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Non Celiac Gluten Sensitivity, By Dr. Millie Lytle ND, MPH, CNS


nutrition articles

April 2014

The Science behind a Gluten-Free Diet: Is Non-Celiac Gluten Sensitivity (NCGS) Evidence-Based Medicine?

By Dr. Millie Lytle ND, MPH, CNS

Background: Celiac Disease

Celiac disease (CD) is a unique autoimmune disorder that occurs in genetically susceptible individuals where symptoms arise after the ingestion of gluten, a protein found in wheat1 and other grains such as spelt, rye and barley. With CD, the immune system generates intestinal inflammation and subsequently induces degeneration of the delicate villi in the jejunum, an area of the small intestine. Even when CD is subclinical, which means immune and morphologic factors are not sufficient to yield a diagnosis, malabsorption syndrome can still result. The medical treatment for Celiac Disease is a gluten withdrawal diet. Risk of CD may decrease with delayed gluten exposure in infants, along with the presence of numerous and varied healthy gut bacteria2. However, despite 0.71% of the US population suffering from CD, only .5% of Americans are on gluten-free diets. What’s more, most people who follow a gluten-free diet have not been diagnosed with Celiac Disease3. There is posibly a period of Non-Celiac Gluten Sensitivity (NCGS) that precedes full-blown CD, and NCGS may exist in some individuals who will never go on to develop CD. Is there medical evidence that surpasses the gluten-free fad that shows that people without Celiac Disease can benefit from a gluten-free diet?

Introduction: Non-Celiac Gluten Sensitivity (NCGS)

There is a gluten-free diet craze going on right now. People are eliminating wheat and other grains from their diet to preserve and improve health, lose weight or just for the sake of trying something trendy. Newly-recognized conditions such as non-celiac gluten sensitivity (NCGS) are increasing awareness for physicians and patients alike, due to the clinical and anecdotal benefits of removing gluten from the diet. Let’s discuss the evidence on withdrawing gluten from the diet in people who do not have celiac disease.

NCGS is an intolerance of gluten that cannot be easily explained through typical celiac disease auto-immune testing. Despite increasing evidence for NCGS, this condition still remains a controversial topic with its disease process not well understood4. The estimated national prevalence of this new condition has been estimated at 0.548%, or half that of CD. To summarize the different types of gluten disorders:

1) Celiac Disease is a well-studied condition that has become a prevalent disease stemming from a heightened immune reaction to gluten.

2) Wheat Allergy is an Immunoglobulin E(IgE)-mediated condition that may cause a plethora of digestive symptoms.

3) NCGS has been recognized as early as the 1980s as a disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food in people who do not have CD or wheat allergy5.Some clinical results suggest the prevalence of NCGS may be significantly higher than that of CD in the US6 since the number of patients who have neither CD nor wheat allergy, but appear to benefit from a gluten-free diet, is evidently increasing4.


Leading NCGC gastroenterologist Dr. David A. Johnson from the University of Virginia Tech says that hybridization of gluten has possibly led to non-celiac gluten sensitivity7. As suspected, some people who do not have CD have symptoms that worsen when exposed to a 3-month gluten challenge, and subsequently benefit with a 3-week withdrawal of gluten. Researchers in one study have concluded that NCGS exists, but no clues to the mechanism were found8. Some alternative health practitioners feel that hybridization of wheat and other gluten-containing grains might not affect the first generation but have an accumulative effect down the genetic line, making it more difficult to pinpoint cause and effect. What hasn’t been researched are the affiliated foods and poor digestive health habits (acidic diet, constipation, antibiotic use, dysbiosis, antacid mediation use) that are partially responsible for poor intestinal health, thus predisposing the subject to gluten sensitivity. What has been revealed is that the complexities of wheat, along with its starchy carbohydrates and protein components such as gluten, can definitely trigger gastrointestinal symptoms in some people.

The Gluten-Free Diet (GFD):

In 2009-2010, the Continuous National Health and Nutrition Examination Survey (NHANES) enrolled 7762 Americans free of Celiac Disease. Results showed that among the 0.548% of the participants following the gluten-free-diet, women (0.58%) follow the gluten-free diet more than men (0.37%). In addition to a rapid relief of gastrointestinal symptoms, the gluten-free diet has been shown to provide more health benefits for those who follow it as compared to their peers who do not follow such a diet, including higher levels of good cholesterol and lower body mass index (BMI)6.

