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Report: Lactose intolerance in
clinical practice
Ritika-Mahmuda Ahmed



1

Introduction
Lactose intolerance, also known as hypolactasia, is defined as a common digestive problem
where the body is unable to digest lactose, a a type of sugar mainly found in milk and dairy
products
...


Molecular structure of lactose shown below

The possession of mammary glands for milk production for their
offspring is a unique feature of mammals and human milk has the
highest concentration of lactose
...
The glucose and galactose are then transported across the
lining of the small intestine
...
Usually milk and dairy
products are avoided to elevate symptoms however some people are
able to tolerate small amounts of these products throughout the day
whilst still controlling symptoms
...
2g per 100 ml of lactose in
mature human milk and 4
...
Some marine mammals such as
seals, walruses and sea lions have almost no lactose in their milk and are therefore lactose
intolerant as their body naturally does not have the enzyme to break down lactose as it is never
needed
...
In
humans however lactose provides an excellent source of energy during infancy as this is a time of
rapid growth and development
...
The H of the -OH group on carbon 1
of galactose is replaced by an organic part
A glycoside is a molecule in which a sugar is bound to another group via a glycosidic
bond
A beta-galactoside is a type of galactoside in which the the glycosidic bond lies above
the plane of the galactose residue

Composition
•

The enzyme itself consists of two subunits: galactosyltransferase and alphalactalbumin

Alpha-lactalbumin:
• It is the primary protein in human milk and is extremely important for infant nutrition
• Composed of 123 amino acids and 4 disulphide bridges
• Calcium binding protein that may have a role in calcium transport
• Rich in amino acid cysteine which is a which is a building block of glutathione, a
powerful antioxidant in the body that plays an important role in immunity
• It is a modifier subunit that causes galactosyltransferase to transfer galactose to
glucose
• During pregnancy alpha-lactalbumin levels are high but are controlled through
hormones and increase significantly when prolactin levels in the later stages of
pregnancy increase
• Therefore, lactose is produced in mammal milk only when needed

Active sites
•
•
•

The enzyme has two active sites: one hydrolysing lactose and the other hydrolysing
phlorizin and a range of other dietary glycolipids
Phlorizin is a glucoside and a glucoside is a glycoside derived from glucose
Continued activity on the phlorizin site explains why enzyme activity is still present after
the usual decrease in enzyme expression after weaning from breast milk

3

Production of the enzyme
220 kDA precursor peptide

Post-transcriptional
modification during
transport to the cell

150 kDA mature protein

Location
•

•
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Lactase is found on the apical surface of
enterocytes and the highest number is in the
mid jejunum
...
It stands for uridine
diphosphate galactose

Glucose:
•

Used for production of ATP

Absorption:
•

Both glucose and galactose are absorbed by the intestinal enterocytes

5

Lactase activity during pregnancy and early life:
Pregnancy
•
•
•

Lactase activity detected at mucosal surface in small intestine
Mucosal surface: linings covered in epithelium which are involved in absorption and
secretion
Up to week 34: increased lactase activity

Birth and early life
•
•
•

Birth: Lactase activity at its peak
First few months after birth: lactase activity decreases = lactase non-persistence
30% of human population has continued lactase activity beyond weaning and into
adulthood —> usually north european descent

North Europeans:
Explanation for persistence
•
•

Relates to introduction of dairy farming 10 000 years ago
Lactase persistence was rare in northern Europe before dairy farming

Types of lactase deficiency:
Congenital
Least lactase activity
• Lifelong disorder
• Failure to thrive
• Can lead to infantile diarrhoea: infection/irritation of the digestive tract
• Extremely rare —> 40 cases in the world until now
• Single autosomal recessive disorder: 2 alleles need to be present for disease to
occur
• Treatment: avoid lactose from birth
•

Primary lactase deficiency (non-persistence)
•
•

Lactase activity decreases after birth
Occurs in majority of humans

Secondary lactase deficiency
•
•
•

Patient originally persistent
Gastrointestinal illness may occur —> damages brush border of small intestine —>
lactose cannot be absorbed
However this is reversible with treatment

6

Lactase activity
•
•
•
•
•

Only 50% of lactase activity needed
Lactase only present when necessary
Persistence due to a mutation in the lactase gene
Non-persistence = wild type
Wild type = it is the allele that encodes the phenotype most common in a particular
natural population
...
In
genetic shorthand it is “+”
...

No singe allele is considered as the standard sequence
...
C
...

5% of British intolerant
17% of Finnish intolerant
In South America, Africa and Asia ==> over 50% non-persistence
Some countries in Asia have 100% non-persistance
Mixed ethnicity = low prevalence
Native ethnic group = high prevalence
Rate of loss of lactase activity varies according to ethnicity
The exact physiological explanation is unknown
Japanese and Chinese lose 80-90% of activity after 3-4 years after weaning
Jews and Asians lose 60-7-% of activity after several years post-weaning
Northern Europeans take up to 20 years to reach lowest lactase activity

8

Diagnosis
Early studies
•
•

Glucose levels measured following 50g intake of lactose
Increase in levels ==> high lactase activity (after 30 mins)

Recent methods
•
•

Jejunal biopsies used: small pieces of tissue removed from lining of jejunum
...

