DADS (diallyl disulfide)

Diallyl Disulfide (DADS): A Comprehensive Reference

1. Identity and Chemical Characteristics

Systematic and common names: Diallyl disulfide (DADS, also designated 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other plants in the genus Allium. It is also encountered in the literature under the trade name "Garlicin." DADS is a compound composed of two allyl groups connected by two sulfur atoms and is a vital organosulfur compound found in garlic.

Molecular formula and physical properties: DADS is yellowish in nature and is insoluble in water, with a chemical structure of C₆H₁₀S₂. It is a clear, yellowish liquid which boils at 138–139 °C (for the typical 80% purity) and has its flash point at 50 °C, a density of about 1.0 g/mL, and a vapor pressure of 1 mmHg at 20 °C. It is non-polar; therefore, DADS is insoluble in water and is soluble in fats, oils, lipids, and non-polar solvents such as hexane or toluene.

Botanical source and relationship to allicin: Allicin is released when garlic or other plants belonging to the family Alliaceae are crushed; DADS is produced during the decomposition of allicin. More specifically, garlic bulb injury caused by cutting, crushing, or ingesting activates allinase (alliin lyase), an enzyme that converts alliin to allicin (diallyl thiosulfinate) via the formation of allyl sulfenic acid. The formation of allicin is extremely fast, with almost half of the alliin converted to allicin within 6 seconds, followed by the release of pyruvic acid and ammonia. Furthermore, allicin is a highly active and unstable metabolite that immediately decomposes into sulfur-containing compounds including allyl sulfides such as S-allyl mercapto cysteine, vinyl dithiins, and ajoene.

Position among garlic organosulfur compounds: Along with diallyl trisulfide and diallyl tetrasulfide, DADS is one of the principal components of the distilled oil of garlic. Other sulfur-containing phytochemicals found in A. sativum include diallyl disulphide (DDS), diallyl trisulfide (DTS), and S-allyl cysteine (SAC), which have a variety of pharmacological properties. Main sulfur compounds identified in garlic include allicin (AC), alliin, S-allylcysteine (SAC), diallyl disulfide (DADS), diallyl trisulfide (DATS), diallyl sulfide (DAS), methanethiosulfonic acid S-methyl ester (MMTS), allyl sulfide (AS), and ajoene.

Other Allium sources: The natural product diallyl disulfide is the major constituent of oil of garlic (Allium sativum) and other members of the Allium genus, including onion (A. cepa).

2. Production and Common Forms/Preparations

Natural extraction: Diallyl disulfide and the related trisulfide are produced by decomposition of allicin, which is released upon breaking the cells of the Alliaceae plants, especially garlic. The diallyl disulfide yield is the highest for the steam distillation of garlic bulbs, which contain about 2 wt.% of diallyl disulfide-rich oil. DADS can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.

Industrial synthesis: On an industrial scale, diallyl disulfide is produced from sodium disulfide and allyl bromide or allyl chloride at temperatures of 40–60 °C in an inert gas atmosphere; sodium disulfide is generated in situ by reacting sodium sulfide with sulfur.

Dietary supplement forms: DADS is encountered commercially as a component of garlic oil capsules and aged garlic extract preparations. Highly diluted, it is also used as a flavoring in food. It decomposes in the human body into other compounds such as allyl methyl sulfide. Allyl mercaptan, allyl methyl sulfide (AMS), allyl methyl disulfide (AMDS), DAS, and DADS have been detected in human breath immediately after consumption of raw garlic and commercial garlic products.

3. Historical and Traditional Use

DADS as a chemically isolated compound is a product of modern science; efforts to identify the active compound in garlic began in the mid-1800s, but it was not until 1945 that Chester J. Cavallito, John Hays Bailey, and Johannes S. Buck at Winthrop Chemical Co. (Rensselaer, NY) described the "antibacterial principle of A. sativum," which they derived from the "essential oil of garlic." The historical record of use, therefore, is inseparable from the broader ethnomedicinal history of garlic itself.

Ancient Egypt: Historically, garlic-derived compounds like DADS were employed in traditional medicine for treating infections, as evidenced by ancient Egyptian remedies documented in the Ebers Papyrus for wound healing and digestive ailments around 1550 BCE.

