Lactose intolerance

Question 1

Lactose is a

Answer 1

◦ disaccharide
 composed of galactose and glucose
◦ found in all mammalian milks
 Human – 5.7-7.2% lactose
 Cow – 5%
 Sheep – 4.8%
 Goat – 4.1%

Question 2

Lactase Nonpersistence?

Answer 2

indicates that brush border lactase activity is only a
small fraction of the infantile level
- 70% of world population

Question 3

Lactose Malabsorption defined

Answer 3

indicates that a sizable fraction of a dosage of lactose
is not absorbed in the small bowel and thus is
delivered to the colon

Question 4

Lactose Intolerance defined

Answer 4

indicates that the malabsorbed lactose produces
symptoms (diarrhea, abdominal discomfort, flatulence,
or bloating)
 this symptomatic response is linked to the
quantity of lactose malabsorbed

Question 5

Why don’t all people with Lactose
Malabsorption have Lactose Intolerance?

Answer 5

◦ no one knows for certain
 rate of gastric emptying
 rate of intestinal transit
 role of visceral hypersensitivity
 role of colonic flora

Question 6

Lactose Intolerance
 S&S

Answer 6

 first described by Hippocrates some 400 years BCE
◦ Gastrointestinal
 Loose stools and/or increased stool frequency
 rarely constipation
 Abdominal bloating and distension
 Abdominal pain/cramps
 Flatulence
 Borborygmii
 Nausea and vomiting (rarely)

Question 7

Lactose Intolerance
 Possible Systemic S&S?

Answer 7

 Muscle and joint pain
 Headaches
 Dizziness
 Lethargy
 Difficulty with short-term memory
 Sore throat
 Increased frequency of micturition
 Acne
 Depression
 Pruritis

May be more related to the ingestion of milk
proteins or other factors in cow’s milk than
lactose

Question 8

Lactose Intolerance – Importance of
Dose
 S&S are Dose-Related –
◦ tolerable dose differs if lactose is consumed with
versus without other nutrients

Answer 8

Lactose Intolerance – Importance of
Dose
 S&S are Dose-Related –
◦ tolerable dose differs if lactose is consumed with
versus without other nutrients

Question 9

Secondary Lactose Intolerance ?

Answer 9

loss of lactase activity in people with lactase persistence or infants

Question 10

Secondary Lactose Intolerance onset?

Answer 10

occurs as a result of any trauma or illness that damages the microvilli of the small intestine
 Giardiasis (Rana et al, 2005)
 Gastroenteritis (Lifshitz et al, 1971)
 Ascaris lumbricoides infection (Carrera et al, 1984)
 Celiac disease (Bode and Gudmand-Hoyer, 1988)
 Radiotherapy (Stryker et al, 1978)(Andreyev, 2007)
 Chemotherapy (Parnes et al, 1994)(Osterlund et al, 2004)
 Rotaviral gastroenteritis (Vesa et al, 2000)
◦ Small Intestinal Bacterial Overgrowth (SIBO)

Question 11

Lactose Intolerance
 Diagnosis ?

Answer 11

◦ Breath testing
 typically administer 25-50g lactose in single dose and
analyse excreted gases
 test result is considered abnormal if there is a rise in hydrogen of
more than 20 ppm above baseline (Law et al, 2010)
 78% sensitivity & 93% specificity (Hovde and Farup, 2009)
 hydrogen non-excretion can occur in up to 20% of patients with
LM
 hydrogen and methane tests – 100% sensitivity & 90% specificity
(Hovde and Farup, 2009)
 Early rise in hydrogen and/or methane indicative of SIBO
 positive rise in gases at/before the 80/90 mins mark of the test
otherwise if lactose reaches colon, you see rise in gases more at 120 minutes post ingestion

Diagnosis –
◦ Lactose challenge
 Unblinded
 24 hour observation of GIT S&S post-lactose load (25g) (Hovde and Farup, 2009)
 any symptoms starting within 5 h after intake of lactose and lasting for
more than 2 h
 86% sensitivity & 78% specificity
 50g lactose load – assess GIT S&S over the next 3 hours (Beyerlein et al, 2008)
 bloating – 70% sensitivity & 69% specificity
 borborygmi – 65% sensitivity & 75% specificity
 diarrhea – 39% sensitivity & 90% specificity
 82% of subjects who developed all 5 symptoms (abdo pain, nausea,
bloating, borborygmi and diarrhea) had a +ve HBT
 Blinded
 some would argue the “gold-standard” for diagnosing lactose intolerance

Question 12

Lactose Intolerance
 Blinded Lactose Challenge?

