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PART V Iatrogenicity of Dietary Supplements, Herbal Products, and Other Nontraditional Therapies in Cardiovascular Medicine Arshad Jahangir Ihor B. Gussak John B. Kostis INTRODUCTION Vitamins, minerals, and herbs are commonly consumed as dietary supplements or medicinal compounds to maintain wellness and to prevent or treat diseases. Vitamins are organic compounds that the body cannot synthesize in sufficient quantities and therefore must be obtained through diet, to act as cofactors in facilitating chemical reactions essential for maintaining normal body functions. They are required only in small amounts and are obtained from natu­ ral plant and animal sources. Minerals are similar to vitamins in that dietary consumption is necessary for the body to function optimally. Herbal supplements are plant products that constitute the largest proportion of complementary and alternative medicine used by consumers in the United States (1). Consuming a well-­ balanced diet fulfills most of the body’s need for vitamins and minerals, negating the need for megadoses promoted by manufacturers of supplements. Despite a lack of evidence for the beneficial effects of vitamins, minerals, or herbal products in the prevention of cardiovascular disease in individuals without nutritional deficiency (2), consumers continue to spend billions of dollars on supplements (3). Their rising demand is due in part to the increasing health consciousness of baby boomers, who actively seek ways to maintain wellness and to slow or delay the pro­ cess of aging (4). In addition, cultural ­ factors and widespread promotion of supplements in the media give the impression that megadoses of vitamins and other natu­ ral products are essential for preserving wellness, adding to their rising demand (5) and unrealistic expectations of disease prevention or even a cure for vari­ ous life-­ threatening conditions (6). Although consumption of natu­ ral supplements on their own is generally considered safe, long-­ term use and megadoses can cause adverse effects directly or through interactions with prescription drugs (7–10). For example, in 2014 the American Association of Poison Control Centers’ National Poison Data System ranked vitamins, other­ wise considered benign, 12th in a list of 25 common substances that lead to serious adverse outcomes (11). Vitamin overdoses with serious outcomes ­ were reported in more than 66,000 individuals, including a substantial number of ­ children (more than 25,000) (12,13). Similar concerns about the use of herbal supplements have been CHAPTER 28 Safety of Dietary and Herbal Supplements Side Effects and Contraindications Sulaiman Sultan, Ahad Jahangir, Ihor B. Gussak, A. Jamil Tajik, and Arshad Jahangir 338 / Safety of Dietary and Herbal Supplements kidney function, or other organ damage; ge­ ne­ tic polymorphism in herb or drug-­ transporting proteins (P-­ glycoprotein, organic anion transporter) or metabolizing enzymes (cytochrome P450); lifestyle choices (smoking, caffeine, alcohol consumption ); and concomitant use of other supplements or medi­ cations. Moreover, supplement-­ related­ factors such as dosage, time of administration, number of active constituents, quality control, contamination, and adulteration also play a large role. ­ These ­ factors become especially impor­ tant in vulnerable populations, such as the el­ derly, pregnant , and immunocompromised.­ Those who are in advanced stages of organ disease (renal, hepatic, neurological, cardiac, pulmonary); are frail and have reduced functional reserves or poor nutritional status; are on polypharmacy; or use medi­ cations with a narrow therapeutic index are at much greater risk (20–23) Metabolism and elimination pathways of both drugs and supplements are often compromised in at-­ risk populations; the kinetics and biological effects on the body can change drastically raised ­ because of disease and drug interactions (7–9). Contamination and adulteration of nutritional and herbal supplements with anabolic ste­ roids (14), stimulants (15), microbial agents (16), metals (17) and other compounds (18,19) pose additional concerns ­ because of unpredictable and dangerous health outcomes. Given the popularity and widespread use of natu­ ral supplements, especially among baby boomers and the el­ derly, this chapter focuses on safety and highlights the potential for adverse effects. For information about interactions between supplements and drugs, see Chapter 29.­FACTORS CONTRIBUTING TO ADVERSE EFFECTS Vari­ ous patient and supplement-­ related ­ factors may contribute to a greater likelihood of adverse effects (see Figure 28-1). Patient-­ related ­ factors include advanced age; body composition; presence of comorbidities; impairment of liver metabolism, • Advanced age • Body mass index • Comorbidities • Concomitant use of medications and supplements • Organ impairment (liver dysfunction, kidney disease) • Genetic polymorphism • Lifestyle (smoking, caffeine, alcohol intake) Patient-Related Factors • Active constituents • Adulteration • Contamination • Dosage • Time of administration • Quality control • Inadequate quality control • Limited information on safety and efficacy • Supplement contamination • Public misperception • Underreporting of adverse...


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