Exposures to 1,3-dimethylamylamine-containing products reported to Texas poison centers

Abstract

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.

Keywords

1,3-Dimethylamylamine dietary supplement poison center

Introduction

Nutritional supplements are increasingly popular even though little is known about their safety and effectiveness.¹ 1,3-Dimethylamylamine (DMAA) is a straight chain aliphatic amine found naturally in geranium flowers (Genus Geranium). Also referred to as forthane, methylhexaneamine, 1,3-dimethylpentylamine, and geranamine, the substance has sympathomimetic physiological effects, operating as a norepinephrine reuptake inhibitor and/or norepinephrine releasing agent. In addition, DMAA may stimulate smooth muscle and act as a vasoconstrictor.² Several small studies have found acute use of DMAA and DMAA-containing products to result in elevation in blood pressure, although this effect may be due to other substances in the product, such as caffeine.^2,3 Moreover, such an effect is known to occur with other weight loss supplements, particularly those containing stimulants.^4

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As a result of its vasoconstrictor action on nasal mucosa, DMAA was originally used in 1940s as a nasal decongestant.¹⁰ However, there are presently no therapeutic uses for DMAA. Currently, DMAA is often combined with caffeine and other ingredients in weight loss and exercise performance enhancing products that can be purchased over the Internet and at health supplement suppliers. In New Zealand, DMAA became available in pill form as a ‘party pill’ drug-of-abuse after 1-benzylpiperazine became a scheduled drug. As a result, the New Zealand government is evaluating whether DMAA should be restricted.¹¹ The substance is on the World Anti-Doping Agency’s 2010 list of prohibited substances.¹²

In December 2011, the United States Army began investigating whether DMAA-containing products were involved in the deaths from heat stroke and heart attack of two soldiers following exercise and in reports of liver and kidney failure, seizures, loss of consciousness, muscle breakdown, and rapid heartbeat in others. As a consequence, DMAA-containing products were removed from Army and Air Force Exchange Service and Navy Exchange stores worldwide on December 3, 2011.¹³

Information on the safety of DMAA-containing products is limited. Subjects in a small study of DMAA-containing products reported sleeplessness, shakiness, anxiety, chills, sweating, nausea, tingling, fatigue, and headaches.³ Case reports have described brain hemorrhage, agitation, nausea, vomiting, headache, confusion, drowsiness, chest pain, palpitations, slurred speech, and cardiomyopathy in individuals who have used DMAA-containing products.^10,11,14 However, these effects might be due to substances other than DMAA in the products, such as caffeine.

Poison centers in the United States are telephone consultation services that assist in the management of potentially adverse exposures to a variety of substances, including dietary supplements.¹⁵ The objective of this investigation was to describe the demographic and clinical characteristics and outcomes of exposures to DMAA-containing products reported to a large poison center system.

Methods

This retrospective study used data from the Texas Poison Center Network (TPCN), which consists of six poison centers that together service the entire state, a population of approximately 25 million. All six poison centers use a common electronic database to collect demographic and clinical information on all exposures. The data fields and allowable data options are standardized by the American Association of Poison Control Centers (AAPCC). Among the data fields are the Verbatim field, a text field used to record the substance that the caller reported was involved in the exposure, and PoisIndex field, a seven-digit numeric code used to code specific substances. The permissible PoisIndex codes are provided by a Micromedex™ database. Related PoisIndex codes are assigned to a seven-digit numeric Generic field.

Cases were all exposures to DMAA-containing products reported to the TPCN. Although the time period 2000–2011 was searched, no cases were found prior to 2010, so the time-period of the study was limited to 2010–2011. Initial investigation indicated that few, if any, DMAA-containing products had PoisIndex codes in the version of the Micromedex database used at the time. Thus, the Verbatim field was searched for the following terms for DMAA or products reported to contain DMAA: 1,3-Dimethylamylamine, Methylhexanamine, Forthan, Forthane, Floradrene, Geranamine, Adrena G™, Tiger Claw™, Jack3d™, Vyperize™, D Stunner™, Razor8™, Methyldrene™, ALLMAX™, Freak n Muscle™, Methyl Fire™, Hemo Rage Black™, Muscle Warfare™, Napalm™, Nitric Blast™, OxyElite Pro™, Pressurge™, Unleashed™, Muscle Spike™, Cellucor M5 Extreme™, Body Octane GAME DAY™, CryoShock™, Flashover™, C4™, Mesomorph™, and PumpFixx™.

Cases were analyzed for product name, year, patient gender and age, reported amount, exposure route, whether the exposure was acute or chronic, circumstances of or reason for the exposure, exposure site, presence of substances other than the DMAA-containing product in the exposure, management site, medical outcome, and reported adverse clinical effects and treatments.

