Is Gluten Sensitivity a Proven Condition?

Source: Cesar Astudillo via Flickr

***This is the second in a series of posts looking at non-celiac gluten sensitivity and autoimmune disease. Go here if you’d like to read the first one. Stay tuned for more posts in this series in the coming days.***

A week or two ago, I had a fantabulous post all typed up and ready to publish, and what do you know, somehow I lost it and there was no saved draft. Serves me right for not working in Word and saving! Since it took me a little while to reconnoiter, I hope you’ll forgive the longer than expected pause in our gluten series.

Without further ado, I hope to be able to share what I think are some interesting findings on the subject of gluten sensitivity. Namely, does non-celiac gluten sensitivity really exist, or is it just the latest diet fad?

Defining Our Terms: Celiac vs. Gluten Sensitivity

Celiac

It helps to start with what celiac is and what NCGS is purported to be. Celiac is an autoimmune disease that has been recognized since the 1960s, although it was described as far back as 100 A.D. In celiac, gluten—specifically the gliadin protein in gluten–triggers an attack by antibodies on the person’s own intestinal walls, leading to the flattening of the villi of the intestines. Those are responsible for absorption of nutrients so they can be circulated in the bloodstream. Thus, celiac people can eat and yet be malnourished.

They may—but don’t always—have gastrointestinal symptoms. They can be underweight or overweight. Many times, celiacs only experience fatigue, foggy thinking, and depression, or they may have mouth ulcers or dental problems.

Celiac is a serious disease that can even lead to organ failure or Hodgkin’s lymphoma, so a diagnosis means lifelong total avoidance of gluten, which is contained in anything made from wheat, barley, rye, or spelt. Because it’s an issue of an immune reaction, even a molecule is enough to set off an reaction that can last up to six months.

Celiac disease is diagnosed by positive blood tests for endomysium (EMA), tissue transglutimase (tTG), and anti-gliadin (AGA) antibodies, which are then followed up with a small intestine biopsy to confirm flattening of the villi on a scale called the Marsh scale.

Surprisingly, CD, sometimes called gluten enteropathy to distinguish it from others, is not the only autoimmune diseases caused by gluten. Physicians recognize that gluten can also attack the brain and nervous system in an autoimmune fashion, resulting in gluten neuropathy, enceopholopathy, ataxia, dermatitis herpetiformis and other conditions that can exist independent of or along with celiac disease.

Gluten Sensitivity

Gluten sensitivity is a condition in which blood tests for celiac markers are currently negative (yes, it is possible to test negative for them and later test positive), yet the person has an adverse, yet more immediate and short-lived, reaction to gluten. This may include diarrhea, gas, nausea, or abdominal pain, but could also be fatigue, depression, or cognitive difficulties. Other alleged symptoms and effects of NCGS are debated.

While intestinal biopsies of GS patients show little to no damage to the villi, blood tests do show elevations of one of the three antibodies tested to identify celiac in about 50% of subjects, and some immune cells in GS subjects are elevated, indicating that inflammation and an immune reaction are clearly taking place.

Many sources make the claim that gluten sensitivity is also related to autoimmune diseases; thus, that Hashimoto’s hypothyroidism, infertility of unknown causes, PCOS, Type 1 diabetes, vertigo caused by an autoimmune inner ear disease, and other conditions can be improved or healed by gluten avoidance. This is a fascinating topic, and it will get a whole post to itself soon.

Currently, there is no medical test that is accepted by the medical community for diagnosing non-celiac gluten sensitivity, so, until there are, GS is said to exist when symptoms occur at or near the time of consumption of gluten and celiac has been ruled out though blood testing. Many people get a diagnosis after doing an elimination/provocation diet where they cut out gluten for a time and then reintroduce it to see if any changed occur.

Some people have made the assertion that gluten sensitivity is the beginning of celiac disease, caught at a point before it has developed into the full-blown disease. They see CD and GS as resting on a spectrum, and warn that if GS is not detected and gluten eliminated before it has time to do more damage, full-blown celiac will result. Recent research, which I discuss below, presented findings that both supported and argued against this idea.

