Home Ingredients Tolerase® G (AN-PEP Gluten-Digesting Enzyme — DSM)
Gut Health

Tolerase® G (AN-PEP Gluten-Digesting Enzyme — DSM)

Aspergillus niger
Evidence Level
Moderate
2 Clinical Trials
3 Documented Benefits
3/5 Evidence Score

Tolerase® G is a purified digestive enzyme from DSM (now dsm-firmenich): AN-PEP, an Aspergillus niger prolyl endoprotease. Unlike our own digestive enzymes, it stays active in the acidic stomach and specifically cuts the proline-rich sections of gluten proteins that human enzymes leave intact. In controlled human studies it broke down most of the gluten in a meal while it was still in the stomach, before it reached the small intestine. It is intended as backup for people who are already avoiding gluten and may run into small, unintended amounts, such as cross-contamination when eating out. Important: it is not a treatment for celiac disease and does not make it safe for people with celiac disease to eat gluten; for them, strict gluten avoidance remains essential.

Studied Dose Taken with meals; studied as high and low enzyme doses defined in proline-protease (PPI) activity units, with the higher dose degrading more gluten.
Active Compound Aspergillus niger prolyl endoprotease (AN-PEP), an acid-stable, proline-specific enzyme.

Benefits

Breaks down gluten in the stomach

In controlled human studies, the AN-PEP enzyme degraded most of the gluten in a test meal while it was still in the stomach, before it could reach the small intestine, and it stays active in the acidic stomach where ordinary digestive enzymes do not.

Supported by Trial 1, Trial 2

Backup for small, unintended gluten exposure

It is designed for people already avoiding gluten who may encounter hidden or cross-contaminating traces, for example when eating out. It targets the leftover gluten that a careful gluten-free diet cannot always prevent.

Supported by Trial 2, Trial 1

Degrades the fragments humans cannot

Parts of gluten are rich in proline, which makes them resistant to human digestion. AN-PEP breaks down these proline-rich fragments, including the gliadin 33-mer peptide central to the gluten immune response, that would otherwise pass through intact.

Supported by Trial 1, Trial 2

Mechanism of action

1

Proline-specific endoprotease

AN-PEP cleaves peptide bonds on the carboxyl side of proline residues. Human gastric and pancreatic proteases handle these bonds poorly, which is why proline-rich gluten peptides normally survive digestion and reach the gut largely intact.

2

Acid-stable, works in the stomach

The enzyme has an acidic pH optimum and stays active under gastric conditions (roughly pH 2 to 5) and in the presence of pepsin, so it begins degrading gluten early, in the stomach, rather than being inactivated like many enzymes.

3

Lowers immunogenic gliadin reaching the gut

By fragmenting proline- and glutamine-rich gliadin peptides, including the 33-mer alpha-gliadin peptide, AN-PEP reduces the amount of intact immunogenic gluten that arrives at the small intestine, where the gluten immune reaction takes place.

Clinical trials

1
AN-PEP Gluten Degradation in a Complex Meal — RCT
PubMed

Randomised, double-blind, placebo-controlled crossover trial of high- and low-dose AN-PEP taken with a gluten-containing meal, with stomach and duodenal contents sampled over three hours (König J, Holster S, Bruins MJ, Brummer RJ 2017, Scientific Reports 7(1):13100, PMID 29026170).

18 gluten-sensitive adults; porridge containing 0.5 g gluten taken with high-dose AN-PEP, low-dose AN-PEP, or placebo.

Both AN-PEP doses significantly lowered gluten levels in the stomach versus placebo, and at least 50% more gluten was degraded in the duodenum in 10 of 13 comparisons. The trial measured gluten breakdown, not symptom relief or protection from intestinal damage.

2
AN-PEP Digests Gluten in the Stomach — RCT
PubMed

Randomised, double-blind, placebo-controlled study infusing a liquid meal containing gluten with or without AN-PEP directly into the stomach of healthy volunteers (Salden BN, Monserrat V, Troost FJ, Bruins MJ, Edens L, Bartholomé R, Haenen GR, Winkels B, Koning F, Masclee AA 2015, Aliment Pharmacol Ther 42(3):273-285, PMID 26040627).

Healthy adult volunteers with an intragastric feeding tube; a meal with gluten plus AN-PEP or placebo.

