Clinical studies concerning non-Celiac gluten sensitivity

Many studies have demonstrated that non-Celiac gluten sensitivity (NCGS) is significantly related to various health conditions, however others have also shown no relationship.  A statement concerning the definition of NCGS and scientific interest in NCGS from the reference below:

 

“GS (gluten sensitivity), which this review will focus on primarily, is a condition in which symptoms are triggered by gluten ingestion, in the absence of celiac-specific antibodies and of classical celiac villous atrophy, with variable Human Leukocyte Antigen (HLA) status and variable presence of first generation anti-gliadin antibodies (AGA). The ‘labeling’ of this disorder was a matter of debate among the panel experts. In order to avoid confusion with CD (Celiac disease), sometimes defined as gluten-sensitive enteropathy, “non celiac gluten sensitivity” (NCGS) appeared as an improved definition.”

 

“The publications on CD doubled every 20 years from approximately 2500 in the period of 1950–70 to ~9500 in the period 1991–2010, with already more than 2000 papers published between 2011 and 2013. Conversely, there were almost no scientific reports on NCGS before 1970 and only a handful number of papers have been published ever since, most of them after 2005. The increase interest in NCGS is testified by the decreased NCGS/CD publication ratio that dropped from 1:438 in the period 1950–70 to 1:10 in the period 2010–13.”

 

  • Catassi C, et al.  Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.  Nutrients. 2013 Sep 26;5(10):3839-53. http://tinyurl.com/mwcf2ep

 

Considering that this reflects roughly 1000 studies pertaining to NCGS in the last 25 years with close to 200 in the last 2 years, my summary here will obviously be grossly incomplete but I will try to highlight some of the different medical conditions for which some aspect of gluten sensitivity is being considered.

 

Studies report the prevalence of NCGS to be between 0.55 – 6%.  NCGS is characterized (in individuals for which Celiac disease has been excluded) by symptoms which occur after gluten ingestion, are improved (within hours or days) after elimination, with relapse following gluten introduction.  NCGS patients commonly report a personal history of food allergy and atopy in infancy.

 

  • Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. http://tinyurl.com/k2zymrx

 

A recent clinical study which broadly assessed symptoms in 78 patients (56 females and 22 males; median age: 38 years) associated with NCGS reported the following:

 

“The most frequent gastrointestinal symptoms were abdominal pain and bloating, often associated and present in 77% and 72% of cases, respectively, followed by diarrhea (40%) and constipation (18%). Approximately 20% of our patients complained of gastroesophageal reflux disease and 10% of our patients complained of aphthous stomatitis. Among extra-intestinal signs, the most frequent symptom was mental confusion or a ‘foggy mind’, defined as a sensation of lethargy elicited by gluten, observed in 42% of cases, followed by fatigue (36%), skin rash (33%), headache (32%), joint and muscle pain (fibromyalgia-like syndrome) (28%), leg or arm numbness (17%), depression and anxiety (15%) and anemia (15%).”

 

·         Volta U, Caio G, Tovoli F, De Giorgio R. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness. Cell Mol Immunol. 2013 Sep;10(5):383-92. http://tinyurl.com/nurd7z4

 

Beyond the things listed here, some of the recent publications pertaining to NCGS are listed below.  Topics which I did not find publications and significant clinical evidence for this relationship yet have seen symptoms greatly improve include urinary incontinence and Hashimoto’s thyroiditis and there are certainly others.

 

Some recent reviews which may be the most useful (and may be more comprehensive than the list below!):

 

·         Volta U, et al.  An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med. 2014 May 23;12:85. http://tinyurl.com/kqts3b5

·         Catassi C, et al.  Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.  Nutrients. 2013 Sep 26;5(10):3839-53. http://tinyurl.com/mwcf2ep

·         Sapone A, et al.  Spectrum of gluten-related disorders: consensus on new nomenclature and classification.  BMC Med. 2012 Feb 7;10:13. http://tinyurl.com/p8eddgr

·         Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906. http://tinyurl.com/9psmxab

