For more than 30 years, the medical profession has debated the existence of an intolerance to the wheat protein, gluten, unrelated to allergy or celiac disease. What is the evidence pro and con?
Is Gluten Sensitivity Real?
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In 1980, researchers in England reported a series of women who suffered from chronic diarrhea that resolved on a gluten-free diet, yet didn’t have evidence of celiac disease, the autoimmune disorder associated with gluten intolerance. The medical profession was skeptical at the time, and even 30 years later, so much so, that much like patients who had irritable bowel syndrome, patients claiming non-celiac gluten sensitivity were commonly referred to psychiatrists because they were believed to have an underlying mental illness. Psychological testing of such patients, however, found no evidence that they were suffering from some psychosomatic hysteria.
The medical profession has a history of dismissing diseases as all in people’s heads—PTSD, ulcerative colitis, migraines, ulcers, asthma, Parkinson’s and MS. Despite resistance from the prevailing medical community each time, however, these health problems have subsequently been confirmed to be credible physiologically-based disorders rather than psychologically-based confabulations.
On the flipside, the internet is rife with unsubstantiated claims about gluten-free diets, which has spilled over into the popular press to make gluten the diet villain du jour. Claims like ‘17 million Americans are gluten sensitive.’ However, it must be remembered that this is also ‘big business.’
When literally billions are at stake it’s hard to trust anybody, so as always, best to stick to the science. What sort of evidence do we have for the existence of a condition presumed to be so widespread?
Not much. The evidence base for such claims was unfortunately very thin because we didn’t have randomized controlled trials demonstrating that the entity even exists. The gold-standard for confirming non-celiac gluten sensitivity requires a gluten-free diet, followed by a double-blind, randomized, placebo-controlled food challenge. Like they give you a muffin and you’re not told if it’s gluten-free or gluten-filled—to control for placebo effects—and see what happens. The reason this is necessary is because when you actually do this, a number of quote-unquote “gluten-sensitive” patients don’t react at all to disguised gluten and instead react to the gluten-free placebo. So it was truly ‘in their heads.’
But we never had that level of evidence until… 2011, when a double-blind, randomized placebo-controlled trial was published, which tested to see if patients complaining of irritable bowel symptoms who claimed they felt better on a gluten-free diet—despite not having celiac disease—actually could tell if they were given gluten-containing bread and muffins or the placebo gluten-free bread and muffins.
They started out gluten-free and symptom-free for two weeks and then they were challenged with the bread and muffins. Here’s what happened to the 15 patients who got the placebo, meaning they started out on a gluten-free diet and continued on a gluten–free diet. They got worse. Just the thought that they may be eating something that was bad for them made them feel crampy and bloated. This is what’s called the nocebo effect. The placebo effect is when you give someone something useless and they feel better; the nocebo effect is when you give someone something harmless and they feel worse. But the small group that got the actual gluten, felt worse still. So, they concluded, this non-celiac gluten intolerance thing may actually exist.
It was a small study, though, and even though they claimed the gluten-free bread and muffins were indistinguishable, maybe at some level the patients could tell which was which. So in 2012, researchers in Italy took 920 patients that had been diagnosed with non-celiac gluten sensitivity and put them to the test with a double-blinded wheat challenge by giving them capsules of filled with wheat flour or filled with placebo powder. And more than 2/3’s failed the test, like they got worse on the placebo or better on the wheat. But of those that passed, there was a clear benefit to staying on the wheat-free diet, confirming the existence of a non-celiac wheat sensitivity. Note they said wheat sensitivity, not gluten sensitivity.
Gluten itself may not be causing gut symptoms at all. See most people with wheat sensitivity have a variety of other food sensitivities. Two thirds are sensitive to cow’s milk protein as well, then eggs were the most common culprit.
So if you put people on a diet low in common triggers of irritable bowel symptoms and then challenge them with gluten, there’s no effect. Same increase in symptoms with high gluten, low gluten or no gluten, calling into question the very existence of non-celiac gluten sensitivity.