The DMAA-containing products are available in a variety of formulations such as capsules and powders. The examination of reported amount was restricted only to those products reported in capsule or tablet form. Since the presence of substances other than the DMAA-containing product might affect the management and outcome of exposures, the analysis of management site, medical outcome, and reported adverse clinical effects and treatments was performed for all the cases and for those cases not involving substances other than the DMAA-containing product.

The medical outcome is assigned by the poison center staff managing the exposure and is based on the observed or anticipated symptoms. Medical outcome is classified according to the following criteria: no effect (no symptoms due to exposure), minor effect (some minimally troublesome symptoms), moderate effect (more pronounced and prolonged symptoms), major effect (symptoms that are life-threatening or cause significant disability or disfigurement), and death. A portion of exposures are not followed to a final medical outcome because of resource constraints or the inability to find subsequent information on the patient. In these instances, the poison center staff record the expected outcome of the exposure. These expected outcomes are grouped into the following categories: not followed but judged as nontoxic exposure (symptoms not expected), not followed but minimal symptoms possible (no more than minor symptoms possible), unable to follow but judged as a potentially toxic exposure. Another medical outcome category is ‘unrelated effect,’ where the exposure was probably not responsible for the symptoms.

Statistical analysis was limited to the calculation of frequencies and means. No analysis of statistical significance was performed. The Texas Department of State Health Services institutional review board considers this study exempt from ethical review.

Results

A total of 56 exposures to DMAA-containing products were identified. The cases had been assigned codes with the following descriptions: unknown dietary supplement/homeopathic (n = 17), multibotanical without ma huan or Citrus aurantium (n = 9), caffeine (n = 5), dietary aid-other over-the-counter (n = 4), Jack3d (n = 3), energy drinks (n = 3), other miscellaneous prescription or over-the-counter drug (n = 3), chemical-general or unknown (n = 2), creatine (n = 2), energy products (n = 2), unknown drug (n = 2), vitamins-multiple (n = 2), homeopathic (n = 1), and symptomatic chemical ingestion (n = 1).

Of all, 45 (80.4%) of the exposures were reported to involve OxyElite Pro, eight (14.3%) Jack3d, two (3.6%) Hemo Rage Black, and one (1.8%) DMAA. No exposures were reported during 2000–2009, 14 (25.0%) in 2010, and 42 (75.0%) in 2011.

All of the exposures occurred by ingestion. Of the ingestions, 38 (67.9%) were unintentional (e.g. accidental ingestion by a child), eight (14.3%) were intentional (e.g. suspected attempted suicide, abuse), nine (16.1%) were adverse reactions to the product, and one (1.8%) was for unknown reasons. Of the ingestions, 54 (96.4%) occurred at the patient’s own residence, one (1.8%) at school, and one (1.8%) at an unknown location. Of the ingestions, 54 (96.4%) were acute, one (1.8%) chronic, and one (1.8%) unknown acute or chronic.

Of the patients, 29 (51.8%) were male and 27 (48.2%) were female. The mean age was 11 years (range 1–40 years). Table 1 presents the distribution of ingestions by patient age group and reported amount. Most of the patients were young children age ≤5 years with 26 (46.4%) being age ≤2 years. The mean reported amount in capsules was similar for patients age ≤5 years and 6–19 years but several times higher for adults. Of the 34 ingestions, where the amount was reported in capsules, 29 (85.3%) involved 1–2 capsules.

Table 1.

Distribution of exposures to 1,3-dimethylamylamine-containing products reported to the Texas Poison Center Network during 2010–2011 by patient age and reported capsules

Age (years)	n (%)	Number of capsules reported	Mean number of capsules (range)
≤5	31 (55.4)	18	1.3 (1–4)
6-19	10 (17.9)	7	1.8 (1–3)
≥20	15 (26.8)	9	5.0 (1–30)
Total	56	34	2.4 (1–30)

No substances other than the DMAA-containing product were reported to have been involved in 47 (83.9%) of the ingestions. Of the nine ingestions involving other substances, the other substances were bupropion (n = 2), vitamin D, fexofenadine, and montelukast (n = 1), aspirin and sodium bicarbonate (n = 1), methylenedioxymethamphetamine (ecstasy; n = 1), quetiapine (n = 1), caffeine (n = 1), dextromethorphan and guaifenesin (n = 1), and acetaminophen and allopurinol (n = 1).

