Clove and Cancer

Researched and written by Keith Bishop, Clinical Nutritionist, Cancer Coach, and Retired Pharmacist.

Cloves are the dried flower buds of the evergreen tree Syzygium aromaticum. They are commonly used as a cooking spice and have been used in traditional medicine for centuries.

Clove, a spice native to Indonesia's Maluku Islands, has been esteemed for centuries in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine (TCM). Historically, it has been utilized to address many ailments, including dental pain, digestive issues, respiratory conditions, and reproductive health concerns. The therapeutic properties of clove are attributed mainly to its rich phytochemical composition, notably eugenol, eugenol acetate, and β-caryophyllene, which confer antimicrobial, anti-inflammatory, analgesic, and antioxidant effects.[i]

In traditional practices, cloves were commonly employed to alleviate toothaches and oral infections, owing to their potent analgesic and antiseptic properties. It also played a role in treating gastrointestinal disturbances such as nausea, vomiting, and flatulence and was used to manage respiratory ailments like coughs and colds. Furthermore, clove has been recognized for its potential benefits in reproductive health, with applications in addressing menstrual irregularities and enhancing libido.

Modern scientific investigations have begun to validate these traditional uses, highlighting clove's broad-spectrum antimicrobial activity against various pathogens, including bacteria, fungi, and viruses. Its antioxidant capacity surpasses that of many fruits and vegetables, suggesting a role in combating oxidative stress-related diseases.[ii]

The enduring presence of clove in both culinary and medicinal contexts underscores its significance as a natural remedy. Ongoing research explores its potential applications in contemporary healthcare, aiming to integrate traditional knowledge with modern therapeutic approaches.

Anticancer Ingredients in Cloves

Cloves contain several bioactive compounds with potential anticancer properties, including:

• Eugenol: Known for its antioxidant and anti-inflammatory effects[iii]
• Oleanolic Acid: Demonstrated anticancer activity in studies.[iv]
• Flavonoids: Such as kaempferol and eugenitin.[v]

The anticancer effects of eugenol from the clove are accomplished by various mechanisms, such as inducing cell death, cell cycle arrest, migration inhibition, metastasis, and angiogenesis (new blood vessel growth to tumors) on several cancer cell lines.[vi]

Clove and Cancer Energy Metabolism

Eugenol has significantly affected cellular energy metabolism, particularly in cancer cells. Studies have shown that eugenol can disrupt mitochondrial function, leading to decreased ATP production, which is crucial for cancer cell proliferation and survival.

In a study focusing on breast cancer cells, eugenol treatment resulted in a dose-dependent reduction in intracellular ATP levels. This effect was attributed to the inhibition of oxidative phosphorylation and fatty acid oxidation pathways, mediated through the downregulation of the c-Myc/PGC-1β/ERRα signaling axis. Such metabolic interference led to selective cytotoxicity in cancerous cells while sparing normal cells.[vii]

Further research on colorectal cancer cells revealed that eugenol impairs energy metabolism and modulates gene expression related to tumor suppression and oncogenesis. Treatment with eugenol increased the expression of tumor suppressor genes like p53 and APC while decreasing the expression of the KRAS oncogene. These genetic alterations corresponded with significant changes in metabolic pathways, including those involving amino acids and nucleotide biosynthesis, further compromising the energy production and survival of cancer cells.[viii]

These findings suggest that eugenol exerts its anticancer effects by targeting and disrupting cancer cells' energy metabolism, leading to reduced ATP production and induction of apoptosis. This mechanism highlights the potential of eugenol as a complementary agent in cancer therapy, aiming to exploit cancer cells' metabolic vulnerabilities.

Eugenol has been studied for its effects on cancer cell metabolism, including its impact on glutamine utilization. While direct evidence of eugenol's effect on L-glutamine production in the human body is limited, research indicates that eugenol can influence glutamine metabolism in cancer cells.

