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6/13/2018
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Carlo Di Lorenzo, M.D
Twitter: @carlodilorenzo1
'Fake News' in GI: Getting to the Truth
about Gluten, PEG 3350 and PPIs
Disclosure
I have the following financial relationships with the
manufacturer(s) of commercial product(s) and/or
provider of commercial services discussed in this CME
activity:
Consultant for: Sucampo, Merck, Allergan, QOL Inc
I do intend to discuss unapproved/investigative uses of
commercial products/devices in my presentation.
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Social media and “fake news” bring a new challenge per
physicians
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The way people see science news nowadays
Why so many “fake news” in GI and Nutrition?
Powerful combination of uncertainty,
public interest, influences of industry and
celebrities
Everybody eats, everybody experiences GI
symptoms
Challenging to do blinded studies in
nutrition science
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• Exposure to gluten causes celiac disease
• Celiac disease affects ~1% of US people
• Celiac disease is easy to diagnose (Ig A
and tTG)
• Avoidance of gluten is the only treatment
for celiac disease
Facts about gluten
Myth
Going gluten free makes me healthier and
improves my athletic performance
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The influence of “celebrities”
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How Many People in the US Are
Embracing a GFD?
Percentage of U.S. Adults Trying to Cut Down or Avoid Gluten in Their Diets Reaches New High in 2013, Reports NPD
Gluten (or Wheat) related disorders
Wheat Allergy~0.1%
Celiac Disease1%
Non-celiacGluten Sensitivity
?%
No gene associated
Largely IgE-mediated
Children and Bakers
HLA-DQ2, DQ8
Autoimmune disease
Any age
No gene associated
Immune-mediated?
Mostly adults
Serum specific IgE
CD autoantibodiesBiopsy
Nodiagnostic marker
There are 3Gluten - related disorders
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*Consumer reports
Who is on a gluten free diet?
Reasons for avoiding gluten
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Reasons for avoiding gluten
Where is the evidence that eliminating gluten helps?
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Collectively the whole group
reported the most severe symptoms
after placebo (P = .012).
The present study showed that the majority of patients
with suspected NCGS are not able to identify when
challenged with gluten in a double-blind placebo-
controlled food challenge, indicating that gluten is not
the cause of their symptoms.
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Does going gluten free enhance sport performance?
Med Sci Sport Exerc 2015; 47:2563-70
Any downside of a gluten free diet?
s
Excess
De
ficie
ncie
s
Zinc
Magnesium
Iron
Vit. B
Vit. D
Calcium
Folate
Dietary Fiber
Kcal intake
Simple CHO
Saturated fats
Lipids
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Test for celiac disease before stopping
gluten
Discourage stopping gluten for other
health benefits or athletic improvement
Monitor for excessive weight gain and
nutrient deficiencies children on a gluten
free diet
Gluten: take home messages
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It has been on the market since 1999
Probably the most investigated drug in pediatric GI
(efficacy for clean-outs and maintenance,
comparative, colonoscopy prep, different ages)
High prevalence of constipation in children with
behavioral and psychiatric disorders
PEG 3350 recommended as 1st line rx in current
practice guidelines
Facts about PEG 3350
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Concerns about PEG 3350
Williams KC, et al. J Pediatr 2018
• Neuropsychiatric events such as seizures, tremors, tics,
anxiety, lethargy, aggression, paranoia, mood swings,
and obsessive–compulsive behaviors such as repetitive
chewing and sucking have been observed in patients
receiving PEG 3350 for treatment of constipation
• PEG 3350 might contain trace amounts of ethylene
glycol, diethylene glycol, and triethylene glycol and
these might contribute to neuropsychiatric adverse
events in children
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Are children with ASD at risk for defecation disorders?
