Rahul S. Pawar

Dietary supplements in the United States are a distinct category of foods intended to increase the intake of certain dietary substances, including vitamins, minerals, and botanicals (U.S. Food and ...

In the United States, melatonin products are widely available as dietary supplements. During the past few decades, melatonin products have gained popularity primarily as a sleep aid, with a variety of product forms available for different age groups of consumers. Recent reports have highlighted a rise in melatonin ingestion among children reported to poison control centers. The increased use of melatonin‐containing products, the diversity in product forms, and reported label discrepancies has emphasized the need for additional research to better understand the marketplace. This work aims to measure melatonin content in products sold as dietary supplements and marketed for children, evaluate method performance across different product categories, and determine if product form has an impact on melatonin stability. One hundred ten (110) dietary supplement products labeled to contain melatonin and marketed towards children were purchased and analyzed using a targeted LC‐MS/MS method validated for the qualitative determination of serotonin and quantification of melatonin, N¹‐acetyl‐N²‐formyl‐5‐methoxykynuramine (AFMK), and N¹‐acetyl‐5‐methoxykynuramine (AMK). Melatonin was identified in 108 of 110 products (98%) with a median concentration of 1.2 mg/g (range: 0.017–130 mg/g) or 1.7 mg/serving (range: 0.042–50 mg/serving). Further, in the tested products, melatonin content ranged from 0% to 667% of the label declaration. This study provides evidence to inform safety assessments and investigate potential factors that may influence reported concentrations, such as product stability and matrix influences.

Since the passage of the 2018 Farm Bill, hemp-containing food products, including those marketed as dietary supplements, have proliferated in the U.S. marketplace, necessitating the development of analytical methods for the identification and quantification of cannabinoids in hemp. Reports suggesting a possible contribution of terpenes on the effects of cannabinoids further expands the demand for analytical methods that can accurately determine the terpenes profile for these products. Due to the complex composition of hemp, one-dimensional chromatographic methods may be proven to be insufficient for unmasking trace level terpenes which may play an important role in the chemical properties of hemp-materials. To address this challenge, a method combining multidimensional gas chromatography (GC×GC) and high-resolution quadrupole-orbitrap mass spectrometry has been developed. The reported method provides accurate analysis of fifty-six terpenes and nine cannabinoids, including but not limited to, CBD and D-9-THC, in various varieties of hemp plant material.

More than 27 million Americans have some kind of thyroid disease. Numerous dietary supplements claiming to support healthy thyroid function and healthy metabolism and balance or promote weight loss are available for purchase in retail stores and on the internet. In the literature, there have been reports of adverse events associated with the consumption of thyroid hormone‐containing products. In this study, an LC‐MS/MS method was developed and validated for the analysis of thyroxine (T4), 3,3′,5‐triiodo‐l‐thyronine (T3), 3,3′,5′‐triiodothyronine (rT3), 3,5‐diiodothyronine (3,5‐T2) and 3,3′‐diiodothyronine (3,3′‐T2) in dietary supplements. Sonication with methanol was used for the extraction of free hormones from nonglandular products. The tissue‐bound hormones from glandular thyroid products were extracted using a modified enzymatic digestion, in which the matrix was first extracted by sonication with methanol and then by enzymatic digestion with proteases. Both extraction methods provided acceptable recovery values between 78% and 116%. Fifty‐eight products making claims related to thyroid management were purchased over the internet from 2017–2018 and quantitatively analyzed for five hormones using the validated methods. Eleven out of 19 glandular products were found to contain quantifiable amounts of hormones. Maximum daily servings were also calculated for each product based on label information. The maximum amount of T4, T3, and rT3 per daily serving in the glandular products were up to 210, 32, and 7.6 μg/day, respectively. In the case of nonglandular products, which were labeled to contain plant extracts, vitamins, minerals, diiodo compounds, and so forth, the amounts of 3,5‐T2 and 3,3′‐T2 were up to 740 and 2700 μg/day, respectively.

