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

Created on 09/27/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5.5 – Audit

St. John's wort, a yellow-flowering plant whose standardized extracts are sold for low mood, offers modest relief of mild-to-moderate low mood with side effects usually milder than prescription antidepressants. Its main active compound makes the body clear many medications faster, which can undermine transplant, clot-preventing, contraceptive, antiviral and cancer medications; with other antidepressants it can cause serious adverse reactions. Its value depends on careful attention to everything else being taken. (Full Review)

Protocol

Standard extract regimen
300 mg three times daily (900 mg/day)
Extract standardized to 0.3% hypericin and/or 1–3% hyperforin; studied range 600–1,800 mg/day
Low-hyperforin regimen
Ze 117 at about 500 mg/day
Narrower efficacy literature for a much smaller interaction profile
Time of day
Divided doses with meals
Morning, midday and evening in trials; meals reduce gastrointestinal upset
Time to effect
Mood effects
2–4 weeks
Plateau by 6–8 weeks
Unexplained physical symptoms
6 weeks
Response assessed after 6 weeks at 600 mg/day
Hot flashes
4–8 weeks
Reductions seen within this window

Benefits

Contraindications
  • Organ transplant recipients taking cyclosporine, tacrolimus or sirolimus
  • HIV treatment with protease inhibitors or non-nucleoside reverse transcriptase inhibitors
  • Chemotherapy or targeted cancer drugs metabolized by CYP3A4 (irinotecan, imatinib, docetaxel)
  • Bipolar I or II disorder, or any past episode of mania or hypomania
  • Schizophrenia or another psychotic disorder
  • Severe depression (PHQ-9 score of 20 or more), psychotic features or active suicidal thoughts
  • Pregnancy or breastfeeding
  • Light-sensitivity disorders (porphyria, cutaneous lupus) or within two weeks of planned photodynamic or laser treatment
  • Within two weeks of elective surgery
    •
Key Interactions
  • Anticoagulants (blood thinners: warfarin, rivaroxaban, apixaban): avoid or monitor closely
  • Serotonergic antidepressants and related drugs (sertraline, fluoxetine, venlafaxine, triptans, tramadol, buspirone): avoid combining
  • Hormonal contraceptives (ethinyl estradiol with norethindrone, levonorgestrel): caution
  • Heart and cholesterol drugs (digoxin, simvastatin, verapamil, ivabradine): caution
  • Sedatives and opioids (alprazolam, midazolam, methadone, oxycodone): caution
  • Sulfonylureas (insulin-releasing diabetes drugs: gliclazide, glipizide): monitor
  • Proton pump inhibitors (stomach-acid reducers: omeprazole, esomeprazole): monitor
  • Dextromethorphan (cough suppressant) and other serotonergic cold remedies: caution
  • Fexofenadine and loperamide (drugs moved out of cells by the P-glycoprotein pump): monitor
  • Serotonergic supplements with additive effects (5-HTP, L-tryptophan, SAMe, saffron): caution
  • Photosensitizing botanicals (bergamot oil, dong quai): caution
  • Red yeast rice (monacolin K): monitor
  • Light-based procedures (ultraviolet phototherapy, bright-light therapy): caution
  • Tyramine-rich foods (aged cheese, cured meats, draft beer): monitor
    •

Risk & Side Effects

  • High: Reduced effectiveness of co-administered medications; mild gastrointestinal upset, headache, dizziness and fatigue
    •
  • Medium:
  • Low: Increased skin sensitivity to sunlight; serotonin syndrome with serotonergic drugs; mania, hypomania or psychosis in susceptible people; impaired glucose tolerance; harm in pregnancy or to breastfed infants
    •
  • Speculative:

Monitoring

Marker Target Why
PHQ-9 score Below 5 (minimal symptoms) Tracks mood response
Fasting glucose 72–90 mg/dL Detects glucose-tolerance effect
HbA1c Under 5.4% Three-month glucose average
ALT Under 25 U/L Baseline liver function
INR (warfarin users only) Prescriber's therapeutic range (usually 2.0–3.0) Detects loss of anticoagulation
Trough levels of narrow-margin drugs Prescriber's therapeutic range Detects faster drug clearance

Cadence: Baseline; 2 weeks (drug levels or INR if applicable); 4 and 8 weeks (PHQ-9 response); 3 months (glucose and HbA1c); then every 6 months while use continues; repeat drug-level check 2 weeks after stopping

Qualitative Assessment

  • Mood, motivation and enjoyment of daily activities
  • Energy and daytime fatigue
  • Sleep quality and restlessness at night
  • Hot-flash frequency and severity (daily diary, for menopausal women)
  • Skin reactions after sun exposure
  • Signs of mood elevation: reduced sleep need, racing thoughts, irritability
  • Breakthrough bleeding in women on hormonal contraception
Not medical advice. Educational distillation of a single evidence review. Confirm any decision with a qualified clinician, especially in the presence of prescription drugs or chronic conditions.