Constituents are often described as water-soluble, alcohol-soluble, or oil-soluble. But solubility behaves more like a continuum. A constituent may be somewhere on the spectrum of sparingly to highly soluble in any given solvent. Rather than asking “is this constituent water-soluble?” the question becomes, “from this herbal matrix, how soluble is this constituent in water, at this temperature, and using this extraction method?”

This is why changing the solvent and extraction method can change the focus and function of a herbal medicine. A standard infusion emphasises constituents that dissolve readily in hot water. Are these the constituents (and associated actions) that we desire in a particular medicine? A tincture made with a given menstruum extracts a different spectrum of constituents from the same herb. Which constituents will we focus on when we adjust the ethanol percentage of the menstruum? An infused oil of that herb will capture yet a different spectrum of constituents, therefore featuring different actions and energetics than the infusion or tincture.

The main influence on solubility is polarity — a property arising from a molecule’s electron distribution. If this distribution is unbalanced (i.e., there is internal charge separation) we have a polar compound. If the distribution is perfectly balanced, we have a nonpolar molecule. And, as with solubility, polarity is a spectrum. Any phytochemical or solvent falls somewhere along the continuum.

The key to solubility is matching the polarity of the solvent to the polarity of the constituents we desire to extract. The old aphorism “like extracts like” applies: higher-polarity solvents (like water) focus on higher-polarity constituents, while lower-polarity solvents (like fixed oils) favour lower-polarity constituents.

Relative polarity of solvents

If you think of water as being 100% polar, then glycerin would be about 81% as polar as water. Pure ethanol would be about 65% as polar as water. These solvents are close enough that they will intermix with each other. Each of these solvents targets a particular group of constituents but there is overlap in what they will extract. Fixed oils and carbon dioxide (CO₂) extract lower-polarity constituents don’t easily mix with water, vinegar, glycerol or ethanol.

Solvent / menstruum	Relative polarity
Water	1.00
Vinegar (like water but also acidic)	~ 1
Glycerin (glycerol)	0.81
Ethanol (100%)	0.65
Olive and other fixed oils	~ 0
Carbon dioxide (CO₂)	~ 0

A tincture is made with a hydroethanolic solvent system (menstruum) containing both mid-polarity ethanol and high-polarity water. By adjusting the ethanol (EtOH) percentage, we are tuning the overall polarity of the menstruum. More EtOH in the menstruum → lower polarity; less EtOH → higher polarity. This is one reason tinctures are so versatile — by choosing the right EtOH–water ratio, we design the menstruum to selectively extract constituents by polarity matching. In other words, menstruum composition strongly influences the phytochemical profile of the resulting tincture (1,5).

Hydroethanolic solvents

“K” is one way to quantify polarity. Since water is highly polar and ethanol (EtOH) is moderately polar, mixing them together in different proportions will create a menstruum with a specific polarity. The higher the % EtOH, the lower the polarity of the hydroethanolic solvent system (menstruum). We tincture different herbs with different % EtOH to match the polarity of the constituents we want to extract from those herbs.

EtOH / Water	~ K	EtOH / Water	~ K
100% water	80	60% EtOH	47
10% EtOH / 90% H2O	74.5	70% EtOH	41.5
20% EtOH	69	80% EtOH	36
30% EtOH	63.5	90% EtOH	30.5
40% EtOH	58	95% EtOH	27.8
50% EtOH	52.5	100% EtOH	25

In herbal pharmacy, “yield” indicates the amount of finished tincture collected. But from a phytochemical perspective, “yield” usually refers to the concentration of a constituent in the product. A high constituent yield is often but not always better. For example, an extraction rich in astringent tannins may be more appropriate in some cases (surface inflammation, excessive secretion) and less appropriate in others (dry conditions, sensitive digestive mucosa). What matters is whether the preparation delivers the appropriate concentration of the desired spectrum of constituents for a particular therapeutic application.

Polarity is central, but several additional factors can influence the concentration of constituents in our extractions:

Temperature

Heat is a kind of kinetic energy that physically increases the extraction of most constituents. At the same time, some kinds of constituents are sensitive and will degrade with excessive heat. We learn to choose the optimal temperature for an extraction solvent, and to apply heat for the right period of time (e.g., infusion vs. decoction).

Time

Longer contact between solvent and herb generally enhances extraction up to a point, but the optimal time is influenced by factors including plant matrix, surface area, agitation, constituent class, and type of preparation.

Surface area

Chopping, grinding, or powdering increases surface area of the plant matrix, facilitating solvent–constituent contact and enhancing extraction. Very fine powders, however, can complicate filtration.

Agitation

Shaking or stirring increases kinetic jostling between solvent and constituents, usually accelerating extraction and constituent yield.

Pressure

Increasing pressure (e.g., in a tightly closed canning jar or electric pressure cooker) usually enhances extraction.

Plant matrix

Constituents may extract somewhat differently depending on how they are packaged within plant tissues. Delicate structures like flowers yield their constituents more readily than tough structures like seed coats or root barks. Cellular structure and co-constituents such as mucilages, tannins, and resins can also alter extractability.

Taken together, these variables should be considered as part of the extraction method; they help explain why preparations of the same herb in the same solvent can be noticeably different. The combination of botanical quality, solvent, and extraction method largely determines constituent yield and product quality.

Water

Water excels for higher-polarity constituents such as mucilages, polysaccharides, sugars, and some kinds of glycosides. It is the preferred solvent for making teas, infusions, and decoctions. Hot water almost always works better than cold water.

Hydroethanolic solvent systems (menstrua)

Lower % EtOH generally favours more polar compounds; higher % EtOH extracts lower-polarity constituents. Rather than a single “correct” percentage for each herb, it’s more accurate to think in ranges that can be adjusted to extract particular constituent families. Depending on your menstruum composition, you can create multiple different medicines from a single herb.

Glycerin and honey

Glycerin is a viscous and polar solvent, often used when alcohol is not desired. It can extract many water-soluble constituents along with a moderate concentration of aromatics, though it is generally less efficient than ethanol for lower-polarity constituents. However, its extraction spectrum can be increased considerably by employing heat, pressure, and agitation. As a solvent, honey behaves similarly to glycerin.

Vinegar

Vinegar is an acidic aqueous solvent. Acidity can change the solubility of certain constituents, particularly alkaloids, by shifting them into more water-soluble ionic forms (1,4). Traditional vinegars and oxymels (made by combining infused vinegars and honeys) offer versatile, alcohol-free alternatives to hydroethanolic tinctures or glycerites.

Fixed oils

Botanical oils such as olive, safflower, or coconut are both therapeutic substances and low-polarity solvents. Herb-infused oils feature low-polarity, lipophilic constituents including many terpenoids and some phenolics, making them valuable for topical preparations. Culinary preparations such as infused ghee or vinegar-and-oil salad dressings can also double as herbal products. Oils are generally unsuitable solvents for mineral salts and polar constituents including mucilages and glycosides.

Supercritical carbon dioxide

Supercritical carbon dioxide (CO₂) extraction is sometimes used for low-polarity constituents (e.g., gingerols from ginger (Zingiber officinale) curcuminoids from turmeric (Curcuma longa), cannabinoids from hemp (Cannabis sativa)). This modern method uses high-pressure, low-temperature conditions, with the advantage that CO₂ leaves no solvent residue in the finished product. CO₂ extracts are good at preserving the characteristic flavours and aromas of herbs. They are especially suitable for use in highly concentrated formulas delivered in capsules. (2)

Betalains are the vivid, water-soluble pigments responsible for red-violet and yellow-orange colours in plants such as beetroot (Beta vulgaris) and prickly pear (Opuntia ficus-indica) fruit, as well as edible greens including red orach (Atriplex hortensis var. rubra) and purslane (Portulaca oleracea). These medicinal food-herbs (and their betalains) have antioxidant, anti-inflammatory, and broad-spectrum bioprotective effects. (3)

Betalains are highly polar. This predicts several practical outcomes:

• They extract readily into water and other higher-polarity solvents such as lower % EtOH menstrua. Betalain extraction decreases as EtOH percentage increases.
• Glycerin and honey can be suitable solvents, especially when gently warmed to decrease their viscosity.
• Vinegar (which is mostly water) is a good solvent for betalains.
• Betalains are not lipophilic; they do not extract well into fixed oils.

As another example, echinacea (Echinacea spp.) contain several important groups of constituents — immunomodulating polysaccharides (IP), alkamides, and polyphenols including phenolic acids and flavonoid glycosides. Each group has a characteristic polarity range (4). IP are quite polar and most soluble in hot water; alkamides have moderate polarity and favour 50–60% EtOH menstrua; and the polyphenols are mid- to higher-polarity constituents that extract fairly well with both hot water and lower % EtOH. 

Since all these constituents are bioactive, which solvent is “best”? We could bypass this question by delivering a dose of the tincture in a water-based extract like an infusion or decoction!

1. Lee JE, Jayakody JTM, Kim JI, et al. The influence of solvent choice on the extraction of bioactive compounds from Asteraceae: a comparative review. Foods. 2024;13(19):3151. https://doi.org/10.3390/foods13193151 
2. Uwineza PA, Waśkiewicz A. Recent advances in supercritical fluid extraction of natural bioactive compounds from natural plant materials. Molecules. 2020;25(17):3847. https://doi.org/10.3390/molecules25173847 
3. Sadowska-Bartosz I, Bartosz G. Biological properties and applications of betalains. Molecules. 2021;26(9):2520. https://doi.org/10.3390/molecules26092520 
4. Petrova A, Ognyanov M, Petkova N, Denev P. Phytochemical characterization of purple coneflower roots (Echinacea purpurea (L.) Moench.) and their extracts. Molecules. 2023;28(9):3956. https://www.mdpi.com/1420-3049/28/9/3956 
5. Ganora L. Herbal Constituents: Foundations of Phytochemistry. 2nd ed. Louisville, CO: HerbalChem Press; 2021. https://www.herbalconstituents.com/book 

Traditionally, herbal supplements were purchased from local health food shops or high-street retailers, where trained staff might answer questions or guide customers toward reputable brands. Today, however, more people are buying supplements online, often from marketplaces offering thousands of products with little or no meaningful governance.

The convenience and sheer range of options have undoubtedly contributed to rising consumption, but they also introduce significant risks. One of the core issues is that the internet provides access to products that may not be subject to the same controls as those sold in stores. As a result, the quality, purity, and even identity of these products can vary widely. This is not to say that all online products are inferior — many excellent, well-established brands operate online — but consumers may assume that all supplements are equivalent, when in reality the variability is substantial.

Further complicating matters is the growing problem of counterfeit products, where consumers believe they are purchasing a reputable brand but are unknowingly buying falsified goods (3).

In response to quality concerns surrounding herbal medicines specifically, the UK adopted the Traditional Herbal Medicinal Products Directive (THMPD) in 2011. This directive established a licensing scheme designed to ensure the quality and safety of herbal medicines based on documented traditional use.

Products registered under this scheme are assessed according to standards similar to those applied to pharmaceuticals, giving consumers confidence in their identity, purity, and safety. Importantly, the directive grants companies’ permission to make medicinal claims — such as that it ‘aids digestion’, ‘promotes sleep’ or ‘relieves fatigue’ — provided these claims are grounded in long-standing traditional use. Any product on the UK market that makes such claims must hold a Traditional Herbal Registration (THR) in order to be legally sold (4).

Food supplements, however, fall under a different regulatory category. Although quality standards exist, the requirements are considerably less rigorous than those prescribed for THR-registered herbal medicines. Enforcement is also far weaker: products found to be adulterated, contaminated, or improperly labelled may remain available online for months, and sometimes reappear even after removal. This patchy oversight creates an environment where poor-quality products can circulate freely, often without consequence.

Research conducted at the UCL School of Pharmacy and the University of Westminster has shed light on the scale of the problem, uncovering numerous issues with supplement quality across a range of popular herbal products. These issues include poor extraction methods resulting in low concentrations of key active compounds, high levels of pesticides, contamination with aflatoxins, and deliberate adulteration intended to reduce production costs and inflate potency claims.

