St. John's Wort for Health & Longevity - Quick Reference Sheet

St. John's Wort for Health & Longevity

Created on 06/29/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 4.8 Audit

St. John's Wort is one of the best-evidenced plants for easing mild-to-moderate low mood, working about as well as standard antidepressants with milder side effects, plus moderate help for menopausal and premenstrual mood. The decisive issue is safety: it weakens a very wide range of medications and product quality varies widely. (Full Review)

Protocol

Dose
300 mg three times daily
900 mg/day total; some studies use 900–1,800 mg/day for moderate depression
Standardization
~0.3% hypericin, 1–4% hyperforin
Match a trial-validated extract (WS 5570, LI 160, ZE 117) where possible
Timing
Split across the day with food
Take the last dose earlier in the day if sleep is disrupted
Time to effect
Mood benefit
2–4 weeks
Fuller effect by 6 weeks with consistent dosing
Menopausal mood
8–12 weeks
Mood and hot-flash improvements build over an 8–12 week course
Topical preparations
Days
Red-oil and cream preparations act over days

Benefits

Contraindications
  • Narrow-therapeutic-index and life-sustaining drugs (immunosuppressants, warfarin, antiretrovirals, hepatitis C antivirals)
  • Serotonergic drugs (SSRIs, SNRIs, MAO inhibitors, triptans, tramadol, buspirone)
  • Hormonal contraception (oral, patch, ring, implant)
  • Bipolar disorder
  • Pregnancy and breastfeeding
  • Surgery (stop ≥5 days before)
Key Interactions
  • OTC medications (dextromethorphan, fexofenadine, serotonergic or adrenergic decongestants)
  • Serotonergic or mood-active supplements (5-HTP, L-tryptophan, SAMe, high-dose saffron)
  • Other photosensitizing botanicals

Risk & Side Effects

  • High: Drug interactions via enzyme and transporter induction
  • Medium: Serotonin syndrome with antidepressants and serotonergic drugs; photosensitivity
  • Low: Gastrointestinal, neurological, and psychiatric side effects; cardiovascular and withdrawal-type effects
  • Speculative: Reproductive and developmental effects; long-term and hepatic effects

Monitoring

Marker Target Why
INR (if on warfarin) Individualized target (often 2.0–3.0) Detect loss of anticoagulation from enzyme induction
Cyclosporine/tacrolimus level (if transplant) Drug- and protocol-specific therapeutic window Detect subtherapeutic immunosuppression risking rejection
HAM-D or PHQ-9 mood score Decreasing toward remission (e.g., PHQ-9 <5) Track antidepressant response and define success
Liver enzymes (ALT/AST) ALT/AST within ~10–30 U/L functional range Screen for rare hepatic effects on prolonged use
Vitamin D / general health panel 40–60 ng/mL vitamin D Context for mood and overall health optimization

Cadence: Mood at 2, 4, and 6 weeks, then every 4–8 weeks while in use; intensify any interacting drug's monitoring when starting and stopping St. John's Wort.

Qualitative Assessment

  • Mood stability and reduction in depressive symptoms
  • Energy levels and motivation
  • Sleep quality and any new sleep disruption
  • Skin sensitivity to sunlight (early sign of phototoxicity)
  • Any signs of overstimulation, agitation, or emerging mania