Cheshire Cat: Where are you going?
Alice: Which way should I go?
Cheshire Cat: That depends on where you are going.
Alice: I don’t know.
Cheshire Cat: Then it doesn’t matter which way you go.

‚Äē Lewis Carroll,¬†Alice in Wonderland


Dear Dr. Aaron E. Carroll,

You don’t know me from Adam, but I feel compelled to write you an open letter here on my trifling¬†little health blog concerning your video on YouTube titled “You Probably Don’t Need to Be on that Gluten-free diet.” As you see, I’ve taken the liberty of inserting it at the top of this post.

Your video first came to my attention when it was featured on not too long ago. From there, it appeared on my Facebook feed courtesy of an old ex of mine who happens to be a retired medical doctor. A couple of other friends on that same platform also shared your video and I see that it’s garnered over 7,000 likes on Facebook.

Bully for you doctor! Isn’t it wonderful to receive positive affirmation for your views?

Now I spend quite a bit of time researching the scientific literature to unravel as best I can the complex mystery that is the gut, the trillions of bacterial inhabitants that call it home, and how this all affects health and longevity in humans.

What began as a journey to cure myself of gastrointestinal distress has since morphed into conveying scientifically grounded information to the hundreds of subscribers who read this blog. Writing it is a labor of love, but also a royal pain in the posterior.

The reason for the latter is that I won’t expound¬†on a topic without thoroughly researching it. That often involves spending valuable time driving to the local university medical center, accessing peer-reviewed literature in their library, reading often obtuse scientific papers and presenting¬†what I’ve learned in a way that is hopefully accessible to a lay public, all while trying to earn a living and lead an otherwise uneventful life.

I concern myself with getting the facts right because I fear losing whatever credibility I’ve earned since I began writing this blog. In other words, unlike some self-proclaimed health bloggers, I don’t make it a habit of reaching into my rectum, grabbing whatever I happen to find there and flinging it ever so furiously at the blinking cursor cruelly taunting me from a blank WordPress page.

The subject of gluten sensitivity has featured prominently in many of my writings, which is the major motivation for this post. But Dr. Carroll, I do have some questions about the conclusions you reached regarding gluten intolerance.

However,¬†before I get to those questions I assume that anyone reading up to this point¬†has already watched the video. If you haven’t, may I ask¬†that you do so now so you can follow along?


Alrighty then, everyone back?


First, let me start by agreeing with you that anecdotes can never prove causality. As we know, people can easily fool themselves. It is, after all, human nature to confuse correlation with causation.

It’s this same self-deception that often leads me to excoriate certain dietary recommendations dispensed by dietitians, nutritionists, and dare I say doctors, who all too often convince themselves that the findings generated by confounder-prone nutritional epidemiology offer any reliable guide for what a human should or shouldn’t eat.

So let me tip my hat to you for defending the scientific method!

And I also agree that self-diagnosis is never, ever to be encouraged. My long time readers know all too well that I have repeatedly discouraged the practice. Anyone who consults with me about their gastrointestinal complaints and has yet to see a licensed physician will be admonished by me to do so forthwith.

But here’s the thing Dr. Carroll. At about six minutes into your video, you begin to reference two studies by Dr. Peter Gibson’s research team located in Australia to support your contention¬†that few people would actually benefit from eating a gluten-free diet.

I’m well acquainted with this research group’s work on Fermentable Oligo-, Di- and Mono-saccharides and Polyols (FODMAPs). I first wrote about that dietary regimen in January of 2013. In a more recent post, I explored the downside risks of long-term adherence to this same diet, so I have kept up with their work.

But I admit some confusion as to how you arrived at your conclusion that going gluten-free is pretty much a useless fad outside of confirmed celiac disease or wheat allergy. If you are¬†directing your comments to healthy individuals devoid of physical or mental illness, then I can’t say I take much issue with your advice, although many people who claim perfect¬†health are often oblivious to symptoms that suggest otherwise.

That said, I imagine that many people who happen upon your video are suffering from intractable health issues, be they physical, mental or both, and in those cases I beg to differ with your reasoning.

I want to briefly review the studies you referenced, but in reverse order if I may. The 2014 paper you cited is titled Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity.

