Stack Genius ingredient guide

St. John's Wort

St. John's wort (Hypericum perforatum) is a yellow-flowered perennial herb native to Europe whose extracts contain hypericin, hyperforin, and other bioactive compounds that influence neurotransmitter systems.

Specialty Compounds & Other Dietary Ingredients 2 sources

Overview

St. John's wort is a bright yellow-flowered plant that has been used in European traditional medicine since ancient times. Modern research identified two families of active compounds, hypericin and hyperforin, that influence multiple neurotransmitter systems including serotonin, dopamine, and norepinephrine. This broad mechanism is what makes the herb pharmacologically active and what makes it interact with an unusually long list of prescription medications.

In supplements, St. John's wort is sold primarily as a standardized extract (typically standardized to 0.3% hypericin or 3% to 5% hyperforin) in capsule and tincture form. It is used in mood-support and emotional-wellness supplement formulas, sometimes marketed for premenstrual and menopausal contexts.

Because of its extensive drug interaction profile, St. John's wort is one of the most important supplements to discuss with a healthcare provider before use. NCCIH has an unusually detailed resource on the herb specifically because of these considerations, and it should be treated as a serious ingredient rather than a background wellness supplement.

Key takeaways

Practical guidance

What to know before adding St. John's Wort

Evidence snapshot

NCCIH's dedicated resource summarizes that St. John's wort has been studied more thoroughly than most botanicals, with clinical trials suggesting effects on mild-to-moderate mood concerns. Results vary and are not uniform across studies. What is unambiguously well established is the drug interaction profile, which is more extensive than for almost any other supplement ingredient.

What to look for on the label

Look for standardization to hypericin (commonly 0.3%) or hyperforin (commonly 3% to 5%). The plant part should be aerial parts (flowering tops). Extract ratios and per-capsule milligram amounts should be clearly disclosed. Reputable products carry prominent drug interaction warnings on the label itself.

What makes a better product

Better St. John's wort products use standardized extracts with disclosed hypericin and hyperforin content, include clear drug interaction warnings on the label, and are made by manufacturers that maintain consistency across lots (important because active content varies with harvest). Cold or low-heat extraction preserves hyperforin, which is heat-sensitive.

Watch-outs

St. John's wort interacts with a very broad range of medications by inducing liver enzymes (CYP3A4, others) and P-glycoprotein transport. Affected drug classes include hormonal contraceptives (can reduce effectiveness), antidepressants (serotonin syndrome risk), warfarin, HIV medications, immunosuppressants, some chemotherapy drugs, digoxin, and many others. It can also increase photosensitivity. Prescription antidepressants and other serotonergic medications are a major red flag because of serotonin syndrome risk.

Dosing & Timing

Clinical studies commonly use 300 mg of standardized extract three times daily (900 mg total) for at least four to six weeks to evaluate effects. Some formulations use higher-hyperforin content and different dose schedules. Taking with food may reduce mild GI upset. Effects, if any, typically develop over weeks rather than immediately.

Safety and interaction context

The drug interaction profile is the primary safety concern. Contraindicated with SSRIs, SNRIs, MAO inhibitors, triptans, and other serotonergic medications. Reduces effectiveness of many drugs metabolized by CYP450 enzymes, including some hormonal contraceptives, HIV medications, immunosuppressants, warfarin, and digoxin. Increases photosensitivity. Not recommended in pregnancy, nursing, or before surgery.

Sources

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This information is general educational content only. Research may be limited, inconclusive, conflicting, outdated, or not applicable to your circumstances. This content does not recommend that you start, stop, or change any supplement, medication, dose, or health routine. Talk with a qualified healthcare professional before making health-related decisions.