The vault guy.

Leonard Rome's lab discovered an odd, abundant component of cells in the 1980s-and he's still trying to figure out what it does.

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.

How a geneticist led an effort to free a convicted serial murderer.

"Science has been heard," says Carola Vinuesa after mother jailed for killing her four kids was pardoned and released.

Latest Alzheimer's antibody is 'not a miracle drug'.

Results on Eli Lilly's donanemab highlight stark risk-benefit trade-offs.

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.

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.

Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylamylamine (1,3-DMAA) and 1,3-dimethylbutylamine (1,3-DMBA).

BACKGROUND: The United States Food and Drug Administration banned the stimulant 1,3-dimethylamylamine (1,3-DMAA) from dietary supplements and warned consumers that the stimulant can pose cardiovascular risks ranging from high blood pressure to heart attacks. OBJECTIVES: We designed our study to determine if a new stimulant similar in structure to 1,3-DMAA has been introduced as an ingredient in supplements sold in the United States (US). METHODS: We analyzed six brands of supplements that listed an ingredient on the label (e.g., Aconitum kusnezoffii, DMHA or 2-amino-isoheptane) that might refer to an analog of 1,3-DMAA. Supplements were analyzed by two separate laboratories using ultra-high-performance liquid chromatography mass spectrometry and reference standards. RESULTS: Two previously unidentified 1,3-DMAA analogs (2-amino-6-methylheptane [octodrine] and 1,4-dimethylamylamine [1,4-DMAA]) and two banned stimulants (1,3-DMAA and 1,3-dimethylbutylamine [1,3-DMBA]) were identified. Octodrine was found at a dose (±95% CI) of 72 ± 7.5 mg per serving. In Europe, octodrine was previously sold as a pharmaceutical in multi-ingredient medications at dosages from 8 to 33 mg. The quantity of octodrine found in our study was more than twice the largest pharmaceutical dose. The other new stimulant, 1,4-DMAA, has not previously been approved for human consumption, and its safety in humans is unknown. 1,4-DMAA was found at dosages between 21 ± 11 mg to 94 ± 48 mg per serving. In addition, two banned stimulants - 1,3-DMAA and 1,3-DMBA - were also identified: 24 ± 7.6 mg to 35 ± 11 mg of 1,3-DMAA and 51 ± 16 mg of 1,3-DMBA. In one product, 24 ± 7.6 mg of 1,3-DMAA was combined with 21 ± 11 mg of 1,4-DMAA. 1,3-DMAA has been investigated as potentially contributing to hemorrhagic strokes and sudden death, whereas the safety of 1,3-DMBA in humans is unknown. CONCLUSION: Two banned stimulants (1,3-DMAA and 1,3-DMBA) and two previously unidentified stimulants (1,4-DMAA and octodrine) were identified in supplements sold in the United States.

Development of NIST Standard Reference Material 2082, a Pathlength Standard for Measurements in the Ultraviolet Spectrum.

New spectrophotometers and cuvettes have been designed to allow the measurement of absorbance values from samples using microliter volume sizes. These measurements are done using short pathlengths to decrease the sample volumes required. The major applications for these spectrophotometers and cuvettes are samples that are difficult to obtain in large amounts, such as proteins and nucleic acids that absorb light in the ultraviolet range. Existing ultraviolet absorbance standards have been designed for longer pathlength measurements. Standard Reference Material (SRM) 2082 was developed to validate the pathlengths of short-pathlength cuvettes and instruments using materials with absorbance spectra that are similar to the most commonly used samples. SRM 2082 consists of three individual components: a blank buffer solution, a solution of the amino acid tryptophan in the buffer, and a solution of the nucleobase uracil in the buffer. The tryptophan solution has an absorbance spectrum (peak at 280 nm) similar to proteins, and the uracil has an absorbance spectrum (peak at 260 nm) similar to nucleic acids. The absorbance values of these solutions were determined using a series of cuvettes with pathlengths from 0.1 mm to 2 mm. The pathlengths of the cuvettes used for the absorbance measurements were determined at the National Institute of Standards and Technology by physical and optical measurements. The effects of temperature and spectral bandwidth variations on the absorbance values of SRM 2082 were also investigated.

Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA.

Oxilofrine (4-[1-hydroxy-2-(methylamino)propyl]phenol) is a pharmaceutical stimulant prescribed in dosages of 16 to 40 mg to stimulate the heart and increase blood pressure. It has never been approved for use in the USA as a prescription drug or as a dietary supplement. Several athletes, however, have been banned from sport for testing positive for oxilofrine and have claimed that they inadvertently consumed oxilofrine in sports supplements. Consumption of supplements containing oxilofrine may also pose serious health risks. For example, one brand of supplements containing oxilofrine has been linked to serious adverse events including vomiting, agitation, and cardiac arrest. We designed our study to determine the presence and quantity of oxilofrine in dietary supplements sold in the USA. A validated ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry method was developed for the identification and quantification of oxilofrine. The separation was achieved using a reversed phase column, mass spectrometry detection, and a water/acetonitrile gradient as the mobile phase. The presence of oxilofrine was confirmed using a reference standard. We analyzed 27 brands of supplements labelled as containing a synonym of oxilofrine ('methylsynephrine') and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6/14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. The drug oxilofrine was found in pharmacological and greater dosages in supplements labelled as containing methylsynephrine. Copyright © 2016 John Wiley & Sons, Ltd.

Combinations of physical activity, sedentary behaviour and sleep: relationships with health indicators in school-aged children and youth.

The purpose of this systematic review was to determine how combinations of physical activity (PA), sedentary behaviour (SB), and sleep were associated with important health indicators in children and youth aged 5-17 years. Online databases (MEDLINE, EMBASE, SPORTdiscus, CINAHL, and PsycINFO) were searched for relevant studies examining the relationship between time spent engaging in different combinations of PA, SB, and sleep with the following health indicators: adiposity, cardiometabolic biomarkers, physical fitness, emotional regulation/psychological distress, behavioural conduct/pro-social behaviour, cognition, quality of life/well-being, injuries, bone density, motor skill development, and self-esteem. PA had to be objectively measured, while sleep and SB could be objectively or subjectively measured. The quality of research evidence and risk of bias for each health indicator and for each individual study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. A total of 13 cross-sectional studies and a single prospective cohort study reporting data from 36 560 individual participants met the inclusion criteria. Children and youth with a combination of high PA/high sleep/low SB had more desirable measures of adiposity and cardiometabolic health compared with those with a combination of low PA/low sleep/high SB. Health benefits were also observed for those with a combination of high PA/high sleep (cardiometabolic health and adiposity) or high PA/low SB (cardiometabolic health, adiposity and fitness), compared with low PA/low sleep or low PA/high SB. Of the 3 movement behaviours, PA (especially moderate- to vigorous-intensity PA) was most consistently associated with desirable health indicators. Given the lack of randomized trials, the overall quality of the available evidence was low.