Geographic spread of traditional use: Allium sativum belongs to the family Amaryllidaceae, has originated in Asia, and is also widely cultivated in Egypt, Mexico, China, and Europe. This plant is highly consumed in Iran, where its foliage, flowers, and cloves are employed in local medicine. All parts of A. sativum — bulbs, leaves, cloves, and flowers — are utilized to prepare mixtures and decoctions to deal with various ailments. It is also a common spice and food additive.

South Asia (Ayurveda): In India, A. sativum is used to treat fever and coughs and is administered topically against scabies, graying of hair, and eczema, as well as against inflammation of the tetanus and lungs.

Pakistan, Nepal, and East Asia: In Pakistan, the plant extract is consumed orally against stomach ailments, respiratory problems, and fever. In Nepal, the Middle East, and East Asia, the plant is applied against fevers, rheumatism, liver disorders, diabetes, colic, intestinal worms, dysentery, flatulence, tuberculosis, high blood pressure, facial paralysis, and bronchitis.

Africa: In Africa, the plant has been reported to be an antibiotic, antiviral, hypolipidemic, hypoglycemic, and antithrombotic agent.

Cardiovascular and anti-infective uses: Because of its multiple antibacterial, choleretic, spasmolytic, and in particular proven anti-atherosclerotic effect, garlic has been cultivated since ancient times in China, India, and Egypt, and its healing effects are used as folk medicine in many countries.

4. Key Constituents and Active Compounds

DADS is itself a major bioactive within a complex family of allium-derived sulfur compounds. Studies on the phytochemistry of garlic indicate that sulfur-containing compounds, such as allicin, are the essential components. Allicin (diallyl-dithiosulfinate) is the most important alkaloid responsible for its beneficial effects. DADS is both a breakdown product of allicin and a pharmacologically active compound in its own right.

Diallyl disulfide (DADS) has a structure comprising two sulfur atoms with two allyl groups and is a major organosulfur compound of garlic. Studies have shown that DADS has many biological functions, including anti-inflammatory, antioxidant, anticancer, and detoxifying effects, which may be determined by its chemical structure.

The broader pharmacological profile of garlic depends on this interrelated family. A substantial number of studies have shown that, thanks to its unique composition of bioactive constituents, garlic exhibits antibacterial, antifungal, immunomodulatory, anti-inflammatory, antioxidant, anticancer, hepatoprotective, gastroprotective, cardiovascular protective, neuroprotective, renal protective, antidiabetic, anti-obesity, and anti-coagulant properties.

5. Established Mechanisms of Action

5.1 Detoxification Enzyme Modulation (Phase I and Phase II Enzymes)

The mechanisms of action of DADS include: the activation of metabolizing enzymes that detoxify carcinogens; suppression of the formation of DNA adducts; antioxidant effects; regulation of cell-cycle arrest; induction of apoptosis and differentiation; histone modification; and inhibition of angiogenesis and invasion.

DADS exerted its anticarcinogenic effect by inhibiting CYP2E1 levels in humans, and CYP2A3 levels in rats, induced by methyl-n-pentylnitrosamine. Based on animal studies, the administration of DADS to rats through gastric intubation reduced the amount of liver CYP2E1 protein by 25%.

Furthermore, treatment with DADS was found to induce the activation of phase II enzymes by protecting Nrf2 from proteasomal degradation of Keap1 and promoting Nrf2 nuclear accumulation, thereby inhibiting the occurrence of chemical-induced papilloma in mice.

5.2 Anti-Inflammatory Signaling

One study provided strong evidence that DADS could inhibit the lipopolysaccharide (LPS)-induced production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) in RAW 264.7 cells, which thus led to the reduction in NO and prostaglandin E2 (PGE2) in activated cells.

Another study on LPS-stimulated neurogenic innate immune cells, BV2 microglia, also found that treatment with DADS significantly inhibited several proinflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, TNF-α, and monocyte chemoattractant protein-1. Recent studies have further confirmed this physiological effect in animal models of neuroinflammation.

When SW480 colorectal cancer cells were treated with DADS, NF-κB nuclear localization and activity were diminished. Interestingly, NF-κB suppression was found to be dependent on DADS inhibition of GSK-3β, a positive regulator of NF-κB.

5.3 Antioxidant Mechanisms

DADS exhibits antioxidant activity by scavenging certain reactive oxygen species (ROS), such as hydroxyl radicals, and inhibiting lipid peroxidation in vitro, as well as inducing endogenous antioxidant enzymes.