However, some researchers have concluded that just because people experience relief of their digestive symptoms when they eliminate gluten for a period of time, this does not equal diagnostic criteria for celiac disease, nor does it support long-term adherence to a gluten-free diet8. It has even been suggested by some medical experts that adherence to a gluten-free diet might cause nutrient deficiencies if people choose to eliminate grain-based products in the process. As more and more people attempt this diet and find relief, this conclusion is up for discussion as there are many gluten-free grains that can be included in the diet to counter the removal, such as rice, teff, quinoa, millet and amaranth.

NCGS and Comorbidities: IBS, Fibromyalgia, Autism, Schizophrenia

Irritable Bowel Syndrome (IBS)

Irritable Bowel Syndrome is an umbrella diagnosis based on lack of morphological cause for symptoms of intermittent constipation and diarrhea. Factors that may contribute to IBS include stress, anxiety, dietary intolerances, bacterial and viral infections, use of antibiotics and other medications, poor colon tone and dysbiosis. Not only are there similar etiologies between NCGS and IBS, but an overlap in occurrence has been detected as well. In one study of 34 patients aged 59-59 years, 56% met the immune criteria of CD9. Despite anti-gliadin antibodies not induced, on a visual analog scale patients’ overall symptoms were significantly worsened within one week of reintroducing gluten: pain, bloating, satisfaction with stool consistency, and tiredness9.Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia1.

Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm that patients with self-perceived NCGS have specific gluten sensitivity. Furthermore, the mechanism(s) by which gluten triggers symptoms has not yet been satisfactorily identified9. What complicates the issue further is that up until now, a lack of testing or biomarkers has been considered a major limitation for clinical trials, making it difficult to differentiate NCGS from a true wheat allergy or Celiac Disease. Additionally, recent research has raised the possibility that, in addition to gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates may worsen symptoms of IBS, as experienced by NCGS patients10.

IBS and Fibromyalgia

A review was conducted that looked at evidence and medical understanding of NCGS, and it was found that NCGS patients are a substantial subgroup of IBS patients highly treatable with dietary modifications. Gluten causes gastrointestinal symptoms by activating the immune system and generating inflammation and gut permeability (leaky gut). But researchers concluded that gluten is just one component of wheat and gluten-containing grains11.

Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are two common central sensitization disorders frequently associated in the same patient, and some of these patients with IBS plus fibromyalgia (IBS/FMS) may actually have undiagnosed Celiac Disease (CD). Seven subjects within the IBS/FMS group who were negative for CD but displayed mild immune markers for CD were started on a gluten-free diet (GFD). In follow up, they showed remarkable improvement in their systemic and digestive symptoms. Therefore, the researchers concluded that a significant number of IBS/FMS patients, while undiagnosed CD patients, can still improve symptoms and possibly prevent long-term CD-related complications with a strict lifelong GFD. This study is the first to show a clinical and immunological relationship to gluten, fibromyalgia and IBS.12

Gluten sensitivity might cause abdominal symptoms in the absence of CD (villous atrophy)13. IgG levels improved post-gluten withdrawal in CD patients and those with IBS not diagnosed with Celiac. This means that positive bloodwork results for serum IgG and immune HLA-DQ2 markers can signal potential responders to a gluten-free diet in IBS in patients who have not been diagnosed with NCGS or CD13.

Dietary Nutrients important for a Gluten-Free Diet

Flax Seed Powder and other nut and seed meals can be used as flour in baking and cooking as a substitute for flour. Flax seed powder can also be used as a substitute for eggs whites in baking and sauces. Flax seed is a natural source of soluble and insoluble fiber, minerals and antioxidant lignans, helping to improve transit time and bowel regularity. It also helps to metabolize harmful estrogens. Does your flour do that?

Probiotics are an excellent gluten-free supplement to address symptoms of irregular bowel movement, leaky gut and various food sensitivities. Probiotics support the gut, the immune system response in the intestines, restore villi and regulate digestion. Probiotics also help regulate serotonin receptors in the gut, improving depression and helping mood. Wow, flour does not do that!

Turmeric and Boswellia extracts are excellent anti-inflammatory herbs with an abundance of research behind them for bowel and colon health. They’ve been used to reduce inflammation in bowel conditions such as Crohn’s disease and colitis, as well as for polyps and colon cancer. They’re also great for joint and body pain that can be caused by consuming too much gluten and other food sensitivities. While flour can actually cause joint pain, these medicinal spices alleviate it.

