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In this work, an easy, safe, simple, and efficient pH‐switchable deep eutectic solvents (DESs)‐based liquid phase microextraction followed by high‐performance liquid chromatography‐diode array detector analysis was developed for the determination of 1,3‐dimethylamylamine (DMAA). The switchability of the obtained DESs was investigated by changing the pH. Then the best‐selected DES was characterized and the application of the selected DES in the extraction of DMAA from sports nutrition and bodybuilding supplements was investigated. The DES synthesized from l‐menthol: oleic acid in a molar ratio of 1:2 had the highest efficiency in the extraction of the target compound. Under the optimum conditions, (50 µL of DES, 100 µL of 4 mol/L KOH, 100 µL of 4 mol/L HCl, extraction time of 40 s and without salt addition) the calibration graph was linear in the range of 0.05–100 µg/kg and limit of detection was 0.02 µg/kg. The relative standard deviations including intra‐day and inter‐day for 10.0 µg/kg of DMAA in real samples were 2.7% (n = 7) and 5.3% (n = 7), respectively. The enrichment factor and percentage extraction recovery of the method were 283 and 85%, respectively. The relative recoveries for DMAA in different samples were in the range of 90%–109%. [ABSTRACT FROM AUTHOR]

1,3-dimethylamylamine (1,3-DMAA) is a simple straight-chain aliphatic sympathomimetic amine, which was used as a nasal decongestant between 1948 and 1983. It reappeared in both dietary supplements as a substitute for ephedrine, and in party pills as an alternative to 3,4-methylenedioxymethamphetamine and/or 1-benzylpiperazine, after these substances were banned. Following its introduction to the market, it became one of the most widely used stimulants, and several case reports started to raise concerns about the safety and adverse effects of 1,3-DMAA. As a result, many countries banned or restricted the sale of 1,3-DMAA. Nevertheless, despite the efforts of regulating agencies, it has been reported that 1,3-DMAA is still found in dietary supplements and has been identified in doping controls. Therefore, the objective of this work is to review both the clinical and forensic aspects of 1,3-DMAA. [ABSTRACT FROM AUTHOR]

Sixty-three men (15–35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects. [ABSTRACT FROM AUTHOR]

1,3-Dimethylamylamine (DMAA) is known to be added to dietary supplements from synthetic sources and, presumably, from natural geranium oil. However, the natural occurrence of DMAA in geranium oil (Pelargonium graveolens) has been controversial as published studies report contradicting findings. It is unclear if the difference in detection of DMMA in Pelargonium species is a result of the loss during extraction methods, different detection capabilities of analytical methods or if the content of DMAA is dependent of the species and geographical origins. Consequently, the purpose of this study is threefold: (1) to compare the analytical performance of mass spectrometry methods for the detection of DMMA, including GC/MS, DART–MS/MS and LC–MS/MS; (2) to evaluate if DMMA is lost during the extraction of essential oils from Pelargonium leaves of species from Brazil testing headspace extraction, and (3) to evaluate if DMMA is naturally present in a variety of essential oils originating from six countries. This study shows that for detection of more volatile compounds, headspace GC–MS proved to be more favorable than hydrodistilled essential oil analyzed by direct injection in GC–MS. DART–MS/MS showed to be a good alternative for identification of essential oils compounds and DMAA without sample preparation; LC–MS/MS proved to be sensitive for DMMA identification. Nevertheless, even after the analysis using mentioned methods, all essential oils and for the first time, the volatile components extracted from leaves, showed to be absent of DMAA, proving that its presence is not natural in these species. [ABSTRACT FROM AUTHOR]