As you correctly stated, 72% of the 147 respondents did not meet the criteria for non-celiac gluten sensitivity (NCGS), either because they had not been tested for celiac disease, or still experienced GI symptoms even after excluding gluten from their diet, or failed to adhere to a¬†gluten-free diet or any combination of the above. Of those¬†who completed the survey, just forty¬†met the criteria of having NCGS as defined by Dr. Gibson’s team.

That of course doesn’t prove¬†that those excluded from this diagnosis did not experience¬†some reaction to gluten with the obvious exception¬†of those who were not actually on a gluten-free diet. It only proves that self-diagnosis is as regrettably rampant in Australia as it is here. It also hints¬†that resolving gut dysbiosis frequently requires more than dietary change.

But I also take issue with these researchers defining¬†NCGS as requiring some evidence of¬†gastrointestinal upset.¬†This criterion seems to be at odds with other¬†published data¬†as I’ll explain shortly.

It was from this group of forty that this same team recruited the thirty-seven participants for the study you referenced immediately before this one: No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates.

The unstated assumption you seem to be making in citing these two papers¬†is that¬†relief from gastrointestinal distress¬†is the sole marker¬†for judging whether going gluten-free is rational, separate from the desire to institute the positive¬†dietary changes you mentioned toward the end of your video. In other words, you appear to be making the argument that if there is no proof that eating gluten-free improves gastrointestinal¬†symptomology, there isn’t any reason to restrict your diet in this manner absent confirmed celiac disease or wheat allergy.

I notice, however, that you hedge your bets a bit when you admit there is probably something to gluten sensitivity, eye roll notwithstanding. But since you stated “it’s likely pretty darn rare,” you make it clear that most gluten avoiders are not making a rational decision.

Now in your opening comments, you tell us that too many celiacs continue to go undiagnosed by their primary care physicians, which is true. But you fail to mention that the reason this is so is because many of these people have what is known as silent celiac disease.

The overwhelming majority of symptoms that silent celiacs relay to their clinician have little or nothing to do with gastrointestinal function. In fact, they experience extraintestinal disorders like depression, anxiety, ataxia, manic-depression, joint and muscle pain, psychosis, peripheral neuropathy, memory lapses, brain fog, certain cancers, dermatological diseases and even schizophrenia.

And because these patients rarely, if ever, complain of gastrointestinal upset it takes on average eleven years for these people to be properly diagnosed in the United States. That’s eleven years of bouncing from one doctor to another, then to a psychiatrist, back to another doctor, once again back to a psychiatrist, and if they’re finally lucky back to a doctor who medically confirms that eating the “Staff of Life” is the root cause of their hellacious health journey.

Which brings me to my first question. How do you know there isn’t a gray area where consuming wheat or other gluten-containing grains causes similar illnesses in those who have¬†been medically screened¬†to be free from celiac disease?

You stated at the end of the video that a patient should ask anyone recommending they go gluten-free in the absence of celiac enteropathy¬†or wheat allergy, even if that person happens to be their physician, to ask for the evidence for that recommendation. As you put it: “I bet there won’t really be any.”


Well doc, I don’t know where you conduct¬†your research, but here in sunny, albeit parched, Southern California, finding that evidence wasn’t terribly difficult¬†to do.

The placebo-controlled, crossover study you referenced was one of two papers featured in my post “Dietary Opioid Peptides, Antioxidant Status, and DNA Methylation.”

You failed to inform your video audience of a curious finding that I highlighted in that article. Not only did those on a FODMAP-elimination diet suffer no increased perception of gastrointestinal discomfort when challenged with gluten, they experienced less distress than those on placebo, so much so that it reached statistical significance.

Aren’t you in the least bit curious as to why?

As I wrote then, I don’t consider this to be a good thing. On the contrary, it may explain much¬†of what I’m about to share.

The Gibson crossover paper was published in the journal Gastroenterology in the Spring of 2013. But another randomized, placebo-controlled crossover study published in April of this year that you seemed to have missed during your research found:

“Short-term exposure to gluten specifically induced current feelings of depression with no effect on other indices or on emotional disposition. Gluten-specific induction of gastrointestinal symptoms was not identified. Such findings might explain why patients with non-coeliac gluten sensitivity feel better on a gluten-free diet despite the continuation of gastrointestinal symptoms.”

