption of food, eventually leading to
indigestion.2

1. Schachter H. Indigestion and Heartburn.1990.


2. Banks PA, et al. Gastroenterol Hepatol (N Y). 2010;6(2 Suppl 5):1-16.

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Physical Examination
 Abdomen is checked for bloating, sounds,
tenderness, pain and lumps
 The skin and eyes are checked for yellow
discoloration

Longstreth et al. https://www.uptodate.com/contents/approach-to-the-adult-with-dyspepsia/print.

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Laboratory Tests

Complete blood count to identify


patients with iron-deficiency anemia

Liver function tests, serum lipase and


amylase to identify patients with
underlying metabolic diseases that may
cause indigestion such as diabetes or
hypercalcemia

Longstreth et al. https://www.uptodate.com/contents/approach-to-the-adult-with-dyspepsia/print.

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Upper Gastrointestinal Endoscopy
Upper GI endoscopy – to diagnose diseases which
may be the cause for indigestion (gastritis, peptic
ulcer disease and stomach cancer)

An upper GI endoscopy is generally recommended


only in patients with indigestion older than 55
years of age

If the patient has the following conditions, upper


GI endoscopy is recommended in patients with
indigestion of any age:
• Family history of cancer
• Difficulty in swallowing
• Evidence of bleeding in the GI tract
• Frequent vomiting
• Weight loss

GI, gastrointestinal.

NIH. https://www.niddk.nih.gov/health-information/digestive-diseases/indigestion-dyspepsia/diagnosis.
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Management of Indigestion

Non-pharmacological Therapy Pharmacological Therapy

Small and frequent meals Proton-pump inhibitors

Avoid alcohol and NSAIDs H2RA

Avoid fatty and spicy foods Prokinetics

Avoid caffeine Antidepressants


NSAID, non-steroidal anti-inflammatory drugs; H2RA, H2-receptor antagonists.

Voisu TA et al. Maedica (Buchar). 2013;8(1):68-74.

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Acid Suppression Therapy

Acid suppressants are the treatment of choice for epigastric pain.

Acid suppressants, usually in combination with prokinetics is


commonly used therapy for indigestion symptoms.

H2RAs are recommended if there is no response to proton-pump


inhibitors.

H2RAs are more beneficial compared with proton pump


inhibitors, but data regarding the same is more heterogenous.

H2RA, H2-receptor antagonists.

Talley NJ. Korean J Intern Med. 2016;31(3):444-456.

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Role of Enzyme Supplementation

Enzyme supplements are used in different combinations,


based on the requirement.

Digestive enzyme supplements play a significant role in


alleviating the symptom of indigestion.

The main digestive enzymes are amylase, protease and


lipase, which are used to digest the proximate principles of
food, namely, carbohydrates, proteins and fats, respectively.

Enzyme supplements are safe and do not have any adverse


effects.

Swami OC et al. Int J Basic Clin Pharmacol. 2017;6(5):1035-1041.

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Need for Right Blend of Enzyme Supplementation

 Since, lipids are triggers for indigestion and associated symptoms, the enzyme
supplement preparation that we are recommending to patients should have
‘Lipase’ as it is the only enzyme which is able to digest lipids.1
 It is observed that, most of the preparations in Indian market marketed as
digestive enzyme supplements ‘do not have Lipase’ enzyme. Thus, these
preparations may not effectively reduce symptoms of indigestion.2
 Thus, it is very critical to choose ‘right’ blend of enzymes and choose the one
which contains all the necessary enzymes for digestion of proximate
principles for holistic management of such patients.3

1. Khodarahmi M. et al. Adv Biomed Res. 2016;5:76.


2. WHO. http://apps.who.int/medicinedocs/documents/s18044en/s18044en.pdf.
3. Ianiro G et al. Curr Drug Metab. 2016 Feb; 17(2): 187-193.

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Acid Suppressants versus Digestive Enzyme Supplementation

Acid Suppressants Digestive Enzyme Supplements

Do not aid digestion but reduce it Increase digestive power

Provide temporary relief Are a lasting solution for GI problems

Some disturb the synthesis of gastric acid Do not interfere with the internal metabolism

Help in complete absorption of nutrients


Block the absorption of nutrients and drugs

Decrease the antimicrobial activity of stomach Promote the antimicrobial activity of stomach

Side effects include constipation, dizziness, loss of appetite,


Well tolerated with minimum side effects
unpleasant taste, nausea and increased thirst

GI, gastrointestinal.

