There are more people than ever suffering from some form of gluten-related health issue – either celiac disease, gluten intolerance or non-celiac gluten sensitivity (NCGS)– all of which can cause digestive discomfort and fatigue. In fact, NCGS is now recognized as a separate condition, where neither allergic nor autoimmune mechanisms are involved. According to a consumer survey, 6% of the US population has been diagnosed with NCGS,1 while 13% of the UK population considers themselves to be gluten-sensitive.2 However, at present, the only option for those who cannot tolerate gluten is a lifelong gluten-free diet.
In recent years, the market for gluten-free products has exploded. One in three consumers (31% of the UK and 36% of the US) are inclined to limit their intake or avoid gluten, despite only 1% being diagnosed with celiac disease.3 While this has helped alleviate the problem of consuming gluten at home,
it can be difficult to eat out, because of the ‘hidden’ gluten in many foods. One in four global consumers try to avoid foods that contain gluten, but this can be challenging when dining out, travelling or during social events.4 In fact, even when following a gluten-free diet, unintentional gluten intake can range from 200 to 3,000 mg/day, depending on how strictly the diet is followed.5,6,7,8
As a result of the growing number of people looking to avoid gluten, coupled with busy lifestyles and the desire for more freedom when eating out, consumers and manufacturers alike are seeking a solution that will bridge the gap in the industry. Recent innovations have led those with gluten sensitivity to turn to the convenience of dietary supplements – to give them peace of mind when traveling or dining outside of their homes. In particular, Aspergillus niger prolyl endoprotease (AN-PEP) is receiving attention as the only dietary enzyme scientifically proven to effectively help break down residual gluten.
What is gluten?
Gluten is everywhere. Modern lifestyles have led to a significant change in both the way grains are cultivated, and how they are consumed. For example, the introduction of commercial breadmaking in the 1960s removed the fermentation step, for a faster, more cost-effective process. However, the fermentation process results in gluten being broken down (predigested). Omitting the fermentation step in commercial breadmaking has led to consumers being exposed to undigested proteins in bread for the first time.
Found in wheat, barley and rye, gluten is a protein complex that is rich in proline, an amino acid. Gluten is comprised of two proteins: glutenin and gliadin. Gluten gives bread its shape, texture and strength, and also provides functional properties for products like cakes and pasta. However, it is also present in less well-known food and beverages, such as sauces, stock cubes, processed meats and confectionery. The human body cannot break down proline-rich proteins efficiently and this is a potential cause of gluten sensitivity. The poorly-digested gluten fragments can be the root cause of adverse responses in some individuals.
The science behind the supplements
The dietary enzyme, AN-PEP, has received widespread interest from supplement manufacturers, following extensive studies carried out on the efficacy of the enzyme for gluten digestion in the stomach.
One particular in vitro trial has been pivotal in proving that AN-PEP specifically degrades the immunogenic parts within gluten proteins.9 The study looked at five alternative digestive enzyme supplements currently on the market, which claim to aid in gluten degradation, and compared them to the effectiveness of AN-PEP. Gluten epitope degradation was monitored by a gluten detection test, R5 ELISA, mass spectrometric analysis of the degradation products, and pro-inflammation T-cell proliferation assays.
The results found that the other enzyme supplements leave the gliadin fragments – glycoproteins implicated in the pathogenesis of celiac disease – largely intact. In contrast, tests confirmed that AN-PEP effectively degraded all nine epitomes in the pH range of the stomach at a much lower dose. As such, AN-PEP was determined to be the most effective of the supplements tested in degrading immunogenic gluten epitopes.
Efficacy of AN-PEP
To further substantiate the evidence for AN-PEP, a double-blind, randomized, placebo-controlled crossover study was carried out to assess the efficacy of the enzyme on gluten degradation in low and high calorie meals.10 12 healthy volunteers, aged 18-45 years, were administered a liquid low- or high- calorie meal (both containing 4g of gluten) into the stomach with either an AN-PEP supplement or a placebo. Their gastric emptying times were then recorded, and samples were taken to confirm the concentration of gliadin. The results found that AN-PEP ‘significantly enhanced’ gluten digestion in the stomach of healthy volunteers. As AN-PEP already degraded most gluten from low calorie meals, increasing meal caloric density (that slows down the gastric emptying) did not further improve the efficacy of the enzyme.
Furthermore, results from another clinical trial that aimed to assess the efficacy of AN-PEP in a physiological meal setting with a low amount of gluten is showing promising results.11 The placebo-controlled, cross-over study looked at 18 self-reported gluten-sensitive subjects over three days. Similarly, the trial found that both high (160,000 protease picomole international [PPI])12 and low doses (80,000 PPI) of AN-PEP significantly lowered the gluten concentrations in the stomach and in the duodenum, compared to the placebo.
