Gluten Intolerance May Not Exist
In 2011, Peter Gibson, a professor of gastroenterology at Monash
University and director of the GI Unit at The Alfred Hospital in
Melbourne, Australia,
published a study that found gluten, a protein found in grains like
wheat, rye, and barley, to cause gastrointestinal distress in patients
without celiac disease, an autoimmune disorder unequivocally triggered
by gluten. Double-blinded, randomized, and placebo-controlled, the
experiment was one of the strongest pieces of evidence to date that non-celiac gluten sensitivity (NCGS), more commonly known as gluten intolerance, is a genuine condition.
By extension, the study also lent credibility to the meteoric rise of the gluten-free diet. Surveys now show that 30% of Americans
would like to eat less gluten, and sales of gluten-free products are
estimated to hit $15 billion by 2016 — that’s a 50% jump over 2013′s
numbers!
But like any meticulous scientist, Gibson wasn’t satisfied with his first study.
His research turned up no clues to what actually might be causing
subjects’ adverse reactions to gluten. Moreover, there were many more
variables to control!
What if some hidden confounder was mucking up the
results?
He resolved to repeat the trial with a level of rigor lacking
in most nutritional research. Subjects would be provided with every
single meal for the duration of the trial. Any and all potential dietary
triggers for gastrointestinal symptoms would be removed, including
lactose (from milk products), certain preservatives like benzoates,
propionate, sulfites, and nitrites, and fermentable, poorly absorbed
short-chain carbohydrates, also known as FODMAPs.
And last, but not least, nine days worth of urine and fecal matter
would be collected. With this new study, Gibson wasn’t messing around.
37 subjects took part, all confirmed not to have celiac disease but
whose gastrointestinal symptoms improved on a gluten-free diet, thus
fulfilling the diagnostic criteria for non-celiac gluten sensitivity.**
They were first fed a diet low in FODMAPs for two weeks (baseline),
then were given one of three diets for a week with either 16 grams per
day of added gluten (high-gluten), 2 grams of gluten and 14 grams of
whey protein isolate (low-gluten), or 16 grams of whey protein isolate
(placebo). Each subject shuffled through every single diet so that they
could serve as their own controls, and none ever knew what specific diet
he or she was eating. After the main experiment, a second was conducted
to ensure that the whey protein placebo was suitable. In this one, 22
of the original subjects shuffled through three different diets — 16
grams of added gluten, 16 grams of added whey protein isolate, or the
baseline diet — for three days each.
Analyzing the data, Gibson found that each treatment diet, whether
it included gluten or not, prompted subjects to report a worsening of
gastrointestinal symptoms to similar degrees. Reported pain, bloating,
nausea, and gas all increased over the baseline low-FODMAP diet. Even in
the second experiment, when the placebo diet was identical to the baseline diet, subjects reported a worsening of symptoms! The data clearly indicated that a nocebo effect, the same reaction that prompts some people to get sick from wind turbines and wireless signals,
was at work here. Patients reported gastrointestinal distress without
any apparent physical cause. Gluten wasn’t the culprit; the cause was
likely psychological. Participants expected the diets to make them sick,
and so they did. The finding led Gibson to the opposite conclusion of his 2011 research:
of the gastrointestinal problems attributed to gluten intolerance.
Jessica Biesiekierski, a gastroenterologist formerly at Monash
University and now based out of the Translational Research Center for Gastrointestinal Disorders at the University of Leuven in Belgium,* and
lead author of the study alongside Gibson, noted that when participants
consumed the baseline low-FODMAP diet, almost all reported that their
symptoms improved!
specifically bread products — are removed when adopting a gluten-free
diet, which could explain why the millions of people worldwide who swear
by gluten-free diets feel better after going gluten-free. Indeed, the rise in non-celiac gluten sensitivity seems
predominantly driven by consumers and commercial interests, not quality
scientific research.