According to reports, DADS may regulate lipid metabolism by: (a) regulating sterol regulatory element-binding protein-1c, apolipoprotein A1, CREB-H, and fibroblast growth factor 21; (b) preventing lipotoxicity by increasing peroxisome proliferator-activated receptor-α and inhibiting stearyl coenzyme A desaturase enzyme-1; and (c) significantly inhibiting lipid peroxidation by regulating malondialdehyde and superoxide dismutase.

5.4 Cell-Cycle Arrest and Apoptosis

The anticancer properties of DADS are attributed to its ability to suppress cancer cell proliferation, impede invasion and metastasis, as well as induce apoptosis, promote differentiation, and facilitate cell cycle arrest.

DADS is the most prevalent oil-soluble sulfur compound in garlic and inhibits cell proliferation in many cancer cell lines. Studies have examined DADS cytotoxicity in a redox-mediated process involving reactive oxygen species (ROS) production. In HCT-116 colon cancer cells, p53-independent cell cycle arrest at G2/M phase was observed with DADS treatment, along with a time-dependent increase of cyclin B1. In addition, apoptosis was also observed upon 24-hour DADS treatment accompanied by activation of p53. DADS application induced a dose-dependent increase and time-dependent changes in ROS production. Scavenging of DADS-induced ROS by N-acetyl cysteine or reduced glutathione inhibited cell cycle arrest, apoptosis, and p53 activation by DADS.

Inducing apoptosis in cancer cells is the main anticancer mechanism employed by most chemotherapeutic drugs. DADS-induced apoptosis was observed to be accompanied by an increase in Ca²⁺ levels and a decrease in mitochondrial membrane potential.

5.5 PI3K/Akt/mTOR and Other Signaling Pathways

Studies reveal that DADS induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

In the cardiovascular system, DADS administration was found to ameliorate the isoproterenol- or streptozotocin-induced cardiac dysfunction via the activation of the nuclear factor E2-related factor 2 (Nrf2) and insulin-like growth factor (IGF)–phosphatidylinositol-3-kinase (PI3K)–protein kinase B (Akt) signaling.

5.6 Antimicrobial Mechanisms

DADS exhibits potent antimicrobial activity primarily through disruption of bacterial cell membranes, achieved via interactions of its disulfide bond with thiol (-SH) groups in membrane proteins and enzymes, leading to leakage of cellular contents and inhibition of key metabolic processes. This mechanism is effective against both Gram-positive bacteria, such as Staphylococcus aureus, and Gram-negative bacteria, including Escherichia coli, as well as fungi like Candida albicans.

The antifungal effect of DADS against C. albicans involves the inhibition of biofilm formation by preventing the conversion of yeast to hyphae.

6. Scientific Evidence by Area of Use

6.1 Cancer Chemoprevention

Overview: DADS, an oil-soluble organic sulfur-containing compound in garlic, has garnered attention in recent years for its demonstrated anti-cancer efficacy in various cancer types such as leukemia, breast cancer, hepatocellular carcinoma, stomach cancer, and prostate cancer.

Colorectal cancer (animal model): DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colonic irritant dextran sodium sulfate (DSS) resulted in the reduction in tumor incidence, tumor number, and tumor burden by 21.54%, 47.3%, and 66.4%, respectively. Further analysis revealed that mice fed the DADS-supplemented diet resolved the initial DSS-induced inflammation faster than those on the control diet, preventing prolonged inflammation and cellular transformation. This is an animal model study; the human equivalent dose noted is a conversion estimate, not a tested human dosage.

Colon cancer cells (in vitro): A study showed that DADS inhibited cell proliferation, G2/M arrest, H₂O₂ formation, and DNA damage induced by benzo[a]pyrene, thereby inhibiting the occurrence of breast cancer.

Prostate cancer (in vitro): The apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells; results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis.

Osteosarcoma (in vitro): MG-63 cells were exposed to DADS at 0, 20, 40, 60, 80, and 100 μM for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADS inhibited osteosarcoma cell viability in a dose- and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADS concentration was increased.

Breast cancer (in vitro and animal models): Oil-soluble compounds derived from garlic, such as DADS, are more effective than water-soluble compounds in suppressing breast cancer. Mechanisms of action include the activation of metabolizing enzymes that detoxify carcinogens, the suppression of DNA adduct formation, the inhibition of the production of reactive oxygen species, the regulation of cell-cycle arrest, and the induction of apoptosis.

