Gluten Part 1- Diagnosis
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Gluten Part 1- Diagnosis

It is estimated that 30-40% of the population has some sort of gluten sensitivity, compared to the <1% who have Celiac disease [Osborne, 2016]. With 70% of those who think they have Celiac disease actually having a gluten sensitive disorder [Osborne, 2016].  Properly differentiating then treating Celiac disease vs. gluten intolerance vs. gluten sensitivity avoids bigger problems down the road. 

Gluten intolerance is the inability to digest gluten, a family of storage proteins found in all grains. This is due to enzymatic insufficiency, and is not an immunological process. Whereas, gluten sensitivity is a genetic immunological, and/or an abnormal auto-immunological response to gluten. Celiac disease is only one consequence, albeit a rare one, of the broad spectrum of gluten sensitivity disorders.  It is harder to diagnose a gluten intolerance compared to gluten sensitivity (Jaffe, 2016).
An individual must have a genetic predisposition in order to react to gluten protein- so genetic testing is perhaps becoming the Gold Standard to clinch the diagnosis. In a paradoxical way, genetic predispositions make an immunological response totally normal. Any autoimmune response is abnormal, but paradoxically a person may also have a genetic pre-disposition towards autoimmune responses that gluten may trigger. Celiac is regarded as an autoimmune manifestation of gluten sensitivity. 

Here is the approved nomenclature for Gluten-related disorders:

  • Non-Celiac Gluten Sensitivity (NCGS). Its prevalence is more than 8 times that of Celiac Disease and includes a mass array of complaints.
  • Celiac Disease
  • Derma Herpeformis
  • Gluten Ataxia-Cerebellar Dysfunction.
The Rule-of-Thumb is that “Everyone with Celiac disease is gluten sensitive, but not everyone with gluten sensitivity has Celiac disease” [Osborne, 2016]. Gluten sensitivity disorders and Celiac disease share common intestinal symptoms such as diarrhea, steatorrhea [fat malabsorption], weight loss, bloating, flatulence, abdominal pain, Mouth / oral ulcers (aphthous stomatitis), bleeding gums, and dental enamel defects/wasting [Osborne, 2016]. But this is where their similarities end, and where a good Functional Medicine history & physical exam, plus lab/ diagnostic testing for the clues clinches the differential diagnosis:
First Clue
The first clue is whether or not the major signs & symptoms are limited to the gastrointestinal tract, or do they include extrintestinal and systemic signs & symptoms. Gastrointestinal symptoms are classic to Celiac disease; extraintestinal are non-classic and rare, but do manifest as havelatent or silent Celiac disease.  They are predominant to malabsorption in children: iron deficiency anemia, short stature, delayed onset of puberty, dermatitis herpetiformis, dental enamel defects, and epilepsy with occipital calcifications.
Gluten sensitivity disorders are associated with extraintestinal manifestations in the majority of those afflicted, and are a major reason for under or mis-diagnosis. Extraintestinal signs and symptoms of gluten sensitivity are many, diverse, and include but are not limited to red flags such as autoimmune diseases of various organ systems [e.g. Celiac, osteoporosis in a younger person, and Hashimoto’s thyroiditis]; strange neurological conditions such as ticks and seizures, and undiagnosable skin disorders. Gluten has been shown to contribute to or cause the following [Gluten Free Society, 2016]:

  • Musculoskeletal – muscle/joint pain, wasting, weakness; osteoporosis
  • Neurological – depression, anxiety, bipolar, ADD, epilepsy, neuropathy
  • Autoimmune – RA, lupus, hepatitis, Addison’s, type 1 diabetes
  • Skin – Psoriasis, eczema, scleroderma, seborrhea
  • Gastrointestinal – IBS, GERD, intestinal migraines

Second Clue
Pathopeumaonic to Celiac disease are histological changes in the small intestines detected via tissue biopsy. With gluten sensitivity, there is no histological change. Nor are there the tissue transglutaminase (tTG) antibodies found in Celiac disease.
Third Clue
If a person does not have a known cause for their systemic complaints, gluten sensitivity should be ruled in or out [Osborne, 2016]. Gluten sensitivity in the absence of Celiac disease indeed exists, and this is a reason for missed diagnosis. If a patient tests negative for Celiac [per tissue biopsy, anti-tissue transglutaminase, anti-gliadin antibodies, and endomysial antibodies], it still does NOT rule out gluten sensitivity. People without Celiac disease can still react to gluten because immunological responses to other types of gluten proteins [other than and including alpha gliadin] vary widely from person to person. The Celiac response is just the one most widely studied [Osborne, 2016].
Rules-of-Thumb on Lab Testing
There is no one test for the different types of immune responses to all the different types of grains & glutens. The standard antibody blood tests have specificity in ruling in reactivity to gluten protein - namely alpha gliadin. But they lack sensitivity in diagnosis the spectrum of gluten-related disorders [Alexander, 2016]. Testing options:
  • Small Intestines biopsy is the gold standard for diagnosing Celiac disease.
  • Antibody testing for Type II [IgA, IgG1 & IgG2, IgM] and Complement CD3 delayed-hypersensitivity [most inflammatory] reactions to gluten. Monoclonal vs. polyclonal antibody testing narrows the field for the false positives.
  • Lymph-response Assay (hsLRA™) by ELISA/ACT™ is perhaps a gold standard test for delayed-food & chemical hypersensitivities to as many as 504 items [not just gluten]. By looking live at lymphocytes, the hsLRA ranks higher than standard antibody testing because it differentiates adaptive delayed-immune responses [vs. Type I immediate IgE allergic response] with a <1% false positive rate: Type II [IgA, IgGs, IgM]. Type III immune complex. Type IV T cell mediated.
  • Genetic/ Epigenic Testing is perhaps a gold standard for diagnosing Non-Celiac Gluten Sensitivity [NCGS]. It confirms a genetic sensitivity to gluten protein in general- without need to identify any and all / known or unknown gluten proteins.

As mentioned earlier, a person must have the genetic predisposition to manifest a gluten sensitivity disorder, including Celiac disease [Alexander, 2016]. And there is also a genetic disposition toward autoimmunity. The genes HLA-DQ, HLA-DR, and HLA-B27 can be triggered by nutritional deficiencies, infections [viruses, bacteria, and other types], and some vaccines.  In any case, once these genes are activated, chronic intestinal mucosal inflammation ensues. This leads to the insidious onset of problems such as leaky gut and malabsorption syndromes that account for the extraintestinal symptoms.

integrative Medicine Tips: 
  1. Genetic Testing: Test kit is mailed to your home. Test 
    results emailed with either a positive or negative answer. 
    Video download explains what you need to know and do if your results are positive. 
    Family discounts are available on 2 or more test kits. Email 
    Dr. Osborne at
  1. FREE OFFERS from Gluten Society:  Leaky Gut Solution Guide + Live Q&A Session with Dr. Osborne upon purchase of his $16 book "No Grain No Pain" and Gluten sensitivity self-test.

Alexander, T. (2016). Gluten related disorders. In Functional Medicine University.

Dharmananda, S. (2005). Gluten in Chinese herbs. In Institute for Traditional Medicine [ITM]. Retrieved from

Gluten Free Society. (2014). Traditional gluten free diets fail. Retrieved from

Jaffe, R. (2016). LRA by ELISA/ACT: Functional tests for immune tolerance. In Functional Medicine University. 

Osborne, P. (2016). Gluten certification. In Functional Medicine University.


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