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Clove - Syzygium aromaticum

Clove (primarily from Syzygium aromaticum, also known as Eugenia caryophyllata) is a spice with a long history of traditional medicinal use. This aromatic flower bud from the Myrtaceae family has been the subject of numerous scientific investigations exploring its potential health benefits. The following review summarizes current peer-reviewed evidence regarding clove's therapeutic properties, dosing considerations, and safety profile.

Image source and license: https://commons.wikimedia.org/wiki/File:Syzygium_aromaticum_on_tree.jpg.
Modified by Peter Jorgensen.

Botanical Classification and Common Names

The primary botanical source of clove is Syzygium aromaticum (L.) Merr. & L.M.Perry, formerly classified as Eugenia caryophyllata Thunb. Common names include clove, cloves, clavos de olor (Spanish), clou de girofle (French), ding xiang (Chinese), laung (Hindi), and kruidnagel (Dutch). It should not be confused with water clover (Marsilea species), clove pink (Dianthus species), or Brazilian clove (Dicypellium caryophyllaceum), which are botanically distinct plants with different chemical compositions and therapeutic properties.

Active Compounds

Clove's biological activity is primarily attributed to eugenol (70-90% of essential oil), eugenyl acetate, and β-caryophyllene. Additional compounds include flavonoids (quercetin and kaempferol), tannins, and triterpenes that contribute to its therapeutic effects. Standardization typically focuses on eugenol content, which is considered the primary bioactive constituent.

Evidence-Based Therapeutic Applications

Based on peer-reviewed research, clove has demonstrated efficacy in the following conditions:

• Pain Management: Topical applications containing 85-95% eugenol have shown efficacy for dental pain, comparable to benzocaine in randomized controlled trials.
• Antimicrobial Effects: In vitro and some clinical studies support activity against oral pathogens, food-borne bacteria, and certain fungi at concentrations of 0.05-0.2% essential oil.
• Antioxidant Properties: Clove consistently ranks among the highest ORAC (oxygen radical absorbance capacity) values of natural products, with demonstrated free radical scavenging in both in vitro and animal models.
• Anti-inflammatory Activity: Experimental models show inhibition of cyclooxygenase-2 (COX-2) and reduction of inflammatory markers by eugenol and clove extracts.
• Digestive Health: Traditional use for dyspepsia has some support from preclinical studies showing increased digestive enzyme secretion and gastroprotective effects.
• Blood Glucose Regulation: Animal studies suggest potential hypoglycemic effects, though human clinical trials remain limited.
• Hepatoprotective Effects: Experimental evidence indicates protective effects against various hepatotoxins in animal models.

Recommended Dosages

Dosage recommendations vary by preparation type and therapeutic application:

• Essential Oil (Topical): 1-2% dilution in carrier oil for most applications; 10-20% dilution for localized dental pain (not to be swallowed).
• Powdered Clove: 0.5-3g daily, typically divided into 2-3 doses.
• Standardized Extracts: Products containing 15-30% eugenol at 100-500mg daily.
• Infusion/Tea: 1-2g of crushed cloves steeped in 150ml hot water for 5-10 minutes, 1-3 times daily.
• Tincture (1:5, 45% ethanol): 0.5-1ml, 1-3 times daily.

It should be noted that many dosage recommendations are based on traditional use rather than clinical trial evidence. Commercial products vary widely in standardization practices, with some focusing on eugenol content (typically 10-20%) while others standardize to total phenolic compounds.

Side Effects and Safety Considerations

While generally recognized as safe (GRAS) for food use, medicinal applications of clove carry potential risks:

• Oral Irritation: Undiluted clove oil can cause tissue irritation, burns, and damage to oral mucosa.
• Allergic Reactions: Sensitization and allergic responses have been reported, particularly to topical applications.
• Anticoagulant Interactions: Eugenol may inhibit platelet aggregation, potentially interacting with anticoagulant medications.
• Hepatotoxicity: High doses of eugenol have been associated with liver damage in animal studies.
• Blood Glucose Effects: Potential hypoglycemic effects may necessitate monitoring in diabetic patients.
• Respiratory Irritation: Inhalation of clove dust or oil may cause respiratory symptoms in sensitive individuals.
• Cytotoxicity: In vitro studies show dose-dependent cytotoxic effects at high concentrations.