Table 2 presents the outcome of the ingestions of DMAA-containing products. 45 (80.4%) of the total ingestions and 39 (83.0%) of the ingestions without substances other than the DMAA-containing product were known or expected to result in an outcome that was grouped as not serious (no effect, minor effect, not followed, and nontoxic or minimal effects expected). No major effects or deaths were reported. The reported clinical effects tended to be cardiovascular, gastrointestinal, or neurological in nature (Table 3). The most frequently reported adverse clinical effects were tachycardia, nausea, and vomiting.

Table 2.

Outcome of exposures to 1,3-dimethylamylamine-containing products reported to the Texas Poison Center Network during 2010–2011

Medical outcome	All cases	Without cosubstances^a
Medical outcome	n (%)	n (%)
No effect	19 (33.9)	16 (34.0)
Minor effect	11 (19.6)	8 (17.0)
Moderate effect	9 (16.1)	8 (17.0)
Not followed—nontoxic	4 (7.1)	4 (8.5)
Not followed—minimal	11 (19.6)	11 (23.4)
Not followed—toxic	1 (1.8)	0 (0.0)
Unrelated effect	1 (1.8)	0 (0.0)
Total	56	47

^aWithout cosubstances indicates that no substances were involved in the exposure except for the DMAA-containing product.

Table 3.

Adverse clinical effects of exposures to 1,3-dimethylamylamine-containing products reported to the Texas Poison Center Network during 2010–2011

Adverse clinical effects	All cases	Without cosubstances^a
Adverse clinical effects	n (%)	n (%)
Tachycardia	16 (28.6)	12 (25.5)
Nausea	9 (16.1)	6 (12.8)
Vomiting	7 (12.5)	4 (8.5)
Agitation/irritability	5 (8.9)	2 (4.3)
Tremor	4 (7.1)	3 (6.4)
Abdominal pain	3 (5.4)	1 (2.1)
Chest pain	3 (5.4)	3 (6.4)
Dizziness	3 (5.4)	3 (6.4)
Headache	2 (3.6)	2 (4.3)
Hypertension	2 (3.6)	2 (4.3)
Elevated creatine phosphokinase	1 (1.8)	1 (2.1)
Diaphoresis	1 (1.8)	0 (0.0)
Electrolyte abnormality	1 (1.8)	0 (0.0)
Hematemesis	1 (1.8)	0 (0.0)
Hyperventilation	1 (1.8)	0 (0.0)
Hypotension	1 (1.8)	0 (0.0)
Mydriasis	1 (1.8)	0 (0.0)
Numbness	1 (1.8)	1 (2.1)
Urinary retention	1 (1.8)	0 (0.0)
Other (unspecified)	9 (16.1)	6 (12.8)
Total	56	47

^aWithout cosubstances indicates that no substances were involved in the exposure except for the DMAA-containing product.

Table 4 shows the management of the ingestions of DMAA-containing products. The majority of patients were managed on site (e.g. at home). Of the 23 patients who were already at, en route to, or were referred to a healthcare facility, 18 (78.3%) were treated or evaluated and released, one (4.3%) was admitted to a critical care unit, two (8.7%) were admitted to a noncritical care unit, and two (8.7%) were lost to follow-up. The most commonly reported treatments were some form of decontamination.

Table 4.

Management of exposures to 1,3-dimethylamylamine-containing products reported to the Texas Poison Center Network during 2010–2011

Variable	All cases	Without cosubstances^a
Variable	n (%)	n (%)
Management site
Already at/en route to HCF	20 (35.7)	14 (29.8)
Referred to HCF	3 (5.4)	2 (4.3)
Managed on site	32 (57.1)	30 (63.8)
Other (unspecified)	1 (1.8)	1 (2.1)
Treatment
Dilution	23 (41.1)	23 (48.9)
Food/snack	11 (19.6)	11 (23.4)
Activated charcoal	8 (14.3)	6 (12.8)
Benzodiazepines	5 (8.9)	4 (8.5)
Intravenous fluids	5 (8.9)	3 (6.4)
Cathartic	3 (5.4)	2 (4.3)
Antiemetics	3 (5.4)	2 (4.3)
Oxygen	1 (1.8)	1 (2.1)
Other (unspecified)	5 (8.9)	3 (6.4)
Total	56	47

HCF: healthcare facility.

^aWithout cosubstances indicates that no substances were involved in the exposure except for the DMAA-containing product.

