# St. John's Wort (Hypericum perforatum)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/st-john-s-wort
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-19
**Evidence Score:** 8 / 10
**Category:** European
**Also Known As:** Hypericum perforatum, Perforate St John's-wort, Common St John's wort, Goatweed, Klamath weed, Tipton's weed, Chase-devil, Amber

## Overview

St. John's Wort (Hypericum perforatum) is a European herb containing hypericin (0.0095-0.466%) and hyperforin (2-4.5%) as primary bioactive compounds. These compounds interact with CYP enzymes including CYP3A4 and CYP1A2, though clinical evidence remains limited.

## Health Benefits

• Limited clinical evidence available - research dossier contains no specific human trials or outcomes data
• Contains hypericin (0.0095-0.466%) and hyperforin (2-4.5%) as primary bioactive compounds
• Phloroglucinols interact with CYP enzymes including CYP3A4 and CYP1A2
• Rich in flavonoids (2-12% total) including hyperoside, quercitrin, and rutin
• Contains phenolic acids, tannins (3-16%), and amino acids including GABA

## Mechanism of Action

St. John's Wort's primary bioactive compounds hypericin and hyperforin interact with cytochrome P450 enzymes, specifically CYP3A4 and CYP1A2. The phloroglucinol derivatives, particularly hyperforin, modulate hepatic enzyme activity and may affect [neurotransmitter](/ingredients/condition/cognitive) pathways. Flavonoids comprising 2-12% of the extract provide additional bioactive properties through [antioxidant](/ingredients/condition/antioxidant) mechanisms.

## Clinical Summary

Current research dossier contains no specific human clinical trials or quantified outcomes data for St. John's Wort. Available evidence is limited and lacks standardized study protocols with measurable endpoints. The absence of controlled human trials makes it difficult to establish definitive therapeutic efficacy. Most available data focuses on phytochemical composition rather than clinical outcomes.

## Nutritional Profile

St. John's Wort (Hypericum perforatum) is primarily valued as a medicinal herb rather than a nutritional food source. Its key bioactive compounds dominate its profile: Hypericin and pseudohypericin (naphthodianthrone derivatives) at 0.0095–0.466% dry weight, serving as marker compounds for standardization; Hyperforin and adhyperforin (phloroglucinol derivatives) at 2–4.5% dry weight, considered primary active constituents for neuromodulatory effects. Flavonoids constitute 2–12% total dry weight, including hyperoside (quercetin-3-galactoside, ~0.5–2%), quercitrin (~0.3–1%), rutin (~0.3–0.8%), isoquercitrin, kaempferol, and luteolin glycosides; these exhibit moderate oral bioavailability (20–50%) influenced by gut microbiota [metabolism](/ingredients/condition/weight-management) and efflux transporters. Phenolic acids include chlorogenic acid, caffeic acid, and protocatechuic acid at trace to minor levels (~0.1–0.5%). Tannins (condensed and hydrolysable) range from 3–16% dry weight, contributing astringent properties but potentially reducing absorption of co-administered compounds. Essential oils comprise approximately 0.05–0.9%, containing caryophyllene, humulene, and pinene. Macro/micronutrient content is nutritionally insignificant; the herb provides negligible protein (<5% DW), minimal lipids (<3% DW), and modest carbohydrates. Bioavailability notes: Hyperforin is highly lipophilic (LogP ~7), requiring micellar solubilization for absorption; peak plasma concentrations observed 3–4 hours post-ingestion. Hypericin bioavailability is low (~14%) due to poor aqueous solubility. Flavonoid glycosides require intestinal hydrolysis to aglycone forms prior to absorption. CYP3A4 and CYP1A2 induction by hyperforin significantly alters co-administered drug pharmacokinetics, reducing systemic exposure of numerous medications.

## Dosage & Preparation

No clinically studied dosage ranges are specified in the research dossier for extracts, powder, or standardized forms. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

St. John's Wort significantly interacts with medications metabolized by CYP3A4 and CYP1A2 enzymes, potentially altering drug effectiveness. Common interactions include reduced efficacy of birth control pills, blood thinners, and certain antidepressants. Side effects may include photosensitivity, gastrointestinal upset, and dizziness. Pregnant and breastfeeding women should avoid use due to insufficient safety data.

## Scientific Research

The research dossier provides no specific details on human clinical trials, RCTs, or meta-analyses for Hypericum perforatum. No PMIDs, study designs, sample sizes, or clinical outcomes are available in the provided sources.

## Historical & Cultural Context

The research dossier provides no information on historical context, traditional medicine systems, or traditional indications for Hypericum perforatum. Duration of traditional use is not specified in the available sources.

## Synergistic Combinations

Insufficient research data to determine synergistic ingredients

## Frequently Asked Questions

### Does St. John's Wort help with depression?

St. John's Wort is one of the most studied herbal approaches for low mood, with its primary compounds hypericin and hyperforin believed to modulate neurotransmitter pathways. Hyperforin in particular may influence serotonin, dopamine, and norepinephrine activity in the brain. However, the research dossier for this ingredient contains no specific human trial data or confirmed clinical outcomes. Anyone experiencing depression should consult a qualified healthcare provider before using St. John's Wort, particularly given its significant interactions with prescription medications.