AN-PEP substantially and significantly reduced the amount of gluten (alpha-gliadin) reaching the stomach and duodenum compared with placebo (P<0.001). A mechanistic gluten-degradation study in healthy people, not a test of symptom prevention.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated in human studies, with no significant enzyme-related adverse effects reported.
As a protein enzyme it could in theory cause an allergic reaction, particularly in people with a mold or Aspergillus allergy.
Not a treatment for celiac disease: it does not make gluten safe for people with celiac disease, who must still avoid gluten completely.
It should not be used as a license to eat gluten on purpose; it is meant only for small, unintended traces.

Important Drug interactions

No specific drug interactions are established for AN-PEP.
As a protein-digesting enzyme, it could in principle act on protein- or peptide-based medications taken at the same time; separate dosing by a few hours if concerned.
If you have celiac disease or another diagnosed gluten disorder, talk to your doctor before relying on any gluten enzyme.

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Frequently asked questions about Tolerase® G (AN-PEP Gluten-Digesting Enzyme — DSM)

What is Tolerase G?

Tolerase® G is a purified digestive enzyme from DSM (now dsm-firmenich): AN-PEP, an Aspergillus niger prolyl endoprotease. Unlike our own digestive enzymes, it stays active in the acidic stomach and specifically cuts the proline-rich sections of gluten proteins that human enzymes leave intact.

What is Tolerase G used for?

Tolerase G is researched primarily for Gut Health. In controlled human studies, the AN-PEP enzyme degraded most of the gluten in a test meal while it was still in the stomach, before it could reach the small intestine, and it stays active in the acidic stomach where ordinary digestive enzym…

What is the recommended dosage of Tolerase G?

The clinically studied dose is Taken with meals; studied as high and low enzyme doses defined in proline-protease (PPI) activity units, with the higher dose degrading more gluten. Always follow the product label and check with a healthcare provider for personal advice.

Is Tolerase G safe, and does it have side effects?

For most healthy adults, Tolerase G is well tolerated at studied doses. Reported effects can include: Generally well-tolerated in human studies, with no significant enzyme-related adverse effects reported. As a protein enzyme it could in theory cause an allergic reaction, particularly in people with a mold or Aspergillus allergy. It may also interact with some medications. Tolerase G is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Tolerase G interact with any medications?

Possible interactions include: No specific drug interactions are established for AN-PEP. As a protein-digesting enzyme, it could in principle act on protein- or peptide-based medications taken at the same time; separate dosing by a few hours if concerned. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Tolerase G?

NutraSmarts rates the evidence for Tolerase G as Moderate (3 out of 5). It is backed by 2 clinical trials and 4 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(4 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. König J, Holster S, Bruins MJ, Brummer RJ. Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting. Scientific Reports. 2017;7(1):13100. doi:10.1038/s41598-017-13587-7.PubMedUsed to support: Randomised placebo-controlled crossover RCT in 18 gluten-sensitive adults: high- and low-dose AN-PEP taken with a 0.5 g gluten meal significantly reduced gluten in the stomach and achieved at least 50% extra gluten degradation in the duodenum in 10 of 13 comparisons. Supports gluten degradation in the stomach; it measured breakdown, not symptom relief.
  2. Salden BN, Monserrat V, Troost FJ, Bruins MJ, Edens L, Bartholomé R, Haenen GR, Winkels B, Koning F, Masclee AA. Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers. Alimentary Pharmacology & Therapeutics. 2015;42(3):273-285. doi:10.1111/apt.13266.PubMedUsed to support: Randomised, double-blind, placebo-controlled intragastric study in healthy volunteers showing AN-PEP significantly lowered the gluten (alpha-gliadin) reaching the stomach and duodenum versus placebo (P<0.001). The pivotal in vivo demonstration that AN-PEP digests gluten in the stomach.
  3. Mitea C, Havenaar R, Drijfhout JW, Edens L, Dekking L, Koning F. Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease. Gut. 2008;57(1):25-32. doi:10.1136/gut.2006.111609.PubMedUsed to support: In a dynamic gastrointestinal model (TIM), the prolyl endoprotease degraded gluten before it reached the intestinal compartment, including gluten in slices of white bread. Mechanistic model evidence, not a human trial.
  4. Stepniak D, Spaenij-Dekking L, Mitea C, Moester M, de Ru A, Baak-Pablo R, van Veelen P, Edens L, Koning F. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol. 2006;291(4):G621-G629. doi:10.1152/ajpgi.00034.2006.PubMedUsed to support: Original characterization of the Aspergillus niger prolyl endoprotease (AN-PEP): it is acid-stable, resistant to pepsin, and rapidly degrades intact gluten and immunogenic gliadin peptides such as the 33-mer. Foundational enzyme-discovery study.