Ginkgo

For example, analysis of ginkgo (Ginkgo biloba) supplements revealed that many products contained added rutin — a cheap flavonoid (as it is abundant in low cost plant sources) — used to artificially boost total flavonoid levels. This allows manufacturers to claim, misleadingly, that their product contains the minimum 24% flavonoids expected of standardised ginkgo extracts.

Some products even included plant species with similar chemical profiles, added as cheaper substitutes for G. biloba. In one particularly concerning case, a product marketed as ginkgo contained none of the plant at all, but instead consisted solely of 5-hydroxytryptophan, a naturally occurring compound with reported antidepressant effects (5).

Rhodiola

A similar problem arose with rhodiola (Rhodiola rosea), a plant long valued in traditional medicine for its adaptogenic properties. Testing revealed that many products either contained or were partially substituted with Rhodiola crenulata, a related species native to China (6). Although chemically similar, R. crenulata lacks rosavin, the compound most strongly associated with the recognised therapeutic effects of R. rosea. Because R. rosea commands a higher price on the global market, substituting or mixing it with R. crenulata provides an economic incentive for manufacturers seeking to reduce costs. While the presence or absence of rosavin can be used to distinguish between the species, the increasing practice of blending the two makes accurate identification more challenging.

St John’s wort

In the case of St John’s wort (Hypericum perforatum), product quality was again highly inconsistent. Many supplements purchased through UK-based websites — but originating from the United States — contained food dyes added to mimic the ultraviolet absorbance of hypericin, one of the plant’s principal active compounds (7).

By absorbing UV light at the same wavelength as hypericin, these dyes allowed manufacturers to create the illusion of higher potency. This type of adulteration not only misleads consumers but also deceives analysts relying on basic UV assays, unless more sophisticated analytical methods are used.

Ashwagandha

Ashwagandha (Withania somnifera) also displayed significant quality variation. Its chemical composition differed markedly from product to product, largely due to differences in extraction methods. Traditional extraction techniques in Asia typically use water, whereas many Western manufacturers use alcohol, altering the phytochemical profile of the final extract. Additional issues included poor labelling, poor tablet disintegration, and, in two cases, contamination with aflatoxins (8).

Although ashwagandha has been banned in Denmark due to concerns about liver toxicity, it is unclear whether these adverse reactions reflect the herb itself or contaminants such as aflatoxins. Another possibility is that non-traditional extraction methods may produce more lipophilic compounds capable of crossing cell membranes more readily, thereby altering the herb’s safety profile

The effectiveness of any herbal product is inherently tied to its quality. Yet the average consumer may struggle to distinguish a high-quality herbal supplement from a poor one. One strategy is to buy products that are certified organic, which ensures that the ingredients are grown without synthetic pesticides and according to strict guidelines.

However, organic certification alone cannot guarantee appropriate manufacturing processes or freedom from adulteration later in the supply chain. Still, companies that invest in organic certification may be less likely to cut corners elsewhere, simply because they are already committed to meeting demanding production standards.

Another pragmatic approach is to choose well-known brands that are also available in major high-street shops, rather than unfamiliar brands sold exclusively online. Products that have undergone the additional scrutiny required to appear in retail stores may, on average, be more reliable than those available only through online marketplaces with little vetting.

Medical herbalists can offer valuable guidance on where to purchase herbs from, and may also suggest alternative preparations — such as teas, tinctures, and glycerites — which are less subject to adulteration than supplements (owing to the herbs being powdered and concealed).

Not only do many herbalists offer products that they have foraged, grown and/or prepared themselves, they will have experience with products from various suppliers and brands. As such, with insight into which products are the highest quality, medical herbalists are a reliable resource to find safe and efficacious herbal medicines. Explore our resources pages to find a herbalist.

International sourcing further complicates quality assurance. While many countries have robust regulatory frameworks for herbal products, the capacity of authorities to enforce these regulations varies widely. Online marketplaces, in particular, offer a loophole through which products can be sold into markets where they might not meet local standards. It is not uncommon for products removed from an online platform due to illegal labelling or identified quality problems to reappear months later, sometimes under slightly altered branding or via a different seller.

In the UK, some degree of industry self-regulation exists. Several organisations offer membership to companies that demonstrate appropriate governance standards and a commitment to producing safe, legally compliant products. These associations — such as the Proprietary Association of Great Britain (PAGB) (9), the Health Food Manufacturers’ Association (HFMA) (10), and the Council for Responsible Nutrition UK (CRN-UK) (11) — enforce strict membership criteria.

While they do not manage day-to-day operations or monitor internal quality systems, they provide an additional layer of accountability. When a product is made by a company affiliated with one of these bodies, consumers can have greater confidence in its authenticity, accuracy of labelling, and legal compliance.

Ultimately, responsibility for regulating food supplements in the UK falls to the Food Standards Agency (FSA), whose mission is to ensure that all food products — including supplements — are safe and of appropriate quality (12). Given the enormous size of the supplement market, the FSA increasingly depends on consumers and industry professionals to report concerns. Its confidential reporting systems allow individuals to notify authorities about mislabelling, substitution, contamination, or other forms of food crime without revealing their identity.

In conclusion, the food supplement market is characterised by a high degree of variability. A higher price does not necessarily indicate higher quality, and two products claiming to contain the same herb may differ dramatically in composition, potency, and safety.

Quality problems range from low concentrations of active ingredients to species substitution, adulteration, pesticide contamination, and the presence of harmful toxins. Therefore, whenever questioning whether a medicinal plant is good, bad, or ineffective, the only meaningful answer is: Which product?

1. Grand View Research. UK Dietary Supplements Market Size, Share & Trends Analysis Report, 2025‑2033. Market report. Accessed January 11, 2026. https://www.grandviewresearch.com/industry-analysis/uk-dietary-supplements-market-report
2. Health Food Manufacturers’ Association (HFMA). Health of the Nation Survey 2021. Published 2021. Accessed January 11, 2026. https://hfma.co.uk/wp-content/uploads/2021/03/hfm_health-of-the-nation_17.pdf
3. Intellectual Property Office. The Effect of Counterfeit Goods. Published 2024. Accessed January 11, 2026. https://www.gov.uk/government/publications/meta-counterfeit-and-piracy-campaign/the-effect-of-counterfeit-goods
4. Medicines and Healthcare products Regulatory Agency (MHRA). Herbal Medicines Granted a Traditional Herbal Registration (THR). Published 2025. Accessed January 11, 2026. https://www.gov.uk/government/publications/herbal-medicines-granted-a-traditional-herbal-registration-thr
5. Booker A, Frommenwiler D, Reich E, Horsfield S, Heinrich M. Adulteration and poor quality of Ginkgo biloba supplements. J Herb Med. 2016;6(2):79‑87. https://doi.org/10.1016/j.hermed.2016.04.003
6. Booker A, Jalil B, Frommenwiler D, et al. The authenticity and quality of Rhodiola rosea products. Phytomedicine. 2016;23(7):754‑762. https://doi.org/10.1016/j.phymed.2015.10.006
7. Booker A, Agapouda A, Frommenwiler DA, Scotti F, Reich E, Heinrich M. St John’s wort (Hypericum perforatum) products: an assessment of their authenticity and quality. Phytomedicine. 2018;40:158‑164. https://doi.org/10.1016/j.phymed.2017.12.012.
8. Kartbayeva E, Seitimova G, Khondkar P, et al. Withania somnifera (Ashwagandha): product quality and implications for consumer safety. Presented at: Joint Symposium on Chinese Medicine, Natural Products, Free Radical Research & Traditional and Complementary Medicine; October 23‑25, 2025; Taichung, Taiwan.
9. Proprietary Association of Great Britain (PAGB). PAGB. Accessed January 11, 2026. https://www.pagb.co.uk/
10. Health Food Manufacturers’ Association (HFMA). HFMA. Accessed January 11, 2026. https://hfma.co.uk/
11. Council for Responsible Nutrition UK (CRN‑UK). CRN‑UK. Accessed January 11, 2026. https://crnuk.org/
12. Food Standards Agency (FSA). Food Standards Agency. Accessed January 11, 2026. https://www.food.gov.uk/

There are three broad types of contaminants, these are physical, chemical and biological. 

Physical contaminants include items such as:

• Wood
• Glass
• Stones
• Insects

Herbal supply chains are susceptible to these contaminants, although certain parts of the supply chain may be more vulnerable. For example, when storing the herbs, if facilities are in a poor condition then this may lead to a higher likelihood of pest infestations resulting in the contamination of herbs with insects. 

Chemical contaminates would include substances like: 

• Acrylamides
• Heavy metals 
• Polycyclic aromatic hydrocarbons (PAHs) 
• Mineral oils 

These can occur as a result of environmental factors as well as processing activities. 

Lastly, biological contaminants are from microorganisms, such as:

• Viruses 
• Bacteria 
• Moulds
• Microbe metabolites mycotoxins

Their occurrences are often a result of poor hygiene practices in the growing and processing of the herb that then causes these harmful microorganisms to develop. Other biological contaminants include those from naturally occurring toxins in plants which can occur when weeds are co-harvested with the herb. Some well-known toxins include pyrrolizidine and tropane alkaloids.

In various herb growing regions across the world, the risk from environmental contamination through soil, air and water is an ever-growing concern. External pressures from climate change, consumer demand and industrialisation all play a role in increasing the likelihood of the presence of these environmental contaminants. 

Climate change will only increase the frequency of these issues — for example, flooding that results in pesticide contamination through contaminated water sources. Increasing consumer demand may lead to constraints in supply which leads to sourcing herbs from regions with known environmental contamination risks. The encroachment of heavy industry in herb growing regions in fast developing countries like India and China can lead to pollution by contaminants such as heavy metals, typically through the soil. There has of late been a concerted effort in some countries to address these issues, but unfortunately the legacy of heavy industrial activities can remain in the soil for some time (3).

Along with the risk of contamination from anthropogenic sources, like heavy industry, the topography and geology of where the herbs are grown can also play a part. For example, herbs that are grown in low lying areas may be prone to flooding from contaminated water sources. The geology is also important as certain rocks e.g. cinnabar, may lead to high levels of mercury in the herbs grown where those rocks are present. Certain herbs can also naturally accumulate heavy metals, some well-known examples include St John’s wort (Hypericum perforatum) and brahmi (Bacopa monnieri) (3,4). Among the 54 heavy metals in nature the most relevant contaminants in herbal medicines are:

• Mercury (Hg)
• Lead (Pb)
• Cadmium (Cd)
• Arsenic (As) (5)

To minimise the risk from environmental contaminants in herbal supply chains an important first step is to check whether the site is suitable for growing herbs. Avoiding agricultural land in heavily industrial areas and if wild collecting, avoiding places that are close to urban infrastructure, such as roads and factories, will help minimise the risk of environmental contamination. As the sources of environmental contaminants are complex and varied, managing these risks can be difficult.

By purchasing herbs from suppliers that have short integrated supply chains, the risk from environmental contaminants will be lower as these suppliers have direct insight or influence over the environmental contamination risks within their supply chain. This contrasts with herbs that are traded in open markets that typically involve longer complex supply chains where there is limited understanding of the contamination risks at origin.

Mycotoxins are a group of over 400 secondary metabolites that develop from fungal moulds when the right environmental conditions arise. These substances are toxic and carcinogenic and can been found in herbal materials (6). Aflatoxin and ochratoxin A are the two most well-known mycotoxin hazards in herb supply and develop from fungi such as Aspergillus and Penicillium. The occurrence of these toxins in herbs such as ginger (Zingiber officinale), liquorice (Glycyrrhiza spp.) and turmeric (Curcuma longa) is well documented. Mycotoxins are usually found in hot and humid climatic regions and as a lot of medicinal herbs are grown in these regions, mycotoxin contamination is a concern. They can directly contaminate herbal plants and their parts during pre- and post-harvest processing, transportation, and storage of herbal medicines (7).