Finally, just to complicate the issue of what we do and don’t mean when we say “gluten sensitivity,” for some time, celiac was also referred to as gluten sensitivity or gluten sensitive enteropathy, so the nomenclature can get rather confusing.

Is Gluten Sensitivity the White Unicorn of the GI World?

Source: Christina Welsh (Rin) via Flickr

Despite there being no test to diagnose NCGS that is accepted by most medical doctors, a company called EnteroLabs does carry a stool test to detect the same markers in the blood, the theory being that antibodies will show up in the gut long before a person has reached a point critical enough for them to start showing up in the blood. I have come across a statement to this effect by a researcher and celiac/GS clinician; however, most doctors would dispute that, and a lot of people who are in the know about these conditions seem to think the EnteroLabs test is simply snake oil.

When I asked my own endocrinologist whether he was aware of gluten causing or exacerbating Hashimoto’s, he began to talk about the connection between celiac and Hashimoto’s but said there wasn’t any other connection to gluten. One reads of many people’s long road to diagnosis of celiac, simply because doctors didn’t think to test or wouldn’t order the tests. One also reads some in the medical community argue that gluten sensitivity hasn’t really been proven.

Yet one has only to spend a few minutes on the Internet to see that a number naturopaths or chiropractors discuss it as absolutely real, and I personally know some very sensible people who say that they or their child’s symptoms have improved or gone away after eliminating gluten.

So has GS just not been accepted by the medical community at large, despite research supporting it or is it actually the case that there’s not any scientific basis to gluten sensitivity, that the claims of the alternative practitioners I was reading were based on either a poor understanding or deliberate exaggeration of the relationship between celiac and other autoimmune diseases, which is a well-established and well-accepted fact?

The Evidence for Gluten Sensitivity: Exhibit A

Until 2011, there was a lot of anecdotal evidence of the existence of NCGS, but not much actual, well-designed research. There were both people that noticed immediate suffering after consuming gluten and people who observed an improvement in many types of symptoms after eliminating gluten and a recurrence upon reintroducing it. Unfortunately, with anecdotal evidence, it’s hard to pinpoint exactly what’s going on. There could be confounders or a placebo effect at work.

But in March of that year, a leading researcher in celiac disease, Allessio Fasano, and his colleagues at the University of Maryland published a study that’s being considered a landmark, wherein they describe what’s happening immunologically with celiac AND gluten sensitivity. The findings were surprising.

I Get Jiggy with Immunology

Source: TheJCB via Flickr

Whereas most people had suspected that gluten sensitivity could be a precursor to celiac, Fasano et al. found that the two conditions employ different immune pathways. Humans actually have two different types of immune reactions: adaptive and innate. If you want very clear animated explanations of this, go here and here. If you want to watch something humorous but make your head spin, go here instead.

The adaptive immune system is the one that begins to create antibodies to a substance, an antigen (like, say, gluten). In other words, after the first time this reaction is triggered, the body records what it has done and makes a Special Ops battalion of antibodies ready and waiting to mobilize and attack that same antigen more quickly and more efficiently when you’re exposed to it next time.

The innate immune system doesn’t work quite the same way. Instead of using antibodies to kill antigens, it uses a process wherein cytotoxic cells, cells that are generally toxic to all kinds of antigens, directly attack whatever has entered your system. In other words, in this reaction, a cell specific for attacking gluten or staph bacteria, or flu virus isn’t used. General soldiers are sent out, rather than ones that have been specially trained to deal with a specific antigen. That’s why you sometimes hear people say that the adaptive immune system is more “sophisticated” and the innate more “primitive.”

What happens in celiac disease is an adaptive reaction. Antibodies to gliadin, tissue transglutaminase, and endomysium are made. Many people suspected gluten sensitivity was the same thing, only it hadn’t risen to a detectable threshold. Instead Fasano and his colleagues found that gluten sensitive subjects were having primarily—but not entirely—an innate immune system reaction.

Important Findings of the Study by Fasano et al.

