PREVALENCE OF ADVERSE REACTIONS TO FOODS

2006 2014

PREVALENCE Adults 3-4% Adults 5%

Children 6% Children 8%

INCIDENCE OF 0.6/1000 patients 1.3/1000 patients

FOOD-INDUCED
HOSPITALIZATIONS

Sicherer SA et al, JACI 2006

Sicherer SH & Sampson HA, JACI 2014
Rudders SA et al, JACI 2014
PREVALENCE OF ALLERGY ACCORDING TO DIAGNOSTIC TEST

Peanuts, milk, egg, fish, crustaceans

Self-reported symptoms - children 12%
Self-reported symptoms – adults 13%
Symptoms plus SPT 3%
Food challenge 3%

Fruits, vegetables/legumes, tree nuts, wheat, soy

Self-reported symptoms 0.02-8.5%
SPT 0.02-4.2%
Food challenge 0.1-4.3%

Rona RJ et al, JACI 2007

Zuidmeer L et al, JACI 2008
SYMPTOM PATTERN FOLLOWING A MEAL CHALLENGE IN FD AND IBS

FUNCTIONAL DYSPEPSIA

Fullness
Pain
Bloating
Nausea
Belching
Epigastric burning

IBS
Bisshops R et al, Gut 2008

Posserud I et al, UEGJ 2013

PREVALENCE OF POSTPRANDIAL SYMPTOMS IN IBS

Bohn et al, Simren et al, Di Stefano et al,

AJG 2013 Digestion 2001 NGM 2016
100

80
Prevalence (%)

60

40

20

0
FOODS CAUSING MODERATE/SEVERE SYMPTOMS IN IBS
Food Questionnaire Number of foods causing symptoms
and IBS severity

Bohn L et al, AJG 2013

Number of food items causing
symptoms (score) and IBS subtypes

Simren M et al, Digestion 2001 Simren M et al, Digestion 2001

 BRAN AND IBS: TIME FOR REAPPRAISAL

Fibre source Better (%) Worse (%) Unchanged (%)

Bran 10 55 33
Cornflakes 0 0 100
Rice Crispies 0 0 100
Porridge 0 12 88
Muesli 0 27 73
Vegetables 3 25 72
Fruit 5 45 50
Pulses 0 25 75
Nuts 0 27 73

Francis & Whorwell, Lancet 1994

PREVALENCE OF SELF-REPORTED FOOD INTOLERANCE IN IBS

Incompletely absorbed carbohydrates

Bohn L et al, AJG 2013

PREVALENCE OF SELF-REPORTED FOOD INTOLERANCE IN IBS

Histamine-releasing

Bohn L et al, AJG 2013

SUMMARY OF HISTAMINE-MEDIATED SYMPTOMS

Diarrhea

Epigastric
Pain, Cramps

Bloating

Maintz L & Novak N, Am J Clin Nutr 2007

 HISTAMINE PRODUCTION AND INACTIVATION PATHWAY

EXTRACELLULAR PATHWAY INTRACELLULAR PATHWAY

Negative Negative
Feedback Feedback
Loop Loop

Maintz L & Novak N, Am J Clin Nutr 2007

DAO SNP AND DAO mRNA EXPRESSION IN PBMCs

CONTROLS WT SNP +

P = 0.002

Maintz L et al, Allergy 2011

SERUM DAO IN IBS WITH AND WITHOUT POSTPRANDIAL SYMPTOMS

IBS with IBS without

Postprandial Postprandial
Symptoms Symptoms
16

12
Serum DAO
(U/ml)

P<0.01
 DAIRY PRODUCTS AND INTOLERANCE SYMPTOMS

Incompletely absorbed carbohydrates

Histamine-releasing

Bohn L et al, AJG 2013

 PATHOPHYSIOLOGY OF CARBOHYDRATE MALABSORPTION

DIET CARBOHYDRATE

MALABSORBED MALABSORPTION
CARBOHYDRATE

OSMOTIC BACTERIAL
EFFECT FERMENTATION

 WATER SCFA
H2 CO2 CH4

DIARRHOEA, ACID STOOLS, PAIN,  INTESTINAL GAS

CARBOHYDRATE INTOLERANCE
DIARRHOEA, ABDOMINAL PAIN, BLOATING, FLATULENCE
 BREATH TESTS AND SMALL BOWEL

­[H2] OR [13CO2] IN
THE EXPIRED AIR

TEST
SOLUTION

BACTERIA

1st Department of Internal Medicine

University of Pavia
 LACTOSE-RELATED SYMPTOMS REPORTED BY PATIENTS

Diarrhea Abdominal Bloating Abdominal Flatus Borborygmi Epigastric Regurg Heartburn Nausea
100 Pain Distention Pain

80
Prevalence (%)

60

40

20

Di Stefano M et al, FISMAD 2010

 PREVALENZA DELL’INTOLLERANZA

28 pazienti

Breath test al lattosio

15 13
positivi negativi

9 4
12 3
hanno non hanno
intolleranti non intolleranti
riferito sintomi riferito sintomi
 PREVALENCE OF SYMPTOMS DURING LACTOSE BREATH TEST