Climate change poses a significant threat to medicinal plants that are particularly susceptible to changes in environmental conditions. The likelihood of contamination increases as the conditions change and become more unpredictable. Certain biological contaminants like mycotoxins are of particular concern as the environment plays a key role in the formation of these toxins and their increasing prevalence due to climate change is well documented.

Research has shown that the effects of climate change such as elevated carbon dioxide levels, environmental temperature rise and the interchange of extreme droughts with extreme rainfalls have a significant impact on mould growth and mycotoxin occurrence (8). As these extreme conditions become more widespread globally, the incidence of mycotoxin contamination and its severity will increase in many herb growing regions even regions that were previously at low risk. 

Herbs are grown in a wide variety of different regions with the infrastructure and access to technology varying considerably. Managing contamination risks in these diverse herbal supply chains is challenging. By using good agricultural and manufacturing practices we can apply common principles to processing activities in different herb growing regions. These practices minimise the risk of contaminants in processing and reduce the risk of contamination from environmental sources. 

Drying herbs is a key activity in most herbal supply chains and is a route where contamination can occur. Herbs are often air dried in many countries which means that herbs can be exposed to infestation by insects, birds, rodents and pests, as well as dust and dirt (9).

Formation of microorganisms during the drying process is also a well-documented issue. If there is inadequate air circulation during drying and there is high humidity the formation of microorganisms will be more likely to occur. By harvesting herbs at the right time (e.g. avoid harvesting in wet conditions), drying in hygienic conditions and ensuring good air circulation the risk of these microorganisms forming will be minimised. 

To reduce the risks of microorganism forming, industrial drying processes are sometimes employed as they can dry the herb quicker than traditional drying techniques (9). However, contamination risks still remain from substances such as PAHs, which form when combustible materials such as wood and oil are used in these processes (10). For example, an oil generator may contaminate the herbal material that you are drying, if it is not adequately ventilated.

Another activity where there is a risk of contamination is when transporting the herb from the field to the processing facility, as the herbs can come into contact with a wide variety of potential contamination sources. An example of this is when mineral oils leach from the vehicles used to transport the herb or from the sacks that they are collected in, which result in the contamination of the herbs.

Through the strict application of good agricultural and manufacturing practices risks from processing contaminants can be controlled. It is important to continually improve these practices as new threats and opportunities emerge. 

Although medicinal herbs are often sourced from around the world, there are still many that can be grown in the UK. If you are growing your own herbs or foraging for them in the wild you still need to be aware that many contaminants found in herbal supply chains will also occur in the UK. However, there will be differences in the types of contaminants found and the severity of the contamination, as environmental conditions are different. 

Also, when growing or foraging your own herbs you have an advantage in that you are able to observe the quality of the herbs directly and can take steps to avoid contamination issues. This is in direct contrast to purchasing herbs where you are reliant on the practices of others within the supply chain to control contamination risks.

Some simple steps to follow when foraging in the wild would include avoiding the collection of herbs from industrial sites, developed land and busy roadsides verges where pesticides will often be applied. Scorched or yellow leaves are a good indicator that pesticides were used. Other signs to watch out for when foraging are bruised leaves or signs of mould on the herb — avoid collecting from these plants.

If growing your own herbs, selecting a good location that is away from obvious contamination risks is essential. Avoid growing near buildings that are in a poor state of repair such as peeling paints which could lead to chemical contaminants. The use of clean water sources when irrigating is critical; so, avoid grey water, which is a pathogen contamination risk. Taking these steps will help to minimise the risk of contaminants when growing or foraging herbs in the UK.

Herbal supply chains face both current and emergent global as well as regional contamination risks. Keeping yourself educated about these contamination risks is important so that you know what to watch out for when purchasing herbs from your supplier. Insights about these risks could come from your herbal network, scientific publications or non-profit organisations like the American Botanical Council, which produce bulletins on herbal quality issues. Wherever practical, purchasing herbs with shorter supply chains helps to avoid the inherent risks in purchasing from long complex supply chains. 

Some simple steps which you could take could include purchasing from suppliers who hold third party accreditation (like GMPs) or food safety accreditation (like BRC) or specific herb industry initiatives like the BHMA HPSS scheme. Asking your suppliers about the origin of the herbs, testing reports for contaminants and details of how they manage quality within their supply chain will enable you to assess whether the supplier is taking proactive steps to manage these risks. If suppliers are unable to provide this it will generally be a good indicator that you may need to look elsewhere.

By knowing more about the origin of your herbs and the contamination risks within these supply chains it will help ensure that you make informed decisions about the quality of the herbs that you purchase.

1. Tripathy, V., Basak, BB., Varghese, TS., T.S. Saha, A. Residues and contaminants in medicinal herbs – A review, Phytochemistry Letters, 2015, Volume 14, 67-78. https://doi.org/10.1016/j.phytol.2015.09.003.
2. Eissa, F., Zidan, N. E.-H. A., & Sebaei, A. S. Contamination of herbs and spices: A 23-year EU RASFF notifications analysis. Journal of Food Safety, 2024, 44 (3). https://doi.org/10.1111/jfs.13131
3. Heinrich, M., Scotti, F., Booker, A., Fitzgerald, M., Kum, KY., Löbel, K. Unblocking High-Value Botanical Value Chains: Is There a Role for Blockchain Systems? Front. Pharmacol. 2019, Volume 10.
   https://doi.org/10.3389/fphar.2019.00396
4. Koorimannil, H., Abdussalalm, A., Chandra, R., Nabessa, S. Bioaccumilation of Heavy metals in Bacopa monnieri (L) Pennell growing under different habitat. International Journal of Ecology and development. 2010, 15.
5. Zuo, T., Li, YL., Wang, Y., Guo, YS., Shen, MR., Yu, JD Li, J., Jin, HY., Wei, F., Ma, SC. Distribution, speciation, bioavailability, risk assessment, and limit standards of heavy metals in Chinese herbal medicines, Pharmacological Research – Modern Chinese Medicine, 2023, 6. https://doi.org/10.1016/j.prmcm.2023.100218
6. Ałtyn I, Twarużek M. Mycotoxin Contamination Concerns of Herbs and Medicinal Plants. Toxins (Basel). 2020, 12(3), 182. https://doi.org/10.3390/toxins12030182
7. Opuni KFM, Kretchy JP, Agyabeng K, Boadu JA, Adanu T, Ankamah S, Appiah A, Amoah GB, Baidoo M, Kretchy IA. Contamination of herbal medicinal products in low-and-middle-income countries: A systematic review. Heliyon. 2023, 9(9). https://doi.org/10.1016/j.heliyon.2023.e19370
8. Kos J, Anić M, Radić B, Zadravec M, Janić Hajnal E, Pleadin J. Climate Change -A Global Threat Resulting in Increasing Mycotoxin Occurrence. Foods. 2023, 12(14), 2704. https://doi.org/10.3390/foods12142704
9. Singh, A., Moradiya, P., Jenish, P. Drying techniques in medicinal and aromatic plants and its impact on, Futuristic Trends in Agriculture Engineering & Food Sciences 2024, 3(9). https://www.doi.org/10.58532/V3BIAG9P3CH6
10. Reflection paper on Polycyclic Aromatic Hydrocarbons (PAH) in herbal medicinal products/ traditional herbal medicinal products (EMA/HMPC/300551/ 2015) of 31 May 2016. https://www.ema.europa.eu/en/polycyclic-aromatic-hydrocarbons-herbal-medicinal-products-traditional-herbal-medicinal-products-scientific-guideline#current-version-9120 Accessed 29th August 2025.
    

Kava-kava (Piper methysticum) is a plant whose roots and other parts have long been used in traditional medicine, and ceremoniously, in Pacific countries for its calming effects. There is modern evidence for its anxiolytic activity, suitable to the management of mild anxiety states. 

Anxiety disorders are the most prevalent among disorders and are a leading cause of disability and economic inactivity. The evidence for efficacy for current over-the-counter and prescription medicines is often lacking, and adverse effects, most especially dependency and withdrawal symptoms, remain a concern for pharmaceutical medications (1). 

Demand for kava as a self-prescribed anxiolytic increased through the 1990s with many products of variable quality being introduced to the UK market, most without regulatory oversight. Medicinal kava products were used elsewhere, and in Germany an estimated 350,000 annual prescriptions were written, with more than one million monthly doses (2).

In 2001, following reports associating kava consumption with incidents of liver damage around the world, the UK Committee on the Safety of Medicines set up an Expert Working Group (EWG) to evaluate the signals. The EWG determined that, against a lack of consistent evidence of sufficient benefit, kava was associated with an unacceptable risk of idiosyncratic hepatoxicity, which could not be minimised or prevented by any regulatory measures other than the removal of kava products from the market. The Statutory Instrument, The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002 followed this assessment (3). However this Order states that the prohibition shall not apply to a medicinal product which is “the subject of a UK marketing authorisation, certificate of registration or traditional herbal registration within the meaning of the Human Medicines Regulations 2012”.

Also in 2002, the UK Food Standards Agency Committee on Toxicity made a similar risk assessment in publishing its own advice on the herbal preparation of kava in foods, which led in turn to the enactment of the Kava-kava in Food (England) Regulations 2002 (4).

Under the Human Medicine Regulations 2012 and subsequent case law applying EU wide medicines legislation, it is almost certain that any future kava product permitted onto the UK market would be determined firstly as a medicinal product, with the subsequent benefit-risk assessment. 

N.B. In UK and EU law, foods have no therapeutic effects or benefits, so no benefit/risk balance can apply. Food safety assessments are made without regard to health benefits.

The Novel Food Regulation 2015/2283 (NFR) provides the harmonised legal framework for non-medicinal products. The NFR takes precedence over national laws in EU member states regarding the marketing of foods and supplements, so because kava has not been listed in the EU’s Union List of Novel Foods, it cannot be sold or marketed anywhere in Europe. However, enforcement is carried out by national authorities, which can lead to variable application.

France and Austria have banned kava outright on the basis of ‘legitimate concerns’ (i.e., public health) and these bans remain valid as long as they do not conflict with EU law (e.g., free trade).

In Germany, court decisions have dismissed the regulator’s ban on kava on the argument that this was disproportionate and unsupported by current evidence. The full legal implications including as an EU Member State are still being worked through the courts.

In the US, kava is legally and widely sold as a dietary supplement, with ‘structure/function’ claims often implying benefits for relaxation and stress relief. In 2020 the Food and Drug Administration (FDA) published a redacted memorandum specifying that kava is not considered Generally Recognised as Safe (GRAS) (5), therefore making kava an unapproved food additive. However, this does not extend to its use as a food (kava steeped in water) or its use as a dietary ingredient (6). The state of Hawaii determined that kava (‘awa’) in its traditional form is GRAS (7).

The Therapeutics Goods Administration initially banned kava and then, after a re-assessment, permitted it with limits of no more than 125 mg kavalactones in solid dosage forms, or 3 g limit in teabags to a maximum daily dose of 250 mg kavalactones. Selected kava preparations continue to be approved as ‘Listed Medicines’ (available over-the-counter for self-treatment) and traditional kava beverages are similarly available.

Benefit

The effect of the prohibition order outside Pacific regions and the USA was markedly to restrict the clinical research necessary to update the British EWG negative assessment. Most human studies have been conducted in Australia. The published clinical trials there have demonstrated that kava extracts can reduce anxiety and depression symptoms (8,9,10). One 2004 review concluded that “kava is the only botanical anxiolytic whose efficacy is supported by evidence from a systematic review of randomized placebo-controlled trials (evidence Level 1 of the National Health and Medical Research Council of Australia)” (11). More recent meta-analyses also support kava’s efficacy in reducing anxiety symptoms, although the effect size in cases of generalised anxiety disorder (GAD) is small (12,13).