Interestingly, despite being informed that avoiding gluten wasn’t apparently doing a thing for their gut symptoms, many participants opted to continue following a gluten-free diet as they subjectively described “feeling better,” so the researchers wondered if avoiding gluten might be improve the mood of those with wheat sensitivity and indeed, short-term exposure to gluten appeared to induce feelings of depression in these patients. But whether non-celiac gluten sensitivity is a disease of the mind or the gut, it is no longer a condition that can be dismissed.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- I Aziz, M Hadjivassiliou, D S Sanders. Does gluten sensitivity in the absence of coeliac disease exist? BMJ 2012 345(NA):e7907
- P D Mooney, I Aziz, D S Sanders. Non-celiac gluten sensitivity: Clinical relevance and recommendations for future research. Neurogastroenterol. Motil. 2013 25(11):864 – 871.
- I Aziz, M Hadjivassiliou, D S Sanders. Editorial: Noncoeliac gluten sensitivity--a disease of the mind or gut? Aliment. Pharmacol. Ther. 2014 40(1):113 – 114.
- A Carroccio, P Mansueto, G Iacono, M Soresi, A D'Alcamo, F Cavataio, I Brusca, A M Florena, G Ambrosiano, A Seidita, G Pirrone, G B Rini. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity. Am. J. Gastroenterol. 2012 107(12):1898 - 906 - quiz – 1907.
- J R Biesiekierski, E D Newnham, P M Irving, J S Barrett, M Haines, J D Doecke, S J Shepherd, J G Muir, P R Gibson. Gluten causes gastrointestinal symptoms in subjects without celiac disease: A double-blind randomized placebo-controlled trial. Am. J. Gastroenterol. 2011 106(3):508 - 14 - quiz – 515.
- P Nijeboer, H J Bontkes, C J J Mulder, G Bouma. Non-celiac Gluten Sensitivity. Is it in the Gluten or the Grain? J Gastrointestin Liver Dis 2013 22(4):435 – 440.
- J R Biesiekierski, S L Peters, E D Newnham, O Rosella, J G Muir, P R Gibson. 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 145(2):320 - 8 - e1 – 3.
- S L Peters, J R Biesiekierski, G W Yelland, J G Muir, P R Gibson. Randomised clinical trial: Gluten may cause depression in subjects with non-coeliac gluten sensitivity - an exploratory clinical study. Aliment. Pharmacol. Ther. 2014 39(10):1104 – 1112.
- P Mansueto, A Seidita, A D'Alcamo, A Carroccio. Non-celiac gluten sensitivity: Literature review. J Am Coll Nutr 2014 33(1):39 – 54.
- S J Genuis. Sensitivity-related illness: The escalating pandemic of allergy, food intolerance and chemical sensitivity. Sci. Total Environ. 2010 408(24):6047 – 6061.
- M Brottveit, P O Vandvik, S Wojniusz, A Lovik, K E Lundin, B Boye. Absence of somatization in non-coeliac gluten sensitivity. Scand. J. Gastroenterol. 2012 47(7):770 – 777.
- A Di Sabatino, GR Coraza. Nonceliac gluten sensitivity: sense or sensibility? Ann Intern Med. 2012 Feb 21;156(4):309-11.
- BT Cooper, GK Holmes, R Ferguson, RA Thompson, RN Allan, WT Cooke. Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology. 1980 Nov;79(5 Pt 1):801-6.
- CC Ferch, WD Chey. Irritable bowel syndrome and gluten sensitivity without celiac disease: separating the wheat from the chaff. Gastroenterology. 2012 Mar;142(3):664-6. Epub 2012 Jan 24.
Images thanks to feeb via Flickr.
In 1980, researchers in England reported a series of women who suffered from chronic diarrhea that resolved on a gluten-free diet, yet didn’t have evidence of celiac disease, the autoimmune disorder associated with gluten intolerance. The medical profession was skeptical at the time, and even 30 years later, so much so, that much like patients who had irritable bowel syndrome, patients claiming non-celiac gluten sensitivity were commonly referred to psychiatrists because they were believed to have an underlying mental illness. Psychological testing of such patients, however, found no evidence that they were suffering from some psychosomatic hysteria.
