It’s funny how diseases get started. Some are pretty obvious: infectious bacteria, viruses, and mutations causing a myriad of cancers. But then, there are those epidemic “syndromes” that have a more questionable origin.

In the 60’s, allergies to petroleum products were all the rage. People moved out of homes—in which they had lived for decades—because they discovered that the walls or the carpets or the stuff in the bathroom cabinet caused them to itch or gave them heart palpitations, headaches, or a foggy mind, or even outright depression. A cottage industry, called “clinical ecology,” sprang up, mostly in the South. People traveled to Texas where they lived for weeks on end in rooms with stainless steel walls (no formaldehyde) to get a diagnosis or to just get relief from the modern world. A colleague of mind, a clinician and a scientist, was so convinced he suffered from this syndrome that he moved out of his home and into a shed that presumably was formaldehyde-free. He even conducted a small clinical trial at the behest of the Society of Clinical Ecologists and found that…the thing didn’t exist. Yes, the effects of formaldehyde on the airways are real. But foggy mind? depression? No. Further investigations uncovered some “inaccuracies” in the medical records, and to add insult to injury, formaldehyde was detected in those stainless steel “clean” rooms.

I was a freshly minted physician at the time, and this episode taught me an invaluable lesson: When a syndrome enjoys sudden popularity and is so vague as to defy a straightforward diagnosis, handle with extreme skepticism.

Now let’s move on to this era’s popular syndrome: Gluten sensitivity or, more accurately, non-celiac gluten sensitivity. But first, let’s distinguish between gluten sensitivity and the well-characterized disorder, celiac disease.

 

What is celiac disease?

Celiac disease is an autoimmune disease that is triggered by gluten in the diet and results in the destruction of the villi (small projections of the small intestine that carry digestive enzymes of their surfaces). The consequences are malabsorption, abdominal pain, bloating, vomiting, diarrhea, weight loss, and fatigue. Symptoms can vary from mild to severe. The definitive diagnosis is made via a specific blood test and intestinal biopsy.

The disease was initially thought to be extremely rare. Ten years ago, it was estimated to occur in 1 in 10,000 people. But due to increased awareness among physicians, the prevalence of the disease has been recently shown to be 1 in 100. However, because of the wide variation in symptoms, only 5% are aware that they have it.

 

What is non-celiac gluten sensitivity?

Awareness of non-celiac gluten sensitivity (NCGS) got its start in the 70’s and 80’s when a few small and poorly designed nutritional and immunological studies were published in third-line publications. But in 2011, a real study—double-blind, randomized, and placebo-controlled—was published by Peter Gibson and his colleagues at Monash University in Australia. They studied 34 people with irritable bowel syndrome who did not have celiac disease, but complained of bad reactions to wheat, a gluten-rich grain. The salient finding was that of 19 patients in the gluten group, 13 (68%) reported that symptoms were not adequately controlled by a gluten-free diet compared with 6 of 15 (40%) on placebo. Pretty damning. Charitably, the authors concluded that

“Non-celiac gluten intolerance” may exist, but no clues to the mechanism were elucidated.”

Gibson, a gastroenterologist, did not just stop there. The fact that gluten did not prove to be the culprit did not mean that the symptoms were not be caused by something else in the food. In 2013, he and his colleagues reported on a second study. Again, they tested 34 people with irritable bowel disease who did not have celiac disease but reported sensitivity to gluten. Initially, all of the patients received a diet low in FODMAPS for 2 weeks. FODMAPS are a group of fermentable carbohydrates that some people have difficulty digesting because of a deficiency of one or more enzymes. Although everyone continued on the low FODMAPS diet, they were randomly assigned to one of three groups: high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for an additional week. This was followed by a washout period of at least 2 weeks. The authors concluded,

“In contrast to our first study… we could find absolutely no specific response to gluten”

Halleluja, scientific integrity at its best.

One of the problems of the two papers was that the NCGS was “self-reported”, namely, the patients made the diagnosis. Another problem was the small number of subjects. Not to let that go unexamined, Gibson conducted a larger study to check if patients who believed they suffered from NCGS indeed had the disease. They recruited 147 patients who completed a questionnaire and then tested with a similar protocol to the previous study. The results largely confirmed the previous findings.

 

My take

There most probably exists a cohort of people who have an undiagnosed celiac disease. The syndrome runs a gamut of symptoms, from severe abdominal pain and chronic diarrhea to headaches and fatigue, but no GI symptoms at all. As mentioned, it is estimated that more than 90% of the people who suffer from celiac don’t know it. Other people may suffer from insufficiency of FODMAP digestion, manifesting in bloating and diarrhea.