It is relevant that by definition GAD requires a medical practitioner’s diagnosis, so the new evidence points to benefits appropriate to self-management of mild to moderate anxiety (3) and this may be the most appropriate indication for future kava use (14).

The new clinical trial data do help to fill gaps in the evidence base for efficacy that was initially considered by the EWG, when they found a mismatch between products for which there was benefit and those more widely available.

Further investigations have identified effects on GABA activity in humans (15,16,17). Another review summarises the potentially positive profile of kava in relation to cancer (18), and there are additional pharmacological updates (19,20,21,22).

In relation to the following section, adverse events in clinical trials associated with kava treatment were not significantly different from those associated with placebo.

Risk assessments

In fulfilment of a pledge by UK Ministers to review the 2002 order within two years, the UK medicines regulator, the MHRA, engaged in a public and international consultation. In October 2005, the EWG, having considered the responses and new evidence available at the time, concluded that the prohibition order remained “justified and proportional”. Notably, however, the EWG was concerned that “further structured research into the precise mechanism of hepatoxicity was required and that although the data presented justified the original prohibition, it also raised many new questions.”

The EWG noted a particular link to idiosyncratic hepatoxicity, which may have involved herb-drug interactions: “Although its specific route of metabolism has not been established, it has been found to induce and inhibit a variety of cytochrome P450 isoforms in vitro and, as such, has the potential to be associated with significant herb-drug interactions.” Ultimately, however, the EWG could not identify a mechanism of hepatoxicity for kava: “none of the proposals could account for all of the cases and many of the proposed mechanisms of hepatotoxicity appeared implausible.”

In one significant initiative to update safety data since this incomplete conclusion a Monograph and Therapeutic Compendium (a quality, therapeutic, and safety review) on kava is being produced by the American Herbal Pharmacopoeia. This work includes authorship and peer review by medicinal plant experts, including physicians, pharmacologists, pharmacognosists, and experts in pharmacokinetics, toxicology, and herb–drug interactions.

The monograph is being finalised for publication, but a pre-published draft of the safety section includes the following conclusion. “Based on critical assessments, any direct hepatotoxic potential for kava is rare and idiosyncratic, or confounded with use of other hepatotoxic substances, including medications. Hepatotoxicity was rarely reported when kava was used within its traditional context.”

Finally, the continued availability of kava in Australia has not been accompanied by adverse event signals from the Therapeutic Goods Administration. In 2019, a relative harm assessment concluded that kava was the least dangerous of 22 substances known to be used for their psychoactive effects (23). Nor are there signals emerging from Poisons Units or elsewhere in the USA.

Quality issues

The EWG added “One of the main pieces of data that would have been useful is a systematic evaluation of the Kava products available, with an audit of the source material used. It would be extremely useful to have a more systematic evaluation of the constituents of the various Kava cultivars to try to determine what the differences are and whether or not these constituents have a significant role in hepatotoxicity.”

Since the prohibitions, quality control standards have been developed internationally to ensure proper identity, purity, and quality of traded material. These have been reviewed in a useful 2016 technical report published by the FAO and WHO (24).

In its conclusion to the 2005 EWG re-evaluation the UK MHRA stated it will “review any new evidence that is submitted in relation to the issue of hepatotoxicity suspected to be associated with Kava and will re-evaluate the prohibition of Kava in unlicensed medicines if significant new data are received.”

There does appear to be a case for such a review to consider the regulated release of kava back into the market, with clear quality standards, controlled dosage, and safety advice including its use with other medications. There could be considerable benefits in having an effective self-care option for people in the wider population and workforce who are suffering increasing levels of anxiety. 

In response to a recent submission raising these points, the UK MHRA recalled that the 2002 Prohibition Order does not exclude applicants applying for a Traditional Herbal Medicine Registration or a ‘Marketing Authorisation’ (full medicines licence) under The Human Medicines Regulations 2012. In this latest response the MHRA stated: “Should a Traditional Herbal Registration or a Marketing authorisation application for a Kava medicinal product be submitted to the MHRA, safety would be reviewed on an application-specific basis and on the currently available evidence” (25). There is, therefore, no prospect of a general review of kava’s safety in use without a manufacturer making a specific application. In the UK and Europe, food use is also unlikely to be permitted while the medicine bar remains.

Regulation is of course an incomplete measure of public protection or restriction: kava is accessed frequently on the internet, without quality control or information as to its safest use.

1. Garakani A, Murrough JW, Freire RC, et al (2020) Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front. Psychiatry 11:595584
2. Ulbricht C. Basch E, Boon, H et al (2005) Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin. Drug Saf. 4, 779–794
3. https://tinyurl.com/4j7de38e
4. https://tinyurl.com/4ukrs44a
5. https://tinyurl.com/tcw7fwwj
6. https://tinyurl.com/4bm83re3
7. https://tinyurl.com/wewhxncu
8. Sarris J, Stough C, Bousman CA, et. (2013) Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 33(5): 643-8.
9. Sarris J, Kavanagh D, Byrne G, et al. (2009). The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology, 205, 399-407. 
10. Sarris J, Byrne GJ, Bousman CA, et al (2020). Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study. Aust N Z J Psychiatry 54(3): 288-2976
11. Jorm AF, Christensen H, Griffith KM, et al. (2004). Effectiveness of complementary and self-help treatments for anxiety disorders. Med J Aust 181: S29-S46
12. Oo S, Henderson P, Pak S. (2018). Kava for Generalized Anxiety Disorder: A Review of Current Evidence.. Journal of alternative and complementary medicine, 24 8, 770-78 
13. Smith K, Leiras C. (2018) The effectiveness and safety of Kava Kava for treating anxiety symptoms: A systematic review and analysis of randomized clinical trials. Complement Ther Clin Pract. 33: 107-117
14. Thomsen M. Schmidt M (2021). Health policy versus kava (Piper methysticum): Anxiolytic efficacy may be instrumental in restoring the reputation of a major South Pacific crop. J Ethnopharmacol 268: 113582.
15. Cribb L, Sarris J, Savage KM, et al (2023). Effect of kava (Piper methysticum) on peripheral gene expression among individuals with generalized anxiety disorder: A post hoc analysis of a randomized controlled trial. Phytother Res 37:5897-5903.
16. Savage K, Sarris J, Hughes M, et al. (2023). Neuroimaging Insights: Kava’s (Piper methysticum) Effect on dorsal anterior cingulate cortex GABA in generalized anxiety disorder. Nutrients 15:4586
17. Savage K, Firth J, Stough C, Sarris J. (2018). GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32:3-18.
18. Soares RB, Dinis-Oliveira RJ, Oliveira NG. (2022) An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava. J Clin Med. 11(14):4039
19. White CM. 2018. The Pharmacology, pharmacokinetics, efficacy, and adverse events associated with kava. J Clin Pharmacol 58:1396-405.
20. Bian T, Corral P, Wang , et al. 2020. Kava as a clinical nutrient: Promises and challenges. Nutrients 12: 3044
21. Meesakul P, Shea T, Wong SX, et al. (2023) Hawaiian plants with beneficial effects on sleep, anxiety, and mood, etc. Pharmaceuticals (Basel) 16:1228
22. Zhang W, Yan Y, Wu Y, et al. (2022) Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis. Pharmacol Res 179:106204
23. Bonomo Y, Norman A, Biondo S, et al. (2019). The Australian drug harms ranking study. Journal of Psychopharmacology 33(7): 759–768
24. FAO/WHO (2022) Kava: a review of the safety of traditional and recreational beverage consumption: a technical report (https://tinyurl.com/yrecnu2u)

Unfortunately finding good quality products can be difficult. Similar to food there are risks with contamination and spoilage.

There are potential risks in many areas; from microbial contamination (E.Coli, aflatoxins etc); heavy metal loads (lead, mercury, arsenic etc) either found at naturally high levels in the soil or from industrial contamination; potentially toxic extraneous materials harvested accidentally with the intended species (pyrrolizidine alkaloids, tropane alkaloids found in Boraginaceae, Asteraceae and Fabaceae and Solanaceae respectively).

Also our environment has unfortunately become polluted with many new-to-nature chemicals that are intentionally or unintentionally applied to crops; pesticides, fungicides and herbicides are persistent in our soils, water and atmosphere and high levels can occur due to over application or from wind-drift and floods.

Hence it is all too common for products to be contaminated. It is also possible that products have intentionally or accidentally been adulterated with incorrect species. The herbal industry faces similar challenges to the food industry; rice is often detected with high levels of arsenic, wheat with pyrrolizidine alkaloids, lentils with E. Coli – and all non-organic foods with pesticides.

Despite rigorous regulations across most countries all sorts of adulterants from sawdust to colouring dyes to pharmaceuticals have been found in over the counter herbal products. Another common problem is that botanical nomenclature is complex and plant names can be mixed up. This has led to poisonous plants being substituted in to products (1) which has lead to dangerous results.

Marker compounds

Plants have hundreds to thousands of secondary metabolites that make up the chemistry of their physiological effects; the essential oils, polyphenols, colourful pigments and array of other phytochemical families all combine to induce their effects. So just having the right species that is perfectly hygienic isn’t enough. You also need the right amount of the ‘actives’ to have an effect. This is where another difference in quality may come in.

What are food grade herbs?

Food grade herbs are typically used in food as the spice-mixes and teas you will find lining the shelves of supermarkets and natural health stores. They may also be used in some food supplements that are fine to use, but their contents and purity may or may not be pharmacopoeial grade.

What are pharmacopoeial grade herbs?

A pharmacopoeia is a collection of quality standards for herbs (as well as vitamins and drugs) that ensures the herbs are of the right quality and can meet the criteria to deliver their expected effects. For example, there is a European Pharmacopoeia, a British Pharmacopoeia, a United States Pharmacopoeia, and an Indian Pharmacopoeia.

How do herbs become pharmacopoeial grade?

To be classed as pharmacopoeial grade, further to the quality criteria mentioned above, the identity of the species must be verified using various microscopic techniques and specialist equipment, such as chromatography (you will all have done something similar to this in school chemistry lessons, using blotting paper).

High Performance Thin Layer Chromatography, Gas Chromatography, distillation, microscopic and organoleptic tests are all used to assess qualitative and quantitative measurement of the species. These methods ensure the right level of compounds, such as the active ingredients of essential oils, polyphenols or flavonoids. And it is these compounds that are associated with certain tastes and effects.

Here are some examples of the different quality if herbs available:

Standard Herb Name	Food Grade ISO 6571/1984	European Pharmacopoeia
Chamomile flowers (Matricaria recutita)	Min. 0.2% essential oil	0.4% essential oil Apigenin Min. 0.25%
Fennel seed (Sweet) (Foeniculum vulgare var. dulce)	Min. 1% essential oil	Min. 2% essential oil (with NLT 80% anethole and max 10% estragole and 7.5% fenchone)
Peppermint leaf (Mentha piperita)	Min. 0.6% essential oil	Cut Leaf Min. 0.9% essential oil Whole Leaf Min. 1.2% essential oil

It is a remarkable fact that 25% of the volume of herbs sold today are from the wild. Sadly much of this is unregulated trade with questionable sustainability or social welfare practices. The people that tend to collect herbs from the wild are often the most marginalised socially, economically and geographically.

It is important when buying herbs that you know that they are grown and harvested with the welfare of the ecosystem and the communities that are harvesting them in mind. Fortunately there are some very progressive action groups working on this; FairWild is the first wild certification organisation; United Plant Savers works to protect threatened medicinal species in the US; Plantlife promotes protection of plants in the UK. Find more information on sustainability in our article on Environmental Sustainability of Medicinal Herbs.

What to look for

Herbal supplement or Botanical supplements are regulated under Food Supplement regulations in the UK (Dietary Supplements in the USA). They have to meet all the standards you would expect any healthy food should meet; manufactured under hygienic conditions with tight specifications for microbial load, heavy metals, pesticides and other chemical contaminants. It should be what ‘it says on the tin’- the species should be correctly identified and it should be the correct part of the plant in the product.