The development of depression reached statistical significance and occurred only after three days of eating gluten in subjects who had previously been on a gluten-free diet. We can only speculate what the effects would be on say anxiety or other mental states had the trial gone on longer.

The researchers hypothesized that these effects could be due to several factors including increases in cortisol, disruption to tryptophan metabolism, the influence of gluten opioid peptides on brain function or changes to gut flora.

But Dr. Carroll, do you know what’s really “curiouser and curiouser” about this paper?

Three¬†of the researchers who wrote it—

[long pause for dramatic effect]

¬†—were the same researchers on the studies¬†you cited to¬†support your claim¬†that going gluten-free in the absence of confirmed celiac disease or wheat allergy is only for those of who enjoy jumping on food-fad bandwagons. (1) And yes doctor, one of the three¬†researchers was none other than Dr. Peter Gibson. In fact, these researchers derived their data from twenty-two of the thirty-seven subjects from the placebo-controlled trial¬†you referenced.

Ain’t that just a hoot? It sure¬†was for me!

Now to be fair, this was a very small study just like the FODMAP study it was derived from. More research in this area needs to be conducted and I eagerly await¬†reading those studies if they’re ever published.

But I can’t help wondering why you avoided mentioning this paper in your video when you referenced this same research group’s other work to bolster your “nothing to see here folks so just move along” claims?

Did you accidentally spill the beer you were drinking on your keyboard making any further research impossible?

Was the internet closed that day?

Or did these findings not fit your preconceived narrative?

According to the CDC:

“…among 235,067 adults (in 45 states, the District of Columbia [DC], Puerto Rico, and the U.S. Virgin Islands), 9.1% met the criteria for current depression (significant symptoms for at least 2 weeks before the survey), including 4.1% who met the criteria for major depression. In this study, increased prevalence of depression was found in southeastern states, where a greater prevalence of chronic conditions associated with depression has been observed (e.g., obesity and stroke).” (2)

That averages out to about one in ten Americans suffering from this mood disorder. Not only that, but as alluded to in this quote, depression is also highly associated with other conditions like stroke, type 2 diabetes, anxiety, insomnia and heart disease. As I’ve written elsewhere on this blog, many of these illnesses are indicative of chronic endotoxemia and deranged cortisol metabolism.

If what you called “a much more sophisticated study design” also demonstrated a statistically significant increase in the onset of depression after only three days of gluten consumption, shouldn’t you have let your audience know?

And how exactly did you fail to come across the fibromyalgia study I wrote about on April 30th of this year? Let me make it easy for you by re-printing the study abstract:

“Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause, and only symptomatic treatment with limited benefit is available. Gluten sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with the manifestations of FM, including chronic musculoskeletal pain, asthenia [weakness], and irritable bowel syndrome. The aim of this report was to describe 20 selected patients with FM without CD who improved when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal biopsy, and HLA typing were performed in all cases. CD was ruled out by negative anti-transglutaminase assay results and absence of villous atrophy in the duodenal biopsy. All patients had intraepithelial lymphocytosis without villous atrophy. Clinical response was defined as achieving at least one of the following scenarios: remission of FM pain criteria, return to work, return to normal life, or the discontinuation of opioids. The mean follow-up period was 16 months (range 5‚Äď31). This observation supports the hypothesis that non-celiac gluten sensitivity may be an underlying cause of FM syndrome.”¬†[emphasis mine]¬†(3)

All I can say is thank [insert favorite deity here] these women started their gluten-free diet¬†before laying eyes on¬†your video. Otherwise, they might still be “enjoying”¬†their wholesome¬†wheat products with no clue as to what was contributing to¬†their living nightmare.

In that post, I listed the following symptoms of this disease:

  • presence of mood and behavioral disturbances
  • bone and/or joint pain
  • muscle cramps
  • IBS, GERD, and other gastrointestinal complaints
  • leg numbness
  • loss of weight
  • chronic fatigue
  • brain fog
  • anemia and other vitamin and mineral deficiencies
  • psoriasis, acne, or other skin outbreaks
  • canker sores

Notice that except for IBS, GERD and other gastrointestinal complaints, none of these symptoms have anything ostensibly to do with the gastrointestinal tract. And again let me re-emphasize that all the women who experienced complete remission had tested negative for celiac disease as assessed by both blood tests and endoscopy.