Skin carcinogenesis (animal model): A study evaluated the prophylactic effect of DADS in chemically induced mouse skin carcinogenesis. A two-stage chemically induced carcinogenesis model by cutaneous application of DMBA and subsequent TPA was established; DADS dose-dependently attenuated skin tumor incidence and multiplicity in the model mice, which was related to the up-regulation of antioxidant enzyme activities and the nuclear accumulation of Nrf2.

Mechanistic breadth: Many studies have demonstrated the anti-cancer potential of DADS and pointed out that cell death induced by DADS is mediated through the activation of apoptosis, cell cycle arrest, and inhibition of proliferation and angiogenesis.

Evidence strength: The overwhelming majority of anticancer evidence for DADS, as of current literature, derives from in vitro cell-line studies and animal models. There are no large-scale randomized controlled trials (RCTs) in humans that have specifically tested isolated DADS as a cancer therapeutic or preventive agent. The mechanisms of action underlying the compound's anticancer activity have not been fully elucidated.

6.2 Anti-Inflammatory Activity

The sulfur-containing constituents derived from garlic, including diallyl disulfide (DADS), have been previously reported to exert anti-inflammatory effects. Diallyl disulfide has been demonstrated to alleviate inflammation in pre-clinical models of inflammatory bowel disease by inhibiting the production of pro-inflammatory cytokines, including IL-6.

In a preclinical inflammation model, male Swiss mice were divided into groups receiving carrageenan, DADS (100 mg/kg), or diclofenac as a reference drug (20 mg/kg); the chosen dose of DADS was selected based on preliminary experiments using 50, 75, and 100 mg/kg. This is an animal study. No robust human RCTs specifically testing isolated DADS as an anti-inflammatory supplement have been identified in the peer-reviewed literature.

6.3 Antimicrobial and Antifungal Activity

Representative minimum inhibitory concentrations (MICs) for DADS range from 10 to 100 µg/mL for common pathogens, with values around 28 µg/mL reported for C. albicans isolates and 100–200 µg/mL for enteric bacteria like E. coli O157:H7.

Studies examined the bacterial growth curve, enterotoxin production, biofilm formation, and swarming motility of Bacillus cereus under DADS pressure. Following treatment with DADS, the production of the enterotoxins Nhe and Hbl, as well as total biofilm formation and swarming ability, showed a decreasing trend with concentration.

In a murine model of intestinal candidiasis, a study identified the mechanism by which DADS ameliorates DSS-induced intestinal C. albicans infection based on systematic analysis of gut microbiota and metabolomics in mice, determining body weight, survival, colon length, histological score, and inflammatory cytokine levels.

Furthermore, DADS demonstrates synergistic effects with antibiotics, such as enhancing the efficacy of gentamicin against multidrug-resistant strains.

Evidence strength: The antimicrobial evidence for DADS is largely in vitro (MIC studies, biofilm inhibition) and based on animal models. Human clinical trials on DADS as an isolated antimicrobial agent are not established in the current literature.

6.4 Hepatoprotective Effects

DADS has been suggested to possess hepatoprotection against alcoholic liver disease (ALD) by a couple of pilot studies, while the underlying mechanisms remain largely unknown. One study investigated the hepatoprotective effects of DADS against ethanol-induced liver steatosis and early inflammation using the chronic-plus-binge mice model and cultured macrophages and hepatocytes. DADS significantly attenuated ethanol-induced elevation of serum aminotransferase activities, accumulation of liver triglyceride, hepatocyte apoptosis, oxidative stress, infiltration of macrophages and neutrophils, and proinflammatory polarization of macrophages in mice livers.

In addition, chronic-plus-binge drinking induced apparent intestinal mucosa damage and disturbance of gut microbiota, endotoxemia, and activation of hepatic NF-κB signaling and NLRP3 inflammasome, which was inhibited by DADS.

The protective effects of DADS against acetaminophen-induced nephrotoxicity may be due to its ability to decrease metabolic activation by inhibiting CYP2E1 and its potent antioxidant, antiapoptotic, and anti-inflammatory effects via inhibition of NF-κB.

Additional studies have reported that the lipid metabolism-regulating activity of DADS may have significant hepatoprotective effects.

Evidence strength: Hepatoprotective evidence for DADS is preliminary and derived from animal and cell-culture models. There are no identified human clinical trials evaluating DADS specifically for liver protection at the time of writing.

