Nonceliac Gluten and Wheat Sensitivity: Review

A Khan et al. Clin Gastroenterol Hepatol 2020; 18: 1913-1922. Nonceliac Gluten and Wheat Sensitivity

This useful review notes that ” there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder.”

Key points:

  • The pathogenesis of NCGS is unclear and there is no known biomarker or diagnostic histologic lesion for this condition.
  • In these suspected patients, it is important to first exclude celiac disease and wheat allergy (especially if a rash with eating). If celiac disease is identified, this allows for appropriate longitudinal followup, strict dietary instructions, and potential screening of at-risk family members.
  • Recent studies have shown that GI symptoms in those labelled with NCGS are frequently due to dietary FODMAPs.
  • In a large meta-analysis study with 1312 adults, only 16% of participants experience gluten-specific symptoms using a double-blind placebo-controlled rechallenge.  In addition, 40% of participants experienced a nocebo response (ie. a greater negative effect than usual due to negative expectation from a dietary treatment)
  • In clinical practice, a single blind placebo-controlled rechallenge trial has been recommended for diagnosis

My take: GFD is often unnecessary and ineffective, even in those who have previously identified gluten as a potential food trigger.  Fructans are more likely to induce gastrointestinal symptoms.

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Wheat Intolerance –Self-Reported in 15%!

A recent study (MDE Potter et al. Am J Gastroenterol 2018; 113: 1036-44 -thanks to Ben Gold for this reference) examined the frequency of wheat intolerance and chronic gastrointestinal symptoms in a randomly selected population of 3542 in Autstralia via a mail survey.

Key findings:

  • Self-reported wheat sensitivity was 14.9%
  • Prevalence of celiac disease (CD) was 1.2%
  • A doctor-diagnosis of CD was associated with functional dyspepsia with an odds ratio (OR) of 3.35.
  • Self-reported wheat sensitivity was independently associated with irritable bowel syndrome with an OR of 3.55 and almost half (45%) have an underlying functional GI disorder.

In a related editorial (pgs 945-8), Imran Aziz makes several useful points:

  • Gluten-free industry has boomed in U.S. with retail sales going from $0.9 billion in 2006 to ~S24 billion in 2020.
  • While previous studies have shown that gluten can induce symptoms in the absence of CD (Biesiekierski JR et al. Am J Gastroenterol 2011; 106: 508-14), more recent rigorous studies have indicated that “gluten-per-se accounts for 1-in-6 cases with the remaining majority either due to fructans (a type of FODMAP or a nocebo effect.”
  • There are no accurate biomarkers of wheat intolerance
  • Dr. Aziz also cautions against adopting a gluten-free diet without proper counseling.  “The greatest concern is whether these diets are safe in the long-run, given the emerging data suggesting cardiovascular, nutritional, metabolic, and microbial changes.”

My take: This study shows that about 1 in 10 individuals have self-reported wheat intolerance; gluten, though, is the actual culprit in less than 20%.

Related Blog Posts:

Fructans, not Gluten, Inducing Symptoms In Patients with Reported Non-Celiac Gluten Sensitivity

As with yesterday’s post, today’s study (GI Skodje et al. Gastroenterol 2018; 154: 529-39) implicates fructans, not gluten, as a culprit in increasing symptoms in those with self-reported non-celiac gluten sensitivity (NCGS).

These researchers performed a double-blind crossover challenge in 59 individuals who had instituted a gluten-free diet (GFD). The symptoms were assessed with a Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) through 3 challenges –gluten, fructan, and placebo.

Key findings:

  • GSRS-IBS mean values for gluten 33.1, for fructan 38.6, and placebo 34.3.  The overall GSRS-IBS value for fructans was significantly higher than for gluten P=.04
  • GSRS-IBS mean values for bloating with gluten 9.3, for fructan 11.6, and placebo 10.1

In a related editorial (K Verbeke, pages471-3), the commentary notes that  alpha-amylase-trypsin inhibitors (ATIs) may be another factor which contributes to symptoms in those with reported NCGS.  ATIs protect plants from pests/parasites by inhibiting their digestive enzymes.  They also resist proteolytic degradation in the human intestine and are known to be potent activators of innate immune cells.

My take: This is yet another study showing that among individuals with NCGS that a GFD is often unnecessary and ineffective.  Fructans are more likely to induce gastrointestinal symptoms; however, their are likely to be several food components which contribute to GI symptoms & sometimes extra-intestinal symptoms.

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Fructans and FODMAPs in Children with Irritable Bowel Syndrome

A recent randomized control trial (BP Chumpitazi et al. Clin Gastroenterol Hepatol 2018; 16: 219-25) evaluated 23 children in a double-blind placebo (maltodextrin) cross-over design (2014-2016) to determine whether fructans (0.5 g/kg/day with max 19 g divided over 3 meals) worsen symptoms in children with irritable bowel syndrome (IBS). Fructans are a commonly ingested FODMAP carbohydrate (oligosaccharides).  All subjects were 7-18 years (median 12.4 years) and met Rome III IBS criteria.

Key findings:

  • Subjects had more episodes of abdominal pain/day while receiving fructan-containing diet (3.4 ± 2.6) compared with placebo-group (2.4 ± 1.7) (P<.01).
  • The fructan group had more severe bloating (P<.05) and flatulence (P=.01).  This was associated with higher hydrogen production (617 ppm/h compared with 136 pph/h) (P<.001)
  • 18/23 (78%) had more frequent abdominal pain with fructan-containing diet and 12 (52%) had fructan sensitivity which the authors defined as having an increase of ≥30% in abdominal pain frequency following fructan ingestion.

My take: While the number of participants in this study is limited, the implications are clear: in children with irritable bowel, fructans frequently exacerbate symptoms. At this time, though, it is not possible to predict which patients with IBS will benefit.

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