Chlorogenic Acid’s Role in Metabolic Health: Mechanisms and Therapeutic Potential



Chlorogenic Acid’s Role in Metabolic Health: Mechanisms and Therapeutic Potential

Summary: This comprehensive review examines chlorogenic acid (CGA), a polyphenol abundant in coffee, fruits, and vegetables, for its pleiotropic effects in preventing and managing metabolic syndrome components like type 2 diabetes, obesity, hypertension, and dyslipidemia. Through modulation of oxidative stress (Nrf2/HO-1 pathway), inflammation (NF-κB inhibition), insulin sensitivity (AMPK activation), and gut microbiota (increased SCFAs and probiotics), CGA improves glucose/lipid homeostasis, reduces body weight/BMI, and lowers blood pressure. Notably, it mitigates diabetic complications including nephropathy, retinopathy, neuropathy, and foot ulcers via tissue-protective mechanisms, with electrospun nanofiber dressings demonstrating hypoglycemic and regenerative benefits in preclinical models. Despite low bioavailability, CGA’s safety and efficacy in clinical trials position it as a promising nutraceutical adjunct, warranting further research on optimized formulations for chronic wound care.

Key Highlights:

  • CGA reduces fasting glucose (e.g., -3.5% in impaired tolerance trials) and HbA1c (-0.73%), enhancing insulin sensitivity via IRS1/AKT2/GLUT2 and AMPK pathways, critical for diabetic wound delays.
  • Anti-obesity effects include BMI/waist reductions (-3.68%/-3.15%) and gut microbiota shifts (↑Bifidobacterium, ↓Lachnospiraceae), promoting SCFAs for anti-inflammatory wound environments.
  • Cardiovascular benefits: Lowers systolic/diastolic BP (-6.9%/-7.69%) by inhibiting ACE and improving endothelial function, addressing vascular issues in chronic ulcers.
  • Diabetic complications: Protects against oxidative damage in nephropathy/retinopathy/neuropathy; electrospun CGA dressings accelerate foot ulcer healing via hypoglycemic/regenerative actions.
  • Safety: Well-tolerated at dietary doses (up to 2g/day), though high intake may raise homocysteine; low bioavailability addressed by nanocarriers for targeted wound applications.

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Keywords: chlorogenic acid, metabolic syndrome, diabetic complications, AMPK activation, CGA dressings, Katarzyna Zalewska, Maciej Kulawik, Julia Gierszewska