# The progress on stevia (Stevia rebaudiana Bertoni): chemical composition, pharmacokinetics, pharmacological effects, safety, applications, and biosynthesis

## TL;DR

This review summarizes the chemical makeup, health effects, safety, and uses of stevia, a natural sweetener, based on recent scientific findings.

## Contribution

This paper provides a comprehensive synthesis of multidisciplinary evidence on stevia glycosides, including their pharmacokinetics, pharmacology, and biosynthesis.

## Key findings

- Steviol glycosides are metabolized by gut microbiota, not the upper gastrointestinal tract, resulting in negligible caloric impact.
- Stevia extracts show antioxidant, anti-inflammatory, and protective effects on liver and kidneys through various mechanisms.
- Advanced biosynthetic methods are being developed to produce next-generation steviol glycosides like Rebaudioside M.

## Abstract

Stevia rebaudiana Bertoni (stevia) is renowned for its natural sweetening properties, attributed to a complex phytochemical profile rich in steviol glycosides (SGs), flavonoids, and phenolic compounds.

A systematic search of PubMed, Web of Science, and CNKI (Jan 2005–Sep 2025) using keywords related to Stevia yielded over 17,600 records. After deduplication and screening, around 200 full-text articles were evaluated. Additional key references were identified through citation tracking. Ultimately, over 140 sources were gathered to create a comprehensive overview prioritizing significant evidence.

The findings reveal that SGs are not metabolized in the upper gastrointestinal tract but are hydrolyzed exclusively by gut microbiota to steviol, accounting for their negligible caloric impact. Stevia extracts and their constituents exhibit a broad spectrum of potent pharmacological activities, including antioxidant, anti-inflammatory, anti-hyperglycemic, anti-hyperlipidemic, and hepatorenal protective effects, mediated through diverse molecular mechanisms. Toxicological evaluations confirm the safety of SGs, establishing an Acceptable Daily Intake of 4 mg kg–1 body weight. Beyond sweetening, Stevia finds applications in functional foods, animal feed, and agriculture. Furthermore, advanced biosynthetic strategies are being developed to overcome the sensory limitations of traditional SGs, with a focus on the enzymatic production of next-generation glycosides like Rebaudioside M.

This review integrates multidisciplinary evidence on SGs—encompassing chemistry, pharmacology, toxicology, applications, biosynthesis, and regulation—to create a cohesive synthesis and actionable visual frameworks. These resources aim to offer an evidence-based foundation for industry professionals, regulatory bodies, and researchers to effectively address critical priorities and identified gaps.