Si Ni San (Frigid Extremities Powder)

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Indications

Western Uses:

• What conditions is Si Ni San used for in modern practice?

  Si Ni San spreads constrained Liver qi that is over-controlling the Spleen and Stomach (flank and epigastric tension, irritability, cold hands and feet from qi constraint), so it is referenced for Liver-Spleen disharmony and hepatobiliary conditions: gastritis, peptic ulcer, cholecystitis, gallstones (cholelithiasis), hepatitis, intestinal obstruction, mastitis, breast lumps (fibroadenoma), hernia, and pancreatitis.

  It is chosen for the Liver-qi-constraint pattern, not for a diagnosis. Intestinal obstruction, pancreatitis and cholecystitis are potential surgical emergencies presenting with severe abdominal pain and need immediate care; a hernia, a breast lump, and hepatitis all require medical assessment. Traditional-use correlates only, not a treatment claim.

  Source: Sacred Lotus sources & references (pattern) + Bensky & Barolet, Formulas & Strategies; biomedical correlates as reference only. Not medical advice.

Originally Appeared In:

• On Cold Damage (Shang Han Lun)

Notes:

• How does Si Ni San differ from Si Ni Tang, and what formula descends from it?

  Si Ni San and Si Ni Tang share a name (both mean roughly “frigid extremities” and both appear in the Shang Han Lun's Shaoyin chapter) but treat opposite mechanisms — this is the single most important distinction to get right when reading either formula's name.

  • vs Si Ni Tang (Frigid Extremities Decoction): Si Ni Tang is built from Fu Zi (aconite), Gan Jiang, and Zhi Gan Cao to rescue devastated, collapsing Yang — true Shaoyin cold with cold extending past the elbow/knee, severe fatigue, watery diarrhea with undigested food, and a faint, almost-imperceptible pulse. Si Ni San contains no warming, yang-rescuing herbs at all; it uses Chai Hu, Zhi Shi, Bai Shao, and Gan Cao to free a constrained qi mechanism, fitting a patient who is not exhausted or collapsing — cold limited to the fingers/toes, a wiry (not faint) pulse, and signs of qi stagnation (distension, irritability) rather than depletion.
  • vs Xiao Yao San: both harmonize Liver and Spleen, but Xiao Yao San adds Dang Gui, Bai Zhu, Fu Ling, Sheng Jiang, and Bo He for a gentler, more tonifying and blood-nourishing approach suited to Liver qi stagnation with underlying blood/Spleen deficiency; Si Ni San is the more purely qi-regulating of the two, without Xiao Yao San's tonifying herbs.
  • Ancestor to Chai Hu Shu Gan San: Chai Hu Shu Gan San (from Zhang Jingyue's Ming-dynasty Jingyue Quanshu) is built directly on Si Ni San's four herbs, adding Xiang Fu, Chuan Xiong, and Chen Pi (and typically substituting the milder Zhi Ke for Zhi Shi) to intensify the qi-moving and mild blood-invigorating action for more pronounced Liver-qi-stagnation pain in the chest, hypochondrium, or epigastrium. A later meta-analysis of 42 randomized trials found Chai Hu Shu Gan San performed favorably against fluoxetine for depression across several subtypes (PMID 29454341) — evidence for the descendant formula, not for Si Ni San itself.

  Source: Shang Han Lun (Zhang Zhongjing) for both Si Ni formulas + Bensky & Barolet, Formulas & Strategies (Xiao Yao San comparison; Chai Hu Shu Gan San lineage) + PubMed 29454341 (Chai Hu Shu Gan San trial evidence, cited for context only).

Clinical Studies & Research:

• Is there modern research on Si Ni San?

  Yes — a 2026 randomized, double-blind, placebo-controlled crossover trial found Si Ni San significantly reduced depression scores compared with placebo in breast cancer patients with mild-to-moderate depression, and separate rodent studies have explored a hepatic lipid-metabolism mechanism. Evidence remains limited in volume, and none of it supports the formula for treating any diagnosed disease.

  • Depression, breast cancer patients (clinical, randomized crossover trial): a four-week-on/four-week-off crossover trial with a two-week washout reported significantly greater reduction in depression scores during the Si Ni San phase than during placebo, with accompanying multi-omics analysis exploring a possible biological mechanism (PMID 41491244).
  • Metabolic-associated fatty liver disease (preclinical, rat model): in rats fed a high-fat, high-cholesterol diet, Si Ni San reduced hepatic lipid deposition, an effect associated with activation of the AMPK/SIRT1 signaling pathway (PMID 37808345). This is animal-model evidence, not a clinical finding.

  Sources: PubMed 41491244; PubMed 37808345. Research context, not a therapeutic claim; direct clinical trial evidence for Si Ni San remains limited to the single trial above.