Hypericin and Hyperforin: The Active Compounds in St. John's Wort

Anyone who looks into St. John's wort (Hypericum perforatum) quickly comes across two names: hypericin and hyperforin. They are considered the characteristic compounds of the plant and appear on many labels as percentage figures. This guide explains, purely from a botanical standpoint, what lies behind these two substances, how extracts are standardised to them, and what you can look for when choosing a product.

What are hypericin and hyperforin?

St. John's wort is a wild-growing perennial whose yellow flowers open between June and August. If you rub a bud between your fingers, a reddish sap emerges – a first visible sign of the pigments it contains. Chemically, the plant is remarkably diverse: it contains several groups of compounds, of which hypericin and hyperforin are the best known.

Hypericin belongs to what are known as the naphthodianthrones, a group of red plant pigments. Together with the closely related pseudohypericin, it is responsible for the dark red colour of the plant's sap. These pigments are found mainly in the small dark glands on the flowers and leaves that give the herb its characteristic, dotted appearance – hence the botanical epithet perforatum ("perforated").

Hyperforin, by contrast, belongs to the group of phloroglucinol derivatives and is one of the plant's bitter compounds. It is chemically much more sensitive than hypericin: hyperforin reacts readily with light and oxygen and breaks down comparatively quickly during drying, storage and processing. This instability is one of the reasons why manufacturing and storing products containing St. John's wort is demanding.

Why these two compounds are considered marker substances

A plant contains hundreds of individual compounds, and their composition varies depending on location, harvest time and weather. For a product to remain comparable from batch to batch, measurable reference values are needed. This is precisely the role that hypericin and hyperforin play: as what are known as marker compounds, they can be reliably measured analytically and serve as the yardstick by which the content and consistency of an extract are read off.

In practice, this means a manufacturer states how much hypericin (often given as "total hypericins", i.e. including pseudohypericin) or hyperforin a product contains. These figures make it possible to see whether a product is a concentrated, standardised preparation or simply ground herb. They are therefore a key quality feature when assessing a product – more on this in the guide Buying St. John's Wort: What to Look For.

Understanding extract ratio and standardisation

Two terms come up again and again with St. John's wort products: the extract ratio (drug-extract ratio, DER) and standardisation. Both describe how concentrated an extract is and how precisely its content has been set.

The drug-extract ratio (DER)

The extract ratio indicates how much dried starting herb was used to obtain one unit of dry extract. A figure such as "3–7:1" means that three to seven grams of raw herb were used per gram of extract. The higher the first number, the more concentrated the plant material. The ratio is given as a range because the raw material is subject to natural variation.

Standardisation to a defined content

Standardisation means the extract is adjusted to a fixed proportion of a marker compound – for example, to a specific percentage of total hypericins. This way, every capsule or tablet in a batch contains a comparable content, regardless of how strong that particular harvest turned out to be. For food supplements, the solvent used is also relevant: aqueous, alcoholic or oil-based extracts dissolve out the individual compounds to different degrees, so the compound profile differs depending on the production method. You can read about the different forms available and how they differ in the article St. John's Wort: Use, Forms and Interactions.

Forms and content: herb, extract, oil

St. John's wort is offered in very different forms, and the content of hypericin and hyperforin varies accordingly:

• Dried herb and tea: here the compounds are present in their natural, non-concentrated amount. How much of this transfers into an infusion depends heavily on water temperature and steeping time.
• Dry extracts in capsules or tablets: these are concentrated and usually standardised to a marker compound. The content is declared most precisely here.
• Red oil (oil macerate): this red-coloured oil, obtained by macerating flowers in vegetable oil, is traditionally used externally. Its red colour comes from the hypericin-related pigments.

Because hyperforin is more sensitive than hypericin, its proportion can vary considerably depending on processing and storage time – a freshly made product, packed tightly and away from light, preserves the bitter compounds better than goods stored loose and exposed to light.

