Isoalliin

Isoalliin at a Glance

Isoalliin — trans-S-1-propenyl-L-cysteine sulfoxide, usually abbreviated PRENCSO — is one of the small family of sulfur-containing amino acids that give the genus Allium its chemistry. In an intact bulb it does nothing at all: it is odourless, non-volatile, water-soluble, and stored quietly in the cytoplasm well away from the enzyme that would act on it ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}.

On this site the molecule arrives through garlic, where it is a genuine but minor constituent — garlic’s cysteine-sulfoxide pool is dominated by alliin, with methiin second and isoalliin a consistently detected third ^{18,19Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →Reference 19Ferioli F et al. · 2022Non-volatile cysteine sulphoxides and volatile organosulphur compounds in cloves of garlic (Allium sativum L.) and elephant garlic (Allium ampeloprasum L.) local accessions from northern and central ItalyView study →}. Isoalliin’s real home is the onion, where it is the principal cysteine sulfoxide and accounts for most of the bulb’s pungency ^{10,12Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →Reference 12Lee EJ et al. · 2009Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contentsView study →}.

That is where the interesting story is. Isoalliin is the starting material for the only well-resolved two-enzyme pathway in Allium chemistry — the one that ends in a volatile compound that makes people cry. Its human pharmacology, by contrast, is essentially unstudied: no clinical trial has ever administered isolated isoalliin, and everything claimed for it downstream belongs to whole onion juice or to mixed thiosulfinate fractions. This page is honest about that split. The mechanism and chemotaxonomy are excellent; the therapeutics are not there.

Why Onions Make You Cry

Garlic’s chemistry is a one-enzyme story: crush a clove, alliinase meets alliin, and the sulfenic acid released condenses with itself to give allicin. Onion runs the same first step on a different substrate — and then adds a second, dedicated enzyme that garlic does not use.

Step 1 — alliinase. Cutting an onion ruptures the compartment separating substrate from enzyme. Alliinase (EC 4.4.1.4), a pyridoxal-phosphate-dependent carbon–sulfur lyase ^{29Reference 29Kuettner EB et al. · 2002Purification, characterization, and crystallization of alliinase from garlicView study →}, cleaves isoalliin into 1-propenylsulfenic acid, plus ammonia and pyruvate ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}. (The pyruvate is not a footnote: because one molecule is released per cleavage, pyruvate concentration is the standard laboratory proxy for onion pungency — and it tracks isoalliin content directly ^{12Reference 12Lee EJ et al. · 2009Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contentsView study →}.)

Step 2 — lachrymatory factor synthase. 1-Propenylsulfenic acid is short-lived and, left alone, would condense into thiosulfinates the way allicin’s precursor does. Instead a second enzyme, lachrymatory factor synthase (LFS), intercepts it and rearranges it into syn-propanethial S-oxide — a small, volatile, membrane-permeant S-oxide that reaches the eye and triggers stinging and tearing ^{1,3Reference 1Imai S et al. · 2002Plant biochemistry: an onion enzyme that makes the eyes waterView study →Reference 3Brodnitz MH · 1971Thiopropanal S-oxide: a lachrymatory factor in onionsView study →}.

The volatile product was pinned down first. Brodnitz and Pascale identified thiopropanal S-oxide as the lachrymatory factor of onion in 1971 ^{3Reference 3Brodnitz MH · 1971Thiopropanal S-oxide: a lachrymatory factor in onionsView study →}, building on Spåre and Virtanen’s 1963 characterisation of the factor and its precursor ^{4Reference 4Spåre C-G · 1963On the lachrymatory factor in onion (Allium cepa) vapours and its precursorView study →}. What stayed unresolved for another three decades was whether the final step was chemistry or biology.

The Second Enzyme Was the Real Discovery

For most of that time the tear factor was assumed to be a spontaneous rearrangement — an inevitable chemical fate of an unstable sulfenic acid, no different in kind from allicin’s formation in garlic. In 2002, Imai and colleagues at House Foods reported in Nature that it is not: a distinct enzyme, LFS, carries out the conversion ^{1Reference 1Imai S et al. · 2002Plant biochemistry: an onion enzyme that makes the eyes waterView study →}.

That reframes the whole thing. If the tear factor were a chemical accident, onions would make you cry as an unavoidable side effect of storing sulfur. Because a dedicated enzyme performs the last step, the lachrymatory factor is a deliberate product — the plant is spending genetic and metabolic resources to make it, which is the signature of a defence compound rather than a by-product ^{2Reference 2Silvaroli JA et al. · 2017Enzyme that makes you cry — crystal structure of lachrymatory factor synthase from Allium cepaView study →}.