The medical profession has a history of dismissing diseases as all in people’s heads—PTSD, ulcerative colitis, migraines, ulcers, asthma, Parkinson’s and MS. Despite resistance from the prevailing medical community each time, however, these health problems have subsequently been confirmed to be credible physiologically-based disorders rather than psychologically-based confabulations.
On the flipside, the internet is rife with unsubstantiated claims about gluten-free diets, which has spilled over into the popular press to make gluten the diet villain du jour. Claims like ‘17 million Americans are gluten sensitive.’ However, it must be remembered that this is also ‘big business.’
When literally billions are at stake it’s hard to trust anybody, so as always, best to stick to the science. What sort of evidence do we have for the existence of a condition presumed to be so widespread?
Not much. The evidence base for such claims was unfortunately very thin because we didn’t have randomized controlled trials demonstrating that the entity even exists. The gold-standard for confirming non-celiac gluten sensitivity requires a gluten-free diet, followed by a double-blind, randomized, placebo-controlled food challenge. Like they give you a muffin and you’re not told if it’s gluten-free or gluten-filled—to control for placebo effects—and see what happens. The reason this is necessary is because when you actually do this, a number of quote-unquote “gluten-sensitive” patients don’t react at all to disguised gluten and instead react to the gluten-free placebo. So it was truly ‘in their heads.’
But we never had that level of evidence until… 2011, when a double-blind, randomized placebo-controlled trial was published, which tested to see if patients complaining of irritable bowel symptoms who claimed they felt better on a gluten-free diet—despite not having celiac disease—actually could tell if they were given gluten-containing bread and muffins or the placebo gluten-free bread and muffins.
They started out gluten-free and symptom-free for two weeks and then they were challenged with the bread and muffins. Here’s what happened to the 15 patients who got the placebo, meaning they started out on a gluten-free diet and continued on a gluten–free diet. They got worse. Just the thought that they may be eating something that was bad for them made them feel crampy and bloated. This is what’s called the nocebo effect. The placebo effect is when you give someone something useless and they feel better; the nocebo effect is when you give someone something harmless and they feel worse. But the small group that got the actual gluten, felt worse still. So, they concluded, this non-celiac gluten intolerance thing may actually exist.
It was a small study, though, and even though they claimed the gluten-free bread and muffins were indistinguishable, maybe at some level the patients could tell which was which. So in 2012, researchers in Italy took 920 patients that had been diagnosed with non-celiac gluten sensitivity and put them to the test with a double-blinded wheat challenge by giving them capsules of filled with wheat flour or filled with placebo powder. And more than 2/3’s failed the test, like they got worse on the placebo or better on the wheat. But of those that passed, there was a clear benefit to staying on the wheat-free diet, confirming the existence of a non-celiac wheat sensitivity. Note they said wheat sensitivity, not gluten sensitivity.
Gluten itself may not be causing gut symptoms at all. See most people with wheat sensitivity have a variety of other food sensitivities. Two thirds are sensitive to cow’s milk protein as well, then eggs were the most common culprit.
So if you put people on a diet low in common triggers of irritable bowel symptoms and then challenge them with gluten, there’s no effect. Same increase in symptoms with high gluten, low gluten or no gluten, calling into question the very existence of non-celiac gluten sensitivity.
Interestingly, despite being informed that avoiding gluten wasn’t apparently doing a thing for their gut symptoms, many participants opted to continue following a gluten-free diet as they subjectively described “feeling better,” so the researchers wondered if avoiding gluten might be improve the mood of those with wheat sensitivity and indeed, short-term exposure to gluten appeared to induce feelings of depression in these patients. But whether non-celiac gluten sensitivity is a disease of the mind or the gut, it is no longer a condition that can be dismissed.
To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.
Please consider volunteering to help out on the site.
- I Aziz, M Hadjivassiliou, D S Sanders. Does gluten sensitivity in the absence of coeliac disease exist? BMJ 2012 345(NA):e7907
- P D Mooney, I Aziz, D S Sanders. Non-celiac gluten sensitivity: Clinical relevance and recommendations for future research. Neurogastroenterol. Motil. 2013 25(11):864 – 871.