Constipation, flatulence and diarrhea more common in
children with ASD than in normal children and children
with other neurodevelopmental disorders (Autism
2009;13:343-55)
Constipation (33% vs 17%) was more common in youth
with autism than in a control population in Olmstead
County (Pediatrics 2009; 124:680-6)
“ASD are one order of magnitude more common in the
constipation clinic than in the general population” (Pediatr
Surg Int 2011;27:353-8)
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“But PEG is in antifreeze!”
http://www.stepin2mygreenworld.com/healthyliving/health/8-foods-that-contain-common-anti-freeze-ingredient/
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But remember, there is nothing special about PEG 3350; it is not the
“Miracle” laxative
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Recovered
Improved
0
10
20
30
40
50
60
70
PEG MOM1 month
follow-up
PEG MOM3 month
follow-up
PEG MOM6 month
follow-up
PEG MOM12 monthfollow-up
%Children whoimproved or recovered
Effect of PEG 3350 vs Milk of Magnesia
Loening-Baucke V et al. Pediatrics 2006; 118:528
PEG vs MOM: P =ns
Compliance rates with the treatment
were 95% for PEG and 65% for MOM
A lot of success can be achieved in childhood
constipation with behavioral interventions
PEG 3350 still to be considered an effective
AND safe treatment for constipated children
No significant advantage of PEG 3350 over
other laxatives in terms of efficacy
When palatability and compliance are an issue,
I still use PEG 3350
PEG 3350: take home messages
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Facts about acid suppression
• Problem of erosive esophagitis has been
solved
• PPI-responsive EoE
• Protection from NSAID induced gastro-
duodenal lesions
• Helps with GI bleeding
• Acid suppression is overused
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FDA and PPI in children
https://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-
Education/Pharmacy-Education-Materials/Downloads/ppi-pediatric-factsheet11-14.pdf
The problem
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Overuse of PPI
Percent of NICU admissions, where lansoprazole,ranitidine, or metocolpramide was administered,among 4 NICUs within a single healthcare system
Barney CK, et al. Advances in Neonatal Care 2009,9:129-131
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Can an accurate diagnosis of infant GERD be based upon symptoms
such as “irritability”?
Diagnosis of GERD in infants?
• Symptoms including regurgitation, colic/irritability, and vomiting are common among otherwise normal infants (Iacono G et al, Dig Liver Dis, 2005;37:432-8)
• Symptoms of GER are indistinguishable from those of food allergy (Venter C , et al JACI 2006;1118; Sampson H.A.
JACI 2004;806, Savino F et al Eur J Clin Nutr. 2006;1304)
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It may make more sense to switch the formula than to
start acid suppression. But if you do, please switch to
a hydrolysate formula
Also important to remember
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Total minutes of crying per day in normal infants
Age (mo) 1-3 4-6 7-9 10-12
Crying time
(min)
121 +/- 105 59 +/-67 72 +/-101 54+/-79
James-Roberts and Halil, J Child Psychol Psychiat 1991;52:951
GERD or
Normalor
Other
Hot off the press
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Besides being ineffective when not used for the right indication, are they actually
bad for you?
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Complications of PPI
Potential risks of prolonged acid suppression
• Effects on vitamins and mineral absorption: IronCalcium Magnesium Vitamin B12
• Infections: Pneumonia C. Difficile Small bowel bacterial overgrowth Other enteric infections
• Necrotizing enterocolitis and candidemia
• Interstitial nephritis (rare, idiosyncratic reaction)
• Myocardial infarction
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Clostridium Difficile: Retrospective study in children
Aliment Pharmacol Ther. 2010;31:754-9
Recurrent C. Difficile
Risk is further increased by concomitant use of antibiotics and
PPI, whereas H2RAs may be less harmful
Kwok CL et al. Am J Gastroenterol 2012;107:1011-9
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Pediatrics 2012;129:e40–e45
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Decreased acid barrier
Altered microbiome
Attenuation of the immune response
Direct effects of the bacteria
Decreased effectiveness of antibiotics
Stark CM et al. J Pediatr 2016;168:16-22
Recently published and all over the lay press…
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Gomm W, et al. JAMA Neurol. 2016 Feb 15
Dementia• 73,679 participants >75 y/o and free of dementia at baseline
• Patients receiving regular PPI medication (n = 2950) were found to have a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70,729)
Difference between association and causation
(courtesy of Jose Garza, MD)
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Take home messages
Prolonged acid suppression should be
used when really needed
Try to wean
Increased risk of infection probably real
Metabolic consequences and increased
risk for MI and dementia not convincingly
demonstrated
Final bit of wisdom in this era
of fake news
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