The structural work supports that reading. Silvaroli and colleagues solved the crystal structure of onion LFS in 2017, in apo form and with a substrate analogue bound ^{2Reference 2Silvaroli JA et al. · 2017Enzyme that makes you cry — crystal structure of lachrymatory factor synthase from Allium cepaView study →}. LFS turns out to have the helix-grip fold of the plant START (star-related lipid-transfer) domain superfamily — the same architecture as the abscisic-acid receptor PYL10 — repurposed as a catalyst. Comparing the two let the authors map the active site and propose a mechanism running through sequential proton transfer and a carbanion intermediate ^{2Reference 2Silvaroli JA et al. · 2017Enzyme that makes you cry — crystal structure of lachrymatory factor synthase from Allium cepaView study →}. A recruited receptor-like fold doing dedicated catalytic work is not what a passive rearrangement looks like.

The Tearless Onion

The clean test of “is LFS really the switch?” is to remove it — and that experiment has been done, twice, by two different routes.

The RNAi route. In 2008 Eady and colleagues silenced the LFS gene in onion by RNA interference, reducing LFS activity by up to 1,544-fold ^{5Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →}. Wounded plants produced far less lachrymatory factor, exactly as predicted. The more interesting result was where the sulfur went instead: with LFS out of the way, more 1-propenylsulfenic acid condensed into di-1-propenyl thiosulfinate — an isomer of garlic’s allicin — and downstream of that the onions accumulated a zwiebelane isomer, di-1-propenyl disulfide, and 2-mercapto-3,4-dimethyl-2,3-dihydrothiophene, compounds previously seen only in traces or not at all ^{5Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →}. Isoalliin’s carbon and sulfur were not lost; they were re-routed.

The non-transgenic route. In 2016 Kato and colleagues produced tearless, non-pungent onions without genetic modification, by irradiating seed with a 20 Gy neon-ion beam and screening the progeny by sensory panel and HPLC ^{6Reference 6Kato M et al. · 2016Production and characterization of tearless and non-pungent onionView study →}. Two tearless bulbs emerged in the third generation; twenty offspring bulbs of each showed no tear induction and no pungency across a 20-person panel, with lachrymatory-factor production roughly 7.5-fold lower than normal onion. Notably, the lesion here was upstream — low alliinase mRNA (under 1% of normal) and correspondingly little alliinase protein — so the entire isoalliin-processing pathway was throttled at step 1 rather than step 2 ^{6Reference 6Kato M et al. · 2016Production and characterization of tearless and non-pungent onionView study →}.

The two routes differ in an instructive way. Silencing LFS removes the tears but leaves alliinase running, so the sulfur is redirected into thiosulfinates. Silencing alliinase removes the tears and the pungency by leaving isoalliin uncleaved. Both are “tearless onions”; they are chemically quite different plants.

Practical follow-ups exist. Rapid phenotyping of LFS-silenced versus normal bulbs was worked out by desorption-electrospray-ionisation mass spectrometry, distinguishing the two by scratching a leaf and recording ions for under half a minute — a breeding-selection tool ^{7Reference 7Joyce NI et al. · 2013Fast phenotyping of LFS-silenced (tearless) onions by desorption electrospray ionization mass spectrometry (DESI-MS)View study →}. And the redirected chemistry turns out not to be inert: thiolanotrisulfide and thiolanotetrasulfide, novel bisthiolane polysulfides isolated from LFS-suppressed onion, inhibited COX-1 in vitro with IC₅₀ values of 720 µM and 464 µM against aspirin’s 3,282 µM in the same assay ^{9Reference 9Aoyagi M et al. · 2021In vitroNovel bisthiolane polysulfides from lachrymatory factor synthase-suppressed onion and their in vitro cyclooxygenase-1 inhibitory activityView study →}.

The Cysteine-Sulfoxide Fingerprint of Allium

Isoalliin is one of a handful of S-alk(en)yl-L-cysteine sulfoxides (ACSOs) that differ only in the group attached to sulfur — and the proportions of those four or five molecules are what chemically distinguish one Allium from another.

