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

St. John's Wort for Health & Longevity

Created on 08/03/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 4.8 Audit

Standardized extracts ease mild-to-moderate low mood about as well as standard antidepressants, with fewer side effects. Weaker signals cover menopausal and premenstrual symptoms, winter low mood, and topical wound care. The defining catch is interference: it speeds the body's drug-clearing systems, quietly weakening birth control, blood thinners, and many other medications. Not shown for severe depression. (Full Review)

Protocol

Dose
900 mg/day
300 mg three times daily
Formulation
0.3% hypericin extract
Standardized hydroalcoholic capsules
Timing
With meals
Split across three daily doses
Time to effect
Notice change
2–4 weeks
First mood improvement
Fuller effect
~6 weeks
Similar to conventional antidepressants
Steady state
A few days
Blood levels stabilize before mood benefit

Benefits

Contraindications
  • Narrow-therapeutic-index medications (transplant immunosuppressants, HIV antiretrovirals, warfarin, DOACs)
  • Hormonal contraception
  • Bipolar disorder
  • SSRIs, SNRIs, or MAOIs
  • Pregnancy or breastfeeding
  • Severe major depression or active suicidality
  • Within ~5 days of scheduled surgery
Key Interactions
  • Reduced levels of statins, digoxin, calcium channel blockers, chemotherapy (imatinib, irinotecan), methadone, theophylline
  • Serotonergic drugs (triptans, tramadol, dextromethorphan)
  • Serotonergic supplements (5-HTP, L-Tryptophan, SAMe, saffron)
  • Light therapy and photodynamic treatments
  • Anesthetics before surgery

Risk & Side Effects

  • High: Drug interactions via enzyme induction
  • Medium: Serotonin syndrome with serotonergic agents; photosensitivity
  • Low: Mild gastrointestinal and nervous system effects; mania in bipolar disorder; discontinuation symptoms
  • Speculative: Rare liver effects; effects on male fertility

Monitoring

Marker Target Why
PHQ-9 0–4 (minimal) Tracks whether mood is actually improving
ALT < 25 U/L (men), < 20 U/L (women) Screens for the rare liver signal and baseline for interacting drugs
INR 2.0–3.0 (if on warfarin) Detects loss of blood-thinning effect from enzyme induction
hs-CRP < 1.0 mg/L Contextualizes the inflammation–mood link and tracks a longevity-relevant marker
TSH 1.0–2.0 mIU/L Rules out thyroid disease masquerading as depression
25-hydroxyvitamin D 40–60 ng/mL Low vitamin D is linked to low mood and is easily corrected

Cadence: Reassess mood and tolerability at ~2 and 6 weeks, then every 3–6 months; for those on an interacting essential medication, add drug-specific checks such as INR within 1–2 weeks of starting and stopping

Qualitative Assessment

  • Overall mood, motivation, and interest in usual activities
  • Energy levels and daytime fatigue
  • Sleep quality and dream intensity
  • Cognitive clarity and concentration
  • Skin sensitivity or rash after sun exposure
  • Signs of over-activation (agitation, racing thoughts) that could indicate a manic switch or serotonin excess