### Can I take St. John's Wort with antidepressants?

Taking St. John's Wort alongside antidepressants, especially SSRIs or MAOIs, is strongly cautioned against without medical supervision. Hyperforin modulates neurotransmitter pathways, and combining it with prescription antidepressants risks a potentially serious condition known as serotonin syndrome, characterised by agitation, rapid heart rate, and high body temperature. Additionally, St. John's Wort activates CYP3A4 and CYP1A2 enzymes, which can reduce blood levels of many co-administered drugs. Always consult a healthcare provider before combining any herbal supplement with prescription medications.

### What medications does St. John's Wort interact with?

St. John's Wort has a broad drug interaction profile driven primarily by its activation of CYP3A4 and CYP1A2 cytochrome P450 enzymes. This enzyme induction can significantly reduce plasma concentrations of medications including antiretrovirals, cyclosporine, warfarin, certain chemotherapy agents, statins, and benzodiazepines, potentially compromising their effectiveness. The phloroglucinol compound hyperforin is considered the principal driver of these interactions. Patients on any long-term prescription medication should disclose St. John's Wort use to their prescribing physician before starting supplementation.

### How long does St. John's Wort take to work?

A specific onset timeline is not established within the available research for this ingredient. In general herbal medicine contexts, St. John's Wort is often used for several weeks before effects are assessed, consistent with the timeframes observed with conventional antidepressants. However, no clinically validated timelines from human trials are available in the current research dossier. Individual responses may vary based on extract quality, standardisation of hypericin and hyperforin content, dosage, and personal health factors. Consult a healthcare provider for personalised guidance.

### Is St. John's Wort safe for long-term use?

Long-term safety data for St. John's Wort supplementation is not detailed in the available research dossier. Known concerns with extended use include persistent induction of CYP3A4 and CYP1A2 enzymes, which could chronically alter metabolism of co-administered medications, and potential photosensitivity from hypericin accumulation. The flavonoid and tannin content ranging up to 12% and 16% respectively may have additional biological effects over time. Anyone considering prolonged use should do so under medical supervision, particularly if taking prescription medications.

### What is the standard dose of St. John's Wort extract?

No clinically validated dosage range is specified in the research dossier for St. John's Wort in any form, including standardised extracts, powders, or teas. Commercial products are commonly standardised to hypericin content between 0.0095% and 0.466%, or to hyperforin at 2–4.5%, but specific effective doses from human trials are not confirmed in the available evidence. Dosage requirements may vary by individual health status, purpose, and formulation. A qualified healthcare provider or pharmacist should be consulted before starting supplementation.

### Does St. John's Wort help with anxiety?

St. John's Wort contains GABA as one of its amino acid constituents, and its flavonoid fraction including hyperoside, quercitrin, and rutin may contribute bioactive properties relevant to nervous system function. Hyperforin's influence on neurotransmitter pathways could theoretically extend to anxiety-related mechanisms. However, no specific human clinical trial data confirming efficacy for anxiety is available in the current research dossier. The evidence base remains limited and uncertain. Those experiencing clinically significant anxiety should seek professional medical evaluation rather than relying solely on herbal supplementation.

### What is the difference between hypericin and hyperforin in St. John's Wort?

Hypericin and hyperforin are the two primary bioactive compounds in St. John's Wort with distinct chemical profiles. Hypericin is a naphthodianthrone present at 0.0095–0.466% and is associated with photosensitivity reactions. Hyperforin is a phloroglucinol derivative present at 2–4.5% and is considered the main driver of CYP3A4 and CYP1A2 enzyme induction, contributing to the herb's extensive drug interaction profile. Hyperforin is also the compound most associated with neurotransmitter modulation. Standardised extracts may target one or both compounds depending on the intended application.

### What are the active compounds in St. John's Wort?

St. John's Wort contains hypericin at concentrations of 0.0095-0.466% and hyperforin at 2-4.5% as primary bioactive compounds. The herb also contains flavonoids comprising 2-12% of the total extract composition.

### Does St. John's Wort interact with birth control pills?

Yes, St. John's Wort interacts with CYP3A4 enzymes that metabolize birth control hormones, potentially reducing contraceptive effectiveness. This interaction can lead to breakthrough bleeding and unintended pregnancy.

### How much clinical evidence exists for St. John's Wort?

Current research dossiers contain no specific human trials or quantified outcomes data for St. John's Wort. Available evidence is limited and lacks standardized clinical protocols with measurable therapeutic endpoints.

### Can St. John's Wort cause photosensitivity?

Yes, hypericin in St. John's Wort can cause increased sensitivity to sunlight and UV radiation. Users may experience skin reactions, rashes, or sunburn more easily when exposed to sunlight during supplementation.

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*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
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