For the 2016-2017 academic year, our second year course IMM250 (Infection and Immunity) saw the introduction of the “IMMpress Prize for Best ‘Science & Society Paper’”. The purpose of this competition is two-fold: first, to emphasize to students the importance of accurate, engaging communication of scientific concepts to the general public; and second, to connect undergrads with science as it is perceived in the “real world”. Congratulations to Jonathan Holoff, our inaugural winner selected from a long list of about 1,000 students. Please enjoy his delightful article on the gluten-free fad and its scientific basis (or lack thereof?!). Many thanks to the IMMpress team for this collaborative effort. – The IMM250 coordinators


gluten-2984643_1280Once upon a time, concern regarding gluten was relegated to the dusty back corners of the internet and health food stores. Over the past few years, however, this awareness has invaded the broader public consciousness, claiming stake over prime shelf-space at the likes of Walmart and Costco. Pasta, ice cream, pizza dough, and beer: all these items and many more are now readily available gluten-free. Nearly as impressive as this product selection is the growing list of maladies for which gluten is purportedly the culprit: bowel problems, eczema, headaches, even ADHD. These claims were enough to get me thinking: are bagels the true cause of my dry skin in the wintertime? Would I be better-off swapping my Adderall prescription for a daily regimen of gluten-free scones? With the cold weather and exam season fast approaching, these questions took on an added sense of urgency.

Getting to the bottom of these claims, however, has proven to be tricky business for science. Anyone keen enough to delve into the scientific literature in search of definitive answers is likely to emerge from the pursuit both weary-eyed and disappointed. And if that now weary-eyed individual is old enough, he or she may be tempted to summarize their findings by quoting former US Defence Secretary Donald Rumsfeld: “There are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know.

But there are also unknown unknowns – the ones we don’t know we don’t know.” Rumsfeld issued this infamous remark in 2002 when he was questioned about the evidence linking the Iraqi government to weapons of mass destruction – but his statement does just as well to sum up the current scientific consensus on the relationship between gluten and disease. So what exactly are the “known knowns”, the “known unknowns”, and the “unknown unknowns” concerning gluten’s effect on health? Does the science validate the growing public concerns and shift in consumer trends of the past few years? And if the science isn’t there, then what’s really driving this craze?

The “known knowns”

This much we know for certain: gluten is a protein complex found in wheat and other grains. When we eat gluten-containing foods, ouragriculture-1845835_1920 body digests it the same way it does any other. It’s broken down into molecular fragments and then absorbed into the bloodstream in the small intestine. As the primary site of nutrient absorption, the small intestine also presents fertile opportunity for pathogen entry into the body. Thankfully, our immune system has coevolved strong defences – both onsite and in the surrounding tissues – that kill off these inadvertently-ingested predators.

Unfortunately, in approximately 1% of the population, consuming gluten triggers an autoimmune response known as Celiac disease. The culprit is gliadin, which is one of the constituent breakdown products of gluten. Celiac patients have a “leaky gut” and this allows for gliadin fragments to pass through their gut wall. These peptide fragments are then detected by immune cells that mistakenly identify gliadin as a foreign pathogen. This triggers the immune system to unleash an inflammatory response that, over time, can damage the epithelial layer of the small intestine. Celiac disease has no cure, but biomarkers exist for definitive diagnosis and the disease can be remedied by adhering to a strict gluten-free diet. Once the inflammatory trigger has been removed, celiac individuals experience a complete alleviation of symptoms.

The “known unknowns”

There is another subset of the population that reports gluten sensitivity. These individuals present with a wide spectrum of symptoms ranging from GI upset and fibromyalgia to cognitive and psychological impairments such as fatigue and depression. The term Non-Celiac Gluten Sensitivity (NCGS) has been coined to describe the condition. What distinguishes NCGS from Celiac disease is that NCGS sufferers lack the diagnostic markers present in Celiac individuals. Furthermore, no plausible biological mechanism has been proposed for how gluten causes the laundry list of NCGS symptoms.

With this background in mind, a small study was conducted in 2011 by researchers in Australia to “determine whether gluten ingestion can induce symptoms in non-celiac individuals.” They found that when gluten-containing food was administered to self-reporting NCGS patients under double-blind conditions, it really did make them sick. The study offered the cautious conclusion: “‘Non-celiac gluten intolerance’ may exist, but no clues to the mechanism were elucidated.”

noodles-1631863_1920The collective reaction that followed shows how even simple scientific results risk misinterpretation by those unfamiliar with how work proceeds in the sciences. As far as many advocates of NCGS were concerned, the matter had been settled. NCGS exists – it was time for everyone to pack up and go home. The researchers behind the study, however, reacted very differently to their own results. The study had demonstrated that the association between gluten-containing foods and self-reported GI symptoms could withstand the rigours of a double-blind trial. Essentially, something real was going on, and determining just what that “something” was required further investigation. A follow-up study was conducted. This time, the investigators removed short-chain carbohydrates (referred to as FODMAPs) from the diet of their test subjects. After isolating FODMAPs as a potential confounding variable, the researchers found that the association between gluten and GI symptoms disappeared.