A study investigating the anti-cancer properties of eugenol on oral squamous cell carcinoma cells (HSC-2) revealed metabolic changes in pathways involving glutamate and amino acids, suggesting that eugenol affects amino acid metabolism, including that of glutamine. These alterations may disrupt energy production and biosynthetic processes essential for cancer cell proliferation.[ix]

Furthermore, research has shown that eugenol inhibits oxidative phosphorylation and fatty acid oxidation in breast cancer cells, reducing ATP production. This energy depletion can impair glutamine metabolism, as glutamine serves as a key substrate for energy generation in cancer cells.

In summary, while more research is needed to fully understand eugenol's impact on L-glutamine production in the human body, existing studies suggest that eugenol can disrupt glutamine utilization in cancer cells, thereby hindering their growth and survival.

Eugenol's Impact on Cancer Stem Cells

Eugenol, the primary active compound in clove, has demonstrated promising activity against cancer stem cells (CSCs), which are key drivers of tumor initiation, metastasis, and therapy resistance. In a study published in Chemico-Biological Interactions, eugenol was shown to induce degradation of β-catenin through N-terminal Ser37 phosphorylation. This significantly reduced breast cancer stem cell markers CD44 and CD24, effectively impairing CSC maintenance and tumor growth. These findings suggest that eugenol may offer a therapeutic advantage by targeting the stem-like cell population within tumors.[x]

Another study reinforced these findings, showing that eugenol reduced CSC-like features and enhanced sensitivity to chemotherapeutic agents in breast cancer cells[xi] and ovarian cancer cells[xii] by promoting apoptosis and suppressing cell migration and invasion.

These studies highlight eugenol’s potential to target cancer at its roots—by weakening the cells that drive tumor relapse—making clove a promising natural ally in integrative cancer strategies.

Clove and Cancer Chemotherapy and Radiation

Emerging research indicates that eugenol may enhance the efficacy of specific chemotherapy treatments. A study published in Molecules demonstrated that eugenol significantly increased the sensitivity of human cervical cancer (HeLa) cells to cisplatin, a commonly used chemotherapeutic agent. The combination of eugenol and cisplatin resulted in a marked decrease in cell viability compared to either agent alone. This synergistic effect was attributed to eugenol's ability to induce apoptosis by activating caspase-3 and modulating pro- and anti-apoptotic proteins such as Bax and Bcl-2. These findings suggest that eugenol could potentially be used to enhance the effectiveness of cisplatin-based chemotherapy regimens.

Additionally, eugenol has been shown to augment the effects of radiation therapy. The same study reported that pre-treatment with eugenol sensitized HeLa cells to ionizing radiation, leading to increased cell death. This radio-sensitizing effect further underscores eugenol's potential as an adjunctive agent in cancer therapy.[xiii]

While these findings are promising, it's important to note that most studies have been conducted in vitro (laboratory cancer cell studies). Further clinical research is necessary to fully understand the potential benefits and risks of incorporating eugenol into standard chemotherapy and radiotherapy protocols.

Clove Source

I use organic clove buds in my coffee and tea. Here is an Amazon link: https://a.co/d/0X3fEih

Cancers Studied

Laboratory and animal research has explored the effects of cloves on various cancers, including:

• Breast cancer[xiv]
• Cervical cancer[xv]
• Colon cancer[xvi]
• Colorectal cancer[xvii]
• Gastic Cancer[xviii] (stomach cancer)
• Glioblastoma[xix] (Eugenol does cross the blood-brain barrier)
• Leukemia[xx]
• Liver cancer[xxi]
• Lung cancer[xxii]
• Melanoma[xxiii]
• Oral cancer[xxiv]
• Osteosarcoma (bone cancer)[xxv]
• Ovarian cancer[xxvi]
• Pancreatic cancer[xxvii]
• Prostate cancer[xxviii]

Human Studies

While most studies on cloves' anticancer effects have been conducted in vitro (in the laboratory) or on animals, some human studies suggest promising results. However, more clinical trials are needed to confirm these findings.

