He Shou Wu Extract: The Complete Scientific Guide

🧬 What is He Shou Wu Extract? Complete Identification

He Shou Wu (Polygonum multiflorum) is a botanical root extract classically dosed at 6–12 g/day in traditional decoctions or 200–1,000 mg/day in modern standardized extracts.

Medical definition: He Shou Wu extract refers to preparations made from the dried root (rhizome) of Polygonum multiflorum (syn. Fallopia multiflora) concentrated into powders, aqueous decoctions, or ethanol-based extracts and sometimes processed via traditional steaming (zhi).

• Alternative names: He Shou Wu, Fo‑ti, Polygoni multiflori radix, Zhi He Shou Wu (processed), Sheng He Shou Wu (raw).
• Scientific classification: Kingdom: Plantae; Family: Polygonaceae; Genus/species: Polygonum multiflorum Thunb.
• Chemical markers: TSG (C20H22O9) and anthraquinones (e.g., emodin C15H10O5).
• Origin/production: Native to central/southern China. Commercial forms: raw powder, zhi-processed root, aqueous decoctions, hydroalcoholic extracts, and standardized extracts (commonly to %TSG).

📜 History and Discovery

He Shou Wu’s usage as a tonic and hair-restorative agent dates back at least a millennium in Chinese materia medica.

• Timeline (selected):
  • Classical era: Documented in Tang/Ming dynasty materia medica for longevity and hair pigmentation.
  • Late 19th–20th c.: Entered Western herbal literature as “Fo‑ti.”
  • 1970s–1990s: Phytochemical discovery of TSG and anthraquinones.
  • 1990s–2010s: Expanded preclinical research (antioxidant, neuroprotective, metabolic effects).
  • 2000s–2020s: Emergence of hepatotoxicity case reports and regulatory attention; improved standardization efforts.
• Discoverers: Use evolved through traditional knowledge rather than a single discoverer; the name references a legendary Mr. He credited with restored hair.
• Traditional vs modern use: In TCM, the processed form (zhi) is preferred for internal tonic uses (hair, kidney/liver nourishment); modern supplements emphasize standardized extracts, often quantified to TSG percentage.
• Fascinating facts:
  • Processing (steaming with black soybean) modifies chemistry—reducing some free anthraquinones and increasing polymeric tannins and glycosides.
  • Market name “Fo‑ti” is Western and not classical Chinese.

⚗️ Chemistry and Biochemistry

He Shou Wu is a complex botanical mixture dominated by stilbene glycosides (TSG) and anthraquinones (e.g., emodin) whose ratios change markedly with processing and solvent.

Molecular composition

• Major constituents: TSG (2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside), emodin, physcion, dianthrones, flavonoids, tannins, and polysaccharides.
• Representative formulas: TSG: C20H22O9; Emodin: C15H10O5.

Physicochemical properties (key points)

• TSG: water-soluble, polar, stable dry, susceptible to hydrolysis of glycoside bond under strong acid or enzymatic action.
• Emodin: poorly water-soluble, lipophilic, susceptible to extensive phase II metabolism (glucuronidation/sulfation).
• Processing impact: Zhi processing reduces free anthraquinones and alters the ratio of active compounds.

Dosage forms

• Raw powder (sheng): used in decoctions; variable composition.
• Processed zhi root: traditional steamed product; historically preferred for tonic use.
• Aqueous extract/decoction: concentrates TSG and polysaccharides.
• Ethanol/hydroalcoholic extract: concentrates anthraquinones (higher hepatotoxicity risk).
• Standardized extracts (%TSG): improved batch consistency but must be accompanied by anthraquinone quantification.

Stability and storage

• Store dry extracts in airtight containers, protected from light, heat, and humidity (15–25°C recommended).
• Avoid prolonged storage at high temperature; glycosides can hydrolyze and anthraquinones may oxidize.

💊 Pharmacokinetics: The Journey in Your Body

PK data are constituent-specific: TSG (water-soluble) and emodin (lipophilic) display distinct absorption, metabolism, and elimination; human PK data are limited.

Absorption and Bioavailability

Absorption: Oral uptake occurs primarily in the small intestine; glycosides (TSG) may be deglycosylated by gut microbiota before absorption while anthraquinones (emodin) are absorbed by passive diffusion when present.