This method is not very effective

Hydrogen breath test
•
•
•
•

50g of lactose taken orally (equal to the amount in 1litre of milk)
Measures hydrogen levels the following 3-6 hours
If the levels are more than 20ppm then it indicates lactose intolerance
Better to measure it after 6 hours

False-negativies
False negativies can occur where there is no excretion of hydrogen
...
Methane producing bacteria use hydrogen to reduce carbon dioxide to methane
2
...
This indicates towards lactose malabsorption but there were no
previous symptoms due to other dietary restrictions
...
(Definition
taken from http://en
...
org/wiki/Genotyping)
Quick and easy
High specificity for lactase gene
It can help differentiate between primary hypolactasia and secondary hypolactasia
However clinically not available yet

Symptoms
•
•
•
•
•
•
•
•

Abdominal pain
Bloating
Flatus
Diarrhoea
Borborygmi: stomach rumble
Occasional vomit and nausea and vomit in extreme cases
Constipation due to methane production
Decreased gastrointestinal motility: Ability to move and actively consume energy in the
process

Lactose stays in the digestive system where it is fermented by bacteria leading to the
production of gases such as hydrogen, methane and carbon dioxide and also short chain
fatty acids
...

The sodium moves down its electrochemical gradient and brings glucose or galactose in
against the concentration gradient
Therefore, lactose intolerant individuals are unable to reabsorb water which causes the
watery diarrhoea

Cow’s milk allergy
•
•

20% of patients with symptoms which would could be linked to lactose intolerance may
have cow’s milk allergy therefore care should be taken when describing symptoms
Very rare in adults

Undetected lactose intolerance
•

In one study of lactose intolerance, 52% of patients did not link their symptoms with
lactose intake

10

•
•

People with definite non-persistence and a history of intolerance were given high
amounts of lactose while blindfolded but this did not cause significant symptoms
Excluding lactose does not always elevate symptoms which could indicate another
problem such as irritable bowel syndrome (IBS)

Intestinal microflora, fermentation and fermented foods
•
•

The gastrointestinal tract has a minimum of 17 bacterial families with over 500 species
having been classified
Highest concentration in the colon with levels up to 1012-13 per mL luminal contents
...

Diet affects symptoms
Lactose intolerance does NOT lead to IBS
IBS patients however are more sensitive to lactose than healthy patients
In two studies 24-27% of IBS patients also had lactose maldigestion
45% of IBS patients have intolerance
30% of those related their symptoms to milk and dairy products
After dietary exclusions only 53% reported improvements
Some IBS patients without maldigestion describe symptoms of intolerance
Studies showed that lactose-free milk causes the same symptoms as lactose, indicating
IBS

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Lactose in food and pharmaceuticals
•
•
•
•
•
•
•
•
•
•

Widely used in food industry
Ingredient for processed food
Bulking agent/filler in pharmaceuticals
Half as sweet as glucose
Has about one sixth of the sweetness of sucrose
Not easily fermented by yeast and does not lead to production of carbon dioxide
There has been a dramatic increase in lactose production: in 1979 about 50 million kg
per year was made but in 2004 300 million kg per year was made
Used as a browning gent
Added to processed chicken
Production of soft drinks and lager beers

Lactose Intake, Restriction, Re-introduction and
nutritional adequacy
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•
•
•
•
•
•
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•
•
•
•
•
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Currently no national UK guidelines for managing lactose intolerance
Lactose non-persistence does not always lead to lactose intolerance
Consuming small amounts of lactose containing food throughout the day should not
lead to severe symptoms
Should the patient have lactose intolerance then a diet plan should be made and
symptom history should be studied
Intolerance should be tested properly before being confirmed
Re-introduction of lactose should be attempted to make sure any unnecessary diet
exemption are not made
This is important as dairy products are needed for calcium intake
If enough calcium is not taken at an early age the likelihood of developing osteoporosis
earlier increases
Current calcium intake recommendation for women over 19 or pregnant women: 125o
mg per day
For men it is 700mg per day
Despite lactose intolerance calcium is still absorbed by the small intestine from dairy
and milk products
After not having lactose for a period of time 12g of lactose could be taken throughout
the whole day
The re-introduction of lactose can help decrease symptoms of lactose intolerance
This suggests that lactose is a prebiotic

If lactose was left in the small intestine for a longer time hydrolysis would take place for
longer which means the symptoms of lactose intolerance decrease
...
Furthermore, unhydrolysed lactose in the small
intestine may be fermented which can help the individual in improving their tolerance of
lactose
...


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