Cysteine sulfoxide	S-substituent	Where it dominates
Alliin	2-propenyl (allyl)	Garlic — and essentially only garlic among common species 10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →
Isoalliin	trans-1-propenyl	Onion, leek, chive, shallot 10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →
Methiin	methyl	Ubiquitous across Allium — and beyond, into the Brassicaceae 10,11Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →Reference 11Krest I et al. · 2000Cysteine sulfoxides and alliinase activity of some Allium speciesView study →
Propiin	n-propyl	Sporadic; present in only a few, not closely related species 11Reference 11Krest I et al. · 2000Cysteine sulfoxides and alliinase activity of some Allium speciesView study →

Kubec and Dadáková quantified ACSOs across twelve commonly eaten alliaceous and cruciferous vegetables and drew the line cleanly: alliin was found only in garlic, while isoalliin was the major cysteine sulfoxide of onion, leek, chive and shallot ^{10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →}. Total ACSO content across the Allium species ranged from 0.59 to 12.3 mg/g fresh weight; the cruciferous species carried methiin alone (0.06–2.45 mg/g fresh weight) ^{10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →}. A later comparative study extended the same picture across garlic, onion, shallot and leek with three chromatographic methods run side by side ^{13Reference 13Kubec R · 2009Chromatographic methods for determination of S-substituted cysteine derivatives — a comparative studyView study →}.

The genus-wide survey by Krest and colleagues, covering flavour precursors in 17 species of the Alliaceae, adds a wrinkle worth keeping. Methiin was the most abundant sulfoxide overall; propiin appeared in only a few, unrelated species; and — the counter-intuitive part — for every protein extract tested, the highest specific alliinase activity was against alliin, regardless of which sulfoxide actually predominated in that plant. Substrate specificity was not related to the relative abundance of the cysteine sulfoxides ^{11Reference 11Krest I et al. · 2000Cysteine sulfoxides and alliinase activity of some Allium speciesView study →}. Onion alliinase, in other words, is not a specialist isoalliin enzyme; it is a generalist that happens to be handed mostly isoalliin.

This is real chemotaxonomy: the ACSO profile discriminates species and, within garlic, even ecotype and growing location ^{18Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →}.

What Isoalliin Becomes

Once alliinase has released 1-propenylsulfenic acid, the sulfur takes several roads. This downstream family — not isoalliin itself — is where any biological activity lives.

• syn-Propanethial S-oxide (the lachrymatory factor) — the LFS product; volatile, eye-irritant, and the reason for everything above ^{1,3Reference 1Imai S et al. · 2002Plant biochemistry: an onion enzyme that makes the eyes waterView study →Reference 3Brodnitz MH · 1971Thiopropanal S-oxide: a lachrymatory factor in onionsView study →}.
• Di-1-propenyl thiosulfinate — the allicin-isomer that forms when two 1-propenylsulfenic acids condense; normally minor in onion because LFS competes for the substrate, and markedly increased when LFS is silenced ^{5Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →}.
• Zwiebelanes — cyclic rearrangement products of di-1-propenyl thiosulfinate, formed non-enzymatically; one isomer accumulates sharply in LFS-silenced onion ^{5,7Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →Reference 7Joyce NI et al. · 2013Fast phenotyping of LFS-silenced (tearless) onions by desorption electrospray ionization mass spectrometry (DESI-MS)View study →}.
• Cepaenes — α-sulfinyl disulfides characteristic of onion. Together with onion thiosulfinates they inhibit the chemotaxis of human polymorphonuclear leukocytes in vitro, the basis of the old anti-inflammatory / anti-asthmatic interest in onion extracts ^{25Reference 25Dorsch W et al. · 1990Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenesView study →}.
• Allithiolanes and bisthiolane polysulfides — derivatives of a 3,4-dimethylthiolane S-oxide skeleton built from 1-propenyl units. Nine groups of allithiolanes were identified as the compounds behind the bitter off-taste of processed onion, with detection thresholds of 15–30 ppm ^{21Reference 21Kubec R et al. · 2018Allithiolanes: nine groups of a newly discovered family of sulfur compounds responsible for the bitter off-taste of processed onionView study →}; the related bisthiolane polysulfides from LFS-suppressed onion carry the COX-1 activity noted above ^{9Reference 9Aoyagi M et al. · 2021In vitroNovel bisthiolane polysulfides from lachrymatory factor synthase-suppressed onion and their in vitro cyclooxygenase-1 inhibitory activityView study →}.
• The pink pigment of cut onion and leek. In one of the more elegant pieces of Allium chemistry, isotope-labelling showed the pigment responsible for “pinking” is a mixture of conjugated bis-pyrrole species in which the C3 side chains and propenylidene bridge derive from the propenyl group of isoalliin, while the C1 units and methine bridge come from methiin ^{20Reference 20Kubec R et al. · 2015Allium discoloration: color compounds formed during pinking of onion and leekView study →}. Isoalliin is literally the source of the colour.
• Cycloalliin — a cyclic sulfoxide routinely quantified alongside isoalliin in both onion and garlic ^{18,22Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →Reference 22Kim S et al. · 2016Change in organosulfur compounds in onion (Allium cepa L.) during heat treatmentView study →}.