• Influencing factors: extraction solvent (ethanol increases emodin exposure), food/fatty meals (increase lipophilic absorption), gut microbiota (modifies glycoside hydrolysis), co-administered enzyme inhibitors/inducers.
• Typical Tmax (animal data): ~0.5–3 hours depending on compound/formulation; human data sparse.
• Relative bioavailability comparisons (approximate, directionally):
  • Aqueous (TSG-rich): relative systemic exposure to TSG is higher compared with ethanol extracts.
  • Ethanol extracts: relative increase in absorbed anthraquinones (emodin) — increases hepatotoxic risk potential.

Distribution and Metabolism

Distribution: Constituents preferentially distribute to the liver and kidney; lipophilic anthraquinones have higher tissue penetration potential than polar glycosides.

• Metabolism: Gut microbial β-glucosidases (deglycosylation), hepatic UGTs and SULTs (glucuronidation, sulfation) are major metabolic pathways; some CYP involvement reported in vitro for anthraquinones.

Elimination

Elimination: Excreted primarily as conjugated metabolites in bile and urine; enterohepatic recycling may occur for some conjugates.

• Half-life (animal/limited human): constituent-dependent, typically hours (reported ranges ~0.5–8 hours in animal studies); human half-lives not well-established.

🔬 Molecular Mechanisms of Action

He Shou Wu’s principal mechanisms (preclinical) include Nrf2 activation, NF‑κB inhibition, SIRT1/PGC‑1α modulation, and effects on mitochondrial and melanocyte function.

• Cellular targets: antioxidant defense enzymes (NQO1, HO‑1), inflammatory mediators (NF‑κB pathway), mitochondrial biogenesis regulators (SIRT1, PGC‑1α), and melanogenesis regulators (MITF, tyrosinase) in follicle models.
• Enzymatic effects: anthraquinones interact with CYPs and may inhibit CYP3A4 and P‑glycoprotein in vitro; phase II conjugation (UGTs, SULTs) is a major metabolic route.
• Molecular synergy: combinations of TSG with polysaccharides and flavonoids produce additive antioxidant effects in assays; traditional processing alters chemical synergy and toxicity profile.

✨ Science-Backed Benefits

Most benefit claims derive from preclinical models; high-quality randomized controlled trials in humans are scarce and no definitive therapeutic claims are approved by the FDA.

🎯 Support for hair pigmentation and hair quality

Evidence Level: Low

Physiology: Proposed restoration of follicular melanocyte function via antioxidative support and upregulation of melanogenesis genes. Effects, if present, are gradual and aligned with hair cycle timing (weeks to months).

Molecular mechanism: Upregulation of MITF/tyrosinase and reduction of oxidative stress via Nrf2 activation (preclinical).

Target population: Early-onset greying and consumers seeking traditional tonic support; not proven for androgenetic or scarring alopecia.

Onset time: Expect weeks to months (commonly >6–12 weeks) for any observable hair changes.

Clinical Study: High‑quality human RCT evidence is lacking in the datasets available to this report; primary support is from cell and animal studies. (See ‘Current Research’ for how to obtain verified human trial citations.)

🎯 Antioxidant and anti-inflammatory systemic support

Evidence Level: Medium (preclinical strong; limited human biomarker data)

Physiology: Enhanced cellular defense against oxidative damage via upregulated phase II enzymes and reduced proinflammatory cytokines.

Molecular mechanism: Activation of Nrf2‑ARE, increased HO‑1/NQO1, and NF‑κB inhibition reported in animal/cell models.

Clinical Study: No definitive RCT with confirmed PMID included here; evidence is primarily from preclinical literature provided in the source dossier.

🎯 Neuroprotective and cognitive support (preclinical)

Evidence Level: Low–Medium

Mechanism: SIRT1/PGC‑1α and Nrf2 pathway activation, increased BDNF in animal models; improved memory tasks reported in rodents after chronic dosing.

Clinical Study: Human trial data are insufficient in the provided dataset to quote a specific RCT or PMID.

🎯 Metabolic effects — lipid and glucose modulation

Evidence Level: Low–Medium

Mechanism: PPAR and SIRT1 modulation, reduced hepatic steatosis in some animal models; human evidence limited.

Clinical Study: No human RCT citations available in this report; claims based on animal data in the primary source.

🎯 Immune modulation

Evidence Level: Low

Mechanism: Polysaccharide fractions stimulate macrophage activity and innate immune markers in vitro and animal studies.

Clinical Study: Human immunomodulatory trials are not available in the verified literature assembled for this document.

🎯 Hepatoprotection in controlled preclinical models (conflicting clinical safety)

Evidence Level: Low and conflicting

Note: Some processed/low-anthraquinone preparations reduce hepatocyte oxidative damage in preclinical models; however, many clinical case reports document hepatotoxicity associated with He Shou Wu products.

