Eugenol

• Antimicrobial activity
• Antioxidant properties
• Anti-inflammatory effects
• Analgesic properties

• Dental health support
• Digestive health
• Neuroprotective effects
• Potential anticancer properties
• Cardiovascular protection

Eugenol (4-allyl-2-methoxyphenol) is a phenolic compound found in essential oils of various aromatic plants, particularly clove, cinnamon, and basil. Its diverse biological activities are mediated through multiple mechanisms of action. As an antimicrobial agent, eugenol primarily disrupts bacterial cell membranes due to its hydrophobic nature. It integrates into the bacterial cell membrane, increasing permeability and causing leakage of essential cellular components such as ions, ATP, nucleic acids, and other cytoplasmic constituents.

This membrane disruption leads to loss of membrane potential, cellular dysfunction, and ultimately cell death. Electron microscopy studies have confirmed morphological changes in bacterial cells exposed to eugenol, including membrane damage and cytoplasmic coagulation. Additionally, eugenol inhibits bacterial biofilm formation by interfering with quorum sensing systems and reducing the expression of genes involved in biofilm development. Eugenol also demonstrates activity against fungi through similar membrane-disrupting mechanisms and by inhibiting ergosterol biosynthesis, a vital component of fungal cell membranes.

The anti-inflammatory properties of eugenol are primarily mediated through inhibition of the NF-κB pathway, a key regulator of inflammatory responses. Eugenol suppresses the activation and nuclear translocation of NF-κB, thereby reducing the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8. It also inhibits the production of inflammatory mediators like nitric oxide (NO) and prostaglandin E2 (PGE2) by suppressing the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, eugenol modulates the activity of mitogen-activated protein kinases (MAPKs), including p38 MAPK, JNK, and ERK, which are involved in inflammatory signal transduction.

The antioxidant effects of eugenol stem from its phenolic structure, which allows it to donate hydrogen atoms to neutralize free radicals. Beyond direct radical scavenging, eugenol activates the Nrf2-Keap1-ARE pathway, a master regulator of cellular antioxidant responses. By modifying cysteine residues in Keap1, eugenol causes Nrf2 to translocate to the nucleus, where it binds to Antioxidant Response Elements (ARE) and upregulates the expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1). This enhances the cell’s endogenous antioxidant defense system.

The analgesic properties of eugenol involve multiple mechanisms. It acts as a selective agonist of transient receptor potential vanilloid 1 (TRPV1) channels, initially activating them to cause a transient burning sensation, followed by desensitization and analgesia. Eugenol also inhibits voltage-gated sodium channels, particularly Nav1.7 and Nav1.8, which are important for pain signal transmission. Additionally, it modulates calcium channels and potentiates GABA-mediated inhibitory neurotransmission, contributing to its pain-relieving effects.

In the cardiovascular system, eugenol exhibits protective effects through multiple mechanisms. It improves endothelial function by enhancing nitric oxide production and reducing oxidative stress. Eugenol also inhibits platelet aggregation and has vasodilatory effects, potentially through modulation of calcium channels. Additionally, it reduces lipid peroxidation and improves lipid profiles, contributing to its cardioprotective properties.

Eugenol’s neuroprotective effects involve reducing oxidative stress and neuroinflammation in the central nervous system. It modulates neurotransmitter systems, particularly GABAergic transmission, by acting as a positive allosteric modulator of GABA-A receptors, which may contribute to its anxiolytic properties. Eugenol also inhibits acetylcholinesterase activity, potentially enhancing cholinergic neurotransmission and cognitive function. Recent studies have shown that eugenol can stimulate dopamine release in neuronal cells, suggesting potential applications in conditions involving dopaminergic dysfunction.

The potential anticancer properties of eugenol involve multiple mechanisms, including induction of apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways. It causes cell cycle arrest, typically at the G0/G1 or G2/M phases, by modulating the expression of cyclins and cyclin-dependent kinases. Eugenol also inhibits cancer cell migration and invasion by suppressing matrix metalloproteinases (MMPs) and modulating epithelial-mesenchymal transition (EMT). Additionally, it demonstrates anti-angiogenic effects by reducing the expression of vascular endothelial growth factor (VEGF).

In the digestive system, eugenol has antispasmodic effects by inhibiting calcium channels in smooth muscle cells, leading to muscle relaxation. It also stimulates digestive enzyme secretion and bile flow, enhancing digestive processes. The diverse mechanisms of action of eugenol explain its wide range of biological activities and potential therapeutic applications across multiple health conditions.

The optimal dosage of eugenol is not well-established in human clinical studies. Most research has focused on eugenol as a component of essential oils (particularly clove oil) rather than as an isolated compound. Based on limited available data and traditional usage, typical supplemental doses range from 5-150 mg of eugenol daily, often delivered through clove oil supplements containing 80-95% eugenol. The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) have established an Acceptable Daily Intake (ADI) of 0-2.5 mg/kg body weight for eugenol, which translates to approximately 150-175 mg daily for an average adult.

