WHAT ARE NUTRACEUTICALS?
Nutraceuticals are commonly defined as any substance that is a food or part of a food which provides medicinal or health benefits, including the prevention and treatment of disease.1 This term includes a broad array of agents such as dietary supplements, isolated nutrients, herbal supplements, and specific food products.2 It is estimated that 77% of Americans use dietary supplements, including more than 70% of adults who are aged more than 60 years.3,4 With an increase in use and variety of nutraceuticals, it is essential that pharmacists are made aware of the potential benefits and risks of the products that are available for consumer use.

MONITORING OF NUTRACEUTICAL PRODUCTS IN THE UNITED STATES
Monitoring of nutraceutical products differs from that of prescription drugs. Nutraceuticals are broadly regulated under the Federal Food, Drug and Cosmetic Act, with more specific regulation for dietary supplements, vitamins, and minerals, falling under the Dietary Supplement Health and Education Act of 1994 (DSHEA). Although the FDA oversees the manufacturing and distributing process of supplements, rigorous clinical trials and investigations of safety and efficacy are not required to market such products. Nutraceuticals are not intended, according to FDA standards, to prevent, treat, or cure disease.5-7

According to the DSHEA, manufacturers and distributors of dietary and herbal supplements must ensure the safety and accurate labeling of their products, to guarantee that they are not adulterated or misbranded.7 If adulteration or misbranding is identified, the FDA is responsible for taking action to ensure safety and remove products from consumer use. For example, in March 2019, the FDA took action against foreign and domestic companies stating false claims for more than 50 supplement products alleging to prevent, cure, or treat Alzheimer disease.8,9 To learn about the latest warnings and alerts regarding the safety of such products, pharmacists can refer to the FDA Dietary Supplement and Advisory List available on the FDA’s website.10

In addition to FDA oversight, the official United States Pharmacopeia (USP) and the official National Formulary are considered national compendia in the United States, accepted as sources to provide official guidance. The USP sets quality standards for drug substances, drug products, excipients, and dietary supplements under federal law in the United States, and USP standards are considered binding under the Federal Food, Drug, and Cosmetic Act for any manufacturer claiming USP approval.11-13 The 4 P’s of quality that the USP provides are: Positive identity, Potency, Purity, and Performance of ingredients in a product.14 Positive identity ensures the listed ingredients are present in the supplement and that rigorous testing and auditing have been conducted for verification. Assessment of potency guarantees the listed ingredients are present in the stated amounts. Purity safeguards against harmful excipients and/or contaminants such as pesticides, mold, and active pharmaceutical agents, to name a few. Performance ensures the formulation will break down and release the appropriate ingredients, allowing absorption via the labeled route of administration.14

USP also provides standards for food ingredients under the umbrella of nutraceutical products. Pharmacists can refer to the Food Chemicals Codex monographs for references regarding assessment of food chemicals and additives.12

UNDERSTANDING NUTRACEUTICAL LABELS
Because the term nutraceuticals refers to both dietary supplements and food products, understanding label information is essential for providing appropriate consultations and prevention of potential harm to patients. Supplement labels provide information regarding suggested use, serving size, percent daily value of the active ingredients, and a list of inactive ingredients, as well as cautions and warnings. The manufacturer’s address, lot number, and notice of potential allergens should also be present. It is important to note that only the potency of the active ingredients is listed on the product label. Inactive ingredients are not tested for strength or potency in the supplement but are verified only as being present in the product.15

Food product labels that fall under the category of nutraceuticals must abide by labeling requirements under the FDA’s Nutrition Facts Labeling Guidance as well. These are also regulated under the Federal Food, Drug and Cosmetic Act. Labeling for food products requires Nutrition Facts labeling, whereas dietary supplements require Supplement Facts labeling. A notable difference in Nutrition Facts compared with Supplement Facts includes the requirement to list “zero” amounts of nutrients in the Nutrition Facts label. Additionally, sources of dietary ingredients and ingredients without a daily reference intake or daily recommended value cannot be listed in the Nutrition Facts panel for foods.16

The images in the figure depict the differences between a Nutrition Facts and a Supplement Facts label.16




USE OF NUTRACEUTICALS IN THE UNITED STATES
As previously stated, the Council on Responsible Nutrition reported that dietary supplement usage has been at an all-time high in recent years, with approximately 77% of Americans reporting using supplements in 2017, and rates have been steadily rising.3 It is estimated that 9 of 10 Americans have some form of nutritional deficiency and 8 of 10 physicians recommend supplements for patient use.3 Additionally, an increased number of millennials adhere to specialized eating plans, such as gluten-free, vegan, vegetarian, and dairy-free diets; this makes their need for nutritional supplementation potentially higher, to ensure that they consume essential nutrients.14,17

Overall, nutraceuticals are used for numerous health purposes. An overview of some common nutraceutical products and their use follows.

