Researchers at Hiroshima University have discovered that fermented stevia extract demonstrates potent anti-cancer properties against pancreatic cancer cells while leaving healthy cells largely unharmed, according to a new laboratory study that could open new avenues for natural cancer therapeutics.
The research team, led by corresponding author Masanori Sugiyama, found that when stevia leaf extract is fermented with plant-derived Lactobacillus plantarum SN13T strain, it becomes significantly more effective at killing pancreatic cancer cells compared to non-fermented stevia extract.
Enhanced Bioactivity Through Microbial Transformation
"Our findings indicate that fermented stevia leaf extract demonstrates significantly greater cytotoxicity than the non-fermented extract at equivalent concentrations, suggesting that the fermentation process enhances the bioactivity of the extract," Sugiyama explained.
The fermentation process creates new bioactive metabolites that can influence biological systems. "To enhance the pharmacological efficacy of natural plant extracts, microbial biotransformation has emerged as an effective strategy," Sugiyama noted. "In this study, we aimed to compare LAB-fermented and non-fermented extracts to identify key compounds that enhance bioactivity, ultimately contributing to the efficacy of herbal medicine in cancer prevention and therapy."
Selective Cancer Cell Targeting
Laboratory tests comparing the effects on pancreatic cancer (PANC-1) cells and non-cancerous human embryonic kidney cells (HEK-293) revealed the fermented extract's selectivity. "Notably, fermented stevia leaf extract exhibited lower toxicity toward the HEK-293 cells, with minimal inhibition observed even at the highest concentration tested," Sugiyama reported.
The research identified chlorogenic acid methyl ester (CAME) as the active anti-cancer compound responsible for these effects. During fermentation, the concentration of chlorogenic acid in the extract dropped six-fold, indicating microbial transformation into the more potent CAME compound.
Mechanism of Action
Co-author Narandalai Danshiitsoodol explained the transformation process: "This microbial transformation was likely due to specific enzymes in the bacteria strain used. Our data demonstrate that chlorogenic acid methyl ester exhibits stronger toxicity to cells and pro-apoptotic effects - which encourage cell death - on PANC-1 cells compared to chlorogenic acid alone."
The fermented extract works through multiple mechanisms, blocking cancer cells at specific phases of their life cycle to prevent multiplication and triggering apoptosis, the natural cell death process. CAME appears to alter the genetic programming of cancer cells by activating genes that promote cell death while suppressing those that help cancer cells grow and survive.
Clinical Context and Future Research
Pancreatic cancer represents one of the most challenging malignancies to treat, with fewer than 10% of patients surviving five years beyond diagnosis. Symptoms typically appear only after the disease has spread, and conventional therapies like chemotherapy rarely result in a cure.
The fermented stevia extract also demonstrated enhanced antioxidant properties compared to its unfermented counterpart, potentially offering additional protection for healthy cells by neutralizing free radicals more effectively.
The research team is planning future studies using mice to better understand the effectiveness of various dosages across the body, representing the next critical step toward potential clinical applications.
Market and Industry Implications
Stevia currently features in over 40,000 food and beverage products worldwide, with the global market valued at $1.47 billion and projected to reach $2.5 billion by 2035. Major manufacturers including PepsiCo, Nestlé, and Unilever have already incorporated high-purity stevia extracts into multiple product lines as sugar replacements.
While these findings represent early-stage laboratory research requiring extensive animal and human studies before clinical applications, they highlight the potential of microbial biotransformation to unlock hidden therapeutic benefits from common food ingredients.