“On current evidence the existence of the entity of NCGS remains unsubstantiated,” Biesiekierski noted in a review published in December to the journal Current Allergy and Asthma Reports.
Consider this: no underlying cause for gluten sensitivity has yet
been discovered. Moreover, there are a host of triggers for
gastrointestinal distress, many of which were not controlled for in
previous studies. Generally, non-celiac gluten sensitivity is assumed to
be the culprit when celiac disease is ruled out. But that is a “trap,”
Biesiekierski says, one which could potentially lead to confirmation
bias, thus blinding researchers, doctors, and patients to other
possibilities. Biesiekierski recognizes that gluten may very well be the stomach
irritant we’ve been looking for.
refining her experimental methods to determine whether or not non-celiac
gluten sensitivity truly exists.
“We need to make sure that this research is as well controlled as possible and is reproducible,” Biesiekierski told RCS, subsequently adding the quintessential adage of proper science.
Source:
Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR.
“No effects of gluten in patients with self-reported non-celiac gluten
sensitivity after dietary reduction of fermentable, poorly absorbed,
short-chain carbohydrates.” Gastroenterology. 2013 Aug;145(2):320-8.e1-3. doi: 10.1053/j.gastro.2013.04.051. Epub 2013 May 4.
Source: Biesiekierski JR, Muir JG, Gibson PR. “Is gluten a cause of gastrointestinal symptoms in people without celiac disease?” Curr Allergy Asthma Rep. 2013 Dec;13(6):631-8. doi: 10.1007/s11882-013-0386-4.
*Section updated 5/16 to reflect Dr. Biesiekierski’s new position.
**Section updated 5/16 to clarify that all of the subjects fulfilled the diagnostic criteria for NCGS.
In 2011, Peter Gibson, a professor of gastroenterology at Monash
University and director of the GI Unit at The Alfred Hospital in
Melbourne, Australia,
published a study that found gluten, a protein found in grains like
wheat, rye, and barley, to cause gastrointestinal distress in patients
without celiac disease, an autoimmune disorder unequivocally triggered
by gluten. Double-blinded, randomized, and placebo-controlled, the
experiment was one of the strongest pieces of evidence to date that non-celiac gluten sensitivity (NCGS), more commonly known as gluten intolerance, is a genuine condition.
By extension, the study also lent credibility to the meteoric rise of the gluten-free diet. Surveys now show that 30% of Americans
would like to eat less gluten, and sales of gluten-free products are
estimated to hit $15 billion by 2016 — that’s a 50% jump over 2013′s
numbers!
But like any meticulous scientist, Gibson wasn’t satisfied with his first study.
His research turned up no clues to what actually might be causing
subjects’ adverse reactions to gluten. Moreover, there were many more
variables to control!
What if some hidden confounder was mucking up the
results?
He resolved to repeat the trial with a level of rigor lacking
in most nutritional research. Subjects would be provided with every
single meal for the duration of the trial. Any and all potential dietary
triggers for gastrointestinal symptoms would be removed, including
lactose (from milk products), certain preservatives like benzoates,
propionate, sulfites, and nitrites, and fermentable, poorly absorbed
short-chain carbohydrates, also known as FODMAPs.
And last, but not least, nine days worth of urine and fecal matter
would be collected. With this new study, Gibson wasn’t messing around.
37 subjects took part, all confirmed not to have celiac disease but
whose gastrointestinal symptoms improved on a gluten-free diet, thus
fulfilling the diagnostic criteria for non-celiac gluten sensitivity.**
They were first fed a diet low in FODMAPs for two weeks (baseline),
then were given one of three diets for a week with either 16 grams per
day of added gluten (high-gluten), 2 grams of gluten and 14 grams of
whey protein isolate (low-gluten), or 16 grams of whey protein isolate
(placebo). Each subject shuffled through every single diet so that they
could serve as their own controls, and none ever knew what specific diet
he or she was eating. After the main experiment, a second was conducted
to ensure that the whey protein placebo was suitable. In this one, 22
of the original subjects shuffled through three different diets — 16
grams of added gluten, 16 grams of added whey protein isolate, or the
baseline diet — for three days each.
