Accuracy of Labeling of Galantamine Generic Drugs and Dietary Supplements.

This study examines the accuracy of labeling for galantamine products formulated as both generic drugs and dietary supplements, as well as tests for contamination with microorganisms.

Presence and Quantity of Botanical Ingredients With Purported Performance-Enhancing Properties in Sports Supplements.

This case series study examines the accuracy of labels of dietary sports supplements containing botanical ingredients.

Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US.

This study assesses the actual measured quantities of melatonin and cannabidiol (CBD) in products marketed and sold in the US as melatonin gummies compared with the quantities declared on their labels.

The unapproved drug centrophenoxine (meclofenoxate) in cognitive enhancement dietary supplements.

INTRODUCTION: Centrophenoxine (meclofenoxate) is prescribed in China and elsewhere to treat a variety of conditions including alcoholism and dementia, but the US Food and Drug Administration has not approved the drug for any indication. We designed our study to determine the presence and quantity of centrophenoxine in dietary supplements sold over-the-counter in the US. METHODS: Supplements were included in our study if the label included (a) the term "dietary supplement" and (b) "centrophenoxine" as a declared ingredient. Supplements were purchased online, and powder from each dietary supplement product was reconstituted in methanol and analyzed using ultra high-performance liquid chromatography. RESULTS: Seven products were analyzed. Centrophenoxine was present in all products in dosages ranging from 79 to 251 mg per serving. Consumers following the maximum recommended daily intake on the label would be exposed to 237 to 752 mg of centrophenoxine per day. Only 1 of 7 products (14%) listed a quantity of centrophenoxine on the label within ±10% of the actual amount. CONCLUSION: Clinicians should be aware and advise patients that cognitive enhancement supplements may contain unapproved and prohibited drugs.

Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database.

This case series assesses the levels of levodopa in Mucuna pruriens supplements available in the US that are included in the National Institutes of Health Dietary Supplement Label Database.

Quantity of phenibut in dietary supplements before and after FDA warnings.

INTRODUCTION: Phenibut is used to treat anxiety, insomnia, alcohol withdrawal and other conditions in Russia. The drug, however, has abuse potential and may cause lethargy, delirium, psychosis and coma. In the United States (US), the US Food and Drug Administration (FDA) has never approved the use of phenibut as a prescription medication, but the drug is available over-the-counter in dietary supplements. More than 80 cases of coma and death have been associated with phenibut consumption and withdrawal, and the FDA recently warned that the drug is not permitted in over-the-counter supplements. We designed our study to determine the presence and quantity of phenibut in over-the-counter supplements before and after the FDA warnings. METHODS: Phenibut products were included if they (a) listed phenibut or a synonym as an ingredient on the label, (b) were labeled as a dietary supplement, and (c) were available for sale both before and after the FDA warning. Supplements were analyzed by liquid chromatography time-of-flight mass spectrometry; quantification was performed by isotope dilution method. RESULTS: Four brands of dietary supplements labeled as containing phenibut met the inclusion criteria. Prior to the FDA warnings, two of the four brands contained phenibut, at dosages of 484 mg and 487 mg per serving. After the FDA warning, all four products contained phenibut, ranging in dosages from 21 mg to 1,164 mg per serving. Phenibut was first detected only after the FDA warnings in two brands, and the quantity of phenibut increased in three of four products after the FDA warnings. Quantities detected per dose were as much as 450% greater than a typical 250 mg pharmaceutical tablet manufactured in Russia. CONCLUSION: Following FDA issuing an advisory that phenibut is not permitted in dietary supplements, the quantity of phenibut increased in 3 of 4 brands of over-the-counter phenibut supplements.

Five Unapproved Drugs Found in Cognitive Enhancement Supplements.

OBJECTIVE: To identify the presence of unapproved pharmaceutical drugs in over-the-counter dietary supplements marketed to improve memory and cognitive function. METHODS: Supplements were identified by searching 2 supplement databases for products labeled as containing omberacetam, aniracetam, phenylpiracetam, or oxiracetam, 4 drugs not approved for human use in the United States. Products were purchased online and analyzed using nontargeted liquid chromatography-quadrupole time-of-flight mass spectrometry methods. RESULTS: In the 10 products tested, omberacetam and aniracetam were detected along with 3 additional unapproved drugs (i.e., phenibut, vinpocetine and picamilon). By consuming recommended serving sizes, consumers could be exposed to pharmaceutical-level dosages of drugs including a maximum of 40.6 ± 0.4 mg omberacetam (typical pharmacologic dose of 10 mg), 502 ± 0.8 mg of aniracetam (typical pharmacologic dose 200-750 mg), 15.4 ± 0.3 mg of phenibut (typical pharmacologic dose 250-500 mg), 4.3 ± 0.1 mg of vinpocetine (typical pharmacologic dose 5-40 mg), and 90.1 ± 0.7 mg of picamilon (typical pharmacologic dose 50-200 mg). Several detected drugs were not declared on the label, and several declared drugs were not detected in the products. For those products with drug quantities provided on the labels, 75% (9/12) of declared quantities were inaccurate. Consumers could be exposed to up to four-fold greater than pharmaceutical dosages and as many as 4 unapproved drugs when using individual products. CONCLUSIONS: Over-the-counter cognitive enhancement supplements may contain multiple unapproved drugs. The health effects of consuming untested combinations of unapproved drugs at unpredictable dosages without clinician oversight in supplements are unknown.