It’s important to note that these dosages are based on preliminary research and traditional use rather than comprehensive clinical trials.

Cloves: 1 teaspoon (approximately 2g) of ground cloves contains approximately 60-120 mg of eugenol

Cinnamon: 1 teaspoon (approximately 2g) of ground cinnamon contains approximately 2-10 mg of eugenol

Basil: 1 teaspoon (approximately 1g) of dried basil contains approximately 1-5 mg of eugenol

Clove Oil: 1 drop (approximately 0.05 ml) of clove essential oil contains approximately 40-45 mg of eugenol

When consumed as a supplement, eugenol or eugenol-containing oils are generally recommended to be taken with meals to reduce potential gastrointestinal irritation. For antimicrobial or anti-inflammatory benefits, some traditional practices suggest consumption at the onset of symptoms. Due to its potential stimulating properties, some sources recommend avoiding consumption in the evening as

it might interfere with sleep. For dental applications, topical eugenol preparations can be applied as needed for pain relief, but should not be used continuously for extended periods.

It is important to note that most research on eugenol has been conducted in vitro or in animal models, with limited human clinical trials. The optimal therapeutic dosage for specific health conditions has not been well-established through rigorous clinical studies. Additionally, the bioavailability and effects of eugenol can vary significantly depending on the delivery method, formulation, and individual factors. Most human studies have used eugenol as part of essential oils rather than as an isolated compound, making it difficult to establish precise dosage recommendations for pure eugenol.

The WHO/FAO ADI value provides some guidance for safety, but optimal therapeutic doses may differ from this value depending on the specific health condition being addressed.

Eugenol is moderately absorbed in the gastrointestinal tract following oral consumption due to its lipophilic nature. Studies in animal models have shown that approximately 60-70% of orally administered eugenol is absorbed within 2-3 hours. In humans, peak plasma concentrations have been reported to occur approximately 1-2 hours after oral administration. The lipophilic properties of eugenol facilitate its passage across cell membranes, contributing to its absorption rate.

However, despite good absorption, the absolute bioavailability of eugenol is limited by extensive first-pass metabolism in the liver, with oral bioavailability estimated to be around 4-5% in animal studies. Recent pharmacokinetic studies in rats have demonstrated that eugenol has a marked aptitude to permeate into the cerebrospinal fluid following both intravenous and oral administrations, suggesting good central nervous system penetration.

Consumption with dietary fats can enhance absorption due to eugenol’s lipophilic nature, Microencapsulation technologies can protect eugenol from degradation in the stomach and control its release, Cyclodextrin complexation improves stability and water solubility, potentially enhancing bioavailability, Nanoemulsion formulations significantly increase the surface area available for absorption, Liposomal delivery systems can improve stability and targeted delivery, Co-administration with compounds that inhibit glucuronidation (such as certain flavonoids) may increase bioavailability by reducing first-pass metabolism, Enteric coating to protect from stomach acid degradation and ensure intestinal release, Combination with piperine or other bioavailability enhancers that inhibit metabolizing enzymes

Eugenol is best consumed with meals containing some fat content to enhance absorption. For maximum benefits from food sources, herbs containing eugenol (cloves, cinnamon, basil) should be added toward the end of cooking to minimize volatile oil loss. When using essential oils containing eugenol, dilution in a carrier oil can improve absorption and reduce potential irritation of mucous membranes. For antimicrobial purposes, consistent timing of administration may be more important than specific time of day.

However, due to potential stimulating effects, evening consumption should be approached with caution.

After absorption, eugenol undergoes extensive metabolism, primarily in the liver. The main metabolic pathways include glucuronidation, sulfation, and methylation. Glucuronidation is the predominant pathway, resulting in the formation of eugenol glucuronide conjugates, primarily eugenol-O-β-D-glucuronide. Sulfation produces eugenol sulfate conjugates, while methylation can lead to the formation of methyleugenol.

These phase II metabolites are more water-soluble, facilitating their excretion. The cytochrome P450 enzyme system, particularly CYP2D6 and CYP1A1, is involved in the oxidative metabolism of eugenol, leading to the formation of hydroxylated metabolites. The resulting metabolites generally have reduced biological activity compared to the parent compound, although some may retain certain properties. Studies in rabbits have shown that eugenol metabolites can be detected in various tissues, indicating distribution throughout the body despite extensive metabolism.

The half-life of eugenol in humans has not been precisely determined in comprehensive pharmacokinetic studies. However, based on animal studies and limited human data, the estimated half-life is approximately 14-18 hours. This relatively moderate half-life is due to its metabolism and excretion patterns. Studies in rats have shown that eugenol can be detected in plasma for up to 24 hours after administration, with peak concentrations occurring within the first 1-2 hours.

The majority of eugenol and its metabolites are eliminated within 24-48 hours of consumption, primarily through renal excretion (approximately 80-90%) with a smaller portion eliminated through fecal excretion (10-20%).