A Related Molecule Worth Not Confusing

Aged garlic extract contains S-1-propenylcysteine (S1PC) — the same 1-propenyl group on cysteine, but without the sulfoxide, and therefore a different molecule from isoalliin. It has its own small pharmacology: a single oral dose of 6.5 mg/kg lowered systolic blood pressure by about 10% at three hours in spontaneously hypertensive rats and increased tail blood flow, while S-allylcysteine and S-allylmercaptocysteine at the same doses did nothing ^{26Reference 26Ushijima M et al. · 2018AnimalEffects of S-1-propenylcysteine, a sulfur compound in aged garlic extract, on blood pressure and peripheral circulation in spontaneously hypertensive ratsView study →}; separately it prolonged IL-10/STAT3 signalling and promoted M2c macrophage polarisation in vitro ^{27Reference 27Miki S et al. · 2021S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signalingView study →}.

The two molecules share a biosynthetic neighbourhood — garlic stores γ-L-glutamyl-S-(trans-1-propenyl)-L-cysteine alongside its allyl and methyl counterparts ^{18Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →}, and that γ-glutamyl peptide pool feeds both the sulfoxide and the reduced amino acid. But findings for S-1-propenylcysteine are not findings for isoalliin, and nothing here should be read across.

What It's Used For

The blunt summary: isoalliin has no isolate pharmacology. No human trial, no animal study, and essentially no in-vitro assay has used the pure sulfoxide as the test article. What exists is activity data for the mixtures it decomposes into, and even those are usually onion juice rather than defined compounds.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every score here is low by design: these are downstream-mixture applications, and the isolated molecule has never been tested. The one high-confidence row is not an application at all but a mechanism, listed separately below the table.

01Antiplatelet (via onion thiosulfinates)Shaky22%In-vitro whole-juice aggregometry, incl. the LFS-silenced-vs-normal comparison ^{8,23,24Reference 8Thomson SJ et al. · 2013Inhibition of platelet activation by lachrymatory factor synthase (LFS)-silenced (tearless) onion juiceView study →Reference 23Briggs WH et al. · 2000Differential inhibition of human platelet aggregation by selected Allium thiosulfinatesView study →Reference 24Cavagnaro PF · 2012Effect of processing and cooking conditions on onion (Allium cepa L.) induced antiplatelet activity and thiosulfinate contentView study →}

02Anti-inflammatory (cepaenes & thiosulfinates)Shaky16%In-vitro leukocyte-chemotaxis inhibition by onion fractions ^{25Reference 25Dorsch W et al. · 1990Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenesView study →}

03COX-1 inhibition (thiolane polysulfides)Shaky11%Single in-vitro study of two novel compounds from LFS-suppressed onion ^{9Reference 9Aoyagi M et al. · 2021In vitroNovel bisthiolane polysulfides from lachrymatory factor synthase-suppressed onion and their in vitro cyclooxygenase-1 inhibitory activityView study →}

04Flavour, pungency & food qualityPromising68%Well-quantified composition/processing chemistry — a food-science result, not a health claim ^{12,20,21,22Reference 12Lee EJ et al. · 2009Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contentsView study →Reference 20Kubec R et al. · 2015Allium discoloration: color compounds formed during pinking of onion and leekView study →Reference 21Kubec R et al. · 2018Allithiolanes: nine groups of a newly discovered family of sulfur compounds responsible for the bitter off-taste of processed onionView study →Reference 22Kim S et al. · 2016Change in organosulfur compounds in onion (Allium cepa L.) during heat treatmentView study →}

Mechanisms

The load-bearing row is the second one. LFS is what separates an onion from a garlic clove, and its existence as a discrete enzyme is why the tear factor counts as a manufactured defence rather than a chemical accident.

Pharmacokinetics

Not characterised. No absorption, distribution, metabolism or half-life data exist for isolated isoalliin in humans or animals — the molecule has never been dosed as an isolate.