Risk Factors for Hospitalization Among Patients with COVID-19 at a Community Ambulatory Clinic in Massachusetts During the Initial Pandemic Surge.

Among patients with COVID-19 evaluated in outpatient settings, factors associated with hospitalization remain poorly understood. Multivariable regressions were used to assess sociodemographic and clinical factors associated with increased odds of hospitalization among patients with confirmed COVID-19 between March 18, 2020 through April 25, 2020 at a community-based outpatient clinic in Massachusetts. Older age, BMI ≥ 25, self-reported dizziness/lightheadedness, temperature ≥ 99.5°F, tachycardia, and oxygen saturation < 95% were associated with increased odds of hospitalization after adjustment for age, sex, and BMI. There was also an association between speaking Spanish as primary language and increased odds of hospitalization (compared to English, adjusted OR = 2.99 [95% CI 1.39, 6.39]). Speaking Portuguese as primary language was not associated with increased odds of hospitalization (compared to English, adjusted OR = 1.83 [0.78, 4.28]). In addition to several clinical risk factors established among inpatients, our study found that primarily speaking Spanish, but not Portuguese, was a marker of hospitalization risk among a diverse outpatient cohort of patients with COVID-19.

Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA) and higenamine.

BACKGROUND: Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest. OBJECTIVE: To determine the presence and quantity of experimental stimulants in dietary supplements labeled as containing deterenol sold in the United States. METHODS: Dietary supplements available for sale in the US and labeled as containing deterenol or one of its synonyms (e.g., isopropylnorsynephrine and isopropyloctopamine) were purchased online. For each brand, one container or subsample was analyzed by NSF International (Ann Arbor, MI) and one container or subsample by the Netherland's National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands). When differences existed between the two containers or subsamples of the same brand, both products were reanalyzed by Sciensano (Brussels, Belgium). NSF International carried out qualitative and quantitative analyses using ultra-high-performance liquid chromatography (UHPLC) quadrupole-Orbitrap mass spectrometry. RIVM performed qualitative and quantitative analysis using UHPLC quadrupole time-of-flight mass spectrometry. Sciensano carried out qualitative analysis using UHPLC quadrupole-Orbitrap mass spectrometry. RESULTS: Seventeen brands of supplements were analyzed. Many brands included more than one prohibited stimulant in the same product: 4 brands (24%, 4/17) included 2 stimulants, 2 (12%, 2/17) combined 3 stimulants, and 2 (12%, 2/17) combined 4 stimulants. The range of quantities per recommended serving size of the 9 stimulants detected were 2.7 mg to 17 mg of deterenol; 1.3 mg to 20 mg of phenpromethamine (Vonedrine); 5.7 mg to 92 mg of beta-methylphenylethylamine (BMPEA); 18 mg to 73 mg of octodrine; 18 mg to 55 mg of oxilofrine; 48 mg of higenamine; 17 mg of 1,3-dimethylamylamine (1,3-DMAA); 1.8 mg to 6.6 mg of 1,3-dimethylbutylamine (1,3-DMBA); and 5.3 mg of 1,4-dimethylamylamine (1,4-DMAA). CONCLUSION: Weight loss and sports supplements listing deterenol as an ingredient contained 9 prohibited stimulants and 8 different mixtures of stimulants, with as many as 4 experimental stimulants per product. These cocktails of stimulants have never been tested in humans and their safety is unknown.

The stimulant higenamine in weight loss and sports supplements.

BACKGROUND: Higenamine is a stimulant with cardiovascular properties recently prohibited in sport by the World Anti-Doping Agency (WADA). Higenamine is also a natural constituent of several traditional botanical remedies and is listed as an ingredient in weight loss and sports supplements sold over-the-counter in the United States. OBJECTIVES: We analyzed dietary supplements available for sale in the United States prior to WADA's prohibition of higenamine in sport for the presence and quantity of higenamine. METHODS: All supplements labeled as containing higenamine or a synonym (i.e., norcoclaurine or demethylcoclaurine) available for sale in the United States were identified. For each brand, one sample was analyzed by NSF International (Ann Arbor, MI) and one sample by the Netherland's National Institute for Public Health and the Environment (RIVM). NSF International carried out qualitative and quantitative analyses using ultra high performance liquid chromatography (UHPLC) with tandem mass spectrometry. RIVM carried out qualitative analysis using UHPLC quadrupole time of flight mass spectrometry for an independent confirmation of identity. RESULTS: Twenty-four products were analyzed. The majority of supplements were marketed as either weight loss (11/24; 46%) or sports/energy supplements (11/24; 46%); two brands did not list a labeled indication. The quantity of higenamine (±95% CI) ranged from trace amounts to 62 ± 6.0 mg per serving. Consumers could be exposed to up to 110 ± 11 mg of higenamine per day when following recommended serving sizes provided on the label. Five products (5/24; 21%) listed an amount of higenamine, but none were accurately labeled; the quantity in these supplements ranged from <0.01% to 200% of the quantity listed on the label. CONCLUSION: Dosages of up to 62 ± 6.0 mg per serving of the stimulant higenamine were found in dietary supplements sold in the United States.