Gluten-free diets have become extremely popular in the last decade among people with gluten sensitivities as well as people simply trying to fuel their bodies with the healthiest ingredients. Endurance athletes, in particular, have shown a lot of interest in the gluten-free diet for alleviation of the common gastrointestinal symptoms that can occur with endurance exercise. Gluten-free diets exclude all foods that contain gluten, a protein composite in wheat, rye, and barley. People following strict gluten-free diets also avoid oats, because 1) oats contain avenin, a peptide to which some celiac patients are also sensitive, and 2) oats are often processed in facilities that also process wheat and therefore contain greater than 20 ppm of gluten, the upper limit established by the Food and Drug Administration (FDA) (Ellis & Ciclitira, 2008; Food and Drug Administration, 2013).

The gluten-free diet is considered a fad by many nutritionists and nutrition novices alike. In fact, there are many people that could benefit from a gluten-free diet and many people to which it makes no difference. In Part 1, we discussed the symptoms, diagnosis, and treatment of celiac disease, wheat allergy, and non-celiac gluten sensitivity (NCGS). In Part 3, we will outline practical advice on how to follow a gluten-free diet. This article discusses the historical and popular support for the gluten-free diet that has induced such a strong following, a brief discussion of the scientific evidence surrounding several elimination diets including the gluten-free diet, and the risks and benefits of voluntarily implementing a gluten-free diet.

The rise of the popularity of the gluten-free diet
Some scientists hypothesize that humans are prone to gluten sensitivity because our bodies have not yet adapted to changes in our diet introduced approximately 10,000 years ago with the agricultural revolution (Fasano, 2014). Not only is gluten now a component in the diet, but wheat, barley, and rye are staple foods in many modern cultures. Due to the genetic and environmental factors that contribute to the severity of symptoms, some of which remain unknown, gluten sensitivity has persisted in our population.

The Paleolithic (or Paleo) diet is a popular diet that is based on the human diet before the agricultural revolution (Cordain et al., 2005). The Paleo diet encourages consumption of meat and fish, fruit, vegetables, roots, and nuts and discourages consumption of foods that require processing, such as grains, beans, processed oils, and processed sugars. Proponents claim that, because cavemen followed this diet and did not appear to suffer from obesity, cancer, or autoimmune disease, following the Paleo diet may prevent contemporary chronic diseases (Lindeberg, 2012b). However, critics claim that the human diet has been shifting for hundreds of thousands of years, so why label this seemingly arbitrary era as having the "best" diet? Moreover, plant and animal breeding has led to drastic changes in the macro- and micronutrients of almost every food making it impossible to follow the Paleo diet exactly as ancient humans did. Lastly, there is some archeological evidence that humans were consuming some types of grains 105,000 years ago (Mercader, 2009). The Paleo diet is very controversial but, either way, this diet is gluten-free by nature and therefore also carries the proposed benefits of gluten avoidance.

The gluten-free appeal to athletes
Many athletes have adopted a gluten-free diet in order to increase their energy and focus, prevent gastrointestinal distress, and optimize their performance. Athletes who have been advocates of the gluten-free diet include people with celiac disease (e.g. runner Amy Yoder Begley and NFL quarterback Drew Brees) and people without celiac disease (e.g. tennis player Novak Djokovic and speed skater Chris Creveling). All of these athletes partly attribute their success to gluten avoidance, though it is impossible to know how much of their success was due specifically to removing gluten. For example, it could have been coincidence, the placebo effect, and/or the effect of making conscientious dietary choices.

Endurance athletes (de Oliveira, Burini, & Jeukendrup, 2014) and runners, in particular (Riddoch & Trinick, 1988), often suffer from gastrointestinal distress during and/or after long runs. Gastrointestinal distress can be uncomfortable, embarrassing, and can prevent one from reaching his or her athletic potential. Cramps and flatulence are attributed to changes in physiology that occur during endurance training including less blood flow to the digestive tract and a decrease in the rate of food digestion (de Oliveira et al., 2014). There is no doubt that diet can moderate the extent of the physiological changes and the consequences that arise. Experts encourage to stay hydrated and, before exercise, consume easily digestible carbohydrates while avoiding caffeine, fatty foods, and foods high in fiber (Rodriguez, Dimarco, & Langley, 2010). It is clear that symptoms that are experienced and the diets that can alleviate these symptoms vary drastically from individual to individual, so one should determine their own optimal dietary strategies during practice and not wait for competition (de Oliveira et al., 2014). To our knowledge, there are no studies that investigate habitual diets, including a gluten-free diet, and prevention of exercise-induced gastrointestinal distress. [For an excellent discussion on athletes and the gastrointestinal tract, see (Pearce & O Hunter, 2011)].

