/Herbal supplements cross-reactivity and the pitfalls of self-medication

Herbal supplements cross-reactivity and the pitfalls of self-medication

Herbal supplements – the pitfalls of self-medication

Herbal extracts have been used for millennia in the treatment of diseases, wounds, for improving of the general health of people and even sometimes for supernatural rituals. In this blog-post thought, I am not going to talk about getting high on those lavender extracts, but rather on the science behind the use and misuse of herbal supplements and the potential implications of both.

The first question to get out of the way is what are herbal supplements

Herbal extracts, in the form of various supplements, are whole plants or certain fractions of plants formulated in an easily ingestable form, which is intended to improve health or to cure a condition. Herbal supplements are not intended as an alternative to food and are not taken for their nutritional value. According to some statistics, the Global Herbal Supplements market was worth a whopping $49.1 billion in 2016 and is expected to almost double its worth by 2022 (Reuters). But here’s more to supplements that you think you know, so keep on reading.

Who makes supplements?


Traditionally, tinkering with plant extracts and tinctures is the realm of pharmaceutical companies looking to find out exactly which one from the whole bunch of molecules present in a traditionally used plant might be providing the beneficial effects observed through the centuries. This is often painstakingly slow and expensive R&D work. It starts with isolating the specific part of the plant that contains the most beneficial substances, through isolating the exact fraction of molecules which potentially hold this effect, to identifying and making enough of the compound (either by further extraction or chemically synthesizing it), and formulating it in a way that is easily digestible and marketable. Such process, can easily take a decade. on top of that, success rates are relatively low and the overall price is high also because safety and efficiency trials must be conducted so that the formulation would be allowed on the market and the the producer’s health claims would be approved. 

Food producers

In recent years, some herbal extracts started being formulated and sold as nutraceuticals or food supplements. Such preparations are still expected to be produced in compliance with certain standards. The dietary herbal supplements produced by the food industry,  often fall under different legislative tabs and are thus exempt from the ultra-strict regulations that herbal medicines are subject too. For supplements, often only safety and purity tests are required by law, but no trials to prove their desired effects.

Only recently EFSA (the European Food Safety Agency) and NIH (the National Institute of Health in the USA) started initiatives to re-evaluate and establish the actual beneficial effects along with the safety of herbal supplements. The proposal to do so is by increasing the requirements for scientific evidence before health claims are made in relation to a product of this type. This, naturally caused some concerns from manufacturers about increased costs for development and unnecessary legislative burden.

Nutritional/health gurus

As it is in many other cases, internet self-proclaimed gurus jumped on the money-wagon with supplements and herbs. Unfortunately, such pseudo-experts often do not understand the potential for beneficial or harmful effects of either herbal preps or nutritional supplements. The internet has played a major role in the boom of use of supplements.

A concerning observation shows that many of the concoctions and formulations which can be purchased on-line do not comply with the regulations for either nutritional, or herbal supplements. Frequently, there are even discrepancies between the composition of separate batches. Even in supposedly standardized products deviations with harmful contaminants have been found. With completely unregulated substances the consumer runs the risk of being exposed to lead, arsenic and other heavy metals at levels many times higher than the allowed safety limit (J. Spink, 2013)

The GOOD and the BAD of herbals and supplements

As I already eluded in the beginning, version of herbal medicine and nutritional supplements have been used by humans for as long as our ancestors have been trying to heal their ill and improve their well-being. No-one in their right mind should argue against the existence of thousands and may be millions of biologically active compounds in plants which can indeed have curative or beneficial effects. The World Health Organisation has an extensive database and a number of documents on this (WHO on traditional medicine).

Hence, again, it comes as no surprise that natural compounds are still today the most prominent hub of inspiration for new pharmaceuticals. There is a significant body of scientific evidence on the benefits of various naturally occurring compounds. Further more research is constantly done to improve on such compounds in order to boost their activity, increase their specificity, and reduce potential negative side effects (one interesting place to start reading is the Science Direct Herbal Medicine database). But, as everything else – the herbals have a flip-, darker, side.

As the Latin saying goes “The dose makes the poison”. This is especially true for products with high natural variation like plant extracts and herbal preparations. Many of the bioactive compounds responsible for the medicinal effects of plants accumulate as a response to the environment of the plant while it is growing. Because of this, there is a huge number of factors which can influence the proportions, concentrations and specific types of compounds which are accumulated in the same species of plant (an Open Access scientific review on the topic).

Next to this natural variation, the methods of preparation and extraction influence greatly the final composition of the supplement, in some cases much more dramatically, than the natural variation (here’s a mini review-comparison on some of those methods). All these factors combined mean that if one product is not strictly and frequently controlled for quality and safety, the risk that it would do more harm than good increases.