What can be said with confidence is that oral exposure to intact isoalliin is largely hypothetical, because the molecule rarely survives to be swallowed. Chewing or chopping brings alliinase to the substrate within seconds, and the reaction is fast enough that intact isoalliin is essentially a property of undamaged tissue ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}. Cooking changes the arithmetic in both directions: alliinase is heat-labile, so boiling a whole bulb inactivates the enzyme and can spare the precursor, while boiling cut onion leaches ACSOs into the water (a 33–69% loss) and frying, steaming or microwaving raise measured ACSO content by concentrating the tissue ^{22Reference 22Kim S et al. · 2016Change in organosulfur compounds in onion (Allium cepa L.) during heat treatmentView study →}. Whether any intact isoalliin is absorbed, and what becomes of it if so, is unknown. In garlic the biosynthetically related γ-glutamyl peptides are known to act as storage forms ^{18Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →}, but that is plant metabolism, not human.

This absence matters: any in-vitro finding for an isoalliin-derived compound must be read against the fact that nobody knows what, if anything, reaches human plasma.

Clinical Trials

None. There are no completed, ongoing, planned or terminated human trials of isolated isoalliin at any dose or in any indication. Human trials involving onion exist, but they test the vegetable or its extract, in which isoalliin is one precursor among several and is consumed already decomposed.

Last checked: July 2026.

Isolate vs. Plant Studies

This is the cleanest case on the site of a molecule whose evidence is entirely plant-level.

No study has used isolated isoalliin as a test article for a biological endpoint. Isoalliin is synthesised and purified routinely — as an analytical standard ^{17Reference 17Hughes J et al. · 2005Synthesis of the flavour precursor, alliin, in garlic tissue culturesView study →} and to calibrate the HPLC, GC and capillary-electrophoresis methods used to quantify it ^{10,13Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →Reference 13Kubec R · 2009Chromatographic methods for determination of S-substituted cysteine derivatives — a comparative studyView study →} — but the standard is used to measure the molecule, never to dose anything.

Every functional result here is one of three things: (a) whole onion juice (the platelet work, including the tearless-vs-normal comparison ^{8,24Reference 8Thomson SJ et al. · 2013Inhibition of platelet activation by lachrymatory factor synthase (LFS)-silenced (tearless) onion juiceView study →Reference 24Cavagnaro PF · 2012Effect of processing and cooking conditions on onion (Allium cepa L.) induced antiplatelet activity and thiosulfinate contentView study →}); (b) a fractionated extract (the cepaene/thiosulfinate chemotaxis work ^{25Reference 25Dorsch W et al. · 1990Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenesView study →}); or (c) a downstream isolate that is not isoalliin — a thiosulfinate ^{23Reference 23Briggs WH et al. · 2000Differential inhibition of human platelet aggregation by selected Allium thiosulfinatesView study →} or a bisthiolane polysulfide ^{9Reference 9Aoyagi M et al. · 2021In vitroNovel bisthiolane polysulfides from lachrymatory factor synthase-suppressed onion and their in vitro cyclooxygenase-1 inhibitory activityView study →}. Even the strongest mechanistic evidence is plant evidence: the LFS knockdowns are transformed and mutagenised onions, and the readouts are tear induction, sensory panels and metabolite profiles in the intact plant ^{5,6Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →Reference 6Kato M et al. · 2016Production and characterization of tearless and non-pungent onionView study →}.

The transferability caveat runs in an unusual direction here. Normally the worry is that a whole-plant result may not belong to the named molecule. For isoalliin the worry is the reverse: the molecule is provably upstream of the whole-plant chemistry — the isotope labelling ^{20Reference 20Kubec R et al. · 2015Allium discoloration: color compounds formed during pinking of onion and leekView study →} and the knockdown metabolite profiles ^{5Reference 5Eady CC et al. · 2008Silencing onion lachrymatory factor synthase causes a significant change in the sulfur secondary metabolite profileView study →} establish that directly — but it can never itself be the active agent, because by the time anything happens it no longer exists.