In June 2012 DMAA (1,3-dimethylamylamine), an ephedrine-like vasoconstricting substance which had been included in many popular sports supplements, became a scheduled substance in Australia, following bans in several other countries. The underlying rationale for this ban was that DMAA use is unsafe. This paper aimed to critically review the available evidence on the acute and/or long-term harms of DMAA. Using five research databases (PubMed, Embase, ProQuest Health and Medical Complete, and Web of Science) and the key terms 'methylhexaneamine', 'DMAA', 'dimethylamylamine', '1,3-dimethylpentylamine' and '2-amino-4-methylhexane', 842 articles were identified once duplicates removed. Sixteen studies met the inclusion criteria and were included in the review. Of the included studies, eight were case studies, which reported on eight patients who presented to emergence departments. All were retrospective in their reporting. The patients displayed various outcomes; while the patients were presenting with serious problems, in most patients conditions subsided on cessation of supplement use. The remaining eight experimental studies were low powered, with a number of studies conducted by a single research group with industry ties, and broadly investigated the effects of DMAA on physiological outcomes. Mixed findings were apparent, although escalations of blood pressure were present on acute dosing, as well as decreases in measures of body weight and body fat. There is a shallow evidence base describing the adverse effects of DMAA and the dose above which such effects may occur. The scheduling of DMAA in many countries may now impede research efforts to determine whether there are safe doses at which DMAA can be consumed. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effects of a supplement containing stimulants, such as caffeine and dimethylamylamine, use on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) among athletes. The study used Web-based version of ImPACT to assess neurocognitive function. Results show the significant effect of stimulant ingestion for the improvement of memory, visual processing speed, and reaction time.

1,3-dimethylamylamine (DMAA) is a common additive in sport supplements that was banned by the FDA in 2013. Specifically, this additive received much publication for its role in causing adverse cardiovascular events, particularly sudden cardiac death. However, it has been our experience that products containing this additive may also lead to acute liver injury and liver failure. We present a series of seven cases encountered by a military treatment facility in Southern California which involved the use of OxyELITE Pro, a sport supplement containing DMAA, that all resulted in acute liver injury with two cases requiring transplant for acute liver failure. To our knowledge, this is the first case series reported involving OxyELITE Pro or other DMAA-containing supplements with a specific focus on acute liver injury. This review is limited by the paucity of clinical studies and trials based on OxyElite Pro and its effect on the liver. The presented cases are notably observation, and no standardized diagnostic or treatment protocol was utilized. This series is important to the general population as a whole due to the prevalence of sport supplement use, and is particularly important for practitioners who work with the military or athletic populations due to the high use in these demographics. These cases are followed by a brief discussion regarding DMAA. [ABSTRACT FROM AUTHOR]

Background: 1,3-dimethylamylamine (DMAA) has been a component of dietary supplements and is also used within "party pills," often in conjunction with alcohol and other drugs. Ingestion of higher than recommended doses results in untoward effects including cerebral hemorrhage. To our knowledge, no studies have been conducted to determine both the pharmacokinetic profile and physiologic responses of DMAA. Methods: Eight men reported to the lab in the morning following an overnight fast and received a single 25 mg oral dose of DMAA. Blood samples were collected before and through 24 hours post-DMAA ingestion and analyzed for plasma DMAA concentration using high-performance liquid chromatography–mass spectrometry. Resting heart rate, blood pressure, and body temperature was also measured. Results: One subject was excluded from the data analysis due to abnormal DMAA levels. Analysis of the remaining seven participants showed DMAA had an oral clearance of 20.02 ± 5 L∙hr-1, an oral volume of distribution of 236 ± 38 L, and terminal half-life of 8.45 ± 1.9 hr. Lag time, the delay in appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes (0.14 ± 0.13 hr). The peak DMAA concentration for all subjects was observed within 3–5 hours following ingestion and was very similar across subjects, with a mean of ~70 ng∙mL-1. Heart rate, blood pressure, and body temperature were largely unaffected by DMAA treatment. Conclusions: These are the first data to characterize the oral pharmacokinetic profile of DMAA. These findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15–30 times lower than those reported in case studies linking DMAA intake with adverse events. Finally, a single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature. [ABSTRACT FROM AUTHOR]

Increased use of dietary supplements is a phenomenon observed worldwide. In the USA, more than 40 % of the population recently reported using complementary and alternative medicines, including botanical dietary supplements. Perceptions that such dietary supplements are natural and safe, may prevent disease, may replace prescription medicines, or may make up for a poor diet, play important roles in their increased use. Toxicity of botanical dietary supplements may result from the presence of naturally occurring toxic constituents or from contamination or adulteration with pharmaceutical agents, heavy metals, mycotoxins, pesticides, or bacteria, misidentification of a plant species in a product, formation of electrophilic metabolites, organ-specific reactions, or botanical-drug interactions. The topics discussed in this review illustrate several issues in recent research on botanical ingredients in dietary supplements. These include (1) whether 1,3-dimethylamylamine is a natural constituent of rose geranium ( Pelargonium graveolens), (2) how analysis of the components of dietary supplements containing bitter melon ( Momordica charantia) is essential to understanding their potential biological effects, and (3) how evolving methods for in vitro studies on botanical ingredients can contribute to safety evaluations. The virtual explosion in the use of botanical ingredients in hundreds of products presents a considerable challenge to the analytical community, and the need for appropriate methods cannot be overstated. We review recent developments and use of newer and increasingly sensitive methods that can contribute to increasing the safety and quality of botanical ingredients in dietary supplements. [ABSTRACT FROM AUTHOR]