Another altogether different phenomenon is the human factor. It has been scientifically proven that people provided with some easily-digestible information and with basic knowledge about medicine tend to overestimate their own ability to judge on the safety and appropriateness of certain type of treatment or health approaches (the SciComm Journal Club made a great summary of this research). A catchy, but insufficient or incomplete information if taken without “a grain of salt” might turn out to be doing more harm than no information at all. Which is not to say that if you are not an expert MD or a scientist, you shouldn’t seek information on how to improve your health and well-being. Instead, if you come across health advice which seems too clear-cut, black and white claiming something is good or bad for you, it’s probably better to consult with a specialist.

Self-medication is a widespread practice, and a dangerous one. It extends through all types of external formulations one can take – from prescription drugs, through over-the-counter medication, to herbal medication and supplements. The dangers of self-medicating should be obvious for everyone but there’s more on the topic by the NIH which has collected a lot of information here. Self-medication with herbal substances can be even more risky than with other medicines exactly because people falsely consider them as safer and their ingredients less active. Many times now science has shown exactly the opposite. 

Science has spoken - herbal supplements can be dangerous

Several peer-reviewed studies have been published, showing that there are considerable risks from frivolously taking herbal supplements. Let’s briefly look at some of the most common ones: 

Toxicity and contaminations

I already mentioned above the potential for contamination with unexpected toxins especially in the case of taking non-standardized and safety scrutinized herbal products. Additionally, some of the most potent biological toxins and poisons are also isolated from plants, so taking a wild change with random herbal isolates can sometimes be as dangerous as playing Russian roulette.

There is an inherent difficulty to threat conditions related to poisoning from herbal products. As they are considered by consumers to be the safest medical products on the market, often their use remains unreported, which hinders finding the root cause of a problem caused by a plant toxin or formulation contaminant (Science Daily talked about the topic).

Unexpected sensitivity

As with any other bio-active compound, the ones in herbal medicines have the potential to cause hypersensitivities, allergies or to influence undiagnosed or underlying conditions. When less than half of the patients inform their doctors that they are using herbal products (stats here), these side effects can remain untreated and worsen the health of the individual instead of improving it. For example, for people with liver and kidney problems, many herbal products are strictly forbidden (peer-review study on the topic).

Cross-reactivity with other medication

Another very real and rarely considered risk is the cross-reaction of the herbal product with another (prescription or not) medication. As many as 1 in every 4 people in the USA with chronic condition admits to taking some sort of dietary or herbal supplement (according to an article published in 2017). Since the general trend is that individuals opt for supplements with various nature independently of their physician’s consultations, it’s safe to assume that a high percentage of these patients also haven’t consulted their doctor for possible cross-reactions with their usual medication. 

A relatively recent systematic review (detailed results of which can be found here) collected and curated all the existing scientific evidence for potential cross-reactivity between prescription drugs and herbal and dietary supplements. The review summarizes a total of 1,491 unique pairs of herbal/dietary supplements-drug interactions. Such interactions could potentially alter the effect of the drugs the patients are taking.

With the great variety of supplements and herbs, the number of potential interactions in each specific case is virtually unpredictable. A herbal compound or a supplement can, for example, increase or decrease the absorption of a medication, altering the intended prescribed doses. Other compounds can completely block the uptake of the medication by irreversibly binding to it and not allowing the body to take advantage of the drug. In yet another type of cases, a herbal bio-active compound might chemically interact with a compound of the prescribed drug and entirely alter its function in the body causing completely unexpected effects.

The verdict - to supplement or not to supplement?

The bottom line is, that like with everything else, one should be careful and considerate of the potential risks of combining drugs and not forget that herbals and dietary supplements can be equally potent as many pharmaceutical drugs.

Many supplements have been developed to save lives and have done so for billions of people, by preventing malnutrition and diseases. It is also irrefutable, that herbal medicines have their place in therapies and that plants continue to provide new compounds based on which we can develop better medications. But the important message is that in all these cases, both herbal medicines and food supplements are taken for a reason and with a very specific aim. Self-prescribing a mouth full of vitamins, supplements and tinctures is probably grossly overdoing it, especially if you live in the developed world.

So if you think that you are lacking a specific nutrient or if you feel that the presence of a certain undesired symptom can be remedied with a herbal concoction, go and consult with a physician you trust and if you want you can still insist on trying herbal medicine before having another drug. Otherwise, if you are lucky enough to not poison yourself, you’d be flushing your money down the toilet at best.