Its Role in Plants

Biosynthesis. ACSOs derive from glutathione, established by radiotracer work and refined since. The route runs by S-alk(en)ylation of glutathione, removal of the glycyl and γ-glutamyl groups, and S-oxygenation ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}. In garlic, three γ-glutamyl transpeptidases (AsGGT1–3) have been identified that remove the γ-glutamyl moiety from γ-glutamyl-S-allyl-L-cysteine — and their strong preference for the non-oxygenated intermediate over the sulfoxide fixes the reaction order: deglutamylation first, S-oxygenation second ^{15Reference 15Yoshimoto N et al. · 2014Garlic γ-glutamyl transpeptidases that catalyze deglutamylation of biosynthetic intermediate of alliinView study →}. The corresponding 1-propenyl storage peptide, γ-L-glutamyl-S-(prop-1-enyl)-L-cysteine, was isolated from chive seed by Matikkala and Virtanen in 1962 ^{16Reference 16Matikkala EJ · 1962A new γ-L-glutamylpeptide, γ-L-glutamyl-S-(prop-1-enyl)-L-cysteine, in the seeds of chives (Allium schoenoprasum)View study →}, and its garlic counterpart (GSPC) is quantified alongside the allyl and methyl peptides in modern surveys ^{18Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →}. Garlic and onion callus cultures fed candidate intermediates confirm the general route while leaving several enzymes unidentified ^{17Reference 17Hughes J et al. · 2005Synthesis of the flavour precursor, alliin, in garlic tissue culturesView study →}. Most of the pathway still awaits characterisation ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}.

Storage and compartmentation. In an intact plant, ACSOs sit in the cytosol of storage mesophyll cells, while alliinase is vacuolar ^{14Reference 14Yoshimoto N · 2019ReviewS-Alk(en)ylcysteine sulfoxides in the genus Allium: proposed biosynthesis, chemical conversion, and bioactivitiesView study →}. That separation is the whole design: the plant carries a large inert reservoir of sulfur that becomes reactive only when a cell is broken.

Ecological function. The system is best read as chemical defence deployed on damage — an inert precursor plus a compartmentalised enzyme equals an on-demand irritant that costs nothing until something bites ^{2Reference 2Silvaroli JA et al. · 2017Enzyme that makes you cry — crystal structure of lachrymatory factor synthase from Allium cepaView study →}. Onion’s addition of LFS to the shared Allium toolkit yields a volatile end product, which extends the deterrent beyond the wound site into the air around it. Garlic, lacking LFS, instead pours its sulfenic acid into allicin, a non-volatile antimicrobial. Same substrate class, two different defensive strategies.

Prevalence in Nature

Isoalliin is effectively confined to the genus Allium. Within it, the distribution is sharp: Kubec and Dadáková found isoalliin to be the major S-alk(en)ylcysteine sulfoxide of onion, leek, chive and shallot, while alliin was restricted to garlic ^{10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →}. Total ACSO content of the Allium species surveyed spanned 0.59–12.3 mg/g fresh weight; cruciferous vegetables carried methiin only, and no isoalliin at all ^{10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →}. A broader survey of 17 Alliaceae species found cysteine sulfoxides and alliinase activity in every sample, with methiin most abundant overall ^{11Reference 11Krest I et al. · 2000Cysteine sulfoxides and alliinase activity of some Allium speciesView study →}.

In onion, the quantitative picture is good. Across short-day cultivars of low, medium and high pungency, isoalliin ran 0.07–0.65 mg/g fresh weight and rose with pungency grade, methiin 0.03–0.16 mg/g, giving totals of 0.12–0.77 mg/g ^{12Reference 12Lee EJ et al. · 2009Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contentsView study →}. In heat-processed onion, isoalliin was measured at 0.34–3.32 g/100 g dry weight ^{22Reference 22Kim S et al. · 2016Change in organosulfur compounds in onion (Allium cepa L.) during heat treatmentView study →}.

In garlic, isoalliin is real but minor. It is one of three ACSOs quantified in Italian garlic and elephant-garlic accessions, where total ACSOs ranged 4,533–15,520 mg/kg fresh weight in white garlic, 6,565–10,643 in red, and 2,759–5,756 in elephant garlic — with elephant garlic showing both the lowest total sulfoxide content and the lowest relative alliin ^{19Reference 19Ferioli F et al. · 2022Non-volatile cysteine sulphoxides and volatile organosulphur compounds in cloves of garlic (Allium sativum L.) and elephant garlic (Allium ampeloprasum L.) local accessions from northern and central ItalyView study →}. In Andalusian garlic, isoalliin was quantified alongside alliin, methiin and cycloalliin across cultivars and locations: purple-type cultivars carried the highest alliin and methiin but the lowest isoalliin, planting date significantly affected both alliin and isoalliin, and genotype contributed little to their variability — the whole organosulfur profile discriminated bulbs by location or ecotype with 81–86% accuracy ^{18Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →}.

The pattern is the useful thing: within a species the ACSOs move somewhat independently, so isoalliin content is not simply a shadow of total sulfur or of alliin.