Patients with Lactose Malabsorption

100 Diarrhea Abdominal Bloating Abdominal Flatus Borborygmi Epigastric Regurg Heartburn Nausea
Pain Distention Pain
80
Prevalence (%)

60

40

20

Patients with Normal Lactose Absorption

100 Diarrhea Abdominal Bloating Abdominal Flatus Borborygmi Epigastric Regurg Heartburn Nausea
Pain Distention Pain
80
Prevalence (%)

60

40

20

Di Stefano M et al, FISMAD 2010

 A RANDOMIZED, DOUBLE-BLIND, CROSSOVER TRIAL
IN SELF-REPORTED SEVERE LACTOSE INTOLERANT PATIENTS

80
Change in Breath H2 Concentration (ppm)

Ordinary Hydrolyzed p
Symptoms
milk milk
60 (240 ml) (240 ml)

Lactose Malabsorbers (21)

21
40 Bloating 0.6 ± 0.1 0.5 ± 0.1 ns
Abdominal pain 0.4 ± 0.1 0.3 ± 0.1 ns
Diarrhea (episodes/day) 0.1 ± 0.0 0.3 ± 0.1 ns
20 Flatus (episodes/day) 10.1 ± 1.5 7.6 ± 1.2 ns

0 Lactose Absorbers (9)

9 Bloating 0.6 ± 0.2 0.5 ± 0.2 ns
Abdominal pain 0.6 ± 0.2 0.4 ± 0.2 ns
Diarrhea (episodes/day) 0.3 ± 0.2 0.2 ± 0.1 ns
-20
Flatus (episodes/day) 11.8 ± 2.3 8.4 ± 1.9 ns
0 1 2 3 4 5
Time (hrs)

Suarez et al, NEJM 1995

SEVERITY OF SYMPTOMS IN LACTASE NONPERSISTENT PATIENTS
One cup of lactose-containing milk twice One cup of lactose-hydrolyzed milk twice
Abdominal Pain Bloating Borborygmi
5 Intolerants Tolerants 5 Intolerants Tolerants 5 Intolerants Tolerants


Mean Symptom score/24 h

Mean Symptom score/24 h

Mean Symptom score/24 h

4 4 4

3 3 3

2 2 2

1 1 1

0 0 0

5 Diarrhea Perceived flatus severity Flatus frequerncy

Intolerants Tolerants
5 Intolerants Tolerants
20 Intolerants Tolerants


Mean Symptom score/24 h

Mean Symptom score/24 h

4 4
15

Number/24 h
3 3
10
2 2
5
1 1

0 0 0

Suarez FL et al, Am J Clin Nutr 1997

 SEVERITY OF SYMPTOMS IN LACTOSE MALABSORBERS

Lact+ Lact -
240 ml milk with breakfast and dinner 240 ml lactose-hydrolyzed milk with breakfast and dinner
1 serving of hard cheese at lunch and dinner 1 serving of hard cheese at lunch and dinner
240 ml yogurt at lunch 240 ml lactose-hydrolyzed yogurt at lunch

Pain Bloating Flatulence

5 Basal Lact+ Lact- 5 Basal Lact+ Lact- 5 Basal Lact+ Lact-

4 4
  4 
Severity Score
Severity Score

Severity Score
3 3 3

2 2 2

1 1 1

0 0 0

Lactose intolerance is not an impediment to the intake of 1500 mg

calcium daily as dairy products

Suarez FL et al, Am J Clin Nutr 1998

 DENSITA’ MINERALE OSSEA
E MALASSORBIMENTO DI LATTOSIO

Malassorbenti Normoassorbenti
Lombare Femore Lombare Femore
0
Densità Minerale Ossea

-0,1

-0,2
(g/cm2)

-0,3

-0,4

-0,5
 METABOLISMO OSTEO-MINERALE
E MALASSORBIMENTO DI LATTOSIO

Normoassorbenti Malassorbenti P

Calcio (mmol/L) 2.39±0.15 2.34±0.15 NS

PTH (pg/mL) 32±6 50±9 NS
25-vitamina D (ng/mL) 29±9 32±8 NS
1,25-vitamina D (pg/mL) 24±9 32±8 NS
PICP (g/L) 134±22 145±32 NS
ICTP (g/L) 2.3±0.3 3.0±0.8 NS
 DENSITA’ MINERALE OSSEA, MALASSORBIMENTO E
INTOLLERANZA AL LATTOSIO

Lombare Femore
Malassorbenti Normo- Malassorbenti Normo-
assorbenti assorbenti
2 Intolleranti Tolleranti Intolleranti Tolleranti
Densità Minerale Ossea

1
(z-score)