DIETARY SUPPLEMENTS AND THE COMMON COLD
Zinc, Echinacea purpurea, nasal saline, honey (buckwheat), geranium extract, and garlic have all been marketed as dietary supplements used for the common cold. Meta-analyses assessing the effectiveness of zinc for reducing symptoms of the common cold have concluded that zinc lozenges shortened the duration of nasal discharge, nasal congestion, sneezing, sore throat, cough, and muscle aches, with minimal adverse effects (AEs) noted.18 Evidence has demonstrated that the use of buckwheat honey showed improvement over placebo for decreasing the frequency of cough and improving the quality of sleep in pediatric patients.19 Echinacea purpurea, nasal saline, geranium extract, and garlic have provided inconsistent results and require improved trials to demonstrate their effectiveness for use in the common cold.20

DIETARY SUPPLEMENTS AND DEPRESSION
Marketing for the use of dietary supplements in the management of depression is widespread; the most common supplements include omega-3 fatty acids, St John’s wort, SAMe, and inositol. Of these therapies, meta-analyses have provided evidence that St John’s wort may have effectiveness in the treatment of mild to moderate depression in comparison with placebo; however, well-controlled trials are needed to confirm its place in therapy.21 It should also be noted that several drug–drug interactions exist with the use of St John’s wort, and pharmacists should be diligent in assessing all medications for interactions before recommending use of the product. Omega-3 fatty acids, SAMe, and inositol have inconclusive evidence and require further assessment before recommendations can be made.22

DIETARY SUPPLEMENTS AND SPECIAL POPULATIONS
Special populations—eg, those who are pregnant and/or nursing; older adults—may be at greater risk for AEs, and caution should be taken when recommending nutraceutical products in these populations. During pregnancy, for example, levels of essential vitamins and minerals such as iron, calcium, and folic acid may decline, but they are required for proper growth and development of the fetus.23 Although prenatal vitamins are readily available without prescription, pharmacists should recommend that patients who are pregnant be assessed by their obstetrician prior to the use of supplements or nutritional products.24 In geriatric populations, the use of nutraceuticals should be monitored because of the increased risk for drug, supplement, and food interactions that may lead to AEs.4 The National Institute on Aging recommends a balanced diet including a variety of healthy foods and fortified food products to maintain adequate nutrition in geriatric patients; however, individuals with malabsorption of nutrients due to disease- or drug-induced nutrient depletions should be assessed by a health care provider to determine need for supplementation.25 For further information, pharmacists can access the US Department of Agriculture Dietary Reference Intake calculator to assess specific nutrient needs in various populations.26

HERBAL SUPPLEMENTS
Herbal supplements are a subset of dietary supplements that contain 1 or more herbs. They are also referred to as botanicals and are made from plants, fungi and/or algae, or a combination of these substances. Herbal products are often sold as teas, extracts, tablets, capsules, or powders.27 Common herbal supplements include green tea, valerian root, cinnamon, Ginkgo biloba, evening primrose oil, black cohosh, and chamomile, to name a few. An ample number of herbal supplements exist, and pharmacists can consult the National Institute of Health’s National Center for Complementary and Integrative Health for current research and recommendations regarding their use.28

PROBIOTICS
Probiotics are also under the umbrella of nutraceutical products. Probiotics generally consist of live microorganisms that can be placed in dietary supplements and fermented foods and in topically applied products including cosmetics. Probiotics may contain a variety of diverse bacteria; the most common include Lactobacillus and Bifidobacterium Yeast, too, such as Saccharomyces boulardii, may be included in probiotic supplements. Probiotics have demonstrated some effectiveness in specific health conditions, such as preventing antibiotic-associated diarrhea, preventing necrotizing enterocolitis in premature infants, treating periodontal disease, and supporting remission of ulcerative colitis. Probiotic use shows promising results; however, studies with consistent formulations and amounts of each culture are needed to establish guidance regarding products. Probiotics are generally safe but should be used cautiously in patients who are immunocompromised and/or critically ill to prevent new infections or worsen current ones.29

DRUG-INDUCED NUTRIENT DEPLETIONS
Drug-induced nutrient depletions pose an additional area for pharmacist consultation regarding use of nutraceutical products. Drug-induced depletions may be mild to moderate in nature and can be corrected through use of nonprescription products. For example, use of histamine-2 receptor blockers has been associated with calcium depletion; therefore, calcium supplementation may be needed, especially in older adults who are at a higher risk of bone fractures and osteoporosis. More severe depletions require evaluation by a health care professional to establish replacement needs, as in the case of the depletion of such electrolytes as potassium and magnesium in the presence of thiazide and loop diuretics. Pharmacists should be aware of common drug-induced nutrient depletions and educate patients regarding the need for nutrient replacement and/or referral for evaluation. The table highlights some common nutrient–drug interactions.30




CONCLUSIONS
Nutraceutical use across the United States is increasing, and this provides an opportunity for pharmacists to counsel patients on the appropriate use of available products. As the number of nutraceuticals increases, it is essential for pharmacists to remain informed on the latest recommendations for their use and safety. Pharmacists can refer to the FDA website for current information regarding the purity, safety, efficacy, and use of nutraceutical products. Product selection should be based on verification of authenticity through national compendia such as the official USP. Only products with a USP label ensure the purity, potency, performance, and presence of the listed ingredients on the label. The need for supplementation is highly patient-specific: It ranges from broad use of multivitamins to specific replacement of nutrients due to drug-induced nutrient depletions and conditional replacement during pregnancy and lactation. A detailed patient history, assessment of current medications, and determination of risk and benefit should guide pharmacists’ recommendations of nutraceutical products. 
 
LUMA MUNJY, PHARMD, is an assistant professor of pharmacy practice, Chapman University School of Pharmacy, Irvine, California.


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