Clinical Efficacy and Safety of <italic>Ssanghwa-tang</italic>: A Literature Review

Objective: This study provided empirical evidence for the clinical application of <i>Ssanghwa-tang</i> (SHT) by reviewing the efficacy and safety of the original formula (O-SHT) and its modified forms (M-SHT) and analyzing trends in herbal modification.Methods: Literature searches across 14 databases up to June 30, 2024, identified 23 eligible studies (6 clinical, 17 experimental), reviewed under PRISMA 2020. Animal dosages were converted to human equivalent doses (HEDs) for comparison with clinical ranges.Results: SHT demonstrated benefits in musculoskeletal performance, cerebrovascular and neurological protection, immune and inflammatory modulation, and management of fever, pain, edema, chronic fatigue, and liver injury. M-SHT formulations were classified into Type 1 (O-SHT-like; focused on musculoskeletal, bone, and neurological outcomes), Type 2 (equal ratio; primarily used in toxicity studies), and Type 3 (<i>Samul-tang</i>-like; evaluated for antipyretic, analgesic, and anti-edema effects). Frequently added herbs included Puerariae Radix (葛根), Atractylodis Rhizoma (蒼朮), and Atractylodis Rhizoma Alba (白朮). Most formulas were used within standard clinical ranges; two antipyretic formulas exceeded typical dosages, though acute and subacute toxicity studies indicated acceptable safety. Evidence regarding long-term safety remains limited.Conclusion: SHT appears effective across multiple domains and safe within standard dosages, with modification patterns influencing therapeutic outcomes. Further clinical trials and long-term toxicology studies reflecting real-world practice are warranted.