Contraindications include pregnancy (due to insufficient safety data), bleeding disorders, pre-surgical periods (discontinue at least 2 weeks before surgery), and known hypersensitivity to clove or related plants in the Myrtaceae family.

Maximum Efficacious Range and Higher Doses

Research on doses exceeding the therapeutic ranges listed above is limited. Studies exploring higher concentrations have primarily been conducted in vitro or in animal models rather than human clinical trials. Systematic toxicity studies suggest that eugenol has an LD50 of approximately 1930 mg/kg in rats, but human safety thresholds remain incompletely characterized. The European Medicines Agency suggests a maximum daily intake of 5mg/kg body weight of eugenol from all sources. Significant knowledge gaps exist regarding long-term consumption of high-dose clove preparations, particularly standardized extracts. Some animal studies suggest hormetic effects (beneficial at low doses, harmful at high doses), particularly regarding hepatic function and oxidative stress markers (Issac et al., 2021).

Commercial Pharmaceutical Products

Several pharmaceutical products incorporate clove or its derivatives:

• Red Cross® Toothache Medicine: Eugenol-based product for temporary dental pain relief.
• ZOE (Zinc Oxide Eugenol): Dental cement used in restorative dentistry and as a temporary filling material.
• Clovacaine®: Combination product containing eugenol and benzocaine for dental anesthesia (available in limited markets).

Most pharmaceutical applications focus on the analgesic and antimicrobial properties of eugenol for dental applications rather than systemic therapeutic effects.

Conclusion

Clove represents a spice with substantial evidence for certain therapeutic applications, particularly in dentistry and as an antimicrobial agent. However, significant research gaps remain regarding optimal dosing, long-term safety, and efficacy for many claimed benefits. The strongest evidence supports its use for temporary dental pain relief and as an antimicrobial agent. Consumers and clinicians should approach clove-based remedies with attention to standardization, potential drug interactions, and appropriate therapeutic contexts. Future research should focus on well-designed human clinical trials to better establish efficacy, optimal dosing, and safety parameters.

References

Alqareer, A., Alyahya, A., & Andersson, L. (2006). The effect of clove and benzocaine versus placebo as topical anesthetics. Journal of dentistry, 34(10), 747-750.

Amir Rawa, M. S., Mazlan, M. K. N., Ahmad, R., Nogawa, T., & Wahab, H. A. (2022). Roles of Syzygium in anti-cholinesterase, anti-diabetic, anti-inflammatory, and antioxidant: from Alzheimer’s perspective. Plants, 11(11), 1476.

Barboza, J. N., da Silva Maia Bezerra Filho, C., Silva, R. O., Medeiros, J. V. R., & de Sousa, D. P. (2018). An overview on the anti‐inflammatory potential and antioxidant profile of eugenol. Oxidative medicine and cellular longevity, 2018(1), 3957262.

Begum, S. N., Ray, A. S., & Rahaman, C. H. (2022). A comprehensive and systematic review on potential anticancer activities of eugenol: From pre-clinical evidence to molecular mechanisms of action. Phytomedicine, 107, 154456.

Cortés-Rojas, D. F., de Souza, C. R. F., & Oliveira, W. P. (2014). Clove (Syzygium aromaticum): a precious spice. Asian Pacific journal of tropical biomedicine, 4(2), 90-96.

Marchese, A., Barbieri, R., Coppo, E., Orhan, I. E., Daglia, M., Nabavi, S. F., ... & Ajami, M. (2017). Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Critical reviews in microbiology, 43(6), 668-689.

Shakeel, F., Alam, P., Ali, A., Alqarni, M. H., Alshetaili, A., Ghoneim, M. M., ... & Ali, A. (2021). Investigating antiarthritic potential of nanostructured clove oil (Syzygium aromaticum) in FCA-induced arthritic rats: Pharmaceutical action and delivery strategies. Molecules, 26(23), 7327.

Vijayasteltar, L., Nair, G. G., Maliakel, B., Kuttan, R., & IM, K. (2016). Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies. Toxicology reports, 3, 439-449.