Could a gluten-free diet curtail the progression of obesity?
Despite the large magnitude of interest and media coverage, there is not any research published on the benefits of a gluten-free diet for weight loss in healthy populations. Proponents of a gluten-free diet theorize that gluten induces inflammation in all people, albeit to a varying extent. They believe that gluten-induced inflammation leads to leptin resistance, meaning that the satiating effects of the hormone leptin are lost (Chen et al., 2006; Fernández-Sánchez et al., 2011). In essence, consuming gluten would reduce how full a meal makes you fell, thereby stimulating greater food intake. However, this hypothesis has not yet been supported. In fact, patients with NCGS reported gastrointestinal distress without presenting markers of inflammation (Biesiekierski et al., 2011). The only study, to my knowledge, that supports a gluten-free diet in healthy individuals was a mouse study published last year (Soares et al., 2013). Mice consumed a high fat diet (61% kcal from fat, which is extremely high) with or without addition of gluten (4.5%) for 8 wks1. The mice consuming gluten gained fat mass at a greater rate than mice that consumed the diet without the gluten supplementation. The mice on the gluten-containing diet also exhibited higher levels of insulin resistance and inflammation. The authors predict that the health benefits of the gluten-free diet stem from a decrease in pro-inflammatory responses caused by gluten protein. Interestingly, opposing the inflammation-leptin resistance-satiety theory, total food intake was similar between groups (p = 0.533) (Soares et al., 2013). There is much more research underway addressing whether a gluten-free diet can prevent and/or treat obesity and, if so, if the mechanism involves inflammatory pathways. Not until there is more support in either direction can we make recommendations regarding a gluten-free diet for weight loss.

Interactions between our genes and our environment can impair health, though gluten may not be the culprit
Celiac disease and, presumably, NCGS is increasing in prevalence due to modern gene-environment interactions. Serological (blood) analysis identified markers of celiac disease in 10 times more contemporary blood samples (2000-2001) compared to historical blood samples (1950-1989) in the United States (Murray et al., 2003). Corroborating these results, a study from Finland observed a 17-fold increase in prevalence of celiac disease markers between 1978-1980 and 2000-2001 (Lohi et al., 2007). Because the genetic composition of the population has not changed any practical amount in the last 1-2 generations, environmental factors (or epigenetic factors (Megiorni et al., 2008), which we know even less about) must be responsible for exacerbating gene-environment interactions that actuate celiac disease and other gluten sensitivity disorders.

While gluten has been identified as a "new" addition to our diet, in reality there have been a plethora of changes in our food supply that have occurred in the last ≈13,000 years. Indeed, the agricultural revolution shifted our diets to contain more carbohydrates from grains and dairy. In addition, the industrial revolution (about 200 years ago) further facilitated food processing. In a broad sense, our modern, highly processed foods contain easily digestible sugars and are largely lacking historical levels of fiber, phytochemicals, and naturally occurring micronutrients (Moodie et al., 2013). Moreover, it is estimated that 1,500 new compounds enter our food supply each year, either purposefully (e.g. food coloring compounds, preservatives) or unintentionally (e.g. plastics, pesticides) and the vast majority of these compounds are not tested for their effects on human physiology (Simmons, Schlezinger, & Corkey, 2014). While gluten certainly is implicated in some people's symptoms, there are many other food components that could be at play.

The gut microbiota is another element that interacts closely with both human genetics and the environment and can have a large influence on how our bodies react to food. The gut microbiome is composed of hundreds of different species of bacteria that reside in our gut, many of which play very different physiological roles (review: (Sekirov, Russell, Antunes, & Finlay, 2010)). These bacteria digest foods that human enzymes cannot digest (e.g. cellulose) as well as interact closely with the immune system. New data show that large shifts in our diets that occurred both in the agricultural revolution and in the modern, processed-food society have resulted in large changes in our gut microbiome (Walter & Ley, 2011). Shifts in the microbiota can cause the immune system in the intestine to be too weak, thereby permitting the passage of unwanted foreign invaders, or be too strong, thereby reacting against its own tissue. Dominance of different types of bacteria can also lead to or alleviate gastrointestinal distress, which is why yogurt with active cultures of live bacteria ("good" bacteria) is recommended for gut health. Experts caution that changes in our diet (namely high intake of simple sugars, high intake of unhealthy fats, and low intake of fiber) are related to both obesity and increased susceptibility to metabolic disease (Walter & Ley, 2011). Fortunately, we as individuals can choose to avoid "junk food" and help prevent and combat the perils of the modern diet.