Major Natural Sources

Source	Part	Isoalliin’s role	Figure
Onion (Allium cepa)	bulb	principal cysteine sulfoxide; sets pungency	0.07–0.65 mg/g fresh wt (raw) 12Reference 12Lee EJ et al. · 2009Characterization of shortday onion cultivars of 3 pungency levels with flavor precursor, free amino acid, sulfur, and sugar contentsView study →
Leek (A. ampeloprasum var. porrum)	stem / leaf base	major cysteine sulfoxide	qualitative 10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →
Chive (A. schoenoprasum)	leaf; seed (γ-glutamyl form)	major cysteine sulfoxide	qualitative 10,16Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →Reference 16Matikkala EJ · 1962A new γ-L-glutamylpeptide, γ-L-glutamyl-S-(prop-1-enyl)-L-cysteine, in the seeds of chives (Allium schoenoprasum)View study →
Shallot (A. cepa var. aggregatum)	bulb	major cysteine sulfoxide	qualitative 10Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →
Garlic (A. sativum)	clove	minor — third behind alliin and methiin	quantified, cultivar/location-dependent 18,19Reference 18Montaño A et al. · 2011Effect of genetic characteristics and environmental factors on organosulfur compounds in garlic (Allium sativum L.) grown in Andalusia, SpainView study →Reference 19Ferioli F et al. · 2022Non-volatile cysteine sulphoxides and volatile organosulphur compounds in cloves of garlic (Allium sativum L.) and elephant garlic (Allium ampeloprasum L.) local accessions from northern and central ItalyView study →
Elephant garlic (A. ampeloprasum)	clove	minor	quantified within total ACSO 2,759–5,756 mg/kg fw 19Reference 19Ferioli F et al. · 2022Non-volatile cysteine sulphoxides and volatile organosulphur compounds in cloves of garlic (Allium sativum L.) and elephant garlic (Allium ampeloprasum L.) local accessions from northern and central ItalyView study →

Discovery & Synthesis

First reported. Isoalliin arrived through the onion tear factor rather than the other way round. Working at the Biochemical Institute in Helsinki, Artturi Virtanen’s group characterised the lachrymatory factor of onion vapours and its precursor in 1963 ^{4Reference 4Spåre C-G · 1963On the lachrymatory factor in onion (Allium cepa) vapours and its precursorView study →}, having isolated the related γ-glutamyl peptide γ-L-glutamyl-S-(prop-1-enyl)-L-cysteine from chive seed the year before ^{16Reference 16Matikkala EJ · 1962A new γ-L-glutamylpeptide, γ-L-glutamyl-S-(prop-1-enyl)-L-cysteine, in the seeds of chives (Allium schoenoprasum)View study →}. The volatile product itself was assigned as thiopropanal S-oxide by Brodnitz and Pascale in 1971 ^{3Reference 3Brodnitz MH · 1971Thiopropanal S-oxide: a lachrymatory factor in onionsView study →}. The name isoalliin records the relationship to garlic’s alliin: same cysteine sulfoxide skeleton, the double bond moved one carbon along — an isomer, not a derivative.

Synthesis. Isoalliin is prepared synthetically as an analytical reference standard, and that is essentially its only commercial existence. Synthetic isoalliin (alongside alliin and propiin) has been made and confirmed by HPLC and NMR for tissue-culture work ^{17Reference 17Hughes J et al. · 2005Synthesis of the flavour precursor, alliin, in garlic tissue culturesView study →}, and reference materials underpin the HPLC, GC and micellar-electrokinetic-capillary methods used to quantify ACSOs in food ^{10,13Reference 10Kubec R · 2008Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatographyView study →Reference 13Kubec R · 2009Chromatographic methods for determination of S-substituted cysteine derivatives — a comparative studyView study →}. No named first total synthesis is well documented in the accessible literature, and there is no bulk industrial production: the molecule is not sold as a supplement, has no drug application, and is not extracted at scale. It is consumed in vast quantities and manufactured in almost none — every gram people eat is grown, not made.

Patents: not yet researched.

Toxicity & Safety

Isoalliin carries a low flag, with a caveat about what it turns into.

The molecule itself is an ordinary sulfur-containing amino acid, present in every onion and leek eaten worldwide, with no reported toxicity, no dose-limiting adverse effect and no interaction data — largely because it has never been isolated and dosed. It is odourless, non-volatile and inert until an enzyme reaches it.

The irritant is the product, not the precursor. syn-Propanethial S-oxide is a genuine ocular and respiratory irritant — that is its function. In practice this is a nuisance rather than a hazard for domestic cooking, but it becomes an occupational exposure in commercial onion processing, which is one of the stated motivations for the tearless-onion programmes ^{6Reference 6Kato M et al. · 2016Production and characterization of tearless and non-pungent onionView study →}. It is worth stating plainly that the tear response is not an allergy and not evidence of harm; it is a small volatile electrophile doing to the cornea exactly what the plant evolved it to do.

Onion toxicity in dogs and cats is a real and separate issue. Allium vegetables cause oxidative, Heinz-body haemolytic anaemia in dogs — feeding cooked onion at 30 g/kg for two days produced falling red-cell counts, rising Heinz bodies and bilirubin, and depressed erythrocyte glucose-6-phosphate dehydrogenase ^{30Reference 30Tang X et al. · 2008An experimental study of hemolysis induced by onion (Allium cepa) poisoning in dogsView study →}. Crucially, the causative agents identified in that literature are organosulfur thiosulfonates such as sodium n-propylthiosulfate ^{31Reference 31Yamato O et al. · 1999Reduced glutathione accelerates the oxidative damage produced by sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogsView study →} — an n-propyl compound, and therefore a descendant of propiin, not of isoalliin’s 1-propenyl chemistry. Isoalliin has not been established as the responsible agent. The practical rule — do not feed onion, garlic, leek or chive to pets — stands regardless of which molecule carries it. Flagged here for completeness, not as an isoalliin-specific finding.

Reproductive and genotoxicity data (prose note). No reproductive-toxicity, developmental-toxicity, genotoxicity or repeat-dose package exists for isolated isoalliin. This is an absence of data, not a finding of safety. Pregnancy and lactation decisions belong to the herb or product page where intake is actually decided, not to a molecule-level phytochemistry page.

Safety at a Glance

✅ Low / no toxicity

• A normal dietary constituent. Present in every onion, leek, chive and shallot eaten; no reported toxicity for the intact molecule at any dietary level.
• Inert until cut. Odourless, non-volatile and biologically inactive in undamaged tissue — it is compartmentalised away from the enzyme that activates it.
• Its enzymatic product is an eye and airway irritant. syn-Propanethial S-oxide causes the familiar stinging and tearing; a genuine occupational exposure in commercial onion processing.
• No isolate safety data whatsoever. No toxicology, no interaction studies, no reproductive data — because the molecule has never been dosed as an isolate. Absence of findings is not evidence of safety.
• Do not feed Allium vegetables to dogs or cats. Onion and garlic cause haemolytic anaemia in pets; the responsible compounds are downstream organosulfurs, not isoalliin specifically, but the household rule is unconditional.

Dosage

There is no dose. Isoalliin is not sold, not supplemented and not administered. No human study has given it in any amount, and no intake recommendation exists.

The only numbers worth carrying are compositional, and they describe food rather than a regimen:

If there is a practical takeaway, it is a culinary one rather than a dosing one: alliinase is heat-labile and the antiplatelet thiosulfinates it generates are destroyed by prolonged cooking, so onion prepared for that property should be cut and allowed to stand before heat, and heated briefly if at all — extensively cooked onion lost activity entirely and, at the harshest treatments, became pro-aggregatory in vitro ^{24Reference 24Cavagnaro PF · 2012Effect of processing and cooking conditions on onion (Allium cepa L.) induced antiplatelet activity and thiosulfinate contentView study →}. Onion’s broader dietary reputation rests on the whole vegetable, quercetin included, not on this molecule ^{28Reference 28Griffiths G et al. · 2002ReviewOnions — a global benefit to healthView study →}.

These are food-composition figures from research, not a personal recommendation.

References

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2. Silvaroli JA, Pleshinger MJ, Banerjee S, Kiser PD, Golczak M (2017). Enzyme that makes you cry — crystal structure of lachrymatory factor synthase from Allium cepa. ACS Chemical Biology. https://pubmed.ncbi.nlm.nih.gov/28708375/
3. Brodnitz MH, Pascale JV (1971). Thiopropanal S-oxide: a lachrymatory factor in onions. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/5546155/
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19. Ferioli F, Giambanelli E, D’Antuono LF (2022). Non-volatile cysteine sulphoxides and volatile organosulphur compounds in cloves of garlic (Allium sativum L.) and elephant garlic (Allium ampeloprasum L.) local accessions from northern and central Italy. Journal of the Science of Food and Agriculture. https://pubmed.ncbi.nlm.nih.gov/35211974/
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27. Miki S, Suzuki J-I, Takashima M, Ishida M, Kokubo H, Yoshizumi M (2021). S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signaling. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/34789834/
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