Gluten Enzymes: Food Freedom or False Promise? - Dr. Michael Ruscio, DC

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Gluten Enzymes: Food Freedom or False Promise?

Until Enzymes Can Help, Here’s How to Improve Your Gluten Tolerance

Key Takeaways:

  • There’s no reliable evidence that gluten enzymes are effective for celiac disease or non-celiac gluten sensitivity (NCGS).
  • Some research indicates that gluten-digesting enzymes may actually worsen some symptoms.
  • Gluten enzyme studies are rare, and many that show enzyme benefits are small, industry-funded, and potentially biased.
  • Many conditions, like SIBO, IBS, and FODMAP intolerance, can masquerade as gluten intolerance.
  • A low-FODMAP diet and probiotics can improve digestive symptoms in patients with celiac disease who have symptoms despite eating a strict gluten-free diet, and in people with NCGS.

Over the past several years, gluten has been singled out as the cause of many gastrointestinal symptoms and other health problems. As a result, gluten-free diets have surged in popularity, and now we even have gluten-digesting enzymes marketed as a safeguard against gluten exposure. 

It would be great if these enzymes worked, especially for people with celiac disease, since more food freedom is always a win in my book. However, the research we currently have doesn’t support the use of gluten-digesting enzymes for people with celiac disease or non-celiac gluten sensitivity (NCGS). 



In this article, I’ll discuss the research on gluten-digesting enzymes and why you probably don’t need to spend your money on them. I’ll also dive into why gluten isn’t always the culprit when it comes to digestive system complaints. Finally, I’ll share the protocol I use in the clinic to help my patients improve their gluten tolerance. Let’s take a closer look at what gluten enzymes are and why the science doesn’t yet support the hype. 

The Gluten Enzyme Hypothesis

Before we dig into gluten enzymes, it’s important to understand why they exist in the first place. What is it about gluten, specifically, that causes problems, and how are gluten enzymes supposed to fix them?

Gluten refers to certain prolines (amino acids like gliadins and glutenins) in wheat, rye, and barley that are difficult to digest. When these large peptides enter the small intestine, they tend to trigger the immune system. The resulting inflammation doesn’t amount to much in many people, but it can cause negative digestive effects in people with celiac disease (an autoimmune disorder in which even small amounts of gluten damage the intestine) and NCGS. 

As their name implies, gluten-digesting enzymes (either pharmaceutical or naturally derived from foods like papaya and barley) aim to help us break down the prolines in wheat, rye, or barley. More complete digestion typically means less of an immune response and fewer digestive side effects. 

Wouldn’t it be great if you could just pop a digestive enzyme supplement before your meal and be safeguarded against gluten? Unfortunately, research hasn’t found this to be the case. 

Do Gluten Enzymes Work for Celiac Disease?

First of all, a strict gluten-free diet is crucial for those with celiac disease, as even minuscule amounts of gluten can disrupt their gut function and have many negative downstream effects.  

I would love nothing more than to tell you that gluten-digesting enzymes work for people with celiac disease. Sadly, the research just doesn’t show they help yet. Right now, the available evidence comes from only a few studies, many of which are small or may suffer from bias that’s typical for studies supported by a company that produces the treatment in question. 

The strongest randomized controlled trial tested an enzyme called latiglutenase in 494 celiac patients who still had symptoms despite having followed a gluten-free diet for a year. (Celiac patients who eat strictly gluten free but still have symptoms might be more sensitive to the miniscule amounts of gluten allowed in certified gluten-free foods.) The volunteers also ate a strict gluten-free diet during the study. Whether they took the enzyme or a placebo, the intestinal damage they had at the start of the study didn’t get better in either group after treatment [1]. 

At the same time, both groups had noticeable improvements in symptoms [1]. How is that possible? Most likely, it was the placebo effect. The patients in both groups thought they were taking something that would help them, and that made them feel better, even though their intestinal cells didn’t improve. Overall, this study found that latiglutenase had no effect in celiac patients. 

A separate analysis of the above trial found that certain celiac patients taking the highest dose of the enzyme had less severe abdominal pain, bloating, and constipation than the placebo group. This evidence suggests the enzyme latiglutenase may actually improve symptoms if taken at a higher dose, but only in celiac patients with anti-gluten antibodies in their blood (15% of celiac patients don’t). However, the trial was conducted by the company that makes the enzyme, so the potential for bias is high, and we have to be cautious about interpreting the results [2]. 

A different, small study found no intestinal damage in people with celiac disease after they ate gluten that contained another gluten-digesting enzyme [3]. Again though, affiliates of the enzyme manufacturer conducted this study, so the likelihood of bias is high enough that we can’t draw any firm conclusions.