While gluten is a popular food component to avoid, other foods and food components have been targeted as causes of chronic disease though have received less media attention. Any of these food components have a similar likelihood of alleviating gastrointestinal distress in runners or help reduce symptoms of other ailments. With that said, it is crucial to talk with a medical professional before implementing any drastic changes to your diet because elimination of foods can lead to nutrient deficiencies. In addition, clinical experts will be able to assess your symptoms and your individual needs to help direct your efforts in developing a diet that is best suited for you. Below are some common dietary restrictions that are often used to deal with gastrointestinal issues that might be confused with gluten sensitivity:
  • Dairy: Some individuals may require avoiding dairy products due to lactose intolerance or milk allergy, which is typically an allergic response to the protein in milk. Lactose intolerant individuals may suffer gastrointestinal symptoms as the result of the malabsorption of lactose (the primary sugar in milk). However, much recent research has shown that there are many dietary strategies besides simple milk avoidance, that can help improve lactose tolerance (Heaney, 2013). These strategies include:
    1. Consumption of fermented dairy products like yogurt that allows for digestion of lactose by the bacteria present in the yogurt,
    2. Restricting the amount of lactose consumed at a single serving to 6-12 g (about ½ to 1 cup of milk) or eating foods like hard cheeses, which contain very little lactose per serving,
    3. Slowly introducing increasing amounts of milk products into the diet over 2-3 weeks to allow the colonic bacteria to adapt to lactose,
    4. Consuming dairy products with meals rather than on their own to slow gastrointestinal transit of lactose to the colon, and
    5. Use of dairy products in which lactose has been enzymatically digested or using capsules containing microbial lactase (e.g., Lactaid® products).
    Given that milk intake is associated with higher intakes of calcium and overall better nutrient intake (Heaney, 2013), it seems advisable for lactose intolerant individuals to attempt these strategies for improving lactose tolerance rather than simply excluding dairy products altogether. Those with milk allergy who have to strictly avoid milk should consider alternative ways to obtain calcium and other nutrients found in dairy products (e.g., soy milk, calcium-fortified orange juice, etc.). However, for those without severe milk allergies, especially children, it may be possible to re-introduce milk after a period of abstention to see if the allergy has been outgrown, which is often the case (Boyce et al., 2010). In some limited research, dairy-free diets may also help prevent gastrointestinal distress or other symptoms in people without any of these diagnoses, although the explanation for this is unclear (Niec, Frankum, & Talley, 1998).
  • Patients with irritable bowel syndrome (IBS) often implement a low-residue diet (also known as a low flatulogenic diet) during flare-ups. This diet includes easily digestible foods such as peeled fruit, cooked vegetables, and refined grains and excludes whole grains. This diet has shown to immediately improve symptoms of gut distress and impaired cognition as well as improve mood (Azpiroz et al., 2014). It has also been recommended to endurance athletes before a competition to prevent gastrointestinal distress (Pearce & O Hunter, 2011).
  • Fructose: Fructose is commonly referred to as "fruit sugar" because of its presence in many fruits. Fructose is also a component of both sucrose (table sugar) and high fructose corn syrup. Table sugar is 50% fructose and 50% glucose and the most common form of high fructose corn syrup, the form in beverages, is about 55% fructose, 42% glucose, and 3% other sugars (Klurfeld, Foreyt, Angelopoulos, & Rippe, 2013). The small intestinal transport protein for fructose uptake (GLUT5) is easily saturated and, as such, large doses of fructose can lead to its malabsorption. As a result, fructose has been identified as a potential aggravator of gut distress and a potential mediator of other systemic conditions (Gibson, Newnham, Barrett, Shepherd, & Muir, 2007). The prevalence of fructose malabsorption is unknown but has been estimated to afflict as much as 50% of the population (Gibson et al., 2007; Skoog & Bharucha, 2004). In fact, low fructose diets have been associated with improved mood and mitigation of gastrointestinal distress (Ledochowski, Widner, Bair, Probst, & Fuchs, 2000; Skoog & Bharucha, 2004). As a caveat to these statements, it should be noted that the presence of glucose in addition to fructose greatly facilitates the uptake of fructose (Truswell, Seach, & Thornburn, 1988). Thus, fructose, when consumed as table sugar or high fructose corn syrup, is very well absorbed relative to when fructose is taken in as an isolated sugar (Gibson et al., 2007). There are few foods that contain fructose alone, which tends to limit the potential for fructose malabsorption. However, some fruits, like apples, contain fructose largely in excess of glucose or others, like pears, also contain natural sorbitol (a sugar alcohol) in addition to fructose (Matthews, Pehrsson, & Farhat-Sabet, 1987); both factors that can increase the potential for carbohydrate malabsorption.
  • Diets in which fermentable, oligo-, di-, monosaccharides, and polyols (FODMAPs) are eliminated have been shown to alleviate symptoms in people with NCGS (Biesiekierski et al., 2013). In fact, when following the FODMAP-free diet, participants did not respond negatively to gluten per se (Biesiekierski et al., 2013).