Origin, harvest and the content of the marker compounds

How much hypericin and hyperforin a plant contains is decided long before processing – namely, in the field. The content of the marker compounds varies depending on sunlight, soil, altitude and harvest time. The upper, flowering shoot tips shortly after blooming are considered especially rich in compounds; woody stem parts, by contrast, contribute little. Traditionally, the herb is therefore harvested around the summer solstice, when flowering is at its peak.

An equally important step follows the harvest: gentle drying. Because hyperforin reacts sensitively to heat and oxygen, drying that is too hot or too long can noticeably reduce the content. Reputable manufacturers document the origin and processing of their raw material and state the content of the marker compounds per batch. This traceability is a good reference point for comparing products objectively.

Interactions: the most important point to know first

St. John's wort is known for the fact that its compounds can interfere with the processes by which the body breaks down numerous drugs. Hyperforin is considered the substance that interacts particularly strongly with the breakdown of other substances in the liver. The result can be that medications taken at the same time are broken down more quickly and therefore become less effective. This point is so important that it takes precedence over every other consideration.

Interactions are especially relevant with:

• hormonal contraceptives ("the pill"): the reliability of contraception can be impaired. Background on this in the guide Food Supplements and the Pill.
• blood thinners (anticoagulant medications),
• certain antidepressants,
• immunosuppressants (for example after transplants),
• as well as other drug groups such as certain heart, HIV or cancer medications.

If you take medication regularly, are pregnant or breastfeeding, be sure to speak with your doctor or pharmacist before using a product containing St. John's wort. This professional guidance cannot be replaced by your own research.

Clearly distinguishing food supplements from medicines

St. John's wort is available both as a registered or approved medicine and as a food supplement – and legally, the two are not the same thing. Medicines go through a regulatory procedure and are intended for a specific therapeutic purpose, about which only the relevant product information and medical professionals can advise. A food supplement, by contrast, is a food: it provides plant extract in dosed form and serves to complement a normal diet, without having the status of a medicine.

For you as a buyer, this means: the figures for hypericin and hyperforin content describe the composition of the product – that is, which compounds are present in what amount. When comparing products, keep in mind that the two product categories may be labelled according to different rules.

What you can look for in terms of quality

From a botanical standpoint, a few features can be named that distinguish a well-made product: a clear statement of the extract ratio, transparent standardisation to total hypericins or hyperforin, origin and batch information, and light- and airtight packaging that protects the sensitive bitter compounds. Dark brown glass bottles or opaque blister packs make more sense here than transparent containers. The production and best-before dates also give clues as to how fresh the extract is.

It's also worth checking the ingredient list: a high-quality product generally gets by with just a few, clearly named components. The more traceably a manufacturer documents content and origin, the better the goods can be assessed.

Frequently asked questions (FAQ)

What's the difference between hypericin and hyperforin?

Hypericin is a red plant pigment from the naphthodianthrone group and is responsible for the reddish colour of the plant's sap. Hyperforin belongs to the bitter compounds (phloroglucinol derivatives) and is chemically much more sensitive. Both serve as marker compounds to which extracts are standardised.

Why is St. John's wort standardised to hypericin?

Because hypericin can be measured well and reliably by analysis, it's well suited as a reference value for stating an extract's content. Standardisation ensures that every batch contains a comparable, defined proportion of the marker compound – despite natural variation in the raw material.

What does the extract ratio mean, for example 3–7:1?

The drug-extract ratio indicates how much dried starting herb was used for one unit of extract. "3–7:1" means that three to seven grams of raw herb were processed into one gram of dry extract. The higher the value, the more concentrated the plant material.

Why does the hyperforin content vary so much?

Hyperforin reacts sensitively to light, oxygen and heat and breaks down comparatively quickly during drying, processing and storage. This is why the actual content depends heavily on the production method, the packaging and the storage time. Light- and airtight packaging preserves the bitter compounds better.

Do I need to watch for interactions with St. John's wort?

Yes, this is especially important. The compounds can affect the breakdown of many drugs – including the pill, blood thinners, certain antidepressants and immunosuppressants. If you take medication, are pregnant or breastfeeding, check with a doctor or pharmacist before use.