1,3 dimethylamylamine or methylexaneamine (DMAA) is a synthetic pharmaceutical patented in the 1940s as a nasal decongestant which can be used as a recreational stimulant. Alleged to occur in nature, DMAA has become a widely used ingredient in sports food supplements, despite its status as a doping agent and concerns over its safety. There is now some doubt as to whether it can be sourced naturally or whether it actually occurs naturally at all. The presence of DMAA was investigated by high performance liquid chromatography (HPLC) in extracts of the leaves and stems of four geranium species and of three well-known cultivars. The amounts of DMAA in commercial geranium ( Pelargonium graveolens) oil and the leading sports supplement which uses the ingredient were also measured. DMAA was not found in any of the leaves or stems or in the commercial geranium oil included in this study. Approximately 30 mg per daily dose was found in the food supplement. Therefore, the amount of DMAA found in the supplement is most unlikely to have been sourced in nature, and it must be concluded that synthetic DMAA, known to be capable of causing severe adverse physiological effects, has been added. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

1,3-Dimethylamylamine (DMAA) is an ingredient in a number of weight loss and exercise performance enhancing products. However, information on the safety of DMAA-containing products is limited. Exposures to DMAA-containing products reported to Texas poison centers during 2010–2011 were identified and selected factors were examined. A total of 56 exposures were found, of which 75.0% were reported during 2011. OxyElite Pro™ was the reported product in 80.4% of the exposures. The patients were 51.8% male and 55.4% age ≤5 years. The patient was managed on site (such as at home) in 57.1% of the cases, and the exposure was known or expected to result in an outcome that was classified as not serious in 80.4%. The most frequently reported clinical effects were tachycardia (28.6%), nausea (16.1%), and vomiting (12.5%). The most common treatments were dilution (41.1%), food (19.6%), and activated charcoal (14.3%). It should be noted that the adverse clinical effects may be due to other ingredients in the DMAA-containing products, such as caffeine. [ABSTRACT FROM AUTHOR]

Background: 1,3-dimethylamylamine (a constituent of geranium), alone and in combination with caffeine, is widely used within dietary supplements. We have recently determined the hemodynamic effects of 1,3-dimethylamylamine and caffeine alone and in combination, using a single ingestion study. However, no study has determined the hemodynamic effects of these ingredients following chronic use. Moreover, no study has determined the effects of these ingredients on bloodborne variables related to health and safety. Therefore, the purpose of this investigation was to assess the hemodynamic and hematologic proile of two different dietary supplements containing 1,3-dimethylamylamine and caffeine (in addition to other ingredients), before and after two weeks of daily intake. Methods: 7 men (24.9 ± 4.2 yrs) ingested the dietary supplement Jack3d™, while 4 men and 2 women (22.5 ± 1.8 yrs) ingested the dietary supplement OxyELITE ProTMonce per day for two weeks. On days 1 and 15, resting heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure were measured and rate pressure product (RPP) was calculated. Fasting blood samples were analyzed for complete blood counts, comprehensive metabolic panel, and lipid panel. These tests were done prior to ingestion of supplement. On days 1 and 15 following blood collection, subjects ingested the assigned supplement (2 servings) and HR, SBP, DBP, and RPP were recorded at 30, 60, 90, and 120 minutes post-ingestion. Results: After 14 days of treatment, resting HR, SBP, DBP, and RPP were not increased (P > 0.05). No significant changes were noted in any measured bloodborne variable, with the exception of an increase in fasting blood glucose with ingestion of Jack3dTM (P = 0.02). In response to acute intake of the supplements, HR, DBP, and RPP were not increased statistically (P > 0.05). SBP was increased with OxyELITE ProTM(P = 0.03), but not with Jack3dTM (P = 0.09). Compared to pre-ingestion and in general, both supplements resulted in an increase in SBP, DBP, and RPP from 5%-15%, with a peak occurring at the 60 or 90 minute post-ingestion time. Conclusion: Acute ingestion of OxyELITE ProTM, but not Jack3dTM, results in an increase in SBP. Chronic intake of two servings per day of OxyELITE ProTM or Jack3dTM over a 14 day period does not result in an elevation in resting HR, SBP, DBP, or RPP. No significant changes are noted in any measured bloodborne variable following 14 days of ingestion, with the exception of blood glucose with Jack3dTM. Longer term intervention studies inclusive of larger sample sizes are needed to extend these findings. [ABSTRACT FROM AUTHOR]