6.5 Cardiovascular Effects

DADS is an oil-soluble sulfur compound responsible for some of the biological effects of garlic and displays numerous biological activities. In the cardiovascular system, DADS administration was found to ameliorate isoproterenol- or streptozotocin-induced cardiac dysfunction via the activation of Nrf2 and IGF-PI3K-Akt signaling.

DADS could inhibit the accumulation or activation of mesenteric adipose tissue macrophages and the release of monocyte chemoattractant protein-1, suppressing the inflammatory response induced by obesity.

Evidence strength: Cardiovascular evidence for isolated DADS is confined to animal and in vitro studies. While the broader garlic literature includes human clinical trials on cholesterol and blood pressure, these involve whole garlic preparations and cannot be attributed specifically to DADS.

6.6 Neuroprotective Effects

It has been reported that DADS can prevent the microglia-mediated neuroinflammatory response and depression-like behaviors in mice.

DADS administration can also produce neuroprotective effects in animal models of Alzheimer's disease and protect the heart, endothelium, liver, lung, and kidney against cellular or tissue injury.

DADS is an allicin extract with detoxifying, antibacterial, and cardiovascular disease protective effects. One study aimed to determine whether DADS can alleviate hypoxic-ischemic encephalopathy (HIE)-induced brain damage in rats and whether it can inhibit pyroptosis via the NLRP3/Caspase-1/IL-1β signaling pathway.

Evidence strength: Neuroprotective evidence for DADS is exclusively preclinical (in vitro and rodent models). No human clinical trials for neuroprotection with DADS have been identified.

6.7 Skin Cancer Chemoprevention (Nrf2 Pathway)

DADS dose-dependently attenuated skin tumor incidence and multiplicity in chemically induced mouse skin cancer models, which was related to the up-regulation of antioxidant enzyme activities and the nuclear accumulation of Nrf2. Furthermore, skin carcinogenesis in Nrf2 knockout mice reversed the activity of DADS. The underlying mechanism was uncovered as DADS promoting the endogenous interaction between p21 and Nrf2, which was critical for impairing Keap1-mediated degradation of Nrf2.

7. Body Systems and Health Areas

DADS, a major bioactive component of garlic, has several beneficial biological functions, including anti-inflammatory, antioxidant, antimicrobial, cardiovascular protective, neuroprotective, and anticancer activities. Based on the available experimental literature, DADS is associated with the following body systems and health areas:

• Gastrointestinal system: Colorectal cancer chemoprevention (preclinical); modulation of gut microbiota; protection against colitis; antifungal activity against intestinal Candida.
• Immune system: Suppression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α); modulation of NF-κB; macrophage polarization.
• Hepatobiliary system: Protection against alcohol- and chemical-induced liver injury via Nrf2 and CYP2E1 modulation; reduction in liver triglyceride accumulation.
• Cardiovascular system: Cardioprotection in animal models of drug- and diabetes-induced cardiac injury; potential lipid metabolism regulation.
• Nervous system: Suppression of neuroinflammation; preclinical models of Alzheimer's disease and depression.
• Oncology (multiple tumour types): Prostate, colorectal, breast, skin, osteosarcoma, leukemia, and hepatocellular carcinoma cell lines — primarily in vitro and animal evidence.
• Renal system: Protection against acetaminophen-induced nephrotoxicity in animal models.
• Integument/skin: Contact allergen; also studied for skin cancer chemoprevention.

8. Dosage Forms and Reported Dosages

The following dosages are as reported in cited scientific sources and do not represent clinical recommendations:

• Animal (mouse) dietary supplementation (colorectal cancer model): Supplementation with 85 ppm of DADS (noted as a 60 mg daily human equivalent dose) in the diet of FVB/N mice treated with AOM and DSS.
• Animal (mouse) anti-inflammatory model: Carrageenan-induced paw edema study used DADS at 100 mg/kg body weight in male Swiss mice.
• In vitro (osteosarcoma cells): MG-63 cells were exposed to DADS at concentrations of 0, 20, 40, 60, 80, and 100 μM for different time periods (24, 48, and 72 h).
• In vitro (antimicrobial): Representative MIC values range from 10 to 100 µg/mL for common pathogens, with approximately 28 µg/mL reported for C. albicans.
• Patch testing (dermatology): Patch testing with 1% diallyl disulfide in petrolatum is recommended when garlic allergy is suspected.