This landmark study makes for pretty dense reading, but it’s also fascinating because, while it doesn’t tell us exactly what GS is, it sheds a lot more light on the subject than simply “Yup, bread makes this patient ‘feel bad.’ “  Here are the broad strokes:

• GS subjects had less leaky gut than either celiac or dyspeptic control subjects. It’s known that CD patients have leaky guts and it’s thought that perhaps this starts the process of gluten being able to cross the intestinal barrier for a reaction to then take place. It was kind of assumed something similar would be going on in GS, but these results seem to say that’s not the case.
• Nearly half of the GS subjects actually did test positive for anti-gliadin antibodies.
• GS subjects who produced the AGA antibody did not all have the HLA-DQ*2 or DQ*8 gene that all celiac have, suggesting that GS, unlike celiac, may not be restricted to a particular genetic subset of people.
• GS subjects had certain higher IELs (intraepithelial lymphocytes) than dyspeptic control subjects, though lower than celiac subjects. IELs are a marker of inflammation in mucosa such as the GI tract and are a prominent feature of celiac. In fact, IELs can mutate into lymphoma, which is why celiac patients are at risk for Hodgkin’s lymphoma. The levels for these among GS subjects were outside the normal, however, so this led the researchers to hypothesize that the adaptive immune system is involved in GS at an intermediate level, though not as critically as it is in celiac.
• At least one toll-like receptor was elevated in GS subjects, and several others were elevated but not to a statistically significant level. That’s important because it lends credence to the idea that GS may precede celiac, since TLRs are responsible for priming for an adaptive response during an innate one.
• This quote by the authors was particularly concise and telling: “In itself, the absence of autoantibodies and intestinal lesions does not rule out the intrinsic toxicity of gluten, whose intake, even in non-CD individuals, has been associated with damage to other tissues, organs and systems besides the intestine.”

Other GS Research

The University of Maryland study is not the only one to indicate (though none quite as clearly) that GS is its own condition. A study from Australia, also in 2011, had people with irritable bowel but no celiac eat bread and muffins for several weeks—but they weren’t told whether they were being given the regular kind or the gluten-free kind. At the end of several weeks, those assigned to the gluten-full camp reported feeling worse. Part of me is not totally satisfied with this methodology, but in the context of other findings, I find it indicative, if not quite conclusive.

In another study, the authors hypothesize that “even in the absence of fully developed celiac disease, gluten can induce symptoms similar to [functional bowel disorder].”

Yet another case study discusses how an initial mistaken diagnosis of lupus was re-evaluated as NCGS on the basis of reactivity to parts of wheat other than just gliadin, some of which were IgA (what is normally tested in celiac) and some of which were IgG or IgE. In other words, the celiac panel gave the all clear, but in this case, the woman was having a reaction via a different immune pathway and to parts other than gliadin.

It’s also well-known that celiac disease is not the only disease in which the body attacks itself, with gluten as a trigger. In numerous papers, Marios Hadjivassilliou and colleagues, who run a celiac and gluten sensitivity clinic in Sheffield, England, detail how, instead of attacking the small intestine, an attack can occur on the brain, resulting in gluten ataxia or neuropathy, or the nervous system, resulting in the characteristic “celiac rash,” dermatitis herpetiformis.

A Clearer Picture

If one thing stands out about the reading I’ve done on gluten sensitivity and celiac–not on popular blogs but in medical research papers–it’s that the issue is not “Does this exist?” but “We know it exists, but what is going on and why is it different from celiac?” At least among the researchers who deal with the details on a daily basis, it’s not the existence but the relationships that are unclear at this point. Whether or not this information all filters down to clinicians in a timely manner is another matter.

Furthermore, as I’ll get into more down the road, gastrointestinal symptoms may not be present even with NCGS. Instead cognitive and nervous system issues may be the only things that indicate a problem. These may be attributable to another factor or condition, but in some cases at least, avoiding gluten may alleviate seemingly unrelated issues, at least in part.

Whether or not gluten sensitivity is a real, valid condition is a prerequisite question to everything else I needed to understand about gluten for my life. I mean, if it doesn’t exist, it certainly can’t be affecting my hypothyroidism or PCOS. If it does, then it’s reasonable to proceed to ask whether or not it could be related to those conditions.

