Clove Extract

• Potent antioxidant protection
• Antimicrobial support
• Anti-inflammatory effects
• Digestive health support

• Oral health maintenance
• Pain relief
• Blood sugar regulation
• Immune system modulation
• Liver protection

Clove extract exerts its biological effects primarily through its rich composition of bioactive compounds, with eugenol (70-90%) being the predominant active constituent, followed by eugenol acetate (15%) and β-caryophyllene (5-12%). The extract’s potent antimicrobial activity stems from multiple mechanisms. Eugenol disrupts bacterial cell membranes by increasing permeability, leading to leakage of cellular contents and eventual cell death. This mechanism is particularly effective against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains.

Eugenol also inhibits bacterial enzymes essential for survival, such as ATPase, histidine decarboxylase, amylase, and protease. For fungal pathogens, clove extract damages cell wall integrity and inhibits ergosterol biosynthesis, a vital component of fungal cell membranes. The antioxidant properties of clove extract are attributed to its high phenolic content, particularly eugenol and gallic acid. These compounds neutralize free radicals through hydrogen atom donation and electron transfer mechanisms.

Clove extract also chelates metal ions that catalyze oxidation reactions and upregulates endogenous antioxidant defense systems by activating nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of antioxidant enzymes like glutathione peroxidase, superoxide dismutase, and catalase. The anti-inflammatory effects of clove extract involve multiple pathways. It inhibits cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes, reducing the production of pro-inflammatory prostaglandins and leukotrienes. Eugenol suppresses nuclear factor-kappa B (NF-κB) activation, a master regulator of inflammation, thereby decreasing the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6).

Clove extract also modulates mitogen-activated protein kinase (MAPK) signaling pathways involved in inflammatory responses. The analgesic properties of clove extract, particularly relevant for dental pain, are mediated through multiple mechanisms. Eugenol blocks voltage-gated sodium channels in neurons, reducing pain signal transmission. It also activates transient receptor potential vanilloid 1 (TRPV1) receptors, initially causing a warming sensation followed by desensitization and analgesia.

Additionally, eugenol interacts with γ-aminobutyric acid (GABA) receptors and inhibits N-methyl-D-aspartate (NMDA) receptors, contributing to its pain-relieving effects. For digestive health, clove extract stimulates digestive enzyme secretion and bile flow, enhancing nutrient breakdown and absorption. It exhibits carminative properties, reducing gas and bloating by relaxing gastrointestinal smooth muscle. The extract’s antimicrobial effects help maintain a balanced gut microbiome by selectively inhibiting pathogenic bacteria while having less impact on beneficial probiotic species.

Clove extract’s effects on blood glucose regulation involve multiple mechanisms. It enhances insulin sensitivity in peripheral tissues by activating peroxisome proliferator-activated receptor gamma (PPAR-γ). The extract inhibits key digestive enzymes involved in carbohydrate metabolism, such as α-amylase and α-glucosidase, slowing glucose absorption. Additionally, eugenol protects pancreatic β-cells from oxidative damage and may stimulate insulin secretion.

The hepatoprotective effects of clove extract are attributed to its antioxidant properties, which reduce oxidative stress in liver cells. It enhances the activity of phase II detoxification enzymes, promoting the elimination of toxins. The extract also inhibits cytochrome P450 enzymes involved in activating certain hepatotoxins and reduces lipid accumulation in the liver by modulating lipid metabolism genes. In the immune system, clove extract enhances both innate and adaptive immune responses.

It increases the activity of natural killer (NK) cells and macrophages, which are crucial for the body’s first line of defense against pathogens. The extract modulates T-cell differentiation and cytokine production, potentially helping to balance immune responses without causing immunosuppression.

Clove extract dosages vary significantly depending on the form, concentration, and intended use. For clove essential oil, which is highly concentrated, typical dosages range from 1-3 drops taken 1-3 times daily, always diluted in a carrier oil or liquid. For standardized clove extract capsules (typically standardized to 30-50% eugenol), common dosages range from 100-500 mg daily, divided into 2-3 doses. Clove tea can be consumed 1-3 times daily, using 1-2 teaspoons of dried clove buds per cup of hot water.