The “unknown unknowns” A significant portion of the population has bought into the gluten-free craze on even more dubious grounds; these consumers believe that ridding their diets of gluten is synonymous with a “healthy lifestyle”. In fact, according to Agriculture Canada, they account for over 75% of the gluten-free market.

The trouble is that these claims are virtually impossible for science to debunk. To begin with, there will never be a randomized control trial to test the hypothesis, “A gluten-free diet is healthier than a gluten-containing diet.” That type of trial would take decades and require thousands of participants, costing billions of dollars. When hypotheses are not testable in laboratory or clinical settings, science often hands them over to epidemiology. However, teasing out what effect (if any) gluten has on incidence rates of chronic disease may lie beyond the reach of epidemiological investigation. In 2007, the New York Times ran an in-depth story on this matter. The article explains that lifestyle factors are extremely challenging to isolate and study. It goes on to quote prominent epidemiologists who believe that in taking on these types of questions, epidemiology may be extending itself beyond the inherent capabilities of the field.

The gluten-free profiteers

While some questions remain unanswered, it’s clear that the science does not justify the recent shifts in consumer purchasing habits. Between 2009 and 2014, the sale of gluten-free products grew 34% annually in the United States – a market trend that is expected to continue. According to one report, Celiac patients now account for a paltry 5% of the gluten-free market. This all begs the question: what’s fueling this craze?

It’s hard to pinpoint the exact origins of the aversion for all things gluten. But like any fad, it has given rise to an industry that seeks tobutton-1398594_1920 reap the benefits. Broadly speaking, the gluten-free business is comprised of two types of companies. First, there are small-to-mid-range companies in the “health and natural foods” industry. Historically, they have catered to a wealthy and health-conscious customer base. These companies have found themselves the serendipitous beneficiaries of the gluten-free diet fad, which originated from within their pre-established product space. Second, are the major food conglomerates like General Mills and Nabisco. These companies had no involvement in initiating the gluten-free craze. However, once a fad is out there, these companies not only adapt to the market, they also shape it though public relations and advertising.

Science and medicine have also been of service (albeit unwittingly) to gluten-free sales. Some have suggested that the 2011 Australian study played a significant role in setting off the market explosion of gluten-free. Doctors may also share some of the blame. Patients that present with GI symptoms in clinical settings want definitive diagnoses. Mary Schluckebier, executive director of the US based Celiac Support Association, speculates that this pressure explains the rise of NCGS. It is a way to “appease impatient patients” in search of a diagnosis. But the FODMAPs study indicates that the label “Non-Celiac Gluten Sensitivity” might be a terrible misnomer.

Conclusion

There is one final point that can be derived from the “known unknowns” analogy. When one has a predetermined agenda, ambiguity and confusion surrounding the evidence can be your friend. And scientific progress – despite the general public’s belief to the contrary – proceeds in messy, ambiguous, and sometimes confusing ways. Whatever the next diet fad may be, those hawking it will surely find sufficient material in the scientific literature to convince themselves and others of their claims. Navigating fact from fad can be challenging, but as for me, I’ve made my decision. This exam season, I’ll be forgoing the gluten-free scones and sticking to a healthy dose of skepticism.

References:

  1. Clemenza, Liliana. “Tolerance to Food Protein and Food Allergy.” IMM250 Lecture 4, University of Toronto. 4 Oct 2016.
  2. Shewry, Peter R et al. The Structure and Properties of Gluten: An Elastic Protein from Wheat Grain.Philosophical Transactions of the Royal Society B: Biological Sciences 357.1418 (2002): 133–142. PMC. Web. 21 Nov. 2016.
  3. Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106:508–514.
  4. Biesiekierski JR, S.L. Peters, E.D. Newnham, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.Gastroenterology, 145 (2013), pp. 320–328
  5. “‘Gluten free’ Claims in the Marketplace.” Agriculture and Agri-Food Canada, 08 Dec 2015. www.agr.gc.ca/eng/industry-markets-and-trade/statistics-and-market-information/by-product-sector/processed-food-and-beverages/reports-and-resources-food-processing-innovation-and-regulations/gluten-free-claims-in-the-marketplace/?id=1397673574797.
  6. Kresser, Chris. “Still Think Gluten Sensitivty Isn’t Real?” Chris Kresser. 23 Aug 2016.
  7. Khamsi, Roxanne. “Gluten Sensitivity May Be a Misnomer.” Scientific American.01 Feb 2014.
  8. Taubes, Gary. “Do We Really KnowWhat Makes Us Healthy?” The New York Times. 16 Sept 2007.
  9. “Sale of Gluten-Free Products Continue to Grow Double Digits on Quality, Selection.” Food navigator USA, 21 Jan 2015. www.foodnavigator-usa.com/Markets/Sales-of-gluten-free-products-will-continue-to-grow-double-digits.
  10. Strom, Stephanie. “A Big Bet on Gluten-Free.” The New York Times. 17 Feb 2014.
  11. Scott, Cameron. “Is Non-Celiac Gluten Sensitivity a Real Thing?” Healthline News. 15 Aug 2016.
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