New Study Reveals Almost 20% Of Celiac Children May Not Heal On A Gluten-Free Diet

Last week as I was glancing through my Google news feed on celiac disease, I came across three headlines that startled me. I had to read each headline twice just to make sure I was reading them right.

Does The Gluten Free Diet Actually Improve Coeliac Disease?

Prolonged Gluten-Free Diets Don’t Heal Guts, New Study Finds

Gluten-Free Diets in Children May Promote Poor Intestinal Health

If you have celiac disease (CD) or if you have a child who has CD, these headlines should startle you as well.

The first and second cast doubt on the efficacy of a gluten-free diet (GFD) for celiacs. The third implies that a GFD may actually harm children.

These headlines, however, actually reflect a rather poor analysis of a recent (Nov/16) study done by the MassGeneral Hospital for Children (MGH) that found that 19% of celiac children still continued to show intestinal damage after at least one year on a GFD.

Further the study did not arrive at the conclusions that these headlines suggest.

Researchers at MGH were not critical of a GFD but because of the study’s findings, they adopted new clinical procedures for managing children with CD.

Let’s see what we can learn from the MGH study, and then see if we can make sense of these headlines.

The Objective In The Recent MassGeneral Hospital Study On CD

This past November, the Journal of Pediatric Gastroenterology & Nutrition released a study by researchers from MGH entitled Value of IgA tTG in Predicting Mucosal Recovery in Children with Celiac Disease on a Gluten Free Diet.

You can read the study here. Click on “article as a PDF” to get the whole text of the study.

The study had two primary objectives

1. To determine the rate of mucosal recovery in pediatric patients with celiac disease on a GFD

Notice that the researchers wanted to determine the rate of intestinal healing in children with CD on a GFD, not whether they healed at all.

2. To determine whether IgA tissue transglutaminase (tTG) correlates with mucosal damage at the time of a repeat endoscopy with duodenal biopsy in these patients

The tTG is a blood test that measures specific antibodies produced in response to gluten. A high tTG titer is suggestive of CD.

It can also be used to see if a patient is adhering to a GFD.

Clinicians have also used the test as a means for measuring the amount of mucosal healing after the start of a GFD. The return to a normal tTG titer was thought to be suggestive of intestinal mucosal recovery.

The researchers in this study wanted to see if the tTG test was indeed an accurate marker of mucosal recovery in celiac children.

Methods Used In The Study

The study included 103 celiac diagnosed children with an average age of 10.6±5.0 years.

Each child had current small intestinal damage rated at Marsh 3.

After an initial tTG test and endoscopy, a follow-up tTG and endoscopy was performed on all children within 1 -12 years of being on a GFD. The mean result for follow-up endoscopy was 2.4 years.

These children were estimated to have an excellent compliance with a GFD.

The Results Of The Study

1. Almost 19% of pediatric patients treated with a GFD had persistent enteropathy.

In other words, in the presence of an excellent compliance with a GFD, 19% of the patients studied continued to have intestinal mucosal damage rated at Marsh 3.

Researchers from MGH were surprised by this result.

Alessio Fasano, M.D., director of the MGH center and co-senior author of the study, noted,

The number of children who don’t heal on the gluten-free diet was much higher than what I expected.

While researchers know that up to 33% of adult celiacs continue to show mucosal damage after going on a GFD this degree of delayed healing was not expected in children.

Researchers anticipated that healing would proceed faster in children because of their intestinal resiliency.

The study did not propose an explanation as to why 19% of children continued to have persistent damage.

2. IgA tTG did not accurately measure mucosal recovery

While researchers found that tTG was accurate in initially identifying CD, it was not a good indicator of how well the intestinal mucosa was healing in CD patients.

The overall positive predictive value of the autoantibody tissue transglutaminase was only 25%.

In other words, the tTG test was only found to be an accurate gauge of mucosal healing 25% of the time compared to a much more accurate biopsy result.

While tTG was effective for diagnosis, it was not as useful for monitoring the rate of mucosal healing.

The Researcher’s Analysis Of The Study

On November 30, the MGH released a statement concerning the study.

In that statement Maureen Leonard, M.D. (co-researcher in the MGH study), stated,

This study confirms that we need to look more aggressively for mucosal healing in all patients, not just adults.

Apparently, because a large percentage of children didn’t show mucosal healing at least 2 years after a GFD, researchers can no longer assume that celiac children heal significantly better than celiac adults.

This means that clinicians will have to investigate celiac children more thoroughly as to whether healing is occurring.

Echoing Dr. Leonard’s call for a more aggressive approach to detect mucosal healing in celiac pediatric patients, Dr. Fasano announced that MGH is changing its clinical approach. He states,

We assumed that healing would occur once a patient was put on the gluten-free diet. Now that we have learned that this is not the case for all celiac patients, we are changing our clinical practice by repeating the endoscopy after one year of the implementation of the gluten-free diet.

Since the tTG test was found to be an inaccurate measure of the rate of mucosal healing, researchers need a more accurate way to discover how much healing is taking place. This is essential for follow-up treatment.

Previously, clinicians recommended an initial single endoscopy with biopsy at diagnosis and follow-up blood testing (tTG) to monitor recovery of the intestinal mucosa.

Because of the invasive nature of endoscopies, clinicians were reluctant to subject children to repeat endoscopies unless there were unexplained symptoms.

Now, however, MGH recommends that until a better non-invasive means that reveals an accurate picture of intestinal healing is developed, the highly accurate endoscopy should be performed on all celiac patients one-year post GFD.

In the study and in MGH’s statement, no criticism was directed toward a GFD for its failure to promote mucosal healing.

The study did raise some questions that will hopefully be answered in the future.