Discussion

This investigation described exposures to DMAA reported to a poison center system servicing a population of 25 million. Such information is important because DMAA can be found in dozens of dietary supplement or performance-enhancing products. However, information on the safety of DMAA-containing products is limited. Moreover, several deaths have been reported where DMAA-containing products had been used, although causality had not been confirmed.¹³

This study is subject to certain limitations. Reporting of most potentially adverse exposures to the TPCN is voluntary. As a result, all potentially adverse exposures to DMAA-containing products in Texas are not likely to have been reported to the TPCN, and those that were reported might not be representative of all such exposures. Whether an exposure had occurred at all, the product involved and the amount usually were reported by the patient or their family or friends and were not verified clinically. Thus, some of the cases included in the study might not have been actual exposures. This is particularly a problem with exposures involving young children, where the exposure sometimes is based solely on finding the child with an open container. In addition, the total number of cases was small, limiting the results of the analyses. However, this investigation may provide impetus for other studies involving larger sets of data.

Perhaps most importantly, almost all of the exposures involved products that contained ingredients other than DMAA. These other ingredients, particularly caffeine, could be at least partially responsible for any observed adverse clinical effects. Investigations examining exposures to DMAA alone would prove useful in determining the relative contribution of the DMAA to the adverse clinical effects observed with products containing DMAA.

One particular limitation of this investigation was the apparent lack of Micromedex codes for all DMAA-containing products. As a result, the codes could not be used to identify potential cases. Moreover, the products were not coded consistently, as evidenced by the 56 exposures being assigned 14 different codes. Instead, the Verbatim field had to be searched for several dozen DMAA synonyms and product names. Although variations on the spelling of the terms were used in the search, some exposures might have been missed if the entry was seriously misspelled or incomplete. That said, this study does indicate that the Verbatim field may be essential for identifying cases when useful codes are not available. This is important because the AAPCC maintains the National Poison Data System (NPDS), a database that contains data from most, if not all, of the poison centers in the United States. Unfortunately, the NPDS does not include text fields such as the Verbatim field.

The exposures to DMAA-containing product identified in this investigation involved only three of the dozens of DMAA-containing products searched for, and 80% were to a single product, OxyElite Pro. There are several potential reasons for this. It may be that OxyElite Pro is the most popular DMAA-containing product in Texas. Alternatively, it may be that OxyElite Pro is more likely than other DMAA-containing products to result in exposures that would lead to contacting Texas poison centers. Unfortunately, information on the use of the various DMAA-containing products in Texas is not available to determine which explanation might be more likely.

Although the TPCN database was examined for the exposures to DMAA-containing product since 2000, exposures only were reported during the last 2 years and three-quarters were reported in 2011. This likely reflects the relatively recent popularity of DMAA-containing products as dietary supplements and performance enhancers. It may be useful to continue to monitor exposures to DMAA-containing product reported to Texas poison centers to determine whether the trend continues, in particular, if action is taken in the United States to restrict sales of DMAA-containing products such as what was done by the United States military in December 2011.¹³

The preponderance of patients were young children. This might be unexpected, since the products do not appear to be intended for that age group. However, all of the exposures involving young children were unintentional, meaning that the children accidently obtained access to products belonging to their parents or others. Adults might consider dietary supplements to be relatively safe and less likely to take the same actions to keep them out of reach of children as they would for products like medications or household cleaning products. However, in light of the potentially serious adverse effects reported with use of DMAA-containing products, it might be useful to advise users of DMAA-containing products to keep them away from children.

The majority of the ingestions in the study were known or expected to be not serious. This is not surprising considering that most of those ingestions with a reported amount involved only 1–2 capsules. However, even such amounts might potentially result in serious effects in young children because of their smaller body mass and possibly different metabolism of DMAA and other ingredients in the products.

Many of the adverse clinical effects observed in this investigation had been reported by others.^3,10,11,14 A number of these clinical effects might be explained by DMAA operating as a norepinephrine reuptake inhibitor and/or norepinephrine releasing agent and vasoconstrictor and causing an elevation in blood pressure.^2,3 Alternatively, some of the clinical effects might be due to the other ingredients in the DMAA-containing products, such as caffeine.

Most of the patients were managed on site, such as at their own residence. Since the majority of ingestions were known or expected to be not serious, management at a healthcare facility would not be necessary in most of the cases. Of note, over one third of the patients were already at or en route to a healthcare facility when the poison center was contacted. This might suggest that many of these patients could have been successfully managed on site and not incurred healthcare costs if the poison center had been contacted first.

In summary, the majority of exposures to DMAA-containing products reported to Texas poison centers occurred in 2011 and involved OxyElite Pro. Most of the patients were children and male. The majority of exposures involved ingestion of 1–2 capsules. The preponderance of the outcomes in the study were known or expected to be not serious and were managed on site.

Footnotes

Funding

This work was supported by a public health emergency preparedness grant (2U90TP617001-11) from the Centers for Disease Control and Prevention.

Conflict of interest

The author declares no conflict of interest.

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