DSM’s Tolerase® G (AN-PEP) is currently the only commercially available enzyme for use in dietary supplements that is scientifically proven to help break down residual gluten. The unique enzyme is aimed at gluten sensitive consumers who are already following a gluten-free diet, and can play a key role in enabling food manufacturers to do more with nutrition in the gluten-free market. Active under stomach conditions, Tolerase® G is stable at low pH conditions, as well as being resistant to pepsin – an enzyme that breaks down proteins into smaller peptides. It is not intended to replace a gluten-free diet, nor treat or prevent celiac disease, but Tolerase® G definitely can provide peace of mind following a gluten-free diet with confidence.
Tolerase® G was notified as a New Dietary Ingredient by the FDA in the US in 2015 and, in 2017, was authorized as a novel food in the EU. Similarly, in Canada, it is listed as a ‘natural health product ingredient’, ‘complementary medicine ingredient’ in Australia, and as a ‘permitted substance’ in New Zealand.
Applying Tolerase® G to everyday life
For gluten-sensitive consumers, it is important that any solution is convenient and easy enough to incorporate into their daily lives. The micro granularity of Tolerase® G means that it has excellent flowability and compressibility for use in tablets and capsules. The dose rate can also be adapted to suit different gluten intolerance sensitivities and the size of the meal consumed.
It is usually recommended that a dose of 160,000 – 180,000 PPIs is taken for diets high in hidden gluten (500 mg/day). Whereas for consumers who are very sensitive, taking twice this dose could prove beneficial.
Convenience, freedom and peace of mind
While the wide range of gluten-free foods and beverages now available on retail shelves is certainly paving the way for consumers with gluten sensitivities, there is still a gap in the market for dealing with residual gluten when eating out, traveling or during social events. With growing awareness of the importance of digestive health, consumers are increasingly looking to convenient solutions that can be taken on-the-go and will provide the freedom that they need.
Although there are several digestive enzyme supplements now available on the market, continual demands by the rising number of discerning consumers interested in the science behind the products, is shaping the direction of the industry. The scientific evidence behind DSM’s Tolerase® G dietary enzyme gives consumers the confidence to follow a gluten-free diet, without fearing the danger of consuming residual gluten. As such, Tolerase® G is a reliable option for manufacturers to do more with nutrition in supporting consumer lifestyles for those with gluten sensitivities.
Program Director Gut Health, DSM
- A. Sapone et al., ‘Spectrum of gluten-related disorders: consensus on new nomenclature and classi cation,’ BMC Medicine, vol. 10, no. 13, 2012, p.1-12.
- I. Aziz et al., ‘A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care,’ Eur. J. Gastroenterol Hepatol. Vol. 26, no. 1, 2014, p. 33-39.
- Mintel, ‘Gluten-free food report’, October 2016 [report].
- Nielson, ‘What’s in our food and on our minds: ingredient and dining out trends around the world’, August 2016 [report].
- F. van Overbeek et al., ‘The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population’, Eur J Gastroenterol Hepatol, 1997, vol. 9, no. 11, p.1097-9.
- E. Hopman et al., ‘Nutritional management of the gluten-free diet in young people with celiac disease in The Netherlands’, J Pediatr Gastroenterol Nutr. Vol. 43, no. 1, 2006, p.102-8.
- E. Hopman et al., ‘Gluten tolerance in adult patients with celiac disease 20 years after diagnosis?’, Eur J Gastroenterol Hepatol. Vol. 20, no. 5, 2008, p.423-9.
- A. Lovik et al., ‘Diet adherence and gluten exposure in coeliac disease and self-reported non-coeliac gluten sensitivity,’ Clin Nutr. Vol. 36, no. 1, 2017, p. 275-80.
- G. Janssen et al., ‘Ineffective degradation of immunogenic gluten epitopes by currently available digestive enzyme supplements,’ PLoS ONE, vol. 10, no. 6, 2015
- B. Salden et al., ‘Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers,’ Aliment Pharmacol, vol. 42, 2015, p. 273-285.
- J. Konig et al., ‘Aspergillus Niger-derived enzyme AN-PEP ef ciently degrades gluten in the stomach of gluten-sensitive subjects,’ Clinical Nutrition, vol. 35, 2017.
- 160,000 protease picomole international [PPI]) is the amount of enzyme that releases one picomole of p-nitroanilide per second from Z-Gly-pro-p-NA under defined assay conditions.