The bioavailability of clove extract varies significantly depending on the form and delivery method. Eugenol, the primary active compound, is lipophilic (fat-soluble) and demonstrates approximately 80-85% absorption when properly emulsified or combined with dietary fats. After oral administration, eugenol is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within 1-2 hours. The compound undergoes extensive first-pass metabolism in the liver, where it is primarily conjugated with glucuronic acid.

This metabolism reduces the systemic availability of free eugenol, with studies indicating that only about 20-35% of the absorbed eugenol remains in its free, active form after hepatic metabolism. Water-soluble components in clove tea or water extracts generally have lower bioavailability (30-50%) compared to oil-based preparations.

Consuming clove extract with a fat-containing meal increases absorption of lipophilic compounds by 30-40%, Emulsified forms of clove oil improve dispersion and absorption in the digestive tract, Liposomal delivery systems can enhance bioavailability by up to 2-3 times compared to standard extracts, Combining with black pepper extract (piperine) may enhance absorption by inhibiting certain detoxification enzymes, Enteric-coated capsules protect active compounds from stomach acid degradation, Sublingual administration of properly diluted clove oil allows for direct absorption into the bloodstream, bypassing first-pass metabolism, Standardized extracts with higher eugenol content (>50%) generally provide better bioavailability of active compounds, Combining with medium-chain triglycerides (MCT oil) can enhance absorption of fat-soluble components, Micronized or nanoparticle formulations increase surface area and improve absorption

For digestive issues, take clove extract 15-30 minutes before meals to optimize antimicrobial effects in the digestive tract and stimulate digestive enzyme secretion. For systemic effects (antioxidant support, anti-inflammatory benefits), take with meals containing some fat to enhance absorption of lipophilic compounds. For oral health applications, use clove preparations after brushing teeth for maximum contact time with oral tissues. When using multiple doses throughout the day, space them evenly (e.g., morning, midday, and evening) to maintain consistent blood levels of active compounds.

For topical applications, apply to clean, slightly damp skin to enhance penetration. When using clove oil for acute conditions like toothache or sore throat, more frequent application (every 2-3 hours) for the first 1-2 days may provide better results, followed by standard dosing. For blood sugar management, taking clove extract 15-30 minutes before meals may help optimize its effects on carbohydrate digestion and glucose metabolism. Cycling clove extract (e.g., 5 days on, 2 days off) may help prevent tolerance development for long-term use and reduce the risk of potential side effects from continuous use.

• Oral irritation and burning sensation when used topically in the mouth (especially with undiluted oil)
• Gastrointestinal discomfort (nausea, stomach upset, diarrhea)
• Allergic reactions (skin rash, itching, swelling) in sensitive individuals
• Temporary numbing or tingling of oral tissues
• Burning sensation on skin when applied topically (especially with undiluted oil)
• Increased bleeding risk due to anticoagulant effects
• Lowered blood sugar levels (may be problematic for diabetics)
• Headaches (rare, usually with high doses)
• Dizziness or lightheadedness (rare)
• Respiratory irritation if inhaled directly (essential oil)
• Potential liver enzyme elevation with very high doses
• Mouth ulcers with prolonged direct application
• Temporary reduction in beneficial gut bacteria with prolonged use

• Known allergy to clove or plants in the Myrtaceae family
• Bleeding disorders or use of anticoagulant medications
• Upcoming surgery (discontinue at least 2 weeks before)
• Diabetes (may enhance hypoglycemic effects of medications)
• Pregnancy and breastfeeding (medicinal doses)
• Children under 5 years (for internal use)
• Severe liver or kidney disease
• Peptic ulcers or gastroesophageal reflux disease (GERD)
• Inflammatory bowel conditions (may irritate sensitive digestive tracts)
• Seizure disorders (high doses of eugenol may lower seizure threshold)
• Hormone-sensitive conditions (due to potential mild estrogenic effects)