Organically certified products that are organically certified have strict controls on traceability and on pesticide levels as well as human welfare standards.

FairWild certification ensures that wild plants have been harvested sustainably and the collectors and community paid fairly.

Some herbal products have a medical licence guaranteeing a level of quality. Across Europe the Traditional Herbal Registration certification mark is applied to products meeting.

Certification for Fair Trade also indicates a full-length value chain relationship enhancing the welfare of the workers and reflecting attention to detail in the ingredients.

Needless to say the world of e-commerce is a bit of a wild west so do be cautious when shopping online. For further information please read this excellent article on herbal quality by Roy Upton.

The body often metabolises herbs and pharmaceutical drugs through the same pathways. It is their influence on these systems that can affect their metabolism.

Interactions between herbs and drugs can occur in four different ways:

1. Additive: Increasing the effect of a drug
2. Reductive: Reducing the effect of a drug
3. Neutralising: Lessening the side-effect of a drug
4. Adverse: A herb and a drug can interact, mildly or severely, causing an undesirable effect

Pharmacodynamic interactions

Pharmacodynamic interactions occur between drugs and herbs in the body influencing how the drugs and herbs affect the body. If an interaction between a drug and a herb takes place then it may be synergistic or antagonistic resulting in an exaggerated or a lessened effect. Theoretically, drugs and herbs that have similar therapeutic activity have an increased potential of interacting.

The highest risk of interaction occurs when simultaneously using drugs and herbs that are anti-coagulant, anti-platelet, anti-diabetic, diuretic or sympathomimetic. Hence it is essential to speak with a herbalist and healthcare professional of taking such drugs and herbs together.

Other factors can be dangerous as well, specifically with gene interactions. For example, St John’s Wort, a herb commonly used for depression is known for interacting with the CYP450 enzyme family. This is very significant because it is this enzyme family that is responsible for metabolizing many drugs like warfarin and oral contraceptives.

Therefore, St John’s Wort inhibiting this enzyme family means that warfarin and oral contraceptives are not metabolized and their activity may be interfered with. Similarly because St John’s Wort is a selective serotonin reuptake inhibitor (SSRI) it should not be taken with Prozac, which is a pharmaceutical SSRI as this can lead to an excess of serotonin potentially leading to serotonin syndrome. Another example, finasteride and saw palmetto are both used to treat enlarged prostates, and so shouldn’t be taken concomitantly.

Pharmaceuticals or herbs with narrow therapeutic indexes can also be potentially dangerous to take together. When a drug has a narrow therapeutic index it means that the window between it not working at all, or becoming very dangerous or lethal is very small. Mixing herbs can disrupt how these are metabolised in the body, and even a slight increase of their levels in the body can be dangerous. Examples of these drugs include; lithium, carbamazepine, ciclosporin, digoxin, phenytoin, warfarin and theophylline.

Contraindications

Some herbs are contraindicated with certain illnesses and so one must check that a herb is safe to with a particular condition. For example, Panax ginseng root is controversial in hypertension, and in acute states such as mania and asthma attacks. Liquorice root is another herb associated with increasing blood pressure when used at high doses over long periods. Most herbs are fine, but each should be checked for their own toxicity and safety issues.  See our herb profiles for specific information. And always discuss with a qualified herbalist or your health provider if you have a specific condition.

It is strongly encouraged that when you are thinking of taking a herb or supplement that you check their interactions. There are some resources for this like books like Stockley’s Drug Interactions or our herb profiles.

Not all interactions have been investigated, but good guiding rules include: 

• If one is taking herbs and drugs for the same illness then discard one (e.g both to lower blood sugar).
• If one is taking herbs and drugs with opposite indications or effects (e.g one to increase and one to lower blood sugar), then do not take both.

When looking for quality products, there are some questions you can ask to help assure good quality. Firstly, a company should be able to tell you where the herbs have come from. If they do not know their supply chain, it leaves more space for contamination and adulteration.

They should also be able to tell you specifically which species are in their product. This means not just their common name (e.g Nettle) but the Latin binomial (Urtica dioica). Common names can indicate an array of different species hence why plant nomenclature is so complicated!

The Latin binomial assures that the correct medicinal species are being used, as some plants in the same family with similar names are not medicinal at all. A wonderful resource to be able to see a species different names, or a names different possible species is the Medicinal Plant Naming Services database. It is also important that the correct part of the plant is used and listed be it root, bark, leaf, flower, fruit or seed.

Additionally be mindful of the ingredients in the product. Many products are full of fillers such as anti-caking agents and bulking agents, synthetic colourings, and flavourings. Unnecessary ingredients indicate a poor-quality product and there is a good chance the plants in there are not good quality either.

Finally, we recommend seeing a qualified herbalist. Particularly if you are pregnant, breastfeeding elderly, seeking medicine foFinally, we recommend seeing a qualified herbalist. Particularly if you are pregnant, breastfeeding elderly, seeking medicine for a child or dealing with serious chronic conditions.

A qualified herbalist will know which herbs are safe for you to take in which doses, as well as be able to source you quality herbs. They will also be able to give you the best treatment plan you need to nurse your way back to optimum health. Find one in our resources section.

1. Tankeu S, Vermaak I, Chen W, Sandasi M, Viljoen A. Differentiation between two “fang ji” herbal medicines, Stephania tetrandra and the nephrotoxic Aristolochia fangchi, using hyperspectral imaging. Phytochemistry. 2016;122:213-222. doi:10.1016/j.phytochem.2015.11.008
2. Schippmann, U. W. E., Leaman, D., & Cunningham, A. B. (2006). A comparison of cultivation and wild collection of medicinal and aromatic plants under sustainability aspects. Frontis, 75-95.
3. Uwe Schippmann, Danna J. Leaman and A. B. Cunningham  Impact of Cultivation and Gathering of Medicinal Plants on Biodiversity: Global Trends and Issues FAO. 2002. Biodiversity and the Ecosystem Approach in Agriculture, Forestry and Fisheries. Satellite event on the occasion of the Ninth Regular Session of the Commission on Genetic Resources for Food and Agriculture. Rome, 12-13 October 2002. Inter-Departmental Working Group on Biological Diversity for Food and Agriculture. Rome
4. Brinker F. Herb Contraindications And Drug Interactions. Sandy, Or.: Eclectic Medical Publications; 1998.
5. Mills S, Bone K. The Essential Guide To Herbal Safety. St. Louis, Mo.: Elsevier Churchill Livingstone; 2005.

The first to highlight the problem of herbal adulteration was Dioscorides in 50 CE, who authored the first systematic pharmacopoeia De Materia Medica (Περὶ ὕλης ἰατρικῆς). He described over 40 tests to examine the quality of herbal products bought from traders in ancient Rome (1).

Most of these were organoleptic but some used simple chemico-physical tests, such as flame tests, solubility, measurements of weight and displacement and other unique properties of authentic herbs such the ability of balsam (probably Commiphora gileadensis (L.) C.Chr., Burseraceae) to be washed clean from a woolen cloth while its adulterants stain (2).

Later Roman authors such as Pliny the Elder (23 – 79 CE) also documented widespread adulteration in food and drugs in his Natural History with methods to detect them (3,4).

The physician Galen (131 – 201 CE) was also aware of adulteration in his supplies, often complaining of fraudulent merchants and asserting the need for a physician to know his materials (5), even suggesting animal testing for the formulated antitoxin theriac (θηριακή) to determine its authenticity (6).

A similar trend emerged in China. In the 5th century, as medicine developed into increasingly specialised roles of harvesters, market-traders and physicians, scholar-hermit Tao Hongjing (陶弘景) wrote his Collected Annotations to the Materia Medica (Ben Cao Jing Ji Zhu, 本草經集注) where he lamented the poor quality of herbs in his day, accusing the market traders of deliberately selling low quality products for profit, and the physicians of being only concerned with looks and unable to recognise genuine potency (7).

To remedy this state of affairs, he hoped his detailed additions to each entry of the earlier 1st century classic, the Divine Farmer’s Materia Medica (Shen Nong Ben Cao Jing, 神農本草經), would help physicians to recognise true potency and value it over cosmetic appearance.

In particular he highlighted the issue of correct species from poor growing regions, lacking the potency of the genuine article, being sold as the real thing. This problem of functional adulteration is very difficult to detect and still pertinent today.

In 659, during the Tang dynasty the world’s first national pharmacopoeia, the Newly Revised Materia Medica (Xin Xiu Ben Cao, 新修本草) was published (8).

The whole country was surveyed for specimens and detailed colour drawings were included to complement textual descriptions. Improvements to authenticating herbal medicines continued with the Extension to the Materia Medica (Ben Cao Yan Yi, 本草衍義) by Kou Zongshi (寇宗奭), an expert in authentication, compiled in 1116 being one of the first printed texts that focused on differentiating authentic from inauthentic herbal medicine (9).

However, it was not until the Origins of the Materia Medica (Ben Cao Yuan Shi, 本草原始) in 1788 that pictures of the prepared herbal materials were included rather than just the live plants.

The medieval period saw little development in the technology for detecting adulteration but instead relied on the development of ethical and legal frameworks to ensure the purity of medicinal herbs.

As the Islamic Golden Age dawned under the Abbasid Caliphate in 9th century Baghdad, a new class of professional pharmacists started writing new pharmacopoeias, beginning with Yuhanna Ibn Masawayh (يوحنا بن ماسويه‎, Romanised: Johannes Mesue), who focused one work on aromatics, including methods of detecting their adulteration (10).

A code of ethics was established for this emerging class who were held to higher standards than regular spice traders and enforced by a government appointed official, al-Muhtasib (محتسب), who inspected pharmacies for potential adulteration, degradation, fraud and excessive profiteering (11).

Saffron (Crocus sativus L., Iridaceae) adulteration was a particular concern due to its culinary and medicinal use in many healing traditions. Often ascribed with magical properties, with its labour intensive harvesting procedure, made it worth its weight in gold (12).

From the 5th to the 15th centuries, an armed guard was charged with inspecting saffron supplies coming into port in Venice and in 1358 the first known food law was enacted in Nuremberg, punishing the adulteration of saffron with death, sometimes by being burnt alive with your own adulterated products.

The scientific revolution ushered an age of using technology to enhance the senses. Magnifying lenses had been known to the ancient Greeks and Romans (13) but the invention of the compound microscope allowed Nehemiah Grew to provide the first vivid descriptions of plant anatomy in 1682 (14,15). Over time new technologies such as fluorescence, confocal microscopy and imaging techniques have added new dimensions to what we can see in order to differentiate plant materials (16).

In 1735 Linnaeus applied scientific methodology to taxonomic classification in his Systema Naturae (17), developing the binomial nomenclature still used today (18). This initiated a systematic method of classifying species and therefore determining which species should be considered authentic or adulterants, and clarifying which species referred to by traditional or local names have the medicinal benefits required of them (19).

The industrial revolution saw a new wave of advances in botanical sciences. The age of chemometric testing began when Mikhail Tsvet demonstrated the first chromatographic technique to separate plant pigments in 1903 (20).

Spectroscopic analysis, observing the unique interactions of the separated compounds with energy from ultraviolet or infrared radiation, or from magnetic or ionising charges, could be used to speculate on their structures with far greater accuracy than smell or taste alone, even detecting deliberate adulteration with drugs, dyes or similar herbal materials designed to be undetectable by routine methods of examination (21).

With increased sensitivity, it became possible to detect new potential contaminants that would have escaped detection or even consideration in the past.

This includes both naturally occurring toxic compounds in plants which can arrive in the supply chain by being inherently present in a species, or by contamination with plants that contain them, heavy metals drawn from the environment, or contamination with artificial substances such as pesticides. Pyrrolizidine alkaloids caused particular concern in herbal medicine, being discovered in several plants considered safe for centuries, such as borage (Borago officinalis L., Boraginaceae), comfrey (Symphytum officinale L., Boraginaceae) and coltsfoot (Tussilago farfara L., Asteraceae). 

