Chapter 58. Toxic Contamination of Nutraceuticals and Food Ingredients
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CHAPTER 58 Toxic Contamination of Nutraceuticals and Food Ingredients Fernando Gil, Antonio F. Hernández and M. Concepción Martín-Domingo INTRODUCTION AND BACKGROUND ingredients (NFI) consist of dietary supplements (e.g., vitamins, minerals, co-enzyme Q, carnitine), herbal Medicinal plants have been used therapeutically products (e.g., flavonoids, Ginseng, Ginkgo biloba, Saint throughout the world as tools of traditional medicine, John’s wort, Saw Palmetto), and bioengineered and pro- from Ayurveda to Chinese traditional medicine. In west- cessed foods (e.g., probiotics, omega-3, fish oil, trans- ern countries, despite the development and production genic plants) purported to benefit health DeFelice,( 1995; of synthetic medicines, the popularity of over the counter Pirotta et al., 2000; NNC, 2014). health foods, nutraceuticals, and medicinal products Lockwood (2007) defines nutraceutical as a term used from plants or any other natural source has recently to describe a medicinal or nutritional component that increased because of the belief that they could be more includes a food, plant, or naturally occurring material effective than conventional therapies for preventing or that may have been purified or concentrated and that treating diseases. This attitude indirectly indicates the is used for the improvement of health by preventing or lack of confidence of the general public in conventional treating a disease. Dolan et al. (2003) considered the term medical treatments. “dietary supplement” to describe a product that contains Several reasons may account for the worldwide one or more of the following ingredients: vitamins; min- growing use of nutraceuticals and dietary supplements, erals; herbs or other botanicals, amino acids; dietary sub- among them being the lower rate of adverse effects as stances used as diet supplements to increase the total compared to conventional drugs and the higher costs of daily intake; or concentrates, metabolites, constituents, many traditional pharmaceutical formulations (Meena extracts, or combinations of these ingredients. The Dietary et al., 2010; Rao et al., 2011; Martínez-Domínguez et al., Supplement Health and Education Act (DSHEA) defines 2014). nutraceuticals as a dietary supplement that may contain Consumers increasingly rely on dietary supplements an herb or other botanical, or a concentrate, metabolite, to maintain mental acuity and to overcome age-related constituent, extract, or combination of any ingredient problems, such as menopause, benign prostate hypertro- from the other categories (Frankos et al., 2010). However, phy, and elevated blood pressure and cholesterol levels, toxic contamination of NFI during any stage of produc- and also to relieve stress (Raman et al., 2004). tion can lead to changes in their quality and safety. The The term nutraceutical was coined by DeFelice to health hazard of these products largely depends on the define any substance that may be considered a food presence of unusually high concentrations of chemical or part of a food providing medical or health benefits. ingredients that may result in toxicity or even fatality if Nutraceuticals may be useful for the prevention and they are consumed (Chan, 2003). treatment of disease or as an alternative to nonconven- Furthermore, the consumption of NFI contaminated tional medicine in primary health care. They include with environmental pollutants by vulnerable subgroups herbal medicines (Ayurvedic, Chinese, Tibetan, African, of the population, such as pregnant women, children, Amazonian, Herbalism), naturopathy, vitamin and min- and elderly adults may become a serious problem if the eral therapy, and homeopathy. Nutraceuticals and food tolerable level of exposure is exceeded. For example, Nutraceuticals. DOI: http://dx.doi.org/10.1016/B978-0-12-802147-7.00058-9 825 © 20122016 Elsevier Inc. All rights reserved. 826 58. TOXIC CONTAMINATION OF NUTRACEUTICALS AND FOOD INGREDIENTS children and toddlers have greater susceptibility to poi- certain NFI, including herbal medicines and raw herbs, soning by heavy metals and metalloids, as opposed to are quite general and only related to microbiological adults because of their lower body weight, resulting in properties and registration of items themselves. In turn, higher dosage of these substances. there are no specific guidelines for active constituents or Risk assessment paradigms might underestimate the toxic contaminants (Cooper et al., 2007). effects of these chemicals on children and the elderly Little information is available on the toxic contamina- (Gomez et al., 2007). For instance, these subpopulations tion of nutraceuticals and dietary supplements except may be more susceptible to