Impact on Hormone-Related Cancers

Clove (Syzygium aromaticum) and its bioactive constituents—eugenol, kaempferol, and oleanolic acid—have demonstrated promising anticancer effects against hormone-related cancers such as breast, ovarian, cervical, and prostate cancers.

In breast cancer, eugenol has been shown to induce apoptosis through the mitochondrial pathway, independently of estrogen receptor status. This suggests its potential efficacy across various breast cancer subtypes, including triple-negative breast cancer. Studies have reported that eugenol upregulates the cyclin-dependent kinase inhibitor p21^WAF1^ and inhibits the proliferation of breast cancer cells both in vitro (laboratory cancer cell) and in vivo (animal studies).[xxix]

Kaempferol, a flavonoid in clove, has exhibited significant anticancer activity in ovarian and cervical cancers. In ovarian cancer cells, kaempferol induces apoptosis and cell cycle arrest by modulating the PI3K/AKT and MEK/ERK signaling pathways. Similarly, in cervical cancer cells, kaempferol has been observed to induce apoptosis through the activation of death receptors and the JNK/ERK-CHOP pathway.[xxx]

Oleanolic acid, another compound found in clove, has demonstrated anticancer effects in prostate cancer models. It induces p53-dependent apoptosis via the ERK/JNK/AKT signaling pathways, leading to cell cycle arrest and tumor growth inhibition.[xxxi]

These findings suggest that clove and its active constituents may offer therapeutic potential in managing hormone-related cancers by targeting specific molecular pathways involved in cancer cell proliferation and survival.

Eugenol from Clove Crosses the BBB

In laboratory and animal studies, eugenol from clove crosses the blood-brain barrier (BBB) and decreases the viability and proliferation of glioblastoma cancer cells.[xxxii]

Clove Eugenol and Chemotherapy

Eugenol, the active compound in clove, has been studied for its potential to enhance chemotherapy effectiveness. Research suggests that eugenol may help increase cancer cell sensitivity to chemotherapy drugs, promoting apoptosis (cell death) and reducing drug resistance. Additionally, its antioxidant properties may help protect healthy cells from chemotherapy-induced oxidative stress.[xxxiii]

Clove Ingredients and Cancer Stem Cells

Clove (Syzygium aromaticum) and its bioactive constituents—eugenol, oleanolic acid, and kaempferol—have demonstrated significant potential in targeting cancer stem cells (CSCs), which are implicated in tumor initiation, progression, and resistance to therapy.

Eugenol has been shown to suppress CSC characteristics by promoting the degradation of β-catenin, a key regulator of stemness. Thus, it reduces the expression of CSC markers and inhibits tumor growth in breast cancer models. Additionally, eugenol enhances the efficacy of chemotherapeutic agents like cisplatin by inhibiting aldehyde dehydrogenase (ALDH)-positive CSCs and modulating the NF-κB signaling pathway.[xxxiv]

Oleanolic acid has been found to inhibit CSC properties by targeting specific signaling pathways. In oral squamous cell carcinoma, it suppresses the Snail signaling pathway, reducing stemness and overcoming cisplatin resistance. Furthermore, oleanolic acid impairs tumor growth by inhibiting CSCs in mammary tumor models, highlighting its potential as a therapeutic agent.[xxxv]

Kaempferol exhibits anticancer effects by modulating various cellular pathways. It has been reported to suppress CSC properties in triple-negative breast cancer cells by inducing DNA damage and cell cycle arrest and inhibiting sirtuin proteins SIRT3 and SIRT6. In glioma stem cells, kaempferol derivatives have been shown to inhibit proliferation and induce apoptosis through the NF-κB-mediated pathway.[xxxvi]

These findings suggest that clove-derived compounds can effectively target CSCs, offering promising avenues for cancer therapy.

Key Findings:

• Eugenol may synergize with chemotherapy and radiation therapy, improving laboratory treatment outcomes.
• It has been shown to reduce drug resistance.
• Its anti-inflammatory effects may help decrease chemotherapy side effects.