·         Kushnir, NM.  Gluten Induced Systemic Disease (GISD) with Distinct Clinical Phenotype Different from Celiac Disease.  World Allergy Organ J. Feb 2012; 5(Suppl 2): S157. http://tinyurl.com/pbxkj5a

 

Gastrointestinal:

Irritable bowel syndrome:

·         Vazquez-Roque MI, et al.  A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013 May;144(5):903-91. http://tinyurl.com/mjvxfmd

Inflammatory bowel disease:

·         Herfarth HH, et al.  Prevalence of a gluten-free diet and improvement of clinical symptoms in patients with inflammatory bowel diseases. Inflamm Bowel Dis. 2014 Jul;20(7):1194-7. http://tinyurl.com/nu4wozn

 

Neurological:

General hypothesis:

·         Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. http://tinyurl.com/opkdfh8

 

Autism:  Clinical studies in this area have primarily looked at a gluten-free, casein-free diet.

·         Lau NM, et al. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155. http://tinyurl.com/ple57xz

·         Whiteley P, et al. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100. http://tinyurl.com/l59cep4

·         Millward C, et al. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003498. http://tinyurl.com/lbjck7x

Schizophrenia:

·         Cascella NG, et al.  Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients. Schizophr Bull. 2013 Jul;39(4):867-71.  http://tinyurl.com/k84k5u3

·         Dickerson F, et al.  Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4. http://tinyurl.com/oeka8vf

Cognition:

·         Perlmutter, D.  Rethinking Dietary Approaches for Brain Health.  Alternative and Complementary Therapies. April 2014, 20(2): 73-75. http://tinyurl.com/lud3js8

Bipolar disorder:

·         Dickerson F, et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disord. 2011 Feb;13(1):52-8. http://tinyurl.com/c46kv7b

·         Dickerson F, et al. Markers of gluten sensitivity in acute mania: a longitudinal study. Psychiatry Res. 2012 Mar 30;196(1):68-71. http://tinyurl.com/ka3tw6m

 

Cerebellar ataxia:

·         Nanri K, et al.  Gluten ataxia in Japan. Cerebellum. 2014 Oct;13(5):623-7. http://tinyurl.com/pa29j3m

Neuropathy:

·         Anderson B, Pitsinger A. Improvement in chronic muscle fasciculations with dietary change: a suspected case of gluten neuropathy. J Chiropr Med. 2014 Sep;13(3):188-91. http://tinyurl.com/of5rbtb

Fibromyalgia:

·         Isasi C, et al. Fibromyalgia and non-celiac gluten sensitivity: a description with remission of fibromyalgia. Rheumatol Int. 2014 Apr 12. http://tinyurl.com/lc2wk9q
 

Renal:

IgA Nephropathy:

·         Smerud HK, et al.  Gluten sensitivity in patients with IgA nephropathy. Nephrol Dial Transplant. 2009 Aug;24(8):2476-81. http://tinyurl.com/pyf9x35

 

Endocrine:

Diabetes:

·         Auricchio R, et al.  In vitro-deranged intestinal immune response to gliadin in type 1 diabetes. Diabetes. 2004 Jul;53(7):1680-3.  http://tinyurl.com/nme5yj6

Thyroid:

·         Valentino R, et al. Markers of potential coeliac disease in patients with Hashimoto's thyroiditis. Eur J Endocrinol. 2002 Apr;146(4):479-83. http://tinyurl.com/33fas8e

 

 

Some studies below for which no effect was demonstrated:

 

IBS: Interesting to note that gluten was demonstrated to not have an effect but reduction of FODMAPs foods did.

·         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. http://tinyurl.com/nbzuk8c

 

Autism:

·         Batista IC, et al. Autism spectrum disorder and celiac disease: no evidence for a link. Arq Neuropsiquiatr. 2012 Jan;70(1):28-33. http://tinyurl.com/mrcmepw

 

 

I hope this information is helpful.  Do note that my summary here reflects a positive bias towards the connection between NCGS and various disease conditions – as it is a non-pharmacological intervention with minimal adverse effects I often consider it (as well as other dietary interventions) as an initial approach.  As this list is not inclusive of all studies pertaining to this topic, please feel free to comment with a study you would like to share!

 

In health,

Dr. Decker