Natural Does Not Mean Safe

*Onyenmechi Johnson Afonne and Emeka Chinedu Ifediba*

### **Abstract**

Medicinal plants are rich sources of natural products, the principal constituents in herbal medicines, utilized for the treatment and prevention of diseases. High consumer expectations for health care, in the face of soaring cost of conventional pharmaceuticals, have popularized herbal medicines in different regions of the world. The consumption of these botanicals and their products has recently gained much impetus with the assumption that since these active principles in them are natural, they are, therefore, safe. Assertive as this idea could be, scrutinizing the perspectives on which it is premised is critical in minimizing probable risk on human health. Most plant parts are repositories of natural toxins, phytosteroids, and bioaccumulated toxicants, all of which are driven by natural processes. Besides intrinsic toxicity possessed by phytotoxins, some innocuous chemicals in medicinal plants can be biotransformed to toxic components. Some chemicals in medicinal plants that are of safety concerns include the endocrine-disrupting chemicals such as phytoestrogens, bisphenol A, and phthalates, among others. The persistent, bioaccumulative, and toxic metals have also been identified in medicinal plants. Some of these chemicals have been found to cause metabolic derangement and carcinogenicity. It is, therefore, imperative that linking natural products to safety should rather be empirical.

**Keywords:** natural, safe, phytotoxin, phytoestrogen, dioxin, toxic metals

### **1. Introduction**

Herbal medicines are the mainstay of complementary or alternative medicine in most developing and some developed countries [1–3]. The use of herbal medicine in history and in different cultures was premised on the discovery of medicinal plants by trial and error, serendipity, or by the observatory science of zoopharmacognosis [4, 5]. Plants have been used as drug by the primitive man and are presently in high demand with increasing acceptability globally. Currently, the demand for plantderived products has increased across the world with the Middle East, Latin America, Africa, and Asia accounting for greater than 85% of the populations predominantly relying on herbal medicine for their health care needs [1]. Medicinal plants are a variety of plants with medicinal properties in some or all of its parts. Parts that have prominently contributed to these properties include the seeds, root, leaf, fruit, skin, and flowers [6, 7]. The rich contents of phytochemicals in medicinal plants have provided the basis for their use in herbal medicines. The World Health Organization (WHO) had defined herbal medicines to include herbs, herbal materials, herbal preparations, and finished herbal products that contain, as active ingredients, parts

of plants, other plant materials, or combinations thereof [8]. The production of plant secondary metabolites (PSMs) is a common phenomenon in the plant kingdom. These chemicals include a wide range of compounds, such as alkaloids, saponin, flavonoids, anthroquinones, terpenoids, coumarins, lignans, polysaccharides, polypeptides, and proteins [9]. Plant secondary metabolites are known to possess diverse physiological roles. They act as signaling compounds to attract pollinators or seed dispersers and defense against threats such as microbes, insects, predators, and abiotic (radiation, temperature, and drought) stress [9–12]. The presence and diversity of these compounds in plant materials are inducible by natural selection (or processes) and new breeding methods that accentuate these protective/adaptive mechanisms [13]. Most of these products found in medicinal plants surely provide a diverse chemical space for drug discovery and management of many health conditions [14, 15]. The search for these products is attracting interest globally especially from Asia, Africa, or Latin America [16].

The curious expression that PSMs are natural products underpins the belief that as "natural" products, medicinal plants are "safe" or "safer" than conventional medicines. Indeed, some PSMs in medicinal plants are intrinsically toxic [17, 18] or are activated by enzyme systems in humans to toxic compounds [19]. There are also certain classes of PSMs with endocrine-disrupting capabilities [20–22]. This perspective that links natural to safety underscores core health issues in the use of herbal medicines. First, adverse effects resulting from the consumption of herbal medicines are usually not reported since consumers generally regard them as safe and, therefore, would not attribute symptoms to their use [23]. Second, the increased toxicity of conventional drugs when taken concomitantly with these "safe" products can also ensue. The abuse of these natural products is also inevitable, posing an incremental risk of toxicity since consumers usually care less about the quantity (dose) and frequency of herb intake. Besides PSMs, "natural processes," such as adsorption and absorption, introduce environmental toxic substances into plant systems, thereby expanding the profile in the chemical composition of plant species. Environmental changes and pollution effects are major determinants in this regard and are critical in the definition of "nature" and "natural" and the safety attributed to their products. A subset of these xenobiotics is carcinogenic and can also cause metabolic derangement in humans on exposure beyond certain threshold. Regulation governing the production and sale of herbal medicines vary from one country to the other under regulatory categories, such as health foods, dietary supplements, natural health products, and functional foods [8]. These categorizations do not suggest safety in anyway but an approach for control and marketing. Therefore, leveraging on the nominal representation of the word "natural" in defining safety is not only ambiguous but also deceptive. Empirical data have shown that natural does not always mean safe in the premise of utility of medicinal plants for therapeutic consequences.