Clinical Study: No human hepatoprotection RCTs are available in the supplied dataset; clinical pharmacovigilance reports of hepatotoxicity are documented elsewhere.

🎯 Anticancer/cytotoxic effects (preclinical)

Evidence Level: Low

Mechanism: Emodin and related anthraquinones induce apoptosis in certain cancer cell lines but exhibit cytotoxicity at concentrations that raise safety concerns.

Clinical Study: No clinical oncologic indications; preclinical only.

🎯 Gastrointestinal motility (laxative) effects

Evidence Level: Medium

Mechanism: Anthraquinone aglycones are converted by gut bacteria to active laxative metabolites stimulating colonic secretion and motility.

Onset time: Typically hours after ingestion when anthraquinone content is sufficient.

Clinical Study: Pharmacology of anthraquinone laxatives is well-established across botanicals; specific He Shou Wu human trials correlating anthraquinone content to laxation are not presented here.

📊 Current Research (2020-2026)

Between 2020–2026 multiple preclinical and case‑report publications addressed He Shou Wu; however, this document does not include live PubMed/DOI lookups and therefore cannot provide PMIDs/DOIs inside these summaries.

If you require validated PMIDs/DOIs and exact quantitative results for studies from 2020–2026, please authorize a web/database search or allow me to fetch PubMed records; I will compile a verified list with consistent citation formatting (Author et al., Year. Journal. [PMID: XXXXXXXX]).

• Summary of research trends: increased focus on TSG pharmacology (antioxidant/neuroprotective), anthraquinone-related hepatotoxicity mechanism studies, and improved analytical quality control (HPLC fingerprinting, anthraquinone limits).
• Regulatory attention: case reports prompted monitoring and product-quality scrutiny.

💊 Optimal Dosage and Usage

Typical modern extract dosing: 200–1,000 mg/day; traditional decoctions generally employ 6–12 g/day of root — these are the commonly observed ranges in commercial and TCM practice.

Recommended Daily Dose (practical guidance)

• Standard supplement range: 200–1,000 mg/day of standardized extract (common market range).
• Traditional decoction: 6–12 g/day of raw or processed root in formulae (not directly comparable to concentrated extracts).
• By goal:
  • Hair/tonic: 300–600 mg/day standardized to TSG (conservative approach).
  • Antioxidant/support: 300–600 mg/day of aqueous extract.
  • Laxative: Not recommended due to safety concerns; anthraquinone-containing extracts cause stimulant laxative effects.

Timing

• Take with meals to reduce GI irritation and moderate absorption of lipophilic anthraquinones.
• Split dosing (morning/evening) may maintain steadier exposure for tonic aims.

Cycle duration and monitoring

• Due to hepatotoxicity reports, conservative cycling advised: 4–12 weeks on, 2–4 weeks off, with baseline and periodic liver function tests (LFTs) for prolonged use.
• Elderly: start low and monitor clinically and with labs.

🤝 Synergies and Combinations

Traditional formulas often pair He Shou Wu with other tonics; modern combinations aim to augment antioxidant effects or modify microbiome-mediated metabolism.

• Rehmannia: Complementary TCM tonic pairing for kidney/liver support.
• Curcumin: Potential additive antioxidant/Nrf2 effects (take with food and consider bioavailability enhancers for curcumin).
• Probiotics: May alter glycoside deglycosylation (TSG → aglycone) and modify pharmacokinetics.
• Antioxidant vitamins: Vitamin C/E for additive antioxidant support (hypothetical synergy).

⚠️ Safety and Side Effects

Hepatotoxicity is the principal safety concern: rare but serious cases of liver injury (ranging to fulminant hepatic failure) have been reported with He Shou Wu products.

Side effect profile (observed)

• Gastrointestinal: nausea, abdominal pain — frequency: common (exact % unknown).
• Diarrhea (anthraquinone laxative effect) — frequency: variable, dose-dependent.
• Elevated liver enzymes / jaundice — frequency: rare but clinically important.
• Allergic reactions — rare.

Overdose

• No clear human toxic threshold; animal LD50s exist but are not clinically translatable.
• Symptoms: severe diarrhea/dehydration, marked nausea/vomiting, and signs of liver injury (jaundice, dark urine).
• Management: immediate discontinuation, supportive care, LFTs, hepatology consultation; report adverse events to FDA MedWatch.

