Natamycin
A naturally fermented antifungal compound, applied to the outer surface of hard cheeses and dried cured sausages to stop mould and yeast growing on the rind.
Natamycin is itself an antibiotic. Researchers have raised concern that dietary exposure through food may exert selective pressure on gut fungi, potentially contributing to resistance to polyene antifungal drugs used to treat serious fungal infections. The evidence is preliminary and contested, but the mechanism is plausible. EFSA also flagged gaps in the long-term toxicology database when it reviewed the additive in 2009.
What is it?
Natamycin, also known as pimaricin, is a polyene macrolide antibiotic produced by fermenting the soil bacterium Streptomyces natalensis. It is a naturally derived compound, though its use in food is as a manufactured extract.
What does it do?
Natamycin binds irreversibly to ergosterol, a sterol found in fungal cell membranes but absent from bacterial and human cells. This binding disrupts membrane permeability, causing leakage of ions and molecules that kills or inhibits the fungus. Because bacteria and human cells lack ergosterol, natamycin has no direct antibacterial action and is not absorbed through the gut in meaningful amounts under normal conditions.
Where you will see it
In the UK and EU, E235 is authorised only as a surface treatment. It is applied to the rind of uncut hard, semi-hard and semi-soft ripened cheeses, and to the outer casing of dried cured sausages. It is not permitted in the interior of the food. On a cheese label, look for 'rind treated with E235' or 'preservative: natamycin' in the ingredients list or alongside it.
What the science says
How it kills mould: a very targeted mechanism
Natamycin targets ergosterol, a molecule found in fungal cell walls but not in human or bacterial cells. This specificity means it acts against moulds and yeasts without affecting the beneficial bacteria in fermented foods or the human gut's bacterial flora. No bacterial resistance to natamycin has been documented in 50-plus years of food use, based on field surveys in cheese warehouses and sausage factories.
Natamycin binds irreversibly to ergosterol in fungal membranes, disrupting permeability and causing cell death. Bacteria lack ergosterol and are unaffected.
Field surveys over more than 20 years of use in cheese warehouses and sausage factories showed no change in the composition or drug sensitivity of contaminating fungal flora.
Antibiotic resistance: a contested but unresolved concern
Natamycin belongs to the same class of antifungal antibiotics (polyene macrolides) as amphotericin B, a drug used to treat life-threatening fungal infections. A series of laboratory and modelling studies from 2015 onwards have argued that dietary natamycin, particularly if consumed in beverages or yogurt in regions where that is permitted, could expose gut Candida species to enough drug to encourage resistance development. If resistance to natamycin transferred to amphotericin B, it could reduce clinical options for treating invasive fungal disease. JECFA (2002) and EFSA (2009) both concluded there was no demonstrated resistance concern at the surface-treatment levels approved in the EU, but subsequent papers described the issue as 'probable but speculative' and called for precautionary restraint.
EFSA concluded there was no concern for the induction of antimicrobial resistance from natamycin used at approved surface-treatment levels on cheese and sausages.
A laboratory study found that repeated exposure of Candida isolates to subinhibitory natamycin concentrations raised minimum inhibitory concentrations in 13 of 20 strains tested; one Aspergillus strain showed increased tolerance to amphotericin B. The authors concluded that the clinical implications were 'probable but speculative'.
Authors raised concern that extended natamycin use in yogurt and beverages (permitted in some countries outside the EU) exposes gastrointestinal fungi to high drug concentrations, representing a greater resistance risk than surface treatment on cheese rind.
Toxicology: limited long-term data, low exposure
Animal studies over two years found no significant increase in tumour rates in natamycin-treated groups compared to controls. Genotoxicity tests in bacteria were consistently negative. However, one rodent study reported natamycin could cause chromosomal changes (micronuclei formation) at very high doses, and EFSA flagged the overall toxicology database as too limited to set its own ADI in 2009. Natamycin is very poorly absorbed from the gut, and estimated dietary exposure from the permitted surface treatment uses falls below 0.1 mg/kg body weight per day even for children at the 97.5th percentile, which is below the JECFA ADI.
