Azienda Ospedaliero Universitaria Careggi, Florence
The term “herbal” often instinctively arouses an immediate sense of stiffened perplexity, caution, mistrust or complete opposition in pharmacologists as well as clinicians, not least of all because numerous active or non-active destabilising factors are present within in the same botanical species. It is also because these factors can vary widely during the lifecycle of a plant, as well as in similar botanical species which can contain very different substances to each other, because of the apparent lack of clear guidelines separating potentially useful plants from those that are useless or harmful, the commercial availability of plant products used as medications, possible environmental contaminants, the pitfalls of drug interactions, not to mention the intrinsic toxicity of well-known substances, like ephedrine for one.
All of this is likely to prevent a rational examination of this world, which is viewed as “other”, as different, and sometimes even as an alternative to medicine, which risks biasing the clinicians and pharmacologists who may, for example, be analysing a suspected adverse reaction to a 'natural' product.
The need for clarification
Firstly, we need to clarify events. It is possible to use single substances of natural origin, which are registered as drugs and supplied with the standard authorisations for release onto the market, but one can also use medicinal plant extracts containing several active substances, which are used in registered medicinal specialties too. In such cases, we have technical data sheets at our disposal, along with those concerning authorisations by national health authorities. With such cases, we talk about controlled phytotherapeutics, which are subject to preventative controls that have already had risk/benefit ratios analysed. Some of these specialty drugs can be prescribed with a mandatory doctor’s prescription; others, however, are available over the counter from pharmacies. Finally, regulations allow plant extracts to be used in the form of galenic preparations, for which the pharmacist has to guarantee the safety and quality of the raw materials used, according to the specifications in reference Pharmacopoeas.
All of this tells us is that an entire section of the plant world, which seems to be uncheckable and unverifiable is, in reality, both verifiable and checkable. Proper and appropriate management of these products in patients is obviously possible, because clinical studies, reviews in the literature, and efficacy tests are available, along with data about the risks, toxicity, pharmacological interactions and allergic reactions. As for ensuring there is sufficient and adequate evidence of their effectiveness however, these two factors are actually the weakest link in the chain whenever a physician uses galenic preparations that are not registered as specialties, for which the physician must assume responsibility.
The shift towards “the other world”
This is the shift towards “the other world” of plant products. Namely that non-medicinal products, products based on herbs which belong to the world of supplements and herbal products in the widest sense, which the regulations “only” intend to act as supplements for diets deficient in a few macro or micronutrient elements, or as a physiologically support for one or more of our bodily functions, which have no therapeutic value. This opens the window to this world, widely and chaotically, to numerous products based on herbs that are not used for medicinal purposes, but which contain active substances, and which may have not only some interesting dietary, nutritional and pharmacological properties, but toxicological properties too. About 40.000 of these herb-based supplements are available on the open market in Italy.
A further consideration which has to be made at this point, is that with such wide availability of natural products lacking the seal of ‘legal drug’ on the market, end users may feel that some kind of self-medication has been authorised, and this can expose them to often underestimated risks. Because, in most cases, self-medication with natural products actually involves non-medicinal products, which are therefore not intended for self-medication, and therefore not checked for this purpose, if they are not contaminated with household products, or prepared after spontaneous herb gathering with all the risks that go with that, like gathering toxic herbs mixed in with healthy herbs, or even gathering healthy herbs from unhygienic places like the side of the road. Or finally, self-medication with natural products at the same time a drug treatment is already underway, disregarding the potential risks of dangerous pharmacological interactions, which can also be fatal.
Whilst wishing to remain optimistic, even if we assume that our patient is taking a natural product, which is qualitatively controlled from a quality and safety perspective, we cannot overlook the fact that herbs are sometimes used, not on the basis of scientifically acquired evidence of effectiveness, but merely on the basis of traditional use. These are therefore entirely untested, not documented by clinical trials, and are only hypothesized in relation to a few pharmacological or epidemiological studies, if at all. Tradition, on the one hand, and studying mechanisms of action on the other hand, are simply two of the tools we can use to define our puzzle, neither of which however is in any way sufficient to ensure effectiveness and safety of use. So, do clinicians or pharmacologists have a reason to be suspicious, cautious and hesitant when discussing “herbs”? The answer is ‘Yes’, certainly, as befits any researcher to anything that emerges from their experiments. A researcher should be equally open to any empirical data if it has been accepted by the scientific community, whether it is their own data or data from other people.
The importance of phytovigilance
This is why phytotherapy (by which we mean that branch of medicine which studies and uses phytotherapies for preventative and curative purposes) cannot ideologically, or in a derogatory way be referred to as “proto-pharmacology” or, conversely, be accepted and viewed as a good, branded “natural medicine” as opposed to official drugs. Medicine is one thing; regulations are usually the same for everything, for both efficacy tests as well as the assessment of undesirable effects. Scientific method remains sovereign.
The special features of phytotherapeutics, which represent a complex of substances, may lie in the improved absorption of certain molecules when inserted into a phytocomplex, or in a synergistic action mechanism in some cases, in toxicity reduction in others, due to the presence of a substance that, for example, impedes the metabolic activation of their toxicity, as happens when you take an infusion of fennel, whose flavenoids prevent toxic activation of estragole.
At the same time, these same peculiarities of phytocomplexes are also responsible for the risks described. The more substances they contain, the greater the exposed risk of allergies, drug interactions, and failures to reach the threshold of pharmacological efficacy The presence of more substances makes it complicated, and sometimes impossible, to conduct an analytical and complete study of the mechanisms of action of phytotherapeutics, such as analysing possible adverse reactions, including the study of causal links between reactions and natural products. This happens particularly when the natural product taken by the patient contains several herbs simultaneously, a condition that is very common when they resort to using uncontrolled self-medication. All of this leads us to underline the importance of the phytovigilance system put in place in 2002 at Mational Health Institute (Istituto Superiore di Sanità, www.epicentro.iss.it) by agreement between the AIFA and the Ministry of Health, because it allows the detection and analysis of spontaneous alerts, a basic study element for understanding possible toxicity mechanisms, as well as for releasing products that are potentially non-compliant with regulatory standards onto the market. A specific system is needed for natural products that are not registered as medicines, those which, in theory, expose people to higher risks, the most significant of which are probably environmental contaminants (like heavy metals and aflatoxins), the presence of quantities of non-compliant substances, types of extract that differs from the one expected, and variable quantities and concentrations of active ingredients, rather than inappropriate clinical use. When confronted by a suspected adverse reaction, quali-quantitave analyses of the implicated product or products becomes important, followed by an assessment of all of the reports as a whole.
- Ann Ist Sup Sanita 2005;41:27-33 CDI NS Pharmacoepidemiol Drug Saf 2008;17:626-35 CDI