1;3 Dmaa
Also known as: 1,3-DMAA, DMAA, methylhexanamine, 4-methylhexan-2-amine, geranium extract, 1,3-Dimethylamylamine
Overview
1,3-Dimethylamylamine (1,3-DMAA) is a synthetic stimulant structurally related to amphetamines. It was formerly used as an ingredient in dietary supplements, particularly pre-workout and weight-loss products, due to its purported effects on energy, focus, and fat loss. DMAA acts primarily by modulating dopamine transporter function, leading to increased dopamine transmission in the brain. Despite claims of natural origin from geranium plants, there is no credible scientific evidence to support this; it is a synthetic compound. Its use has been associated with significant safety concerns, including cardiovascular risks and potential for abuse, leading to regulatory bans and warnings from health authorities worldwide.
Benefits
DMAA exhibits acute stimulant effects, including increased energy, alertness, and potentially enhanced exercise performance. Mechanistically, it acts as a competitive inhibitor of the dopamine transporter (DAT), increasing dopamine availability in the brain, albeit with a lower affinity than d-amphetamine. Anecdotal reports and some small trials suggest improved mental performance capacity and increased training motivation, particularly among athletes and bodybuilders seeking ergogenic effects. However, quantitative data on performance enhancement are limited, and there are no robust, large-scale randomized controlled trials (RCTs) demonstrating clinically significant benefits. The observed effects are acute, consistent with stimulant pharmacodynamics, but the overall evidence for efficacy is weak compared to the well-documented safety risks.
How it works
DMAA primarily exerts its effects by binding to and inhibiting the dopamine transporter (DAT), which is responsible for the reuptake of dopamine from the synaptic cleft. This inhibition leads to increased extracellular dopamine levels, enhancing dopaminergic signaling in the central nervous system. The mechanism involves competitive inhibition of DAT, and it also influences transporter endocytosis through cocaine- and cAMP-sensitive mechanisms. This increased dopamine availability contributes to the stimulant effects, such as heightened energy, focus, and alertness. Beyond its central nervous system effects, DMAA also exhibits sympathomimetic properties, leading to physiological changes like increased heart rate and blood pressure.
Side effects
DMAA is associated with significant safety concerns, particularly cardiovascular adverse events. Common side effects, reported in over 5% of users, include headache, nervousness, tremors, increased blood pressure, and palpitations. Less common side effects (1-5%) can involve panic attacks, seizures, and stress-induced cardiomyopathy. Rare but severe adverse events, occurring in less than 1% of cases, include hemorrhagic stroke and death, as documented in case studies. DMAA poses additive cardiovascular risks when combined with other stimulants or sympathomimetics. It is contraindicated in individuals with cardiovascular disease, hypertension, anxiety disorders, and during pregnancy. Young, healthy males have reported severe adverse events, and its safety in elderly populations or those with pre-existing comorbidities is not established. Regulatory bodies like the FDA have issued warnings due to these serious risks.
Dosage
There is no established minimum effective dose for DMAA, and due to its significant safety concerns, no validated clinical dosing guidelines exist. Historically, supplements typically contained 25-75 mg per serving. Doses exceeding 75 mg have been associated with an increased incidence of adverse events. The maximum safe dose is undefined, and regulatory agencies have issued warnings against its use due to safety risks rather than providing dosage recommendations. Acute stimulant effects are generally observed within 30-60 minutes post-ingestion. DMAA was primarily used in oral supplement form, and other routes of administration are not recommended. Its absorption factors are not well characterized but are likely influenced by food intake and co-ingestion of other stimulants. No specific cofactors are required for its action.
FAQs
Is DMAA safe to use?
No, DMAA has been linked to serious cardiovascular adverse events, including increased blood pressure, heart rate, and rare but severe incidents like hemorrhagic stroke. It is banned or restricted in many countries and by sports organizations due to these safety concerns.
Does DMAA come from geranium plants?
No, there is no credible scientific evidence to support the claim that DMAA is naturally derived from geranium plants. This claim is considered misleading, and DMAA is a synthetic compound.
How quickly does DMAA work?
When ingested orally, the stimulant effects of DMAA typically manifest within 30 to 60 minutes after consumption, consistent with its rapid absorption and action on the central nervous system.
Can DMAA improve workout performance?
Some users report increased energy, focus, and motivation during workouts with DMAA. However, robust clinical evidence from large-scale, well-designed studies demonstrating significant performance enhancement is lacking.
Is DMAA legal?
No, DMAA is banned by the U.S. Food and Drug Administration (FDA) and many international sports organizations. It is considered an illegal ingredient in dietary supplements due to its significant health risks.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10353075/ – This experimental pharmacology study, conducted on cell cultures, found that DMAA acts as a competitive dopamine transporter inhibitor. It demonstrated amphetamine-like effects on DAT endocytosis, providing mechanistic insight into how DMAA increases dopamine levels. While highly relevant for understanding its mechanism, the findings are limited to in vitro conditions and lack direct human data.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6056667/ – This systematic review and logistic regression analysis of multiple studies (n≥30 per group) indicated that DMAA-containing products were associated with increased mental performance capacity and participation in competitions. The study used observational data, which may be subject to confounders, but employed appropriate statistical methods. It highlights perceived benefits but lacks the rigor of randomized controlled trials.
- https://www.fda.gov/media/169553/download – This FDA Scientific Memorandum, based on regulatory review of human case reports and small trials, documented reports of toxicity associated with DMAA, including hemorrhagic stroke and death. It also noted increased blood pressure and heart rate in small studies. The memorandum reflects strong regulatory concerns regarding DMAA's safety, despite the reliance on case reports rather than large-scale RCTs.
- https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1157413 – This review and case report series published in JAMA Internal Medicine linked DMAA to serious adverse events, including stroke and death. It also concluded that there is no credible evidence for DMAA's natural origin and confirmed its stimulant effects. This authoritative review underscores the significant clinical relevance of DMAA's risks, though it acknowledges the absence of large-scale RCTs to definitively prove causality.
- https://www.heraldopenaccess.us/openaccess/1-3-dimethylamylamine-dmaa-a-brief-history-and-review-of-anecdotal-and-laboratory-findings – This narrative review and meta-analysis, which included an analysis of caffeine co-administration in 5 trials, discussed DMAA's popularity in pre-workout supplements. It highlighted the limited clinical data supporting its efficacy and emphasized the predominance of safety concerns. The review's quality is moderate due to the limited number of trials and potential confounding by caffeine, but it effectively summarizes the lack of robust clinical evidence.
