Chlorogenic Acid
Multifaceted polyphenol with broad-spectrum anticancer activity and clinical trial validation
Summary
- Broad-Spectrum Activity: Effective against multiple cancer types with up to 86% tumor inhibition
- Clinical Validation: Ongoing Phase I/II trials for glioma with proven tolerability
- Multiple Mechanisms: Apoptosis, cell cycle arrest, immunomodulation, and chemosensitization
- FDA Recognition: Approved by China FDA as natural anticancer drug
What is Chlorogenic Acid?
Chlorogenic acid (CGA) is a polyphenol compound abundant in coffee beans (especially green coffee beans and extracts), tea (burdock tea), fruits, and vegetables. Known for its antioxidant and anti-inflammatory properties, CGA has demonstrated promising anticancer effects through multiple biological mechanisms, making it a valuable natural agent for both cancer prevention and therapy.
Clinical Recognition
CGA is approved by the China Food and Drug Administration as a natural anticancer drug and is considered safe for consumption. It shows moderate bioavailability and low toxicity, with doses up to 1,000 mg/kg showing no adverse effects in animal studies.
Key Anticancer Mechanisms
| Mechanism | Description | Key Pathways/Targets | Evidence Examples |
|---|---|---|---|
| Apoptosis Induction | Promotes programmed cell death via mitochondrial dysfunction | ↑Bax, caspase-3/9; ↓Bcl-2 | 73% apoptosis in MDA-MB-231 at 100 μM |
| Cell Cycle Arrest | Halts progression, often at G0/G1 phase | ↑p21; c-Myc sumoylation | 70% G0/G1 cells at 50 μM |
| Metastasis Inhibition | Suppresses cell migration, invasion, and EMT | ↓NF-κB, PI3K/Akt, MMP-2/9 | 86% tumor inhibition in lung xenografts |
| Immunomodulation | Enhances immune response, repolarizes macrophages | M2→M1 shift, ↑CD8+ T cells | Glioblastoma macrophage repolarization |
| Metabolic Disruption | Reduces ATP production, increases oxidative stress | ↓mitochondrial OCR, ↑ROS | ATP reduction in U87MG glioma cells |
| Chemosensitization | Overcomes drug resistance, reduces toxicity | ERK/MAPK inhibition, Nrf2 protection | Enhanced 5-FU, cisplatin efficacy |
Cancer-Specific Effects
Breast Cancer
IC50 ~20 μM in MDA-MB-231; reduces lung metastases; improves survival via NF-κB/EMT modulation
Liver Cancer (HCC)
57% tumor growth inhibition (75 mg/kg); synergizes with regorafenib via PI3K/Akt
Lung Cancer
Differentiation induction in H446 xenografts; stem cell marker reduction (CD44)
Glioma/Brain Tumors
57% growth inhibition in C6 models; crosses blood-brain barrier; ongoing Phase I/II trials
Cholangiocarcinoma
IC50 57 μM in RBE cells; G0/G1 arrest, EMT inhibition, enhances cisplatin
Tongue Cancer
Robust growth inhibition via EGFR-AKT-MMP9 axis in cellular and organismal models
Clinical Evidence & Trials
Clinical Trials
Phase I/II trials for glioma (NCT02728349, NCT03758014) report good tolerability, with Phase II ongoing as of 2025. The median overall survival for advanced GBM patients in the effective dose group of clinical trial NCT03758014 was 21.4 months, which is notably better than historical data.
Gene expression studies highlight modulation of apoptosis/inflammation genes, supporting combination therapies
Impressive Preclinical Results
Maximum Efficacy
Up to 86% tumor volume reduction in lung cancer xenografts at 200 mg/kg
Excellent Safety
No toxicity at doses up to 1,000 mg/kg in animal studies
Chemotherapy Enhancement
Synergizes with 5-FU, doxorubicin, cisplatin while protecting normal tissues
Natural Sources & Bioavailability
Top Chlorogenic Acid Sources
#1 Green Coffee Beans
Highest concentration (6-12% by weight)
#2 Regular Coffee
70-350 mg per cup (varies by roasting)
#3 Fruits & Vegetables
Apples, pears, berries, artichokes
Additional sources: Tea, potatoes, tomatoes, and various herbs. Green coffee extracts provide the most concentrated supplemental form.
Enhanced Bioavailability
Microbial metabolites like 3-PPA improve CGA's bioavailability. The compound shows good oral absorption and can cross the blood-brain barrier, making it effective for brain tumors.
Additional Benefits & Properties
Beyond Cancer: Additional Properties
- PARP-1 Inhibitor: Blocks DNA repair in cancer cells
- Differentiation Inducer: Promotes cancer cell differentiation to less aggressive forms
- Ammonia Reduction: Evidence suggests CGA may help lower blood ammonia levels by influencing the gut microbiome and inhibiting ammonia-producing bacteria. A study found that burdock root tea rich in CGA inhibited ammonia production in human fecal cultures and reduced blood ammonia levels in mice, possibly by increasing beneficial short-chain fatty acids and reducing gut pH.
- Iron Absorption Inhibitor: Potent inhibitor of nonheme iron absorption
- RAS Interaction Reduction: Interferes with oncogenic RAS signaling
Synergistic Combinations
Research-Supported Synergies
- Hesperidin: Enhanced anticancer effects when combined with this citrus flavonoid
- Cinnamaldehyde: Synergistic activity with cinnamon's active compound
- Conventional Chemotherapy: 5-FU, doxorubicin, cisplatin, regorafenib
Mechanism Highlights
Glioblastoma Breakthrough: Repolarizes tumor-associated macrophages from immunosuppressive M2 to anti-tumor M1 phenotype
Multi-target Approach: NF-κB inhibition links anti-inflammation to apoptosis and EMT suppression across multiple cancer models
Excellent Safety Profile
Clinical Tolerability: Phase I/II trials demonstrate good safety in glioma patients
Regulatory Recognition: Approved by China FDA as natural anticancer drug
High-Dose Safety: No toxicity at doses up to 1,000 mg/kg in animal studies
References & Further Reading
Nature Scientific Reports: Chlorogenic acid inhibits glioblastoma growth through macrophage repolarization
Theranostics (2019): Cancer cell differentiation induction study
ScienceDirect: Esophageal cancer growth inhibition via BMI1 and SOX2 downregulation
MDPI (2024): Synergy with cinnamaldehyde in cancer treatment
PubMed (26344206): Comprehensive review of anticancer mechanisms
Clinical Trials: NCT02728349, NCT03758014 - Ongoing glioma trials with demonstrated tolerability
Disclaimer: This information is for educational purposes only and should not replace professional medical advice. While chlorogenic acid shows excellent safety and promising clinical results in ongoing trials, more research is needed to establish optimal dosing and long-term efficacy for cancer treatment. Always consult with qualified healthcare providers before beginning supplementation, especially during active cancer treatment or if taking medications.
Last updated: September 2025
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