These have no obvious toxic effects in moderate doses but long term use can cause irreparable liver and lung damage, even leading to cancer (22). The use of these herbs has since been voluntarily suspended by most professional herbalist associations (23) but potential contamination of other herbs and foods with plants that contain PAs is harder to control. These toxins are too widely distributed in nature to ever make total eradication feasible and as little as one ragwort (Senecio sp. L., Asteraceae) per hectare of St. John’s Wort (Hypericum perforatum L., Hypericaceae) is enough to exceed the suggested threshold of 1.0 μg PAs daily (24).

However, through implementation of Good Agricultural and Collecting Practices combined with batch testing using a combination of chromatography and spectroscopy, it is hoped that exposure can be kept within safe limits. Tropane alkaloids have caused a similar concern, often ending up in the supply chains through accidental contamination with Datura sp. or Convolvulus sp. and these too are managed with chemometric and spectroscopic analysis to ensure levels are below the regulatory limits (25).

Likewise, pesticides are monitored with published reports containing chromatographic-spectroscopic analysis (26,27) with similar monitoring of heavy metals (28).

This field continues to advance with more refined techniques and computing power to analyse the data providing even more sophisticated models (29). Initiatives like the High Performance Thin Layer Chromatography Atlas of plants (30) aim to publish the chemical fingerprint of every species, against which unknown samples can be compared to determine the species or the presence of adulterant chemicals.

Within a few years of the first Nature papers on human DNA fingerprinting being published by Alec Jeffries in 1985, the technique had revolutionised botanical sciences (31). DNA analysis enabled faster and more precise taxonomic classification, based on snippets of genetic code, than the traditional system and could even determine distinctions between apparently identical species or from fragments that had been cut and no longer had distinguishing characteristics visible.

For example, the Chinese names of some medicinal herbs, such as Mu Tong and Fang Ji, may both refer to several separate species, one of which is a toxic Aristolochia species (A. manshuriensis and A. fangchi respectively) containing aristolochic acids that cause kidney damage, while the other is not (Clematis armandii Franch., Ranunculaceae or Akebia trifoliata (Thun.) Koidzumi seu quinata (Houtt.) Decne., Ranunculaceae and Stephania tetrandra S. Moore, Menispermaceae respectively) and can be used safely (32).

It can be almost impossible to tell dried, cut specimens, powders or extracts apart and while some countries have responded with outright bans on all species where confusion could happen (33), others have implemented testing and analysis to regulate imports (34). An integrated approach of chemometric testing for the presence of aristolochic acids combined with DNA barcoding to ensure correct species (35) seems to be the best option to enable herbal medicine to continue to be practiced effectively and safely without unnecessary restrictions.

Similar to, and complementing, the chromatographic atlases of plants, databases of genetic information such as the Barcode of Life Data (BOLD) (36), the NCBI Genome Database (37) and the Medicinal Materials DNA Barcode Database of Traditional Chinese Medicines (38) have been developed enabling samples to be compared against verified specimens.

Modern chemometric and genetic analysis of plants have undoubtedly enhanced the quality assessment of herbs, but they are not without their drawbacks. Chemometric analysis often relies on identifying active ingredients or known adulterants and searching for these markers to determine the quality of the medicine but the effects of many herbal medicines cannot be traced to single compounds and in many cases their mechanisms remain unknown, requiring new strategies to be considered (39). DNA fingerprinting can also be problematic when applied to extracts where the DNA is often degraded after processing (40).

The ultimate purpose of herbal medicines is to have a biological effect which is difficult to determine without functional testing on a biological system. Some forms of adulteration, like that highlighted by Tao Hongjing, may pass chemometric and genetic analysis, especially where a specific drug compound is not the key to the herb’s activity, or in formulae where there may be too many markers to effectively search for them all.

Until recently the only methods of functional testing were either animal experiments, which are ethically problematic (40) and only provide limited information (42), human trials, which are very expensive to run in an area that is chronically underfunded, or by observation of the effects of each batch in the clinic, which is less than ideal.

Mitochondrial testing presents a new and exciting opportunity for the functional analysis of the quality of herbal medicines. Mitochondria stand at the centre of biological activity, not only providing the energy required for most biological functions but being integral to almost every aspect of multicellular life (43). Their broad range of functions has even led to suggestions that they may be behind similarly broad traditional concepts fundamental to life such as Qi (44).

Changes in mitochondrial function have been implicated in many states of health and non-inheritable disease including metabolism, stress responses, inflammation, ageing, cancer, cardiovascular and neurological function (45), and immune responses to viral infections including SARS-CoV2 (46).

Many of these have been traditionally attributed to Reactive Oxygen Species (“free radicals”) generated as by-products from the mitochondrial respiration process and treated with antioxidants.

However, current research shows that the picture is far more complex, with antioxidants failing to show an improvement in living subjects (47), maybe even eliminating the beneficial effects of exercise triggered by a moderate rise in free radicals (48) and having contradictory results in cancer, where free radicals induce both the proliferation and the self-destruction of cancer cells (49).

Through the use of dyes that react with specific mitochondrial processes, fluorescent microscopy and highly sensitive probes that can measure the oxygen consumption rate or temperature changes in a culture of cells, it is possible to generate a mitochondrial profile of the effects of herbal substances on specific tissues (50).

Besides gathering invaluable information on the potential mechanisms of many herbs, this approach also provides a novel method of functional evaluation, closer to the clinical effects than chemical or genetic profiles can provide on their own.

Moreover, it could be used routinely on herbal batches for the purposes of quality, safety and efficacy assessment, while being less ethically problematic than testing on animals and less costly than running conventional human trials.

The Research Centre for Optimal Health is at the forefront of this research methodology with several PhD and postdoctoral projects currently being undertaken and papers already published (50,51,52,53,54). We have also developed a high-throughput testing pipeline that is able to rapidly determine the biological potency of individual herbs and herbal formulas as well as being able to analyse how herbal medicine may improve mitochondrial health in humans.

For further information about mitochondrial testing contact Prof. Jimmy Bell at: J.Bell@westminster.ac.uk.

Acknowledgements: Thanks to Pukka Herbs for providing the PhD scholarship funding for Steve Woodley.

