Gluten-Free –No Evidence It is Helpful for Healthy Individuals

A recent study (ID Croall, et al. Gastroenterol 2019; 157: 881-3) provides additional data indicating that a gluten-free diet does not confer health benefits to healthy individuals.

A double-blind randomized placebo 2-week trial with 30 healthy adults divided subjects into two groups –some received flour sachets to consume with organic gluten (14 g) and some received a gluten-free blend (rice, potato, tapioca, maize, buckwheat flour). Both groups were instructed to take their flour sachets twice a day along with a gluten-free diet (GFD).

Key finding: The group receiving gluten did not experience any increase in gastrointestinal symptoms or fatigue compared to the placebo group.

My take: While this study lasted only 2 weeks and had a small sample size, nevertheless, it adds to the literature indicating that a GFD is unlikely to be beneficial in otherwise healthy individuals. Those who stick with a GFD should seek the help of a well-qualified dietician.

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Portland, OR. Portland aerial trams –between the city’s South Waterfront district and the main Oregon Health & Science University (OHSU) .

Economic Costs of Gluten Free Diet

A recent study (AR Lee et al. Nutrients; 2019, 11, 399). Open access: Persistent Economic Burden of the Gluten Free Diet) quantifies the additional costs of a gluten free diet (GFD) in the U.S. Thanks to Kipp Ellsworth for this reference.

The authors conducted a “market basket” study to establish the cost of a GFD. “A market basket is a group of products that are purchased by consumers …for this study, the market basket was food that would necessitate a GF substitute, including staple foods, snack foods, and commonly used ready-made or convenience meals.”

Key findings:

  • GF products were more expensive, overall the increase was 183%.  This is an improvement from a 2006 study which found the increase overall at 240% (adjusted for inflation).
  • Mass-market products were 139%  more expensive than wheat-based versions

Discussion:

  • Cost is identified as a frequent reason for nonadherence with diet, cited by 33% in one study
  • Overall, the burden of GFD is more frequently related to the restrictive nature of the diet which leads to a negative impact on quality of life. According to the authors, in one study (Am J Gastroenterol 2014; 109: 1304-11), treatment burden for celiac was ranked higher than for diabetes hypertension, and congestive heart failure

My take: This study shows the significant economic burden of a GFD.  In Italy, the  “government offers celiac patients vouchers to buy gluten-free food — up to 140 euros per month.” (NPR: Italy, Land of Pizza and Pasta)

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Evidence-Based IBS Treatment Recommendations from ACG

A recent  American College of Gastroenterology Task Force conducted a systematic review (AC Ford et al. The American Journal of Gastroenterology 2018;113:1–18 ) to update management recommendations for irritable bowel syndrome -Link:

American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome

The highlights of this report are summarized at Gastroenterology & Hepatoloy: Highlights of the Updated Evidence-Based IBS Treatment Monograph

A few excerpts:

“There have been numerous studies performed on the roles of diet and dietary manipulation in IBS. Three fairly firm conclusions were made following the review of these studies: (1) the low–fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet seems to be effective for overall IBS symptom improvement; (2) a gluten-free diet is not effective for symptom improvement; and (3) conducting tests to detect various types of allergies or intolerances in order to base a diet on those results does not appear to be effective. Of these 3 conclusions, the most impressive data that came out of the research was the evidence for the low-FODMAP diet. Not only were there more studies on this diet, but the results were fairly consistent and favorable, at least for the short-term management of IBS.”

” We did not find evidence supporting the idea that prebiotics and synbiotics were effective in IBS management… In ­contrast, studies demonstrated that probiotics did improve global gastrointestinal symptoms, as well as the individual symptoms of bloating and flatulence in patients with IBS. However, determining which probiotic is best was difficult”

“Three prosecretory agents are available: linaclotide (Linzess, Allergan/Ironwood Pharmaceuticals), lubiprostone (Amitiza, Takeda), and plecanatide (Trulance, Synergy Pharmaceuticals), with plecanatide being the most recently approved agent. All 3 of these agents had convincing data to support their use in patients with constipation-predominant IBS

My take: In IBS patients, if dietary therapy is recommended, current evidence favors a low FODMAP diet rather than a gluten-free diet.