Analyzing the data, Gibson found that each treatment diet, whether
it included gluten or not, prompted subjects to report a worsening of
gastrointestinal symptoms to similar degrees. Reported pain, bloating,
nausea, and gas all increased over the baseline low-FODMAP diet. Even in
the second experiment, when the placebo diet was identical to the baseline diet, subjects reported a worsening of symptoms! The data clearly indicated that a nocebo effect, the same reaction that prompts some people to get sick from wind turbines and wireless signals,
was at work here. Patients reported gastrointestinal distress without
any apparent physical cause. Gluten wasn’t the culprit; the cause was
likely psychological. Participants expected the diets to make them sick,
and so they did. The finding led Gibson to the opposite conclusion of his 2011 research:
“In contrast to our first study… we could find absolutely no specific response to gluten.”Instead, as RCS reported last week, FODMAPS are a far more likely cause
of the gastrointestinal problems attributed to gluten intolerance.
Jessica Biesiekierski, a gastroenterologist formerly at Monash
University and now based out of the Translational Research Center for Gastrointestinal Disorders at the University of Leuven in Belgium,* and
lead author of the study alongside Gibson, noted that when participants
consumed the baseline low-FODMAP diet, almost all reported that their
symptoms improved!
“Reduction of FODMAPs in their diets uniformly reducedCoincidentally, some of the largest dietary sources of FODMAPs —
gastrointestinal symptoms and fatigue in the run-in period, after which
they were minimally symptomatic.”
specifically bread products — are removed when adopting a gluten-free
diet, which could explain why the millions of people worldwide who swear
by gluten-free diets feel better after going gluten-free. Indeed, the rise in non-celiac gluten sensitivity seems
predominantly driven by consumers and commercial interests, not quality
scientific research.
“On current evidence the existence of the entity of NCGS remains unsubstantiated,” Biesiekierski noted in a review published in December to the journal Current Allergy and Asthma Reports.
Consider this: no underlying cause for gluten sensitivity has yet
been discovered. Moreover, there are a host of triggers for
gastrointestinal distress, many of which were not controlled for in
previous studies. Generally, non-celiac gluten sensitivity is assumed to
be the culprit when celiac disease is ruled out. But that is a “trap,”
Biesiekierski says, one which could potentially lead to confirmation
bias, thus blinding researchers, doctors, and patients to other
possibilities. Biesiekierski recognizes that gluten may very well be the stomach
irritant we’ve been looking for.
“There is definitely something goingCurrently, Biesiekierski is focused on maintaining an open mind and
on,” she told RCS, “but true NCGS may only affect a very small
number of people and may affect more extraintestinal symptoms than first
thought. This will only be confirmed with an understanding of its
mechanism.”
refining her experimental methods to determine whether or not non-celiac
gluten sensitivity truly exists.
“We need to make sure that this research is as well controlled as possible and is reproducible,” Biesiekierski told RCS, subsequently adding the quintessential adage of proper science.
“Much, much more research is needed.”This article was first published at RealClearScience.
Source:
Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR.
“No effects of gluten in patients with self-reported non-celiac gluten
sensitivity after dietary reduction of fermentable, poorly absorbed,
short-chain carbohydrates.” Gastroenterology. 2013 Aug;145(2):320-8.e1-3. doi: 10.1053/j.gastro.2013.04.051. Epub 2013 May 4.
Source: Biesiekierski JR, Muir JG, Gibson PR. “Is gluten a cause of gastrointestinal symptoms in people without celiac disease?” Curr Allergy Asthma Rep. 2013 Dec;13(6):631-8. doi: 10.1007/s11882-013-0386-4.
*Section updated 5/16 to reflect Dr. Biesiekierski’s new position.
**Section updated 5/16 to clarify that all of the subjects fulfilled the diagnostic criteria for NCGS.