Unfortunately, if doctors can’t yet agree on a test to accurately identify GS, it leaves the door open for people who don’t have celiac but who do have legitimate immune reactions taking place and medical reasons to avoid gluten to be lumped in with people who avoid gluten simply as a means of weight loss or “feeling better.”  The fact is, I’m not sure “feeling better” is such a dumb reason in its own right, but it may be that a gluten-free lifestyle allows some people to feel better for reasons other than the cessation of a damaging immune response.

Next in this series, I’ll cover the issue of the relationship between gluten sensitivity, Hashimoto’s hypothyroidism, and other autoimmune diseases that is alleged by some.

We’ve said gluten sensitivity is looking more and more like primarily an innate immune reaction, while Hashimoto’s hypothyroidism and all autoimmune diseases are adaptive. So if two different things are going on, is it even possible for one to affect the other? If so, are there any putative mechanisms that could cause a cross-linkage to happen? I’ll share what I’ve learned about that soon!

*******

I love to hear back from y’all! What’s been your experience with gluten and going gluten-free? Have you found the need to justify to yourself or others that gluten sensitivity is not simply a fad? If you know yourself to be gluten sensitive, what was your path to finding that out?

Why I’m Considering Going Gluten-Free

Source: Wheat Initiative
http://www.flickr.com/photos/wheatinitiative/7215324182/

***This is the first in a series of posts looking at non-celiac gluten sensitivity and autoimmune disease. Stay tuned for more posts in this series in the coming days.***

I really wasn’t planning on writing a post on gluten-free today, but in the spirit of putting what’s on my mind out there, here I am, doing just that. I’ve been researching the gluten-free diet/lifestyle/eating plan for a few months. This would involve completely eliminating wheat, barley, rye, spelt, and everything made from them (pasta, bread, pie, cake, tortillas, and even some sauces) I was strongly considering it before Christmas, but it just seemed overwhelming, so I put that idea down for a while.

Now I’m coming back to it and finding that some of the details of what I learned have turned a little rusty in my brain, and there were some questions to which I never really found a satisfying answer. Plus, I thought that there might be some of you who are evaluating gluten-free for yourselves or just want to know what all the hype is about.

Believe me, I started from the point of view that, for a lot of people, it was probably just that: hype. I’m not referring to people with notable digestive problems when I say that–or even kids with autism or unexplained skin rashes and allergies. My attitude had much less to do with ever having thought, about someone else, “Oh, that person is making a big deal out of nothing”  and a lot more to do with a) holding myself to a high standard of proof before saying I have a medical necessity for it, and b) wanting a reasonable assurance that if I go to all this trouble, it has a fair chance of actually helping me.

The things I’ve come across during my research have made me believe that there’s much more than “hype” to all the gluten-free buzz.

Why I Care

I was diagnosed with hypothyroidism at 15 and PCOS at 18 and have had many of the attendant symptoms. On paper, my thyroid numbers look good. I take my medicine, Armour thyroid, religiously, and it shows in terms of vastly improved lab numbers as compared to a few gap periods when I was not on medication in the past.

Sometimes when thyroid patients are not thriving on levothyroxine (Synthroid), they do better when they switch to Armour because it contains both T3 and T4. I was on Synthroid for the first five years after I was diagnosed, and it’s definitely true for me that I feel better on Armour.

Yet in terms of energy (especially), mood, cognition, other hormone levels, liver enzymes, and to some extent, cholesterol and blood sugar, all of which are medically established to be consequences of hypothyroidism, there is a general negative trend. It’s pretty clear that while the medicine may be controlling my thyroid numbers, it’s not mitigating the progression of any of thyroid disease’s other effects on my body–or at least not enough.

And I don’t accept that. I don’t accept that after you’ve taken your little pill, if it’s not doing everything that needs to be done, that’s it. I also don’t accept that the answer is to add more pills as more issues pop up.

Is Hypothyroidism a Big Deal?

Because I’ve been hypothyroid my entire adult life, I don’t exactly know what it’s like to feel “normal,” to have as much energy as other people do. Rather than mope about it, my strategy has frequently been to ignore it and have the same expectations from myself as for other people in terms of what I can accomplish, how much rest and sleep I need, what kind of exercise I can do, and (sometimes) what I can “get away with,” dietarily.