💊 Drug Interactions

He Shou Wu constituents (notably emodin) interact in vitro with CYP3A4 and P‑glycoprotein and its hepatotoxic potential can interact additively with other hepatotoxic drugs; exercise caution with several medication classes.

⚕️ Anticoagulants / Antiplatelet agents

• Medications: warfarin (Coumadin), clopidogrel (Plavix), aspirin.
• Interaction type: pharmacodynamic + potential PK via CYP modulation.
• Severity: High
• Recommendation: Avoid or monitor INR closely; consult prescriber.

⚕️ CYP3A4 substrates (statins, benzodiazepines)

• Medications: atorvastatin, simvastatin, midazolam.
• Interaction type: metabolic inhibition potential.
• Severity: Medium
• Recommendation: Caution; monitor for increased drug effects or adverse events.

⚕️ Hepatotoxic drugs

• Medications: isoniazid, high-dose acetaminophen, amiodarone.
• Interaction type: additive hepatotoxic risk.
• Severity: High
• Recommendation: Avoid combination when possible; if unavoidable, monitor serial LFTs.

⚕️ P‑gp substrates

• Medications: digoxin, tacrolimus.
• Interaction type: PK via transport inhibition.
• Severity: Medium
• Recommendation: Monitor drug levels and clinical signs; consult specialist for narrow‑index drugs.

⚕️ Immunosuppressants

• Medications: tacrolimus, cyclosporine.
• Interaction type: PK and possible PD.
• Severity: High
• Recommendation: Avoid or monitor blood levels closely; consult transplant team.

🚫 Contraindications

Absolute contraindications

• Active liver disease or unexplained prior liver injury.
• Known allergy to Polygonaceae family botanicals.
• Concurrent use of highly hepatotoxic drugs when monitoring is not feasible.

Relative contraindications

• Chronic alcohol use, obesity, viral hepatitis, metabolic syndrome.
• Concurrent anticoagulation (warfarin) without INR monitoring.

Special populations

• Pregnancy/breastfeeding: Not recommended—insufficient safety data.
• Children: Avoid—no validated pediatric dosing.
• Elderly: Use cautiously; start low and monitor LFTs and drug interactions.

🔄 Comparison with Alternatives

Compared with other adaptogens, He Shou Wu is unique for traditional hair/pigmentation claims but carries distinct hepatotoxicity concerns that make alternatives like Panax ginseng or Rhodiola preferable for general adaptogenic aims.

• Processed (zhi) vs raw (sheng): zhi generally favored in TCM and may have lower free anthraquinones.
• Aqueous vs ethanol extracts: aqueous favors TSG (safer profile); ethanol enriches anthraquinones (higher risk).

✅ Quality Criteria and Product Selection (US Market)

Choose products with clear botanical ID, processed/root specification, %TSG assay, anthraquinone quantification, GMP manufacturing, and accessible CoA from third‑party labs.

• Look for third‑party certifications: NSF, USP Verified, ConsumerLab (when available).
• Required tests on CoA: HPLC fingerprinting, emodin/total anthraquinone level, heavy metals, microbial limits, and residual solvents for ethanol extracts.
• Avoid vague proprietary blends and products lacking CoA transparency.

📝 Practical Tips

• Prefer processed (zhi) aqueous extracts standardized to TSG with documented low anthraquinone content.
• Start low (e.g., 300 mg/day) and monitor liver function for >8–12 weeks of use.
• Take with meals; avoid concurrent high-risk drug combinations without consulting providers.
• Report suspected adverse events to FDA MedWatch and preserve product lot/CoA for investigation.

🎯 Conclusion: Who Should Take He Shou Wu Extract?

He Shou Wu may be considered by individuals seeking traditional tonic support (hair pigmentation, antioxidant support) who accept that evidence is predominantly preclinical and understand hepatotoxic risks; prioritize processed aqueous extracts with third‑party testing and consult a clinician before use—especially those with liver disease or taking interacting medications.

Appendix: Research and Citation Limitations

This article synthesizes the supplied primary-source dossier and accepted mechanistic pharmacology principles; it does not include live PubMed/DOI lookups or specific PMIDs/DOIs for 2020–2026 studies.

If you require a follow-up document containing verified, itemized study citations with exact quantitative results and PMIDs/DOIs (formatted Author et al., Year. Journal. [PMID: XXXXXXXX]), please permit a direct literature search or provide access to PubMed/DOI data and I will compile the requested, fully verified citations and integrate them into the article sections and benefit claims.