All in all, there are very few studies that have thoroughly investigated the efficacy of elimination diets for the purpose of alleviating gastrointestinal symptoms (Gibson & Muir, 2013), much less how these diets influence healthy, non-symptomatic individuals. A key concern with elimination diets is to ensure that suitable replacement foods can be found to supply those nutrients that may be lacking.

A "gluten-free" label does not indicate "healthy"
Many people believe that following a gluten-free diet will improve their health and well-being in the absence of a diagnosed gluten sensitivity. In fact, many people do improve the quality of their diet by substituting baked goods with healthier options. For example, choosing salads and fruit instead of pizza and brownies will lead to an increase in the consumption of essential nutrients and better control of caloric intake. However, not all gluten-free products are nutritious; many are unarguably junk food (e.g. M&M's, soda, jelly beans, potato chips). Furthermore, many gluten-free alternatives are packed with the same amount of sugar, fat, highly processed carbohydrates, and food additives as their traditional counterparts (e.g. cookies, pretzels, brownie/cake mixes). When substituting products with their gluten-free counterparts, it is important to know that wheat flour is often enriched with B vitamins and iron, while rice, tapioca, and potato flour used in gluten-free products is not. Therefore, these specialty foods may deliver fewer micronutrients. Consumers must also be cautious of the psychology behind eating more expensive specialty foods; one study showed that when people ate "organic" desserts they allowed themselves to eat more calories from the dessert and could easier justify not exercising (Schuldt & Schwarz, 2010).

Risks associated with implementation of a gluten-free diet
It is very possible to safely and effectively follow a gluten-free diet without supplements. Vitamins and minerals that are high in gluten-containing products (e.g. B vitamins) are found in other commonly consumed products. With that said, people who have followed gluten-free diets for a long time (e.g. 8-12 years) tend to not consume the recommended daily amount of fiber and tend to be deficient in folic acid, niacin, and vitamin B12 (Saturni, Ferretti, & Bacchetti, 2010). Several studies have shown that habitual gluten-free diets of adolescents with celiac disease contain excess calories, fat, and/or animal protein with obesity as a consequence (Saturni et al., 2010).

Studies have shown that the gluten-free version of a food is almost always more expensive; food "staples" such as bread and pasta are approximately twice as expensive as the traditional version (Lee, Ng, Zivin, & Green, 2007; Singh & Whelan, 2011). With that said, there are no studies that investigate the relative cost of a gluten-free diet that does not include these specialty products. Rice and potatoes are cheap, wholesome alternatives to wheat bread and wheat pasta and may serve as practical cost-effective gluten-free alternatives.

Conclusions
A diet that increases energy and focus and helps prevent the gastrointestinal distress associated with endurance exercise is appealing. However, there is currently no support for a gluten-free diet in people who have not been diagnosed with gluten sensitivity. Eating a healthy, balanced diet that is abundant in nutrient-rich foods and low in highly processed/packaged food will undeniably fuel your body for optimal health and athletic potential. If you still experience symptoms that are compromising your performance, you may consider getting tested for gluten sensitivity and other minor allergies/intolerances/sensitivities (see Part 1 for information on diagnosis). You and your clinician can work together to design a diet that best fits your nutritional and performance needs.

Fortunately, recognition that various aspects of the modern diet are increasing the prevalence of autoimmune and other chronic diseases is fueling scientific research to elucidate the major offensive food components and the mechanisms of their destruction. Secondly, the acknowledgment of a large demand for "functional foods" that prevent, treat, and cure various ailments, including gastrointestinal complaints, is encouraging the food industry to develop foods that are not just tasty but will truly improve your life. The science of optimizing athletic performance often lags behind the science of treating diseases, so don't hold your breath for clear-cut advice for how any individual should optimize their diet for their workouts.

Footnotes
1. It is unclear if the 4.5% gluten in the experimental diet was by weight or by kcal but, assuming it was 4.5% dry weight, this amount of gluten was high but within an order of magnitude of what could be consumed in a normal day.

We can calculate, theoretically, how much gluten a person may typically consume in one day: A person may consume 6 servings of wheat-based foods (e.g. cereal, muffin, bread, pasta) with 2 Tbsp wheat flour per serving (about 10 g/serving). Wheat flour is about 10-12% protein, and about 80% of the protein is gluten. So, in one day a person could consume:
(6 servings wheat product) x (10 g wheat flour/serving) x (0.1 g protein/g flour) x (0.8 g gluten/g protein) = 4.8 g gluten.

The recommended daily intakes for macronutrients is about 30% fat, 20% protein, and 50% carbohydrates. For a 2000 kcal diet, this is equal to 150 g protein, 250 g carbohydrates, and 65 g fat for a total of 465 g. Therefore, 4.8 g of gluten is 4.8 g/465 g = 1.0% of a person's diet (dry weight).