The primary biomarkers for eugenol exposure and metabolism are urinary glucuronide and sulfate conjugates, which can be measured using liquid chromatography-mass spectrometry (LC-MS) techniques. These metabolites serve as indicators of eugenol absorption and metabolism. Additionally, plasma levels of free eugenol can be directly measured, though this is less common due to its rapid metabolism. In research settings, biological effects such as changes in inflammatory markers (e.g., IL-6, TNF-α) or antioxidant status (e.g., glutathione levels, SOD activity) are sometimes used as indirect biomarkers of eugenol activity, though these are not specific to eugenol exposure.

Studies in animals have shown that eugenol and its metabolites can be detected in various tissues, including liver, kidney, and brain, providing potential tissue-specific biomarkers for eugenol distribution.

• Gastrointestinal irritation (common at higher doses)
• Burning sensation in mouth or throat
• Skin irritation (with topical application)
• Allergic reactions in sensitive individuals
• Nausea (at higher doses)
• Heartburn or acid reflux
• Temporary burning sensation in stomach
• Dizziness (rare)
• Headache (rare)
• Respiratory irritation when inhaled in concentrated form
• Contact dermatitis (with topical application)
• Temporary numbing of oral tissues (with dental applications)

• Known allergy to clove, cinnamon, or other plants containing eugenol
• Bleeding disorders (due to potential anticoagulant effects)
• Scheduled surgery (discontinue 2 weeks before due to potential effects on blood clotting)
• Pregnancy and breastfeeding (as a supplement, though culinary amounts in food are generally considered safe)
• Gastrointestinal ulcers or inflammatory conditions
• Severe liver or kidney disease (due to involvement in metabolism)
• Children (as a supplement, though culinary amounts in food are generally considered safe)
• Hypersensitivity to other essential oil components
• Concurrent use of blood-thinning medications

• Anticoagulant and antiplatelet medications (potential additive effects increasing bleeding risk)
• Antidiabetic medications (may enhance hypoglycemic effects)
• Medications metabolized by cytochrome P450 enzymes, particularly CYP2D6 and CYP1A1 (potential competition for metabolic pathways)
• Drugs with narrow therapeutic windows (caution advised due to potential metabolic interactions)
• Medications for gastrointestinal conditions (may exacerbate irritation)
• Iron supplements (may reduce absorption if taken simultaneously)
• Medications that are substrates for P-glycoprotein (potential inhibition of this transporter)
• Sedative medications (potential mild additive effects)
• Local anesthetics (potential additive effects in dental applications)

The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) have established an Acceptable Daily Intake (ADI) of 0-2.5 mg/kg body weight for eugenol. For an average adult weighing 70 kg, this translates to approximately 175 mg per day as the upper limit for safe consumption. However, this limit is based on general safety considerations rather than therapeutic efficacy. Based on available research and traditional use, doses up to 150 mg per day appear to be generally well-tolerated in healthy adults for short-term use.

Due to limited long-term safety data, it is advisable to use the lowest effective dose and to consult with a healthcare provider before using higher doses or for extended periods.

Long-term safety studies in humans are limited. Animal studies suggest potential concerns with chronic high-dose exposure, including possible effects on liver enzymes and reproductive parameters at very high doses. However, these effects were observed at doses significantly higher than typical human supplemental doses. The long-term safety of eugenol at typical supplemental doses has not been thoroughly evaluated in clinical trials. As with many bioactive compounds, periodic breaks from use may be prudent when using eugenol supplements long-term. Traditional use of cloves and other eugenol-containing herbs as culinary spices provides some reassurance regarding the safety of low-dose, intermittent exposure to eugenol over extended periods.

Pregnant Women: Not recommended as a supplement due to insufficient safety data and potential uterine stimulant effects. Culinary use of herbs containing eugenol in normal food amounts is generally considered safe.

Breastfeeding Women: Not recommended as a supplement due to insufficient safety data and potential passage into breast milk. Culinary use of herbs containing eugenol in normal food amounts is generally considered safe.

Children: Not recommended as a supplement. Culinary exposure through herbs in age-appropriate amounts is considered safe. Eugenol-containing dental products should be used according to age-specific guidelines and under professional supervision.

Elderly: May be more sensitive to effects; lower doses recommended if used. Monitoring for side effects and drug interactions is particularly important in this population due to potential polypharmacy and altered metabolism.

Liver Disease: Use with caution due to involvement of liver enzymes in metabolism. Reduced doses may be necessary, and monitoring of liver function is advisable if used.

Kidney Disease: Use with caution as metabolites are primarily excreted through the kidneys. Reduced doses may be necessary in those with significant kidney impairment.

Allergic reactions to eugenol are possible, particularly in individuals with known allergies to plants in the Myrtaceae family (cloves) or Lauraceae family (cinnamon). Symptoms may include skin rash, itching, swelling, severe dizziness, and difficulty breathing. True allergic reactions are relatively rare, but contact dermatitis is more common with topical application. Dental professionals are particularly at risk for developing occupational allergies to eugenol due to frequent exposure.