The use of DNA-based methods to authenticate botanical dietary supplements has been vigorously debated for a variety of reasons. More comparisons of DNA-based and chemical methods are needed, and concordant evaluation of orthogonal approaches on the same products will provide data to better understand the strengths and weaknesses of both approaches. The overall application of DNA-based methods is already firmly integrated into a wide array of continually modernizing stand alone and complementary authentication protocols. Recently, the use of full-length chloroplast genome sequences provided enhanced discriminatory capacity for closely related species of Echinacea compared to traditional DNA barcoding approaches (matK and rbcL). Here, two next-generation sequencing approaches were used: (1) genome skimming and (2) PCR amplicon (metabarcoding). The two genetic approaches were then combined with HPLC-UV to evaluate 20 commercially available dietary supplements of Echinacea representing “finished” products. The trade-offs involved in different DNA approaches were discussed, with a focus on how DNA methods support existing, accepted chemical methods. In most of the products (19/20), HPLC-UV suggested the presence of Echinacea spp. While metabarcoding was not useful with this genus and instead only resolved 7 products to the family level, genome skimming was able to resolve to species (9) or genus (1) with the 10/20 products where it was successful. Additional ingredients that HPLC-UV was unable to identify were also found in four products along with the relative sequence proportion of the constituents. Additionally, genome skimming was able to identify one product that was a different Echinacea species entirely. ^* Current address: Center for Veterinary Medicine, U. S. Food and Drug Administration, College Park, Maryland, United States Received: 10 July 2020 Accepted after revision: 11 December 2020 Publication Date: 14 January 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Citrus aurantium, commonly known as bitter orange, is a popular dietary supplement ingredient sold worldwide. Bitter orange supplements are sold primarily as weight management and sports performance products and have gained popularity after Ephedra products were banned from the US market. Supplements containing synephrine are reported to exhibit adverse cardiovascular effects especially in the presence of caffeine. In this study, an LC–MS/MS method was established to quantify five natural amines (synephrine, octopamine, tyramine, N‐methyltyramine, and hordenine) and four synthetic phenethylamines (phenylephrine, methylsynephrine, etilefrine, and isopropyloctopamine) in dietary supplements sold in the US. The method was validated and found to have acceptable performance to accurately measure analytes in complex botanical products. The average recoveries from a blank matrix were 88–125% with an RSD of 0.5–7.0%. Fifty‐nine products labeled to contain bitter orange peel, extract, or its amines were purchased and their amine content was measured. Several products were found to contain higher amounts of amines than that expected from a typical bitter orange extract. Of the 23 products that made label claims for synephrine, only 5 products (22%) were within 80–120% of labeled synephrine content. The presence of synthetic amines, methylsynephrine (up to 240 mg/daily serving), and isopropyloctopamine (up to 76 mg/daily serving), whose effects in humans are not known, were detected in six products and one product, respectively. While the use of methylsynephrine and isopropyloctopamine are not permitted in dietary supplements, hordenine, N‐methyltyramine, and octopamine are currently listed on the FDA's Dietary Supplement Ingredient Advisory List.

The multi‐billion dollar dietary supplement industry is global in reach. The industry has been criticized for problems related to poor quality control, safety, misbranding, and adulteration. In this review, we describe how the US Food and Drug Administration (FDA) regulates dietary supplements within the framework of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The Dietary Supplement Health and Education Act of 1994 (DSHEA), which amended the FD&C Act, gave the FDA the authority to promulgate Good Manufacturing Practices for dietary supplements and required that manufacturers provide the FDA information supporting a conclusion that the ingredients are reasonably expected to be safe if the dietary ingredients were not marketed in the USA before 15 October 1994. Recent amendments to the FD&C Act require that serious dietary‐supplement‐related adverse events be reported to the FDA and provide the agency with mandatory recall authority. We discuss the presence of naturally occurring (e.g. Ephedra, Citrus aurantium, Acacia) and synthetic (e.g. β‐methylphenethylamines, methylsynephrine, α‐ethyl‐phenethylamine) biologically active phenethylamines (PEAs) in dietary supplements and of PEA drugs (e.g. clenbuterol, fenfluramine, sibutramine, lorcaserin) in weight‐loss products. Regulatory actions against manufacturers of products labelled as dietary supplements that contain the aliphatic amines 1,3‐dimethylamine and 1,3‐dimethylbutylamine, and PEAs such as β‐methylphenethylamine, aegeline, and Dendrobium illustrate the FDA's use of its authority under the FD&C Act to promote dietary supplement safety. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

In addition to their widely recognized use as dietary supplement ingredients, plant-derived compounds are increasingly used as natural sweeteners. The search for nonnutritive sweeteners has been stimulated over the last 20–30 years by concern over demonstrated or suspected relationships between consumption of sucrose and high-fructose corn syrups and a variety of health-related conditions. In the USA, there is increased use of plant extracts known to contain highly sweet terpenoids. Purified extracts of Stevia rebaudiana (Bertoni) containing the diterpene glycosides stevioside and rebaudioside A are popular as sweeteners and are also used as dietary supplements, and soft drinks and nutritional and energy shakes incorporating extracts of Siraitia grosvenorii (Swingle) fruits containing sweet triterpene glycosides such as mogroside V are also on the market. Here, we review recent studies on these two important sources of noncaloric natural sweeteners, including analytical methods used to identify and quantify specific constituents and structural features relating to their sweetness. We also review the generally recognized as safe status of specific components and their status with respect to review by the Joint FAO/WHO Expert Committee on Food Additives.