Risks of Consuming Cloves

No specific evidence directly links excessive clove consumption to an increased risk of cancers. Still, it is always advisable to consume cloves in moderation and consult a healthcare provider for personalized guidance.

While moderate amounts used in cooking or herbal remedies are generally safe, high-dose clove or clove oil can pose serious health risks. One of the most concerning effects is liver toxicity. Eugenol, in high concentrations, has been linked to hepatic necrosis and liver enzyme elevation in both animal studies and human case reports. According to the LiverTox database, large ingestions of clove oil can cause liver injury, even though it is considered safe at therapeutic levels.[xxxvii]

Another significant concern is bleeding risk. Eugenol has been shown to inhibit platelet aggregation, which can increase the risk of bleeding, especially when combined with anticoagulant medications like warfarin or aspirin. A 2024 study published in BioFactors confirmed that eugenol significantly reduced platelet activation in human blood samples, highlighting the need for caution in individuals with bleeding disorders or those undergoing surgery.[xxxviii]

High-dose clove oil ingestion may be hazardous in children. Case studies have reported instances of severe toxicity, including seizures, coma, and acute liver failure, following ingestion of as little as 8–10 mL of clove oil. In one documented case, a 15-month-old child developed fulminant hepatic failure after consuming clove oil, resulting in a fatal outcome.[xxxix] Please note that this is a much higher dose than discussed below.

These findings underscore the importance of using clove products with care, especially in concentrated forms like essential oils or supplements. While cloves remain a valuable herbal ally in moderation, high doses should be approached with clinical caution and medical oversight.

How to Consume Cloves

Clove buds and oil are potent. Three cloves or two drops of clove oil per day appear safe. While promising, more clinical studies are needed. Always consult a healthcare professional before incorporating clove or eugenol into your treatment plan.

Cloves can be consumed in various forms:

• Clove Buds: Used in cooking or brewed as tea.
• Powdered Cloves: Added to recipes or smoothies.
• Clove Capsules: Taken as supplements.

Check out my favorite supplements: https://www.prevailovercancer.com/pathway 

Potential Side Effects

Cloves may cause side effects such as:

• Allergic reactions
• Gastrointestinal discomfort
• Blood thinning effects.

Interactions with Medications

Cloves may interact with:

• Blood-thinning medications
• It may be advisable to stop clove consumption 1-2 weeks before surgery to decrease prolonged bleeding tendencies.
• Please use this link to check for your medication and clove interactions. https://www.drugs.com/drug_interactions.html
• Hormone-blocking drugs
• The impact of eugenol on tamoxifen, anastrozole, letrozole, and exemestane is not extensively documented in medical literature. However, here are some considerations based on their mechanisms of action and potential interactions:
• Tamoxifen: Tamoxifen is metabolized by liver enzymes, including CYP2D6. Eugenol has been shown to influence liver enzyme activity, which could theoretically alter tamoxifen's metabolism and efficacy. This interaction might affect the drug's ability to block estrogen receptors effectively.
• Anastrozole, Letrozole, and Exemestane: These aromatase inhibitors reduce estrogen production in postmenopausal women. Eugenol's potential estrogenic or anti-estrogenic effects could theoretically interfere with the action of these drugs. Additionally, eugenol's impact on liver enzymes might influence the metabolism of these medications, potentially altering their effectiveness or side effect profiles.
• Given the lack of direct studies on these interactions, it is crucial for patients to consult their healthcare provider before using eugenol or clove-based supplements alongside these hormone therapies.

Reference Sources

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[xxxii] Spigarelli R, Spisni E, Magalhães M, et al. Clove Essential Oil as a Source of Antitumoral Compounds Capable of Crossing the Blood-Brain Barrier: A Focus on the Effects of β-Caryophyllene and Eugenol in a Glioblastoma Cell Line. Int J Mol Sci. 2024;26(1):238. Published 2024 Dec 30. doi:10.3390/ijms26010238 https://pmc.ncbi.nlm.nih.gov/articles/PMC11720353/

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