Answer 12

◦ a clinically-useful, inexpensive tool for diagnosing
lactose intolerance
◦ two tubs - labelled A and B
◦ put 25g lactose in one tub and 25g glucose (aka
dextrose) in the other
 keep track of which is which!
 patient does not know the contents of each container
◦ get patient to mix entire contents into 250ml
warm water and drink on an empty stomach first
thing in the morning
◦ patient observes S&S over the 5 hours

Question 13

Lactose Intolerance
 Conditions associated with

Answer 13

◦ IBS
 LM diagnosed in 68% of Italian IBS sufferers (Vernia et al, 1995)
 LM detected in 24% of IBS patients vs 6% of controls (Bohmer & Tuynman, 1996)
◦ Celiac disease
 high prevalence of CD in those previously diagnosed with LI (Ojetti et al,
2005)
◦ Crohn’s disease
 83% of Crohn’s patients (active) had LI (von Tirpitz et al, 2002)
 49% of Crohn’s patients in remission (Eadala et al, 2011)
◦ Fructose intolerance
 LI subjects more likely to malabsorb fructose (Mishkin et al, 1997)
◦ Autism
 lactase deficiency found in 58% of autistic kids <5 yo and 65% of
older children (Anglo-American population)

Question 14

Lactose Intolerance - Management
 Probiotics – Strain Specific Efficacy

Answer 14

◦ utilise strains with demonstrated efficacy
 Lactobacillus casei Shirota and Bifidobacterium breve
Yakult
 Lactobacillus acidophilus LA-5 (Lin et al, 1991)
 Previously named strain LA-1
 Lactobacillus acidophilus DDS-1

Question 15

what is lactulose?

Answer 15

◦ semi-synthetic disaccharide
◦ prebiotic
◦ produced from lactose

Question 16

Lactose Intolerance - Management
 Lactulose benefits?

Answer 16

 Lactose challenge after 3 wks lactulose
 H2
excretion - 43% reduction (P<0.02)
 4 hr symptom score - 52% reduction (P<0.05)
 threefold increase in stool β-galactosidase activity

Question 17

Lactose Intolerance - Management
 Lactulose WARNING?

Answer 17

◦ Warning – lactose malabsorbers may
experience more S&S at commencement of
lactulose therapy than lactose digesters (Teuri et al, 1999)
 start cautiously (i.e., low dose)

Question 18

Lactose Intolerance - Management
 Galactooligosaccharides (GOS)

Answer 18

◦ Azcarate-Peril et al, 2017
 Lactose tolerance after GOS treatment:
 71% (25/35) reported reduction of at least one symptom (pain,
bloating, diarrhea, cramping, or flatulence) at day 33
 69% (24/35) reported symptom reduction at day 66 when eating
lactose containing foods
 Microbiota changes after GOS:
 increased relative abundance of Faecalibacterium, Bifidobacterium,
and Lactobacillus
 increases seen in a number of Bifidobacterium species

Question 19

Lactose Intolerance - Management
 Intestinal Adaptation –

Answer 19

◦ continued daily ingestion of lactose results in
adaptation (Hertzler and Savaiano, 1996)(Briet et al, 1997)(Pribila et al, 2000)
 reduced values on HBT
 reduced GIT S&S
◦ via alterations in the colonic microflora
 increased β-galactosidase activity
 modification of H2 handling (e.g., methane
production)

Question 20

Lactose Intolerance - Management
 Treatment of Secondary Lactose
Intolerance –

Answer 20

◦ strategies discussed above:
 low lactose diet
 supplemental lactase
 appropriate probiotic strain supplementation
 lactulose or GOS supplementation
 lactose colonic adaptation
◦ treat the SIBO (if present)
 See Week 6 content

◦ Promote healing of the small intestine
 Saccharomyces cerevisiae var boulardii Biocodex
strain
 improves intestinal disaccharidase activity (Buts et al, 1986)
 77% upregulation of intestinal lactase activity
 has healing effect on small intestinal mucosa
 trophic effects on the small intestine (Buts et al, 1994)
 promotes normalisation of villi post-trauma (Guillot et al, 1995)
 Glutamine
 primary fuel source for enterocytes
 speeds healing of damaged enterocytes