Supplement analysis backed by scientific evidence · PT

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Strong evidenceStress & mood

St John's Wort

St John's Wort is the rare herbal supplement with genuinely strong efficacy data — it works about as well as standard antidepressants for mild-to-moderate depression, with better tolerability. The catch is that it is also the single most dangerous herb for drug interactions, capable of causing contraceptive failure and transplant rejection.

What the science says

  • Treats mild-to-moderate major depression Strong evidence

    A Cochrane review of 29 randomised trials in 5,489 patients found Hypericum extracts superior to placebo and comparable in efficacy to standard antidepressants including SSRIs and tricyclics. Effect sizes were notably larger in German-speaking-country trials than elsewhere, suggesting the true effect is somewhat smaller than the pooled figure implies.

  • Better tolerated than standard antidepressants Strong evidence

    In the same Cochrane analysis, patients on Hypericum were substantially less likely to drop out because of adverse events than those on older tricyclics, and modestly less likely than those on SSRIs. Rates of sexual dysfunction and weight gain are generally lower than with SSRIs.

  • Treats severe depression Limited evidence

    Trials in severe or treatment-resistant major depression are few and results are inconsistent, and most positive trials enrolled mild-to-moderate cases. It should not be used as monotherapy for severe depression, suicidality or bipolar depression.

  • Reduces menopausal or premenstrual symptoms Limited evidence

    Several small trials report improvement in hot flushes and PMS symptoms, sometimes in combination with black cohosh. These studies are small and heterogeneous, and the interaction risk with hormonal therapies is a serious practical barrier.

Dosage & safety

Studied doseTrials most commonly used a standardised extract at 300 mg three times daily (900 mg/day), typically standardised to 0.3% hypericin or 3-6% hyperforin; some trials used up to 1,800 mg/day. Onset takes 2-4 weeks, with 6-12 weeks needed for full assessment. Extracts differ substantially in hyperforin content — hyperforin is the constituent that drives the interaction problem, and low-hyperforin preparations interact less.
SafetyThe interaction profile is the dominant safety issue. St John's Wort is a potent inducer of CYP3A4, CYP2C9 and P-glycoprotein and is the herb most frequently implicated in clinically significant herb-drug interactions. It reduces plasma levels of hormonal contraceptives, causing breakthrough bleeding and documented contraceptive failure and unintended pregnancy; use an additional non-hormonal method. It can cause transplant rejection by lowering cyclosporine and tacrolimus, and reduces the effectiveness of warfarin, direct oral anticoagulants, HIV protease inhibitors and NNRTIs, many chemotherapy agents, digoxin, statins, anticonvulsants and theophylline. Combining it with SSRIs, SNRIs, triptans, tramadol or MAOIs risks serotonin syndrome. It causes photosensitivity, especially in fair-skinned people at higher doses, and can trigger mania or hypomania in people with bipolar disorder. Stopping it abruptly can also destabilise levels of drugs whose metabolism it was inducing. It is a prescription-only medicine in some countries, including Ireland, and is restricted in others. Tell every prescriber you take it, and do not start it without checking your full medication list.

Scientific references

Where to buy

Swanson Vitamins, Full Spectrum® St. John's Wort, 375 mg, 120 Vegan Capsules

View on iHerb

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