Overall, both strong and weaker studies show that gluten enzymes appear to be safe for people with celiac disease. But there isn’t any good evidence yet to recommend gluten enzymes for protecting their intestines or improving their symptoms. The few studies that showed symptom improvement were either small or likely suffered from bias, but you may want to keep an eye out for latiglutenase. Someday, we could have more high-quality research that shows it can benefit many people with celiac disease.

If you have celiac disease, the best practice is to continue to follow a strict gluten-free diet. Now, let’s look at what the research says about non-celiac gluten sensitivity.

Do Gluten Enzymes Work for NCGS?

Non-celiac gluten sensitivity is diagnosed when celiac disease has been ruled out, but you are still intolerant to gluten. Compared to celiac disease, there’s even less research studying the effects of gluten-digesting enzymes on NCGS, but what we do have suggests they’re probably not beneficial. 

In a small randomized controlled trial, participants were given either a gluten enzyme (endopeptidase P10160) or a placebo while reintroducing gluten into their diets for 3 weeks. Both groups had significantly more abdominal pain and worse stool consistency when they reintroduced gluten, which suggests the gluten enzymes were not helpful [4]. 

Another small randomized controlled trial found gluten-sensitive people had no difference in symptoms whether they ate enzyme-treated bread, normal bread, or bread low in gluten [5]. 

A third small randomized controlled trial did find a benefit from taking a papaya-derived gluten-digesting enzyme during a gluten challenge. However, the study was conducted by the enzyme company and was single-blinded, meaning the researchers knew who received the enzymes and who received the placebo [6].

The bottom line on gluten enzyme research is there’s no reliable evidence at this time to support their use in people with celiac disease and NCGS [1, 4, 5]. Studies that did support using gluten enzymes were small and tended to have lower-quality designs and a greater likelihood of bias. 

I think we can all agree that’s a disappointing reality. But there’s still plenty of reason to feel hopeful—even without the promise of gluten enzymes, you can still improve your ability to tolerate gluten. I’ll share the steps I use to help my patients improve gluten tolerance. But before I do, I want to discuss why it’s important to consider your overall gut health rather than singling out gluten when it comes to your symptoms. 

Is Gluten Always the Culprit?

I’ve noticed a push in the integrative and functional medicine industry to encourage the vast majority of people to follow a gluten-free diet. I feel this is a mistake because the prevalence of gluten-related conditions is actually very low. 

Here’s what I mean: Celiac disease affects anywhere from 0.7 to 1.4% of the global population [7]. The prevalence of NCGS is more difficult to determine, with estimates ranging from 5–77% [8, 9]. Does this mean the majority of us are gluten intolerant? Not at all. Instead, it speaks to the enormous challenge of diagnosing NCGS and the likelihood that what many people think is a gluten problem is actually something else. Here are some other health conditions that may masquerade as gluten sensitivity:

  • FODMAP intolerance (including lactose intolerance) [5, 9, 10, 11]
  • Small intestinal bacterial overgrowth (SIBO) [12, 13, 14]
  • Irritable bowel syndrome (IBS) [9, 15]
  • Dysbiosis [9]
  • Inflammatory bowel disease (IBD) [9, 15]
  • Diverticular disease [9]
  • Microscopic colitis [9]
  • Non-responsive celiac disease (when you still have symptoms despite eating a strict gluten-free diet) [16]
  • The nocebo effect: it’s like the placebo effect [17, 18], but it occurs when you expect something to harm you, and you experience harm from it as a result [5]. 
  • Alpha-amylase/trypsin inhibitors in wheat (non-gluten molecules that prevent the body’s natural enzymes from breaking down wheat) [5

All of these conditions and factors have symptoms that could respond well to a gluten-free diet, which makes it easy to assume gluten ingestion is the cause of your distress. While a strict gluten-free diet is crucial for those with celiac disease, I’ve come to realize that many people without celiac may be avoiding gluten for no reason. 

I’m a food-first clinician, but I’m not a fan of unnecessary dietary restriction. The research and my experience in the clinic tell me that, while gluten may contribute to symptoms in some cases, other correctable factors could be underlying your gut issues. Let’s explore this in more detail so you can grasp how I go about helping my patients improve their gluten tolerance.

Improving Gluten Tolerance Without Enzymes

Although current research suggests that gluten-digesting enzymes aren’t helpful, not all hope is lost. Science-based solutions like a low-FODMAP diet and probiotics can be very helpful for improving food intolerance in general, including gluten sensitivity.

So, if you don’t have celiac disease and you’ve been avoiding gluten indefinitely, there are natural ways to reintroduce it back into your diet if that’s what you desire. Let me start by describing the low-FODMAP diet and why it may be the missing link for improving your symptoms.

Low-FODMAP Diet

FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) are fermentable carbohydrates that feed intestinal bacteria. For people with too many bacteria in the small intestine (which is common in those with celiac disease or NCGS), eating foods high in FODMAPs can trigger gastrointestinal symptoms like diarrhea, constipation, gas, bloating, flatulence, and abdominal pain [12, 13, 14, 19]. That’s great, you might be thinking, but what does that have to do with gluten? 

