Natamycin: The Natural Antifungal That Protects Cheese and Yogurt

Most food additives get their safety evaluation from rodent feeding studies and chemical analysis. Natamycin is different. It’s been used as a prescription antifungal medication in ophthalmology since the 1950s, which means it went through the kind of clinical scrutiny that food additives rarely face.

That medical history is one of the reasons its safety profile is as strong as it is.

Where Natamycin Comes From

Natamycin is produced naturally by Streptomyces natalensis, a soil bacterium first isolated in South Africa. The commercial product is harvested from bacterial fermentation, the same production method used for many pharmaceutical antibiotics.

It belongs to the polyene antifungal class, the same group as amphotericin B (used to treat serious systemic fungal infections) and nystatin (a common topical antifungal). The polyene family is well-studied. Researchers have understood the basic mechanism of action for decades.

How It Kills Fungi

Fungal cell membranes contain a sterol called ergosterol. Human cell membranes use cholesterol instead. Natamycin binds specifically to ergosterol. When it binds, it forms pores in the fungal membrane, disrupting the cell’s ability to regulate what moves in and out. The cell loses ions and other molecules it needs to function, and it dies.

The selectivity for ergosterol over cholesterol is what makes natamycin safe for human use. Your cells don’t have ergosterol, so natamycin has nothing to bind to in your body. It passes through largely intact.

This is a meaningful distinction from preservatives that work by broadly interfering with metabolism. Natamycin has a specific molecular target that only fungi possess.

Applications in Food

Natamycin is most commonly used as a surface treatment on cheese rinds. Hard cheeses like Gouda, Edam, and Swiss are typical candidates. The compound prevents mold from growing on the exterior during aging and distribution without affecting the bacterial cultures inside the cheese that drive ripening and flavor.

This selectivity matters for cheese producers. The wrong preservative applied to cheese would kill the ripening bacteria along with the mold, destroying the product’s flavor and texture. Natamycin’s fungal specificity makes it ideal.

In some markets, natamycin is also used in yogurt, sour cream, and cottage cheese to extend shelf life by preventing mold growth at the surface. You’ll find it listed as “natamycin” or “E 235” depending on whether you’re reading a US or European label.

The Medical Ophthalmology Connection

Natamycin 5% ophthalmic suspension is sold as Natacyn and has been an FDA-approved treatment for fungal eye infections since 1978. It’s used to treat fungal keratitis, an infection of the cornea caused by organisms like Fusarium and Aspergillus.

The fact that the same compound is applied directly to human eye tissue, one of the most sensitive and delicate tissues in the body, and is considered safe for medical use says a lot about its toxicity profile. Eye medications have strict safety requirements. Corneal tissue is not forgiving.

Bioavailability and Absorption

One of the key features of natamycin from a food safety perspective is its very low oral bioavailability. Studies in animals and humans show that it’s poorly absorbed from the gastrointestinal tract. Most of what you consume passes through unchanged.

This limits systemic exposure dramatically. Even when consumed as a food additive, the compound doesn’t meaningfully accumulate in tissues. It stays in the gut and exits. The EFSA review from 2009 specifically highlighted this low absorption as a factor in its safety assessment.

Regulatory Status

The FDA approved natamycin for use on cheese surfaces under 21 CFR 172.155. It permits use at up to 20 mg/kg on the surface, with none detectable at a depth of 5 mm from the surface, confirming that it doesn’t penetrate into the interior of the cheese.

EFSA’s 2009 scientific opinion evaluated the compound and established an ADI of 0.3 mg per kilogram of body weight per day. Typical food exposure falls well below this level given the surface-only application and low migration into food.

What the Labels Mean

If you see natamycin listed as an ingredient on yogurt or cottage cheese, it’s in the product itself (usually added to the surface or to the product to prevent mold on stored portions). On hard cheese, it’s applied to the rind. Either way, the amounts are small, the compound is well-characterized, and the safety record is extensive.

This is one of those cases where knowing the backstory actually makes the additive seem more reassuring, not less. Sixty-plus years in ophthalmology, a clear mechanism of action, minimal absorption, and regulatory review on both sides of the Atlantic.