• Anticoagulant and antiplatelet medications (warfarin, aspirin, clopidogrel) – increased bleeding risk
• Antidiabetic medications – enhanced hypoglycemic effect
• Monoamine oxidase inhibitors (MAOIs) – potential for hypertensive crisis
• Iron supplements – may reduce iron absorption
• Antibiotics – may enhance or interfere with antibiotic effects (consult healthcare provider)
• Antacids – may reduce clove oil absorption
• Immunosuppressants – may counteract immunosuppressive effects
• Medications metabolized by cytochrome P450 enzymes (CYP2B6, CYP2C9, CYP2D6, CYP3A4) – potential altered drug metabolism
• Sedatives and central nervous system depressants – may enhance sedative effects
• Proton pump inhibitors and H2 blockers – altered absorption of clove compounds

For clove essential oil: 400-600 mg daily of standardized extract (containing 30-50% eugenol) or 9-12 drops of diluted clove oil daily, divided into 3-4 doses. Higher doses increase the risk of side effects without necessarily improving therapeutic outcomes. Long-term use (beyond 3-4 weeks continuously) is not recommended without periodic breaks to prevent potential adverse effects on beneficial gut bacteria and development of sensitization. For topical application, concentrations above 2-3% in carrier oil may cause skin irritation and should be avoided.

For oral/dental applications, direct application of diluted oil should be limited to 3-4 times daily for no more than 7 consecutive days.

In the United States, clove and its extracts are generally recognized as safe (GRAS) for use as a food flavoring and spice under 21 CFR 184.1257. As a dietary supplement, clove extract falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994, which means it can be marketed without prior FDA approval as long as no specific health claims are made regarding the treatment, prevention, or cure of diseases. The FDA does not evaluate the safety or efficacy of clove supplements before they reach the market but can take action against products found to be unsafe or making unsubstantiated health claims. For dental applications, eugenol (the primary active compound in clove oil) is approved as an analgesic for temporary relief of dental pain and is used in various dental materials.

Clove oil is not approved by the FDA for internal use as a drug and cannot be marketed with therapeutic claims for treating specific conditions. For external use in cosmetics and topical products, clove extract and oil are permitted with appropriate concentration limits due to potential skin sensitization concerns.

Eu: In the European Union, clove is listed in the European Medicines Agency (EMA) database of herbal substances. The Committee on Herbal Medicinal Products (HMPC) has established a community herbal monograph for Syzygium aromaticum, recognizing its traditional use for symptomatic treatment of mild inflammation of the oral mucosa and as a topical anesthetic for temporary relief of toothache. For food use, clove extract is regulated under Regulation (EC) No 1334/2008 on flavorings and is approved as a food additive. As a food supplement, clove products must comply with the Food Supplements Directive 2002/46/EC. Clove essential oil is subject to restrictions in cosmetic products under the Cosmetic Products Regulation (EC) No 1223/2009, with limitations on concentrations due to potential allergenic and sensitizing properties of eugenol, which must be declared on product labels when present above certain thresholds.

Canada: Health Canada has included clove in the Natural Health Products Ingredients Database with a medicinal ingredient monograph. It is approved for use in Natural Health Products (NHPs) with specific guidelines for dosage, contraindications, and warnings. Clove essential oil is permitted in NHPs for oral use at specified dilutions and dosages, with appropriate cautionary labeling. For topical use, clove oil is recognized for temporary relief of toothache and as a counterirritant for muscle and joint pain. For food use, clove extract is regulated as a food flavoring agent. Clove products must have a Natural Product Number (NPN) to be legally sold in Canada as natural health products.

Australia: The Therapeutic Goods Administration (TGA) in Australia regulates clove extract as a listed complementary medicine when used for therapeutic purposes. Products containing clove must be included in the Australian Register of Therapeutic Goods (ARTG) before they can be marketed. Clove essential oil is subject to specific labeling requirements and restrictions on therapeutic claims. For food use, Food Standards Australia New Zealand (FSANZ) regulates clove extract as a food flavoring substance. Eugenol is listed in the Poisons Standard (the SUSMP) and is restricted in certain applications due to safety concerns at high concentrations.

Low to medium, depending on concentration and quality

For high-quality clove essential oil (with 80-90% eugenol content), the cost ranges from $0.20 to $0.75 per effective daily dose (1-3 drops). Standardized clove extract capsules typically cost $0.15 to $0.50 per effective daily dose (100-300 mg). Whole cloves or ground clove powder for tea or culinary use is the most economical form, costing approximately $0.05 to $0.15 per effective dose.

