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

St. John's Wort for Health & Longevity

Created on 09/22/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

St. John's Wort is a flowering plant sold as a standardized oral extract for low mood. It eases mild-to-moderate low mood about as well as standard antidepressant medications, with fewer side effects; menopausal, premenstrual, and seasonal signals are weaker. The defining issue is interference, not toxicity: it speeds drug clearance, quietly weakening birth control, blood thinners, and transplant medicines. (Full Review)

Protocol

Standard dose and formulation
900 mg/day
300 mg three times daily of a hydroalcoholic extract standardized to ~0.3% hypericin; up to 1,800 mg/day for partial responders.
Competing approaches, presented without a default
High- vs low-hyperforin extract
High-hyperforin (WS 5570, LI 160) maximizes potency at full interaction risk; low-hyperforin (Ze 117) aims to reduce enzyme induction. Neither is established as superior.
Best time of day
With meals, split across the day
Taken with meals to reduce stomach upset; no circadian requirement. Doses weighted earlier where restlessness or sleep disturbance occurs.
Time to effect
Mood benefit
2–4 weeks
About 2–4 weeks of consistent dosing before change is noticed.
Fuller effect
~6 weeks
Similar to conventional antidepressants; no change by 6 weeks argues against continued benefit.
Intended duration
4–12 weeks
A defined course rather than a lifelong supplement; trials run 4–12 weeks.

Benefits

Contraindications
  • Any narrow-therapeutic-index medication (transplant immunosuppressants, HIV antiretrovirals, warfarin or DOACs)
  • Reliance on hormonal contraception
  • Bipolar disorder
  • Any SSRI, SNRI, or MAOI
  • Pregnancy or breastfeeding
  • Severe major depression or active suicidality
  • Within about 5 days of scheduled surgery
Key Interactions
  • Prescription drug interactions (reduced drug levels via enzyme/P-gp induction): statins (simvastatin), cardiac drugs (digoxin), anticonvulsants (carbamazepine), chemotherapy agents (imatinib), methadone, theophylline
  • Serotonergic prescription drugs (additive effect): triptans (sumatriptan), tramadol
  • Over-the-counter medication interactions: dextromethorphan; drugs cleared by CYP3A4
  • Supplement interactions (additive serotonergic): 5-HTP, L-Tryptophan, SAMe, saffron
  • Supplements with additive antidepressant intent: omega-3 fatty acids, saffron, SAMe
  • Other intervention interactions: light therapy, photodynamic treatments, surgery (anesthetics)

Risk & Side Effects

  • High: Drug Interactions via Enzyme Induction
  • Medium: Serotonin Syndrome with Serotonergic Agents; Photosensitivity
  • Low: Mild Gastrointestinal and Nervous System Effects; Induction of Mania in Bipolar Disorder; Discontinuation Symptoms
  • Speculative: Rare Liver Effects; Effects on Male Fertility

Monitoring

Marker Target Why
PHQ-9 (depression symptom score) 0–4 (minimal) Tracks whether mood is actually improving
ALT (liver enzyme) < 25 U/L (men), < 20 U/L (women) Screens for the rare liver signal and baseline for interacting drugs
INR (blood-clotting time) Condition-specific (typically 2.0–3.0 if on warfarin) Detects loss of blood-thinning effect from enzyme induction
hs-CRP (inflammation marker) < 1.0 mg/L Tracks the inflammation–mood link and a longevity-relevant marker
TSH (thyroid function marker) 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: Baseline; reassess mood and tolerability at about 2 and 6 weeks, then every 3–6 months during continued use. On an interacting essential medication, add drug-specific checks (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
  • Any skin sensitivity or rash after sun exposure
  • Signs of over-activation (agitation, racing thoughts) suggesting a manic switch or serotonin excess