Material guide: isovaleric acid — the database writes 'stinky feet,' and it is not a figure of speech

About a 5 minute read.

The short version

• Name: isovaleric acid, also 3-methylbutyric acid, CAS 503-74-2, FEMA 3102
• Odour type: cheesy; odour: sour, sweaty, cheesy, tropical, dairy, acidic, pungent, fruity, ripe, fatty
• Strength: high (recommend smelling in a 1.00% solution or less), rank 3; substantivity 400 hours
• Storage: refrigerate in tightly sealed containers; shelf life 12 months
• Suppliers: 67; boiling point 175–177 °C, melting point −29 °C
• It is the foot odour molecule, made by a bacterium living on your skin

An evaluation entry uses the word "disagreeable"

The odor_descriptions field holds six descriptions. Two are worth quoting whole:

at 1.00% in propylene glycol. sour stinky feet sweaty cheese tropical (Luebke, William, tgsc, 1989)

Rancid, Cheese, Disagreeable.

Seeing "disagreeable" in a commercial materials database is unusual. I have read the evaluation fields for well over a hundred materials in this series, and most of them stay neutral — even something like indole gets "fecal," not "bad."

This record gives up on neutrality.

And "stinky feet" is literal

What Ara and colleagues did in the Canadian Journal of Microbiology in 2006 was direct: analyse the components of foot odour, isolate the organisms that make it, establish the mechanism.

As a result, foot odor was found to be derived from isovaleric acid, which is produced when Staphylococcus epidermidis, a resident species of the normal cutaneous microbial flora, degrades leucine present in sweat.

Sweat itself has no smell. Leucine is an amino acid in it; the resident bacteria on your skin metabolise it, and this material is the by-product.

They also detected Bacillus subtilis on the plantar skin of subjects with strong foot odour, and showed that species to be closely associated with the increase.

The end of the paper is the part for perfumers

The second half of Ara's paper looks for inhibitors, and where they looked was the fragrance shelf:

We screened various naturally occurring substances and fragrant agents that inhibit microbial production of foot odor without disturbing the normal microbial flora of the human skin. As a result, we identified citral, citronellal, and geraniol as fragrant agents that inhibit the generation of isovaleric acid at low concentrations.

Three ordinary perfumery materials suppress the bacterial production of a fourth one.

Citral (135 suppliers), geraniol, citronellal — all in this database, all foundational on the citrus/rose line.

They are not masking it. They are suppressing the organism that makes it. Worth remembering, even though it has no direct bearing on your formula.

The underarm works the same way, with a larger sample

Lam and colleagues ran a bigger study in Microbiome in 2018 — 180 samples across three skin sites (underarm, neck, head) at two time points (1 h and 8 h after a bath), in pre-pubescent children and teenagers:

Significant positive correlations were observed between odor intensity and the relative abundance of Staphylococcus hominis, Staphylococcus epidermidis, and Cutibacterium avidum … Metabolic pathway analysis highlighted the association of isovaleric and acetic acid production (sour odor) from enriched S. epidermidis (teen underarm).

Same organism, same molecule, different site.

And when someone cannot metabolise leucine

Isovaleric acid has a third way of appearing.

Sakamoto and colleagues, in the Tohoku Journal of Experimental Medicine in 2015, studied isovaleric acidemia, an autosomal recessive inborn error affecting leucine metabolism, caused by a deficiency in the enzyme that oxidises isovaleryl-CoA:

Clinical features of IVA include poor feeding, vomiting, lethargy, developmental delay, metabolic acidosis, and a characteristic "sweaty foot" odor.

The smell is a diagnostic clue. (It is now a newborn screening target by tandem mass spectrometry, so in most cases nobody has to rely on a nose.)

One molecule, three origins: the bacteria on your feet, a teenager's underarm, and a person who cannot metabolise leucine.

So why do 67 suppliers sell it

Because of one sentence in notes:

Isovaleric acid has a strong pungent cheesy or sweaty smell, but its volatile esters have pleasing scents.

This acid is a raw material for raw materials. Isoamyl acetate is banana; ethyl isovalerate is fruit candy. They start here.

It has its own uses too. The flavor field reads cheesy, dairy, creamy, fermented, sweet, waxy, berry — evaluated at 50 ppm. Cheese and fermented flavour work needs it.

In perfumery it is a trace animalic/sweat modifier. Strength rank 3, evaluate below 1%, substantivity 400 hours — a one-drop mistake follows you for four hundred of them.

Two field details picked up along the way

One: its toxicity field uses ml/kg and µl/kg at once.

oral-rat LD50 2 ml/kg (Union Carbide Data Sheet, 1972) skin-rabbit LD50 310 µl/kg (same)

I wrote about these units last time. This record has a specific gravity (0.923–0.928), so the conversion works:

• 2 ml/kg × 0.9255 ≈ 1,851 mg/kg (oral)
• 310 µl/kg × 0.9255 ≈ 287 mg/kg (dermal)

287 mg/kg dermal is on the low side. Most aroma materials' rabbit dermal LD50 reads "> 5000 mg/kg," which means they tested to the ceiling and nothing happened. This one does not.

Two: the occurrence field lists "dolphin fat."

That field runs to dozens of natural sources — apple, banana, beer, cheese, cocoa, coffee, honey, ham, hops, cypress, geranium — and wedged among them is dolphin fat.

I do not know where that entry came from, but it is a useful reminder: this field sweeps up every source anything has been detected in, and it is not a list of places you could obtain it from.

How to use it

• Trace amounts. Rank 3, evaluate below 1%, and it stays 400 hours.
• Refrigerate it. This material sits in the 145 records told to refrigerate, a group that is 13.8% carboxylic acids.
• It is a modifier, not a lead. It builds realism on the leather, animalic and cheese/fermented lines.
• Mind the 287 mg/kg dermal figure. It is an acid and it irritates.
• If you want what it does without what it smells like, use its esters.

What this doesn't establish

• I have not smelled it. This is fields, whole-database statistics, and three papers.
• Those three are microbiology and medicine, not fragrance research. I cite their account of where this molecule comes from and touch none of their body-odour product applications.
• Ara 2006's inhibition result holds under their experimental conditions. I did not check whether it has been replicated, and I have no doses.
• I converted both LD50s using the specific gravity. I did not go to the original Union Carbide data sheet.
• "Most materials read > 5000 mg/kg" is an impression from the records I have read, not a database-wide count.
• I did not trace the "dolphin fat" entry.
• I did not check IFRA's text for this material.