hyperforin

PhytochemicalPhloroglucinolBest with a meal

What is it

Hyperforin is a prenylated phloroglucinol compound from St. John's wort (Hypericum perforatum) now thought to be the principal active responsible for antidepressant effects of the herb.

Evidence for 1 use

AI-assisted evidence assessment — talk to your doctor before relying on any single supplement.

Mild to moderate depression

Strong Evidence

St. John's wort extracts containing hyperforin show comparable efficacy to SSRIs for mild to moderate depression in multiple RCTs and meta-analyses, but with significant interaction risks.

How it works

Hyperforin inhibits reuptake of serotonin, norepinephrine, dopamine, GABA, and glutamate by activating TRPC6 channels, in a mechanism distinct from classic SSRIs. It is also a strong activator of the pregnane X receptor (PXR), which drives induction of CYP3A4 and P-glycoprotein and is the cause of St. John's wort's many drug interactions.

Dosage

Clinical St. John's wort extracts are often standardized to 3-5% hyperforin and dosed at 300 mg three times daily.

When and how to take it

St. John's wort with hyperforin is typically taken with meals two or three times daily.

1 commercial form

Compare the main delivery options and what they’re best suited for.

St. John's wort extract standardized to hyperforin

Most common research and consumer form.

Hyperforin is orally bioavailable; concentrations track with extract type.

Safety

Reasonably well tolerated for short to medium term in depression trials. Adverse effects include GI upset, dry mouth, fatigue, and photosensitivity at high doses.

Who should be cautious

Avoid combining with serotonergic medications, hormonal contraceptives, antiretrovirals, immunosuppressants, and many other drugs. Discuss with a clinician or pharmacist before starting. Pregnancy and breastfeeding data are limited.

Interactions

Hyperforin causes the major drug interactions of St. John's wort through CYP3A4 and P-glycoprotein induction. Affected drugs include hormonal contraceptives, antiretrovirals, immunosuppressants, warfarin, and many others.

Food sources

St. John's wort plant

Amount
varies
%DV
—

Frequently asked questions

Is hyperforin sold by itself?⌄

Rarely. It is usually present as part of a standardized St. John's wort extract.

Why does hyperforin cause so many drug interactions?⌄

It activates the pregnane X receptor, which induces CYP3A4 and P-glycoprotein, increasing breakdown of many medications. Always check interactions with a clinician or pharmacist.

References

hyperforin on Wikidata — Wikidata link

hyperforin on NIH DSLD (US supplement label database) — NIH Dietary Supplement Label Database link

Research on hyperforin (PubMed search) — PubMed link

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Evidence-based·How we grade evidence

Disclaimer: These statements have not been evaluated by the FDA. This page is educational, not a substitute for personalized medical advice. Evidence grades are AI-assisted assessments — talk to your doctor before starting any new supplement, especially if you’re pregnant, breastfeeding, on medications, or managing a chronic condition.