How many fibromyalgia patients do you think a primary care physician sees during his or her professional career? How many of them have ever counseled these patients to avoid gluten as a possible way to resolve their disease? And of those who have, how many of their patients will now hesitate to do so because of your video?

On February 6th of 2013, I published an article titled: “Can You Eat Your Pasta and Have it Too.” In that post I wrote about a randomized, placebo-controlled crossover¬†study showing how adding inulin, a prebiotic, to wheat pasta decreased markers of intestinal permeability caused by consuming this food in young, healthy Italian men.

Do you think a leaky gut is a good thing doctor? You probably don’t know this, but gluten increases the expression of intestinal zonulin. The up-regulation of this protein causes gaps between gut epithelial cells to open allowing anything that happens to be in the intestinal lumen to slip through thus provoking inflammation.

This increase in zonulin expression¬†is particularly prolonged in anyone unfortunate enough to carry either the HLA-DQ2 or HLA-DQ8 genetic haplotype, the same haplotypes that predispose to celiac disease. In the United States, it’s estimated that fully 50% of the population carries at least one of these genetic markers,¬†although no one has any real idea how prevalent they truly are.

To quote the world’s reigning authority on this topic:

“The gastrointestinal tract has been extensively studied for its digestive and absorptive functions. A more attentive analysis of its anatomo-functional characteristics, however, clearly indicates that its functions go well beyond the handling of nutrients and electrolytes. The exquisite regional-specific anatomical arrangements of cell subtypes and the finely regulated cross-talk between epithelial, neuroendocrine, and immune cells highlights other less-studied, yet extremely important, functions of the gastrointestinal tract. Of particular interest is the regulation of antigen trafficking by the zonulin pathway and its activation by intestinal mucosa-microbiota/gluten interactions. These functions dictate the switch from tolerance to immunity and are likely integral mechanisms involved in the pathogenesis of inflammatory and neo-plastical [tumor] processes.

The classical paradigm of inflammatory pathogenesis involving specific genetic makeup and exposure to environmental triggers has been challenged recently by the addition of a third element, the loss of intestinal barrier function. Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food-derived environmental triggers [gluten] or changes in gut microbiota all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer. This new theory implies that once the pathological process is activated, it is not auto-perpetuating. Rather, it can be modulated or even reversed by preventing the continuous interplay between genes and the environment. Since zonulin-dependent TJ [tight junction] dysfunction allows such interactions, new therapeutic strategies aimed at reestablishing the intestinal barrier function by downregulating the zonulin pathway offer innovative and not-yet-explored approaches for the management of these debilitating chronic diseases.” (4) [emphasis mine]

Now Dr. Carroll, one of the “therapeutic strategies aimed at reestablishing the intestinal barrier function” is going gluten-free because that food protein reliably increases zonulin expression. Taking prebiotics and probiotics are also “therapeutic strategies” that do the same, but even I foster some reservations¬†about¬†their efficacy given the amount of wheat¬†consumed by the typical American.

And what, Herr Doktor, are we to make of this German study published in 2012:

“Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill- defined component of innate immunity in celiac disease. We identify the a-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4‚ÄďMD2‚ÄďCD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients‚Äô biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.” [emphasis mine] (5)

In your esteemed medical opinion, do you honestly believe that consistently ingesting a food that triggers the same immune receptors activated by lipopolysaccharides is really the best way to maintain vibrant health?

Mind you, we are no longer talking about gluten here, but another constituent of wheat—one of its highly evolved natural plant pesticides that along with wheat germ agglutinin, exacts a toll on any animal (including us) that happens to eat it.

Here’s yet another study that seems to have escaped your attention, “Gluten sensitivity masquerading as lupus erythematosus:”

“Gluten sensitivity has been likened to ‚Äė‚Äėa many-headed hydra‚Äô‚Äô because of its diverse manifestations. Although most physicians may be familiar with the classic presentation of gluten sensitivity as an enteropathy (CD) [celiac disease], it is worth bearing in mind that the prevalence of CD in the ‚Äė‚Äėhealthy‚Äô‚Äô population in European countries and the USA is as high as 1%. Therefore, for every patient presenting to a gastroenterologist with the classical presentation of one or more of diarrhoea, abdominal discomfort, bloating, weight loss, steatorrhoea, and/or anaemia, there are eight patients without gastrointestinal symptoms (silent CD). Furthermore gluten sensitivity may solely present with neurological dysfunction (ataxia and peripheral neuropathy being the commonest). Only a third of patients presenting with neurological dysfunction due to gluten sensitivity will have evidence of an enteropathy on duodenal biopsy. The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity. [emphasis mine]

Did you get that doc?