- I Aziz, M Hadjivassiliou, D S Sanders. Editorial: Noncoeliac gluten sensitivity--a disease of the mind or gut? Aliment. Pharmacol. Ther. 2014 40(1):113 – 114.
- A Carroccio, P Mansueto, G Iacono, M Soresi, A D'Alcamo, F Cavataio, I Brusca, A M Florena, G Ambrosiano, A Seidita, G Pirrone, G B Rini. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity. Am. J. Gastroenterol. 2012 107(12):1898 - 906 - quiz – 1907.
- J R Biesiekierski, E D Newnham, P M Irving, J S Barrett, M Haines, J D Doecke, S J Shepherd, J G Muir, P R Gibson. Gluten causes gastrointestinal symptoms in subjects without celiac disease: A double-blind randomized placebo-controlled trial. Am. J. Gastroenterol. 2011 106(3):508 - 14 - quiz – 515.
- P Nijeboer, H J Bontkes, C J J Mulder, G Bouma. Non-celiac Gluten Sensitivity. Is it in the Gluten or the Grain? J Gastrointestin Liver Dis 2013 22(4):435 – 440.
- J R Biesiekierski, S L Peters, E D Newnham, O Rosella, J G Muir, P R Gibson. 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 145(2):320 - 8 - e1 – 3.
- S L Peters, J R Biesiekierski, G W Yelland, J G Muir, P R Gibson. Randomised clinical trial: Gluten may cause depression in subjects with non-coeliac gluten sensitivity - an exploratory clinical study. Aliment. Pharmacol. Ther. 2014 39(10):1104 – 1112.
- P Mansueto, A Seidita, A D'Alcamo, A Carroccio. Non-celiac gluten sensitivity: Literature review. J Am Coll Nutr 2014 33(1):39 – 54.
- S J Genuis. Sensitivity-related illness: The escalating pandemic of allergy, food intolerance and chemical sensitivity. Sci. Total Environ. 2010 408(24):6047 – 6061.
- M Brottveit, P O Vandvik, S Wojniusz, A Lovik, K E Lundin, B Boye. Absence of somatization in non-coeliac gluten sensitivity. Scand. J. Gastroenterol. 2012 47(7):770 – 777.
- A Di Sabatino, GR Coraza. Nonceliac gluten sensitivity: sense or sensibility? Ann Intern Med. 2012 Feb 21;156(4):309-11.
- BT Cooper, GK Holmes, R Ferguson, RA Thompson, RN Allan, WT Cooke. Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology. 1980 Nov;79(5 Pt 1):801-6.
- CC Ferch, WD Chey. Irritable bowel syndrome and gluten sensitivity without celiac disease: separating the wheat from the chaff. Gastroenterology. 2012 Mar;142(3):664-6. Epub 2012 Jan 24.
Images thanks to feeb via Flickr.
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Title
Is Gluten Sensitivity Real?
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
More than 10,000 articles have been published on gluten in medical journals—intimidating even for me! Combined with the multi-billion dollar financial interests on both sides, it makes for a difficult task. But I think I did it! This is the first of a 3-part video series summarizing the best available science on gluten. The others are: Gluten-Free Diets: Separating the Wheat from the Chat and How to Diagnose Gluten Intolerance.
Why this apparent increase in food sensitivities in recent decades? It could be because of pollutant exposure (see Alkylphenol Endocrine Disruptors and Allergies and Dietary Sources of Alkylphenol Endocrine Disruptors).
You might also be interested in my newer 2022 video, The Potential Harm in Unnecessary Gluten-Free Diets.
What can we do about preventing so-called atopic diseases (like allergies, asthma, and eczema)? See my videos Preventing Allergies in Adulthood and Childhood. The weirdest example of an emerging food sensitivity may be the tick-bite related meat allergy story I review in Alpha Gal and the Lone Star Tick and Tick Bites, Meat Allergies, and Chronic Urticaria.
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