The fact is, though, that–without wallowing in it–I have a condition. No one tells diabetics to just buck up, “be normal,” and not worry about it because everyone recognizes they have a condition and it places some limitations on them. With hypothyroidism, it’s easier to be in denial about the gravity of my condition because the effects haven’t been as widely publicized as diabetes and because many of the effects develop slowly, like heart disease or cancer, and won’t reach a threshold of diagnosis until many years down the line.

But it’s sobering to realize that, in fact, diabetes is something that lies around the bend for a lot of hypothyroid people, as well as heart and liver disease. It starts out as a disease that affects your weight, energy, and cell respiration, when underneath all that, what it’s doing is affecting your vital organs and entire body.

PCOS is another autoimmune disease that may seem to affect one organ but is actually systemic. Ovarian problems are really just the tip of the iceberg.

Both conditions ought to be taken seriously.

A Possible Connection to Gluten?

Perhaps because I don’t accept that a pill or pills are all that can be done for me, I’ve always been open to other means of healing, particularly diet, exercise, and herbal medicine. My problem–which I fully admit–is that I’ve seldom been consistent enough to see an improvement, and that’s something I’m working on.

As I may have mentioned in the past, I’ve done other lifestyle diets. Pesco-vegetarian, food combining, vegan, and WAPF (loosely), to varying degrees of success in terms of weight loss and energy. I’m kind of burnt out on restrictions. However, about a year and a half ago I read an article by Chris Kresser discussing a possible connection between hypothyroidism and gluten intolerance–and, as I read on, I found out that it’s not only hypothyroidism but many other autoimmune conditions, another of which is PCOS. That was when I first began paying any attention to the gluten issue.

It may be hard for some people to understand why all the fuss. After all, while I do have a few pounds to lose, I’m only about 5-10 pounds over the weight I should be for my height. Some people comment that in years past, people couldn’t get fancy foods or afford to turn down any available food “and they did okay.” I get that, and I don’t want to be that fussy person, that “special case”–really, I don’t. But then again, there were a lot of modern illnesses people simply didn’t get very often then and also a lot of illnesses people just suffered through.

Even though it’s tempting to just hop on any bandwagon that would help me feel better, and even though I usually don’t require 10 peer-reviewed studies to try a (reasonable) alternative remedy, those who claim there’s a gluten-thyroid connection claim you have to go off it–down to the last molecule–for as much as 6 months to give it a fair shake. That’s a big undertaking and a lot to ask of your family. Eating out, parties, get-togethers, and even cooking at home would be difficult. Maybe that’s why I’ve invested more research in this than some other things I’ve tried. To ask others to go to that trouble for me, I want to make sure I really have a good reason. I also want to be fairly sure that this has a chance of improving my health.

So I began looking into it. Over the next few days, I’ll be sharing the information I’ve gathered and the questions I’ve tried to find answers to, like:

• Has it been medically established that non-celiac gluten sensitivity is a legitimate condition?
• Has it been proven that gluten can affect the thyroid and cause autoimmune diseases? If so, how?
• Has it been proven that a gluten-free diet can improve or eliminate autoimmune thyroid disease and other autoimmune conditions?
• How do you find out if you are celiac or gluten sensitive? What tests are considered valid?
• Can a person have celiac disease or gluten sensitivity if they don’t have digestive symptoms?
• If you are celiac or gluten sensitive, what can you do about it? Is it a feasible lifestyle?

I’ll give you a spoiler, though: based on the medical studies I’ve read, I am now convinced that non-celiac gluten sensitivity is a legitimate disease, and I believe there are plausible pathways by which it could create or have an effect on autoimmune diseases, specifically hypothyroidism. In addition, there are a lot of suspicious co-morbidities between celiac disease and almost every other autoimmune disease you can imagine. While correlation doesn’t prove causation, that’s an important part of the picture.

If I were a professional scientist, I would have to hold out for conclusive, overwhelming proof in order to make public recommendations. But I’m not. I’m me. My n equals 1, and the standard of proof is different. It has to be simply that there’s reasonable cause to believe a gluten-free diet will help my condition and won’t be detrimental in the process.

If you’ve considered going gluten-free for a particular health concern, especially an autoimmune disease, I hope that the information I’ll be posting over the next few days will help you better understand the issue, as it helps me to synthesize everything I’m learning.