-1

-2
p<0.001 NS p<0.001 NS
p<0.01 p<0.01
 METABOLISMO OSTEO-MINERALE,
MALASSORBIMENTO E INTOLLERANZA AL LATTOSIO

Normoassorbenti Malassorbenti

Tolleranti Intolleranti

Calcio (mmol/L) 2.39±0.15 2.35±0.14 2.31±0.15

PTH (pg/mL) 32±6 49±9 54±9
25-vitamina D (ng/mL) 29±9 30±8 35±9
1,25-vitamina D (pg/mL) 24±9 29±8 35±9
PICP (g/L) 134±22 140±31 159±35
ICTP (g/L) 2.3±0.3 2.9±0.8 3.8±0.9

P<0.05
 CORRELAZIONE TRA DENSITA’ MINERALE OSSEA E
SEVERITA’ DEI SINTOMI

r=0.73 r=0.74
p=0.001 p=0.001
Score

Score
DMO Lombare (z-score) DMO Femorale (z-score)
 INTROITO ALIMENTARE DI CALCIO,
MALASSORBIMENTO E INTOLLERANZA AL LATTOSIO

Normoassorbenti Malassorbenti
Intolleranti Tolleranti
1000
Intake di Calcio (mg/die)

750

500

250

0
P<0.001
 CORRELAZIONE TRA INTROITO ALIMENTARE DI
CALCIO, DENSITA’ MINERALE OSSEA E SEVERITA’
DEI SINTOMI

Introito di Ca P

DMO Lombare 0.69 0.001

DMO Femorale 0.73 0.001
Score dei Sintomi -0.77 0.001
 RISCHI DELL’INTOLLERANZA AL LATTOSIO

• L’intolleranza al lattosio interferisce con il

raggiungimento di un adeguato picco di massa ossea

• La severità dei sintomi ed un ridotto apporto di calcio

sembrano essere i meccanismi responsabili

• La diagnosi ed il trattamento di questa condizione

dovrebbero quindi essere particolarmente tempestivi
ORAL CARBOHYDRATE LOAD AND MALABSORPTION

Lactose Lactose
20g 10g
100
Σ 5,6,7 hr breath excretion

80

60
(ppm)

40

20
Normal range

Di Stefano M et al, 2009

INTOLERANCE AND DAIRY PRODUCT INTAKE

Shaw AD et al, J Clin Gastroenterol 1999

VISCERAL HYPERSENSITIVITY AND INTOLERANCE SYMPTOMS IN
LACTOSE MALABSORPTION

Di Stefano M et al, NeuroGastroenterol Motil 2007

FACTORS DETERMINING SYMPTOMS IN LACTOSE INTOLERANCE

No Severe
Symptoms Symptoms

Lactase activity

Lactose load

Gastric emptying rate

Transit rate

Colonic compensation
FOOD INTOLERANCE: SCIENCE-DRIVEN OR INDUSTRY-DRIVEN?

Spence D, BMJ 2013

 LACTASE GENETIC POLYMORPHISM AND LACTOSE BT
Pts Age C-13910 G-22018 H2-BT Symptoms
1 19 OMO OMO POS SI
2 20 OMO OMO POS SI
3 20 OMO OMO POS SI
4 21 OMO OMO POS SI
5 22 OMO OMO POS SI
6 23 OMO OMO POS SI
7 24 OMO OMO POS SI
8 25 OMO OMO POS SI
9 26 OMO OMO POS SI
10 28 OMO OMO POS SI
11 37 OMO OMO POS SI
12 41 OMO OMO POS SI
13 47 OMO OMO POS SI
14 50 OMO OMO POS SI
15 51 OMO OMO POS SI
16 66 OMO OMO POS SI
17 25 OMO OMO POS NO
18 32 OMO OMO POS NO
19 36 OMO OMO POS NO
20 36 OMO OMO POS NO
21 46 OMO OMO POS NO
22 50 OMO OMO POS NO
23 76 OMO OMO POS NO
24 17 OMO OMO NEG NO
25 22 OMO OMO NEG NO
26 23 OMO OMO NEG NO
27 18 ETERO ETERO NEG NO
28 28 ETERO ETERO NEG NO
29 30 ETERO ETERO NEG NO
30 40 ETERO ETERO NEG NO
31 45 ETERO ETERO NEG NO
32 50 ETERO ETERO NEG SI

Di Stefano M et al, DLD 2008

AGREEMENT BETWEEN LACTOSE BT AND SNP OF LACTASE GENE

Agreement

Age

Di Stefano M et al, DLD 2008

NOCEBO EFFECT IN PATIENTS UNDERGOING LACTOSE BREATH TEST

N=40
MALABSORBERS NORMAL ABSORPTION
n=27 n=13

Symptom Symptom Symptoms

No Symptoms
ONLY ALSO after
symptoms after lactose
after lactose after glucose glucose

n=6 n=12 n=13 n=2 n=7

Intolerants NOCEBO ? Tolerants NOCEBO NOCEBO

Di Stefano M et al, 2017

RECOMMENDATIONS OF NIH CONSENSUS ON LACTOSE INTOLERANCE
TEST

Detailed History

Lactose- or Elimination
gluten-related Diet +
symptoms Symptom diary

DBPCT Diagnosis
H2-BT

Diagnosis
GRAZIE PER LA VOSTRA
ATTENZIONE !!!