Clove extract offers excellent value for specific applications, particularly for oral health and as a natural antimicrobial. When compared to conventional dental analgesics, high-quality clove oil provides comparable temporary pain relief at a fraction of the cost, though with a shorter duration of action. For antimicrobial purposes, clove extract is more economical than many essential oils with similar properties, such as tea tree or oregano oil, while providing comparable efficacy against a broad spectrum of pathogens. The concentrated nature of clove essential oil means a small bottle (15 ml) can last for months of regular use, improving its long-term value proposition.

However, the wide variation in product quality significantly impacts cost-efficiency. Low-cost products often contain diluted oil or clove stem oil with lower eugenol content, potentially providing less therapeutic benefit despite the lower price point. For antioxidant support, clove extract ranks among the most cost-effective options based on ORAC value per dollar spent, outperforming many more expensive antioxidant supplements. The most cost-efficient approach may be targeted, short-term use for specific conditions rather than continuous supplementation.

For digestive issues, enteric-coated capsules provide better value despite higher cost, as they deliver active compounds directly to the intestines where they’re needed. When considering the full economic impact, clove extract may offer indirect cost savings by potentially reducing the need for over-the-counter medications for minor ailments like toothache, muscle pain, or digestive discomfort. For culinary use, whole cloves provide the best value, as they can be used multiple times (in infusions) before discarding and retain their potency longer than pre-ground forms.

Properly stored clove essential oil typically maintains its potency for 3-5 years from the date of production, with minimal degradation of active compounds during

this period. Standardized clove extracts in capsule or tablet form generally have a shelf life of 2-3 years

when stored according to manufacturer recommendations. Clove-infused carrier oils have a shorter shelf life of approximately 1-2 years, as the carrier oil may oxidize even if the clove compounds remain stable. Dried clove buds used for teas or culinary purposes maintain their aromatic compounds for about 2-3 years

when properly stored in airtight containers away from light and heat.

Store clove essential oil in dark amber or blue glass bottles to protect from light degradation, as UV exposure can accelerate the breakdown of eugenol and other active compounds. Keep all clove preparations in cool, dry places away from direct sunlight and heat sources, ideally at temperatures between 15-25°C (59-77°F). Tightly seal containers after each use to prevent oxidation and evaporation of volatile compounds. Refrigeration can extend the shelf life of clove-infused oils but is not necessary for essential oils or dried buds.

Avoid storing near strong-smelling substances as clove products may absorb other odors or release their aroma into nearby products. For capsules and tablets, keep in their original containers with desiccant packets if provided to protect from moisture. If transferring essential oil to another container, use glass rather than plastic, as the concentrated compounds can degrade certain plastics over time and may leach chemicals from the plastic.

Exposure to oxygen – Causes oxidation of eugenol and other phenolic compounds, reducing antimicrobial and antioxidant properties. Oxidized eugenol may form dimers and polymers that alter the oil’s viscosity and efficacy., Ultraviolet light – Accelerates degradation of essential oil components, particularly eugenol and eugenol acetate, which can break down into less active compounds., Heat – Temperatures above 30°C (86°F) accelerate volatilization and chemical changes in the essential oil compounds. Prolonged exposure to high temperatures can cause polymerization of eugenol., Moisture – Can promote hydrolysis of certain compounds, particularly eugenol acetate, which may convert to eugenol and acetic acid. Also increases the risk of microbial contamination in dried herb and extract products., Metal ions – Particularly iron and copper, can catalyze oxidation reactions of phenolic compounds in clove extract, accelerating degradation. Contact with metal containers should be avoided., Improper dilution – Using the wrong carrier oils or diluents can affect stability and bioactivity. Some carrier oils may accelerate oxidation of clove compounds., Fluctuating temperatures – Repeated warming and cooling can accelerate degradation through condensation and expansion effects, potentially introducing moisture into the product., pH extremes – Highly acidic or alkaline environments can alter the chemical structure of eugenol and other compounds, potentially reducing their therapeutic activity.