1. Riddle, J.M. (1985). Dioscorides on Pharmacy and Medicine. Austin: University of Texas Press.
2. Foster, S. (2011a). A Brief History of Adulteration of Herbs, Spices, and Botanical Drugs. HerbalGram 92: 42-57. Available at: https://www.herbalgram.org/resources/herbalgram/issues/92/table-of-contents/feat-hxadulteration/ [Accessed 17 Sep 2021]
3. Pliny the Elder. The Natural History. Trans. Bostock, J. & Riley, H.T. (1855). Available at: https://www.perseus.tufts.edu/hopper/text?doc=Plin.+Nat.+toc [Accessed 22 Sep 2021].
4. Bush, J.F. (2002). “By Hercules! The More Common the Wine, the More Wholesome!” Science and the Adulteration of Food and Other Natural Products in Ancient Rome. Food and Drug Law Journal, 57(3): 573-602. Available at: https://www.jstor.org/stable/26660496 [Accessed 26 Sep 2021]
5. Thorndike, L. (1922). Galen: The Man and His Times. The Scientific Monthly, 14(1), 83–93. http://www.jstor.org/stable/6569 [Accessed 24 Sep 2021]
6. Karaberopoulos, D., Karamanou, M., & Androutsos, G. (2012). The theriac in antiquity. Lancet (London, England), 379(9830), 1942–1943. https://doi.org/10.1016/s0140-6736(12)60846-0
7. Liu, Y. (2021). ‘Transforming Poisons’ in: Healing with Poisons: Potent Medicines in Medieval China. University of Washington Press: Seattle. Available from: https://uw.manifoldapp.org/read/healing-with-poisons-d74f2492-5f8c-4898-8cd1-546023f82ab8/section/69b5c6b9-093c-4946-8c17-3fd351944c06 [Accessed 13 Sep 2021]
8. Liang, Z. & Zhao, Z. (2017) The Original Source of Modern Research on Chinese Medicinal Materials: Bencao Texts. J Altern Complement Integr Med 3: 045. https://doi.org/10.24966/ACIM-7562/100045
9. Brand, E. (2018). Herbal Identification: The Clinical Implications of an Ancient Art. Legendary Herbs [Blog] 19th March 2018. Available at:  https://legendaryherbs.com/herbal-identification-the-clinical-implications-of-an-ancient-art/?v=79cba1185463 [Accessed 22 Sep 2021]
10. Tschanz, D.W. (2003). A Short History of Islamic Pharmacy. Journal for the International Society for the History of Islamic Medicine 1:11-17. Available at: https://www.ishim.net/ishimj/3/03.pdf [Accessed 21 Sep 2021]
11. Saad, B. & Said, O. (2011). Contributions of Arab and Islamic Scholars to Modern Pharmacology. In: Greco-Arab and Islamic Herbal Medicine: traditional system, ethics, safety, efficacy, and regulatory issues, pp. 87-100. Hoboken, NJ: John Wiley & Sons, Inc.
12. Farhan, S., Shamsi, S., Alam, T. & Perveen, A. (2020). Saffron (Crocus sativus L.): A Review of its Ethnopharmacological value. Am. J. PharmTech Res. 2020; 10(4). https://doi.org/10.46624/ajptr.2020.v10.i4.005
13. Bardell, D. (2004). The Biologists’ Forum: The invention of the microscope. BIOS, 75(2), 78–84. <a href="https://doi.org/10.1893/0005-3155(2004)75https://doi.org/10.1893/0005-3155(2004)75<78:tiotm>2.0.co;2
14. Grew, N. (1682). The anatomy of plants : with an idea of a philosophical history of plants : and several other lectures read before the Royal Society. London: W. Rawlin. Available at: https://archive.org/details/mobot31753000008869 [Accessed 25 Sep 2021]
15. Wragge-Morley A. (2012). ‘Vividness’ in English natural history and anatomy, 1650–1700. Notes and Records of the Royal Society of London, 66(4), 341–356. https://doi.org/10.1098/rsnr.2012.0045
16. Lopez, S. G. (2021). A brief history of optical microscopy. [Blog] John Innes Centre 12th May 2021. Available at: https://www.jic.ac.uk/blog/a-brief-history-of-optical-microscopy/ [Accessed 20 Sep 2021]
17. Linnaeus, C. (1735). Systema naturae : in quo proponuntur naturae regna tria secundum classes, ordines, genera et species. Paris: sumptibus Michaelis-Antonii David. Reprint 1744. Available at: https://archive.org/details/CaroliLinnaeiSy00LinnA [Accessed 25 Sep 2021]
18. Gordh, G. & Beardsley, J.W. (1999). ‘Taxonomy and biological control’. In Bellows, T. S. & Fisher, T. W. (eds.). Handbook of Biological Control: Principles and Applications of Biological Control. pp. 45–55. Academic Press.
19. Foster, S. (2011b). Towards an Understanding of Ginseng Adulteration: The Tangled Web of Names, History, Trade, and Perception. HerbalGram 111: 36-57. Available at: https://www.herbalgram.org/resources/herbalgram/issues/111/table-of-contents/hg111-feat-ginsengadult/ [Accessed 20 Sep 2021]
20. Jung, Y. S., Rha, C. S., Baik, M. Y., Baek, N. I., & Kim, D. O. (2020). A brief history and spectroscopic analysis of soy isoflavones. Food science and biotechnology, 29(12), 1605–1617. https://doi.org/10.1007/s10068-020-00815-6
21. Booker, A., Agapouda, A., Frommenwiler, D.A., Scotti, F., Reich, E. and Heinrich, M. (2018). St John’s wort (Hypericum perforatum) products – an assessment of their authenticity and quality. Phytomedicine 40: 158-164. https://doi.org/10.1016/j.phymed.2017.12.012. Epub 2017 Dec 28.
22. Koleva, I.I., van Beek, T.A., Soffers, A.E.M.F., Dusemund, B. & Rietjens, I.M.C.M. (2011). Alkaloids in the human food chain – Natural occurrence and possible adverse effects. Molecular Nutrition & Food Research, 56(1), 30–52. https://doi.org/10.1002/mnfr.201100165
23. Etheridge, C. (2016). Pyrrolizidine alkaloids – a practitioner’s perspective. EHTPA. Available at: https://bhma.info/wp-content/uploads/2016/07/Pyrrolizidine-alkaloids-a-practitioners-perspective-Chris-Etheridge-23.06.2016.pdf [Accessed 24 Sep 2021]
24. HMPC (2016). Public statement on contamination of herbal medicinal products/traditional herbal medicinal products with pyrrolizidine alkaloids. London: European Medicines Agency. Available at: https://www.ema.europa.eu/en/documents/public-statement/public-statement-contamination-herbal-medicinal-products/traditional-herbal-medicinal-products-pyrrolizidine-alkaloids_en.pdf [Accessed 24 Sep 2021]
25. Stratton, J., Clough, J., Leon, I., Sehlanova, M. & S. MacDonald (2017). Monitoring of tropane alkaloids in foods. FeraScience Ltd./UK Food Standards Agency. Available at: https://www.food.gov.uk/sites/default/files/media/document/fs102116finalreport.pdf [Accessed 24 Sep 2021]
26. Liang, C. P., Sack, C., McGrath, S., Cao, Y., Thompson, C. J., & Robin, L. P. (2021). US Fod and Drug Administration regulatory pesticide residue monitoring of human foods: 2009-2017. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment, 38(9), 1520–1538. https://doi.org/10.1080/19440049.2021.1934574
27. PRiF (2020). Report on the pesticide residues monitoring programme: Results of Quarters 4 2020. DEFRA. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1000503/prif-monitoring-2020-quarter4.pdf [Accessed 24 Sep 2021]
28. EFSA (2021). Metals as contaminants in food. [online]. Available at: https://www.efsa.europa.eu/en/topics/topic/metals-contaminants-food [Accessed 24 Sep 2021]
29. Fitzgerald, M., Heinrich, M., and Booker, A. (2020). Medicinal Plant Analysis: A Historical and Regional Discussion of Emergent Complex Techniques. Frontiers in Pharmacology 10: 1480. https://doi.org/10.3389/fphar.2019.01480
30. HPTLC Association (2020). The International Atlas for Identification of Herbal Drugs [online]. Available from: https://www.hptlc-association.org/atlas/about-hptlc-atlas.cfm [Accessed 9th Nov 2020]
31. Nybom, H., Weising, K. & Rotter, B. (2014). DNA fingerprinting in botany: past, present, future. Investig Genet 5, 1. https://doi.org/10.1186/2041-2223-5-1
32. HMPC (2005). Public statement on the risks associated with the use of herbal products containing Aristolochia species. London: European Medicines Agency. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/public-statement-risks-associated-use-herbal-products-containing-aristolochia-species_en.pdf [Accessed 24 Sep 2021]
33. MHRA (2014). Banned and restricted herbal ingredients. Available at: https://www.gov.uk/government/publications/list-of-banned-or-restricted-herbal-ingredients-for-medicinal-use/banned-and-restricted-herbal-ingredients [Accessed 24 Sep 2021]
34. Martena, M. J., van der Wielen, J. C., van de Laak, L. F., Konings, E. J., de Groot, H. N., & Rietjens, I. M. (2007). Enforcement of the ban on aristolochic acids in Chinese traditional herbal preparations on the Dutch market. Analytical and bioanalytical chemistry, 389(1), 263–275. https://doi.org/10.1007/s00216-007-1310-3
35. Wu, L., Sun, W., Wang, B., Zhao, H., Li, Y., Cai, S., Xiang, L., Zhu, Y., Yao, H., Song, J., Cheng, Y. C., & Chen, S. (2015). An integrated system for identifying the hidden assassins in traditional medicines containing aristolochic acids. Scientific reports, 5, 11318. https://doi.org/10.1038/srep11318
36. iBOL (2020). DNA Barcoding: A tool for specimen identification and species discovery. [ONLINE] Available at https://ibol.org/about/dna-barcoding/ [Accessed 16th Nov 2020]
37. NCBI (n.d.). Genome Database. Available at: https://www.ncbi.nlm.nih.gov/genome/browse/ [Accessed 19 Sep 2021]
38. Wong, T.-H., But, G. W.-C., Wu, H.-Y., Tsang, S. S.-K., Lau, D. T.-W. and Shaw, P.-C. (2018). Medicinal Materials DNA Barcode Database (MMDBD) version 1.5—one-stop solution for storage, BLAST, alignment and primer design, Database 2018: bay112. http://doi.org/10.1093/database/bay112
39. Thomford, N.E., Senthebane, D.A., Rowe, A., Munro, D., Seele, P., Maroyi, A. and Dzobo, K. (2018). Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences 19(6): 1578. https://doi.org/10.3390/ijms19061578
40. Parveen, I., Gafner, S., Techen, N., Murch, S. J., & Khan, I. A. (2016). DNA Barcoding for the Identification of Botanicals in Herbal Medicine and Dietary Supplements: Strengths and Limitations. Planta medica, 82(14), 1225–1235. https://doi.org/10.1055/s-0042-111208
41. Ferdowsian, H. R., & Gluck, J. P. (2015). The ethical challenges of animal research. Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees, 24(4), 391–406. https://doi.org/10.1017/S0963180115000067
42. Bracken M. B. (2009). Why animal studies are often poor predictors of human reactions to exposure. Journal of the Royal Society of Medicine, 102(3), 120–122. https://doi.org/10.1258/jrsm.2008.08k033
43. Lane, N. (2018). Power, Sex, Suicide: Mitochondria and the meaning of life. Oxford: Oxford University Press.
44. Wallace D. C. (2008). Mitochondria as chi. Genetics, 179(2), 727–735. https://doi.org/10.1534/genetics.104.91769
45. Javadov, S., Kozlov, A. V., & Camara, A. (2020). Mitochondria in Health and Diseases. Cells, 9(5), 1177. https://doi.org/10.3390/cells9051177
46. Nunn, A., Guy, G. W., Brysch, W., Botchway, S. W., Frasch, W., Calabrese, E. J., & Bell, J. D. (2020). SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing. Immunity & ageing : I & A, 17(1), 33. https://doi.org/10.1186/s12979-020-00204-x
47. Berger, R. G., Lunkenbein, S., Ströhle, A. and Hahn, A. (2012). Antioxidants in food: mere myth or magic medicine? Critical reviews in food science and nutrition 52(2): 162–171. https://doi.org/10.1080/10408398.2010.499481
48. Pingitore, A., Lima, G.P.P., Mastorci, F., Quinones, A., Iervasi, G. and Vassalle, C. (2015). Exercise and oxidative stress: Potential effects of antioxidant dietary strategies in sports. Nutrition 31(7-8): 916–922. https://doi.org/10.1016/j.nut.2015.02.005
49. Assi, M., & Rébillard, A. (2016). The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts. Oxidative medicine and cellular longevity, 2016, 9579868. https://doi.org/10.1155/2016/9579868
50. Woodley, S. B., Mould, R. R., Sahuri-Arisoylu, M., Kalampouka, I., Booker, A., & Bell, J. D. (2021). Mitochondrial Function as a Potential Tool for Assessing Function, Quality and Adulteration in Medicinal Herbal Teas. Frontiers in pharmacology, 12, 660938. https://doi.org/10.3389/fphar.2021.660938
51. Nunn, A. V., Guy, G. W., & Bell, J. D. (2016). The quantum mitochondrion and optimal health. Biochemical Society transactions, 44(4), 1101–1110. https://doi.org/10.1042/BST20160096
52. Henley, A. B., Yang, L., Chuang, K. L., Sahuri-Arisoylu, M., Wu, L. H., Bligh, S. W., & Bell, J. D. (2017). Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’. PloS one, 12(1), e0170917. https://doi.org/10.1371/journal.pone.0170917
53. Mould, R. R., Botchway, S. W., Parkinson, J., Thomas, E. L., Guy, G. W., Bell, J. D., & Nunn, A. (2021). Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H. Frontiers in molecular biosciences, 8, 630107. https://doi.org/10.3389/fmolb.2021.630107
54. Sahuri-Arisoylu, M., Mould, R. R., Shinjyo, N., Bligh, S., Nunn, A., Guy, G. W., Thomas, E. L., & Bell, J. D. (2021). Acetate Induces Growth Arrest in Colon Cancer Cells Through Modulation of Mitochondrial Function. Frontiers in nutrition, 8, 588466. https://doi.org/10.3389/fnut.2021.588466

Early pharmacopoeias (e.g., Pharmacopoeia Augustana 1601; Pharmacopoeia Londinensis 1618) were predominantly books of recipes for extracts, syrups, and oils and provided guidance for relative standardization of medicinal preparations, many of which were Galenical, relatively crudely extracted, herbal preparations.

Over time, pharmacopoeias (e.g., British Pharmacopoeia 1864) introduced standards of identity and quality for individual herbal medicines. Many of these reflected relative generality, sometimes not specifying plant species (e.g., acacia) but notably included information regarding the identifying morphological characters, origin, collection practices, and drying conditions of the drug material, clearly the primary considerations of early herbalists and plant collectors.

Another early pharmacopoeia, the Dispensatorium Lippiacum (Scherf 1792) introduced organoleptic characterizations and the use of magnifiers as part of the assessment criteria for plant medicines. Interestingly, the Dispensatorium Lippiacum was described as “predominantly addressing handcraft savvy pharmacists in small towns” (Friedrich no year), a description that could readily be applied to numerous traditional herbal extract (tincture) manufacturers in the US today.

In addition to being predominantly recipe books of relatively crude herbal preparations, some of the earliest of formal pharmacopoeias (e.g., Augsberg Pharmacopoea 1613), attempted to resist the ever-growing movement to use Paracelsun “chemical” medicines. According to history of pharmacy scholar George Urdang (1882–1960), in a decree of the Augsburg Senate in 1582, the apothecaries (druggists) were “admonished” not to prepare or offer for sale “substances which are known to be detrimental or poisonous, such as Labdanum minerale, the so-called antimony, also Turpethum minerale and other purging mecurials.”

Many of the precepts of the Paracelsun use of powerfully acting drugs, were in direct opposition to the empirical lineages of Galenists and Hippocratists. However, soon after, in 1589, the London College of Physicians proposed that the chemicals, salts, extracts, and metals of Paracelsus be included in the London Pharmacopoeia. This was eventually realized in 1618 with the inclusion of calomel (mercury chloride) among the medications for internal use.

While the juxtaposition of Paracelsun ideologies and those of the Galenists where in great part an attempt of the Paracelsuns to not blindly follow the empirical philosophies of the ancients, and were very much attempting to apply scientific experimentation in medicine, Galenists were alarmed at what they saw as the introduction of highly poisonous substances that had no basis of safety or efficacy into medical practice. As noted, this trend laid the groundwork for modern drug development that predominates today.

Another development marking the distinction between traditional and modern drugs was the introduction of chemical testing methods into pharmacopoeial monographs. Prior to analytical chemistry, the focus of pharmacopoeias and materia medicas was on morphology as the primary identity test and proper harvesting conditions and organoleptic characters as the primary criteria by which herb quality was assessed.

The Pharmacopoea Wirttembergica (1741) was the first pharmacopoeia to introduce chemical testing of drugs, a trend that continued as analytical chemistry advanced and chemically characterized drugs became dominant. Whereas the earliest pharmacopoeias and materia medicas reflected a relatively herbal-botanical approach to the assessment of herbal medicines, later Western pharmacopoeias, persisting to the current day, deferred to chemistry.

Pharmacopoeias codify the standards of identity, purity, quality, and testing for herbal drugs, traditional and modern. Generally speaking, if a pharmacopoeia does not provide a monograph for a specific drug then the drug cannot be traded commercially.