A two-year rat study found no significant difference in numbers or types of tumours between natamycin-treated groups and controls.
EFSA noted that the available toxicological database on natamycin had limitations including the design of animal studies, a small number of animals, unclear genotoxicity findings in some tests, and a lack of adequate long-term carcinogenicity studies. EFSA did not set its own ADI as a result.
One rodent study reported micronucleus formation at high doses (400 and 800 mg/kg), suggesting potential aneugenicity at doses far above those encountered in food.
Estimated dietary exposure from natamycin in its authorised EU surface-treatment uses was below 0.1 mg/kg body weight per day at the 97.5th percentile for children, below the JECFA ADI of 0-0.3 mg/kg body weight.
Where it stands with the regulators
Who should be careful
No declarable allergen group is formally associated with natamycin. People with known sensitivity or allergy to natamycin itself (identified via pharmaceutical exposure, as it is also used in eye drops and topical antifungals) should look for 'natamycin', 'pimaricin', or 'E235' on cheese and dried sausage labels, typically noted as 'rind treated with preservative E235'. Immunocompromised individuals, for whom polyene antifungal drugs such as amphotericin B are a treatment option, may wish to be aware of the ongoing academic debate about resistance.
The honest read
The science on natamycin is more involved than a typical food preservative because it is an antibiotic drug, not merely a synthetic chemical. The EU restricts it to surface use only, at low levels, precisely because regulators want to limit dietary exposure. The antimicrobial resistance debate is real but currently unresolved: two groups of researchers have published concerns, while JECFA and EFSA maintain that resistance is not a demonstrated problem at EU-authorised use levels. The toxicology database was explicitly called limited by EFSA in 2009, with gaps in long-term carcinogenicity data, though the same review judged that actual exposure from permitted uses was low enough to be acceptable. This is an area where the regulator's working conclusion and the academic debate are not yet fully aligned.
Related additives
Common questions
Is E235 banned in the UK?
No. E235 natamycin is an authorised food additive in the UK, listed on the UK FSA approved additives register (last updated April 2025). It is permitted only for surface treatment of certain hard and semi-hard cheeses and dried cured sausages. It is not permitted inside the food or in other food categories.
Is natamycin an antibiotic, and does that matter?
Yes, natamycin is a naturally produced polyene macrolide antibiotic. It belongs to the same drug class as amphotericin B, which is used to treat serious fungal infections in hospital settings. Researchers have raised concern in peer-reviewed papers that widespread dietary use could encourage fungal resistance to this class of drug. EFSA and JECFA have assessed the concern and concluded that EU-level surface-treatment uses do not pose a demonstrated resistance risk. The debate is ongoing in the scientific literature.
What foods contain E235?
In the UK and EU, E235 is authorised only on the outer rind of hard, semi-hard and semi-soft ripened cheeses (such as Gouda, Edam, and some Cheddar), and on the outer casing of dried cured sausages such as salami. Cheese labels typically note 'rind treated with preservative E235' or 'natamycin'. It is not in the cheese body itself, only the surface layer.
Is E235 vegan?
Natamycin itself is produced by bacterial fermentation, not from animal sources. However, many cheeses that use E235 are not vegan, as they are made from animal milk. Whether a specific product is vegan depends on the food it is applied to, not the additive itself.
Sources
- EFSA Panel on Food Additives and Nutrient Sources: Scientific Opinion on the use of natamycin (E 235) as a food additive. EFSA Journal 7(12):1412
- JECFA: Natamycin (Pimaricin). Food Additives Series 48. WHO/FAO Joint Expert Committee on Food Additives
- UK FSA Approved Additives and E Numbers
- UK Regulated Products register: E235 Natamycin
- Dalhoff A et al: Does use of the polyene natamycin as a food preservative jeopardise the clinical efficacy of amphotericin B? A word of concern. Clinical Microbiology and Infection
- Dalhoff A: Does the use of antifungal agents in agriculture and food foster polyene resistance development? A reason for concern. International Journal of Antimicrobial Agents
- Natamycin: a natural preservative for food applications, a review. Applied Microbiology and Biotechnology (PMC8595390)
- WHO JECFA database: Natamycin
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