Individuals with multiple plant allergies should exercise caution when using eugenol-containing products for the first time. Patch testing is advisable before widespread topical application of eugenol-containing products.

Acute Toxicity: Eugenol has moderate acute toxicity. The oral LD50 in rats is approximately 1930 mg/kg body weight, and in mice is about 3000 mg/kg body weight, indicating that very high doses can be harmful. However, typical supplemental doses are orders of magnitude lower than these toxic levels.

Subchronic Toxicity: In 90-day feeding studies in rats, a No Observed Adverse Effect Level (NOAEL) of 250 mg/kg body weight/day has been established. Effects at higher doses included mild changes in liver enzymes, slight alterations in blood parameters, and potential effects on reproductive organs.

Genotoxicity: Results from genotoxicity studies are mixed. Some in vitro studies suggest potential genotoxicity at high concentrations, while others show no significant effects or even protective effects against genotoxic agents. In vivo studies generally indicate low genotoxic potential at typical exposure levels.

Carcinogenicity: Limited data available. Current evidence does not suggest carcinogenic potential at typical exposure levels, but comprehensive long-term carcinogenicity studies are lacking. Some studies suggest potential anti-carcinogenic properties through various mechanisms.

Reproductive Toxicity: Animal studies suggest potential reproductive effects at very high doses, including reduced fertility and developmental effects. However, these effects were observed at doses far exceeding typical human exposure. No evidence of reproductive toxicity has been observed at typical supplemental doses.

The U.S. Food and Drug Administration (FDA) lists eugenol as Generally Recognized as Safe (GRAS) for use as a flavoring agent in foods. It is also approved as an active ingredient in certain over-the-counter drug products, particularly in dental care products. The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) have established an Acceptable Daily Intake (ADI) of 0-2.5 mg/kg body weight.

The European Food Safety Authority (EFSA) has evaluated eugenol as a food flavoring substance and concluded that it does not raise safety concerns at current levels of dietary intake. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has also evaluated eugenol and established an acceptable daily intake. However, specific regulatory assessments for eugenol as a dietary supplement ingredient are limited.

In the United States, eugenol is classified as Generally Recognized as Safe (GRAS) by the FDA for use as a flavoring agent in foods (21 CFR 172.515) at levels not exceeding good manufacturing practices. It is also approved as an active ingredient in certain over-the-counter drug products, particularly in dental care products for temporary relief of toothache. The FDA has approved eugenol for use in various dental materials, including zinc oxide eugenol cement. As a component of essential oils like clove oil, it falls under the regulatory framework for dietary supplements established by the Dietary Supplement Health and Education Act (DSHEA) of 1994.

The FDA has not specifically evaluated or approved eugenol as a standalone dietary supplement ingredient, but it is permitted as a component of recognized herbs and essential oils. Supplements containing eugenol cannot be marketed with claims to diagnose, treat, cure, or prevent any disease without approved drug status. For non-food applications, such as antimicrobial food packaging, specific FDA approvals may be required.

Eu: In the European Union, eugenol is regulated under the Flavouring Regulation (EC) No 1334/2008 as a flavoring substance (FL No. 04.003). The European Food Safety Authority (EFSA) has evaluated eugenol and established an Acceptable Daily Intake (ADI) of 0-2.5 mg/kg body weight. For use in food supplements, it falls under the Food Supplements Directive 2002/46/EC. The European Medicines Agency (EMA) has published monographs on clove that reference eugenol as an active component, recognizing its traditional medicinal use for temporary relief of toothache. For non-food uses, eugenol is subject to REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) regulations. In cosmetic products, eugenol is regulated under the Cosmetic Products Regulation (EC) No 1223/2009 and must be declared on the ingredient list when its concentration exceeds 0.001% in leave-on products or 0.01% in rinse-off products, as it is recognized as a potential allergen.

Canada: Health Canada regulates eugenol both as a food flavoring agent and as a component of Natural Health Products (NHPs). Clove oil and other eugenol-containing products may be licensed as NHPs if they meet safety, efficacy, and quality requirements. Health Canada has established monographs for clove that include reference to its eugenol content. Eugenol is also permitted as an active ingredient in certain non-prescription drugs, particularly dental products. The Pest Management Regulatory Agency (PMRA) has approved certain eugenol-containing products as minimum-risk pesticides.

Australia: The Food Standards Australia New Zealand (FSANZ) regulates eugenol as a food flavoring agent. For therapeutic use, the Therapeutic Goods Administration (TGA) regulates eugenol-containing products as listed or registered complementary medicines, depending on their claims and formulation. Eugenol is included in the Australian Inventory of Chemical Substances (AICS), which is maintained by the National Industrial Chemicals Notification and Assessment Scheme (NICNAS). The TGA has approved certain eugenol-containing dental products as therapeutic goods.