adverse effects associated for herbal drugs. Hence, this review is based largely with ingestion of low doses of heavy metals found in on medicinal plants, assuming that they comprise the Hypericum perforatum, commonly known as St. John’s majority of NFI. wort, widely used for the treatment of mild to mod- Herbs can be collected indiscriminately from non- erate forms of depression. Herbal remedies are also cultivated and nonenvironmentally friendly areas by frequently used by pregnant women regardless of the untrained people and placed into the market with- scarce information about their safety during pregnancy out any control. This means that consumers might be and breastfeeding. In addition to the risk of miscarriage exposed to herbal products potentially contaminated from several herbs (e.g., nettle, passionflower, and aloe), with pesticides, heavy metals and metalloids, myco- a number of epidemiologic studies suggest that cer- toxins, or radioactivity, or adulterated with drugs tain herbs (e.g., those rich in unsaturated pyrrolizidine (Figure 58.1). The presence of forbidden pesticides or alkaloids) are associated with embryotoxic or fetotoxic excessive amounts of regulated pesticides and heavy effects (de Smet, 2002; Gurib-Fakim, 2006; Rodriguez- metals depends on the source of herbal materials and Fragoso et al., 2008). whether or not they are grown in a contaminated area. Because potential interactions between pharmaceu- Moreover, chemical toxins may come from unfavorable tical formulations and herbal products (or other NFI) or wrong storage conditions or chemical treatment dur- cannot always be predicted, unexpected effects can ing their storage. In turn, the presence of drugs could be observed because of a change in the magnitude of the be related to unprofessional practices of manufactur- effect of conventional drugs (Shaw et al., 1997). These ers. Ideally, the consumption of NFI products should be types of interactions can be of either a pharmacokinetic strictly controlled and is pertinent to better knowledge or a pharmacodynamic nature (Rodriguez-Fragoso of the levels of different contaminants (specifially heavy et al., 2008). One of the most important pharmacoki- metals and pesticides) in raw materials (Chan, 2003; netic interactions occurs between herbal products and Meena et al., 2010; Harris et al., 2011). drug-metabolizing enzyme systems, particularly the Phytotherapy has a very long tradition and has been cytochrome P450 (CYP450) isoenzymes. This type of inter- popular for centuries. Medicinal plants have a long his- action has great importance in clinical practice because tory of therapeutical use throughout the world and still CYP450 isoenzymes metabolize a large number of drugs constitute an important part of traditional medicine. In and chemicals. Also, important genetic polymorphisms the last quarter of the past century, the therapeutical use of CYP450s have been reported to modify drug disposi- of herbal products has increased in developed countries tion in different populations. For instance, the interac- tion between peppermint oil and some CYP450 isoforms (CYP1A2, CYP2C19, CYP2C9, and CYP3A4) may modify levels of drugs metabolized by these isoforms (Maniacal Heavy metals and Wanwimolruk, 2001; Unger and Frank, 2004). Metalloids Oligoelements Pesticides Good manufacturing practices (GMP) and other legal requirements must be met to avoid adverse reactions Nutraceuticals or product quality deficiencies as a consequence of the and rapid growth of health-related foods and supplements Food (Genuis et al., 2012). Ingredients In the United States, the DSHEA establishes regula- Radioactive tions and limits label claims on dietary supplements. In Mycotoxins Contamination Europe, food supplements are converged by the Directive Adulteration 2002/46/EC and herbal medicinal products are converged and by Directive 2004/27/EC. However, there is no formal Undeclared Chemical legislation regulating nutraceutical products (Gulati and Substances Berry Ottaway, 2006; Martínez-Domínguez et al., 2014). Although conditions for importation of pharmaceutical FIGURE 58.1 Main toxic contaminants in nutraceuticals and food products are rigorous, the guidelines for importation of ingredients. NUTRACEUTICALS CHEMICAL CONTAMINATION IN NUTRACEUTICALS AND FOOD INGREDIENTS 827 because of their popularity among consumers and the Although raw materials are typically and supposedly widespread opinion that “natural products” implies free of substances that are currently added to patent “harmless products” and the lack of toxic effects. Their medicines, they could contain relatively low levels of easy accessibility and relatively low cost also have con- toxic compounds, particularly heavy metals and pesti- tributed to an increased use; however, their popularity cides. The majority (>95%)