Questions Raised By The Study

Since only 103 patients were studied we don’t know if the 19% number would change if a larger number of patients were studied. It’s possible that the percentage could be higher or lower.

There were a number of questions this study raised, but since it was not designed to answer them researchers chose to remain silent.

I will mention them because they are important for the future treatment of celiacs.

1. Why didn’t 19% of celiac children heal when placed on a GFD?

If there was excellent compliance with a GFD, why didn’t these children heal?

Theoretically, if the offending agent (gluten) is removed, then there should cease to be an inflammatory autoimmune reaction.

Also, in theory, if tTG titers are normal, that should mean that there are no antibodies being produced indicating that there is no autoimmune reaction.

If there is no autoimmune reaction taking place then there should be no new intestinal damage occurring.

Indeed, the study didn’t indicate that there was a worsening of the condition, only that there was still Marsh 3 damage.

So the question is why didn’t the mucosal damage heal?

I believe researchers don’t yet have sufficient information to answer this question.

Some proposed reasons for persistent mucosal damage are a lack of adherence to a GFD, cross-contamination of gluten in the diet, persistent inflammation, persistent leaky gut, or a disruption of the intestinal microbiome.

See my post here on why some celiacs don’t heal on a GFD.

2. Were There Nutritional Deficiencies In The 20% That Showed Delayed Healing?

The study reported that all the participants were counseled on a GFD by a dietician and most received follow-up dietary support.

While I know it wasn’t the scope of this study to investigate the possible nutritional deficiencies in those who had persistent damage, I still would be curious to know if there were any.

Did the diets of the 20% show any vitamin, mineral, or other micronutrient lack that could cause a delay in healing?

Were there any deficiencies revealed on blood panels that might reveal malabsorption problems that could be responsible for the persistent damage?

3. Did The 20% Who Displayed Delayed Healing Maintain A Pro or Anti-Inflammatory Diet?

Since CD is an inflammatory disease, a GFD that reduces gut inflammation could promote healing.

Standard GFDs are not necessarily anti-inflammatory. Simply replacing gluten-containing foods with highly processed non-gluten grains and other foods might encourage further inflammation.

Again, I know a dietary investigation was not within the scope of this study, but I would be curious to know if diet plays a part in persistent mucosal damage.

4. What Is The Next Clinical Step If Compliance To A GFD Is 100% And There Is Persistent Mucosal Damage?

If there’s persistent mucosal damage after starting a GFD, what is the next step in the practical treatment of the CD patient?

The is what the study stated,

Long-term complications including growth trajectory must be monitored and further study evaluating available
treatment options beyond the GFD and timing of subsequent endoscopies in patients found to have persistent enteropathy must be established.

The researchers did not elaborate on what those treatment options are.

If a follow-up endoscopy reveals persistent damage after a GFD is there another treatment option?

I personally would like to see more studies on the effect of an anti-inflammatory diet on persistent mucosal damage in CD.

I’m sure CD researchers all over the world are trying to answer these questions. I pray they find answers soon.

Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children

In late August 2016, Dr. Fasano and others published a comprehensive list of guidelines for the management of children with celiac disease.

If you have a child with celiac disease and you haven’t seen these recommendations, I urge you to take a look at them. See here.

Even If you don’t have a child with celiac disease but you know someone who does, send it along to them. Even if they’ve already read them, they’ll thank you for caring and understanding.

Okay, let’s get back to how this study was misinterpreted by some websites.

Misinterpretation Of The MassGeneral Study

Bloggers know the power of headlines. A carefully designed title will increase the odds of someone clicking on their article and reading it.

However, authors will often use a shocking or over-dramatized headline just to draw in a reader. It’s called click-bait.

The above headlines certainly got my attention. I opened each one and read the article associated with the headline.

As we have seen, the headlines do not really make sense in light of the MGH study.

Does The Gluten Free Diet Actually Improve Coeliac Disease?

According to the MGH study, yes, it does in 80% of pediatric celiac patients. The 20% not healed may heal in the future or need a GFD plus something else.

However, without a GFD no celiac patient will heal.

Do prolonged GFD’s heal guts?

The MGH study did find that a prolonged GFD contributed to the healing of 80% of pediatric celiac patients’ intestinal mucosa. So this title is just clearly inaccurate.

Does a GFD in children promote poor intestinal health?

Nowhere in the MGH study did it report that there was something wrong with a GFD or that it promoted poor intestinal health.

Persistent mucosal damage was not the result of a GFD, and the children did not get worse on a GFD.

One criticism of a standard GFD is that it could be lacking in some vitamins and other nutrients.

However, I haven’t seen any evidence that this would create intestinal damage.

Beware Of Misleading Headlines Concerning Celiac Disease

I don’t know why these websites used these misleading headlines to report on the MGH study.

I have my suspicions.

There are millions of people forsaking gluten for reasons other than celiac disease or non-celiac gluten sensitivity.

This includes people who prefer a paleo type diet where grains are off limits and those who are on low carb diets.

Now add to this the many celebrities touting the health benefits of shunning gluten, and you have a significant number of non-celiac people who don’t eat wheat bread.

The media has labeled a GFD a fad diet and will look for any evidence to belittle it.

Am I sure this is the reason? No. But I can’t think of any other reason for such provocative headlines.

It’s unfortunate because these headlines have the potential to confuse and distort the use of a GFD in CD.

When you see health articles, read the headlines carefully, and then read the whole article and the original studies to make sure it’s the truth.

What did you think of the study? We would love to hear from you.

Read this next

How I Overcame My Fear of Going Gluten Free

Can a Gluten Free Diet Heal Adult Celiac Patients?