L-Glutamine powder is the main amino acid for healing enterocytes, the cells of the small intestines. After years of eating the wrong foods, inflammation can damage the tight junctions of the intestines, causing inflammation and systemic symptoms. L-Glutamine can be taken twice or three times daily to address chronic digestive issues and systemic symptoms related to food sensitivities such as eczema, depression, inflammation. L-Glutamine can help heal the gut in long-standing food sensitivities, digestive issues and leaky gut syndrome.

Protein powders can be used in baking instead of flour. Choose vegetarian sources such as non-GMO Soy and Whey proteins to supplement flour. When using protein powders, consider their sweeteners and flavorings. For instance, vanilla-flavored protein powder is a great substitute for the flour, sugar and vanilla flavoring in cookies. You just need to add equal parts apple sauce to make up for the sugar you won’t be needing after all. Similarly, chocolate protein powder can be used in brownies or your favorite gluten-free chocolate bread pudding recipe.

To go completely gluten-free can be a challenge for many people who are accustomed to relying on bread, pasta, cereals and baked goods as staples in their diet. Once people are introduced to the wide variety of gluten-free options, how to read ingredients lists, and where to purchase alternatives, following a gluten-free diet becomes much more manageable. Switching from a bread-based diet can be a challenge, but much of it is about exposure and willingness to try something new. Research is strong on the possibility that Non-Celiac Gluten Sensitivity can be widely missed in those suffering from IBS and other digestive issues. NCGS, Celiac Sprue and disease sequelae may be rising in the public due to widespread use of the herbicide round-up and Genetic Modification of Food (GMO)14, creating a cited epidemic of kidney disease, iron and D3 deficiency, and other malabsorption syndromes. Although NCGS likely represents only the tip of the iceberg as it pertains to the role of food in IBS11, evidence now shows more sensitive biomarkers than previously understood.

Most importantly, Celiac Disease alone does not determine rationale for eliminating gluten from the diet. Routine care following a negative Celiac Disease test should include a gluten elimination period for those suffering from digestive conditions including IBS, and even mood disorders and fibromyalgia. Gluten elimination is strongly evidence-based, and shows increasing promise for populations who show signs of Celiac Disease but test negative for the actual disease.


1 Sharma TR, Kline DB, Shreeve DF, Hartman DW.Psychiatric comorbidities in patients with celiac disease: Is there any concrete biological association? Asian J Psychiat. 2011;4(2):150-1.

2 Sellitto M, et al. Proof of concept of microbiome–metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS ONE 7(3):e33387 (2012);

3 Rubio-Tapia ALudvigsson JFBrantner TLMurray JAEverhart JE. The prevalence of celiac disease in the United States. Am J Gastroenterol. 2012;107(10):1538-44.

4Mooney PD, Aziz I, Sanders DS. Non-celiac gluten sensitivity: clinical relevance and recommendations for future research. Neurogastroenterol Motil. 2013;25(11):864-71.

5 Bruins MJ. The clinical response to gluten challenge: a review of the literature. Nutrients. 2013;5(11):4614-41.

6 DiGiacomo DV, Tennyson CA, Green PH, Demmer RT. Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition Examination Survey 2009-2010. Scand J Gastroenterol. 2013;48(8):921-5.

7 Johnson, DA. Going Gluten-Free: Value Beyond Celiac Disease? Medscape Gastroenterology. Online March 04, 2013

8 Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106:508-514

9Biesiekierski JR, Muir JG, Gibson PR. Is gluten a cause of gastrointestinal symptoms in people without celiac disease? Curr Allergy Asthma Rep. 2013;13(6):631-8.

10Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, et al. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013;5(10):3839-53.

11Eswaran S, Goel A, Chey WD. What role does wheat play in the symptoms of irritable bowel syndrome? Gastroenterol Hepatol. 2013; 9:85-91.

12Rodrigo L, Blanco I, Bobes J, de Serres FJ. Remarkable prevalence of celiac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study. Arthritis Res Ther. 2013;15(6):R201.

13Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007;5:844-850. 

14Anthony Samsel A, Seneff S. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Interdisciplinary Toxicology. 2013; Vol. 6(4): 159–184.


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