However, in herb-friendly societies, such restrictions do not apply. Most pharmacopoeias worldwide are relatively consistent in the fields of information they provide. The primary principle of pharmacopoeial monographs is to ensure the proper identity of the herbal ingredient to be used in a drug and develop minimal standards of quality and purity, so that when a pharmacopoeial-grade drug ingredient is used it will deliver the intended activity.

Some of these pharmacopoeial monograph standards are consistent with herbal assessment practices employed by traditional herbalists. Others are a result of the ever modernization of herbal medicines including the requirement for chemical testing that often overshadows traditional assessment techniques as discussed below.

Most pharmacopoeias lack information that is essential to procuring a high quality herbal medicine and rather create a minimum standard of acceptance. This influences many product manufacturers to produce products that meet a minimal quality standard rather than an optimal quality standard.

For example, the North American botanical goldenseal root (Hydrastis canadensis) contains from 2.5% to 6% of berberine alkaloids. Most pharmacopoeial standards (e.g. AHP, USP) formally require for the botanical to contain not less than 2.5% berberine alkaloids, the lowest amount the plant contains. In contrast, a traditional herbalist attempts to determine optimal harvest times in order to prepare an optimal medicine.

In most all cases, the interface between the medical practitioner, the classical botanical pharmacognosist, and the resultant pharmacopoeial standard has been largely lost creating a significant disassociation between the manufacture and practice of medicine, a connection that traditionally was much more integrated.

Approximately 74% of countries do not have their own pharmacopoeias. Of these countries lacking their own pharmacopoeia, approximately 56% utilize the monographs of the European Pharmacopoeia (EP) or United States Pharmacopeia (USP); approximately 30% utilize no pharmacopoeia; and, perhaps most telling, 78% of countries do not include herbal medicines in their national drug lists (WHO 2005).

In both developed and developing nations, unless provisions for access to non-official plant drugs are in place, or at the very least not restricted, availability to traditional herbal drugs can be impeded, a situation currently in place in the US where there is no regulatory allowance of traditional herbal medicines.

The following fields of information are contained in the majority of pharmacopoeial monographs worldwide. Different pharmacopoeias give greater or lesser emphasis to certain fields of information over others. Compliance with all aspects of the monograph in developed countries, most represented by the pharmacopoeias of China, the European Union, Iran, and the United States, is required, a requirement that contains redundancy and, in some cases, unnecessary testing, all of which drives the cost of traditional herbal medicines up.

Pharmacopoeial definition

Most monographs begin by defining the medicinal substance. This definition establishes the identity of the material being used and oftentimes, the minimum quality of the ingredient to be used, usually determined by the presence of a specific quantity of a chemical compound as noted in Table 3.

The pharmacopoeial definition is often the first body of information that establishes that a chemical test is required for acceptance of the herbal drug. Chemical testing is especially relevant when most of the activity of the botanical can be assigned to a specific constituent, when there is a narrow therapeutic to safety window of the drug, or when the medicinal qualities of the plant cannot be discerned through sensory analysis.

Generally speaking, and specifically regarding relatively safe herbal drugs, chemical testing has great value as a complement to organoleptic assessment. Chemical assessment is most critical for the more toxic of herbal medicines that possess a narrow therapeutic window.

However, analytical chemistry does not take the place of ensuring optimal times of harvest and proper drying, processing, and storage conditions. Chemistry can more fully inform these practices, but in itself is not sufficient to render analytical techniques such as botany, microscopy, and sensory evaluation obsolete or inferior to other techniques (see Macroscopic and Sensory [Organoleptic] Evaluation below).

Pharmacopoeia	Definition
European Pharmacopoeia (EP)	Whole or cut, dried flowering tops of Hypericum perforatum L., harvested during flowering time. Content: minimum 0.08 per cent of total hypericins, expressed as hypericin (C30 H16 O8; Mr  504.4) (dried drug).
United States Pharmacopoeia (USP)	St. John’s Wort consists of the dried flowering tops or aerial parts of Hypericum perforatum Linne´ (Fam. Hypericaceae), gathered shortly before or during flowering. It contains not less than 0.04 percent of the combined total of hypericin (C30H16O8) and pseudohypericin (C30H16O9) and not less than 0.6 percent of hyperforin (C35H52O4).

Macroscopic and sensory (organoleptic) evaluation

All pharmacopoeia monographs include a morphological description of the plant drug under various descriptive headings such as: Identification in the European Pharmacopoeia; Botanic characteristics in the USP; and Description in the Ayurvedic Pharmacopoeia of India and Pharmacopoeia of the People’s Republic of China.

These sections primarily give the relative form, size, shape, and physical features of the crude plant drug. These were the primary criteria used by traditional herbalists and early pharmacognosists in discerning the authenticity of the plant drug material. Great emphasis was similarly placed on plant morphology in the numerous pharmacognosy works of the 19^th and early 20^th centuries (e.g., Flückiger and Tschirch in 1887; Mansfield 1926; Sayre 1917; etc.).

Detailed instruction was provided in how an appropriate macroscopic/morphological assessment was to be performed on various plant parts. Today there is a plethora of references (e.g; Applequist 2006; Leon and Lin 2018; Pfaender 1991; Wichtl 2004; Zhao 2009; 2014) on the morphological assessment of crude plant drugs that provide a scientifically valid means for identifying a large number of medicinal plants to determine conformity with pharmacopoeial identification specifications.

Organoleptic assessment was, historically, and among herbalists today, the most important suite of characters for determining the relative quality of a crude plant drug. Organoleptic evaluation of plant material includes an assessment of the flavor, aroma, texture, and sensation experienced by the assessor and requires a specialized skill set akin to those required by food scientists and sommeliers, but to a much lesser degree. From a botanical medicine sense, flavor is broadened to include the sensation of texture and mouth feel.

Flavor arises when chemicals in foods (and herbs) react chemically with receptors on taste buds (gustatory calyculi) on the tongue, mouth, and throat. The tongue is covered with 2000–5000 taste buds, each one containing 50–100 taste receptor cells. In modern food sensory evaluation, five basic flavors are recognized: sweet, sour, salty, bitter, and umami.

This latter umami flavor was defined by the Japanese to describe the “savory” flavor of the commonly used food flavoring monosodium glutamate (MSG). There are relatively few herbs that possess this flavor and so its relevance to organoleptic assessment of botanicals is limited. More relevant are the flavors recognized in traditional herbal medicine systems, namely, sweet, sour, bitter, salty, pungent, and in Ayurveda, astringent, which is more accurately a mouth feel, but never-the-less, regarded as a flavor for purposes of describing herbal actions.

From an evolutionarily perspective, flavors are either aversive or desirable and inform human decisions about what and what not to eat. At a very basic level, the sweet flavor typically identifies high-energy foods; strongly bitter and or strongly acrid flavors are undesirous and may indicate a poison.

Flavors contribute part of the sensation of foods, and are complemented by aroma detected by olfactory epithelium receptors, texture detected mechanically such as through nerves in muscles, temperature through thermoreceptors, and sensations of coolness (peppermint leaves or oil), heat (cayenne, black pepper), and pungency (cloves, ginger root) through chemical sensations detected by skin and mucous membranes (chemesthesis), all of which are referred to by some as the “nature” of the herb.

In some cases, the flavors directly correspond to medicinally active constituents as established in western science, such as menthol from peppermint; capsaicin and piperine from cayenne and black pepper, respectively; and eugenol and gingerol from cloves and ginger root, respectively. Medicinally, menthol is an active constituent in topical analgesics. Menthol triggers cold-sensitive TRPM8 receptors in the skin.

It is through this mechanism that the familiar cooling sensation when inhaled, ingested, or applied topically is experienced (Eccles 1964), while menthol’s analgesic properties are mediated through a selective activation of κ-opioid receptors (Galeottia et al. 2002).

• The yellow color and bitter taste of the Chinese herb huang lian (Coptis spp.) (Zhao and Chen 2014) and the North American goldenseal root (Hydrastis canadensis) is correlated with berberine content, the herbs’ putative primary active constituent
• The mucilaginous content of herbs such as slippery elm (Ulmus fulva), flax seed (Linum usitatissimum), and psyllium seed (Plantago ovata), as determined by the swelling index included in most pharmacopoeias, is correlated with the soothing and moistening nature of the herbs
• The bitter flavor of Ganoderma species is correlated with immuno-modulating triterpenes (Kubota et al. 1982; Nishitoba et al. 1989)
• The numbing effect of Echinacea angustifolia root experienced when chewed is correlated with isobutylamides, which are among the most biologically and pharmacokinetically relevant of echinacea constituents (Woelkart et al. 2005).

These are only a few examples where there is a clear association between herbal flavors, known active constituents, and pharmacological effects.

Prior to the advent of chemistry, traditional herbal systems developed a very sophisticated system of sensory assessment that formed the didactic basis for understanding the pharmacology of the herbs. These systems also linked sensory qualities found in nature with sensory qualities of pathology and health (hot, cold, moist, dry, etc.), and then correlated those with the sensory quality of plant drugs.

On a philosophical level, Chinese medicine assigns the five specific flavors identified in that system to five organ complexes, respectively; bitter to the heart; sweet-spleen/pancreas; pungent-lungs; salty-kidneys; sour-liver.

Each taste is considered to have specific attributes such as bitter substances are draining and drying; salty substances soften and attract moistness; sweet substances nourish; pungent substances disperse; and sour substances astringe.

Chemically, bitter substances often correspond to alkaloids and certain triterpenes; sweet substances to carbohydrates and complex sugars (e.g. polysaccharides); pungency to volatile oils; salty substances to mineral salts; and sour to flavonoids and plant acids. While these basic flavor-chemistry correspondences are simplistic and not specific to disease complexes from a Western medical approach, they form the basis of pharmacology that is completely unified in the diagnostic system of Ayurvedic and Chinese medicine.

While herbalists historically did not specifically know what compounds were correlated with what activity, they recognized that it was the whole herb and the predominant nature of the herb that was considered active and that the quality of the herbal drug was discerned, and often directly correlated, to its sensory characteristics. These relationships were then either proven or disproven through experience and refined over centuries.

In Ayurveda and TCM, this system of sensory relationship between nature, humans, and medicines, is still actively applied by almost all herbal practitioners and has been integrated somewhat by some western herbalists. It is this very system that uniquely correlates qualities of nature, with qualities possessed in plants, with qualities reflected in anatomy, physiology, and pathology, creating a unified system based on natural principles of human health that is, itself, a microcosm of nature and is the traditional antecedent to individualized medicine.

This is yet another stark differentiator between traditional and modern systems whose diagnostic systems seldom look at the nature of the person but rather defer the understanding of human health and pathology to machines that generate often arbitrary values that reflect symptomatic changes in a statistical norm but says little about the individualistic needs of the human being.

This is one of the very reasons why there is a rapid and increased recognition of traditional herbal systems worldwide. It is not a fad, but a universal need to restore humanistic values to human health. The relationship with the plant itself is reflected in numerous herbal traditions as follows:

“The crude drug is the foundation of the pharmaceutical preparation… the [pharmacognosist] must be able to judge of the intrinsic qualities of drugs. This last is the most important part of the art of pharmacognosy, for while it is easy to learn to identify different drugs it is difficult to obtain the experience necessary to judge of quality shades….The study of crude drugs is most important.” – John Uri Lloyd (1849-1936)

 “Visual inspection provides the simplest and quickest means by which to establish identity, purity and, possibly, quality. If a sample is found to be significantly different, in terms of color, consistency, odor or taste, from the specifications, it is considered as not fulfilling in the requirements.” – WHO (1998)

“The way of using herbs, there is one way, there is no other. That is to master the herb’s nature and flavor, and to understand its yin and yang. Only with this understanding, even if the herbs are many, can you achieve desired results.” – Zhang Jingyue (1563–1640) Jingyue Quanshu (Complete Works of Jingyue)