Some, if not all, people diagnosed with lupus and many other diseases¬†may actually be reacting to wheat even when there’s no evidence of autoimmune damage to the small intestine.

There is also no solid proof that having celiac disease is a necessary precondition for the development of gluten ataxia. (6) For those of my readers who don’t know what gluten ataxia is, it’s an autoimmune reaction to gluten separate and apart from celiac disease that irreversibly causes destruction of brain cells in the cerebellum. This leads to progressive impairment in how a person walks as well as their overall coordination.

Hey doc, it’s almost like researchers keep coming across¬†that amorphous gray area I questioned you about at the top of this post. Why this whole issue of gluten intolerance doesn’t seem to be as black and white or as cut-and-dried as you led your YouTube and Facebook followers to believe, now does it?

Now I could continue¬†writing about gluten’s connection to autism, psychosis, type 1 diabetes and schizophrenia (7) (8) (9) (10) (11), but I have to get back to earning the money I need to pay my bills. But I think I’ve made my point that not only is gluten sensitivity real,¬†many researchers from across the globe are now beginning to examine just how big a problem it truly¬†is.

So let me pose some final questions to you doctor.

Does it really serve the public interest to rib those who decide to go gluten-free in the hopes of avoiding some of the diseases I just wrote about? Or who, like me, experienced resolution of some long-standing health issues even after my doctors determined I didn’t have celiac disease? Issues like insomnia, chronic constipation, intractable¬†dental plaque, muscle aches and joint pain, brain fog and mood swings, canker sores, recurring sinus infections, acne, night-time breathing difficulties, headaches, anxiety and acid reflux.

Yes, yes, I know, I know these are nothing more than anecdotes and as you stated in your video, “The plural of anecdote is not data.”¬†But the studies¬†I just highlighted¬†suggest that¬†resolution of these health problems was not merely¬†due to a nocebo effect.

Now far be it from me to claim that gluten grains are the only suspect foods we should concern ourselves with¬†in regards to the gut, the microbes that reside therein, and overall health. I’ve written extensively on other problematic foods like polyunsaturated fats, fructose, artificial sweeteners¬†and alcohol.

Nor do I discount how the composition of gut flora plays a major role in gluten grain intolerance.¬†It’s highly likely that the increases seen over the past few decades in the prevalence of celiac disease and gluten sensitivity—not to mention other food allergies—is directly related to the devastation wrought on the human microbiome; a devastation that was caused in no small measure by the indiscriminate dispensing of antibiotics courtesy of your profession.

Nevertheless, whenever I speak with anyone who I suspect has a leaky gut, one of the pivotal recommendations I make is to completely eliminate gluten grains from the diet. This is by no means a cure-all doctor, but the last thing these people need is to eat a food that adds gasoline to an already raging inflammatory fire.

Now I must admit that I do so envy your confidence doctor, really I do. I wish I could be as self-assured as you are when it comes to telling complete strangers that eating wheat is entirely safe absent celiac disease. That cocksure bravado would certainly be an asset in my line of work.

But there’s a hackneyed saying that by the time a physician retires, 50% of what they learned in medical school is proven¬†false. Given what’s happened in the field of gut flora research, I suspect this adage contains more than a modicum of truth.

It’s humbling, and somewhat¬†frightening, to realize that what you think you know to be true may in fact be proven wrong. Any scientifically minded person is always haunted by that possibility.

But in your case doctor, the last thing that comes across in your video is any semblance of humility. Maybe your audience would be better served by you spending less time in front of a camera and more time perusing the scientific literature.

I’ll leave you with another one of my favorite quotes from that other Carroll. For¬†some reason viewing your video brought it to mind:

‚ÄúI don’t think…”

“Then you shouldn’t talk, said the Hatter.‚ÄĚ

Best regards,

Ray Medina

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