But these two diseases don’t account for epidemic proportions of people who self-diagnose as NCGS. Thirty percent of the U.S. population attribute a variety of symptoms to gluten. Do 90 million people walk around with bellyaches, bloating, diarrhea, headaches, and fatigue? If so, Donald Trump may be right: Our country is in the toilet. But just like his portrayal of the U.S., this is simply not credible. If you suffer from these GI symptoms, by all means, see your doctor and get a proper blood test and a biopsy, to rule out celiac disease. I would venture a guess, though, that most people will turn out to suffer from “epidemicitis” (that’s a made-up word so don’t bother to Google it), and just like the “hypoglycemic epidemic” of a few years ago, this one will pass as well.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

8 COMMENTS

  1. A friend of my wife tried a gluten-free diet for a couple of weeks, without any real medical reason, and since then she has developed what it seems like a gluten-allergy, or at least sensitivity, when she re-introduced gluten to her diet, which she did not have before. Of course, n=1 data, but I would in general not advise people to jump on the gluten-free bandwagon without proper justification, or you might end up with the real thing afterwards.

  2. My husband went gluten free and immediately his vitamins and minerals, which were mediocre with supplementation, became perfect without. After being gluten free for 4 months he accidentally ingested some and had 6 weeks of bloating, diarrhea and falling zinc. B12 and ferritin levels.

  3. I wish you were right and NCGS didn’t exist. Whatever you like to call it, it has blighted the last 23 years of my life. In fact I am sure you’re absolutely wrong. I react to all cereals to some extent – and wheat and maize/cornflour almost immediately affect my heart, which goes into atrial fibrillation, while my brain becomes cloudy and I get a headache. To have the coeliac test you need to eat wheat for several weeks. One meal which included wheat and I’d be hospitalised, if not dead. I ate some wheat by mistake in 2012 and had to be rushed to hospital. So I don’t care which label you put on me, or whether you call it my imagination – I’m staying away from them. And as I didn’t even know about gluten intolerance or coeliac problems when this problem first occurred in the early 90s, I don’t see how I could be following any fashions. Maybe Mike has a point about pesticides. I heard a farmer boasting on TV last week of how well his wheat stood up – because he used fungicides four times during the growing season. As well as the other chemicals. Shudder. Or maybe Monsanto’s carefully bred seeds are resistant to humans as well as to pests. Or maybe doctors don’t know everything, well of course they don’t. I’m not getting at doctors. They can be wonderfully helpful. But no one is perfect.

    • Anna, your symptoms are real, and if you didn’t include corn flour I would have guessed that that you suffer from classic celiac disease. The fact that one slice of bread gives rise to a violent reaction is characteristic of celiac. I would urge you to see a gastroenterologist for a complete workup, including blood tests and biopsies (not less than 6 samples). As to your comment about physicians’ lack of knowledge – I agree completely. Despite all the scientific progress, the practice of medicine is still an art. Years ago it was shown that 50% of what we teach in medical school would prove incorrect within 5 years. You can view such a finding as a testament to the rapid progress being made in medicine. We should also view it as a call for exercising humility about the extent of our knowledge.

  4. The second study mentioned above is based on three groups using various ratios of whey/gluten, both proteins linked to porous gut. This study is flawed, it should have used another type of control protein.

    • Celiac disease is not a consequence of a “porous gut”, but due to intestinal lymphocytes and antibodies to gliadin, a component of gluten. Whey does not contain gliadin, or any peptide sequence that cross-reacts with gliadin.

  5. Do you think there is any truth to the idea that the sudden uptick in apparent gluten intolerance coincides with newer wheat harvesting practices, in which farmers poison the wheat to kill it before harvesting it, because it is easier on their equipment. The idea is that trace amounts of the herbicide used in this process remain after washing and some are more tolerant of it than others. Interestingly, a friend of mine who becomes ill eating wheat products in the US went on vacation and on numerous occasions, ate pasta made in Italy and was unexpectedly fine. Upon return to the US and hoping for an inexplicable miracle cure, they resumed eating wheat foods and immediately became sick again.

    • Your friend’s experience is really impressive and raises the very questions you are raising. If the sudden rise in wheat sensitivity is real then something, still unknown, has changed. What this mysterious factor could be is open to speculation, and good biochemical, toxicological, and immunological studies should provide the answer.

LEAVE A REPLY

Please enter your comment!
Please enter your name here

This site uses Akismet to reduce spam. Learn how your comment data is processed.