Beneficial Synergistic Roles of Flavonoids and Vitamin C Against Inflammatory Complications, Cancer, and Cardiovascular Diseases: A Comprehensive Review

Flavonoids and vitamin C are two of the most extensively studied dietary bioactive compounds, with growing evidence supporting their roles in the modulation of oxidative stress, inflammation, thrombosis, and cancer progression. Flavonoids, a diverse subclass of polyphenols, exhibit promising antioxidant, anti-inflammatory, and anticancer properties. However, their clinical translation is frequently hindered by poor solubility, limited stability, and low bioavailability. Vitamin C (ascorbic acid), a well-known established antioxidant that can also exert pro-oxidant effects at pharmacological concentrations, demonstrates anti-inflammatory, antithrombotic, immune-modulatory, and endothelial-protective activities across various experimental and clinical disease models. Recent studies have highlighted a promising synergistic interaction between flavonoids and vitamin C, wherein flavonoids enhance the stability, recycling, and intestinal absorption of vitamin C, while vitamin C augments the antioxidant capacity and cellular bioactivity of flavonoids. This review critically summarizes current evidence regarding the independent and combined effects of flavonoids and vitamin C, with particular emphasis on their roles in cancer, cardiovascular diseases, and inflammation-related complications. Key molecular mechanisms, including redox signaling modulation, inhibition of pro-inflammatory pathways, and regulation of thrombosis- and angiogenesis-related processes, are discussed. Furthermore, therapeutic opportunities, limitations, and challenges related to bioavailability, dosing strategies, and clinical translation are addressed. Understanding the synergistic actions of flavonoids and vitamin C may provide valuable insights for the development of novel nutraceutical formulations or adjuvant therapeutic approaches in chronic and inflammation-driven diseases.