1. Swami OC, et al. Int J Basic Clin Pharmacol. 2017;6(5):1035-1041.

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Lipase Enzyme Supplement

Lipase is a digestive enzyme that aids the hydrolysis of triacylglycerols.

The complete digestion of lipids is done by lingual, pancreatic and


enteric lipases as they hydrolyse the ester bond of triglycerides into
free fatty acid and glycerol.

Lipases are widely used in enzyme supplementation for treatment of


different digestive disorders.

Swami OC, et al. Int J Basic Clin Pharmacol. 2017;6(5):1035-1041.

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Lipase Enzyme Supplement

- Lipases are produced by plants, animals and microorganisms

- Higher level of importance is given to microbial lipases due to their following


attributes:
• Good catalytic activities
 Greater stability over wide pH
 High yields
 Simple genetic manipulation
 Faster growth of microorganisms on inexpensive media
 Good safety profile

Swami OC, et al. Int J Basic Clin Pharmacol. 2017;6(5):1035-1041.

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Activated Dimethicone for Bloating
 Bloating is one of the main symptoms of indigestion.1
 Dimethicone is a flexible silicone polymer which is used as an oral anti-foaming agent, anti-
flatulent and anti-bloating agent.1
 Activated dimethicone (also known as simethicone) is formed when dimethicone is mixed
with silicon dioxide. It relieves the pain bloating caused due to trapped gas.1
 Flatulence is relieved by activated dimethicone as it prevents mucus formation around the gas
pockets in the gastro-intestinal tract.1
 Activated dimethicone works by lowering the surface tension of the gas bubbles and then
forms a large gas bubble out of all the small bubbles, which is then expelled in the form of a
belch or flatus.1
 In a study, there was 60% reduction in severity of abdominal discomfort after use of activated
dimethicone.2

1. Medicine India. https://www.medicineindia.org/pharmacology-for-generic/1376/dimethicone.


2. Holtmann G, et al. Aliment Pharmacol Ther. 2002;16(9):1641-1648.

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Combination of Pancreatin and Activated Dimethicone

 Pancreatin, when combined with activated dimethicone, relieves indigestion


and its symptoms such as bloating and abdominal discomfort.1

 Lipase enzyme supplement is known to reduce fullness and early satiation.2

 Dimethicone relieves flatulence.3

1. Fiebr A et al. Clin exp gastroenterol. 2011;4:55-73.


2. Levine ME et al. Gut and liver. 2015 Jul;9(4):464.
3. Martindale, Pharmaceutical press 2011. 37th ed; vol b: 2591-2592.

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Role of Alpha Galactosidase as an Anti-flatulent

 Beans, vegetables (especially cruciferous vegetables like broccoli, cabbage,


and cauliflower), peanuts, lentils and heavy carbohydrate laden foods can
cause gassiness and bloating.

 These foods have carbohydrates that are linked to proteins or fats (known as
glycoproteins or glycolipids) which aren’t effectively broken down in the gut;
these poorly digested particles then serve as a food source for intestinal
bacteria.

 Alpha Galactosidase helps digest complex sugar and fat (glycoproteins and
glycolipids) which thus reduces intestinal gas formation and alleviate bloating
and flatulence.
Dig Dis Sci. 2007 Jan;52(1):78-83.

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Key Takeaway Points
 Indigestion is characterized by pain, bloating, postprandial fullness, belching, nausea and
vomiting. It is common in elderly and in diabetic population.
 Indigestion can be diagnosed mainly by medical history evaluation and physical examination.
Laboratory tests and upper gastrointestinal endoscopy may be done at specialist level.
 Lipids are a major trigger of indigestion symptoms, which are common after intake of fatty,
spicy food.
 Acid suppressants in combination with prokinetics are commonly used as first line therapy
for indigestion symptoms, but usually may be ineffective.
 Digestive enzyme supplements play a significant role in alleviating the symptoms of
indigestion. Lipase containing preparations should be chosen to provide holistic indigestion
management.
 Activated dimethicone (simethicone)/Alpha galactosidase act an an anti-flatulent in used for
the management of bloating.

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