Synthesis Methods

Natural Sources

Quality Considerations

Clove has a rich and extensive history of use spanning over 2,000 years across multiple civilizations. Native to the Maluku Islands (formerly known as the Spice Islands) in Indonesia, cloves were one of the most valuable spices in ancient trade routes. In ancient China, as early as 200 BCE, cloves were not only used as a spice but also as a breath freshener. Court officials were required to hold cloves in their mouths when addressing the emperor to ensure fresh breath.

Chinese traditional medicine incorporated cloves for treating digestive ailments, diarrhea, hernia, and ringworm, as well as for their warming properties according to Traditional Chinese Medicine principles. In Ayurvedic medicine from India, dating back over 2,000 years, cloves (lavanga) were used for dental pain, respiratory conditions, and digestive disorders. Ayurvedic practitioners valued cloves for their ‘katu’ (pungent) and ‘ushna’ (hot) properties, which were believed to balance ‘kapha’ and ‘vata’ doshas. Ancient Romans also prized cloves for their aromatic properties and medicinal uses.

Pliny the Elder mentioned cloves in his ‘Natural History,’ noting their use in preserving food and treating various ailments. By the 4th century CE, cloves had become an important trade commodity in the Roman Empire. In medieval Europe, cloves gained prominence after Arab traders introduced them more widely. 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.

European folk medicine used cloves for toothache, nausea, and as a digestive aid. The famous ‘thieves’ vinegar,’ allegedly used by thieves to protect themselves while robbing plague victims, contained cloves among other herbs. In traditional Indonesian and Malaysian medicine, cloves were used for multiple purposes, including treating infections, reducing inflammation, and as an aphrodisiac. Local healers would prepare clove infusions for respiratory conditions and apply clove oil topically for fungal infections and muscle pain.

The dental applications of clove have perhaps the longest continuous use in history. Across multiple cultures, from China to Europe to the Middle East, clove oil was applied directly to aching teeth and gums for its analgesic and antimicrobial properties. This practice continues today in modern dentistry, where eugenol (the active compound in cloves) is still used in dental materials and temporary fillings. During the Age of Exploration in the 15th and 16th centuries, control over the clove trade became a major factor in colonial expansion.

The Portuguese, Dutch, and British fought for control of the Spice Islands largely due to the value of cloves and nutmeg. This period saw cloves spread more widely throughout the world, along with knowledge of their medicinal applications. In the 19th century, as modern medicine began to develop, researchers started investigating the chemical components of cloves. Eugenol was first isolated from clove oil in 1827 by German chemists, leading to a better understanding of its properties and potential applications.

Throughout the 20th century, scientific research has validated many traditional uses of cloves, particularly their antimicrobial, analgesic, and antioxidant properties. Modern applications have expanded to include clove derivatives in food preservation, dental materials, and as natural insect repellents. The concentrated essential oil, as used in modern supplements, is a relatively recent development, becoming popular in the late 20th century as interest in natural alternatives to conventional medicine grew. Traditional uses focused more on the whole herb, infused oils, and water extracts (teas).

Hu, Q., Zhou, M., & Wei, S. (2018). Progress on the Antimicrobial Activity Research of Clove Oil and Eugenol in the Food Antisepsis Field. Journal of Food Science, 83(6), 1476-1483. doi:10.1111/1750-3841.14180, Sharifi-Rad, J., et al. (2021). Biological Activities of Essential Oils: From Plant Chemoecology to Traditional Healing Systems. Molecules, 26(9), 2614. doi:10.3390/molecules26092614, Mittal, M., et al. (2018). Phytochemicals in Oral Health: Anti-inflammatory and Anti-microbial Effects of Plant-derived Compounds on Oral Cells. Archives of Oral Biology, 95, 40-47. doi:10.1016/j.archoralbio.2018.07.016

Evaluation of clove extract as an adjunct therapy for periodontal disease (ClinicalTrials.gov Identifier: NCT04523389), Clove oil-based topical formulation for diabetic foot ulcers (EudraCT Number: 2021-003456-18), Effects of standardized clove extract on postprandial glucose levels in prediabetic adults (ISRCTN Registry: ISRCTN15937589), Comparative efficacy of clove oil and benzocaine for temporary relief of dental pain (ClinicalTrials.gov Identifier: NCT04789045)