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near Banff

Image above -Parker Ridge Trail

Is it Helpful to Check Celiac Serology Titers After 3 Months of a Gluten Free Diet?

A recent prospective study (D Petroff et al. Clin Gastroenterol Hepatol 2018; 16: 1442-49) with 345 pediatric patients with biopsy-proven celiac disease (CD) examined serologic response to a gluten-free diet (GFD) between 2012-2015.

Key findings:

  • Mean TTG IgA concentration decreased 14-fold after 3 months of a GFD.  The study assay used kits from EUROIMMUN.
  • TTG IgA remained above 1-fold ULN in 83.8% and above 10-fold ULN in 26.6%.
  • Deamidated gliadin IgA (DGL IgA) decreased in the vast majority but did not distinguish response of GFD from random fluctuations.
  • The authors note that symptoms improved in most on GFD, but short-term response could reflect “regression to the mean…for a considerable share” as symptoms improved in the non-GFD group as well.

In their discussion, the authors reference a large study (n=487) which showed mean normalization of TTG IgA of ~400 days; longer times were noted in those with type 1 diabetes and higher baseline values.

My take: This study, while showing that TTG IgA levels improve after 3 months of a GFD, helps solidify my opinion that in those who are improving, followup serology could be obtained later.  My practice is to have followup serology after 6 months of a GFD in the majority of patients.

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Lake Moraine, Banff

More Sensitive Detection of Gluten Free Diet Adherence

A recent cross-sectional study (K Gerasimidis et al. JPGN 2018; 67: 356-60) examined the use of fecal gluten immunogenic peptide (GIP) to assess for adherence with gluten free diet (GFD) in biopsy-proven celiac disease (CD).

GIP reflects recent gluten consumption.  There is a commercially-available kit available (Ivydal GIP Testing) –though I am uncertain about how its reliability compares to the GIP measured in this study.

In the study, the authors note that GIP positivity can occur with as little as 100 mg of gluten/day ingestion.  GIP is a 33-mer peptide from α2-gliadin that is stable against breakdown by gastric, pancreatic, and intestinal brush border enzymes.

Key findings of this study:

  • GIP was detectable in 16% of patients with previous CD diagnosis (N=67)
  • GIP was detectable in 95% of newly-diagnosed CD patients (n=19) and was detectable in 27% at 1 year afterwards.
  • When compared with traditional indicators of GFD adherence (eg. TTG levels, Biagi score, clinical assessment), 4 out of 5 children with detectable GIP were missed

My take: Fecal GIP for celiac disease adherence has similar potential as a biomarker as calprotectin has for IBD.  A normal GIP appears to be much more sensitive at detecting gluten ingestion.

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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%.

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Celiac Disease: How Long Is a Gluten Free Diet Needed? (30 Year Data)

A recent study (L Norsa et al. JPGN 2018; 67: 361-6) examines data from 197 patients with celiac disease (CD) (out of a cohort of 337) who had a diagnosis established before 1985. The authors examined three groups: lifelong strict GFD (n=133), discontinued GFD (n=29), and no GFD (22).  A total of 63 had follow-up endoscopy data available, with 29 in lifelong GFD, 20 in discontinued GFD, and 14 in no GFD.

Key findings:

  • In those with followup endoscopy, in those with lifelong GFD 27 of 29 (93%) had no atrophy (Marsh 0-1-2) on histology, in those with discontinued GFD 12 of 20 (60%) had no atrophy on histology, and in those with no GFD 8 of 14 (57%) had no atrophy on histology.
  • Thus, among the group with long-term poor adherence to gluten-free diet, almost two-thirds showed no recurrence of villous atrophy on duodenal biopsies.
  • In the entire cohort of 197, there were no apparent differences in autoimmune diseases between those receiving lifelong GFD (26%) compared to the other two groups, 17% and 23% respectively.

Limitations:

  • retrospective design.
  • initial diagnosis was more than 30 years ago & there are significant differences in the diagnostic approach currently
  • sample size

My take: This study indicates that some individuals who have been diagnosed with celiac disease may be OK with ongoing gluten consumption. Those who maintained a GFD were much more likely  to have no villous atrophy on duodenal biopsies.

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