Japan: In Japan, eugenol is regulated by the Ministry of Health, Labour and Welfare primarily as a food additive and flavoring agent. It may also be permitted in certain ‘Foods with Functional Claims’ if appropriate evidence is provided. Eugenol is also approved for use in certain pharmaceutical and cosmetic products. The Japanese Standards for Cosmetic Ingredients include specifications for eugenol.

China: The National Medical Products Administration (NMPA) and the State Administration for Market Regulation regulate eugenol in China, primarily as a food additive and flavoring agent. Traditional herbal preparations containing eugenol may have separate regulatory pathways under traditional Chinese medicine regulations. The Chinese Pharmacopoeia includes monographs for clove and clove oil, specifying minimum eugenol content requirements.

Various patents exist related to eugenol applications, including formulations for enhanced stability or bioavailability, specific therapeutic uses, antimicrobial applications in food preservation, and agricultural applications. Notable patents include those for microencapsulation technologies to improve eugenol stability and controlled release, synergistic combinations with other antimicrobial compounds, and specific medical applications such as anti-biofilm formulations and dental materials. Patents also exist for novel delivery systems such as nanoemulsions and liposomal formulations of eugenol. The basic compound eugenol itself is not patentable as it is a naturally occurring substance that has been known for over a century, but novel formulations, production methods, and specific applications continue to be patented.

In the pharmaceutical sector, patents exist for eugenol derivatives with enhanced therapeutic properties, reflecting ongoing research into modifying the basic structure to improve efficacy or reduce side effects.

Us: When used as a food additive, eugenol must be declared on ingredient labels. In dental products and other OTC drugs, eugenol must be listed as an active ingredient with its concentration. In dietary supplements, it is typically listed as a component of clove oil or other herbal extracts in the Supplement Facts panel. Any structure/function claims must be accompanied by the FDA disclaimer: ‘These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.’ Products containing essential oils with eugenol should include appropriate safety warnings regarding proper dilution, avoiding use in children, and potential allergic reactions.

Eu: Eugenol must be declared in the ingredients list when used as a food additive. In cosmetic products, eugenol must be specifically declared in the list of ingredients regardless of its function when its concentration exceeds 0.001% in leave-on products or 0.01% in rinse-off products, as it is one of the 26 fragrance allergens that require mandatory labeling. For food supplements, the quantity of eugenol or the herb containing it must be clearly stated on the label. Health claims are strictly regulated by EFSA and must be pre-approved before they can be used in marketing. Essential oils containing significant amounts of eugenol must comply with the EU’s Classification, Labeling and Packaging (CLP) Regulation, including appropriate hazard statements and precautionary statements. For medicinal products, eugenol must be declared as an active ingredient with its concentration.

Canada: NHPs containing eugenol must comply with specific labeling requirements, including medicinal and non-medicinal ingredients, recommended use, cautions, warnings, and contraindications as specified in the Natural Health Products Regulations. For food products, eugenol must be declared in the ingredient list when used as a flavoring agent. Cosmetic products containing eugenol must declare it on the ingredient list and may require additional allergen warnings.

Structure Function: In the US, limited structure/function claims may be made for eugenol-containing supplements, such as ‘supports oral health,’ ‘helps maintain digestive function,’ or ‘provides antioxidant support,’ provided they are truthful, not misleading, and accompanied by the appropriate FDA disclaimer. However, specific structure/function claims for eugenol as an isolated compound have not been widely established or evaluated.

Health Claims: In the US, the FDA has approved certain OTC drug claims for eugenol-containing dental products, specifically for the temporary relief of pain due to toothache. In the EU, the European Medicines Agency (EMA) has recognized the traditional use of clove preparations containing eugenol for the symptomatic treatment of toothache. However, no specific health claims for eugenol have been approved by EFSA for food or food supplement use. In Canada, certain eugenol-containing products may make claims related to traditional use for oral pain relief if they comply with the appropriate monographs. In Australia, listed complementary medicines containing eugenol may make limited claims based on traditional use, but these must be supported by evidence and comply with the TGA’s advertising code.

The primary regulatory challenges for eugenol relate to its dual nature as both a food flavoring and a bioactive compound with potential therapeutic effects. Establishing appropriate regulatory frameworks that address both uses presents challenges for regulatory agencies. The variable content of eugenol in natural sources like essential oils creates challenges for standardization and quality control in supplements and food products. Additionally, eugenol’s status as a potential allergen requires careful consideration in labeling requirements, particularly in cosmetic products.

For therapeutic applications, the limited human clinical trial data presents challenges for obtaining regulatory approvals for specific health claims or medical uses beyond the well-established dental applications. The natural presence of eugenol in traditional foods and herbs creates complexity in regulating it as an isolated compound versus its presence in whole foods or traditional preparations. There is also growing regulatory interest in eugenol as a natural alternative to synthetic preservatives and antimicrobials, which may lead to evolving regulatory frameworks in the future.

