CD: Villous Atrophy (2006)


Janatuinen EK, Kemppainen TA, Julkunen RJK, Kosma VM, Maki M, Heikkinen M, Uusitupa MIJ. No harm from five year ingestion of oats in celiac disease. Gut 2002; 50: 332-335. 

PubMed ID: 11839710
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To assess the safety of long-term ingestion of oats in the diet of celiac patients.
Inclusion Criteria:
From 1995 study: Age 18 or older, normal or almost normal villous architecture after GFD consumption for at least one year. Newly diagnosed subjects must have subtotal or total villous atrophy.
Exclusion Criteria:
From 1995 study: Any medical condition sufficiently serious to interfere with trial or constitute risk to patient, previous or current corticosteroid treatment for CD, history of complications of CD, neurological, cardiovascular, pulmonary, metabolic, hematological or endocrine disorder hindering participation, drug or alcohol abuse, mental impairment, lack of cooperation, any other reason for villous atrophy, diets containing oats.
Description of Study Protocol:


  • From 1995 study: All new patients with subtotal or total villous atrophy diagnosed at the Kuopio University Hospital between December 1, 1988 and December 31, 1990 were included in the study.


  • From 1995 study: Randomized Controlled Trial.

Blinding used (if applicable)

  • From 1995 study: Single blinded study; examining physicians did not know diets of patients.

Intervention (if applicable)

  • From 1995 study: Patients randomly assigned according to sex to either the oat group or control group. Adults with CD in remission were followed for six months and 40 with newly diagnosed CD were followed for 12 months.
  • This study: After the initial phase of six to 12 months, patients in the oats group were allowed to eat oats freely in conjunction with an otherwise GFD. After five years, subjects in oats group and control group were re-examined.

Statistical Analysis

  • All analyses were carried out using both per protocol and intention to treat principles. Results are presented as means±SD or median with range. Differences between groups assessed by Student's two-tailed t-test or Mann-Whitney U test. 95% confidence intervals were calculated for the differences in the changes between the two groups.
Data Collection Summary:

Timing of Measurements

  • Nutritional status, duodenal mucosal histopathology and histomorphometry and laboratory parameters including antiendomysial (EMA), antireticulin (ARA) and antigliadin (AGA) antibodies after five years.

Dependent Variables

  • Nutritional status: Determined through four-day food records and compliance questionnaire
  • Duodenal biopsy specimens obtained through endoscopy at the duodenal bulb and at five-cm intervals thereafter as far down as possible, two specimens per level. Assessed as normal, partial, subtotal or total villous atrophy. Mononuclear cell infiltration graded as none, mild, moderate or severe.
  • IgA and IgG AGA measured using inhouse solid phase ELISA
  • IgA ARA and IgA EMA determined by indirect immunofluorescence.

Independent Variables

  • In 1995 study, subjects received oat products. For this study, oat products were not provided free of charge and subjects purchased rolled oats from general stores. There was no systematic monitoring of oat purity, but author notes that oat products used in Finland have been found to be free of gluten contamination.
Description of Actual Data Sample:

  • Initial N: From 1995 study, 52 subjects with CD in remission and 40 subjects with newly diagnosed CD. During this study, all subjects were considered "old" since diagnosis had been made at least five years earlier. 45 original subjects in oat groups, 47 original subjects in control groups. 
  • Attrition (final N): After five years, 39 subjects in oats group and 42 in control group were contacted. 35 subjects in original oats group (23 still eating oats, 13 men, 22 women) and 28 in control group (10 men, 18 women) on conventional GFD were examined. Four subjects from oats group withdrew without reason. One patient in control group withdrew due to pregnancy, two due to malignancy and 11 withdrew without reason.
  • Age: Mean age of oats subjects was 53±12 years, mean age of control subjects was 52±10 years. 
  • Ethnicity: Not mentioned. 
  • Anthropometrics: There were no significant differences in BMI or change in BMI, nutritional status or routine lab data between two groups at five year exam.
  • Location: Kuopio University Hospital, Finland.
Summary of Results:

Oats Group (All, n=35) P-value for difference Oats Group (Oats, n=23) P-value for difference Control Group (n=28)

Villous Atrophy Change

-0.55±0.54 0.54 -0.55±0.51 0.75 -0.52±0.45

Histomorphometric Index Change






Mononuclear Cell Infiltration Change






Other Findings

  • During the five-year follow-up, mean intake of oats in the oats group was 34 g/day (10-70 g).
  • There were no significant differences between controls and those patients consuming oats with respect to duodenal villous architecture, inflammatory cell infiltration of the duodenal mucosa or antibody titres after five years of follow-up. In both groups, histological and histomorphometric indices improved equally with time.
Author Conclusion:
Our results confirm that ingestion of oats does not result in any duodenal mucosal damage in adult CD patients examined using histological, histomorphometric and immunological methods. In conclusion, our results show that even long term use of moderate amounts of oats included in a GFD in adult patients with CD is safe. If allowed, most patients with CD prefer some oats in their diet.
Funding Source:
Foundation associated with industry:
Reviewer Comments:

It is likely that the original study subjects would continue eating oats if they were not suffering from any symptoms. About 1/3 of the original oat group switched back to conventional GFD without oats (author noted that the primary reason for discontinuing oats was doubt about its safety at that time). Authors did not describe why all original subjects were not contacted for this study. Oat purity was not monitored.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? No
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes