Diallyl Sulfide

Diallyl Sulfide at a Glance

Diallyl sulfide (DAS) is the simplest member of garlic’s allyl sulfide series — two allyl groups joined by a single sulfur atom, where diallyl disulfide has two sulfurs and diallyl trisulfide has three. It is not present in an intact clove. It appears when garlic’s reactive thiosulfinates — headed by allicin — break down under heat, which is why it is a constituent of steam-distilled garlic oil rather than of fresh garlic ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.

In most head-to-head assays DAS is the least potent of the three. Cytotoxicity, calcium signalling and membrane effects all track the number of sulfur atoms, and DAS sits at the bottom of that gradient ^{16,17Reference 16Jan CR et al. · 2012Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cellsView study →Reference 17Tsuchiya H · 2008Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidityView study →}. It also cannot do the thing that gives the polysulfides much of their cardiovascular pharmacology: releasing hydrogen sulfide requires a sulfur–sulfur bond that DAS does not have ^{15Reference 15Benavides GA et al. · 2007Hydrogen sulfide mediates the vasoactivity of garlicView study →}.

What makes this molecule worth a page anyway is a single, unusually clean property the other two do not share as strongly. DAS is an inhibitor of cytochrome P450 2E1 — the enzyme that turns nitrosamines, carbon tetrachloride and paracetamol into their toxic metabolites ^{1,2Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}. That mechanism is defined at the enzyme level, replicated in animal protection studies against exactly those insults, and confirmed in humans in a small phenotyping study ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}. It is also the reason the compound belongs in an interactions conversation rather than a supplements one.

The CYP2E1 Story

This is the spine of the molecule. CYP2E1 is not a generic detox enzyme — it is a bioactivator. Several important toxicants are relatively harmless until CYP2E1 oxidises them: dimethylnitrosamine and other nitrosamines to DNA-alkylating species, carbon tetrachloride to the trichloromethyl radical, and paracetamol/acetaminophen to NAPQI. Block the enzyme before the exposure and you blunt the injury.

How It Inhibits the Enzyme

DAS hits CYP2E1 by two distinct routes at once ^{1Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →}:

• Competitive inhibition by the parent molecule. DAS competitively inhibits CYP2E1-mediated p-nitrophenol hydroxylase and dimethylnitrosamine demethylase activity in rat liver microsomes, and the inhibition is selective — potent against nitrosamine substrates, much weaker against nitrosomethylbenzylamine, and essentially absent against benzphetamine and ethylmorphine ^{1,2Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}.
• Suicide inactivation by its own metabolite. CYP2E1 oxidises DAS to diallyl sulfoxide and then to diallyl sulfone (DASO₂), and DASO₂ is a mechanism-based inactivator: preincubation destroys the enzyme in a time- and NADPH-dependent, saturable process that consumes the microsomal P450–CO binding spectrum and is not rescued by added nucleophile (Kᵢ 188 µM) ^{1Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →}. Metabolite work identified the likely final step — CYP2E1 activating the terminal olefin of DASO₂, the classic route by which terminal alkenes destroy the P450 that oxidises them ^{3Reference 3Jin L · 1997AnimalMetabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in ratsView study →}.

The practical shape of this in a live animal: after a single 200 mg/kg oral dose in rats, liver microsomes showed only modest inhibition at 3 hours but about 80% loss of nitrosamine-demethylase activity at 18 hours, with immunoblots confirming suppressed CYP2E1 protein ^{2Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}. The effect is not instantaneous — it builds as the metabolite accumulates.

The Human Confirmation

Almost everything DAS does is rodent work, with one exception. In a volunteer phenotyping study using chlorzoxazone as a selective CYP2E1 probe, a single oral dose of 0.2 mg/kg DAS significantly reduced CYP2E1 activity (n = 8, p = 0.024) — the in-vivo human counterpart of the microsomal data ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}. This is a small pharmacodynamic study, not an efficacy trial, but it is a genuine human confirmation that the mechanism translates, and at a dose low enough to be plausible from a concentrated garlic-oil product.

The Direction Is Not Fixed

The honest complication: acute inhibition is not the whole story. When purified DAS (>99%) was given to rats intraperitoneally every day for 14 days at 100 µmol/kg, CYP2E1 activity came out 1.6-fold higher than control — DAS was the only one of the three allyl sulfides to raise it ^{14Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →}. Its own metabolism also induces CYP2B1: the same 18-hour rat microsomes that had lost 80% of their nitrosamine-demethylase activity showed a 6-fold rise in pentoxyresorufin dealkylation ^{1,2Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}. So the net enzyme effect depends on dose, route and timing, and “DAS inhibits CYP2E1” should be read as a description of acute exposure rather than a steady state.

Where It Sits on the Polysulfide Gradient

Garlic’s three diallyl sulfides are routinely written about as if interchangeable. They are not — and the differences run in a consistent direction with chain length.

Cytotoxicity and calcium signalling rise with sulfur count. In renal tubular (MDCK) cells, the order for both intracellular calcium elevation and loss of cell viability was DAS < diallyl disulfide < diallyl trisulfide, a gradient the authors attribute directly to the number of sulfur atoms ^{16Reference 16Jan CR et al. · 2012Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cellsView study →}. Membrane work agrees: the allyl sulfides rigidify model membranes with potency tracking the polysulfide, and DAS is the weakest member tested ^{17Reference 17Tsuchiya H · 2008Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidityView study →}. In leukaemia cells, garlic essential oil and diallyl disulfide produced the strongest apoptotic and differentiating effects, with DAS not among the leaders ^{19Reference 19Agassi SFT et al. · 2020Potentiation of differentiation and apoptosis in a human promyelocytic leukemia cell line by garlic essential oil and its organosulfur compoundsView study →}.

Hydrogen-sulfide release requires a bond DAS does not have. Human red blood cells convert garlic-derived organic polysulfides to H₂S, and the yield is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms; the sulfur–sulfur nucleophilic-substitution route that liberates H₂S is available only to compounds with n > 2 sulfurs, and vasorelaxant potency tracked H₂S yield ^{15Reference 15Benavides GA et al. · 2007Hydrogen sulfide mediates the vasoactivity of garlicView study →}. A monosulfide has no S–S bond, so the H₂S-donor story that underwrites much of diallyl trisulfide’s cardiovascular pharmacology does not carry over to DAS.

Phase II enzyme induction also skips it. In the same 14-day rat study, diallyl trisulfide (at 10 µmol/kg) and diallyl disulfide (at ten times that dose) significantly raised glutathione S-transferase, quinone reductase and glutathione peroxidase — DAS did not, and in the carbon-tetrachloride injury model it was the two polysulfides, not DAS, that protected through phase II induction ^{14Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →}.

But the gradient is not universal. In the murine colonic nuclear-aberration assay, DAS and S-allylcysteine were the only two of nine organosulfur compounds to significantly reduce dimethylhydrazine-induced damage — leading the authors to conclude that an allyl group attached to a single sulfur atom was the structurally important feature ^{11Reference 11Sumiyoshi H · 1990AnimalChemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compoundsView study →}. Chain length predicts cytotoxic potency well; it does not predict everything.

An Oil Constituent, Not a Fresh-Garlic One

Where a compound comes from matters for what a dose of it means. Fresh garlic contains essentially no diallyl sulfide. An intact clove stores alliin; crushing releases alliinase, which makes allicin; allicin and its fellow thiosulfinates are unstable and decompose — under the heat of steam distillation — into the diallyl mono-, di-, tri- and tetrasulfide series.

HPLC analysis of commercial garlic products drew the line cleanly: thiosulfinates were released only from cloves and garlic powder, while the diallyl, methyl allyl and dimethyl sulfide series were the exclusive constituents of steam-distilled garlic oil products — oil macerates instead carried the vinyldithiins and ajoenes, and aged aqueous-alcohol extracts contained none of these non-ionic sulfur compounds at all ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}. Content varied up to 33-fold between brands of steam-distilled garlic oil ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.

Two consequences follow. First, DAS has no role in the living plant — it is a thermal artefact of garlic’s defence chemistry, not a metabolite the plant makes or uses. Second, the product you take determines whether you get any: garlic oil capsules deliver the sulfide series, garlic powder delivers thiosulfinate potential, and aged garlic extract delivers S-allylcysteine — three different molecules with three different pharmacologies from one bulb.

What It's Used For

Almost all of DAS’s biology is rodent chemoprotection built on one mechanism, with a single small human study touching the mechanism itself and none touching an outcome.

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. Only the enzyme-level row has any human data; every outcome row is animal-only, which caps the scores by design.

01CYP2E1 inhibitionPromising68%Enzyme kinetics + mechanism-based inactivation + rat in vivo + one human phenotyping study ^{1,2,3,4Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →Reference 3Jin L · 1997AnimalMetabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in ratsView study →Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}

02Hepatoprotection (paracetamol & CCl₄)Promising48%Replicated mouse/rat models across three decades, mechanistically tied to reduced bioactivation ^{6,7,8Reference 6Wang EJ et al. · 1996AnimalProtective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in miceView study →Reference 7Li M et al. · 2019AnimalDiallyl sulfide treatment protects against acetaminophen-/carbon tetrachloride-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in miceView study →Reference 8Elkhoely A · 2019AnimalDiallyl sulfide ameliorates carbon tetrachloride-induced hepatotoxicity in rats via suppressing stress-activated MAPK signaling pathwaysView study →}

03Chemoprevention of chemically-induced cancerShaky44%Colon, lung and oesophageal carcinogen models in mice and rats ^{9,10,11,12Reference 9Hong JY et al. · 1992AnimalInhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lungView study →Reference 10Wargovich MJ · 1987Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancerView study →Reference 11Sumiyoshi H · 1990AnimalChemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compoundsView study →Reference 12de Boer JG et al. · 2004AnimalChemoprotection against N-nitrosomethylbenzylamine-induced mutation in the rat esophagusView study →}

04Antioxidant / Nrf2 organ protectionShaky26%Single-group rat nephrotoxicity model ^{13Reference 13Kalayarasan S et al. · 2009AnimalDiallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar ratsView study →}

05Direct tumour-cell cytotoxicityShaky22%In-vitro only, and DAS is the weakest of the three allyl sulfides tested ^{16,17,18,19Reference 16Jan CR et al. · 2012Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cellsView study →Reference 17Tsuchiya H · 2008Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidityView study →Reference 18Sundaram SG · 1993Impact of organosulfur compounds in garlic on canine mammary tumor cells in cultureView study →Reference 19Agassi SFT et al. · 2020Potentiation of differentiation and apoptosis in a human promyelocytic leukemia cell line by garlic essential oil and its organosulfur compoundsView study →}

Mechanisms

The load-bearing row is the first: DAS is one of the tidier natural-product examples of a compound whose entire in-vivo protective profile can be traced to a single, named, mechanistically characterised enzyme interaction.

Pharmacokinetics

DAS is a small lipophilic thioether, given orally or intraperitoneally in every study cited here. Its metabolism is unusual in that the enzyme it inhibits is also the enzyme that activates it: CYP2E1 oxidises DAS at the sulfur atom to diallyl sulfoxide (DASO) and then to diallyl sulfone (DASO₂), and DASO₂ is the species that destroys the enzyme ^{1,3Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 3Jin L · 1997AnimalMetabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in ratsView study →}. Beyond sulfur oxidation, DAS and DASO are extensively oxidised at the allylic carbon and terminal double bonds; ten distinct glutathione conjugates were identified in the bile of dosed rats, including allyl glutathionyl disulfide and S-allylglutathione, with DASO and DASO₂ also reacting with glutathione non-enzymatically ^{3Reference 3Jin L · 1997AnimalMetabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in ratsView study →}. Timing matters more than usual for this molecule: hepatic CYP2E1 inhibition in rats is modest at 3 hours and near-maximal at 18 hours after a single oral dose, consistent with a metabolite-driven mechanism rather than a parent-drug one ^{2Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}.

Human ADME is not established. There is no published human Cmax, half-life or oral bioavailability for DAS; the only human measurement is a pharmacodynamic one — the fall in CYP2E1 probe activity after 0.2 mg/kg ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}.

Clinical Trials

There is one human study of diallyl sulfide, and it measured an enzyme, not an outcome ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}. No efficacy trial — hepatoprotective, chemopreventive or otherwise — has been conducted. A review of the field states plainly that DAS’s own toxicity and allergenicity have kept it out of clinical development, with effort redirected toward synthetic DAS analogues that inhibit CYP2E1 without being good substrates for it ^{5Reference 5Rao PS et al. · 2015Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1View study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a plant constituent, the isolate is almost the whole evidence base — and that is a strength here rather than a gap. The enzyme kinetics ^{1Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →}, the in-vivo inhibition time course ^{2Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}, the metabolite mapping ^{3Reference 3Jin L · 1997AnimalMetabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in ratsView study →}, the human phenotyping dose ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}, the NNK and dimethylhydrazine tumour studies ^{9,10Reference 9Hong JY et al. · 1992AnimalInhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lungView study →Reference 10Wargovich MJ · 1987Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancerView study →} and the paracetamol/CCl₄ protection ^{7,8Reference 7Li M et al. · 2019AnimalDiallyl sulfide treatment protects against acetaminophen-/carbon tetrachloride-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in miceView study →Reference 8Elkhoely A · 2019AnimalDiallyl sulfide ameliorates carbon tetrachloride-induced hepatotoxicity in rats via suppressing stress-activated MAPK signaling pathwaysView study →} all used purified DAS at stated doses; the 14-day comparison used sulfides of >99% purity ^{14Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →}.

Where whole garlic does appear, it complicates rather than supports the attribution: fresh garlic homogenate protected against paracetamol hepatotoxicity in its own right ^{6Reference 6Wang EJ et al. · 1996AnimalProtective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in miceView study →}, and garlic essential oil outperformed DAS in leukaemia-cell assays ^{19Reference 19Agassi SFT et al. · 2020Potentiation of differentiation and apoptosis in a human promyelocytic leukemia cell line by garlic essential oil and its organosulfur compoundsView study →} — in both cases the plant material contains a mixture in which DAS is a minor component, so plant-level effects cannot be assigned to it. The reverse caution is the more important one here: because DAS is the weakest allyl sulfide in most direct comparisons and the only one with no H₂S-donor capacity ^{15,16Reference 15Benavides GA et al. · 2007Hydrogen sulfide mediates the vasoactivity of garlicView study →Reference 16Jan CR et al. · 2012Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cellsView study →}, findings for diallyl disulfide and diallyl trisulfide should not be borrowed for it.

Prevalence in Nature

Diallyl sulfide is a decomposition product of Allium thiosulfinate chemistry, not a stored plant metabolite. Intact garlic holds alliin; damage generates allicin and its relatives; heat then converts those into the diallyl sulfide series. It follows that the compound’s “occurrence” is really a statement about processing: steam-distilled garlic oil is where it lives, while oil-macerated products carry vinyldithiins and ajoene instead, and aged aqueous-alcohol extracts carry neither ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.

Within distilled garlic oil it is a minor member of its own series. GC-MS of a commercial garlic essential oil put diallyl trisulfide at 50.4%, diallyl disulfide at 25.3% and diallyl sulfide at 6.25%, with diallyl tetrasulfide, allyl methyl disulfide and various dithiins and dithianes making up most of the remainder ^{21Reference 21Zhao NN et al. · 2013Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae)View study →}. Related Allium species carry the series too but skew even further away from the monosulfide: chive (Allium schoenoprasum) oil was found to have “a very low concentration of diallyl monosulfide in comparison with the other diallyl sulfides” ^{22Reference 22Rattanachaikunsopon P · 2008Diallyl sulfide content and antimicrobial activity against food-borne pathogenic bacteria of chives (Allium schoenoprasum)View study →}. Garlic oil also contains the shorter-chain dimethyl sulfide and methyl allyl sulfide series alongside the diallyl one ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.

Major Natural Sources

Source	Material	Reported diallyl sulfide content
Garlic (Allium sativum)	steam-distilled essential oil	~6% of the oil 21Reference 21Zhao NN et al. · 2013Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae)View study →
Garlic (Allium sativum)	fresh clove	effectively none — thiosulfinates only 20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →
Garlic (Allium sativum)	aged aqueous-alcohol extract	not detected 20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →
Chives (Allium schoenoprasum)	oil	present, “very low” relative to the polysulfides 22Reference 22Rattanachaikunsopon P · 2008Diallyl sulfide content and antimicrobial activity against food-borne pathogenic bacteria of chives (Allium schoenoprasum)View study →

Steam-distilled garlic oil products vary up to 33-fold between brands in total sulfide content, so a percentage figure without a product analysis says little about dose ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.

Discovery & Synthesis

Diallyl sulfide has been known as a component of distilled garlic oil since the early era of essential-oil chemistry; the precise first-isolation record is not documented here. Its pharmacological career, by contrast, has a clear starting point: a 1987 report that gavage-administered DAS inhibited dimethylhydrazine-induced colon cancer in mice by 74% ^{10Reference 10Wargovich MJ · 1987Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancerView study →}, followed within a year by the discovery that it selectively inhibited hepatic nitrosamine metabolism ^{2Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →} and, by 1991, the full characterisation of CYP2E1 as its target and diallyl sulfone as the suicide inactivator ^{1Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →}.

Synthesis is trivial. As a simple symmetrical dialkenyl thioether, DAS is made by reacting an allyl halide with a sulfide salt — a standard thioether coupling — and every study cited here used purified synthetic or synthetically-verified material, with the 14-day rat comparison specifying >99% purity ^{14Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →}. Commercial DAS is therefore a manufactured research chemical and flavour ingredient, not a garlic extract; nobody distils garlic to obtain it. Current medicinal-chemistry interest is in DAS analogues designed to inhibit CYP2E1 selectively while being poor substrates for it, so as to separate the protective effect from the compound’s own toxicity ^{5Reference 5Rao PS et al. · 2015Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1View study →}.

Patents: not yet researched.

Toxicity & Safety

The safety picture here is genuinely two-sided, and neither side is about acute poisoning.

The Interaction Is the Real Issue

DAS’s defining property is inhibition of a human drug-metabolising enzyme, demonstrated in humans at a low oral dose ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}. CYP2E1 handles chlorzoxazone, ethanol at higher concentrations, paracetamol’s minor oxidative route, isoniazid, and the defluorination of halogenated volatile anaesthetics. Inhibiting it is protective against toxicants that CYP2E1 activates, but it necessarily slows clearance of substrates the enzyme normally removes. Concentrated garlic-oil products are therefore a plausible — if unquantified — source of a CYP2E1 interaction, and the study authors specifically raised the possibility of an additive effect from habitual Allium consumption ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}. Adding to the complexity, DAS also induces CYP2B1 in rats ^{1,2Reference 1Brady JF et al. · 1991Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolitesView study →Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →}, and on 14-day repeated dosing raised rather than lowered CYP2E1 activity ^{14Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →} — so the direction of any interaction depends on dose and duration.

Isolate Toxicity

A review of DAS’s therapeutic potential is direct about why the compound itself has not advanced: it notes appreciable allergic reactions and toxicity, since DAS affects normal cells as well as target ones, and frames analogue development as the way around this ^{5Reference 5Rao PS et al. · 2015Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1View study →}. The animal protection doses are also very high relative to any plausible human intake — 100–400 µmol/kg ^{7Reference 7Li M et al. · 2019AnimalDiallyl sulfide treatment protects against acetaminophen-/carbon tetrachloride-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in miceView study →}, 150 mg/kg ^{13Reference 13Kalayarasan S et al. · 2009AnimalDiallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar ratsView study →}, 200 mg/kg ^{2,9,10Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →Reference 9Hong JY et al. · 1992AnimalInhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lungView study →Reference 10Wargovich MJ · 1987Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancerView study →} — so the favourable rodent risk-benefit does not transfer to a supplement.

What Dietary Exposure Actually Looks Like

Culinary garlic delivers essentially no DAS ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}. Meaningful exposure requires steam-distilled garlic oil, where DAS is roughly 6% of an oil whose total sulfide content itself varies 33-fold between brands ^{20,21Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →Reference 21Zhao NN et al. · 2013Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae)View study →}. Whole-garlic safety questions — bleeding risk, gastrointestinal upset, surgical caution — belong to the garlic monograph and to allicin/ajoene, not to this molecule.

Reproductive and developmental toxicity for isolated diallyl sulfide is not characterised in the literature reviewed here, and no verdict is issued on this molecule page; pregnancy and lactation are decided on the herb or product page where intake is decided.

Safety at a Glance

⚠️ Moderate toxicity

• Dietary exposure is negligible. Fresh, crushed or cooked garlic contains essentially no diallyl sulfide — it is a steam-distillation product, so ordinary culinary use is not a meaningful source ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}.
• It inhibits CYP2E1 in humans. A single 0.2 mg/kg oral dose measurably reduced CYP2E1 activity in volunteers, so concentrated garlic-oil products carry real potential to alter the clearance of CYP2E1 substrates ^{4Reference 4Loizou GD · 2001The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazoneView study →}.
• The enzyme effect can reverse with repeated dosing. Acute exposure inhibits CYP2E1, but 14 days of dosing in rats raised it ~1.6-fold, and DAS separately induces CYP2B1 — net direction depends on dose and duration ^{2,14Reference 2Brady JF et al. · 1988AnimalEffect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activitiesView study →Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →}.
• Preclinical doses are far above any dietary intake, and a review of the field cites allergic reactions and toxicity to normal cells as the reason DAS has not been developed clinically ^{5Reference 5Rao PS et al. · 2015Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1View study →}.
• Do not read the polysulfides onto it. DAS releases no hydrogen sulfide, is the weakest of the three in cytotoxicity assays, and does not induce phase II enzymes — diallyl disulfide and trisulfide findings are not transferable ^{14,15,16Reference 14Fukao T et al. · 2004The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachlorideView study →Reference 15Benavides GA et al. · 2007Hydrogen sulfide mediates the vasoactivity of garlicView study →Reference 16Jan CR et al. · 2012Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cellsView study →}.

Dosage

There is no established human dose for diallyl sulfide, and no product is standardised to it.

The gap between the human probe dose (0.2 mg/kg) and the animal protection doses (roughly 11–200 mg/kg) is two to three orders of magnitude, which is the single most useful number here: the dose that demonstrably changes an enzyme in a person is nowhere near the dose that protects a rodent’s liver. In practice, human exposure comes from steam-distilled garlic oil products, whose sulfide content varies up to 33-fold between brands ^{20Reference 20Lawson LD et al. · 1991Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic productsView study →}, so no reliable intake figure can be given. These are doses studied in research and are not a personal recommendation.

References

1. Brady JF, et al. (1991). Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/1807447/
2. Brady JF, et al. (1988). Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities. Cancer Research. https://pubmed.ncbi.nlm.nih.gov/3167846/
3. Jin L, Baillie TA (1997). Metabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in rats. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/9084912/
4. Loizou GD, Cocker J (2001). The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Human & Experimental Toxicology. https://pubmed.ncbi.nlm.nih.gov/11530830/
5. Rao PS, et al. (2015). Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1. Current Drug Metabolism. https://pubmed.ncbi.nlm.nih.gov/26264202/
6. Wang EJ, et al. (1996). Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice. Toxicology and Applied Pharmacology. https://pubmed.ncbi.nlm.nih.gov/8560468/
7. Li M, et al. (2019). Diallyl sulfide treatment protects against acetaminophen-/carbon tetrachloride-induced acute liver injury by inhibiting oxidative stress, inflammation and apoptosis in mice. Toxicology Research. https://pubmed.ncbi.nlm.nih.gov/30713662/
8. Elkhoely A (2019). Diallyl sulfide ameliorates carbon tetrachloride-induced hepatotoxicity in rats via suppressing stress-activated MAPK signaling pathways. Journal of Biochemical and Molecular Toxicology. https://pubmed.ncbi.nlm.nih.gov/30811752/
9. Hong JY, et al. (1992). Inhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lung. Carcinogenesis. https://pubmed.ncbi.nlm.nih.gov/1587006/
10. Wargovich MJ (1987). Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancer. Carcinogenesis. https://pubmed.ncbi.nlm.nih.gov/3815744/
11. Sumiyoshi H, Wargovich MJ (1990). Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds. Cancer Research. https://pubmed.ncbi.nlm.nih.gov/2379172/
12. de Boer JG, et al. (2004). Chemoprotection against N-nitrosomethylbenzylamine-induced mutation in the rat esophagus. Nutrition and Cancer. https://pubmed.ncbi.nlm.nih.gov/15623463/
13. Kalayarasan S, et al. (2009). Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/19374873/
14. Fukao T, et al. (2004). The effects of allyl sulfides on the induction of phase II detoxification enzymes and liver injury by carbon tetrachloride. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/15046820/
15. Benavides GA, et al. (2007). Hydrogen sulfide mediates the vasoactivity of garlic. Proceedings of the National Academy of Sciences. https://pubmed.ncbi.nlm.nih.gov/17951430/
16. Jan CR, et al. (2012). Effect of allyl sulfides from garlic essential oil on intracellular Ca2+ levels in renal tubular cells. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/23163425/
17. Tsuchiya H, Nagayama M (2008). Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidity. Journal of Biomedical Science. https://pubmed.ncbi.nlm.nih.gov/18506599/
18. Sundaram SG, Milner JA (1993). Impact of organosulfur compounds in garlic on canine mammary tumor cells in culture. Cancer Letters. https://pubmed.ncbi.nlm.nih.gov/8287376/
19. Agassi SFT, et al. (2020). Potentiation of differentiation and apoptosis in a human promyelocytic leukemia cell line by garlic essential oil and its organosulfur compounds. Anticancer Research. https://pubmed.ncbi.nlm.nih.gov/33109572/
20. Lawson LD, Wang ZJ, Hughes BG (1991). Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic products. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/1775579/
21. Zhao NN, et al. (2013). Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae). Journal of Economic Entomology. https://pubmed.ncbi.nlm.nih.gov/23865201/
22. Rattanachaikunsopon P, Phumkhachorn P (2008). Diallyl sulfide content and antimicrobial activity against food-borne pathogenic bacteria of chives (Allium schoenoprasum). Bioscience, Biotechnology, and Biochemistry. https://pubmed.ncbi.nlm.nih.gov/18997412/

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