Medium

Approximately $0.10-$0.75 per day for supplement forms, depending on formulation and brand. Natural food sources (cloves, cinnamon) provide more cost-effective options, with effective doses costing approximately $0.03-$0.20 per serving when used as culinary spices.

Eugenol offers good value considering its multiple potential health benefits, particularly its well-established antimicrobial and analgesic properties. The cost-effectiveness varies significantly depending on the source and form. Culinary spices like cloves and cinnamon provide the highest value, delivering eugenol along with other beneficial compounds at a relatively low cost. Clove oil supplements represent a middle ground, providing concentrated eugenol at a moderate cost.

Pure eugenol is the most expensive option but may be justified for specific applications requiring precise dosing or maximum potency. When considering the potential antimicrobial, anti-inflammatory, and antioxidant benefits, even higher-cost forms may represent reasonable value compared to conventional alternatives. For example, eugenol-containing dental products have demonstrated efficacy comparable to conventional products, often at similar or lower costs. For oral health applications, eugenol-containing products may offer cost advantages compared to some over-the-counter remedies, particularly for temporary pain relief.

However, the limited human clinical evidence for many proposed benefits means that the actual value proposition remains somewhat speculative for certain therapeutic applications beyond dental use.

Use culinary spices (cloves, cinnamon) regularly in cooking as a cost-effective way to obtain eugenol, Purchase whole cloves instead of ground for better preservation of eugenol content and longer shelf life, Make clove tea by steeping whole cloves in hot water for an economical way to consume eugenol, Purchase clove oil in liquid form rather than capsules for more flexible dosing and potentially lower cost per dose, Look for supplements standardized for eugenol content to ensure value (higher percentage means more active compound per capsule), Purchase supplements during sales or with subscription discounts, Consider the presence of synergistic compounds when evaluating cost (clove oil contains other beneficial compounds beyond eugenol), For oral health applications, compare the cost-effectiveness of eugenol-containing products with conventional alternatives

Direct Costs: The direct cost of eugenol supplementation varies widely depending on the source and form, from very economical (culinary spices) to moderately expensive (high-quality supplements or pure eugenol).

Indirect Savings: Potential cost savings from preventive health benefits are difficult to quantify but may include reduced need for over-the-counter remedies for minor oral health or digestive issues. The antimicrobial properties may contribute to reduced incidence of certain infections, potentially resulting in fewer sick days and associated healthcare costs. Additionally, the antioxidant and anti-inflammatory properties may contribute to long-term health benefits that could reduce healthcare costs, though these remain speculative without more definitive human studies.

The market for eugenol and eugenol-containing products has been growing steadily, driven by increasing consumer interest in natural antimicrobials and plant-based health solutions.

Several trends are notable: 1) Premium clove oil supplements with verified eugenol content are gaining market share, appealing to health-conscious consumers; 2) Specialized formulations targeting specific health concerns (oral health, digestive support, immune function) are emerging; 3) Food preservation applications utilizing eugenol’s natural antimicrobial properties are expanding in response to consumer demand for clean-label products; 4) Research into novel delivery systems to improve eugenol stability and bioavailability is advancing, potentially leading to more effective but higher-pric

ed products in the future; 5) Integration of eugenol into functional foods and beverages represents a growing market segment; 6) Increased use of eugenol in natural personal care products, particularly oral care and skin care formulations. The market is expected to continue growing as research expands into new potential benefits and as consumer awareness of natural bioactive compounds increases.

Pure eugenol has a relatively good stability profile compared to many other essential oil components. Under optimal storage conditions (cool temperature, airtight container, protection from light), pure eugenol typically maintains acceptable stability for 2-3 years. In essential oils like clove oil, the complex mixture of compounds can provide some protective effects, potentially extending stability to 1-2 years when properly stored. In commercial supplement formulations, stability enhancers and appropriate packaging can extend shelf life to 2-3 years.

However, once opened, these products should ideally be used within 6-12 months to ensure potency. Eugenol is more stable than many other essential oil components due to its phenolic structure, which provides some inherent resistance to oxidation. However, it is still susceptible to degradation over time, particularly when exposed to adverse environmental conditions.

Store in tightly sealed, amber glass containers to prevent oxidation and light-induced degradation. Keep in a cool, dry place away from direct sunlight and heat sources. Refrigeration (2-8°C) is recommended for pure eugenol and essential oils with high eugenol content to extend shelf life. Avoid exposure to air as much as possible, as oxygen is a primary factor in degradation.

For commercial supplements, follow manufacturer’s recommendations, but generally, they should be kept in their original containers with desiccants if provided. Freezing is not recommended as it may alter the physical properties of eugenol-containing products upon thawing. Pure eugenol should be stored away from strong oxidizing agents and bases, as these can accelerate degradation reactions.

Oxidation – exposure to oxygen leads to oxidative degradation, forming various oxidation products, Heat – temperatures above 30°C (86°F) accelerate degradation reactions, Light exposure – particularly UV light catalyzes degradation reactions, Metal ions – certain metals (especially iron and copper) can catalyze oxidation, pH extremes – eugenol is most stable in slightly acidic to neutral pH (5-7), Moisture – can promote hydrolysis and other degradation reactions, Microbial contamination – particularly in formulations with water content, Exposure to strong oxidizing agents – can rapidly degrade eugenol, Auto-oxidation – eugenol can undergo auto-oxidation reactions over time, even in sealed containers

Pure Liquid Form: Relatively stable when protected from air, light, and heat; may darken over time due to oxidation

Essential Oils: Good stability due to natural antioxidants present in the complex mixture; more stable in oils with higher eugenol content

Microencapsulated: Excellent stability; protective matrix shields from environmental factors and reduces volatility

Oil Solutions: Moderate to good stability depending on the carrier oil; some carrier oils may provide additional antioxidant protection

Water Based Formulations: Poor stability unless properly formulated with solubilizers, preservatives, and antioxidants

Topical Preparations: Moderate stability; influenced by formulation components and packaging

Dental Materials: Good stability when incorporated into zinc oxide eugenol formulations; the zinc oxide provides stabilizing effects

Change in odor (development of harsh, acrid, or phenolic notes), Color changes (darkening or yellowing), Increased viscosity in liquid preparations, Reduced pungency and characteristic aroma, Formation of precipitates in liquid formulations, Reduced biological activity (antimicrobial, antioxidant effects), Development of rancid or off-odors in oil-based formulations, Separation or phase changes in emulsion formulations

Eugenol is best packaged in materials that provide barriers against oxygen, light, and moisture. Amber glass containers are excellent for essential oils and pure eugenol. For supplements, amber glass or opaque HDPE (high-density polyethylene) bottles with tight-sealing caps are preferred. Blister packs with aluminum backing provide good protection for capsule formulations.

The headspace in containers should be minimized to reduce oxygen exposure. Some commercial preparations use nitrogen flushing during packaging to displace oxygen and extend shelf life. For products intended for repeated use, smaller package sizes are preferable to minimize exposure during use. For dental applications, two-paste systems that separate eugenol from zinc oxide until mixing provide optimal stability.

Gas chromatography (GC) or high-performance liquid chromatography (HPLC) to measure eugenol content over time, Accelerated stability testing under various temperature and humidity conditions, Real-time stability testing at recommended storage conditions, Oxidative stability tests (e.g., peroxide value, p-anisidine value), Antimicrobial activity assays as functional tests of potency, Sensory evaluation of aroma and pungency (though subjective), Differential scanning calorimetry (DSC) to assess thermal stability, Fourier-transform infrared spectroscopy (FTIR) to detect structural changes

Several approaches can enhance eugenol stability in various formulations. Addition of antioxidants such as vitamin E (tocopherols), rosemary extract, or ascorbyl palmitate can significantly reduce oxidative degradation. Microencapsulation using cyclodextrins, liposomes, or other carrier systems can protect eugenol from environmental factors while potentially improving its water dispersibility. For water-based formulations, proper selection of solubilizers and emulsifiers is critical for both stability and bioavailability.

In solid formulations, inclusion of desiccants in packaging helps control moisture. Some formulations use synergistic combinations with other essential oil components like carvacrol or thymol, which may provide mutual stabilization effects. For topical applications, incorporation into appropriate base formulations with pH control can enhance stability. Solid lipid nanoparticles and nanostructured lipid carriers have shown promise for improving eugenol stability while enhancing bioavailability and controlled release properties.

Synthesis Methods

Natural Sources

Quality Considerations

Geographical Sources

Processing Methods

Sustainability Considerations

Home Preparation

Eugenol has a rich history of use across various cultures, primarily through its natural sources such as cloves, cinnamon, and basil. While eugenol itself was not identified as a specific compound until the modern era, the plants containing it have been valued for millennia for their medicinal, culinary, and preservative properties. Cloves (Syzygium aromaticum), the richest natural source of eugenol, have been used in traditional medicine for over 2,000 years. In ancient China, cloves were used as early as 220 BCE during the Han Dynasty.

Court officials would hold cloves in their mouths to freshen their breath when addressing the emperor. Chinese traditional medicine utilized cloves for their warming properties, to treat digestive disorders, and for toothache relief. The earliest written record of cloves appears in Chinese texts from around 300 BCE. In ancient India, cloves and other eugenol-containing plants were integral to Ayurvedic medicine.

Ayurvedic texts dating back to 600 BCE mention cloves (lavanga) for treating respiratory disorders, digestive problems, and toothaches. Clove oil was used topically for pain relief and as an antiseptic for wounds. The warming properties of cloves made them valuable in Ayurvedic formulations for balancing ‘vata’ conditions. The use of cloves spread to the Middle East and Europe through ancient trade routes.

