Safety evaluation of non-genetically modified food enzyme D-allulose 3-epimerase

If you are sourcing enzymes for D-allulose production, here is one you can cross off the approved list for now. The European Food Safety Authority (EFSA) opinion on a D-allulose 3-epimerase preparation ends with an unusual statement. The expert panel could not complete the safety assessment. That matters because the enzyme is meant to be used in a specialty carbohydrate process that many formulators are watching closely.

Background: why D-allulose 3-epimerase matters

D-allulose is a low-calorie rare sugar with physical properties close to sucrose. It is made by isomerizing fructose. The enzyme that performs this reaction is D-allulose 3-epimerase. It converts D-fructose into D-allulose in one step.

The preparation reviewed in this paper comes from a non-genetically modified source. That point appears directly in the title. The enzyme is not produced by a recombinant strain. For buyers who need non-GMO claims, that sounds attractive. But the safety review did not finish.

The paper appears in the EFSA journal under DOI 10.2903/j.efsa.2024.8702. The product is a food enzyme preparation. The intended process is the isomerization of D-fructose to produce D-allulose. The active enzyme is present in non-viable cells. Those cells are used in immobilized form. That means the enzyme stays in the reactor while fructose passes through.

What the study did

The expert panel reviewed data submitted by the applicant. The aim was to determine whether this food enzyme preparation is safe under its proposed conditions of use.

The proposed use level is precise: no more than 27 mg TOS per kg of D-fructose. TOS means total organic solids. It is a standard way to express enzyme dose in food enzyme evaluations.

The enzyme preparation is not intended to remain in the final food product. It is immobilized, and the cells are inactive. The process itself is well understood. The chemistry of converting fructose to allulose is not exotic. Still, the safety evaluation stalled.

What the panel reported

The key finding is not about toxicity. It is about missing certainty. The expert panel stated that it could not complete the assessment. The abstract gives no further detail on the reason. We do not know whether the gaps were toxicological, microbiological, or related to the manufacturing strain. We only know the outcome.

No acceptable daily intake was set. No conclusion was reached on the safety of the food enzyme. No authorization is linked to this opinion.

Here is what the paper tells us:

Item	Detail
Enzyme	D-allulose 3-epimerase
Source	Non-genetically modified
Reaction	Isomerization of D-fructose
Product	D-allulose
Process form	Non-viable cells, immobilized
Proposed dose	27 mg TOS/kg D-fructose
Safety assessment	Not completed

That table is short. It captures the problem. The proposed use is clear. The regulatory outcome is not.

What it means for manufacturers

Do not treat this opinion as a green light. A food enzyme that has not completed EFSA’s safety assessment has no EU authorization. If you formulate allulose for the EU market, you cannot rely on this enzyme preparation as an approved processing aid.

Does that mean D-allulose is unsafe? No. This opinion does not prove harm. It simply does not prove safety. There is a difference. A formulator who uses an unapproved enzyme takes on regulatory risk. Ingredient buyers should ask suppliers for the status of their dossier and any future resubmission.

There is also a practical angle. The proposed dose of 27 mg TOS/kg fructose is useful data. If you are comparing allulose production routes, you can use that number as a benchmark. But a benchmark is not approval.

Questions formulators ask

Does this EFSA opinion ban the enzyme? No. It does not ban anything. It says the panel could not complete the evaluation. That leaves the enzyme without a positive safety conclusion.

Can I still use this enzyme outside the EU? Possibly. Regulatory systems differ. But many global manufacturers follow EFSA opinions as a reference. An incomplete EFSA assessment creates friction in other markets too.

What should I ask my supplier? Ask for the EFSA opinion number. Ask whether the dossier has been resubmitted. Ask for the reason the assessment was incomplete. A supplier with nothing to hide will share that information.

Closing thought

This paper is a reminder that “non-GMO” does not equal “approved.” The enzyme is non-genetically modified. It also is not fully assessed. The route to D-allulose remains promising, but this specific enzyme preparation has not cleared the regulatory bar. Buyers should keep the DOI on file and watch for an updated opinion. Until then, treat this one as pending, not proven.