Background: 1,3-dimethylamylamine is a commonly used ingredient within dietary supplements. Our prior work with this agent indicates a transient increase in blood pressure (systolic in particular) following oral ingestion of a single dosage, but no significant increase in resting blood pressure following chronic ingestion. Moreover, intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicate minimal or no change in bloodborne markers of health. The present study sought to extend these findings by using a 10-week intervention trial to determine the change in selected markers of health in a sample of men. Methods: 25 healthy men were randomly assigned to either a placebo (n = 13) or to a supplement containing 1,3-dimethylamylamine (n =12) for a period of 10 weeks. Before and after the intervention, resting blood pressure and heart rate were measured, and blood samples were collected for determination of complete blood count, metabolic panel, and lipid panel. Results: No significant differences were noted between conditions for blood pressure (P > 0.05), although systolic blood pressure increased approximately 6 mmHg with the supplement (diastolic blood pressure decreased approximately 4 mmHg). A main effect for time was noted for heart rate (P = 0.016), with values decreasing from pre to post intervention. There were significant main effects for time for creatinine (increased from pre to post intervention; P = 0.043) and alkaline phosphatase (decreased from pre to post intervention; P = 0.009), with no condition differences noted (P > 0.05). There was a significant interaction noted for low density lipoprotein cholesterol (LDL-C) (P = 0.043), with values decreasing in the supplement group from pre to post intervention approximately 7 mg • dL-1 (P = 0.034). No other effects of significance were noted for blood borne variables. Conclusion: These data indicate that a dietary supplement containing 1,3-dimethylamylamine does not result in a statistically significant increase in resting heart rate or blood pressure (although systolic blood pressure is increased -6 mmHg with supplement use). The supplement does not negatively impact bloodborne markers of health. Further study is needed involving a longer intervention period, a larger sample size, and additional measures of health and safety. [ABSTRACT FROM AUTHOR]

The CE method employing an indirect UV detection for the enantioseparation of 1,3-dimethylamylamine (DMAA), widely used in various preworkout and dietary supplements labeled as a constituent of geranium extract has been developed. The dual-selector system consisting of negatively charged sulfated α-CD (1.1% w/v) and sulfated β-CD (0.2% w/v) in 5 mM phosphate/Tris buffer (pH 3.0) containing the addition of 10 mM benzyltriethylammonium chloride (BTEAC) as the chromophoric additive was used for the enantiomeric separation of DMAA stereoisomers with the LODs in the range of 7.82-9.24 μg/mL. The method was partly validated and applied for the determination of the stereoisomeric composition of DMAA in commercial dietary supplements to verify the potential natural origin of DMAA., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A sensitive and reliable method of liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/ MS) was developed and validated for determining 1,3-dimethylamylamine (1,3-DMAA) and 1,4-dimethylamylamine (1,4-DMAA) in geranium plants (Pelargonium graveolens). The sample was extracted with 0.5 M HCl and purified by liquid-liquid partition with hexane. The parameters for reverse-phase (C18) LC and positive ESI/MS/MS were optimized. The matrix effect, specificity, linearity, precision, accuracy and reproducibility of the method were determined and evaluated. The method was linear over a range of 0.10-10.00 ng/mL examined, with R(2) of 0.99 for both 1,3-DMAA and 1,4-DMAA. The recoveries from spiked concentrations between 5.00-40.00 ng/g were 85.1%-104.9% for 1,3-DMAA, with relative standard deviation (RSD) of 2.9%-11.0%, and 82.9%-101.8% for 1,4-DMAA, with RSD of 3.2%-11.7%. The instrument detection limit was 1-2 pg for both DMAAs. The quantification limit was estimated to be 1-2 ng/g for the plant sample. This method was successfully applied to the quantitative determination of 1,3- and 1,4-DMAA in both geranium plant and geranium oil.