Well, many gluten-containing foods are also high in FODMAPs, which may be the actual source of your symptoms. One randomized controlled trial found that people with self-reported NCGS were likely experiencing symptoms from the fructans (high-FODMAP carbohydrates) in wheat, rye, and barley—NOT from the gluten [10]. 

In fact, it’s hard to find foods with gluten that are low in FODMAPs—a rare example is sourdough made from spelt. But there’s also a wide variety of gluten-free foods that fit into the high-FODMAP category and may be bothering you without you realizing it. 

So, if you don’t have celiac disease and you react to foods that have gluten, you may want to consider FODMAP intolerance as a cause. Otherwise, if you simply cut out gluten because you assume it’s the culprit, you could be missing out on more complete healing from reducing FODMAPs instead. 

And if you have celiac disease, but your symptoms linger despite following a strict gluten-free diet, a low-FODMAP diet may benefit you, too. One study found significant improvement in GI symptoms and psychological well-being in celiac patients who followed a low-FODMAP, gluten-free diet for 3 weeks [20].

I do want to mention that for most people, a low-FODMAP diet isn’t a long-term meal plan. Instead, you traverse through a process of removing high-FODMAP foods for a trial period. During this phase of elimination, you’re also working to heal your gut and restore balance. Ideally, after a few weeks, you can reintroduce the eliminated foods slowly and have significant improvements in your ability to tolerate them—even those that contain gluten. 

If you find you still need to keep your FODMAPs low, you can customize a low-FODMAP diet to your needs by eating small amounts of some higher-FODMAP foods. Monash University, in Melbourne, Australia, has done most of the pioneering work on the low-FODMAP diet. They offer a very useful app that will familiarize you with low-, medium-, and higher-FODMAP foods, and help you figure out how much (or little) of each you can tolerate before having symptoms.

In any case, a low-FODMAP diet can be very impactful toward reducing symptoms you’ve long attributed to gluten. And if you need a boost, probiotics are another science-based option for helping you tolerate more foods, including those that have gluten in them.  

Probiotics 

Probiotics can foster broad corrective action in the gut by improving microbial balance, taming an overzealous immune system, and quelling inflammation [21, 22, 23, 24]. This makes them a great option for people with both NCGS and celiac disease. 

Research on using probiotics to treat NCGS is scarce, but one non-randomized trial found that when people with NCGS took Bifidobacterium longum, they had less frequent and intense GI and non-GI symptoms, and improved stool consistency [25]. The study couldn’t say the probiotic had caused the improvements, but the findings were promising nonetheless.

The data regarding celiac disease is more robust, with a number of randomized controlled trials having found that probiotics improved digestive symptoms in celiac patients [26, 27]. Probiotics may also help kids with celiac disease (who follow a gluten-free diet) to take fewer trips to the bathroom [28]. 

You may be wondering if it matters what strain of probiotic you take. While a specific strain (Bifidobacterium infantis) may be especially helpful for people with the most severe celiac symptoms, it’s probably not necessary to seek out a specific type of probiotic [29]. Let me explain:

There are three categories of probiotics:

  • Category 1: Lactobacillus and Bifidobacterium blends
  • Category 2: Saccharomyces boulardii (a probiotic yeast)
  • Category 3: Soil-based bacteria of various Bacillus species

In the clinic, I recommend a triple-therapy approach to probiotics, which simply means I use all three categories of probiotics in combination. High-quality clinical trials, including a meta-analysis, found that when probiotic formulations with multiple categories were compared with single strains, the multi-strain versions were more effective at treating gut conditions like IBS and constipation [30, 31, 32]. 

This mirrors my experience in the clinic, where I generally see the best results with patients who follow a triple-therapy protocol. This is not to say that there’s anything wrong with using one category of probiotic, but a multi-category approach covers all of the bases and tends to lead to better results overall.

Heal Your Gut to Improve Gluten Tolerance

Do gluten enzymes work? At this point, there’s no quality research to suggest gluten-digesting enzymes can help you tolerate gluten if you have celiac disease or non-celiac gluten sensitivity. In fact, some research suggests they could even make some symptoms worse. However, I am open-minded and hopeful that future, unbiased research may uncover a benefit.

If you have celiac disease, it’s best to strictly avoid gluten. If you do follow a gluten-free diet closely and still have lingering symptoms, FODMAPs could be bothering you. Consider trying a low-FODMAP diet and probiotics. 

If you think you have gluten intolerance or NCGS, it’s worth considering other possible causes like poor gut health and FODMAP intolerance. Working your way through the Great-in-8 action plan in my book Healthy Gut, Healthy You can help you restore vibrant health and ultimately allow you more food freedom without unnecessary dietary supplements.

The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you.

➕ References
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