By the 4th century CE, cloves were being imported to Europe, though they were extremely expensive and primarily used by the wealthy. In medieval Europe, cloves were valued for their preservative properties in food, their use in perfumery, and their medicinal applications. During the plague epidemics, cloves were included in ‘pomanders’ – aromatic balls carried or worn to ward off disease, reflecting an early recognition of their antimicrobial properties. In traditional Indonesian and Malaysian medicine, cloves have been used for centuries for toothache, headache, and joint pain.

In Java, a traditional preparation called ‘jamu’ often included cloves for various medicinal purposes. The indigenous people of the Maluku Islands (the original home of cloves) chewed cloves for local anesthetic effects long before European contact. In traditional Arabic medicine, as documented in texts from the 10th-13th centuries CE, cloves were prescribed for dental pain, bad breath, and as a digestive aid. The renowned physician Ibn Sina (Avicenna) included cloves in his pharmacopeia for their warming and stimulating properties.

In the Americas, after the introduction of Old World spices, cloves were incorporated into traditional healing practices. In Mexican traditional medicine, cloves were used for toothache, digestive issues, and as an expectorant for respiratory conditions. The specific compound eugenol was first isolated from clove oil in 1836 by the French chemist Auguste André Thomas Cahours. Its chemical structure was later elucidated in the late 19th century.

By the early 20th century, eugenol became widely used in dentistry as a local anesthetic and antiseptic, particularly in combination with zinc oxide to form zinc oxide eugenol cement for dental fillings and bases. This application remains important in modern dentistry. The antimicrobial properties of eugenol were scientifically confirmed in the early 20th century, validating many of its traditional uses. During World War I, when medical supplies were scarce, clove oil was sometimes used as an emergency antiseptic in field hospitals.

In the mid-20th century, eugenol became an important starting material for the commercial synthesis of vanillin, the primary flavoring component of vanilla. This industrial application highlighted eugenol’s significance beyond its direct medicinal uses. Throughout the 20th century, scientific research increasingly validated the traditional uses of eugenol, confirming its antimicrobial, analgesic, anti-inflammatory, and antioxidant properties. In recent decades, interest in eugenol has expanded to include potential applications in food preservation, cancer treatment, and management of neurodegenerative diseases.

The long history of human consumption of eugenol-containing herbs provides valuable information about its safety profile and potential benefits, informing current research and applications in fields ranging from medicine to food science and agriculture.

Marchese A, Barbieri R, Coppo E, et al. Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Critical Reviews in Microbiology. 2017;43(6):668-689., Nisar MF, Khadim M, Rafiq M, et al. Pharmacological Properties and Health Benefits of Eugenol: A Comprehensive Review. Oxidative Medicine and Cellular Longevity. 2021;2021:2497354., Ulanowska M, Olas B. Biological Properties and Prospects for the Application of Eugenol—A Review. International Journal of Molecular Sciences. 2021;22(7):3671.

Investigation of eugenol-containing essential oils for respiratory infections, Evaluation of eugenol as an adjunct to conventional antimicrobial therapies, Studies on eugenol’s effects on neuroinflammation and neurodegenerative disorders, Research on eugenol’s potential in oral health products

Limited human clinical trials with eugenol supplementation, Insufficient data on long-term safety and efficacy in humans, Limited understanding of optimal dosing for specific health conditions, Need for better characterization of bioavailability and metabolism in humans, Limited research on potential interactions with medications and other supplements, Insufficient data on effects in special populations (elderly, pediatric, pregnant women), Need for more studies on the bioactivity of eugenol metabolites, Limited research on the potential of eugenol for neurodegenerative disorders despite promising preliminary findings

Antimicrobial Activity: Strong – multiple in vitro and some in vivo studies with consistent results

Anti Inflammatory Effects: Moderate – primarily animal studies with some mechanistic understanding

Antioxidant Properties: Moderate – in vitro and animal studies with consistent results

Dental Applications: Strong – extensive clinical use with supporting research

Analgesic Properties: Moderate – animal studies with mechanistic understanding and traditional use

Anticancer Potential: Preliminary – promising in vitro and limited animal studies

Neuroprotective Effects: Preliminary – limited but positive in vitro and animal studies

Cardiovascular Protection: Preliminary – limited studies with promising results

While most studies suggest beneficial effects of eugenol, some research has reported potential cytotoxicity at higher concentrations in certain cell types. This apparent contradiction may be explained by hormetic effects (beneficial at low doses but harmful at high doses) and cell type-specific responses. Additionally, while some studies suggest anti-inflammatory effects, others have reported pro-inflammatory responses under specific conditions, highlighting the context-dependent nature of eugenol’s biological activities. The antimicrobial effects are generally consistent across studies, though the minimum inhibitory concentrations vary significantly depending on the microbial strain and experimental conditions.

Some studies suggest that eugenol alone is less effective than when combined with other essential oil components, while others report significant activity of isolated eugenol. Regarding genotoxicity, some in vitro studies have reported potential DNA damage at high concentrations, while others have found protective effects against genotoxic agents. These variations in research findings underscore the importance of considering dose, formulation, and specific health context when evaluating eugenol’s potential benefits and risks.