No standardized, evidence-based human clinical dosage for DADS as an isolated supplement has been established in the peer-reviewed literature reviewed for this article.

9. Safety Considerations and Interactions

9.1 Allergic Contact Dermatitis

All parts of the garlic plant, when damaged, release the potentially irritating and allergenic sap. Diallyl disulfide, allicin, and allyl propyl disulfide have been identified as the principal low molecular weight allergens. Allergic contact dermatitis is generally considered as being caused by diallyl disulfide.

Diallyl disulfide is an important allergen in garlic and onion that is known to cause contact dermatitis. Garlic is the most frequent cause of contact dermatitis in the fingers and pulpitis in housewives and suppliers, and may result in various cutaneous manifestations, most commonly chronic pulpitis of the first three fingers.

In a documented case of an occupational dermatosis, a cook showed a positive type-IV patch test reaction for diallyl disulfide, a low molecular weight garlic ingredient, and strong non-irritant reactions in scratch chamber tests with fresh garlic. Both allergic type-IV contact dermatitis and protein contact dermatitis were identified as co-existing pathomechanisms.

9.2 Systemic Allergic Reactions

Clinical trials have consistently shown that "garlic breath" and body odor are the most common (and well-documented) complaints associated with garlic intake. Case reports have highlighted the possibility that garlic use may cause allergic reactions (allergic contact dermatitis, generalized urticaria, angioedema, pemphigus, anaphylaxis, and photoallergy), alteration of platelet function and coagulation (with a possible risk of bleeding), and burns when fresh garlic is applied on the skin, particularly under occlusive dressings.

9.3 Anticoagulant / Drug Interactions

Garlic may enhance the pharmacological effect of anticoagulants (e.g., warfarin, fluindione) and reduce the efficacy of anti-AIDS drugs. Garlic's anticoagulant properties have been linked to reports of bleeding; however, clinical trials find conflicting results.

9.4 CYP2E1 Inhibition and Drug Metabolism

DADS exerted its anticarcinogenic effect by inhibiting CYP2E1 levels in humans and CYP2A3 levels in rats. Based on animal studies, the administration of DADS to rats through gastric intubation reduced the amount of liver CYP2E1 protein by 25%. Because CYP2E1 is involved in the metabolism of various drugs and xenobiotics (including ethanol and acetaminophen), inhibition of this enzyme by DADS has the theoretical potential to alter the metabolism and toxicity of CYP2E1-substrate drugs, though this specific interaction has not been established in human clinical pharmacokinetic studies.

9.5 Physical/Chemical Irritancy

Diallyl disulfide has a strong garlic smell. In the context of occupational or topical exposure, direct skin contact with concentrated DADS or fresh garlic preparations can cause irritant and chemical burns, particularly under occlusion.

9.6 Metabolism and Decomposition in the Body

Diallyl disulfide decomposes in the human body into other compounds such as allyl methyl sulfide. Allyl mercaptan, allyl methyl sulfide (AMS), allyl methyl disulfide (AMDS), DAS, and DADS have been detected in human breath immediately after consumption of raw garlic and commercial garlic products. Metabolites such as N-acetyl-S-(2-carboxypropyl)-cysteine, N-acetyl-S-allyl cysteine, and hexahydrohippuric acid have been detected in human urine by HPLC, GC, and mass spectrometry and their combinations.

9.7 Chromosomal Effects

DADS has been reported to induce chromosomal effects in preclinical studies, though the mechanistic and toxicological significance of this finding in humans at dietary or supplemental doses remains to be established.

10. Limitations and State of Evidence

The scientific literature on DADS is substantial in terms of volume, but it is heavily weighted toward in vitro cell-culture experiments and animal models. The 2021 systematic review published in Evidence-Based Complementary and Alternative Medicine (which evaluated the biological functions of DADS — anti-inflammatory, antioxidant, antimicrobial, cardiovascular protective, neuroprotective, and anticancer activities — and discussed the underlying molecular mechanisms) underscored the breadth of preclinical evidence but also highlighted the relative scarcity of human clinical data specific to DADS as an isolated compound. Most positive human data comes from studies of whole garlic or garlic-based formulations that contain DADS alongside many other active components, making attribution to DADS alone methodologically difficult. Large-scale, adequately powered randomized controlled trials in humans using characterized DADS preparations have not been reported to date.

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